Cardiac Pacemakers

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Designof cardiac pacemakers/ edited by John Webster.

p. cm.
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Includes bibliographical references and index.
ISBN0-7803-1134-5
1. Cardiac pacemakers. I. Webster, John G., 1932- II. IEEE
Engineeringin Medi’cineand BiologySociety.
RC684.P3D47 1995 95-7390
617.4’ 120645---dc20 CIP
Design of
Cardiac Pacemakers
Edited by
John G. Webster
University of Wisconsin, Madis.on
~, IEEE
PRESS
TECHNICAL
ACTIVITIES
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Contents
Preface xi
Normal Conduction System of the Heart 1

James R. Bowers
1.1 Ionic bdsis of the resting potential 1

1.2 Membranechannels and cardiac cells 4
1.3 Cardiac action potentials 6
1.4 Electrical excitation and muscle contraction 9
1.5 Anatomyand function of the heart 10
1.6 Sequenceof excitation 11
1.7 Production of the electrocardiogram 13
1.8 References 14
1.9 Instructional objectives 14
2 Control Systems of the Heart 15

Corey L Brown
2.1 Cardiac control factors 15

2.2 Autonomicphysiology and control 19
2.3 Hormonal control 31
2.4 References 32
3 Mechanisms of Cardiac Arrhythmias 34

Geoffrey M. Weinberg
3.1 Automaticity 35
3.2 Triggered rhythms 41
3.3 Slowed conduction and block 47
3.4 Reentry and unidirectional block 52
3.5 Simultaneous impulse generation and conduction abnormalities 61
3.6 References 62
4 Diagnosing Arrhythmias
Valtino X. Afonso
4.1 Principles of electrocardiography 64

4.2 Monitoring strategies 71
4.3 Intracardiac electrophysiologic techniques 75
4.4 Arrhythmias from the sinus node 77
4.5 Atdoventricular block 83
4.6 Bundle branch block 87
4.7 Preexcitation arrhythmias 93
4.8 Supraventricular ectopics 96
4.9 Ventricular ectopics 99
4.10 References 103
CONTENTS
5 Artificial Pacing 105

MohammadH. Asgarian
5.1 Artificial pacemakerunit 105

5.2 Pacing synchrony 107
5.3 Temporary pacing 108
5.4 Pacing indication 111
5.5 Pacing designation 115
5.6 Pacing mode 122
5.7 Pacing selection 127
5.8 References 128
6 Electrodes, Leads, and Biocompatibility 132

Brian K. Wagner
6.1 Pacemaker electrodes 132

6.2 Leads 149"
6.3 Biocompatibility 153
6.4 References 157
Battery 161
John G. Webster
7.1 Materials 161

7.2 Manufacturing 164
7.3 Endof life 165
7.4 Powerpriority 169
7.5 References 169
8 Pacemaker Sense Amplifiers 171

David M. Beams
8.1 Requirements 171

8.2 Continuoustime circuits 179
8.3 Discrete-time (switched-capacitor) circuits 188
8.4 Blanking circuits 202
8.5 Other circuits 203
8.6 Pacemakersand electromagnetic interference 207
8.7 References 211
Logic Flow and Timing Diagrams 215

Beejahn A. Afsari
9.1 Single chamber pacemakers 215

9.2 Dual chamber pacemakers 219
9.3 References 227
CONTENTS
10 Logic Implementation 228

Surekha Palreddy
10.1 Microprocessor-based pacemaker unit 228

10.2 Pacemaker requirements 229
10.3 Choice of electronic technology 229
10.4 Pacemakersystem architecture 231
10.5 Dual clock control of microprocessor 238
10.6 Analog-to-digital converter 241
10.7 Safety features 244
10.8 Why CMOS? 247
10.9 References 249
11 Pulse Output 251

Michael K. Laudon
....... 11.1 Considerations for output design 251

11.2 Description of output circuitry 258
11.3 ,Electrode reeovery~tirne 265
11.4 Lead measurement 271
11.5 Output circuit protection 273
.... 11.6 References 275
!t~ :~ 11.7 Instructional objectives 276
12 External Programming 277

Kevin M. Hugo
12.1 Hardware interface 277

12.2 Software interface 283
12.3 Pacemaker follow-up and care 286
12.4 References 288
13 Rate-Adaptive Pacemakers 290

Timothy Harvey
13.1 Introduction 290

13.2 Sensors 291
13.3 Control strategies 300
13.4 Conclusion 303
13.5 References 304
14 Rate-Adaptation by Motion 305
’.~ ~’: Kevin T. Ousdigian
14.1 Humanactivity and heart rate 306

14.2 Sensors currently used 310
14.3 Pressure-based approaches 316
14.4 Accelerometer-based approaches 325
CONTENTS
14.5 Studies on motion-based rate-adaptive pacemakers 328

14.6 Summaryof sensing techniques and designs 330
14.7 References 331
15 Rate Adaptation by Temperature 335

Mark J. Mayotte
15.1 Bodytemperature production and regulation 335

15.2 Hardware requirements 341
15.3 Software requirements: the algorithm 345
15.4 Additional features of CVTrate-adaptive pacemakers 364
15.5 Follow-up functions of CVTrate-adaptive pacemakers 364
15.6 Overall advantages and disadvantages of CVTrate-adaptive
pacemakers 365
15.7 Improvements in CVTrate-adaptive pacemakers 366
15.8 References 366
¸16 Rate Adaptation by Electrogram and Intracardiac Impedance 369
Clark Hochgraf
16.1 Benefits of using intracardiac signals for rate adaptation 369

16.2 Sympathetic tone ~-"°- 370
16.3 Biopotential-based measurementsystems (Q-T interval and
depolarization gradient) 373
16.4 Impedance-based measurement systems 380
16.5 Circuit implementations 388
16.6 Performance evaluation 393
16.7 Future of cardiac signal-sensing methods 394
16.8 References 395
16.9 Instructional Objectives 396
17 Rate Adaptation by Minute Ventilation 397

John G. Webster
17.1 Advantagesand disadvantages of minute ventilation 397

17.2 Measuring electrical impedance 397
17.3 Signal processing 398
17.4 Interference 400
17, 5 Automatic modeswitching 400
17.6 Minuteventilation and body activity sensors 401
17.7 References 403
18 Antitachycardia Pacing 405

Rex S. Piper
18.1 The first antitachycardia pacemaker 405

18.2 Antitachycardia treatment alternatives 406
18.3 Antitachycardia theory 407
CONTENTS ix
18.4 Tachyarrhythrnia detection 411

18.5 Termination algorithms 414
18.6 Prevention pacing 415
18.7 Reported results 419
18.8 Commercial devices 420
18.9 Third generation ATPdevices 423
18.10 References 424
19 lmplantable Cardioverter-Defibrillators 427

Adrianus Djohan
19.1 Implantable cardioverter-defibfillator history 427

19.2 Suddencardiac death 429
19.3 The ICD device 430
19.4 Battery 431
19.5 Power supply down-conversion and regulation 432
19.6 Pulse generator circuit 435
19.7 Lead system and implantation techniques 439
19.8 Arrhythmia detection 440
19.9 Parameters of programmabledefibrillator (Cadence CT-100from
Ventritex) 441
19.10 Third-generation ICD 445
19.11 References 446
UWPacemaker Tester 448

Mark D. Werkheiser
20.1 Pacemakertesting 448

20.2 Providingthe test signal 450
20.3 Measuringthe pacing signal 451
20.4 Testing algorithms 453
20.5 Ref~ences 459
Appendix: Microprocessor-based pacemaker design 460

Surekha Palreddy
A.1 Rate-adaptive pacemakers 460

A.2 Microprocessor design 461
A.3 Software algorithm: AV-responsiverate-adaptive algorithm 462
A.4 Design process 465
A.5 Program execution 469
A.6 References 469
Glossary 471
Index 476
Preface
This book provides information on the design of cardiac pacemakers. As a

professor of electrical engineering, I teach medical devices and instrumentation and
am n~turallyinterested in the design details of a cardiac pacemaker.It is the most
importanildevice electrical enginee~ have contributed to medicine with sales over
$i :billi0h per year. I I hope this book will enable readers to understand cardiac
p~emak~er design details so they are preppedto contribute to this expandingfield..
. i:’: ihoped to developthis book someyears ago but could find iittie infoiTmation
in the literature. Designers in pacemakercompanieswould not reveal their designs
to me because of the high competition amongpacemaker companies. Recently I
fdO~d
¢~ed~y of the details ofpresented
design~informati0n design in in
patents and was ’therefore able to develop the
this book.._
~ Me&ronic;Inc. provided me with a ~!atab~e of patents. The ..contributors are
~l,frpin ~e Departmen~of Electrical Engineering at the University of Wi~bnsln~
~.~a~on,~.Wedivided up the toPics, .developed the chapters, and reviewed each
other ~s work to form a first draft. I sent this for review to several pacemaker
~p~p a0i~s and~received invaluable suggestions .for improvement. I am most

preciative for theefforts of thg following, pers0ns whoorg ~anized their Colleagues
tO perform reviews at their companies:~ Wa]te~H, Olson of Medtronic, Inc.; Max
M, Sciaaldach Of Biotr0nik,Inc.; Bruce M~St~in~aus ~o(( Telectronics Pacing
S~?st~ms;, Rob~ Sneed ~f intennedics In c.; and lVaSant Padmanabhanof Cook
i.i( ’ Ch~ipter. l provides the backgrouiid ~matedalnecessary to unders)and normal

ffirictioning of the heart. It starts with cardiac cells, moveson to th~ specialized
conduction system, then to the resulting, electrocardiogram. Severalf~ict0r~ Cause
the intrinsic :heart rat eto V~. Ch~apter2 discusses autonomiccontrol ofhemrate.
This knowledgeis needed tb design a pacemakerthat varies its rate in response tO
the body’s needs.
In the diseased hear3, the normal excitation pathways may becomeblocked~
Unwanted~pac!ngcenters mayassert control. Chapter 3 describes the mechamsms
that cause the resulting arrhythmias. This information will li~lp u~ design
pacemakersthat replace lost cardiac function. The electrocardiograph monitors the
el~9~cal sigoal of the heart. Chapter 4 shows us howto use the electrocardiogram
~0 ’~agn0~se ~ti~hmias. Fromthese diagnoses, we can determine the underlying
problemand’ devise strategies for artificial pacemakerdesign.
Chapter 5 outlines the required componentsof an artificial pacemaker. It
discusses temporary and permanent pacemakers, pacing indication, designation,
mode,and selection. In addition to the pulse generator, the pacemakermust have a
lead and electrode to deliver the pulse to the heart. Chapter 6 describes the
electrode tip, whichhas an increased effective area to lower the voltage required to
pace. It describes the necessary biocompatible materials required so that the lead
will not cause the formation of blood clots.
A battery f’dls half of the volumeof a typical pacemaker.Chapter 7 describes
the manypower sources that have been considered and the details of the presently
used lithium iodide battery. It also includes circuits for extending the lifetime of
the pacemaker and indicating the end of battery life. Cardiac waveforms are
detected by sense amplifiers which use switched-capacitor circuits to minimize
power consumption. Chapter 8 presents many circuits and electronic design
xii PREFACE
techniques for amplifiers, filters, and comparators. It also discusses techniques for
minimizingelectromagnetic interference.
Artificial pacemakers contain microprocessors. Chapter 9 describes the
rhythm required of the artificial pacemakerand details the functions of all the
timers that are required to either wait for durations to expire or to reset whenthe
heart provides intrinsic waveforms. ChaPter 10 shows howthese sensed waveforms
control the timers and provide safety features whenmalfunction occurs.
Chapter 11 shows how the cardiac muscle responds to output pulses of
varying durations and amplitudes~ This~, chapter also details the circuitry that
provides this output pulse. Physicians cani~se telemetry to changeparameters in an
implanted pacemaker. Chapter 12 describes howthese telemetry systems operate
and the safety codes that prevent inadvertent modification of stored parameters.
These programmingdeVices also extract stored data such as histograms of beat
intervals.
Early pacemakers operated at a fixed rate. The next four chapters address
methods that permit rates to vary. Chapter 13 outlines several methods for
designing rate-~esp0nsiv e pacemakersthat increase the heart ~ate in response to
exercise. The next tb_/ee chapters illustrate howthe rate c~ be increased through
the use of sensors: in Chapter 14 with piezoelectric sensors to sen§e body naotion;
in Chapter 15 with a thermistor to sense increase in blood temperature; in Chapter
16 to sense events in the electrogram or to use intracardiac impedance,in Chapter
17 to sense th6racic impedanceand calculate minute ventilation.
The heart maylapse into the undesii~ably high rateof tachycardia: Chapter 18
shows howcarefully timed pacings from the antitachy pacemakercan interrupt the
tachycardia and restore normalrhythm. If the ~heart rliyttim should proceed tO
ventricular fibrillation, there is a wayto restore it to normal.Chapter19 showsthat
the implantable cardioverter-defibrillator can provide a Stepped response of shocks
to restore normal rhythm.
Testing cardiac pacemakers is important. Chapter 20 shows the-detailed
design of a simple pacemakertester. The tester can v~r), its rate to electronically
exercise the response .of the pacemaker. The boisk appendix provides the design
and software of a microprocessor-based pacemaker. A glossary provides
definitions of manywordsin both Cardiology and electronics:
I would welcomeyour suggestions for improvementof future editions.
John G. Webster
Madison, Wis~ot~sin
NormalConduction System of the Heart
James R.. Bowers
Knowledge of the excitability characteristics of cardiac cells is essential in

understandingartificial pacemakers.Thepurposeof this chapter is to realize the
origin of cardiaccell electrical activity and howit correspondsto heartbeatrhythm.
This involves examiningimpulseformationand conductionof activity to various
parts of the heart. Thechapter concludeswith a discussion on the origin of the
e!ectrocar~ogram.A survey of pertinent physiologic and anatomicalmaterial is
presented, however,textbooks coveting ahatomy,physiology, electrophysiology,
~d Cardiologyare suggestedfor further study.
1.1 IONIC BASIS OF THE RF~TINGPOTENTIAL
Theelectrical potential difference betweenthe inside and outside of a cardiac cell

membrane ~depends~on the ionic concentration gradients across the cell membrane
and the relati~,erpermeability of the membrane to the ions present. This steady
electrical potential-across the membrane
(resting-potential) can be explainedusing
simpleconceptsfrom physical chemistry.
Figure 1.1 Showsa: simple modelcell. Theonly permeableionin this cell is
potassium.Theion concentrationdifferenceis similar to that organordinarycardiac
celL, Other ions such as sodiumand calciumare. present in real cardiaccells but
will be ignored for the moment.Since the concentrationinside,-the cell,is much
higher than outside the cell, what prevents the potassiumions from leaving the
cell?
¯ Intracellular Extracellular
K~" 4 mM
0 mV
Figure 1.1: The modelcell membrane is only permeable to potassium ions. The concentration
gradient tends to drive potassiumout of the cell (shaded arrow) and the potential difference
drives potassiuminto th~ cell. At equilibrium the two forces are balancedahd no net potassium
flows. The potassiumconcentration is expressedin millimoles (mM):
DESIGN OF CARDIAC PACEMAKERS
The answer is that the ions are not capable of leaving the cell due to the
development of a charge separation across the membrane.The charge separation
creates a membranepotential, which hinders further diffusion. As the ions leave
the cell, positive charges accumulate on the outer surface of the membraneand an
excess of negative charge remains on the inner surface. Whenthe membrane
potential becomes sufficiently large; further net movementout of the cell is
stopped. The concentration gradient equals the electrical gradient at this point and
electrochemical equilibrium has been established. Ions still pass back and forth
across the membrane,however, there is no net movement~of potassium.
The question then arises as to howlarge the potential must be to cancel the
chemical gradient. The potential necessary to achieve electrochemical equilibrium
is defined as the potassium equilibrium potential. The potential depends on the
difference between the logarithms of the extracellular concentration [Ko+] and
intracellular concentration [Ki+]:
EK-- !n . --0.027 [~-~]-- (v)

(1.1)
This is the Nernst equation for potassium wh~re R is the thermodynamic gas
constant, Tthe absolute temperatt~e, ~ the valence of the ion (in this case +1), and
F the Faraday constant. At mammalianbody temperature"(37*C) the expression
RT/zF is approximately 27 mV.Figure 1.2 shows typical ion equilibrium potentials
for cardiac muscle cells. The resting potential 0f cardiac muscle cells is about
-90 mV.
Note that the electrostatic and electrochemical forces tend to pull sodiumions
into the cell. The actual inward flux is small, however, since the sodium
permeability is very small at the resting potential. This is also true for calcium.
Given normal potassium concentrations found in cardiac cells,~ Fxt. (1.1) gives
goodapproximationof the resting potential. Tiffs indicates that the resting cardiac
cell is mostly permeable to potassium. The resting potential..can be measured
experimentally by using a glass microelectrode with.a tip diameter.of 0.1 #m to
puncture ~the membraneof4he cell without greatly damaging it~ The membrane
then seals around the glass electrode and~a voltage measurement can be made
relative to the external medium.
Ion Extracellular Intracellular Equilibrium

concentration concentration potential
(aM) (my)
+
Na 145 72
+
K 4 135" -95
Ca++ 134
Figure 1.2 Table indicating typical ion concen~iio/Is and resting potential for typical cardiac
muscle cells. The intracellular concentrations are estimates of the free concentrations in the
cytoplasm. (Modified from Ten Eick, R. E., Baumgarten, C. M,, andSinger, D. H.: Prog.
Cardiovasc. Dis. 24: 157, 1981).
In a real cell~ it is necessary to consider the contributions of other permanent

ions~ Byassumingsteady state conditions, that is, the sumof ionic fluxes are zero,
thef01i0wingconstant fieid equation is deriv6d:
NORMAL CONDUCTION SYSTEM OF THE HEART 3
+ a[Na
] + l[Cl ]
Era=
-- ln ÷ ÷
(1.2)
Equation (1.2) differs from the Nernst equation in that it includes the ionic
permeabilities in addition t6 concentrations. If is knowna~ the ConStant field
equation because it is derived assumingthat theelectric field within the membrane
is.~,gd: ~ ,F_zluation 1.2 is flso knownas the Goldman-Hodgkin-Katz(GHK)
p¢~i~i~i!iy
eqU~0fi ~t~r’ coefficient for ion
its, developers: emx.represents
The iarger._the permeability,,
the membranepotential the
andgreate~ it~
Px istile
contribuiJontoward the membranepotential. In cardiac cells, Changesin membrane

~tentiaJi!~e mainly due to potassium, Sodiumand calcium~ Cl~oride ions have
little effect 0n the resting potential or action potential and Will .no longer be
cons~dered~ .... "
._, Wecan’alsouse an electrical model to represent multiple.ionic contributions
t~ the n~embrane potential. Figure 1.3 sht~ws.,the electricalequivalent for
potassium, sodium and calcium where the battery potential is calculated from the
Nernst equation and the conductance represents membranepermeability.. Cm
red~,resents the membranecapacitance that stores the transmembranepotential
difference,Simplecircuit analysis reveals that for a given ion the ionic current is:
Ix = gx (Vm-Ex)
(1.3)
Intracellular
Extracellular --"
Figure1.3 Electrical equivalentof a cardiaccell membrane~. Theequ~bdum voltages predicted

by the Nemstequationare shownas batteries. Thec0nductances~gNd, gKand gca modelthe
membrane permeabilityfor the respective ions. Themembrane’c~pa~it~nce iS Cm.~ ~ereasein
an ions conductance
(lowerr~sistance)will drive vmtowardthat ~on’~equilibriumpotential.
If the transmembraneconductance to a particular ion is increased~.the ~al

transmembrane electrical potential difference will move toward the battery
potential of that ion. For example, if gNa were suddenly increased, the membrane
potential Vmwould move toward ENa (+70 mV). This is what occurs _during
action potential whengNa transiently increases. The ionic mechanismof the-action
potential is discussed in section 1.3. ,~
The relative-concentrations inside and outside the cell aremaintained by
active transport of ions across the membrane: The active transport process
transports three sodium ions out of the cell and two potassium ions in for each
4 DESIGN OF CARDIAC PACEMAKERS
molecule of ATP(adenosine triphosphate) hydrolyzed. The active transport

mechanism of ions to create the chemical gradient is known as the sodium-
potassium pumpand restores the sodium-gradient at the expense of the sodium-
potassium ATPase enzyme.
1,2 MEMBRANE CHANNELS AND CARDIAC~CELLS
Ionic currents across cell membranesmove through hydrophilic pores called

channels. Such channels mayhave relatively little ior~ selectivity oi: maybe
selective for a single ion such as sodium. Ion channels fluctuatebetween~open and
cli~sCd states. The channels are usually closed during th~ resting state exctpt for the
channels responsible for the resting potential.-The channels in cardiac-tissue are
mainly controlled’ by the membranepotential but can be affected by other stimuli.
The cardiac tissue consists of a network of fibers, which are connected to each
other by intercalated disks. The brief transient flow of ions through membrane
channels is responsible for the electrical signals generatedin the heart.
Call membranesconsist of a lipid bilayer and embeddedproteins. Figure T.4
shows the lipid molecules are arranged in a bilayer approximately 6 nmthick, with
the hydrophilic heads facing outwardand their liydrophObic tails extending to the
middle of the layer: Embeddedin this lipid bilayer areprotein molecules. Someof
these proteins span the bilayer and makecontact with both the extracellular fluid
andthe cell’s interior.
Embedded "
Figure 1.4 Cell membranecomposedof fatty bilayer embedded

with proteins. Someproteins
that exist throughthe membrane
formion channels.
Figure 1.5 showsthe basic structure of a channel protein. The protein forms a
pore, through whichions can move.A region of the pore acts as a selectivity filter,
regulating ion permeation according to size and molecular structure. The channel
gate:allows or prevents ionsTm~m crossing the membrane.,Theopen or closed state
of the :gate depends on the magnitude of the voltage across the membrane.This
control mechanismis knownas voltage-activation.
NORMAL CONDUCTION SYSTEM OF THE HEART
~F~.~)
,,,,nslsts of a lectivi
se .. ty filter (S) and_a gate ((3). Thoylterdrestricts ~o~a_.~ormnt~
+ .... ~t~ A)lowsions .to ~ass through the memoranean canbe regulated by membran
voltage.
~ .Efficient operation of the heart depends on the ability of fibers to work
synchronously~ Figure 1.6 shows the connection of mdivxdual umnucleate cells to
forn~_~_.a branched network of muscle fibers. The connection is formedat the cell
endsby intercalated disks. These disks consist of accumulations of dense material
on the insides of the two cell membranesto fix the cells iogether and allow the
filaments of the contractile apparatus in one cell to pull on those of the next cell in
the line. The flow of electrical signal from one cell to another.is facilitated by the
presence of gap junctions between the cells. The junctions allow a low,resistance
path for the current to flow and resemble the membranepores discussed earlier.
Moregap junctions are present wherethe fibers are in contact longitudinally than
side to’side. Electrical conductiontherefore proceedsfaster parallel to the long axes
of the fibers than in the direction perpendicularto the fibers. Thefiber i~ striated in
appearance due to bands of thick myosin and thin actin filaments aligned
tz~nsverseto the long direction.
Intercalated Gap
disks Fiber bands junction "
Nucleus
/(enlarged)
%~___ / ~. ~//
’ ." f ve~b~te he~ cells. ~e ~rc~at~ ~s~ c~t c~ac cell~. ~p
sp~o ~uY ~m ~1~ m ~=.

DESIGN OF~CARDIAC PACEMAKERS
1.3 CARDIAC ACTION POTENTIALS
Cardiac cells are capable of their membrane

regenerative,
fiber when adequately
adequate stimulus is one to its threshold value.
The size and shape of the action as it propagates downa
muscle fiber. A Stimulus Othe~ it producesa full
size action potential. That is termed an all-or-nothing
response. D~s~ussion demands use of the
terms polarization, At rest, because of :the
resting potential, the cell is said to~.~ larized., Achangein the membranevoltage
from -90 mVto -70 mVis a depolarization since it is a decrease in the potential
difference. A change in membrane potential from -90 mV to -100 mV is
hyperpolarization.
Twodifferent typesof responses are found in cardiac cells.. Onetype, the fast
response, occurs in the normalmyocardial fibers in the atria and ventricles and in
the specialized conducting fibers in these chambers. The left side of Figure 1.7
shows a typical fast response. The other type 0f action potential is knownas the
slow’response: This type is found in the sinoatrial (SA)node, the atrioventricular
(AV) node, and the~specialized tissue that conducts impulses from the atria
ventricles. Fa~t responses Can be converted to slow responses in regions~of the
heart that have been damaged. ~ ¯
Fast aCtiOnpotential Slowaction potential

I
-~ 25-F ~’~---’ ......... r .... - - - -
E -60-- ~-
-90-- ]--- T T
0 0.1 0.2 0.3 0 0.1 0.2 0.3
......... Time,(ms)
Figure1.7 Twodifferent,typ~of acti6n’ p0tentiaJsare foundin cardiacmusclefibers. Thefas!

action potential has a morenegativemembrane potential and much-sh~a-per
upstrokethan the
slowactionpotential.
Figure 1.7 shows that the resting potential is more :: negative in the fas!
response cells and the upstroke is significantly steeper. ~A!s0, the,ampfi~deand the
overshoot is greater in the fast response: Furthermor~e,~the~amp~md-e of:tlie’action
potential and the,slope of th~:upstroke are ~po~anf factors dete~ining
conduction velocity downa muscle fiber. Therefore, the conduction velocity in
tissue characterized by the slow response is slower th~ in tissue exhibiting fas!
response ~tion p~tentials. This is"~portant since stoP’velocity often!~ads t~
conduction block.
NORMAL CONDUCTION SYSTEM OF THE HEART 7
_~, ~ Similar to the ionic basis of the resting potential~ there is an ionic basis to the
action potential. ~Figure1.8 showsa typical fast response action potential. Therapid
upstroke of the action potential is designated, phase 0. Immediately after the
upstroke, there is a brief period of partial repolarization (phase I), followed by
plateau region (phase II). The potential then becomesmore negative (phase III)
imtil~the resting state is attained. Theinterval fromthe completionof repolarization
until, the beginningof the next action potential is phase IV.
II
0 III
Time (ms)
1
’ ~’~gNa
I
I
0
I
..~
"0
|_j " .
0
0 0.~1 - 0.2 0.3
Time(ms)
Figure.1.8 Theshapeof the fast actionpotentialcan be explainedin termsof sqAti,’um,calcium

aii~ potassiurn conductancechanges. The: conductanceaxis Shows-relativemagnitudeand
di~on0f’theindividualion flow.’Thesharpupstrokeof the action potential is dueto the steep
influx Of sodium,the plateauis dueto steadycaleiuminfluxandthe mpolarizationis duet? the
outflow,of potassium.
. Theupstroke resdts_from be raPid flow of ions i!~ward: ~iS i~due

t~:~both ,the electfieal.and chemic~gra~ents tendiligtoforc~~0dium ion~ ’into the
cell. The sodium ehanuels are Vbl{~ge acfivated’a~d allow more s~qm’ion~ tb
flow ~ as the membranepotential becomesless negative. :Therefore, th~ effe~t On
sodium conductance is regenerative. A small depolarization increases the number

of open sodium channels, resulting in more depolarization, which again increases
the numberof open sodiumchannels, An electrical analogy to this type of behavior
is positive feedbackand explains the sharp upstroke. This process is responsible.for
the large and abrupt increase in sodiumconductanceshown’in: Figure 1.8. Oncethe
influx of sodium comesto an abrupt halt, the outward diffusion of potassium and
inward diffusion of calcium becomes predominant. During phase II the calcium
and potassium currents approximately cancel each other. Slowly, the calcium
current diminishes and the repolarizing potassium current dominates. This brings
the membranevoltage back to its resting value. The sl0w response involves slow
calcium or sodium/calcium channels so that the slope of the upstroke is greatly
diminished.
Oncethe fast response has been initiated, the cell is no longer excitable until
sometime in the middle of the final repolarization stage. This period is knownas
the absolute refractory period. The interval between the beginning of the action
potential and whenanother action potential can be fired is knownas the effective
refractory period. During the relative refractory period action potentials can be
evokedbut are smaller in magnitude. Also, during the relative refractory period it
takes a stronger stimulUs than normal to evoke the action potential. Figure 1.9
showsthe refractory periods and changein amplitude for action potentials initiated
during the effective and relative refractory period.
I Strong ’
c¯
.-
x~
, timu
us’..t,..
! , . Normal
’ imulus
~
-90- L
l~(.., / .
Figure1.9 Theabsoluterefractoryperiod(ARP)lasts throughoutthe plateauphaseof the action

potential. Astrong stimulusin the relative refractory period(RRP)causesa reducedaction
potentialandnoactionpotentialis possibleduringthe effectiverefractoryperiod(ERP).
The effective refractory, period of the slow response frequently" extends

beyond the final repolafization (phase HI). Even after the membranevoltage has
returned ,to the resting level it maynot be possible to evoke an action potential.
During the relative refractory period the excitability prog~ssively improvesdespite
NO~-CONDUCTION SYSTEM OF THE HEART 9
refractory period-in slow fibers accounts for the increased susceptibility to

,conduction blocks.
~ ::- Figure 1.10 showsthe propagation of an action potential downa musclefiber,
As, each-region of the membranegenerates an all-or-nothing action potential, it
depolarizes and excites the adjacent nonactive region and gives dee to a propagated
regenerative impulse. It is the spread of electrical current that depolarizes adjacent
regions of membrane.Onceinitiated, the action potential in a cell cannot double-
back on itself and reverse the direction of propagation. This is because, the region
behind the wavefront is in a refractory period, The sodium conductance is still
inactivated and the potassium conductance is high so that backward conducting
regenerative response cannot occur.
Membranestarting
Muscle fiber Local current flqw to depolarize
---’ 7
f~ Reponariza~:ladzed Resting ~
~) region )region membrane)
Direction of action potential propagation

I~igureLlO Theconduction of anactionpotentialdown a cardiacfiber is shown as a, sectionof
depolarization (sodium in)followedby repolarization(potassium ont). Thelocal current
discharges the resting membrane whilethe previoussectionof membrane charges backto the
resting potential. Thevelocityof the action potential then dependson howfast the membraneis
dischargedand recharged-through the membrane capacitance.
The conduction velocity depends on the rate-at which the membrane

capacitance ahead of the wavefront can discharge by the spread of positive charge.
The rate of discharge depends on the amount of positive charge flowing and the
properties of the fiber, that is, the membranecapacitance and the internal resistance
of the. fiber. If the resistance is low, larger currents flow and the membrane
discharges faster. The low internal resistance of large diameter fibers causes them
to conduct action potentials faster than small fibers. Fast type action pOtentials
propagate faster because the amplitude is muchgreater than the slow.type. The
larger voltage amplitude causes more local current to flow and the membrane
discharges more quickly.
1.4 ELECTRICAL EXCITATION AND MUSCLE CONTRACTION
The connection between cardiac action potentials and muscle contraction depends
on ,internal calcium concentrations activating .filaments within the cell. Duringthe
plateau region of the action potential calcium is flowing into the eell.Thi~ causes
in~rnal stores of calcium to be released into tbe cell cytoplasm., The:con~ntration
of internal calcium increases fifty times its normal restinglevel~ This increase in
calcium concentration results in myosinheads attaching to the thin actin filaments
at a particular angle. This cross-bridge undergoes a structural change where the
10 ¯ ~DESIGN OF CARDIAC PACEMAKERS
heads:tilt from 90~to45*, drawing the thin filament along with them.-This
produces an overall shortening of the muscle fiber. Active ion pumpsthen move
the calcium out of the intracellular space and the muscle relaxes. Both contraction
and relaxation phases require ATPhydrolysis. Figure 1.11 shows this actin and
myosin contraction mechanism.
ldyosin
¯ = ~ % . / Myosin head
Figure1.11 Myosinheadsbondto the actin fdamentand the h~dstilt from90" to45°, drawing
the thin actin filamentalong.Thisresults in a museularcontraction.
1.5 ANATOMY AND FUNCTIONOF THE HEART
The heart consists of two pumpsin series, one to propel Moodthrough the lungs
for exchange of,oxygen and carbon dioxide (pulmonary. circulation) and the other
to, prope!bloodto al!:other tissues of the body(systemic circulation). Figure 1", t
sliows.th~ basic st~eture of the heart and the ~ direction of blood"flow2 The
ventricles provide the pumpingof the blood and the contractile phase is Called
systole. The resting phase of the heart is called diastole. The atria function as
fillingand holding Chamberswhile the ventricles, contract.and,also prime the
ventricles.
The pericardium ~ a sac-that encloses the entire hea~ and the cardiac portion
of ~e blood vessels~ ...This sac contains a small amountof fluid which .provides
lubtication for continuoOsmovementof.the heart, The material.,of the pericardium
is mechanicallyStiff so.that it prevents large and-rapidincreases in cardiac..size.
This helps to prevent overdistension of:the chambers:.
The. cardiac valves eonsist.-~f thin flaps of. flexible,, tough fibrous gssue,
Movement of the valve flaps is.essentially passives.and the~otient~tion of.the valves
is responsible for the unidirectional flow of blood in the heart. The tricuspid -~alve
is composedof three cusps and lies between the tight atrium and tight ventricle.
The mitral valve has two cusps and separates the left atrium and left ventricle.
Strong fitaments (da0rdae tendin~ae)~e~attacltedi to, thor free .ends of the val~es and
prevent the valves from opening when the ventricles contract. The pulmonary
valve and aortic valve are semilunar valves and consist of three cup-like cusps
attached ~to the ’valve:tings.-These,’valves provide unidirectional flow ,out, -of ,the
ventricles. Revergal:0f blood~ flow ;towardthe-ventricles, causes ~the: euspsto snap
flow intothe venlrieles. .~~ ,-~:
~Tlae (1) eells~that
initiate ~ and eohdtiet impulsesl arid (2) :eells that\ibesideseonducting, respond
stimuli~b3/e~eting. The latter ConstitUte the Worldngmuseulatureof the hearVor
ttie my6cardium.The myocardiumof the vemtieles is aftincti0nal syncytium, that
NORMAL, CONDUCTION SYSTEM OF :’I~IEHEART 11
is, ,the cells are not electrically insulated Or mechanically separated from one
anoti~r~A stimulus, arising at any point in the ventricle spreads to cause complete
contraction of both ventricular chambers. The same applies to the atria.-The atria
and ventricles are.not connected except for the AVnode.
To head’
and
From
head
and
Right
lung.
Left
lung
Right
coronary Right
artery Atrium
To trunk
andlegs
artery
Fromtrunk
andlegs (1) Tricuspidvalve
(2) Pulmonaryvalve
(3) Mitral valve
(4) Aortic valve
Fi~ ~1~j2S~hematic the direction
showing ofblood
flow the heart:
through
~ ~~ ~iTheeleftfiCal bb~is~of.theheart provides rhythmicityto Causethe. me,Ironical

~oning of the heart.-~Figure 1.13 ’shows this elec~cal part Of thb heart, ~tfich is
knO~ as the spe,~iM~e~i ~onducfing system~ The conduction system~m~kes~ up
o~’a s~alI, p~irt b~.~e total.mass:Therefore’, the myocardial-ceH~~of theatria and
vefitricles provide ~a larger electrical ~ignal than the whole ~of the’specialized
conduction tissue. Each specialized conducting tissue is ex~d~in the following
Excitation of the heart normally proceeds: from the sin.oatrial ~($A) node which.is
the physiological pacemaker of the heart. From the SAnode, excitation spreads
12 , i, DESIGN OF CARDIAC PACE~KE~
through both atria to the atrioventricdar (AV)node,whence,, via the bundle o~ His
and its two brancbes, it reaches the Purkinje network, w~ehcarries the impulse to
the ventricular muscle: Activation of the ventricular muscle takes place from
endocardium (inside of heart)to epicardium (outside of the heart) and from
apexof the ventricles to the base.
Fi .g~re 1.13 Specializedcondti~onsystemandrepresentativeelectric activity fromvarious

regions of the heart. A typical ECGsignal is shownat the’bottom.(@Copyright1969CIBA
PharmaceuticalCompany, Division of CIBA-GEIGY Corp..Reproduced,with permission, from
TheCibaCollectionof MedicalIllustrations, by FrankH.Netter, M.D.All rights reserved.)
Theproperties of automaticity(ability to initiate its ownbeat) ar :1 ~ ayt hm.ici,ty

(regularity of beats) are in~nsic t~ the hei~-’t. If the heart is remov,~: ’~to:
and, ~..cial~y perfused, the rhy~ ~.mic contraction will eontinu~ for It considerable
period~0f time," The SAnode has the.fastest rate of spontaneous der o|arization~f
about,70 beats.per~minute at rest. The AVnode h~8.the he,x~ hi, best order,, of
rhythmicity atla frequency of 40-60 b,ea~ per ’miniJt~Fi.nai|y; ithe’ [ ~kinje fibers
of the. ventricle can operate as the physiologic pacemakerat a f~quency.of o.nly
25-40.beats.per. minute.
The SA node is typically 15 mmlong, 5 mmwide, and 2 mmthick. Figure
1.13 shows the anatomical position and Figure 1.14 shows a typical action
potential. The automaticity is due to, the slow depolarization during phase IV until
the threshold potential is reached. The depol .~zation afi’ses from a, slowinward
leak of sodiun~ and calcium. This causes a~other action tentialto fire. heart
rate is inversely proportional to the period between SA node action potentials.
Figure 1.14 shows the SApacemaker potential and. indicates the-three following
potential sites of influence_on the heart :rate: ~ .
NORMAL CONDUCT/ON SYSTEM OF THE HEART 13
II
0
Threshold potential
Time ~ ,Maximaldiastolic potential (MDP)

~
Figure1.14 Changes
in pacemaker
potentialinfluenceheartrate.
1. if the :threshold potential is madeless negative, heart rate decreases becauseit

takes moretime to reach the threshold potential.
2. If the slope of the diastolic depolarization decreases, the heart rate decreases.
3. If the maximaldiastolic potential (MDP)is v0ade~moreaegative,the heart rate
decreases.
The.’cardiac action potential proceeds along the internodal pathways in the

atr’mm ~nd ultimately reaches the AVnode?This node~is 22 mmlong, 10 mmwide
and 3 mmthick. The response of AVnodal tissue is of the sl0w type. This allows
atrial contraction to complete and permits optimal filling of the ventricles. Also,
the refractory period of the AVnode extends~well beyond the period of complete
repolarization. Conductionthen continues .through the. bundle of His and passes
down the septum approximately 12 mmand then divides into the right and left
bundle branch~s. Tl~e action potentials are of the fast type and serve t~ pass signal
from the atriato~the ventficles~: These branches ultimately split into ~the Purkinje
s~stem. The conduction velocity of the action potential over the Purkinje fiber
~systemis the fastest of any tissue within the:heart at approximately1-4 rn/s. This
permits rapid activation of the endocardial surface of the ventficles~ The waveof
excitation then spreads from endocardiumto epicardium (outside of heart):
1.7 PRODUCTION OF THE ELECTROCARDIOGRAM
Electrical activity of the heart is due to autorhythmicity of the SAnode whichleads

to contraction of the entire cardiac muscle. Theaction potentials of all of the heart
cells can then be measuredexternally. This is referred to as an electrocardiogram
or ECG.
The bottom of Figure 1.13 shows a typical scalar electrocardiogram. The
important features of the waveformare labeled PQRSand T. Figure 1.13 shows the
action potentials of specific cardiac cells and wherein time they are initiated. The
P waveresults from a summationof atrial muscle action potentials. The delay from
theSA node to the AVnode is represented by the P-R interval and is knownas the
atrioventricular conduction time. Conductionthen occurs through the bundle of His
to the myocardialfibers of the ventricles. Ventdculardepolarization appears as the
QRScomplex. Repolarization of the ventricles is seen as the T wave. SomeECG
waveforms show an ad&fional wave ..aft~ er the T wave. This is called the U wave
and its origin is attributed to Slow repolarization of ventricular papillary muscles.
1.8 REFERENCES
Aidley, D. J. ~1978.The physiology of excitable cells. 2nd Ed. Cambridge:Cambridge

University
Berne, R. M., and Levy, M. N. 1988. Physiology. 2t~d Ed. St. Louis: C.V. Mosby.
Dangman,K. H., and Miura, D. S. (eds.) 1991. EleCtrophysiology and pharmacologyof the
hea~. NewYork: Maw,el Dekker.~1991.
Despbl~odl0~;~A:; and Silb~rha~l~S. C61oratlas ofphysioi~gy. 4th Ed~: NewYork: Thieme
MedicalPublishers.
Keynes, R. D., and Aidley, D.L 1991. Nerve and muscle. 2rid Ed. Cambridge:: Cambridge
University Press.
Nieholls, J. G., Martin A. R., and Wallace, B. G. 1992. Fromneuron to brain. 3rd Ed.
Sunderland, MA:Sinaner Associates.
Webster~,~I. G, (ed.) 1992. Medicalinstrumentation: application and design, 2rid Ed. Boston:
~H0ugliton~Mifflin.
1.9 INSTRUCTIONAL OBJECTIVES
1,.1 Determinethe extraeellular;Concentration of-sodiumin~ a cell given :a,cell potential of

+70 ~V, intracellularsodium concentration of 10 remandall other~ionic permeabilifies are
1.2 ~ :~ribe the~funeti0n of the ffl~er and the ght~ in ~ i0n e~el. ~
1.3 EXpthin.,~,~Wthd action potential is able to propagated0~.;h’~usclefiber unattenuated,
1:4’ Describethe characteristics of fast and~slow,my0eatdialfiberS~ ¯~
1.5 Deserib~,~whynormalconductionvelocity varies~in my.o~=~:at~ fibers. ¯ , .
1.6 SkeWh ~e .~anatgmyof the heart atld indicate di~tio~ ofbl~0odflow throughall valves.
1.7 Sket~i ~t~d iab~l the cardiac eondu~ti0n~system ahd indicfite thespontan~usfrequency of
each structure.
1.8:- Explain,howchangesin’:the sinus nodepacemaker~potentials can change:theheart rate.~
1.9 Giv~the seq,uenceof electrical, excitation:through.thec~nducfi,on system.
1.i0 Drawa tYPi~ ECGwaveformand label~all waves(P, QRS,.T)and intervals. Explain what
is happehiiagelbctficall~ within the h~artduringeach Wave or interval.’
2
Control Systems of the Heart

CO~ey L. Brown
In order for the development of cardiac pacemakers to occur successfully, the

engine~t? must fully comprehendthe control systems ~of the heart. The integrative
progresses ~that occur ~within the cardiac environmentoften makeit difficult to gain
such understar~ding. Someof the heart’seontr01 pathways remain uncertain in
detail, while others offer a more diverse opportunity for control. This
opportunity appears to exist in the autonomicnervous system (ANS), as it plays
large role in! cardiac control and regulation. Moreover, a large amount~ of
information is available regarding its physiological interactions. This chapter
therefore focuses mainly on the innervation Of the ~ANSat~d its control
mechanisms.Other influtnces at the lowest and fhe highest levels of integrative
cardiac control are included to provide a comprehensiveoverview.
2.1 CARDIAC CONTROL FACTORS
The.cardiac system:is .self-regulating. It is nearly, impossible to consciously

increase or decrease contraction rate due to its involuntary.0peration. The large
number of influential factors affecting cardiac performance combine in a
complexmanner,thus providing the ability to a ~dapt quickly and efficiently~to the
needs of the body. This is accomplished by two pathways. The intrinsic pathway
represents the alterations occurring within the myocardial cells which do or do
nol~ depend on a change in the initial myocardial fiber length. The extrinsic
pathway occurs primarily through neural and humoral adaptations (Levy, 1973).
Figure 2.1 shows a hierarchical display of these pathways. These discrete
interrelated biological interactions indicate that regulating any certain
physiological controlpathway is not easy. Often, it is difficult to measure a
quantifiable parameter accurately, For example, the current techniques for
measuring the end,diastolic volume of the ventricles are not able to provide
predictable values (Levy, 1982). This is mainly due to the large number
factors on whichthe end-diastolic vo!~ ~umedepends.
Figure 2.2 shows that changes in venous return and atrial pressure will have
a direct influence on the end-diastolic volume. Note that a l~ge number of
influences regulate bo~ parameters (venous return and atrial pressure), creating
"2nd level effects". These"2nd level effects, are actually what. makeit difficult to
calculate the end~diastolic volume.
The. intrinsic pathways represent the changes within the physical
microenvironment of the heart. They are induced in three ways: preload,
aftedoad, and contraction frequency. Preload refers to the initial tension prior to
a contraction of the myocardial fibers. The preload mechanism is volume
~
dependent and is the basis for the understanding of the Frank-Starling effect~
Therefore, afterload refers to the tension exerted on the myocardial fibers
immediately after contraction. This is measured by ventricular elasticityma
parameter that is difficult to quantify as a result of complexgeometry. The last of
the inducers is contraction frequency, otherwise knownas heart rate. This is a
well knownand measurable parameter. It plays a key indicating role for the
condition of the heart and is easy to precisely measure, providing information on
the heart’s condition.
Intrinsic adaptations
I Extrinsicadaptations
I
I
’madl
I c mic,*fa=oI ,+a
I Neural
ors
!
~ ~r----], Hormonal II r-.I SYmpatfieticl
I Parasympathetic
~Card;ac performance ~
Figure2.1 Hierarchicaldisplayof influential factors onoverall cardiacperformance.
The Frank-Starling law also provides essential information regarding the

heart’s condition. It is a complex derivation of physical forces based upon
properties of elasticity in the heart. In summation,the law states that an increase
in contraction force ~will occur Whenan increase in muscle fiber stretch occurs. A
nonlinear relationship exits between the two parameters and length-tension
mechanisms are those which govern this relationship. Figure 2.3 graphically
demonstrates the Frank-Starling law.
Meanwhile, the extrinsic pathway is madeup mainly of chemical and neural
influences. They are provided from fll regions of the body and are integrative in
nature. Figure 2.1 shows that the chemical factors contributing to the extrinsic
pathways are ionic, gaseous, and hormonal. Ionic Contributions are promoted
through excitation-contraction coupling actions. Gaseous influences arise from
changes in oxygen and carbon dioxide levels in the blood. The major effects of
the hormonal components are coupled with the neural factors. There is much
interdependency between the autonomic nervous system and the byproducts of the
humoral factors. Specifically, norepinephrine (NE) and epinephrine (EPI)
responsible for the combinedeffects.
There are no direct independent regulatory actions of the heart knownto
date. Thus, local intracardiac changes produce global differences ranging from
cellular to organ levels in order for homeostasis to exist. Manyaspects Of the
extrinsic pathway are measurable. They also play a more dominant t01e in
cardiac autoregulation. Hence, it ’is believed, that the most SucceSsfulme~trls ~of
control exist here. Figure 2.2 displays knownextrinsic mechanismsand their
effects upon each other which ultimately regulate the functionality of the
CONTROL SYSTEMS OF ’THE HEART 17
II Rdngby artedal baroreceptors
I ~’as~mP=het~l
I Syn-e=h=~c
activityI I Syrnp~c
activit~
I activitv~tohearlI I t~ h~J~rt I I to arterioles |
02
I
I ,~pirat~ movement~
Osmoladty
-Eicanoids~
Bmdykinin
Myogenicresponse
Substancesrelease
dudnginjury
~ , :
8 I End-diastofic
~olurne : -- - ? "~""
I,I I :~ *.e,o,.,co,=~on
I
II ~! I I Anaiotensinll I I , I acuityI I I 1~o.~) I
t ili,,’ ..... ’
~_.
I ./~,~,~,vo~,~l
, .1 ’ .I
.I .,~r,r~to " ,
~1 "P’ . -J
~/ I c.~c
o.t~ut
I
Meani
Figure2.2 Rowchartof extrinsicinfluencescontro]]ihicardiacfunction:Solidlines indicate

d~tlyproportional
effects.Dashedlines indicateinverse]!)roportionai
effects.
cardiovascular system, These factors interact with each other to maintain bulk
flow conditions throughout the body. At any given time, at least 5% of_the total
circulating blood travels through the capillaries. This is actually the goal and
most important aspect of the system. For it is this 5%that provides the essential
nutrients and removal of metabolic end products at the cellular level, keeping the
individual alive.
In Figure 2.2, the top third represents "the neural input factors, the middle
third represents the chemical and physical influences, and the bottom third of the
diagram characterizes cardiac performance. A comprehensive .systems flow
18 DESIGN OF~ CARDIAC PACEMAKERS
diagram is presented in order to explicitly detail the process of cardiac control:

Manyfactors considered in figure 2.2 are not measurable as a means of control,
The purpose here is to present the intricacy of the system whichcontributes to the
difficult regulation process.
200
100
Ventricularend-dib.stolic volume
(ml)
Figure 2.3 The Frank-Starling law of the heart. As the amount of exercise or stress on the
cardiovascular system inere ~a~es, movementalong the curve to the right occurs. (From Rhoades,
R., and Pflanzer, R. 1992. Humanphysiology. Saunders.)
The solid line arrows indicate directly proportional affects upon the
succeeding factor. Thus, an increase in sympathetic activity to the heart resulting
from a decrease in arterial baroreceptor firing, causes an increase in heart rate.
Likewise, the dashed line arrows indicate inversely proportional affects upon
succeeding factors. An increase in parasympathetic activity to the heart causes a
decrease in heart rate. Onecan easily verify the regulatory effects by following
any of the pathways. For example, hemorrhagingor other disturbances that cause
a decreas~ in the meanarterial blood pressure (MABP)would cause a directly
proportional decrease in the firing by the arterial baroreceptors. This sudden
alteration within the body would then have multiplicative effects. They would
either be excitatory or inhibitory. Hence, the decrease in arterial baroreceptor
firing would cause increases in the sympathetic activity to the veins, heart, and
arterioles and a decrease in the parasympathetic activity to the heart. These
changes, after causing further alterations of their respective succeeding
parameters, would ultimately create an increase in cardiac output and total
peripheral resistance. These alterations reestablish the biological norm for the
MABP which is approximately 90 mmHg2 Any other effects causing disturbances
in the model result in. integrative cooperation on all levels, restoring normal
conditions. However,often certain parts of the body are either degenerated or
dysfunctional, making it extremely’-difficult for this natural-autoregulatory
process to succeed. In these cases, the engineer must provide solutions.
Figure 2.2.~ by no meansattempts to represent all’influential factors of the
heart. Other influences may exist that have not been.-determined to date. Any
significant factors that exist are compiledin Figure 2:2. Significant factors are
CONTROL SYSTEMS, OF THE HEART 19
those which cause a moderate increase or decrease in cardiac performance

(cardiac output, total peripheral resistance, heart rate, and stroke volume). The
construction of the multiparametrie model helps identify the.required relevant
data to optimize the clinical efforts and reduce .the costs of obtaining significant
and meaningful data. ~-
There are also two well-developed ways of viewing the cardiac control
system. Central-peripheral or peripheral-central are both analytically effective.
The difficulty remains in the identification’ of the controlling factor and the
controlled factor.
In a central-peripheral analysis, the brain is perceived to control circulation.
This is performed by specific afferent (baroreceptor) signals and by self-
examination. The brain is informed through numerous afferent nerves regarding
local organ conditions, thus any afferent activity would cause a cardiovascular
response governed by central nervous control. The brain acts as the Controlling
factor and the cardiovascular response is the controlled factor~ ~
The ~peripheral-central analytical viewpoint considers independent organ
operation. The heart adheres to Starling’s law, whereby the filling process
dictates its performance.Renal controlled filling of the ~;aseular~ s~S~ei~exists
without exterior control influences and organs operate by autoregulation
(Strackee, 1993).
This natural autoregulatory loop viewed througheither perspective ensures a
timely response to situations of local malfunctions.. At the same time, intuitive
foresight is necessary for the engineer to decide where the most effective point of
intervention exists.
Finally, the remainder of this chapter presents different control systems,
providing insight towards developing soi~itions. The ANSis currently recognized
~at~important.controlling factor (Schaldach, 1992) and is therefore presented
great detail; Thecoordination of other control systemsis also detailed..
2,2 AUTONOMIC PHYSIOLOGY AND coNTROL
The i~nnervation of all tissues other than skeletal muscle is through the ANS.~The
ANScoordinates bodily functions needed for, survival~and acts tO regulate the
e~nvir00me~nt necessary for cells to function properly, Although inherent
rbyth.~lmcity of.the heart is due to its natural pacemaker, the sinoa~ial node,
cgn.tinuouscontrol of heart rate is dependent on the relative balance between
sympathetic, parasympathetic, hormonal, and chemicalimpulses delivered frpm
the brain to the sinus node.
2.2.1 Physiology
It is important to understand the humanphysiology that exists amongthe

neural componentsbefore proceeding to the discUSsion of its control. Figur~ ~2.4
shows that the ANSconsists of two divisions: central and peripheral. The ~central
division is 6omposed of the hypothalamus, brain stem, and the spinal cord,
~he, reas the peripheral division ~ composedof the ner~.es that innervate .the
6i~g~s of th~b0dy~-There are .t~w~otypes: sympathe~i~ and parasympa&etic. The
b~sis for this, further subdivision ~S du~o anatomical an~ physiOlogical
~fferences within the ANS.These nerve fibers include both affere~ (sensory)
and efferent (motor) neurons. The autonomic_process operates in the following

manner. First, it transmits sensory information from the visceral organs to the
central ANS(affector stimuli)..Then, instructions :are sent from the central ANS
to the smooth muscles and other cells of those organs, producing an automatic
response (effector stimuli).
Domalroot
CentralANS PeripheralANS
Sensorynervefrom
visceralorgan
Target
organ
Ventralroot
ganglion
nerve
cell Postganglionic
nerve
cell
~ ganglion
Autonoticm
Figure 2.4 The information pathwayof the autonomicnervous system.,’ Bo~hautonomic

of transmittingsignalsfromandto their effectororgans.
divisionsexhibitsimilarprocesses
The function of the central division of the ANSis less integrative than the
peripheral division. ActiVity of the hypothalaiiaus is more~direcfly ,related .to
control of the adrenal gland. Hence, the discussion of its regulatory process is
included in the section on humoral control. The organization in the brain stem is
actually not well understood’ withrespect to eardiac Control..The, processes
occu~ng in the region-are extremely complex and laci~ ~ precise definidbn.
However,information regarding the spinal cord .struCture is available iti~detail:
The preganglionic nerve cells are locatext in the interomedial lateral cell ~61~n~
They have sensory fibers that enter-the spinal cord from the d0rsalroots e~g
information from the target, organ, Whilefibers-leave fr0m the Ventral roots. ~The
cell bodies of the sensory fibers are located in the dorsal ’root ganglia. Both the
sympathetic and parasympathetic subdivisions exhibit this organization.
The peripheral division exhibits distinct and intricate modesof operation:
This is essential due to the unpredictable actions of the cardiac system. The two
branches of the ANSoriginate from different’level~ 0f ~he’ spinal cord. The
sympathetic nerves that innervate the heart leave the th0raciJ region of the spinal
cord between’T1 & T4 (Figure 2.5). They te~itate a~ ~esinus bode, conduction
system, atria, ventricles, ~ and coronary: v~els. All ~bl00dvessels recei#e
s~mpathetic fibers. In addition; Organ~yst~msare activated ~Simultaneously,,
piaying"an important role during stress ~r~spbnses: ~ In compariso~ tli~
and
parasympathetic nerve fibers leave the s~infl cord from the br~in stem
terminate at the sinoatrial and atrioventficul~ nodeS, atrial and ven~cul~
CONTROL SYSTEMS OF THE HEART 21
musculature and coronary vessels. Not all vessels receive input from this branch.
It alsoaetivates ~fferent organ systems more independently.
. The two subdivisions of the autonomic nervous system also differ in location
of ganglia. Most .of the sympathetic ganglia lie close to the spinal cord and form
two chains,, one rOn each side. They are knownas the sympathetic trunks. The
celiac,-superior mesenteric, and inferior mesenteric ganglia make up the
collateral ganglia, They lie closer to the innervated organs, farther awayfrom the
spinal~.~¢0rd (Figure 2.5). In contrast, the preganglionic fibers of the
parasympathetic subdivision have long myelinated and unmyelinated axons. As a
result, they innervate postganglionic nerve cells grouped near or in the target
organ. This provides for very short axons of the postganglionic parasympathetic
nerve cells. These ganglia can act either as automatic relay stations wherebythey
do not change the information they transmit to the target organ, or as important
integrating centers capable of generating individualized responses. Figure 2.5
demonstrates the origin and pathway of the autonomic nerves. The specific
attachment of neural networks to-the heart is complexand still being researched.
This specificity, once determined, will enhance opportunity for cardiac control.
Dorsal motor
nucleusof vagus
~ Superiorcervical /~.
~idbrain~ ganglia I
}(,7-~ ganglia I 1~ ~ cardiacbranc-h
I1 g~lnfed°r--.~--~-~
~cervical
=’~.I~’ "¯
-.--4 Stellate ganglia--~ , ~ ~ ,-,=r~i=~,~

h ....h ! / I ] stem
.......... I /!
’ : ’ I I I/
~ Spinal cord ’,
,
,
Sympathetic Preganglionic ~rves P~ra~alhelic
~ ~ = Poslganglionicnerves
Figure2,5 Theanatomicaldisplay of the autonomicnervoussystem. Thediagramdepicts the

ima.. i;ryalion 0f the heart by both the sympatheticand parasympathetic
nervoussystems.The
~r~l;angtioniefibers fromboth divisions areshownby the solid lines. Dashedlines Showthe
,10~ifion of the postganglionicnervefibers. Thesympatheticpreganglionic
fibers extendfromthe
first, to fourth thoracic Vertebrae.TheparasympatheticpreganglioniC~nervefibers are shown
extending~omthe dorsal motornucleus of the vagus nerve. (FromVander,A. 1990. Human
physiology.5th Ed. McGraw. Hill.)
The ’physiological differences are more complexin detail (Figure 2:6). This
difference lies in the types of neurotransmitters and receptors available for
synaptic activity in each of the ANSbranches. The two major neurotransmitters
in the ANSare acetylcholine and norepinephrine (NE). Cholinergic and
adrenergic fibers are those that transmit acetylcholine and NE respectively:
Acetylcholine is released at the synaptic terminals ofall preganglionic neurons. In
postganglionic nerve cells, NEis found in the terminals of sympathetic fibers,
while acetylcholine is found in the terminals of the parasympathetic fibers. ’The
sympathetic branch sometimes contains acetylcholine in the terminals of
postganglionic fibers that innervate the skeletal muscleblood vessels. ~¯
Muscadnic
Pmasympathetic
¯ recept°r
I
"
Preganglionic Postganglionic
Nicotinic neurons ce~s
neuroll=$ Ganglia ~
Sympathetic
I):-recptor
Figure2.6 Theneurotransmitterflowprocess of the sympatheticand parasympathetic nervous

systems.Nicotinicreceptors in the g~glia of ttie presynapticneuronsof both systemsaccept
acetylcholine(ACH).Muscarinicreceptors of the parasympathetic postganglionieneuronsalso
acceptAcH.Alphaandbeta receptorsof the sympatheticpathwayhavespecific bindingsites for
norepinephrine(NE).(FromRhoades,R., andPflanzer, R. 1992.Human physiology.Saunders.)
Manyof the drugs that stimulate or inhibit various componentsof the ANS
affect receptors for acetylcholine and NE. The acetylcholine receptors on the cell
bodyof postganglionic neuronsare different from the -recept~ors on target cells~,of
the p~sympathetic branch,. Cholinergic receptors ard.,eitht~ nicotinic, those 6n
pos~ganglio~ic neurons,: or muscarinic~ thos~ on.~a~et c~lls such las.-cardia~
musele: This classification evolves from receptor~activation by ~nieotineLor
museadne.Similarly, there are two types of adrenergic :receptors, alpha (tz),and
beta (fl). Generation of a second messenger and :a greater sensitivity
isoproterenol by the receptors is the means for their differentiation (Vander,

1990).,:
The t~ and fl receptors have subtypes ¢tl, 0:2 and ]~1, t2 respectively. Their
classification is due to anatomical location. The location of txl and/~1 receptors is
onpostsynaptic target cells of sympathetically innervated organs, while it2
receptors exist on the presynaptic terminals of noradrenergic fibers. The fll
receptors are equipotent to NE and epinephrine, whereas/~2 receptors are more
responsive to epinephrine, thus suggesting their activation by circulating
hormones rather than by sympathetic stimulation. Figure 2.7 demonstrates the
effects of the cholinergic and adrenergic influences on target organs.
Area affected Parasympathetic Receptortype Sympathetic ,

(cholinergic) (adrenergic)
Decreasein heart rate ~11 ,.Increasein heartrate.
~V node Decrease in conduction fll Increasein conduction
Increase
in contractility
’ in contractilit~
Ventricles Decrease . Increasein’~ontmctility
¯ ~ ; ...... ~ .. in contractility(minor)
Coronary arterioles Dilates Constricts, dilates
Veins "~ . " :~ None " Constricts
Dilates ~ ~ : .....
Figure 2.7 Effects of autonomic nervous activity throughout the coronary system.
Neurotransmitter
receptortypesdiscussedin section2.2.1 are also listed.
The ANS has four basic effects on cardiac performance. They are
chronotropic (heart rate), inotropic (heart muscle contractility), dromotropic
(conduction delay in the AVnode), and bathmotropic (excitability). Inotropic
effectSare easily measurable and thus are useful in: monitoring sympathetic and
parasympathetic activity. Positive inotropic effects are exhibited by the
sympathetic branch. Overall, the enhancementof calcium into the effector cell
during the plateau phase of the action potential occurs (see Chapter 1). The
parasympathetics cause negative inotropic effects. The sympathetic branch also
experiences positive Chronotropic and dromotropic effects. Likewise, the
parasympathetic branch expedence~negative’ effects.
Ba~thmotropic changes are-minor influences as a result of sympathetic
stimulation and offer no means for control. The sympathetic nerves ~act to
increase the excitability of the myocardial cells by lowering the threshold
potential. This parameter is not only minor in it~ ~ influential aspects but
conceivably unmeasurable as well.
A number of methods exist that facilitate the monitoring of ANSactivity.
Systolic time intervals, ventricular ihotropic parameters, and stroke volumecan
all be monitored by intracardial impedance measurements. The pre-ejection
period (PEP) represents the time interval between the onset of ventricular
excitation and the opening of the semilunar valves and is also a measure of ANS
activity. Sympathetic activity acts to decrease the PEP duration, while the
parasyfiapathetics lengthen it (Schaldacl~, 1992).
In any Control system i~ is essential to determine what is being controlled and
what is doing the controlling. In the case of the cardiac system it is ex~ident that
the meanartedolar blood pressure is the factor being controlled in a closed loop
system. However,during exercise the baroreceptor operation is shut downand no

longer acts as a control factor. In addition, the MABP
is too difficult to measure
due ~to the force of blood flow inside the cardiac muscle eliminating it as a
measurable parameter for control. Another major controlling factor is the ANS
and any measurable signal representing ANSactivity may be used as a rate-
adaptive methodto meet the individual needs of the patient. The range in signal
recognition is opportunistic towards the development of an efficient control
process.
2.2.2 Sympathetic control
In examining the control system, we must consider the proper and most effective
parameters. These are no longer only cardiac output, medal pressure, and heart
rate. Metabolic alterations, chronotropic, inotropic, dromotropic, and
bathmotropic changes are reflex response mechanisms that neural components
effectively regulate. Of these, inotropic responses appear to provide the most
useful measure of sympathetic activity (Schaldach, 1992). The duration of the
pre-ejection period (PEP) facilitates this reasoning. However,we must ponder all
of the alternatives in order to gain enoughinsight towards the establishment of an
efficient Control parameter.
The sympathetic contribution to the overall operation of the heart appears to
be substantial. The vast amountof research that focuses on developing the proper
control pathwaysindicates that direct nervous control of myocardial effector cells
provides a specialized and extremely efficient regulatory action (Randall, 1973).
Hormonaland heterometric (intrinsic) controls are no longer beiieved to be the
major or predominant control mechanisms.The neural innervation specifically at
local control levels remains unknowndue to the intricate meshworkof the nerve
fibers. However,information obtained so far provides an optimistic foresight in
achieving this goal; characterization of local neuron pathways for control
purposes by using stimulation techniques. Until this occurs, specific control
options are limited.
Local sympathetic effects
A large amount of work performed on the sympathetic peripheral nerves

indicates a highly localized contractile response. Szentivanyi et al. (1967) discuss
the specific distribution of these nerve fibers to muscle cells resulting from this
specificity. It is widely knownthat stimulation of the cervical or stellate ganglion
results in a positive it~otropic response in the ventricles and other Surfaces of the
heart. Randall et al. (1984) also show that a more localized stimulation of the
sympathetic nerve fibers results in an increased localized response. The response
is found coming from a smaller surface area of myocardial tissue that contains
the distribution of individualized nerve attachments. Increasing the distance of the
stimulation site from the heart revealed an independent regulation of the localized
myocardial tissues. The .magnitude of the change in localized inotropic response
decreases with an increase in distance from the localized myocardial tissue. " i
It is apparent that differences exist betweenthe stimulation sites of the right
and left sympathetic nerve branches. Positive chronotropic effects .result from
increases~i n concentration of norepinephrine and stimulat{bn of the right and left
ansae subclavia, both anterior and posterior. The right sympathetic nerve elicits a
greater increase in heart rate than the left sympathetic nerve. Positive
chronotropic effects indicate the high probability of a sinus rhythm due to the
stellate excitation. The left side predominantlycauses an increase in contractile
force (positive inotropic effects). Stimulation of the stellate nerve can produce up
to a 35-45%increase in fight atrial inotropic activity. The left atria exhibits no
response to such stimulation. Hence, if a neural rate-adaptive pacemakeris used,
it wouldnot be effective to sense the left atria if stimulating or pacing the stellate
nerve. Subsequently, this is an important consideration for lead placement.
Another sympathetic nerve called the recurrent cardiac also elicits positive
inotropic activity in the atria and considerable positive inotropic activity in the
fight ventricle (Woolseyet al., 1967). Notice that the left ventricle does not show
such activity: Similar circumstances exist here that were just mentioned above.
The craniovagal nerve is believed to contain only parasympathetic fibers.
Hdwever,~.’Woolseyet al. (1967) measured inotropic, chronotropic, and blood
pressure increases in the fight and left atria after the administration of atropine,
an inhibitor, of parasympathetic neurotransmitter activity. Ventricular increases
up t030%were also obtained, thus indicating a strong likelihood that sympathetic
fibers are present in the craniovagalnerve.
Wodseyet al. (1967) also indicate that the left thoracic vagus and the
ventrolateral cardiac nerves contain no sympathetic innervation of either, the SA
or AVnode. This is a result of insignificant increases in heart rate or contraction
force upon~stimulation. They did find that norepinephdnecaused distinct positive
inotr0pic Changes throughout the myocardium. This is an extremely common
finding and considered well known. Therefore, the specificity of myocardial
innervation is regionally distinct as well as sensitive to electrode pulse location.
Bbiiefits of sympathetic mapping
Thelarge~ number of sympathetic inputs to the heart provide a network of

opportunities for coronary control. Overall, sympathetic nerves have an
~ mportant influence on the dynamic performance of the heart. Recently, the
eUkal ~fluences of myocardial functionality indicate a potential of overpowering
the traditi0nal length-tension mechanisms.
Intracardiac distribution of sympathetic nerves provides accessibility to
artificial stimulation for pacing purposes: Once the sympathetics attach to the
heart, their distribution is through subepicardial pathways awayfrom the point of
entry. The benefit of mappingthese subepicardial pathwaysis the ability to obtain
_positive inotropic responses from within the myocardial tissue. Thus,
coordination with certain time inte~alS such as th~ PEPor ventricular inotropic
p~ameter (VIP), mayprovide successful pacing control as *they do not interfere
with the natural Control pathways. In addition, the PEPis not affected by heart
rate. Therefore, there isno risk of any positive feedback.
Dynamic performance of sympathetic nerves
Observing the dynamic performance of sympathetic control provides information

regarding parameter control. Implications of sympathetic inputs to the heart for
overall control of stroke volume are common.Randall (1984) shows ventficular
function.curves that are different from work done by Starling. They differ in that
they show no decrease in ventricular performance after an initial increase as a
function of increasing filling pressure (end-diastolic volume). The work
26 DESIGN OF CARD~C PACEMAKERS
producedat a given filling pressure progressively increases with an increase ~ in

sympatheticactivity if the heart rate is maintainedconstant.
This process is extremely important to be able to analyze. Exercising,
biking, and walking (even up/down stairs in cases of the elderly) are actions
performedevery day that easily alter the frequency of sympathetic activity in the
cardiac nerves. This results in cardiac acceleration and compensation as
necessary. Hence, the provision of supplemental acceleratory factors is necessary
to augmentventricular filling~ Increased rates of tension developmentand faster
ejection velocity occur with shorter systolic periods while maintaining a constant
stroke volume.
Sympathetic impulses altering cardiac performance are highly predictable if
the other factors~modifying myocardial contractility are kept constant. Increases
in ventricular and aortic pressures are clearly evident upon sympathetic
stimulation. Interestingly, differences exist between left and fight sympathetic
stimuli..Left cardiac sympathetic stimuli exhibit increases in ventricular inotropie
effects without altering chrtnotropic activity. Whereas, right sympathetic
stimulation exhibits positive chronotropic effects in addition to the others.
Inotropic activity and: pressure~ changes
The increase in ventricular contraction strength, causes an increase in pressure

change amongsympathetically stimulated hearts (during physical activity or
emotional moments) compared to resting hearts. There is also a more rapid
decrease in intraventricular pressure during isovolumic relaxation in the
sympathetic stimulated case. The result of these inotropic actions is a shorter
systole duration in the ventricular myocardium. Also, the length of diastole
increases during each cardiac cycle. The time interval changes in conjuction with
sympathetic stimulation can be used as a control mechanismfor pacing. This is
another example of the greater benefits that monitoring inotropic activity can
have over chronotropic and dromotropic activities.
Positive inotropic activity causes the heart to empty faster and more
completely. These positive in0tropic effects produce subsequent medal pressure
pulses. The pulses are characterized by a greater systolic pressure rise than
diastolic, a larger rise in systolic ejection, and a shortened isometric contraction
period. These changes in ejection time can provide important information for
cardiac pacing and control.
Blood enters the ventricle from the atrium under a greater pressure and fills
more rapidly. For constant cardiac cycle lengths, the diastole period is lengthened
allowing for greater relaxation and filling of the ventficles~ These influences are
import,ant during high heart rates. They allow for a more efficient cardiac
function, postponing the occurrence of heart failure as muchas possible.
Decreasing the pressure in the carotid sinus increases the force of atrial
systole by increasing sympathetic activity and decreasing vagal activity to the
heart. Ventricular end-diastolic pressure and cardiac fiber length are varied by
these baroreceptor mechanisms. Changes in systemic pressures act to modify
ventricular inotropy, thus facilitating maximal operation under extreme
conditions.
Randall (1984) show~-that the heart is not completely dependent on the
node pacemakercells’to induce cardiac acceleration. Heart rates obtained before
and after SAnode excision are-not significantly different whenleft and right
stellate ganglion stimuli are administered. Thus, other supraventdcular sites such
as the Bachman’sbundle, inferior left atrium and coronary sinus contribute to the
overall control of heart rate. Positive chronotropic regulation occurring in
alternative locations is beneficial for engineering purposes. These locations
provide supplemental opportunities for sensing’ in order to improve cardiac
performance.
2.2.3 Parasympathetic control
,Parasympathetic control of the heart, often contributes inverse effects in

comparison to sympathetic influences. In this manner, it serves the humanbody
as an autoregulatory mechanism. However, experin~ents show that vagal
stimulation , can act as a positive influence towards cardiac performanceif proper
stimulation timing intervals are exhibited (Randall, 1984).
The extensiveness of parasympathetic control ranges from vagal brain
centers to peripheral aspects within the heart and coronary ~,essels. Inotropic,
chronotropic; and dromotropic effects of parasympathetic control need to be,well
understood for effective cardiac pacing. Descriptions of these influences provide
effective control options.
Influences in the SA node
Rosenblueth and Simeone(1934) indicate that the percent chronotropic change

induced by parasympathetic stimulation ,is independent of any sympathetic
activity. Thus, sympathetic, and parasympathetic influences on the SA :node are
independent of each other.- Warner and Cox (1962)report that the cardiac
response time to parasympathetic stimuli is faster than that of the sympathetics.
Hence, steady state response is obtainable within a few beats with parasympathetic
stimulation. :
Shortly-after a brief vagal stimulus (stimulus given to any of the
parasympathetic nerves), the Cell membrane becomes hyperpolarized. This
releases acetylcholine at the vagal endings :and diminishes the potassium
conductance of the autonomic cells, thereby producing the hyperpolarization.
These ~changes4n potassium concentration are responsible for a secondary
increase in chronotropic length. Also, this chronotropic deceleration indicates a
reduction~in the slope of SAnode potential during diastole (Randall, 1984). The
primary and secondary phases of deceleration are characteristically separated by
a~brief phase of cardiac acceleration. A dip exists between the S-T portion of the
cardiac potential curve, causing the brief acceleration period, During this phase,
the maximaldiastolic potential in the SAnode rises slightly to a less negative
value dueto an increase in sodiu~n conductance. As.vagal stimulation continues,
the ventricles but not the atria increase towardsa steady-state value.
Manyinvestigators show that :~a brief vagal stimuli can have about:a 15-s
influence on the heart rate. The-exact influence depends on the timing of the
stimuli in the cardiac cycle. For example, if the cervical vagus nerve is stimulated
once each cardiac cycle, the chronotropie response will depend,on the~ timing of
the stimuli~relative to the phase of the cardiac cycle. Simultaneous sympathetic
activity and the administrationof glucagon are two other factors that: can alter the
relationship.between the cycle phase and chronotropic response. Itispossible that
the engineer can use the different responses along the timing interval as a means
of control.
28 DESIGN OF CARDIAC~ PACEMAKERS
Vagal activity enhances the synchronization of SAnodalceIls whenrepetitive

brief bursts of pulses occur rather than equally spaced pulses during vagal
stimulation. As the stimulation frequency of repetitive pulses increase, the P-P
interval lengthens (Levy, 1970). These results confirm the negative chronotropic
effects of vagal stimuli. However,a linear relationship does not exist between
stimulation frequency and cycle length. In fact, a small change in stimulation
frequency can result in a large change in cardiac cycle length (Randall, 1984).
an increase in stimulation frequency occurs, a nonlinear decrease in cardiac cycle
length results. Wallick shows similar behavior in the AVnode (Wallick, 1979).
The innervation of the SA node occurs by the fight caudovagal and
craniovagal nerves and by the fight and left thoracic vagus nerves. They travel
along the superior vena tara, across the surface of the left superior atrium,
dorsal to the aorta, and enter the heart through the superior pulmonary veins.
There are other minor parasympathetic entrances to the heart. However,they are
severed during surgical entrance. Hariman (1980) shows that the clusters
pacemaker cells are in poor communication in the SA node, thus the conduction
velocity is slow betweenthe cell clusters. Repetitive ~vagal activity coordinates the
cell clusters:in the SAnode providing the aforementionedsynchronization.
Influences in the A V node
Both steady state and dynamiccontrol exist in vagus-regulated atrioventricular

conduction. The parasympathetic nerves depress AVconduction-or display what
are knownas negativedromotropic effects. Continuous supramaximal series of
vagal sti.mulation prolong AVconduction time (Ifisawa et al., 197,1).
Bradydysrhythmias with vadable:~degrees of heart block also resdt from-similar
continuous stimulation~ Irisawa et al. (1971) also show that the negative
dromotropic effects were linear as a function of stimulus intensity.~Block does
not occur until conduction time is lengthened about 60% from normal. ~The
degree of dromotropic change is also dependent on simultaneous slowing of the
SAnode (Martin, 1977). In contrast to the combinatorial effects found inthe
node, the AVnode experiences independent alterations by the two branches of the
autonomic nervous system.
Single stimuli or short bursts of stimuli .to the parasympathetics .are
preferred towards studying the dynamics of dromotropic effects. Levy shows, the
variability of single stimuli experiments whenthe heart rate is not controlled by
pacing (Randall, 1984). Whenthe heart rate is held constant by pacing, single
stimuli elongate the AVconduction time. As with the SAnode, the timing during
the phase of the cardiac cycle is important. As a decrease in.:the rate.~of
stimulation from the first stimuli occurs, the magnitude of the change in AV
conduction will. decrease. In addition, the magnitude of response to a single
stimuli is also dependentupon the atrial conductionrate.
The mechanismresponsible for these results remains uncertain. However,
Hoffman (1960) shows an increase in action potential duration when
conduction is lengthened due to electronic effects. In contrast, Levy (19,82)
proposes: that itis due to longer refractory periods of the AVconduction system
than’ the duration of the associated action potential (Randall, 1984): Hence,
conflicting reports of the mechanismmakeit difficult to characterize as a means
of cardiac control. If in fact longer refractory periods .are responsible for the
changes in conduction, control opportunities would exist based upon the timing of
the refractory periods.
Combined chronotropic and dromotropic influences
It is.rare and difficult to observe heart rate and conduction changes due to
parasympathetic stimuli. De Beer (1977) successfully measured the effects on
conduction using step changes in atrial pacing rate and parasympathetic
stimulation. The results show an exponential time course of AVconduction after
a step.change in atrial pacing. Maximalparasympathetic stimulation increases the
exponential time constant by a factor of four. These effects are independent of
sympatheticactivity. _
Levy and Martin (1977) also provide a focus on the interaction between the
effects of AVconduction and heart rate. In order to measure the combined
effects, stimulation to an unpaced and paced heart is necessary. Comparingthe
recordings of the heart rate and AVconduction time provides interesting results
from ~similar parasympathetic stimuli. Their results indicate considerable
nonlinear interactions betweenthe direct and indirect vagal effects.
Twomechanismscause these results. First, the vagal stimulus altered the
atrial activation patterns indicating a shift in the cardiac pacemakingsite. Second,
by increasing the cycle length, the depressive effects of acetylcholine on AV
conduction improve (De Beer, 1977). The details which remain unclear are the
interactions betweenthe heart rate and parasympatheticactivity.
Acetylcholinesignificantly reduces the atrial action potential. This results in
a reduction of the atrial refractory period upon parasympathetic stimulation
(Zipes, 1974), Acetylcholine effects on ventricular refractory periods remain
unclear. It is certain that acetylcholine antagonizes adrenergic effects. The dispute
exists over the degree of independent control of refractoriness by the
parasympathetics. Regardless, the lengthening of refractory periods is beneficial
in terminating arrhythmias whichare sustained by a reentrant circuit. Conduction
can be stopped if the refractory period is lengthened enough. This allows for the
interruption of the reentrant feedback that maintains the arrhythmia.
Control of inotropic effects
Vagal., stimuli also control inotropic effects both in the ventricle and atria. De
Geest (1965) successfully shows negative inotropic effects up to 25%in the
ventricles during maximalvagi stimulation. The regional distribution of efferent
vagal,fibers is highly specific. Theinotropic effects are stronger at the base of the
ventricle than at the apex. This is useful in determining the placement of
electrodes if pacing by neural rate-adaptive mechanismsfor maximaleffects.-
Atrial inotropic effects are more sensitive to vagal influences than
ventricular effects are. This is due to higher concentrations of cholinesterase and
richer intrinsic and extrinsic parasympatheticinnervations. These factors result in
more rapid onset and termination responses. Also, the diffusion distance of
acetylcholinein the atria is mucli smaller than in the ventricle. However;these
can not be independent factors as Priola et aL (1980) indicate. "The,ventricular
responses to intracoronary injections of acetylcholine have a slower onset and
slower time course than do the atrial responses" (Randall, 1984),
Ventrieular,standstill occurs: during vagal stimulation having an effect on
cardiac function:This is usually-followed by a brief period of positive
chronotropy. Overdrive suppression is the mechanismthat .accounts for these
events: The sinus rate is much faster than the ventrieular pacemakers- alone.
Therefore, continuous overdrive of the idioventricular pacemaker cells occurs
30 DESIGN OF-CARDIAC PACEMAKERS
during normal operation. Inhibition of only the atrial and AVjunctional

pacemakers would result from this mechanism, revealing the suppression of the
SAnode on the idioventricular pacemakers. Ventricular standstill results from
these events. Mostof the overdrive suppression in the atria is due to the release of
acetylcholine and the subsequent release of catecholamines. However, in the
ventricles, the presence of potassium outside the cell membranecauses an initial
decrease of the maximaldiastolic potential which is thenfollowed by an increase
above normal values. Onceventricular drive occurs, the potassium concentration
diminishes.
Thus, it is important to determine the proper timing of the burst of vagal
activity. Dependingon-.the phase impulse, contraction mayeither be completely
or negligibly depressed. Both the SA and AVnodal regions are sensitive to this
timing. Also, the ventricles and atria are .independently sensitive, to
parasympathetic stimuli. This is important for maximizingthe sensing roll of a-
pacemaker if neural ~rate-adaptive techniques are used, ~
2~2~4 Sympathetic.vagal interactions
Sympathetic, vagal interactions are quite important when considering coronary

control. Many of the parasympathetic and sympathetic, postganglionic nerve
endings lie close together in the walls of the heart. This results, in complex
interactions whenboth branches of the ANSare stimulated simultaneously. Levy
(1982) explains these interactions as accentuated antagonism. Under certain
circumstances, the presence of sympathetic activity enhancesthe inhibitory effects
of the parasympatheticactivity. . .¯
The mechanism regarding this unusual result is well understood. Both
presynaptic and postsynaptic levels influence these interactions. The synapse is
clearly between the postganglionic nerve ending and the effector cell. The
presynaptic mechanism involves the inhibition of norepinephrine re!ease
cholinergically from the postganglionic sympathetic nerve terminals. The
postsynaptic mechanism involves interactions .at the effector cells. These
interactions are governed by the cyclic nucleotides, cAMPand cGMP.Randall
(1984) shows, "Either the addition of cholinergic antagonists or concurrent
stimulation of the vagal - nerves resulted in the reduction of. norepinephrine
released by the standard sympathetic~ stimulation." The details of such mechanisms
are complex and not usefulin considering cardiac control. The most important
aspect of these combined interactions is the increase of vagal effects during
simultaneoussympathetic activity.-
2.2.5 Neural control of blood pressure
The maintenance of blood pressure is necessary for blood flow to the organs and
cells of the, body. Althoughit is~difficult to measurethis parameter as a means,of
cardiac control, it warrants focus as an influential factor in the cardiac control
system (Figure 2.2). The desired mean arterial blood pressure is 90 mmHg.
Baroreceptors located on strueturesin the heart such as the aortic arch and
carotid sinus sense the blood pressure. Pressures above 90 mm,Hgcause the
stretch receptors to expand and discharge moreaction potentials. If~the pressure
drops below 90,mmHg; the inverse occurs.-
The response to changes in the~ meanarterial blood pressure is complex,
involving several, areas of the brain. , Whenthe pressure rises above 90 mmHg;
CONTROL SYSTEMS OF ~THE HEART 31
the increased action potential activity in the fibers from baroreceptors activates a
cardiovascular regulatory center in the brain stem. This is the depressor center
andcauses a reduction in blood pressure (Figure 2.8). Neurons in the depressor
center,synapse with preganglionic sympathetic nerve cells to inhibit their
activation, This inhibition of sympathetic’nerve cells i~educes the heartYs force of
contraction and chronotropic activity. It also reduces the vasoconstriction of
blood vessels. The depressor center also activates the nucleus of the vagus,
another region of the brain stem which directly reduces heart rate. The net result
of these actions produces .a reduction in the meanarterial blood pressure. Figure
2.2 shows a complete pathway of events.
Heart
Higher
centers
center
Vessels
Rp
Figure 2.8 The hypothalamus control of MABP.CO, Pa, and Rp are cardiac output, arterial
pressure, and total peripheral,resistance respectively.
Decreases in blood pressure below 90 mmHg cause the baroreceptors to

activate the cardiovascular presser center, whichis .also located in the brain stem.
The ~pressor center increases blood pressure in response, to sudden,decreases such
as those due to hemorrhages, The presser cent~r~ stimulates, the~ preganglionic
sympathetic nerve cells to increase heart rate and inotropic effects. In addition,
blood vessels constrict. Hence, the net effect of these actions incre~es the mean
arterial blood pressure. For example, the hypothalamusaffects ~the ~egulation of
b!o,.0d pressure by, its excitatory inputs to the~., presser center and preganglionic
sympatheticneurons causing it ,to increase. These observations clearly indicate the
sympathetic control of peripheral resistance. ,~
2.3 HORMONAL CONTROL
The hypothalamus plays an important role in hormonal control. Indirectly,

activation of the dorsal hypothalamusincreases blood pressure, while the ventral
hypothalamus decreases blood pressure. These responses are commonlyknownas
the tight or flight responses. Figure 2,9oprovides the figh~f0r flight ~esponsesof
th~ h~othalan~usdirectly relat~a tO cardiac coi~trol. Tl~ese i~esponses.prepare the
body during momentsof stress whenblood vessels to.the skeletal muscles need to
dilate and positive chronotropic and inotropic effects are~neeessary. ¯
The’respoases are mediated by the activatioh of tht:~adr~nal gland. The
adrenal gland in turn secretes catecholamines (epi~nephdne and noi?epinephdne)
and glucocorticoids, The adrenal gland consists of’an outer area ,knownas the
adrenal cortex. This is where the production of glucoeorticoids occurs, ~The
central area is the adrenal medulla and is responsible for the secretion of the
catecholamines.-A direct connection of nerve fibers from the hypothalamusto the

interomedial lateral nuclei (IML) and from it to the cells in the medulla carries
out the release of catecholamines from the adrenal medulla. The :catecholamine-
secreting cells of the adrenal medulla function as postganglionic sympathetic cells.
Of the synthesizing cells in the adrenal medulla, 20%produce norepinephrine.
Changes in physiological fight or flight response

1. Increased blood pressure
2. Increased heart rate
3. Increased force of heart contraction
4. Increased heart conduction velocity
5. Increased depth and rate of ventilation
6. Shift of blood distribution towards skeletal muscle and heart
Figure2.9 Physiologicalresponsesby the hypothalamus

pertainingto.cardiac control.
The catecholamines that circulate in the blood affect the same receptors and
target organs as postganglionie nerve cells. However, their actions are not as
discrete as those generated by sympathetic nerve cells because they enter the
blood. Circulating catecholamines have positive inotropic and chronotropic
effects, causing the arteries of the skeletal and coronary musclesto dilate. The net
effect of these actions is to provide more blood to skeletal muscles, heart, and
brain and to reduce blood flow to the vegetative organs in the body.
Several factors influence the function of the adrenal medulla. Anindividual’s
emotional state is a primary factor. The hypothalamus operates as the brain
center for emotion. Stress-induced increases in nerve cell activity in the
hypothalamus activate preganglionic sympathetic neurons. These preganglionic
neurons then innervate and activate the adrenal medulla; Causing the secretion of
epinephrine and norepinephrine into the blood stream. Other factors such as the
extreme loss of blood, hypothermia; ~and hypoxia will also activate the adrenal
medulla, attempting to correct functional disorders and maintain a constant
internal environment.
For control purposes, it is:difficult to design a pacemaker that is rate-
adaptive to the kinetic turnover rate of catecholamines ~in the adrenal medulla.
However, they do play an integrative role in sympathetic activity, which can
cause secondaryeffects at the cardiac level.
2.4 REFERENCES
Cotten, M. 1972.Regulationof catecholamine metabolismin the sympatheticnervoussystem:

Pharmacol. Re~., 24: 165-166.
De Beer, E., Boom, H., and Naafs,B., 1977.Thecombined influenceof the stimulusfrequency
of the vagalnervesahdthe atrial stimulusinterval on the atdoventd~ular conductiontime.
Cakdiovasc.Res., 11: 47-54. ~
De-Geest,H:, Levy,’M,N., Zieske, H., and. Lipman,R., 1965~Depressionof ventricular
contractilityby stimulationof the vagusnerves.Circ. Res., 17: 222-235.
Hadman, R., Hof~man, B:; andNaylor,[~., 1980.Eleetde~activity fromthe sinus noderegionin
conscious dogs. Circ. Res., 47: 775-791. ~ ’ ": ’i ¯ ~
H0ff~anl~ B.~. and~ranefield,P.i ’1960;ElectrophySiotogy of the heart. New Y0rk.’McGraw~Hill.
Irisawa, H., Caldwell, W., and Wilson, M., 1973. Neural regulation of atrioventrieular
conduction~ Jap, J. Physiol., 224: 997-1005.
Levy, M.N. and Vassalle, M. (eds.) 1982. Excitation and neural control of the heart. Bethesda,
MD:AmericanPhysiology Society.
Levy,M. N., Iano, T., and Zieske, H., 1972.Effects of repetitive bursts of vagal activity on heart
rate. Circ. Res., 30: 286-295.
Little, R. C. (ed.) 1980. Physiblogyof atrial pacemakersand conductive tissues. MountKisko,
NY:Futura.
Martin, P., 1977. The influence of the parasympathetic nervous system on atdoventricular
conduction.Circ. Res., 41: 593-599.
Porter, R., 1974. The physiological basis of Starling’s law of the heart: A Ciba Foundation
symposium.NewYork: Associated Scientific.
Pdola, D. V., 1980.Intrinsic innervation of the canineheart. Effects on conductionin the atrium,
atrioventricular node, and proximalbundlebranch. Circ. Res., 47: 74-79.
Randall, W. C. (ed.) 1984, Nervous control of cardiovascular function. NewYork: Oxford
University Press.
Rhoades, R., and Pflanzer, R. 1992. Humanphysiology. NewYork: Saunders.
Rosenblueth,A. and Simeone,F. A. 1934. The interrelations of vagal and accelerator effects on
the cardiac rate. Am.J. Physiol., 110: 42-55.
Schaldach, M., 1992. Electrotherapyof the heart. NewYork: Springer-Verlag.
Sideman,S. and Beyar, R. (eds.) 1985. Simulation & control of the cardiac system (1, 2, 3).
Boca Raton, FL: CRCPress.
Strackee, J., and Westerhof,N. 1993. Thephysics of heart andcirculation. Philadelphia:Institute
of Physics Publishing.
Szentivanyi,M. J., and Pace, J. P. 1967. Localizedmyocardial,responses to stimulationof cardiac
¯ ~sympatheticnerves. Circ. Res., 21: 691-702.
vander," A. 1990. Humanphysiology. 5th Ed. NewYo~k: McGraw Hill.
Wallick, D.’W., and Levy, M. N., 1979. Effects of repetitive bursts of vagal activity .on
atrioventricular junctional rate in dogs. Am.J. Physiol., 237:275-281.
Warner,H. R. and Cox, A., 1962. A mathematicalmodelof heart rate control by sympatheticand
vagus ~fferent information. J. AppLPhysiol., 17: 349-355.
Wo01~y’,M. D., Brody, D. A., and Arzbaecher, R. C., 1967. Measurementof spontaneous
rn0rphologiealvariations in the electrocardiographic p-wave.Comp.in Biomed.Rest, 1: 265-
275.:
Zat].chetti,: A,, and Bartorelli, C. (eds.) 1970. Cardiovascularregulation in health and. disease.
Milan:Instituto di RicercheCardiovascolari.
Zipes, ’D., Mihalick, M., and Robbins,G., 1974. Effects of selective vagal and stellate ganglion
stimulationon atrial refractoriness. Cardiovasc.Res., 8: 647--655.
2.1 Explainthe difference betweenthe intrinsic and extrinsic pathwaysof cardiaccontrol.

2.2 Describe specifically howa decrease in arterial baroreceptor fh’ing wouldcause arterial
pressure changeto occur.
2.3 Explainhowthe Frank~-StarlingLawis used in cardiac pacing.
2.4 List the neurotransmitterand receptor for each branchof the ANS (all options).
2.5 Describewhythe postganglionicparasympatheticnerve cells haveshort axons.
2.6 Define the four basic effects of the ANSon cardiac performance.Be specific for both
sympatheticand parasympatheticdivisions and indicate whetheran increase or decrease is
inducedas a result.
2.7 Explainhowthe individualized responseof the peripheral distribution of sympatheticscan
be usedas a control optionof myoc~wdial’tissue contttactiOn.
2.8 Briefly explain the parasympatheticinnervatioia and control of the SAnodepacemaker cells.
2.9 Describe the sympathetic and parasympathetic nerves that mainly control cardiac
performance.
2.I0Explain theprocess ofoverdrivesuppression anditsControl ofventricular pacemakercells.
2.11Explain theprocess of"accentuatedantagonism"~
2.12Describetheneural effects
ofdecreasing catecholamine concentrations.
3
Mechanismsof Cardiac Arrhythmias

Geoffrey M. Weinberg
Be still my beating heart.

-- Poets, lovers, and musicians
As one can tell from the often repeated quote above, manypeople over the years
have placed a great deal of emphasis on the heart’s rhythm, but none have hadso
great an interest as those who suffer physical ailment: the cardiac patient.
Deviation in the :heart’s rhythm from physiologically normal behavior is often
associated with reduction in the quality of life--if: it doesn’t result in death.
Clearly, restoration of the heart’s natural rhythmis desirable. To meet this goal,
the physician or pacemaker engineer must first understand the underlying
mechanisms of ~he’ cardiac arrhythmia. This chapter provides a,,working
knowledgeof the causes for and mechanisms.of cardiac rhythm disturbances..
three . groups:,
¯ Cardiac arrhythmias
arrhythmias of classified’by
may be abnormal impulse
theirinitiation,
underlying abnormalities of
mechanisms into
impuls~ propagation, or simultaneous abnormalities of both impulse formation

and propagation. Figure 3.1 expands on this classification while providing the
basic outline of this chapter.
Mechanismsof cardiac arrhythmias

Abnormalities of impulse initiation
Automaticity
’Normal automaticity
Abnormal automaticity -
Triggered activity
Early afterdepolarizations
Delayed afterdepolarizations
Abnormalities of impulse conduction
Slowed conduction and block
Reentry’andunidirectional block
Ordered reentry
Randomreentry
Combinedabnormalities
Phase 4 block ~
Paras),stole
Figure3.1 Classification of cardiac arrhythmiasby mechanism. FromHoffman,B. F. and M.
R. Rosen.1981.Cellular mechanisms for cardiac arrhythmias.CirculationResearch,49: 1-
15.
MECHANISMS OF CARDIAC ARRHYTHMIAS 35
3.1-: AUTOMATICITY
A~tomaticity is the ability to generate a spontaneous action potential: Given the

proper conditions, this action potential can spread over the heart and initiate a
brat by the mechanismsdescribed in Chapter 1. All cardiac calls can display this
property, but, in a normal heart, most do not. Dependingon the location within
the he~a~ therefore, automaticity maybe may be classified as either normal or
abnormal, In certain cases, either normal or abnormal automaticity mayresult in
arrhythmias.
Sections 3.1.1 and 3.1.2 define normal and abnormal cardiac tissue. Section
3.1.3 describes the mechanisms for enforcing the normal sequence of cardiac
excitation, and sections 3.1.4 and 3.1.5 discuss the arrhythmias that resdt from
error in normal pacemaker control.
3.1.1 Normal automaticity
Cardiac cells that are normally automatic are called pacemakercells, and Figure
3.2 shows a hypothetical membrane potential recording. The cell does not
maintain a constant resting membranepotential but slowly depolarizes from the
maximaldiastolic potential until reaching the threshold. Uponreaching threshold,
the cell depolarizes rapidly; the result is initiation of an action potential. This
slow depolarization is called phase 4 depolarization or diastolic depolarization,
and Chapter 1 describes the mechanismsthat give rise to this behavior.
0 ~--~ ~--~ Threshold
Maximal diastolic potential Phase4 depolarization
Figure3.2 Hypotheticalmembrane potentials froma pacemaker cell. Thecell doesnot achievea

constantresting potential followingan actionpotential but repolarizesto a maximaldiastolic
potential andthenslowlydepolarizesuntil threshold.Thisslowdepolarizationis called phase4
depolarization
or diastolicdepolarization.
As described in Chapter 1, the dominant pacemaker of the heart is normally

the ~sinus node which fires at the rate of 60-100 beats per minute in the adult.
Other cells capable of spontaneous diastolic depolarization are found in the
specialized fibers of the atria, AVjunction, and the His-Purkinje system. Normal
rates in adults are 40-60 beats per minute in the AVjunction (AVnode and His
bundle) with more distant pacemakers generating spontaneous impulses-at even
lower rates. In vitro, peripheral Purkinje fibers usually beat at less than 12 beats
per minute (Lazzara, 1980).
,’ These nonsinus pacemakers are called latent or escape p~cemakers. Should
th’e sinus node fail, the next fastest pacemakerusually assumesthe role of pacing
th~heart..This secondary paCemake~’liesdormant (latent) untiI ~ the sinus node is
removed, allowing the latent pacemaker’s-rhythm to become visible. The
mechanismfor maintaining the pacemaker hierarchy will be discussed in section
3:1.3.
A pacemaker’s rate is determined by three factors:: the maximal diastolic

potential, the threshold potential, and the rate or slope of diastolic depolarization
(dd in Figure 3.3(a)). Figure 3.3(b) shows that a more negative maximaldiastolic
potential of the cell membranecauses depolarization over a greater voltage range;
therefore, it takes longer to reach threshold and the rate of impulse generation
slows (dashed curve). Conversely, a more positive maximal diastolic potential
increases the pacemakerrate. Figure 3.3(c) shows that a less negative threshold
potential results in an increased depolarization time to threshold, decreasing the
pacemaker rate, A more negative threshold potential, therefore, increases the
pacemaker impulse generation rate. Figure 3.3(d) shows the effect of changing
the rate of diastolic depolarization. Decreasing the rate (reducing the slope)
results in increased time to reach threshold which slows the pacemaker rate.
Increasing the slope results in an accelerated rate of impulse formation.
(a)
(b)
Tpl"-"
(c)
(d)
Figure3.3 (a) Normal pacemaker activity with spontaneousdiastolic depolarization(dd). (b)

Thepacemaker rate decreaseswith a morenegativemaximal diastolic potential. (c) Thepacemaker
rate decreaseswitha morepositivethresholdpotential. (at) The.pacemaker rate decreaseswitha
decreasein the slope of the diastolic depolarizationphase.From
Wit,A. L. andM.J. Janes. 1992.
Theventriculararrhythraiasof ischemiaandinfarction. Theelectrophysiologicalmechanisms.
FuturaPublishing.
3.1.2 Abnormal automaticity
Unlike the specialized pacemaker cells discussed above, normal atrial and
ventricular myocardial cells do not exhibit-automaticity, Workingatrial and
ventricular cells do not normally have spontaneous ~astolic depolarization nor do
they spontaneously.initiate impulses even.after .haviog been unstimulated ,for long
periods of time. Whena cell’s resting potential has been lowered below its
normal levels (made more, positive), however, spontaneous diastolic
depolarization mayoccur and cause repetitive impulse initiation. This is called
MEC~NISMS OF CARD~C ARRHYTHMIAS 37
depolarization-induced automaticity or abnormal automaticity. Figure 3~4 shows

this effect. Note that a reduced membranepotential is not the only criterion for
abnormal automaticity: if it were, the sinus node would have to be considered
abnormal. Thedistinction between normal arid abnormal automaticity is that the
latter occurs in cells which have undergone major changes from their normal
membran~ ~potentials (Wit and Rosen¢ 1989). Whether the result of experimental
investigations or cardiac disease, abnormal automaticity only occurs in cardiac
cells ~whenmajor reductions have occurred in the membranepotentials.
0 Musclefiber
potential
B
-80 mV
C
A A
Microelectrode
current
Figure3.4 Abnormal automaticityin normalcardiac tissue results fromchangingthe baseline

transmembrane potential. (A) Stimulatinga normalcardiac fiber showsthe appropriateaction
potential;(B)Nospontaneous actionpotentialsare initiated if the fiber is not stimulated.Raising
the membrane potential to -50 mVby a current appliedthrougha microelectrode (C) results
spontaneousactionpotentials. Thecardiactissues reverts to normalbehavioruponrestorationof
the normalmembrane potential. FromWaldo,A. L. andA. L. Wit. 1994.Mechanisms of cardiac
arrhythmiasandconductiondisturbances.In R. C. SchlantandR. W.Alexander (ed.) Theheart,
arteries, andveins. 8th ed. Withpermissionof McGraw-Hill, Inc.
Abnormalautomaticity is not confined to any specific latent pacemaker cell

type but can occur anywhere in the heart, and the required membranepotential
can vary from -70 to "30 mV. Cells in the Purkinje system, for example, which
exhibit~normal automaticity at large membranepotentials, also. show .abnormal
aut0maficity with reduced membranepotentials.
It is likely that several different ~aechanismscause abnormalautomaticity by
affecting pacemaker ion currents, but it is unclear which mechanism is
responsible in each of the different pathological conditions in which abnormal
automaticity occurs. One possible mechanismis a decrease in outward K+ current
which normally repolarizes the cell; incomplete repolarization could result in a
reduced maximal depolarization (Frame and Hoffman, 1984). The action
potential that results from abnormal automaticity may be the slow response type
which depend on slow, inward Ca2+ channels because the Na+- channels
responsible for the fast response are deactivated at reduced membranepotentials
(Waldoand Wit,. 1994).
A clinical example of abnormal automaticity is acceleratedidioventricular
rhythm caused by Purkinje cells in an ischemic region after myocardial infarct.
In this arrhythmia, normally quiet Purkinje fibers in the .damaged hemmuscle
suddenly assume control of the heartbeat. This may .be explained by examining
the results of the myocardial infarct. Occlusion of blood supply .tO a’ given
myocardial region results in insufficient oxygenation (ischemia)bringing about
rapid changes in the electrolytes of the tissue (Clark, 1992). Loss of + and
uptake ofNa+ (Ca2+, H+ and .water accumulate as well) within the ischemic cell-
result in a reduced membranepotential which can lead to automaticity. Note that
arrhythmias caused by abnormalautomaticity will not be visible unless the rate of
the abnormal focus is greater than the dominant pacemaker.
3.1.3 Pacemaker suppression
Normally the pacemaker of the heart, the sinus node maintains its dominanceby
depolarizing all other potential pacemakersbefore, they have.a chance to initiate a
beat. Figure 3.5 shows that the sinus node simply outpaces all other latent
pacemakers, resetting them before’ they reach threshold on their own. This is not
the only mechanism, however, by which the pacemaker hierarchy is enforced.,
Overdrive suppression and cell-to-,cell interactions also work to suppress latent
pacemakers.
Sinus node 0 ~.
B
Latent 0 ~_
pacemaker T ......
A
Overdrive 0 ....
suppression
T-~-
Figure3.5 Pacemaker suppression.(A) ThesinUs:nodeoutpacesthe latent pacemaker causing

to f’Lrebeforeit ~reaches
its threshold(T)spontaneously. If the sinus;node:is removed(B).andthere
is nooverdrivesuppression,the latent pae.emakerinitiates actionpotentialsat its naturally~slower
rate (longerperiod)(C), In the presenceof overdrivesuppression,diastolic depolarization
inhibited(D), Thishas b~nexaggerated f0r clarity.
Overdrive suppression
The~bottomtrace of Figure 3.5 indicates that not only ~-are the latent pacemakers
prevented fromreaching threshold~when being driven by the-sinus node, the
slope of their diastolic depolarization is actually inhibited. This effect is called
overdrive suppression and can be demonstrated by stimulating a Purkinje fibe!~.at
a rate of 90 impulses/min. It takes more than 20 s after :termination of~ the
stimulation before the first spontaneous impulse arises. The r~ate ~gradually
increases until normal intrinsic rates have been restored (Van Capelle, 1987).
The mechanism of overdrive~ suppression is ion-based. Na+ enters a cell
during each action potential, and, when. a pacemakercell is driven at rate faster
than its intrinsic rate, the intracellular concentration of Na+ +.
increases. The. Na
K+~ pumpactivity,increases in an attempt.to ~re8tore normal, transmembrane
electrolyte gradients. Since the pump-extrudes 3 Na+for each 2 K+ brought in,
there is a,,net positive~ current out of~the ~ell w~chhyperpolarizes th~membro~e
and- counteracts diasto!ic~depolarization (Frame~and- Hoffman~1984). Although=
this hyperpolarization is slight, only_ a few~extra millivolts are enoughto cause
slowing or even completf,, suspension of spontaneousdepolarization. ~
Chapter 1 indicates that the ion channels of the cardiac membraneare

voltage regulated; in fact, as the resting membranepotential is reduced, fewer
Na÷ channels are active. The amount of Na÷ .that enters the cell during
stimulation, therefore, is directly related to the resting membranepotential: small
+
membranepotentials result in few active Na+channels and small amounts of Na
+
entering the cell while large membrane potentials lead to many active Na
channels and a correspondingly large Na+ influx.
This voltage regulated Na+ influx has important effects on overdrive
suppression, Since abnormal automaticity occurs at reduced resting membrane
potentials, the amountof Na+ flowing in during each stimulation is reduced. The
activity of the Na+-K + pump, therefore, is not increased to the same degree that
occurred in the normal situation described above. Since the Na+-K+ pumpis
responsible for the overdrive effect, abnormal automaticity does not display the
magnitudeof overdrive suppression that occurs in normal automatic cells, In fact,
the amount of overdrive suppression of spontaneous diastolic depolarization is
directly related to the membrane potential at which the :automaticity is displayed.
Purkinje fibers with automaticity at depolarized potentials of -60 to -70 mVstill
exhibit some overdrive suppression, although less than those fibers with
automaficity at -90 mV.Purkinje fibers rarely show overdrive suppression at less
than -6OmV(Dangman and Hoffman, 1983).
Cell to cell interactions

Ele~t~0nic interaction between pacemaker cells and nonpacemakercells in the
surrounding myocardiummay also suppress subsidiary pacemakers. This may be
impofthnt in preventing AVnodal automaticity in which ’the AVnodal cells~
which have an intrinsic pacemaker rates nearly as fast as the sinus node’s, can
capture the heart. While these cells are not easily suppressed by overdrive, they
may be suppressed by current flowing between the node and the surrounding
atrium. Because non-pacemaking cells have rnembrane potentials that are more
negative than .the pacemaking cells, the resulting current flow between them
counteracts the diastolic depolarization, inhibiting automaticity (Wit and Rosen,
1989).
3.L4:Arrhythmias arising from the sinus node
Because the sinus node is the dominant pacemakerof the heart, alterations in its
rate maylead to an’hythmias. Sinus tachycardia results whenthe sinus node fires
at rates.in excess of 100 beats per minute. Conversely, sinus bradycardia occurs
whenthe, sinus node fires, at less than 60 beats ~per minute, .Note that ~either of
these two conditions maybe either normal or abnormal. Sinus.tachycardia can be
the appropriate response to external factors ~such as exercise, fever, or
hypotension. In well,conditioned athletes, sinus bradycardia can be the normal
response to exercise-increased parasympathetic stimulation.. In the average
person, however, sinus bradycardia more often reflects an abnormality of the
sinus node and escape pacemakers due to disease, .abnormalities in
parasympathetic stimulation, or outside factors such as drugs (Myerburg et al.,
1994)
3.1.5 Arrhythmias arising from ectopic pacemakers -~
ArrhythmiaS due to automaticity also result when the site of dominant
pacemakingshifts from the sinus node to any ectopic (nonsinus) pacemaker. Sinus
node dominance can be compromisedin several ways: sinus node suppression of

subsidiary pacemakers may be. reduced, inhibitory influences between
nonpacemaker and pacemaker cells may be removed, or secondary pacemakers
maybe enhancedso that they fire faster than the sinus node.
Removal of sinus inhibition
The normal sinus inhibition of subsidiary pacemakerscan be removedfor’several

reasons. Sinus node disease or increased parasympathetic activity may slow or
stop all sinus activity (Burne and Levy, 1988). The sinus impulse can also
blocked by exit block, sinoatrial block or AVblock (see section 3.3). On the
other hand, an ectopic pacemakermaybe protected from suppression if it is in a
region that exhibits entrance block. This type of block, however, must allow the
protected pacemaker’s impulses to propagate into the surrounding heart tissue
(unidirectional block is discussed in section 3.4). A protected pacemakeris called
a parasystolic focus, but since a parasystolic focus is the result of a combination
of abnormalities in impulse generation and conduction, it will be discussed later
in section 3.5.
Even with normal sinus rates, however, there may be little overdrive
suppression of pacemakers with abnormal automaticity. The result is-that even
temporary sinus pauses or a long sinus cycle time can allow an ectopic beat, even
if its rate is less than the sinus rate, to capture the heart for one or more beats~
Because of the effects of overdrive suppression, normally automatic pacemakers
wouldmost likely remain quiet during the relatively short sinus pauses. It is also
possible that the depolarized membranepotential at which abnormal auto~aficity
occurs might result in entrance block whichcould lead to parasystole.
Removal of cell to cell interactions
The second cause for ectopic rhythms is the removal of inhibitory influences of
the surrounding myocardium. Decreasing the coupling between latent pacemaker
cells and the surrounding nonpacemakertissue mayremove the inhibitory current
flow described in section 3.1.3 and allow the latent pacemakersto fire at their
intrinsic rates. Coupling can be reduced by fibrosis, which can separate
myocardial fibers, or by factors that increase the intracellular Ca2+levels (Waldo
and Wit, 1994). Fibrosis in the atrial portion of the AVjunction mayfreethe
nodal pacemakersfrom suppression by the atrial tissue and allow them to control
the ventricular rhythm. Purkinje fiber pacemakers may be separated from
damagedventdcular muscle cells during myocardial infarct allowing the Purkinje
fibers to fire at their normal, intrinsic rates (Waldoand Wit, 1994), Note that
someinhibition of the sinus node is still necessaryfor impulseinitiation to shift tO
uncoupled pacemaker sites because they still have slower intrinsic rhythms than
the sinus node and are subject to suppression:
Enhanced pacemaker activity
The third mechanism of shift to an ectopic rhythm is enhanced pacemaker

activity. Even during normal sinus rhythm, ~ enhanced latent pacemaker may
become active. One cause may be increased sympathetic nervoiis activity~
Sympathetic release of. norepinephrine enhances the: slope of diastolic
depolarization, increasing the rate .of pacemakercells. Sympathetic stimulation,
therefore, may allow the ectopic membranepotential to reach threshold before

the sinus node can suppress it, resulting in a premature impulse or automatic
rhythm (Winkle~ 1983). In the subacute phase of myocardial ischemia, increased
activity of the sympathetic nervous system mayenhance automaticity of Purkinje
fibers, al!gwing them to escape sinus node suppression (Waldoand Wit, 1994)..
. Enhancementof normally latent escape pacemaker activity may not require
sympathetic stimulation, however. First, flow of current between ~normal tissue
and partially depolarized cardiac tissue in an ischemic region might enhance
automaticity in the normal region (Katzung et al.; 1975). Secondly, inhibition
the electrogenic Na+-K+ pump due to hypoxia or ischemia decreases the
repolarization current, resulting in a net increase in inward current and possibly
in enhanced automaticity. Finally, stretching enhances normally latent
pacemakers. Stretch can induce rapid automatic rates in Purkinje fibers with
normal r maximaldiastolic potentials and mayoccur in areas after acute isChemia
or in ven~ricular aneurysms in hearts with healed infarcts. Stretch of the
ventricles can also induce arrhythmias in the intact heart although the origin of
the ~ectopic impulses has not yet been ide~ntified (Waldoand Wit, 1994).
A~with normal pacemaker cells, tile firing rate of an abnormally automatic
focus mayalso be raised above that of the sinus node, leading to arrhythmias~
This, of Course; presupposes that the abnormal focus is nor suppressed by the
Sinus n0de or blocked from exciting the surrounding myocardium. The firing
rate is directly related to the level of membranepotential. The greater the
depolarization, the faster the rate. Experimentshave shownfiring rates in muscle
and Purkinje fibers of 150 to 200 impulses per minute at membranepotentials
less than -50 mV,sometimeseven allowing the ectopic focus to capture the heart
(Waldo and Wit, 1994).
3.2 TRIGGERED RHYTHMS
Triggered rhythms are caused by afterdepoladzations which are oscillations in

the membranepotential, following an action potential. There are two types of
afterdepolarizations. One occurs.early during the repolarization of .the
membrane~ an early afterdepolarization, and the other occurs after the
repolarizati0n is complete or nearly’ complete, a delayed afterdepolarization.
Wheneither type is large enoughto reach threshold, the resulting action potential
is called a triggered action potential. Triggered activity, therefore, differs from
automaticity in, that ,at least one action potential (the trigger) comesbefore the
t~ai~iof, praises. Automatic rhythms can arise spontaneously following long
periods l~cking in electrical activity; whereas, . triggered rhythms cannot arise
spontaneously. Triggered activity will cause arrhythmias whenimpulse initiation
shifts from the sinus node to the triggered focus. For this, the rate of triggered
impulses .must be faster than the rate of the sinus node, an event that maybe
br0¢ght.about whenthe.sinus node has been slowed or "mhi’bited, whenit has been
blocked, or whenthe triggered focus is intrinsically faster,
Section 3.2.1 describes early afterdepoladzations while section 3.2.2
discusses delayed afterdepolarizations..Each section defines the characteristics of
the ~afterdepolarization, the mechanismsthat Causeit, the arrhythmias that result,
and the likely effects of electrical stimulation.
42 DESIGN OF CA~C PACEMAKERS
3.2.1 Early afterdepolarizations
Early afterdepolarizations (EADs) occur during repolarization of an action

potential initiated from a normal membranepotential. They appear as sudden
positive changes in membranepotential; instead of following thenormal course
of repolarization, the membranesuddenly shifts toward depolarization (Figure
3.6). As will be shownbelow, this shift can result from any factor that decreases
outward current (carded by +) or i ncreases t he i nward current ( carded b y N+
or Ca2+).
Characteristics of early afterdepolarizations
can also
Early occur during the rapid
afterdepolarizations often rep01adzation ~ Of
arise from the phaseof
eplatea~ 3 (see Figurepotential
an action 1.8). Figur
b’ut
3.6(a) shows a subthreshold EADfollowing an action potential,..but, in some

cases, the EADcan reach threshold and trigger a second action potential before
the repolarization of the first ~ has comp!ete~.iThis second acfiot~potential may
also i~ e ~foliowed by an EADwhich ca~, trigger another impulse., Figurei3.6(b)
shows tMs triggered rhythm. Note that the train of impulses.occurs~ .at ~h¢ ~educed
membranepotential at which the EADsoriginate. Also, uMike,au~maticiiy, thcrb
could have been no EADand no train of triggered potentialsmithout the initial
action potential.
0
-90 mV
(a) (b)
Figure3’.6 (a) Normaltransmembrane potential of a Purldnje fiber during propagationof

action potential followedby
a subthresholdearly afterdepolariZation(EAD) shown’by a dashed
line. (b) Normalactionpotentialpropagation
followedby twoEADS that reachthreshold-resulting
in ~two,morespgntaneous~tion potentials. FromWaldo,,A. L. and A. L; Wit. !994. Mechanisms
ofcardiacarrhythmiasandconduction~s ~tur~,.,~ces. In R. C. Sch!~tandR. W.~Alexander(ed.)
Theheart/arteries,andveins. 8th ed. Withpe~s~i0n of McGraw2:Hiil~ Inc.
The membranepotential at which’the triggered action potentials ~tccur

determines both the rate of tri:ggered activity and whether the triggered sequen~
can propagate ’into the surrounding tissue. At’the more positive .membrane
potential of the plateau, , the rate of triggered activity is morerapid ~than~ if the
EADoccurs later duriilg phase 3 repolarization. Triggered action .potentials
during plateau have sl0w upstrokes, however, and conduction of these action
potentials may~sometimesblock. "The faster upstrokes’of:the l~iterE:~s, al[ow
them to propagate more easily:: TheSe’ upstroke ’veltcity differences Can"be
explained:by~ the specific cUrrents fietbce at the time..~ ,L.’a~ phase 3 triggered
up~trokes arClikely tobe e~ed by the fast a~h’ng Na+ Ch~n~ls; but atplateau
and early~phase 3 iwhere the ~ Na+channds are~inaetivated, ’ action potentials are
most likely caused by the slower Ca2÷channels (Waldoand .Wit, 1994).
Mechanisms of early aflerdepolarizations and triggered rhythms
Early afterdepolarizations can occur in almost any type of cell but have been
most studied in cardiac Purkinje fibers and ventricular muscle calls. EADsand
triggered activity have been produced experimentally under a variety of
conditions, most causing marked delays in repolarization of heart cells. Slow
heart rate and drug toxicity are.:two examples (Bigger, 1994). Events that
increase inward current Componentsor decrease outward currents are expected to
result in conditions favorable to EADs(Wit and Rosen, 1989).
Whenthe rate of stimulation is markedly slowed, the outward current
+~
generated bythe Na+-K÷pumpis ~reduced, especially whenthe extracellular K
is lower than normal. At physiological ranges of cycle lengths (1000-700 ms),
EADshave occurred rarely in the studies on isolated cardiac fibers, but as cycle
lengths increase and repolarization is prolonged, EADsare more likely to occur.,
Another important observation is that a longer drive cycle results in a greater
number of impulses triggered by. EADS(Waldo and Wit, 1994)
Once EADshave reached a steady-state amplitude ata constant drive cycle
length, ,any event that shortens the drivecycle reduces the EADamplitude (Waldo
and Wit, 1994). A single .premature,~depolarization accelerates repolaxization and
will reduce the accompanyingEAD.Triggered activity, therefore, is not likely to
follow a premature stimulus. Treatments ~that shorten action potential ’duration
are therapeutic. Rapid pacing, increasing extracellular K+ concentration, and
drugs that increase K+ conductance tend to eliminate EADand triggered activity.
+
Note that each of these methods shares common property: increased K
conductance in heart muscle (Bigger, 1994).
Arrhythmias caused by early afterdepolarizations
Torsade de,pointes is a ventficular tachycardia characterized by alternating

positive and negative,QRS polarity and changing-amplitude .in an undulating
pattern over 5 to 20.beats. Because experimental arrhythmias that resemble
torsade de pointes are induced~ by agents known to induce early
afterdepolarizations, it is hypothesizedthat naturally occurring torsade de pointes
may sometimes be caused by EADs (Cranefield and Aronson,.. 1:988).
Antiarrhythmic drugs which prolong the ~duration of Purkinje~fiber.. action
potentials such as sotalol and quinidine can cause EADs.and triggered actiyity.-
Both drugs block the repolarizing K+ current, and the arrhythmias associated
with their use may also,result fromEADs(Waldo and Wit~ 1994).
As mentioned above, slowing the heart rate facilitates the appearance of
early afterdepolarizations; therefore, it.seems likely that sometachycardias that
follow bradyeardia are the result of EA_Dtriggered activity. It~has also been
suggested,’that~taehycardias in patients with long QTintervalsyndrome(in ~hich~
there maybe along action potential duration) maybe triggered (Wit ~andRosen~
1989).
Effects of :electrical stimulation on .early afterdepolarizations , ~
Overdrive stimulation :should prevent triggered~tachycardias since rapid

stimulation ,,usually decreases the dura~tion~of the action p~tential~ and; as
mentionedabove, any: event whichshortens the drive cycle length tends :to reduce
EADamplitude. On the other hand, once overdrive stimulation is stopped, the
44 DESIGN OF. CARDIAC PACEMAKERS
tachycardia mayreappear asthe action potential duration lengthens. Like cells

with abnormal automaticity, overdrive does not easily terminate or suppress
tachyarrhythmias resulting from EADs(Wit and Rosen, 1989).
3.2.2 Delayed afterdepolarizations
Delayed afterdepolarizations (DADs)are small transient depolarizations (about

10 mV)that occur shortly after the maximaldiastolic voltage has been achieved
during repolarization of an action potential (Figure 3.7, solid line).~Under
normal conditions, cells in the coronary sinus and in the AVvalves can present
DADs, ,but under abnormal conditions, many cell types can generate them
(Bigger, 1994).
I tt I t
t
-90 mV ":-: "rk~X-~

~
Figure3.7 Thesolid line showsa transmembrane action potential followedby a subthresh0td
delayedafterdepolarization(DAD). Thedashedtrace showsthe result if the DADreaehes
threshold
and triggers extra action potentials. FromWaldo,A. L. andA. L. Wit. 1994.Mechanisms of
cardiacarrhythmias andconductiondisturbances.In R. C. SehlantandR. W.Alexander (ed.) The
heart, arteries, andveins. 8th ed. Withpermi~Siori
of McGraw-Hill,Inc.
Characteristics of delayed afterdepolarizations
Triggered impulses occur whenDADsreach the threshold potential for activation

of the upstroke of the action potential (Figure 3.7, dashed line). ’Each triggered
action potential may also be followed by a DADthat may or may not reach
threshold.: If it doesn’t~ no additionalaction potentials are evoked. Often, the first
triggered action potential is followed by a short or long train of triggered action
potentials. Note that the rising phase of the afterdepolarization maymerge with
upstroke of the evoked action potential. The resulting transmembranepotential
-recording may look like diastolic depolarization of a normal~ automatic:
paeemaker~ :As with early afterdepolarizations, however, cells with DAD~
triggered activity are unable to generate an action potential spontaneously. They
requirea stimulating action potential to initiate rhythmicactivity.
Mechanisms of delayed aflerdepolarizations and triggered rhythms
Delayed afterdepolarizations usually occur in a variety of conditions that feature~

an increase inmyoplasm and sarcoplasmic reticulum (SR) levels of.Ca 2+ above
normal ,levels. The SR is a specialized: tubule system that surrounds the muscle
fibers and stores Ca2+needed for~mnscle-contraction. During an,action potential;
Ca2+ flows into the call. This initial rapid change of Ca2+ levels causes the SR to
release even more Ca2+, enhancing contraction of the cell. Repolarization of the
membranethen induces the SR to sequester the freeCa2+, allowing relaxation. If
intracellular Ca2+ is very high or if catecholamines or cyclic adenosine
monop_hgsphate are. present (both of which enh~, agce,sarcoplasmic uptake of Ca2+),
the Ca2~levels ,in ,the SRmayrise to a critical level, .resulting in a secondrelease
of Ca2a", ~This secondary release of Ca2+ results ina oscillatory, transient inward
(TI) current across the membranewhich is responsible for the DAD,Howthe
second release of Ca2+ causes the TI is still unclear, however. After one or more
afterdepolarizations, intracellular Ca2+ levels drop because Na+-Ca 2+ exchange
extrudes Ca 2+, and the stops oscillating. (Waldo and Wit,
1994).
One cause of DAD-tri is digitalis toxicity. One possible
mechanismis that di pumpresulting in a measurable
+
increase in Na +
doses, The increased intracellular Na
concentrations decrease the Na+ gradient that drives the Na+-Ca2+ exchange,
reducing Ca2+ extrusion a~d~increasing intracellular Ca2+ levels. The result is a
net inward Na+ current which C~ lead to DADs(Cranefield and Aronson, 1988).
Catecholamines are also an accepted cause of DADs.They mayc~iuse delayed
afterdepolarizations by increasing the slow inward Ca2+ current as well as
enhancing sarcoplasmic uptake (Wit and Rosen, 1989)~
Delayed afterdepolarizations and triggered activity mayalso occur without
pharmacological agents, catecholamines, or increased levels of Ca2+. Triggerable
fibers have been found in animal models and in apparently normal humanatrial
myocardial cells (Wit and Rosen, 1989).
Because the transient inward current that causes delayed afterdepolarizations
is at its maximum around -60 mV,the possibility of triggered activity depends on
the level of the membranepotential. In digitalis toxic Purkinje fibers, there is a
i:ahge of maximaldiastolic potentials near-70 mVok, er which the amplitude of
DADsis greatest (Wasserstrom and Ferrier. 1981). WhenDADsoccurat these
favorable membranepotentials, any action that hyperpolarizes ordepolarizes the
membrane tends to reduce the amplitude of the DADsand suppress any DAD--
triggered rhythms (Waldo and Wit, 1994). Simil~ly, if there are no DADsin the
presence of digitalis and the membraneis outside this Wiridow, any ~/ction that
iJrings the’membrane into this range often induces DADs. A similar DAD
dependende on membrane potential has been shown in atrial fibers of the
coronary sinus and Purkinje fibers from infarcts (Waldoand Wit, 1994).
: Delayed afterdepolarization amplitude is affected by the duration of the
action potential. Longer action potentials allow more Ca2+ to enter the cell,
favoring DADs.Drugs such as quinidine, which prolong action potentials (APs),
may increase DADamplitude while those such as lidocaine~ which shorten the
action potential duration, maydecrease DADamplitude (Waldo and Wit, 1994).
Delayed afterdepolarization amplitude also depends on the number of action
potentials preceding it. After a period of inactivity, a single APwill result in a
smallDADor noneat all. With continued stimulation, the DADsincrease in
amplitude and triggered rhythms may occur (Waldo and Wit, 1994).
The period of stimulation~ however, also affects DADamplitude; triggered
activity can arise if this cycle length is ~?educedbelowsome~Cridcal value. Figure
3.8 shows this cycle length dependencyin an atrial fiber located in the canine
~oronary sinus. Stimulation with a cycle period of 2000 ms resulted in a 5 mV
DAD f611owingthe last stimulated action potentialS. In the center, stimulating the
c611s every 1500 ms led toa final afterdep~larization amplitude of 15 inV. On the
right, a drive cycle period of 1200 ms ended in triggered activity with a 20 mV
¯ ~kDjust before initiation. A decrease in the len~ ~f even~ single driVe cycle,
~ premature impulse for example, results in an increase in the amplitude of the
DAD that follows the premature beat, and arrhythmias caused .by DADscan be
eXpeCtedtb be initiated by aspontaneous or paced increase in heart rate (Wit and
Cr~mefield, 1977).
7500 msec
------’----4
50 mV
2000 1500 1200
Figure 3.8 Effects of stimulation frequency on delayed afterdepol~ization amplitude.

Decreasingthe period(increasingthe frequehcy)r~sults in in~reascdD~amplitudes.Reproduced
with permissionfromWit, A. L. andP. F. CranefiCld.Triggered.and-autOmaticactivity in the
canine coronarysinus. CirculationResearch,41: 435-,445, Copyright1977AmericanHeart
Association.
" Th.~se delayed afterdepolarization mechanismshave an interesting effect on

triggered rhythms caused by delayed afterdepolarizations; they often terminate
spontaneously. In triggered rhythms induced .bycatecholamines, the rate
gradually slows until ~e activity stops. This sP0nmne0us
temfin’. ~ation is cau~sed, in
part, by an~ increasein the intracellular Na+ that results from the increased
numbe r of actaon potenttals dur~,ng the tachycardia. The actavlty of the Na+-K
pumpincreases to return the ~ell to normal ion. concentrations, but, as with
automatic cells, the pumpgenerates a net outwardcurrent, whichincreaseS. ¯ the
maximal diastolic potential and pushes the membrane out of ~el"windo~’,
conducive to DADs.A sufficient increase in pumpactivity will tei:minate die
~iggered rhythm (Wit and Rosen, 1989).
¯ ..~Spontaneous :termination in a digitalis induced rhythm, on the ot~er h~and~
probably
n operates by a different mechanism.Termination in characterized by~a
acceleration in rate and a decrease inaction potential, amplitude and
depolarizafibn. Sin~e digitalis inhibits Na+-K+pump,termination is’ likely to be
i~elated to the Na+ or Ca2+ buildup in the cell following the increase in rate. ~The
ionic buildu p may.decrease the gradients leading t0 ~ADs~until ~ey ~an no
longer reach threshold and trigger action p0’tentials (Wit a.hd Rosen, 1989)r ¯
Arrhythmias caused, by delayed afterdepo.~arizations
Delayed afterdepolarizations can reach threshold: to "cauSe triggered action

potentials especi~ly if the rate of stimulation is fas~ enough. Digitalis induced
ventricular arrhytfimias can be irlitihted "by pacing at "rapid"~ates, and as toxicity
increases, the DAD train iner6~tses~ Inttoducd6n 0f cateCholaminesinto the
coronary sinus causes atrial tachycardia with the characteristics of triggered
a~tivityl (Malfatto et aL, ~1988)~ ~omenaturally occurring atrial t~chy~dia~
induce~i by the sympathetic nervous system; therefore, are probably c~Used by
DADs. Ventricul’~r’muscle and Purkinje fi~s can also develop I~sqh~th~
presence Of catecholamines, and sympathetic sfilnulation mayc~ii~se fio~6:bf~e
ventricular arrhythmias that accompanyexercise, ischemia, or infarction (Waldo
and Wit, 1994).
Effects of electrical stimulation on delayed afterdepolarizations
As mentioned above, an increase in heart rate ~or a premature stimulus may

im’tiate a triggered tachycardia. Paradoxically~ overdrive or a premature stimulus
mayalso terminat~ triggered tachycardias due to delayed afterdepolarizations:
During abdef period of overdrive which is only moderately faster than the
triggered rate, the maximal diastolic potential often decreases (becomes ~less
negative)~ Following the overdrive, the triggered rhythm mayactually be faster
than it was before, possibly because of the reduced maximalpotential. The result
is acceleration whichis hardly the desired effect. The accelerated rate then slows.
and the maximal~diastolicpotential increases to pre-overdrive levels.
If the overdrive stimulation is increased to a critical rate or duration,
however, termination of the rhythm may occur. For example, following
overdrive suppression in a catecholamine dependent triggered rhythm, the
maximaldiastolic potential becomesmore negative and the rate slows until the
activity stops. This is brought about by increased Na+-K+pump, activity.
÷
Overdrive increases the numberof action potentials per second,~ and, since Na
flows into the cell with each action potential, the total concentration of
intracellular Na+ also increases. The Na+-K÷pumpincreases to compensate and
generates a net outward current which tends to hyperpolarize the cell.
Termination occurs whenthe membranepotential-is pushed out of the windowof
value~.favorable to DADs. This is similar to the mechanism described for
spontaneous termination (Wit and Rosen,. 1989).
Overdrive stimulation also terminates digitalis induced rhythms, but as
described during the discussion of spontaneous termination, the mechanism~does
not depend on increased Na+-K ÷ pumpactivity. It is likely ~ that termination
depends on accumulation of Na+ or Ca2+ in the cell resulting from overdrive
(Wit and Rosen, 1989).
A single premature stimulus mayalso end triggered activity. This stimulus is
followed by an increased hyperpolarization. Because thenext
~ depolarization starts
from a morenegative potential, it maynot be able to reach~ threshold, terminating
the .tachycardia. A premature stimulus is more likely, to terminate a triggered
tachycardia if a period of overdrive precedes it (Wit and Rosen, 1989).
3.3 SLOWED CONDUCTION AND BLOCK
Thus far, the mechanismsfor arrhythmia have been defects in impulse formation.
Now,abnormalities of impulse conduction will be examined.
Delay of cardiac impulses can occur anywhere in the heart, and it can be
general or localized. Therapy witha typic IC antiarrhythmic ~g, fo~ exam~.ple,
leads to delay in all cardiac tissue, while tissue injured in infarction mayconduct
impulses slowly even though the surrounding tissue conducts normally. On the
other hand, conduction delay maybe normal: one example is the ~increased~time
for AVnodal conduction of a premature beat. Conduction delay Will play alarg~
role in tachycardias Causedby reentry (section 3.4)
If the delay is extreme, the impulse maybe blocked. There are .two ~forms of
block: bidirectional and unidirectional. Because unidirectional block is so
intimately~ tied with reentry, discussion of this will be also postponeduntil section
3.4.
3.3.1 Conduction delay
Areas of slow conduction maybe anatomically normal; the AVnode, for example
introduces an electrical delay between the atria and ventricles that allows
ventricles to fill completely before theycontract. Areas of slow conduction, on
the other hand, mayexist where they are not normally expected. This latter type
of Slow conductionis not present during normal sinus rhythm but is functionally
present during an arrhythmia. Tissue. damaged by myocardial infarct is one
example.
There are several causes of slow conduction that maylead to arrhythmias:
changes in membrane current, changes in the cable properties of the cell,
anisotropy, or changes in gap junction resistance.
Changes in current
The speed and amplitude of depolarization in cardiac fibers is governed by the

membranepotential of the tissue. Changes from normal .membrane potentials,
therefore; mayresult in slowed conduction and arrhythmias.
Recall that the fast Na+ channels are. responsible for the speed of the action
potential upstroke, Because Na+ channels are voltage gated, the fraction of open
channels depends largely on the membranepotential., level at which the cell is
activated. Immediately after depolarization, the’~Na+ channels: are inactivated
because of the positive membranepotential. During repolarization, progressive
numbersof channels are reactivated. If the cellisstimulated before repolarization
has completed, not all the channels will be able to pass the Na+ ions. The inward
Na+, current and the resulting speed and amplitude of activation are reduced
becausenot all the channels are active.
500 v/s 200 v/s 100 v/s 50 v/s
-90 mV -80 mV -70 mV -60 mV
-90 mY
Figu~?3.9. Therelationship between actionpotentialslewrate. vs. membr.ane potentialat the time
of actwatlon. (a) Slewrate decreasesw~threducedmembrane potentials. (b) Theeffect
prematureStimulusoncardiactissue that has previouslybeenactivated.Thedashedline at stimulus
Aghowsthat the rate of depolarizationis reducedbecausea stimulus occurredat a reduced
membranepotential.. Apremature stimulusat Bresults in a fastexaetionpotentialthanthe stimulus
at. A,but it is not fully normalbecausethe tissue has not fully repolarized.FromWaldo,A. L. and
A. L. Wit. 1994. Mechanisms of cardiac arrhythmias~andconductiondisturbances. In R. C.
SchlantandR. W.Alexander(ed.) Theheart, "arteries, and:~,eins.Sthed. Withpermissionof
McGraw-Hill; Inc.
Figure 3.9(a) shows that the action potential slew rate decreases with
decreasing resting membranepotentials. Figure 3.9(b) shows that the amplitude
MECHANISMS ~OF CA~C AR~THMIAS 49
of the resulting action potential depends on the degree to which the cell has
repolarized (greater repolarization results in increased amplitude of the second
action potential). Because these impulses are conducted by partially inactivated
fast Na+ channels, they are called depressed fast responses.
There is also a slow response inward current carried by Ca2+ channels,
which contributes to the upstroke.of the action potential. The threshold for the
Ca2÷ channels is about-30 to -40 mVcompared ÷
with the -70 mVof the fast Na
channels; therefore, this current inactivates muchmore slowly. In cells with
resting membranepotentials smaller than -60 mV(when membraneconductance
is very low or whencatecholamines are present) this normally weak current may
produce .action potentials that propagate slowly and are prone to block. Slow
response action potentials can occur in diseased cardiac fibers but can also occur
in some .normal tissue of the heart such as the cells of the sinus and AVnodes
where:the maximal diastolic potential is normally smaller than -70 mV(Waldo
and Wit, 1994).
Changes in cable properties
Stowedconductioncan also be explained in terms more familiar to the engineer:

cardiac fibers can be modeledas cylindrical cables.
The electrotonic spread of any change in membranepotential is determined
by the.~’length~ constant"of the cell. In a cylindrical cable of uniform properties,
this length.constant, ~, is given by
Membrane Resistance
Internal + External Resistance (3.1)
Physically, a change in potential on the fiber Will cause the potential one
length constant away to change by about lie ~of the applied potential. With a
greater length constant, a point fUrther out along the. fiber can be stimulated. The
Velocity of conduction, therefore, increases with,an increasing 2L (the distance
covered per unit time is greater). If all other influences are held constant, the
conduction velocity will increase when the membraneresistance increases and
decrease wheneither or both of the longitudinal resistances increase (Cranefield
and Aronson, 1988):
The length constant typically ranges from 0.5 to 225 mm,meaning that a
100 mVaction potential will cause cardiac tissue two ~,away (1 to 5 mm)
depolarize to threshold. In a passive cable, a 100-mV impulse causes a
depolarization at two ~, of 100/e2 or approximately !3.5 inV. Cardiac fibers are
not passive, however. The effective length constant is reduced during .the
upstroke of an action potential’ in an excitable fiber so that the actual ~voltages
experienced at two length constants will be somewhatdifferent (Cranefield and
Aronson, 1988).
The external longitudinal resistance (resistance to current flow in the
extracellular space) can rise significantly if the extracellular space is reduced
during swelling of injured cells, This swelling mayoccur, during ischemia; in
fact,..., merely~interruptingperfusion,, which. ~. causes. . a loss of "stiffness" in the
tissUes, can also cause an increase in intracellular resistance. Ischemia mayalso
me the lntracellular longitudinal resmtance by uncouphngat the location of
the intercalated discs or ischemia may. lower membraneresistance by increasing
external K+ (Cranefield and Aronson, 1988).
A nisotropy
The cable properties just mentioned also form the basis of cardiac anisotropy:
conduction velocity depends on the direction in which it is being measured.
During conduction, axial current flows from one cell to the adjacent cell through
the gap junctions of the intercalated disks. These disks form a major source of
resistance along~the fiber bundle. The structure of the myocardiumthat governs
placement of these disks, therefore, has a large effect on fiber resistance and
conduction.
Muscle fibers are arranged in unit bundles in which cells are tightly
connected with each other. Each unit bundle is connected with others but the
connections only occur in a lateral direction at intervals.of 100-150 #m (Waldo
and Wit, 1994). The result is that the myocardiumis better connected along the
long axis because of the low frequency of connections between the unit bundles
and the high frequency of connection within the bundle itself. The result is a
reduced axial resistivity relative to a transverse direction and a corresponding
difference in conduction velocity predicted by cable theory.
There are two types of anisotropy: uniform and nonuniform. Uniform
anisotropy (Figure 3.10(a)) is characterized by an advancing wavefront that
smoothin all directions (longitudinal and transverse .to fiber-direction). In one
experiment in normal.septal muscle, conduction in the longitudinal direction was
found to be 0~51 rrds and in the transverse ~ direction 0.17 rrds (Spach and Dolber~
1985). As the direction of propagation changed between the two, the conduction
velocity changed monotonicly (Waldo and Wit, 1994).
Intercalated disks Fibrous ingrowth
M-usclefib-er I uscle
fiber\
Longitudinal Longitudinal
axis axis
(a) Uniform anisotropy (b) Nonuniform anisotropy
Figure3.10Anisotropy.Thecardiacfibers are arrangedparallel to eachother. (a) In fiber~wi~

uniformanisotropy,intercalateddisks connectthe cells Withineachfiber andthe cells between
fibers. Becausethe disks joiningcells withinthe fiber are broadandnumerous,
resistivity in the
longitudinaldirection is ,low. Fewerconnectionsbetweenfibers result in a highertransverse
resistivity. (b) Nonuniform anisotropic fibers lack connectionsbetweenfibers, resulting n
increasedtransverseresistance.
Cardiac tissue exhibiting nonuniform anisotropy is tightly coupled

electrically in the longitudinal :direction but not in the transverse direction: there
are areas in which the connections bdtWeenparallel fibers are absent (Figure
3.10(b)). As a result, propagation inthe ~ansverse direction is interrupted so that
the action potential must takta highly irregular, zig-zag conduction path (Spach
and Dolber, 1986). There is also a nonuniformtransition in conduction velocities
between the two directions (normal anisotropic has a continuum of velocities
MECHANISMS~OF CARDIAC ARRHYTHMIAS 51
between the two perpendicular directions). In a study using pectinate muscles

from older patients, the meanfast velocity was 0.69 m/s and slow velocity was
0:07 m/s, a ratio of nearly 10 despite the normal resting potential and fast action
potential of the atrial cells (Waldoand .Wit, 1994).
Nonuniform anisotropic properties can arise when the muscle bundles
become separated transversely by the ingrowth of fibrous tissue. These
longitudinally oriented insulating boundaries prevent connections,-thereby
increasing the resistance. This can occur with age or with disease. In healing
infarcts, fibrosis can separate the surviving muscle bundles in the epicardium
over ~the infarct, reducing side-to-side connections. Measurements show
conduction to be about four times faster in the longitudinal direction (Bigger,
1994).
Anisotropy is not limited to. the tissue level, however. On~a macroscopic
scale anisotropy can influence conduction at sites where bundles of cardiac fibers
come together. Marked slowing can occur at fiber junctions where there is an
abrupt changeof fiber direction. As the fibers cometogether, they are less likely
to be oriented longitudinally: transverse conduction mayresult as the impulse
passes from one fiber to the next. The result is increased axial resistance
(Gardner et al., 1984). Cable-like structures without extensive branching, such
theHis bundle, bundle branches, or Purkinje fibers, conduct ~ faster and with a
greater safety factor than ~tissues With extensive three-dimensional branching
(Bigger, ’1994):
Changes in gap junction resistance
An inc, rease in intracellular-resistance may also’result from~increased gap

junction resistance (iOns can not moveas freely). Computermodeling showedthat
conduction velocity cotfld be decreaseddramatically by increasing disk resistanee;
Decremental conduction and block result (Rudy. and Quan, 1987).
Intracellular Ca2+ may be the most important influence on gap junction
resistance’in pathological, situations. A significantrise in intracellular Ca2+
increases, resistance to current flow through the junctions and eventually leads to
phyg:iological uncoupling Of the calls (Waldoand Wit, 1994). Intracellular 2+
can rise with ischemia.
Delay with normal conduction
Cardiac signal conduction maybeslowed even though Conduction velocities along

the route are normal. An increased path length .’explains what would appear to be
a paradoxical situation. For example, a lesion or a defect along the conduction
route from the sinus node to the AVnode would force the impulse to take the
longer detour. The impulse is delayed because it has to travel a greater distance,
not because it is movingslowly.
3.3.2 Conduction block
Block of cardiac impulses can occur under several different scenarios. An

impulse mayarrive, at ~tissue that is-unexcitable because the-tissue is still
refractory after a recent depolarization or because the tissue isabnormally
depolarized. Block mayoccur because the strength of the propagating wavefront
is insufficient despite the fact that tissue is fully excitable (decrementalconduction
DESIGN OF CA~IAC PACEMAKERS
and block). It mayalso occur because tissue is intrinsically unable to conduct

(scar tissue from prior infarct or surgical incision).
If block does occur, arrhythmias may arise in several different ways.
Normally, if the sinus impulse fails to propagate to right atrium (sinus node exit
block or sinoatrial block), an ectopic-pacemakerwill take control of the heart. If
the AVconduction system is blocked so that the ventricles are not stimulated at an
appropriate rate, an ectopic pacemakerdistal to that block mayassumecontrol of
pacemaking. Under some conditions, .however, an escape pacemaker may not
arise quickly enough’or at a clinically significant rate. A period of asystole (an
absence of electrical or mechanical activity), marked bradycardia or both may
appear, Block mayalso appear in one of the bundle branches.
The blocks discussed above prevent conduction of impulses in both
directions. A special form. of block, unidirectional block, will be discussed in
detail in the next section.
3.4 REENTRY AND UNIDIRECTIONAL BLOCK
Normally, the action ,potential from the sinus node dies out after orderly
depolarization of the atria, AVconduction system, and the ventricles. The
impulse does not usually conduct backwardsbecause the tissue just stimulated~is
refractory and, therefore, unable to generate a second action potential. As a
result, the normal heart must wait for new sinus pulse for each subsequent heart
beat.
Reentry occurs whenthe action potential does not die out but continues, to
propagate and-reactivate the heart. Almost all clinically, important
tachyarrhythmias are due to reentry (Waldo and .Wit~ 1994). Reentry can occur
almost anywhere in the heartand can assume manysizes and shapes.
Section 3.4.1 explains the concept of reentry by example. Section J3~4.2
outlines reentry classifications. Section 3.4.3 explains the general requirements
for .reentry. while section 3.4.4: describes in detail one of the most important
requirements: unidirectional block. Finally, section 3.4;5 introduces reflection: a
special case of reentry.
3.4.1 Circus reentry example
Reentry was first demonstrated in 1906 by Mayer in the excitable ring of a

jellyfish, and .his experiment serves as a convenient illustration of the basic
properties of reentry.
Figure 3.11 shows Mayer’s experiment. At the center of the loop of jellyfish
is a hole which serves as a central area of block around which the reentrant wave
can circulate. Figure 3.11(a) shows the normal case. Stimulation at a single point
results in two wavefronts that circulate around the ring in opposite directions.
Whenthey reach each other, they are extinguished because the cells on either side
are refractory.
Figure 3.11(b) shows a unidirectional block created by compressing the
jellyfish tissue. The wavefront rotating clockwise is stopped at the block, but the
counter-clockwise pulse continues.to travel. Immediately after stimulation, the
compression~is ~removed(Figure 3.11 (c)), By the.time the counter-clockwise
pulse reaches the point where the block had been, the tissue is past its refractory
period. This can occur if the pulse must pass through, regions of slow conduction
or if-the loop is large enough that even at normal conduction speeds, the tissue
has time to recover its excitability. The counter-clockwise pulse can then reexcite
tissue that it has already passed through. This process continues, with the pulse
circulating to, stimulateitself.
./-lo~e
Jellyfi~,,~hRing
(a) Stimulation (b) (c)
Figure3.11 Mayer’sexperimentdemonstrating reentry. (a) Stimulationresults in extinguished

propagationwavewhen~e two branchesmeet. (b) Applicationof a compressionblock stops
blo~kwise,ex.cigtion.
(C) ~Theblockis removed quickly.Becauseof the tim~to traversering, the
e0~nter~qIockwlse
pulsesees excitabletissue andthe pulseinitiates anotherloop. Froifi Waldo,
A.
Li ~d A:’L: Wit. 1994.Mechanisms of cardiac arrhythmiasand Conduction disturbances~In R.
C~:SchlanrandR. W.Alexander (ed.) Theheart, arteries, andveins. 8th ed: Withpermissionof
McGraw-Hill, Inc.
If the block is bidirectional, each pulse circulates until it reaches the block
and dies. The cells behind the wavefront are refractory and ,unable to be
stimulated againwhile thecells ~ahead are incapable of being stimulated. Thus, the
unidirectional block is essential for initiating the reentrant rhythm.
The wavefront will continue to circulate provided a few. prerequisites have
been met; reentry requires a region of unidirectional block, a central unexcitable
area .~ound which to circulate, and an action potential wavelengththat is shorter
than the length of circuit. Wavelengthis defined as the product of the conduction
velocity of the circulating wavefront and the effective refractory period of the
tissue ~0f the. reentrant circuit (Waldoand Wit, 1994). The effective refractory
period is defined as the time between the beginning of depolarization and the time
at which be earliest impulse is,capable of further propagation in the conduction
system (Alpcrt~ 1980).
3.4.2 Classification
Reent~ Can~occur in manydifferent forms and it is useful to classify them on the

basis of their pathways.
Ordered reentry
Reentry in Whichthe Circulating wav~front continuously reenters the same stable

pathway is called ordered reentry. Ordered reentry usually consists of a well-
defiiaed anatomic pathway, an exampleof which is the reentrant circuit in Wolff-
Parkinson-White (WPW)syndrome, an AVreentrant tachycardia. ~ In this
arrhythmia, impulses travel from the atrium down through the AVnode ~d His-
Purkinje system into the ventricle and then back through an accessory AV
connection.
Ordered reentry need not be defined by an anatomical pathway,, however.
FunctiOnal circuits which depend on cellular electrophysiological ’~roperti~s can
54 ~ DESIGN OF CARDIAC PACEMAKERS
also cause ordered reentry if these properties are conf’medto a specific location
and reentry occurs .only in that location.
Examples of ordered reentry are atrial flutter, most monomorphic
ventricular tachycardias, AV nodal reentrant tachycardia, AVreentrant
tachycardia with an accessory pathway, and sinus node reentrant tachycardia.
Random reentry
In randomreentry, propagation occurs .in reentrant pathways that continuously

change their size and location with time. Someexaml~lesare ~tdal fibrillation and
ventricular fibrillation.
3.4.3 Prerequisites
Fromthe Mayerexample of reentry, it is clear that a reentrant circuit requires

that several prerequisite conditions be satisfied. ~
1. Reentry requires a suitable region of heart with electrical characteristics
capable of supporting reentry. Additionally, for random reentry, the path must
contain a critical mass of cardiac tissue to sustain the Several simultaneously
circulating reentrant wavefronts. It is virtually impossible to achieve ~ sustained
fibrillation in ventricles of very small normal mammalianhearts and just as
difficult to achieve sustained fibrillation of the normal atria (Waldoand Wit,
1994).
2. The excitation wavefront must encounter Unidirectional block. Without
unidirectional block, the case described in Figure 3,1 l(a) results: the waveform
extinguishes itself whenit meets the other br~ch of the impulse.
3. The activation wave must be able to circulate, around ~a central area of
block. In the jellyfish experiment the h01e prevented the impulse ,from taking a
short cut across the ring where it mayhave extinguished in the still refractory
tissue.
4. Tissue initially activated must have sufficient time to. recover excitability.
There must always be a gap of excitable (either fully or partially) tiss~ie ahead
the circulating wave. ~
5. Reentry ,requires an initiating trigger which brings one or more of the
conditions to a critical state. The trigger starts the cycle by being blocked on one
path and circulating around the other way. Note that the trigger beat may
unrelated to the reentrant tachycardia and may occur by any mechanism.: One
possible but unrelated trigger mayoccur during catheterization of the heart. The
catheter may stimulate a premature beat if it forcibly hits the heart wall (a
mechanical cause). Also, the trigger need not be premature; it may be a normal
sinus beat. In permanent nonparoxysmal AVjunctional reentrant, tachy~.di~ar
there exists permanentunidirectional block and a region of very sl0w CondUttion.
The sinus impulse has enough delay through the circuit that it always finds
excitable tissue (Waldoand Wit, 1994).
Several of the prerequisites will nowbe discussed in more detail, but since
unidirectional block is so important to reentry, it will be discussed in its own
section 3.4.4.
A~eas ofslow conduction in reentry
TheWavelength of the ~circulating reentrant waveform is the product of

conduction velocity of the wavefront and the effective refractory period Of the
~ MECHANISMS OF CARDIAC ARRHYTHMIAS
tissue through which the waveis propagating. Recall that the effective refractory
55
period is defined as the time between the beginning of depolarization and the
earliest time.at which an impulse is capable propagation. (Alpert, 1980). For
reentry to occur, the wavelengthof reentrant excitation must be shorter than the
length of the pathway. This guarantees that the impulse always finds excitable
tissue.
Note that an area of slow conduction is not absolutely required. Reentry can
occur at normal conduction velocities so long as the path length is long enough.
The jellyfish ring is one example. For virtually all clinic~ally relevant reentry
circuits due to ordered reentry, however, the path length would be too small (or
the reentrant wavelength would be too. large) given a constant speed of
cOnduction. The action potential would travel too quickly around the circuit and
reach tissue that is still refractory; thus, almost all the reentrant arrhythmias have
regions of slow conduction (Waldoand Wit, 1.994);
Areas of slow conduction arise by the mechanismsdiscussed in section 3.3.
Conductionslow enough to cause reentry mayoccur in diseased cardiac cells with
persistently small membraneresting potentials of about -60 to -70 mV.At these
potentials, about 50%of the Na+channels are inactivated. Slow response action
potentials can also occur in somenormaltissue of the heart such as the cells of the
sinusand AVnodes where the maximumdiastolic potential is normally .smaller
than,.-70 mV.Slow conduction is a normal property of these nodes, and either
node maybe a critical portion of a reentrant circuit, for example AVreentrant
tachycardia.
Slow conduction in reentry mayalso be caused by other factors besides those
that affect current. Anisotropic circuits usually remain fixed and can cause
ordered reentry. Anisotropy can slow conduction enough to cause reentry in
small anatomic circuits or in functional pathways: circuits in nonuniform
anisotropic bundles can be as small as 2 to 4 mm2.Also~:the~oircuits are elliptical
or rectangular because of the directional differences in ~0nd~tion with the long
axis in the direction of the fast, longitudinal direction. Circuits with this shape
can have a smaller size than circular circuits such as the leading Circle (see below)
Changes in the effective refractory period of the cardiac tissue mayalso
facilitate reentry~ A decrease in the refractory period decreases the wavelengthof
reentrant impulse, thereby decreasing the necessary size of the reentrant circuit.
If the wavelengthdecreases, the need for slow conduction also decreases.
The effective refractory period of cardiac, fibers maybe shortened during
rapid tachycardias because of rate-dependent shortening of action potential
duration. In atrial muscle the refractory period is shortened by acetylcholine
released during vagal stimulation makingatrial fibrillation easier to induce.
Action potential durations and effective refractory periods are also decreased in
the ventricle during reperfusion following small periods of ischemia or in some
of the ventricular muscle ceils in chronic i~chemia (Waldoand Wit, 1994).
Changesin gap junctional resistance and other factors that affect the fibers"
cable properties are also expected to contribute to the slow conduction necessary
for most forms of reentry.
Thd reentrant substrate
Reentrant tissue can be located anywherein heart, and the circuit can have a great
numberof shapes, sizes and types of cardiac tissues. The reentrant ~substrate can
56 DESIGN OF CARD~C PACE~KERS
be anatomic such as a loop of fibers in tbe.Purkinje system; it canbe functional

and defined by electrophysiological properties of the tissue as shown.in modelsof
atrial flutter; or it can be a combination of the two as has been suggested for
someintraatrial reentrant rhythmssuch as atrial flutter or ventricular tachycardia
Central area of block in reentry
The central area of block necessary for reentry may be anatomical (static),
functional (dynamic), or combination of the two. Anatomicblock is the result
a nonconductive region .in the center of the reentrant, circuit. One example is
atrial flutter found in patients whopreviously have had a ,Mustard procedure to
repair transposition of the great vessels (Waldo and Wit, 1994). The procedure
involves makinga large incision in the atrial wall:
Functional block occurs when there is .a block of impulses in otherwise
excitable cardiac tissue. During the healing phase of myocardial infarction, a
dynamic block may be formed in the ischemically damagedbut surviving cells
(Bigger, 1994). The ventricular excitation wavefront enters the ischemic zone
find an arc of refractoriness. The excitation wave movesslowly around the edges
of the arc and around the back until it reaches a point near the. center which by
this time has recovered its excitability. The wavefront then conducts through .the
center and back downthe sides for a reentrant circuit causing tachycardia. Figure
3.12 shows the reentrant pathway.
Figure3.12 Dynamic blockleadingto reentry. (a) Theimpulsefinds the central portionof the
isehemicarea refractoryandis blocked.Theimpulsetravels slowlyaroundthe central blockand
aroundthe backside.(b) Bythis time the central portionhas regainedits excitability andthe
wavefrontconductsbackto whereit Started.Frtm Bigger, J. T. 1994.ElCetropl~ysiology,
diagnosis,and management.In R. C. Schlantand R. W.Alexander(ed.)Theheart, arteries, and
veins. 8th Ed. Reproduced
with permissionof McGraw-Hill, Inc.
3.4.4 Unidirectional block
Unidirectional block results whenimpulse cannot conduct in one direction along a

bundle of cardiac fiber but can conductin the opposite direction. It is critical for
the initiation of reentry and can arise in a numberof different ways.
Regional differences in refractory period
If there are differences in the duration of the effective refractory period that
occur in adjacent areas, conduction of an appropriately timed premature impulse
maybe blocked in the region with the longest refractory period.
In Figure 3.13(a), a premature beat arises in a region of short refractory
period. Tl~etop t~a~e shows a quick decline from the maximally depoladze~l
MECHANISMS OF CARDIAC ARRHYTHMIAS $7
level~ Becausethe tissue has been stimulated previously, conduction downthe left
path blocks: That tissue on the left has a long refractory period, and, since the
strength~of:the action potential is related to the membranelevel at which it is
evoked(section 3.3.1), the second potential ~is too weak to initiate another
depolarization. Conduction precedes downthe-right path, however, because that
tissuehas a short refractory period and has had time to repolarize almost fully.
Figure 3.13(b) completes the reentrant circuit. By the time the wavefront
circulates to the left branch, the tissue has had time to recover its excitability.
Since. the tissue at the top and the right of the-circuit have short refractory
periods, they too are excitatory. If the time around the loop is long enough for
the left branch to repolarize sufficiently before the next stimulation, reentry will
continue.
(a)
.~ ~_..Premature beat
Blocked / / Conducted
Long refractory Short refractory

period I ¯ I period
(b) r~/~ J~ Reentrant action

I v ~/~ potentials
Secondaction "-J ~]- "L--*’:’"~\
potential J¯ [ \
period period
Figure3.13 Reentryaroundan anatomicallydefmedcircuit with tmidirecdonalblock causedby

regionswithdifferingrefractoryperiods.(a) Apremature,
beatis blockedin the left branchbecause
its longrefractoryperiodrendersthe tissue unableto Oreagain. Theactionpotentialpropagates
throughtheright b~anch,whichexhibitsquickrecovery(short refractoryperiod). ’(b) Bythe
the right br~hactionpotential reachesthe left branch,the tissue is readyto be stimulated.A
teentrant waveform has beenestablished.FromWit, A. L. andM.J. Janes. 1992:Theventricular
arrhythmias of ischemiaandinfarctio~Theelectrophysiological mechanisms.FuturaPublishing.
Notice that in order-for the unidirectional block to occur, the premature

impulse must arise in a region with a short effective refractory, period so that it
occurs i~efore the action potentials in the left pathwayhave repolarized. Also, the
unidirectional block created is transient, and this type of block can cause initiation
not only in anatomiccircuits but also in functional circuits.
An exampleof functional reentry based on refractory period differences has
been termed the leading circle model. Small .pieces of isolated.;~rabbitleft atrium
are stimulated to a stable reentrant tachycardia by precisely timed premature
impulses inregions previously activated at regular rates (Alle~siejet:al,, t977).
premature impulse blocks in fibers with long refractory periods and eventually
returns after the area has recovered (section 3.4.4). Figure 3.14 shows that the
excitation circulates around a central area ,that is kept refractory because it is
constantly depolarized by the circulating wavefront (a:functional central area of
block). The circumference of theleading circle may be as small as6 to 8 mmand
represent a pathway that is just long enough to allow for stimulation even though
the tissue is still partially depolarized. Conduction through the depolarized
circuit, therefore, must be slowed.
Figure 3.14 Leadingcircle reentry. Theprematureimpuiseblocks in the fibers with long

refractoryperiods(0) andconductsin the short refractoryfibers (1 - 5). Theimpulseeventually
returnsto the site of initiation, but, by that point, the tissuehas recovered (6 and0). Thecentral
area of blockremainsblockedby the constantdepolarization of the radially conductedimpulses.
The different refractory periods of the atrial fibers in close proximity with
each other madethe reentry possible, and canine modelsindicate that atrial flutter
may operate by.the leading-circle mechanism(Waldo and Wit, 1994).
For reentrant arrhythmias due to regional differences in refractory periods,
therefore, both a trigger (the premature impulse) and the appropriate substrate
(reentrant circuit) are needed. The cause of the trigger is quite different from the
arrhythmia it initiates.~ .~It mayarise s~ontaneouSlyby ai~t0maticity or maybe
result of triggered activity. It mayeven be induced by electrical stimulus during
programmedstimulation.
The differences in the effective refractory periods (called the dispersion)
required for a reentrant circuit maybe quite small.In the atria, the minimal
dispersion could be in therange 11 to 16 ms, well within normal physiological
range of variation. In the ventricles, where the refractory periods are much
larger, the difference betweenthe longest and shortest refractory period duration
is on the order of 40 ms. Unlike. the atria, the differences in refractory periods is
not large enough to allow reentry initiated by premature impulses. Differences in
refrac.tory periods must be increased to 95 to l~5.ms before a premature stimulus
can trigger a reentrant circuit (Waldoand Wit, 1994).
The refractory period’s dispersion is not theonly factor that determines a
premature impulse’s ability to stimulate reentry, however. Relatively long and
short refractory areas must be reasonably dose to each other so that, a premature
stimulus can reach the areas of long action potentials in enough time to cause
block. The size Of block is also critical. If it is too small, an impulse traveling
through the area of unidirectional block maynot be~delayed sufficiently to allow
the site of the prematurebeat to repolarize.
Asymmetrical depressionof-excitability
Unlike the transient block~discussed above, unidirectional block may also be

persistent and independent of a premature stimulus. It is often associated, with
MECHANISMS ,OF CARDIAC ARRHYTHMIAS 59
depression of transmembranepotentials and excitability of cardiac-fibers (section

3.3;1). This block might occur if a pathological condition affects the heart
asymmetrically. . For example~action potential upstrokes in a bundle of fibers may
be diminished by reduction of blood flow to the fibers, but the depression maybe
greater at ,one end of the bundlethan at the other.
In.Figure 3.15, a poorly perfused region of cardiac tissue experiences its
greatest reduction in signal conduction on the right side. ,An impulse approaching
from ~the~left (solid arrows), will pass through areas of increasing resistivity
creating=action potentials that,are smaller than the previous one until they are too
weakm~.depolarize ~the normal tissue at the right end. An impulse from the right
side, however; does propagate through the depressed region (white arrows). The
large:current from the normal impulse propagates far into the region and past the
area of enhanced resistivity. This stimulates an action potential in the middle of
the region that maypropagate with enoughstrength to clear the site of block.
DecreasingExcitability ...."
Figure 3.15 Asymmetrical differences in conductiondepressioncan give rise to persistent

UnidireCtional block.Theshadedregionof the cardiacfiber bundlehas reducedactionpotential
conduction withthe~ greatestarea of depressionoccurring,onthe.rightside: Anactionpotential
initiated fromthe left is progressively
reduceduntil it cannqlongerinitiate an actionpotential
(blaqkarrows).Theactionpotentialfromthe fight is able =tocigar ~ large areaof depressionand
propaga~ethrough the block(whitearrows);Reprintedfrom.Wit~’A ~. L~~ andRosen.1989.In P.
~V.~M~ieFarlane and T. D; Veitch Lawrie(ed.) Comprehehsive electroCardiology,theory and
practice in healthanddisease. Copyright1989,page826, with kind permissionfromElsevier
ScienceLtd.,TheBoulevard,Langdon Lane, .Kidlington0X51GB,UK.
Geometric factors causing unidirectional block
Ge0metri,c factors related to tissue architecture mayinfluence impulse conduction

ahd perhaps lead to unidirectional block. Normally~impUlSesCan conduct rapidly
ih ~ ~i~her i~ire~tion of cardiac fibers. This condu~ignis asymmetrical, however,
butit is usually of no physiological significance (Wit andRosen~i989):.
Thi~ a~y~met~ is the result ~f several factor~: Bundles 6~ muscle are
composed of interconnecting and frequently branching fibers of different
~et~ers. ~n impulse in one direction encounters ~ different seq0ence: of fiber
diameter Changesthan an impulse propagating in the other direction: ~the pa~way
c~qfigu,ra,tion is not th~ same in each direction. ......
¯ ~Theoret~cal analys~s ~nd~cates that tm[ ulses flowing from small d~ameter
fib~,C~to’iarge diameter fibers experience a decrease in conduction~e!oeity atthe
junction because the larger fiber acts to sink the ,flowing current (there is
suddenly more membraneto depolarize to threshold) (Wit and Rosen, 1989).
Whenan impulse flows into a region with an abrupt increase in branching,

conduction transiently slows because of the larger current sink nowprovided by
the increased membranesurface area. Fromlarge to small fibers, an increase in
conduction velocity is predicted.
Theoretically, if there is enoughof a difference in the two cable diameters,
an impulse conducting from a small to large fiber will block while the impulse
flowing the other way will continue unimpeded. Junctions between Purkinje-and
muscle cells are probable sites for unidirectional block based on this mechanism.
At certain places, propagation from muscle to Purkinje fibers is possible while
propagation from Purkinje fibers to muscle is not. The asymmetryresults from
difference in mass between the Purkinje fiber bundle (the small diameter cable)
and the large muscle layers (large diameter cable). It is not likely this makesthe
normal heart likely to exhibit reentry because the myocardiumis quickly .excited
by the many other Purkinje-to-muscle junctions where the geometry is not
sufficient to cause block. If myocardial conduction has been slowed and the
coupling resistance at the junctions has been increased due to ischemia, however,
these sites maybecomeimportant in initiating reentry (Waldoand Wit, 1994).
It is unlikely that geometric disparities large enoughto cause unidirectional
block exist except at the Purkinje-muscle junctions mentioned above. There is a
large safety factor for conduction: an action potential is carried by an excess of
current over the amountneeded to stimulate the next group of cells to threshold.
Unidirectional block due to fiber differences, therefore, requires an abnormal
action potential and decreased excitability (Waldo and Wit, 1994). A weakened
stimulus brought about by an increased resting membranepotential mayallow the
directional differences to seem exaggerated. The signal may then block in one
direction.
Anisotropic properties of cardiac muscle mayalso at times contribute to the
formation of unidirectional block. In anisotropic muscle, the safety factor for
conduction is lower in the longitudinal direction than in the transverse direction,
a fact that is opposite to that predicted by continuous cable theory. This low
safety factor is due to a large current load associated with the low axial resistivity
and large membranecapacitance in the longitudinal direction. In uniformly
anisotropic muscle, a decrease in inward current during depolarization mayresult
in a proportionally greater slowing of longitudinal conduction than of transverse
conduction. This inward current mayoccur during a premature impulse. Block,
however, usually occurs simultaneously in both directions. In nonuniform
anisotropic muscle, however, premature activation can result in a longitudinal
block even while the transverse conduction continues (Waldoand Wit, 1994).
In contrast, when the coupling resistance between cells is increased,
conduction of all impulses will be blocked in the transverse direction first. This
occurs because there are fewer gap junctions connecting the muscle bundles
transversely than longitudinally (Figure 3.10(b)). Increasing the coupling
resistance reduces the number of functional transverse connections below the
level needed to maintain conduction before a similar event occurs in the
longitudinal direction. Unlike longitudinal block of a premature impulse that is
transient, block in transverse direction by increased coupling resistance is
bidirectional and should not cause reentry (Waldoand Wit, 1994)~
Anisotropy can also result in unidirectional block at sites of muscle bundle
branching. The rapid change in fiber direction causes slowing of the wavefront
and this, coupled with insufficient axial current caused by a depressed action
potential upstroke, can result in a unidirectional block (Wit and Rosen, 1989).
MECHANISMS OF~ CA~J:I~C’ S 61~
Reflection ~’~~
is used to describe reentry in a linear bundle in which two,~excitable

by ~an area of depressed conduction: :’~
t.16 shows two fibers in a depressed region. The top,fiber also
~, unidirectional block. Animpulse approachesfrom the left at position I,
bul~~ bundle blocks. The impulse travels through the: ~region of slow
conduction along the bottom fiber until it reaches the other side of the
dhidirectional block where it propagates in a retrograde direction. By this time,
beeii~se’ ’of the slowedconduction, the original site of initiation has regained its
CJtci~bility’ and the impulseexits both fibers at position II.
Reflection results in a premature beat that mayinduce fibrillation by acting
as~e trigger for another reentrant circuit (Genes, 1984).
II ~/~ Depressed
~re ~i6Refiecfion in two fi~rs in a region of d~re~d conduction.~Thetop fi~r ~SO

co~~fion~ hick. ~ impu~ ~ifiated at I, bl~ in the top fi~r but ~n~ues~on~
~~c¢ on ~ o~er side,~the impulse p~pagates in a re~ograde ~tion to e~t both
fi~.From Wit,A. L. ~d J. T. Bigger. 1975. ~e el~Uophysioio~ of le~ ~hy~as;
possible elef~ophysiological mechanismsfor lethal ~rhythmias accomp~ying~yoc~
~he~a ~d inf~fion. Circu~t~n, 52 (~: 9~115.
SIMULTANEOUS IMPULSE GENERATION AND

CONDUCTION ABNORMALITIES
Many6f the arrhythmias already discussed rely on the interaction of’ several
simu~eous abnormalities; however, often, they were unrelated. Reentry, for
exami~i~, requires certain areas of delayed conductionas well as a trigger to start
the reentrant rhythm, The source of the trigger is not ,relevant; it on|y:..matters
that~a trigger occurs. In the next two examples, the arrhythmia arises from a
specific combination of both abnormal impulse generation and conduction:
3.5.1 Parasystole
A ’ lat~rit
.... pacemaker maybe protected from overdrive suppression if it is
surrounded by a region that blocks sinus impulses (entrance block). This block
mustbe unidirectional, however, so that the latent pacemaker impulses can
propagate into surrounding myocardium. A protected pacemaker is called a
parasyst~o!ic focus. An impulse mayexit the focus and excite ~e heart ’if the
outsidetissue is not refractory. The results can be premature, beats or even
tachycardia.
3.5.2 Phase 4 block
Block of an impulse may occur if an impulse arrives at a-location (the His bundle
or bundle branches for example) that is partially depolarized during spontaneous
phase 4 depolarization (diastolic depolarization) but has not yet reached
threshold. This spontaneous diastolic depolarization can depolarize the tissue
sufficiently to inactivate the fast Na+ channel, resulting in failure of propagation
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3~.1 : Explainthe differences betweennormaland abnormalautomaticity.

3.2 Whatcauses abnormalautomaticity?
3.3 Define.overdrive pacing. Howdoes it affect automaticrhythms?
3.4 E£plainh0w’automatieity maycause arrhythmias. ~
3.5" ¯ E~i~lainthe causesof early afterdepolarizations. .
3:6 , Howdo early, afterdepolarizationslead to eardiae arrliythmias?
3,7 Explainthe causesofdelayedafterdepolarizations....
3.8 HO~do delayedafterdepolarizations lead to cardiac arrhythmias?
3.9 WllhtiSthe difference betweena triggered~i~ythmand an automaticrhythm?
3.10 DesCribethe conditionsthat lead to areas Of slowedconductionin the:heart.
3.11 :Howdoes bidirectional conductionblock cause arrhythmias?
3.12 r~ reentry using the jellyfish modelas an:example.
3. ! 3, ~Dese.ribe the classification systemof reentrantarrhythmias.
3.14’ iDiseu~sthe ~ssential features that allowreentry to occur?
3/15 Ekpi~iinhowa unidirectionalblock mightarise in the cardiac tissue.
3.16 ~, Definereflection. Why is it significant?
4
Diagnosing Arrhythmias
Valtino X. Afonso
The main step before using artificial pacemakersto managean abnormality in the
pacing or conduction system in the heart, is the diagnosis of the arrhythmia. The
effectiveness of the pacemakeras a therapeutic device depends on the accuracy of
the diagnosis of the abnormality. ~
The electrocardiograph noninvasively measures a standard I2-1ead
electrocardiogram, which is used to analyze the electrical activity in the heart.
Diagnostic criteria obtained .from the 12-lead electrocardiogram provide
discriminatory information to diagnose different abnormalities. Literature on the
subject explains the various techniques used to diagnose arrhythmias and also uses
the word interchangeably with dysrhythmia. Automated analysis to compute
features of the electrocardiogram has improved the ability to diagnose
arrhythmias. Features of the morphologyof these signals, which are summarized
in tables within this chapter, help diagnose abnoi~aaalities that mayrequire ,the
insertion of a pacemaker as therapy Ambulatorymonitoring provides the ability
to monitor patients on a long-term basis in order to detect transient arrhythmias.
During stress testing, patients are monitored for arrhythmias while performing
physical activity. In order to supplement diagnosis based on the
electrocardiogram, invasive electrophysiologic studies use transvenous
multielectrode catheters to record electrical signals directly from the cardiac
muscle. These invasive techniques include electrical stimulation of the
myocardium to assess functionality of the cardiac system.
This chapter provides information on the techniques, signals, and
interpretation of the 12-lead electrocardiogram and intracardiac signals used for
diagnosing arrhythmias.
4.1 PRINCIPLES OF ELECTROCARDIOGRAPHY
An electrocardiograph is an instrument that measures and records the

electrocardiogram (ECG), the electrical activity generated by the heart.
Electrodes placed on various anatomical sites on the body help conduct the ECG
to the electrocardiograph. The ECGalone is not sufficient to diagnose all
abnormalities possible in the pacing or conduction system of the heart. The
interpretation of the 12-lead ECGprovides a differential diagnosis for many
arrhythmias.
DIAGNOSING ARRHYTHMIAS 65
4;1.1 The electrocardiograph
The electrical current generated by the heart is conducted through the pairs of
electrodes and leads, and is amplified, recorded, and processed by the
electrocardiograph. The wires connecting the pairs of electrodes on the surface of
the body to the electrocardiograph are called leads. The different features and
modules of a typical electrocardiograph include the protection circuitry, lead
selector, calibration signal, preamplifier, isolation circuit, driver amplifier,
memorysystem, microcomputer, and recorder or printer (Neuman, 1992).
The protection circuit prevents any damagedue to high voltages that may
a~ear as inputs to the electrocardiograph. This is useful in situations such as
wt~n a patient is being defibrillated. ~ The lead selector can be controlled by an
operator or automated, and provides the ability to record from various
combinations of the leads connected to the patient. The electrocardiograph is
usually calibrated before an acquisition session by a 1-mVcalibration signal
Whichis applied to each channel recorded. The output for the calibration signal
should be the same for each channel recorded.
The preamplifier stage consists of a differential amplifier with a high CMRR
(common-mode-rejection ratio). The high CMRR ensures that any potential
the patient’s body that is common to both inputs of the differential amplifier is
not amplified by the electrocardiograph. The preamplifier stage feeds an isolation
circuit, which acts as a barrier by preventing more than 10/~Aof 60-Hz current
flowing through the patient to ground even under the fault condition of the
patient accidentally comingin contact with 120 V from the power line.
The input of the driver amplifier circuitry is at-coupled and this prevents
the output of further amplifier stages from saturating due to the offset in the
input signal. The ECGis then filtered with an upper comer frequency (3 dB)
150 Hz and amplified sufficiently so that it can be recorded. Modern
electrocardiographs include an analog-to-digital converter (ADC)to digitize the
signal. Data segments of the ECGfrom each lead, and other relevant information
of the patient can be stored in memory. A microcomputer in the
electrocardiograph also enables the operator to select leads to record, process
ECGsignals, perform preliminary arrhythmia analysis and other related tasks.
421;2 ~Lead systems
Twelve leads usually comprise a diagnostic ECGrecording: six limb leads (three
bi ,1~ lar and three unipolar), and six unipolar precor:dial leads. Theinstantaneous
¢~diaC scalar voltages resulting from the electrical activity in the ~eart is
measured in each of the 12 lead~, Since the cardiac vector varies in m~ignitode
wi~ fime~ overa three:dimensional space, it is important to knowits presentation
(i.e. appearanceor projection) in each of the 12 leads of the ECG. .~
¯ t~igure 4.1 sh0ws the lead placement to acquire the 12-lead ECG.The leads
Can be Categorized into the frot~tal i~ads (I, II, ~I, aVR,aVL, and aVF), and the
transverse leads (V1, V2, V3, V4, V5, and V6~). The frontal leads measure the
projection.of the Cardiac vector on :the frontal, plane of the bi0dy. The frontal
plane i s parallel to tile floor whenlying supine. The transverse or precordial
leads measure the projection of the cardiac Vectoron the h0dzontaI plane, (i.e.
the plane that is parallel to the floor whenstanding).
.Le~ads I, Ii, and iii of the frontal plane ~ .are bipolar. They record the
differdnces between two points on the body. Figure 4.1 ~hows that lead I is
measured between an electrode on the left arm (the positive electrode) and
electrode on the fight arm. The three-dimensional cardiac vector projects into
each of the bipolar leads, indicating the strength and direction of the
instantaneous cardiac vector (Luna, 1993).
v!. -l’wc’r
Figure4.1 Theinstantaneous
cardiacvectorprojectsinto eachof the leads, resultingin different
morphologies.ECGsketches are that of anormalmorphology.LeadsV1-V 6 use the Wi!son’s
centralterminal(WCT),whichis formedby the three resistor network.
Leads aVR(on the rightarm), aVL(on the left arm), and aVF(6n the
are Unip0!ar leads. They measure the potential difference on the limbs with
respect ’t0a reference point formedby the ~two resistors between limb electrodes
(Figure 4.1). For example, lead aVRis measured between an dectrode’ on the
right arm, and a reference point formedvia a resistor to the left arm and ~mother
resistor to the 16ft foot. These leads ’Show°the cardiac vector pr0jection ~ on the
frontal plane, and are amplified by about50%(i.e. aUgrnented) so that their
amplitudes are comparableto those of the bipolar leads.
’ The six precot:dial leadS~’ Vi tO V6,: ~a~e u~p01ar and measure the cardiac
vector projefh0n ~on ~e tiorizOntaFpl~e. ’These pree~rdial leads are measured
with respecf tb the e Wilson central te~al which is formed by a three.tesist0r
ne~twork ~ shown i n Figure 4A. V1 and V2 areplaced on thefqurth intercostal
space to the right and left, .respectively, I of. tbe= sternum~The V4 electrode, i~s
placed on the fifth intercostal space at the left ~idclavi~ular iine~ The V3
electrod
’ e lies between V2 and V4. Electrode V5 is placed to the left of V4 on the
anterior axillary line, and V6 is placed on the same’level as V5onthe midaxillary
line;~:.It is-important to account for the position of these electrodes when
interpreting the ECGon leads V1 through V6. The precordial leads measurethe
potential between each of V1 through V6 and the Wilson’s central terminal
formed as shownin Figure 4.1.
, The 12-lead ECGprovides ,various viewpoints of the three-dimensional
instantaneous cardiac vector that are somewhatredundant, and this is ltelpful in
providing discriminatory information for diagnosing abnormalities in the pacing
and conduction system of the heart.
4.L3 Cardiac vector-ECG correlation
Theelectrical activity due to the specialized cells in the heart results in an electric
potential on the surface of the body. Each cell can be modeledby a dipole, and
the superposition of the potentials from the dipoles for all of the cells in the
myocardiumresults in a three-dimensional cardiac vector for the heart at each
instant in time. The cardiac vector at each instant of time represents the net
electrical activity in the heart.
Figure 4.2 shows the Hexaxial reference system which is used in the
diagnosis of certain abnormalities. The Hexaxial system shows the orientation of
the front.al-plane leads. The various orientations of each lead result in a different
projection of the cardiac vector onto that particular lead. A meanelectrical axis
as a function of time, during the depolarization and repolarization phases of a
cardiac cycle can be calculated. Forexample, the electrical axis of ventricular
depolarization, ,~QRS,represents the a~,erage of the instantaneous cardiac vectors
during ventricular depolarization. The ~Ql(S,Usually lies between aVL and aVF
in Figure 4.2. It is easy to diagnose left and right axis deviation, LADand RAD
respectively. In LAD,lead I is predominantly positive (i.e, R waveis positive)
and both leads II and III are predominantly negative (i.e. R wave is small or
absent). Both II and III must be predominantly negative, i.e. if in lead II the
°
-90
Normal range
~
of QRSa~
RAD
Figure4.2 TheHexaxialsystemshowsthe orientationof the frontal planeleads. Duringleft axis

deviation(LAD)itbe
meanaxis of the QRSwill be less than -30°. RAD:
right axis deviation.
wave is smaller than the R wave, LADis not present. If lead II is equiphasic (R
and S waves have equal magnitudes), then there is borderline LAD.In RAD,lead
I is predominantly negative and both II and III are predominantly positive
(Bennett, 1989).
Figure 4.3 shows the Einthoven triangle superimposedon the locus of points
formed~in the frontal plane by a normal instantaneous cardiac vector, the
vectorcardiographic loop during one cardiac cycle. The measured ECGon each
lead is a projection of the instantaneous cardiac vector. The P loop corresponding
to atrial contraction, projects onto leads I, II, and III as an upwarddeflected
wave. However, the S wave is projected onto lead III remarkably more than~.in
leads I and II. The instantaneous orientation of the cardiac vector, and the
orientation of the lead determine whether there is a positive going or negative
going waveform on the lead. Thus the different leads of the 12-lead ECGshow
various projections of the phases in the cardiac cycle~
.,\ /
¯ QRS
e
" T
~~ "~~’ P ’
Time (II
I~ ~1 Time
Figure4.3 For a normalECG,the instantaneouscardiacvector projectsinto lead IH with a more

negativeS wavethanin lead I. Thedashedline indicates howthe QRScomplex projects ontolead
I. Shadedareas representkeysegmentsof the ECG.
4.1.4 Characteristics of.a normal ECG
In order to inte~ret the 12-lead ECGand use it to diagnose abnormalities, it is

important to know the normal characteristics of the ECG,and understand the
mechanisms underlying the generation of each segment of the ECG.Figure 4.4
shows the various fidueial points in the ECG,and typical values of the various
intervals measured from the ECG.
The P waveis caused by atrial depolarization. The duration is normally not
greater-than 110 ms. The normal shape of the P wave does not include any
notches or peaks.-It is normally positive in leads I, H, aVF, V4 to V6. It is
riormally~:negative in aVR. It canbe positive, negative,, or diphasic in the

remaining leads. If it is diphasic, then the negative componentcomes after the
positive componentand is not excessively broad or deep. An absent P wave in the
ECGmay,signify sinoatrial block, an abnormality in which the impulse from the
SAnode is not conducted to the AVnode.
S’T
segment
I
! interval ’ interval___~.i
0.28-0.43
~.4.4 Thefiducial points on a typical ECG provide diagnostic informationsuch as the QRS
wi~Ith,for evalttatingthe pacingandconduction
phasesof the heart.
~The,QRScomplexisa general term representing activation in the ventricles

andis a result.of the depolarization Of the ventricles. The duration is normally
less thhnloo ins. The Q and S waves represent negative (downward)deflections
on the plot of the lead, and the R waverepresents positive(upward) deflections,
The Q wave comes before the R wave, and the R wave comes before the S wave.
Not all of the Q, R, and S componentshave to be present on any particular lead.
The actual QRSmorphologyis specified using the letters, q, Q;r, R, s, and S. An
upper case letter signifies a bigger size of the wavethan the corresponding lower
case letter. For example, a QRSmorphology consisting of a small downward
defl~ti0n; followed ’by a large upward’ deflection, and then a ’small ~d0wnward
defl~cfion would ~be labeled as qRs. Normally, the initial portion Of the QRS
complex is a narrow q wave in leads I, V6, and aVL, and a narrow rin lead V1
which may sometimes be absent. The end portion of the QRSnormally has an S
wave i~n V1, andan R wave in V6 (i.e. no downwarddeflection~after R wave in
V6). A QRScomplex duration of more~than 120 ms can reflect an abnormality
due to intraventricuiarconduction: ~ : -
The T wave results from ventricular repolarization. The normal
morphologyof the T wave is rounded and asymmetrical. In the normal ECGit is
positive in leads I, H, V3, to V6, andnegative in lead aVR:Thepolarity may
vary in leads HI, V1 and V2. The polarity is positive in aVLand aVF, but it may
be negative if QRShas a small amplitude.
.~,, Th~ S~TTsegment is measu/ed from the en~of QRScomplexO~point) to ~e
onset "~’ of the T wave. This segment represents the"~arly stage of ven~ula~
,i~,~’, .~ ¯ ~ , " - ¯ ~ -,: .... ¯ ’~’ .i~ ~ ’. " ... ¯ , ,.
repMartzati0n and under normal conditions ts lsoel¢etric (constan! potently);
maybe~ sfighfly ~lcvated inleads I, H, III;i and th~ prec6rdi~leads2 Iris no.ally
not depi~e~§ed in any lead. A markeddiSplacement of th~ S’T segrnent signifies
coronary artery disease (e.g. a marked elevation could suggest myocardial

~nfarction).
The P-R interval represents the atrioventricular (AV)conduction time, i.e.
the time required for the electrical impulse to propagate, from the sinus node
through the atrium and the AVnode to the ventricles (which results in
ventricular depolarization). The normal range of the P-R interval is 120 ms to
200 ms. This interval can vary with heart rate.
The Q-T interval reflects the total duration of ventricular systole, and ks
measured from the onset of the QRScomplex to the end of the T wave. Normally
the Q-T interval is less than half the precexling R-R interval. Q-T lengthening
may be caused by bradycardia or hypothermia.
The U wave, which is not.always recorded on the ECG,follows the T wave
and usually has the same polarity as ’the T wave. It is recorded bes~ in leads V3
and V4. It becomes more evident with hypokalemia, bradycardia, and age (Luna,
1993).
4.1.5 Evaluating diagnostic criteria
It is important to knowhowuseful the diagnostic criteria or features (e.g. wide

QRS> 120 ms) obtained from the ECG,or any other signal, are for detecting
abnormalities. The sensitivity, specificity, and predictive value of a Certain
diagnostic criteria provide iniY~rrhati0n about the discriminatory:effect of th~
criteria.
The sensitivity of a diagnostic criterion is defined as. the ~ercentage of
people withthe abnormality whohave the diagnostic ~rit¢fion, If al[,subj~ects who
have,the disease manifest the criterion or feature, then~the~diagnostic criterion is
said to have 100% sensitivity ....
¯ " TP
Sensitivity of a criterion (%) - TP + FN (100)
where TP (true ~ositive) represents the nUmij~r of subject with theabnormality

whohave the erh, edon, and ~ (false negative)~represents the numberl of subjects
with the abnormality ~hodonothave~aecfi~¢d~nr The!ower the sens~tivi~); of
¯ ~
the criterion, the~large~ the numberof false negative cases, ¯
~,, The speeifiCit~/(SP)Of ~ test s def’med ~the, pe ~eatage, ~Sf nOrma[~ubjdcts
who. do not have ,the criteri0n ifor abnormality. The Smaller the number of
normalsubjects likely to have’the diagnos~ccriterion, the m0~gspecific the teg~,
TN
~.~Specifieity of a criterion (%)~ ;I’N + FP (100)
sents the of ects without ~h6
t by using
of~the criteria.
DIAGNOSING ARRHYTHMIAS ~ 71
4.2 MONITORING STRATEGIES
Someof the’ techniques used in acquiring information on the cardiac muscle

include ~ ambulatory ECGmonitoring, exercise stress testing, and automated
arrhythmia analysis. Each of these techniques are optimized to detect, record~
analyze, and diagnose an abnormality in the electrophysiologic system of the
heart.
4.2.1 Ambulatory ECGmonitoring
Ambulatorymonitoring is a noninvasive technique used for correlating between a

patient’s symptomsand the presence of arrhythmias, evaluating an antian-hythmic
drug therapy, classifying risk in postmyocardial .infarction patients, and
monitoring pacemaker func~tion such as recording heart rate with different
activities (Luna, 1993). Since the occurrence of abnormal cardiac electrical
behavior mayoccur sporadically or in response to certain stimuli, it is important
to record the ECGover long periods of time.
,. ¯ Holter recording is a technique for acquiring a Continuous ECG.Magnetic
tape, and more: recent!y solid-state memoryis used to store:recordings of the
ECG.~:In the former technique the.signal is stored on tape in analog form
(frequency-modulated systems are,. also used),: and in the lat,ter case digital
compression algorithms maybe usedto store long-term digital, data~ofi a limited
memory. bank. ModemHolter .systems provide sophisticated~, static RAM
technology which can store data recorded .eye,many ,days~ TwoECGleads are
often used to ensure an accurate interpretation of the ECG.~T!!. e recorder is small,
lightweight, and acceptable for the patient t o. wear. Holter monitors can acquire
and process the ECGin real time. Current :ambulatory monitors can make
recordings for several days.
Analysis of the 24-h tape requires 30 to 60 min to obtain information of
arrhythmias and S-T~s.egment changes. A report of a.compressed version of the
ECGis usually available for the clinician to validate the automatedresults given
by,~ ~e.,.monitor. Modernscanners include ~features to~provide~a tabulated
summaryof relevant data, :and record and analyze the Q-~;I" interval variability
overa long period. Luna (1993) shows that the variabili,ty of the ~Q-Tinterval
postmyocardial infarction patients can be useful ~to stratify risk of malignant
ventri.eular arrhythmias. .. ~.~,~,~
Holter recording is useful for patients whohave transien t symptomswhich
suggest a cardiac abnormali~: Man~patients with a~varigty of symptomssuch as
palp~ta~ons, dizziness or syncope.(tra,ns~ent ,loss .of consciousness), a prev!o~s
ischemic stroke, and chest.,pain are diagnosed ~ith H01ter rec0rdin#. Holter
re~ordin~gs ~,are used to corr~lat6 the patient’s ~ymptomswith~ihe presence Of
arrhythmias, Patients wearing Holter monitors ~sually keep a record of actiyities
and times when their symptomsoccur, so ~at ,~ activities may be correlated
with the ECGrecording.
.Holter monitoring,provides a method
mechanisms of arrh~as. Luna (1993)~re~rts
tapes of patients whodied while being m~n,i.torc~,, i.e..
sudden death~ Ventricular tachycardia
the cases, and bradycardia accounted for the remmnmg
monitoring ~is also used to document pacemaker m
heart rate with different activities. It can also be useful to detect any malfunctions
in the pacemaker pacing or sensing functions. Current ambulatory monitors
include a separate channel for recording the pacing stimulus, and can
automatically~ provide information concerning failure to capture, failure to sense,
failure to generate an impulse, and percent of beats paced. Even though these
features are "currently reliable for single-chamber pacemakers, additional work
needs to be done for the automatic evaluation of dual-chamber pacemakers
analysis (Greenspon and Waxman,1992).
4.2.2 Exercise stress testing
Exercise stress testing is used to, evaluatethe cardiovascular response (changes in

blood pressure, heart rate~ and 02 consumption) to exercise. It is useful in the
diagnosis and evaluation of ischemic heart disease, and the assessment of cardiac
arrhythmias.
The heart extracts 70%of the oxygen" carded by the blood flowing through
the myocardium. During exercise, an increase in myocardial oxygen demand
must be matched by an increase in coronary blood flow~ otherwise isehemia will
result. In thepresence of ischemic heart disease (IHD), coronary blood;flow
cannot increase adequately to meet the demandsof the myocardiumfor 02..This
results in ischemia and maybe manifested by p~ (angina), changes in the ECG
S-T segment, Ventricular dysfunction, or arrhythmias (Heger et al., 1993):
Exercise ~ipacity is deseribedusing the "double product," the product of
heart rate and blood pressure. The exercise testing methodologyis designed to
produce an increase in ~heart ~rate ~to~ 85%~t090%of the statistical maximum,fOr
the patient’s age and sex. Theexercise testing is carried~0ut in a suitable
temperature, in an environment equipped for cardiorespiratory emergencies. A
bicycle or treadmill-is used, and the Bruce or Ellestad protocols are the ones most
widely used. The exercise protocols involve multiple stages of increments in
intensity of exercise, over minimal intervals of three minutes. Patients are
monitored for symptoms suchas precordialpain, and hemodynamicchanges. The
12-lead ECGi~ acquired with the patient supine, and standing prior-to the test,
during each step ~ the exercise protocol, immediately following the exercise, and
at 2-rain intervals after the exercise for 10 ~min(Hegeret al.,. 1993;.Luna,1993).
S-T segment changes, are the most reliable ECGdiagnostic criteria of
myocardial ischemia. S-T segment changes during the exercise test is dueto an
intracellular potassium loss resulting from an imbalance between the myocardial
02 supEly and demand: The"S~Tsegment ehangeS"can be isoeleetfic, junctional
(near’thg J p0int of the ECG),a.horizontaldepression, down-sloping, slow rising,
or elevated. A’~marked horizontal or d0wn-sl0piiag S-T segment below ~the
isoelectric line and whichpersists for 80msis interpreted as a positive test. The
depth; of the S-T segment depression correlates- roughly with the extent of,the
e0ronary artery disease. The ~tei’pretation of the exercise test should~take itito
account the workloadof the e~erci~e, the heart rate and’ blood pressure response,
and the presence or absence of arrhythmias or symptoms.False positive and false
negative rest/Itsare possibl~~during situations of !eft bundle branch block, left
ventn’~eular hypertrophy, W61ff-Parkinson2-Whitesyndr6ine, and ehangesd~ie to
digi~s(Hegerefal., 1993; ~na, 1993)~ ..... ’ " ~ ..... .. " ~, ~
~
~ ~e mbst i~po~t indic~ifion~ for exercise’ stress testing are f6r precordi~
pain, an ~ariy diagnostic of isehemie he~ disease, and evaluation of a theraPY
~sueh,~ pacemakers) for arrhyth~as. In patients with coronary artery disease
without heart failure, exercise stress tests are important in that ECGchanges
provide the information about the course of the disease. Exercise testing has
limitations as a diagnostic method. Besides the false result possibility mentioned
earlier, death, ventricular fibrillation, myocardial .infarction, or serious
arrhythmias could occur during the exercise (Luna, 1993).
4.2.3 Computer analysis of the ECG
Over the past few years there has be4man increased trend toward processing, of
electrocardiogram (ECG) data by microcomputers. Many systems have been
designed .and implementedto perform, signal processing tasks such as 12-lead off-
line and real time ECGanalysis, Holter tape analysis, and real time patient
monitoring. All of these applications.require an accurate detection of the QRS
segment of the ECG.A few of the techniques that have been developed to process
the ECGinclude QRScomplex detection, signal averaging, and S-T-segment
analysis.
QRS detection
There are many QRSdetection algorithms,reported in the. literature. ~ One

example is the real-time QRSdetection algorithm developed by Pan and
Tompkins (1985) and further described by Hamilton and ~Tompkins(1986).
recognizes QRScomplexes based on analyses of the slopei amplitude, and width.
The ECGsignal is passed through a bandpass, filter in order to attenuate
noise.: The bandpass fdter passes the QRSenergy .centered at 10 Hz, and attenuates
~and
the ~also
low frequencies characteristic of P and T waves, and baseline drift,
attenuates the higher frequencies associated with electromyographic noise and
power~lineinterference. Differentiatitag; the bandpassedECGsignal results in the
QRS complex being distinguished from the other ECG~waves. A nonlinear
squaring transformation of’~the differentiated, bandpassed ECGserves to
accentuate the high frequencies associated .with the QRScomplex.., The squared
waveform then passes through a moving window(about 150 ms long) integrator.
Adaptive thresholds are applied to the output of the moving~window integrator,
and the differentiated ECGitself resulting in preliminary detection of the QRS
complex. ¯
Signal-averaging
Life-threatening ventricular arrhythmias; ~following myocardial infarction are
most often due-to re-entry of aslow and fractionated wavefront in the ventricle.
Studies performed on electrograms from the border,zone between ~normal and
infarcted, myocardiumshow,that these,, areas ~depolarize ~late, reflecting :slow
conduetion:i’~.Thus abnormal, :~fragmented electrical acti~vity is due to the slow
inhomogeneousconduction in this,zone. These fragmented electrical signals were
recordedin patients with sustained;ventricular tachycardia. These eltetrical
signals, the late potentials, occur, after the QRScomplexor,in the S-T segmentof
th~ surface ECGas low-amplitude, high-frequency signals. Signal averaging of
these late potentials.
involves selecting anormal cardiac:cycle as a ,,template,
comparing subsequent waveforms with the template, and averaging subsequent
waveforms which are normal., As more beats are-averaged the noise in theECG
is minimized. After signal averaging~ the averaged waveformis high,pass filtered
at about 40 Hz to remove, theS-T segment and the T wave, and thus the late
potentials are enhanced.
Computer processing of the signal-averaged ECGinvolves computing the
QRS duration, mean square root voltage of the last 40 ms (MSR), and the
duration of the low-amplitude signal (LAS) (amplitude less than 40/,tV). A
duration greater than 110 ms, MSRless than 20 ~tV, and LASgreater than 38 ms
is considered a positive test for late potentials (Macfarlaneand Lawrie,’: 1989).
Frequency analysis is also performed to characterize the ECGnear the QRS
complex. Studies have ~dem0nstrated an increase in high-frequency components,
20 to 50 Hz, of the signals from ventricular’taChycardia patients comparedto that
from normal patients. Frequency-domain techniques may demonstrate the
preSer~ce of late potentials in situationg Whentime-domain techniques are not
usefulsuch as when bundle:~branch block is present (Macfarlane and Lawfie,
1989; Luna, 1993).
S-T segment analysis
Tompkins (1993) reports on techniques used in biomedical digital~ signal
processing. It is important to design signal processing algorithms to make
measurementsof any changes.in the S-~T segment.
Weisner et al. (1982).designed a microprocessor-based device for analyzing
the S~-T segment,-Anyeffieient ~technique is used to detect the approximate
location Of the QRS:waveform.~The Rwaveis then defined as the maximal, value
within 60 ms of the ~QRSdetection mark,. The Q waveis the first inflection point
before the ~RwaVe;An. inflection point, is detected by a Change in the sign of
slope, zero slope, or a significant changein ~slope. TheS ,point is located as the
first inflection point after_the R, wave,~AHanning digital-filter can be applied to
smooth noisy ECGdata before ~ealculating the slope. By searching between the P
and Q wavesfor, a 30~ms ~ interval~ of zero slope, the isoelectrie line of the ECG
can be located ands.measured. Measurements of;the QRS duration, R peak
magnitude relative, to the isoelectrieline,-and the R-R interval can then .be
obtained. .........
The ~T point is~.defmed at the onset~of the T wave. The J point is the first
inflection point after the S point, or maybe the S point itself in certain ECG
waveforms. The T point is found by first locating the T wave peak (the maximal
absolute value, relative to the isoelectric line, between J + 180 ms and R +
400 ms). If a noisy signal does not permit the T point to be found, the upper
search limit sample point is used. The T point is then found by detecting a 35-ms
period on the R side of theT, wave which.has values within one sample anit of
each other: If theT point cannot,be detected it defaults to J + 120 ms,
With these EI2G features; S-T segment measurements can: be ~made by a
windowedsearch method~ Two-boundaries, the J ÷ 20 msand theT point,define
the windowlimits~The,point Of maximaldepression or elevation in the~windowis
then identified: S:T~segment levels can be expressed as :the absolute.change
relative to the isoelectrie line, The S-T slope is defined as the amplitude
difference between:,~the S-T-segment point ’and the T point, divided by the
corresponding time interval. The~S-T area is~also ~caleulated ~by summing,.all
sample values between the J and T points.’after subtracting the~ isoelectric.line
from eaehpoim.~ A S-T~,index is ,calculated as the~sum of the S-~T segment and
one-tenth of~the S-T sl0pe.. -~ ,~ ~
: ~,:.~Based on,the S-T,segment measurements obtainedin the above analysis;
changesin the’blood supply to themyocardiumcan be analyzed~
DIAGNOSING ARRHYTHMIAS- ~ 75
4.3 INTRACARDIAC ELECTROPI~,SIOLOGIC TECHNIQUES
Techniques for recording from and stimulating specific sites within the r heart
have been developed. The ability to record the electrical activity from the sinus
node, His-bundle, and fight ventricle, and .perform endocardial cardiac mapping
and programmedelectrical stimulation have improved remarkably. Intracardiac
electrocardiographic techniques are usefutin the diagnosis :and the management
of arrhythmias. Diagnosis based on the surface ECG has been greatly
supplemented because of the correlation with data available from intracavitary
studies.
4.3.1 His bundle electrogram
The His bundle electrogram (HBE)helps, .in dfie~ining the loea~on

atrioventficular block. It can also provide .additional discriminatbry information
in addition to that available from the 12qead EcG,~t9. diagnose.~bnormalities.
The His bundle electrogramcan be obtained by .an invasive procedure, or it can
be acquired by processing the ~surface ECG.
~.,, The Scherlag technique (Seherlag,~ 1969), uses an easy, reproducible ’method
for acquiring the HBEinvasively. A catheter, with bipolar electrodes, iS inse~
through the femoral vein and strategically placed near the tricuspid valve, which
is near the Hisbundle ~ea,: :Figure 4.5 shows the various !oqations where
Catheters ~can be placed within the heart to record from the atria;~ind iventficles.
Bynoting the .electrical activity at different ~sitegw~thinthe hea!~t,~..it ispossible to
note the conduction times within the conduction system of the"heart. This is
knownas endocardial-mapping, and abnormal or normal activation of the heart
can be determined from this procedure. Recordingelectrical activity .in the fight
atrium and d, ght ventricle, is easy since the catheter can access these locations.
However,to record activation in the left atrium a catheter can be inserted into,the
carotid si, nus and th~s provides accessto the posterolnfefior (towards tfie.bac,~ ~d
towards the bottom) partof the left atrium.
Catheters
eatheters within’the ~a :ahd Ventriclesprovideaccessi

actl~y."The
A~-H’iiit~i-val
~onducti6nthroughtheAVnode.TheHwaveisa result of the His bundleaetivati’on:~.IIIi lead
~ of ~e ~surfaceECG;HRA:eleetrogramfromthe upperright a~um;4-lBE~ e~!eetrogramfrom
the Hisbundlenearthe topof fightventricle.
Figure4.5 shows a typical signal thatcan ,be recorded from an intracavitary

study. The HBEshows the A, H, and V waves. The A wave is a result of atrial
activation in the area of the septum close to the AVnode. The A wave is
coincident with the middle portion of the P wave of the surface ECG. TheH
wave is a result of the His bundle activation and can be a small biphasic or
triphasic deflection occurring during ’the isoelectric portion of the P~Rsegment
of the ECG.The V wave is a resultof the activation of the ventricles, and this
coincides with the QRScomplex(Helfant, 1974)~
Figure 4.5 shows a signal from the high right atrium (HRA)~witha P wave
that coincides with the onset of the P waveon the surface ECG.Thusit. is possible
to measure the conduction time within the atria, by measuring the time from the
P wave on the HRAto the A wave on the HBE.The P-R interval of the ECGcan
be split into the P-A, A-H, and H-V intervals~ The P-A interval is .measured
from the onset of the P wave on any surface ECG(or HRA)to the beginning
the A wave. The A-Hinterval is me~uredfrom the onset of the A wave to-initial
deflection Of the His bundle~activation in the HBE.This interval is a.relatively
accurate measure of conduction through the AVnode. The H-V interval is
measured from the onset ’of the Hwave to the onset of the V wave or any
manifestation of ventricular activity onthe ECG.This interval is a measure of the
time of conduction through the His bundle, bundle branches, major fascicles and
Purkinje fibers. Figure 4.6 showstypical values of each of these intervals.
¯
Basal ’ ..... Conduction time (ms)¯
’’ bpm PLR : P~A :A--H

64+15 154+19 37+_ 11 78± 18
’7 + 13 162+19. ’ 27+9 92+-19 J43 +-6
i7 + 10 172 + 11 43 + 14 88 + 21 41 +-4
Figure4.6TheP~-Rinterval on the surface ECGcan be segmentedinto theP’A,A±H,?.and H-V

intervals:measurable
fromthe HBE.TheH-Vinterval meas/Lres the time of Conduction
throughthe
Hisbundle,bundlebranches,majorfascicles andPurkinjefibers, bpm:beats per minute(Helfant,
1974).
It is possible to detect a beat blocked at the AVnode by noting if there is an

A wave with no accompanying H wave. A beat Blocked below the A~nod¢in the
lower segment of the His bundle, or the fascic!esbelow it, is seen(i~an A wave
accompanied by an H wave but withno V/.~aV¢. It is iO\portah~:to analyze
multiple surface ECGleads along with the i~tr~ca~itary d~tr0gr~s iii order
for accurate measurements of the intervals to be made ~hen a
particular cardiac activation is isoelectric in one lead
The His bundle activation can also be detected by the surface
ECG. Averaging a sequence of cardiac cycles, which have been ali~ned to a
fiducial point (such as the R wave), results in randomnoise in, the signal being
attenuated and the signal of interest, the His bundle signal enhanced. There are
limitations to this approach in patients with irregular rhythms or changing AV
conduction times. Another approach utilizes a beat-by-beat approach i~n w~ich
averaging ~s performed on five sunultaneous samplmg, ne~by sites, resuit~g m a
real-time on-line signal. Further processing is performed and the average is
computedonly if not more than one of the five sampled channels is out of phase
with the rest. The resultant waveform then includes the His-Purkinje related
signal (Macfarlane and Lawrie, 1989).
Utilizing an esophageal pill electrode the electrogram from the atrium can be
recorded and atrial pacing can also be performed. Burack and Furman (1969)
reported a case study in which a patient was paced in an asynchronousf’Lxed,rate
pacing mode for 36.h, and then paced in the demandpacing mode for 24 h. A
transvenous~ electrode, 58 cm long, was passed through the nose into the
esophagus, and was placed posterior to the left ventricle about 4 em above the
esophageal-gastric junction,. This technique can also be used :in the case of a
patient who cannot perform the exercise stress test protocol.. The esophageal
electrode is used to pace the left atrium and increase the heart rate (Heger et al.,
1993).
4.3.2 Programmedelectrical stimulati6n
In order to study the factors that initiate, terminate and sustain Ventricular
tachycardias. (VT)~it is importar~t to reproduce these as reliably a~ possible.
Using programmed electrical stimulation (PES), it is possible to itiitiate clinical
tachycardia i~ patients whohave the arrhythmia spontaneously..The therapy for
the induced atrhythmia depends on the medical history of the pafient~
PES was initially used to study the mechanismsof elinica!. - arrh~as. For
example, re,entry was found to be the operative meeh~ism.of::~ecurrent
Sustained ventricular tachycardia. The activation pattern of the arrhythmias can
be mappedusing end0cardial and epicardial catheter ,re~ordingg;.~d the site Of
origin of the arrhythmia identified: Further studies, in the area demonstrate that
PEScan be used to select antiarrhythmic drugs for therapy, but this is not often
reliable. The ability to induce the clinical arrhythmia allows the activation
sequence during the VT to be recorded and analyzed, and the influence of drugs
on the VT to be studied (Greenspon and Waxman,1992)/~
PESinvolves stimulation of the heart muscle, usually at the right ventricle
apex. S’tudies in the literature showthat performing PESat a seeondSite in the
right ventricle might help to induce VT. The North American Society~of Pacing
and Electrophysiology recommendsa protocol involving a pulse duration of 1.5
tO 2 ms, at twice the diastolic threshold; with up to three extrastimnli (Greenspon
and Waxman,1992),.
Different ventricular arrhythmias can result from PES. :The-induced
arrhythmias are classified according to their duration and morphology.. A
sustained (greater than 30 s) VT is one witha rhythm faster than 100 bpm.
monomorphicVT is one with a constant morphology, whereas-a pblymorphie VT
is one where the morphology changes frequently. Monomoi’phie arrhythmias
suggest that there is only one arrhythmie focus that has a stable entrance °and exit
site.
PESis increasingly being Used in clinical~studies.~Based on PESstudies
patients are selected for antitachycardia ~pacing, automatic iraplantable
defibrillators, and surgical ablative techniques.
4.4 ARRHYTHMIAS FROM THE SINUS NODE
The SA node, under normal conditions, acts as the .heart’s natural pacemaker by
generating impulses at a rate of about 60 to 100 times/min in most adults at rest.
The SAnode is affected by the parasympathetic and sympathetic nervous system,

hormones, medication, and other pathologic factors. A normal sinus rhythm is
one in which the heart beats at a regular rate due to the impulse which is
generated in the SA node and propagated through the normal conduction system
of the heart. Any abnormalities in the SA node result in an ECGmorphology
different from .that in normal sinus rhythm. Someof these abnormalities may
warrant the use of an implanted pacemaker as-a therapy and include sinus
bradycardia;~sinus tachycardia, SAblock,- sinus arrest, and sick sinus syndrome.
Figure 4.7 providesa summaryof some of the characteristics of the surface ECG
used in, diagnosing betweenabnormalities in the SAnode.
Diagnostic criteria
Type HR (bpm) P-R (ms) Morphology Particulars
Brad. < 60 N ’~ ~ P:N; QRS:N " Low HR
Tach. > 100 Sh/Lo P:N; QRS:N
Block N, varies N p:dropped . PP: (shortens beat
~
.... 2* ~ ~ sometimes dropped)i(related
Arrest N, Varies N P:N; QRS:N, ’Abh~pt stop of
SSS ’ Diagnostic c.riteria related to the p~cular abnormb.lity.

Figure4.7 Diagnosticcriteria for differentiating’betweenarrhytltmiasofthe sinus nbde.The
diagnostic’criteria maydifferif concurringwith anotherarrhythmia.Brad:bradyeardia;Tach:
tachyc~a;SSS::sick sinus~syndrome;HR:heart rate; N:norrdal;Sh:~short;.Lo:long;/: or.
4.4.1 Sinus bradyeardia
In sinus bradycardia the~heart rate is less than60 bpni. This heart rate is .the
distinguishing criteria from normal sinus rhythm, The impulse is generated in the
sinus node, and is propagated through the horror conduction system of the heart.
Sinus bradycardia .may be seen in healthy adults who.have~exercised
regularly during their life and thus have increased cardiac muscle tone. Increased
parasympathetic activity., certain .types of medication, and organic disease of the
heart also result in sinus bradycardia.
The distinguishing feature from the surface ECGis the lower heart rate. The
morphology, of~the different components in the ECGare the same .as.that for
normal
a. sinus rh~. Figure 4.8 shows, an ECGtracing of sinus bradycardi
Diagnostic:criteria: ,The rate is less than ,60 bpm; rhythm is regular;
interval is normal; all P waveshave the same shape and are upright in leads I, II,
aVF, ~and V4 to V6: QRScomplex is normal,, but may be different due to other
abnormalities (Conover, 1986).
Because of the lower heart rate, the cardiac output may decrease and this
results in a lower supply of blood to the brain and other organs of the body. If
the heart rate is not very low in this arrhythmia, then the patient will not have
any major symptoms. However, if the~:heart rate isvery low, s~ptoms .that are
commonto marked low cardiac output are observed. These symptoms include
dizziness, weakness, chest pain and pressure, shortness of breath, low blood
pressure, and lower pulses detectable at the;limbs.
DIAGNOSING ARRHYTHM|AS~ ~ 79
Figure4.8 Thetop trace manifestsbradycardia,i.e. a slowerheart rate, as compared

to the
bottomgraphshowingtachycardia.5 big boxes= 25 smallboxes= 1 s. FromChou,T. C. 1986.
Electrocardiography
in clinicalpractice.2rid Ed.Grune&Stratton.
, If the, symptomsare persistent and the patient cannot tolerate them; then
tre~ent is warranted. Medication is reduced if it caused .the bradycardia, or
~nisteled to. increase heart rate. A tempo~a,~ pacemaker ’is often ~sed when
there has been damage to the cardiac muscle such as with acute myocardial
iiifarctipn, if the symptomsdo not disappear then a ¯permanent’ pacemaker is
required (Catalano, i993)..~ ’
4;4.2 Sinus tachycardia ¯
Sinus tachycardia results whenthe SAnode generates impulses at a rate greater

tha~ l~:bpm, and these impulseS are propagated through:the normal conduction
system of the heart.
Physical activity, fever, and anxiety are some of the events that result in
sinus tachycardia. Medications that affect the heart directly, or via the central
nervous system also cause sinus tachycardia. Hormonessuch as thyroid cause
increased heart rate. Damageto the cardiac muscle due to infarction, heart
disease, and infection also cause sinus tachycardia (Catalano,. 1993).
The surface ECGmanifests a normal morphology with heart rates above
100 bpm. The increase in heart rate (or ~ decrease in the R-R interval) in most
cases results from the decrease of the T-P interval, although ~ is possible to have
a shortenedor lengthened P-R interval (Chou, 1986). Fi~e 4.8 shows an ECG
tracing of sinus tachycardia.
Diagnostic criteria: The rate is greater than 100 bpm; th.e rhythmis regular;
the P-R interval may be normal, very long or~ ~very short due to other
pathologies; all P waveshave the same morphology,and are upright in leads I, II,
aVF, and V4 to Vt; QRScomplex is normal, or wide due to other abnormalities
(Conover, 1986).
Patients with sinus tachycardia for a few~ days are prone to heart failure
because the heart muscle does not have a chance to rest. If the tachycardia is
inte~ttent the patient usually does not have any. symptoms. At a heart rat~
~/an 160 bpm, the cardiac output begins to decrease; ~d patients begin tO
have symp~Jmssu~has chest pain, chest pressure, shortneSs of breath, occasional
palpitations; low blood pressure, or a fluttering .feeling in the cbest (Catalano,
1993).
Treatment is required to reduce the heart rate until good cardiac output is
obtained. The cause of the tachycardia (fever, anxiety, exercise) should
alleviated.
4.4.3 SA block
SAblock results whenthe impulses generated at me SA node are either delayed

or not conducted to the AVn~de. The blockcan ~classified into first, second or
third degree block, depending on the degree ofabnormality in the impulse
transmission.
The electrical activation of the SAnode does not showup as a deflection on
the surface ECGleads. Thusin first-degree SAblock it is not possible to diagnose
this arrhythmia directly from the surface ECG,but there is a delay in the
conduction of the impulse from the SA nodeto the AVnode. In second:degree
AVblock there is a larger delay in the conduction of the impulse from the SA.
node and this is detectable on the surface ECG.In second-degree SAblock type I,
there is progressive shortening of the P-P interval in the conducted beats before
an impulse ~s not conductedand abeat :is dropped. This is due to increasing delays
near the sinus node:In second:degree SA block type II, impulses are not
conducted from the SAnode, and thus the P-P interval is a multiple of the basic
normal Sinus rhytlun. For example, during 2:1 second-degree block of type II,
every other impulse of the SA node results in a QRScomplex and thus this
arrhythmia is difficult to differentiate from sinus bradycardia.
Third degree SAblock results when the impulses generated at the SA node
are not conducted to the AVnode. This situation is not differentiable from sinus
node arrest using the surface ECG. P waves are absent because atrial
depolarization does not occur, and the patient depends on the activity of another
pacemaker in the cardiac pacing system such as from the AVjunctional, area.
Figure 4.9 shows the different manifestations of SAblock.
1" SAblock
2" SAblock
Figure4.9 Thesinus nodeactivation doesnot appearon the ECG.Thevertical lines indicate

sinus nodeactivationinstants. During1" SAblockthcre’is a delaybetweensinus nodeacti~,ation
andatrial activation. During2: i SAblockthe abnormalitycannotbe distinguishedfromsinus
bradycardia.In third degreeblockonly the ventrieularescape,rhythmis recorded.FromChou,T.
C. 1986.Electrocardiographyin clinicalpractice.2ndEd. Grime&Stratton.
DIAGNOSING, ARRHYTHMIAS 81
Diagnostic criteria: The rate is normal but it varies because of pauses; the
rhythm is irregular; P-R interval is normal; QRScomplex is normal but may
change as a .result of other pathologies; in type I block, P-P intervals shorten
tmtil,a~P waveis dropped and the resulting pauses are twice the shortest cardiac
cycle; in type II block the P-P intervals are a multiple of the cardiac cycle
(Conover, 1986; Chou, 1986).
Patients do not have any symptomsif the blocks are transient. In more
persistent cases patients complain of skipped beats. If the pauses between two
heartbeats are3 s or more, patients maybegin to feel dizzy, weak, chest pressure
or pain; or even have a transient syncope. If the patient had a recent myocardial
pathology then the patient should be monitored (Catalano, 1993).
Treatment is warranted in situations when the blocks are severe and
persistent and there is hemodynamic compromise. If medication caused the
arrhythmia then the dosage is reduced. Atropine IV is used to stimulate the SA
node and to improve the conduction through the atria. If the block is caused by
myocardial infarction then a temporary pacemakeris used until injury due to the
infarction is healed. If the sinus block appears to be a permanent condition, and
symptoms attributable to bradycardia are persistent, then an. implantable
pacemaker is mandated (Catalano, 1993). Studies in the literature. report that
sudden death dug to :bradyarrhythmia were-more related to depressed
automaticity and (or) SA block, than to AVblock.(Luna, 1993),
4.4.4 Sinus arrest
Sinus~ arrest occurs whenthe SAnode-ceases activity and .does not generate the
impulses necessary to maintain a minimal rate. In this,, situation subsidiary
pacemakers within the natural pacing system (AV junction or ventricles) take
over and result in a heart beat, i.e. an escape rhythmis generated.
Since the sinus node does not generate an impulse in: this abnormality, the
surface ECGdoes not manifest a P wave, or. P-R interval, .There is a long pause
in,the ECGuntil a subsidiary pacemakergenerates an impulse that causes a heart
beat.A, slower rhythm is then generated by the escape rhythm from a pacemaker
in ’the AVjunction or ventricles. Sinus arrest should be differentiated from SA
block. Pauses in sinus node activity ofup.to 2.0 s due to high vagal tone maybe
found infit, young people (Bennett, 1989). Figure 4.10 shows a prolonged period
of sinus arrest.
Figure 4.10 The ECGshows periods of sinus arrest. AVblock is also present. From Chou, T.
C. 1986. Electrocardiography in clinicalpractice. 2nd Ed. Grune &Stratton.
Patients with sinus arrest mayhave serious symptomswhenthe pauses in the

are long (3-9 s), and frequent, The symptomsare similar to those for low
tc output. Tlie patient may feel dizzy, fightheaded, weak and may .h~ve
]~s of transient syncope (Stokes-Adams syndrome). Shortness of breath,
chest pressure or pain, low blood pressure, and weak irregular pulses are also
manifested (Catalano, 1993).
Diagnostic criteria: The rate is normal, but it varies due to the’pauses; the
rhythm is irregular; all P waves, when present have the same shape; QRS
complex is normal unless other pathologies are present; there is an abrupt
interruption of the sinus rhythm. The P-P interval betweenthe pause has no fixed
relationship to the normal P-P interval (Chou, 1986; Conover, 1986).
Some patients may have no symptoms and very little hemodynamic
compromisedue to sinus arrest. However,there is the potential for sinus arrest to
develop into asystole (no activity in the cardiac ~muscle). Thus these patients
should be monitored if not treated. In other patients who manifest symptoms,
dosage of medication which may have induced the arrhythmia should be reduced.
Medication to stimulate the sinus node is administered to increase SAactivity. If
the sinus arrest is caused by cardiac disease, such as that of the coronary arteries
or acute infection;, then a permanent demandpacemaker is implanted (Catalano,
1993; Conover, 1986).
4.4.5 Sick sinus syndrome
On the surface ECG.the sick sinus syndrome (SSS), manifests itself as severe
sinus bradycardia, sinus arrest, SA block, bradycardia,~alternating with
tachycardia i.e. tac-hy-brady syndrome,chronic atrial fibrillation whichcontinues
even after cardioversion, and AVjunctional escape rhythm (Chou, 1986).
junctional escape rhythm results whena pacemaker in the His bundle triggers a
heart beat if the SAimpulse is abnormally impeded.
Twenty-four-hour ambulatory ECGrecordings are often used to obtain
diagnostic information of episodes of bradycardia or tachycardia. If symptoms
and rhythm disturbances are infrequent, then intracardiac electrophysiological
testing maybe helpful (Bennett, 1989). Sinus bradyeardia and tachycardia are
normal during sleep and physical exertion, respectively:
Diagnostic criteria: The rate is either fast or too slow; the rhythm is
irregular; the-P-R interval may be abnormal; the, QRScomplex is~ normal
~although other pathologies mayprolong it; distinguishing features mayinclude
severe sinus bradycardia, sinus arrest, atrial standstill,, SA block, sinus
bradycardia with recurring atrial fibrillation, bradycardia-tachycardia, transient
asystole following tachycardia or cardioversion, paroxysmalatrial fibrillation, or
inability of sinus node to accelerate in respOnseto, exercise (Conover,1986).
Intracavitary electrophysiologic studies of the sinus node ’function and
sinoatrial conduction time are performed to diagnose and select therapy for
patients. The sinus node canbe suppressed if artificially stimulated at rates higher
than its intrinsic rate. The sinus node recoverytime is the time between the last
artificial pacing of the sinus node and the first spontaneous firing of the sinus
node. The sinoatrial cor~duction time can be measured directi~using the sinus
node electrogram, which records the electrical activity close to the sinus node,
and the atrial electrogram which records atrial activity (Macfarlane and Lawrie,
1989). Thb criteria of sinus recovery time and-sinoatrial conduction time are
sensitive, but not specific to SSS. Morethan 40%of pacemakers implanted are
due to SSS (Luna, 1993).
Patients with SSS have symptoms, and are treated, according to the
particular type of the arrhythmia.- Medicationsthat increase the heart rate (for
bradycardiaCondition) would tend to increase the heart rate of the tachycardia
condition in a tachy-brady syndrome. For ~tacliy-’brady syndrome, an e~fective
tre:atment is to administer cardiac depressant medications that control the
supraventricular ~tachycardia and then implant a :permanent demandartificial

pacemakerto maintain a minimal heart rate (Catalano, 1993).
4.5 ATRIOVENTRICULAR BLOCK
In atrioventricular (AV)block the impulses generated at the SA node are either

delayed or-bl0cked in the conduction pathway .between the AVnode and the
ventricles. A first-degree block results in a .delay of the~6~dueted impulse, a.
second-degree block results in intermittent or periodic impulses being blocked,
and a third-degree block results in a complete block of the impulse from the SA
node to the ventricles. These detays in the conduction of the impulse are
manifested on the surface ECGand the His bundle electrogram by increases in
certain intervals. Figure 4.11 describes some of the features of the surface ECG
used in diagnosing AVblock.
Diagnostic criteria
Type HR (bpm) P-R(s) Morpholo[y Particulars
1". N > 0.2 P: N; QRS:N i P followedby QRS
2",i r, ’ N Increases P: N/blocked R-R with block is
until QRS: N shorter than twice P-
locled ¯ P
2"~¢II N N P:. (N/block) P-R interval fLxed,

QRS: ’ " dropped beats :
(N/broad)
3* <60 P: regular ~P and QRSare not
QRS: narrow associated
or broad " ~
Figure 4.11 Diagnosticcriteria for differentiating betweenarrhythmiasof AVblock, The

diagnosticcfitedamaydiffer if concurdng
withanotherarrhythmia~
HR:heart rate; N:normal;P: P
~va~6of ECG;R-R:R-Rinterval of ECG;P-P: P:P interval of ECG;H-V:HLV interval Of HBE;
/:
4.5.1 First-degree AV block
During first-degree AVblock the impulse frOm~the SA node is delayed aS it

travels to the atrial conduction system. The P-R interval reflects the conduction
time of the impulse through the AVconduction system, and with AVblock is
greater than 210 ms.
Thus all the P waves on the surface ECGhave an associated QRScomplex
following it. In most situations, the delay occurs in the AVnode, but rarely does
it occur within the a~-ia or bundle of His (Bennett, 1989). This is validated from
the HBEwhich also gives a more precise location of the block. The delayin the
AVnode shows up asa prolongation inthe A-H time of the HBE.Very rarely
the P-A interval (conduction time between SA node and AV:node) prolonged
(,HelfanL 1974). Figure 4~12(a) shows an ECGtrace manifesting first-degree
block.
(a)
Ill
(b)
(c)
’,
:::
Figure 4.12 (a) First-degree AVblock. (b) Type I second-degree AVblock with the
Wenckebachphenomenon. (c) TypeHsecond-degreeAVblock. (d) Third-degreeAVblock.
Chou.T. C. 1986.Electrocardiography
in clinicalpractice.2ndEd. Grtme&
Stratton.
Diagnostic criteria: The rate depends on the SA node and is normal; rhythm
is regular; QRScomplex is normal; the P-R interval is greater than the normal
value of 200 ms; each P wave is followed by a QRScomplex.
First-degree AVblock by itself does not cause patients to have any
symptoms,and is not usually treated (Catalano, 1993). Howeverif the arrhythmia
is associated with myocardial infarction the situation could progress to a higher
degree block. The patient needs to be monitored in these situations. If the patient
has persistent symptoms(due to a coexisting abnormality) then medication
prescribed. If the H-Vinterval is between 55 ms and 75 ms, a pacemaker should
be used on patients with persistent symptoms.If the H-Vinterval is greater than
75 ms, a pacemaker must be used (Macfarlane and Lawrie, 1989).
4.5.2 Second-degree AV block, Type I
In type I second-degree AVblock (Mobitz I), there.is an increase in the delay

the AVnode for each consecutive heart beat until the impulse from the SA node
is not conducted. This sequence of incremental delays may be persistent or
intermittent.
The incremental delays at the AVnode are manifested on the surface ECGas"
consecutive beats with increasing P-R intervals, wifla conduction of the impulse to
the ventricles, until one beat. isnot conducted and results in a P wavewithout its
associated QRScomplex. This is known as the Wenckebach phenomenon. The
periodicity of the beats is usually given by two numbers (e.g. 4:3 means 3
waves in every 4 are conducted).
~ ~DIAGNOSING~ ARRHYTHMIAS ~ 85
After the noneonductedbeat, the AVconduction:recovers, and the. sequence

starts again with the first beat having a normal P-R: interval. The increment in
the P-R interval in the subsequent (second conducted).,beat is usuallythe largest
(Chou, 1986; Bennett, 1989). The following conducted beats also have prolonged
P,R intervals but not with increments as large as~the second conducted beat.
¯ , The SA node ~provides impulses at regular intervals independent of
conduction abnormalities in:the AVnode. Since the P-R interval progressively
prolongs, the corresponding R-R interval shortens, This happens due to the
consistent, rate,of the P,-wave, and the .increasing P-R interval, whichresults~ in a
decreasing R-R interval. Similar reasoning explains the R-R interval containing
the blocked P wave being shorter than the sum of two P-P intervals. This
situation is not always noticeable since sinus arrhythmia and parasympathetic
activity change the SArate and P-R interval. Figure 4.12(b) shows an ECGtrace
mariifesting type I~second:degree AVblock.
"~The l-IBEreveals progressive prolongation in the AHinterval if the block is
at the AVnode (Helfant, 1974). Sometimesthe block can occur in the His bundle
and~then :the H wave in the HBEis split. The split in the H wave of the HBE
progressively lengthens until a beat is blocked and then the A waveis followed by
onlyone’part,of the split H wave (Chou, 1986).
..... :Diagnostic criteria: Progressive lengthening of the P-R interval until a P
wave is blocked; shortening of the R-R interval until a P wave is blocked; the R-
.R ~inte~al containing the: blocked P waveis shorter than twice the P-P interval;
the rate is normal; rhythm is irregular; P-R interval > 200 ms; QRScomplexis
normal (Conover, 1986).
~ Pal~ients who have a slow heart rate and then present this arrhythmia
complaiii~’With symptoms related to low cardiac output, such as dizziness,
weakness, transient syncopal (fainting) events, chest pressure or pain, slow
irregiilar.pulse, and a low blood pressure. A patient might sometimes feel a
"skipped~beat" whenthe blocked beat occurs.
,~If~the ,arrhythmia-is transient there is no specific treatment. In more
persistent eases~medication maybe administered, and in drastic cases (as in when
the HVinterval is greater than 75 ms), a permanent demand pacemaker is
prescribed(Macfarlane and Lawrie, 1989; Catalano, 1993).
4.5.3 Second-degree AV block, Type II
Type II second degree AVblock (Mobitz II) is less commonthan type I and
usually involves abnormal conduction in the His bundle or the bundle branches.
In ~second degree block there is intermittent failure of conduction of the
impulses to the ventricles, and this is manifested on the surface ECGas P waves
without its associated QRScomplex. The abnormality lies in the His bundle or
bundle branches as comparedto in the AVnode as with fn’st-degree AVblock. If
the block is in the bundle branches the QRScomplexes are broad (Bennett 1989;
Chou, 1986). Figure 4.12(c) shows an ECGtrace manifesting type II second,
degree AVblock.
A block can be .in the His bundle itself, in which case the QRScomplex~is
narrow. -The HBEthen shows the A and H waves following the P wave.of the
ECG~It is also possible to have conduction abnormalities within the His bundle
(Helfant~~1974).
Diagnostic criteria: The rate is normal; the rhythmis irregular; P-R interval
is normal (120 - 200r ms), fixed and consistent, but some P waves are-not
conducted; the QRScomplex may be broad if the .conduction defect is in the

bundle branches (Chou, 1986; Conover, 1986).
Symptomsthat patients complain of depend on the heart rate, and vary from
lethargy to more severe cases such as respiratory arrest. Seconddegree, type II,
block is treated immediately since it is associated with sudden death and slow
ventricular rates (Bennett, 1989). Medication maybe administered to increase the
SA rate, a temporary pacemaker may be required if the arrhythmia has
developed after myocardial infarction. A permanent pacemaker should be
implanted if the arrhythmia does not clear 72 to 96 h after it developed
(Catalano, 1993).
4.5.4 Third-degree AV block
Complete AVblock (or third-degree block), occurs when there is a total

interruption of the transmission of atrial impulses to the ventricles. The-block
occurs at the AVnode or below the AVnode.
The .ventricular depolarization (if any) is triggered by a subsidiary
pacemaker, Somepatients may have a regular P-P interval and different regular
R-R interval. There is some controversy as to the meanings of AV dissociation
and complete A V block. In AVdissociation, the atrial rate is slower than the
ventricular rate, whichresults from a ventricnlar ectopic site .which intrinsically
paces faster than the SAnode. In completeAVblock, .the atrial.rate is faster than
the ventricular rate (Chou, 1986; Catalano, 1993). Figure 4.12(d) shows an
trace manifesting third-degree AVblock.
The shape of the QRSdepends on the site of the block and is narrow, if the
block occurs near the .His bundle. The rate is likely to be that of a pacemakerin
the AVnode or His bundle (40 to 60 bpm). The QRScomplex is wide and has
idioventricular rate (20 to 50 bpm)if the block occurs belowthe bundle of His.
Helfant (1974) reports on studies of patients with complete heart block, ,The
HBEshows the site of the block to be below the level of the. AVnode when the
QRScomplexes are wide (greater than 120 ms), and the heart rote is a slow
idioventricular rate (less than 45 bpm). But with complete congenital heart block
when the QRS is of a normal morphology, the His bundle potentials are
temporarily associated with ventricular activity and not with atrial activity.
Diagnostic criteria: The rate is less than 60 bpm; the rhythmis regular; the
P-R interval is not relevant; the QRScomplex is narrow or broad depending on
the location of the subsidiary pacemakerand the. site of the block; distinguishing
features include regular P waves with a rate less than 130/min; QRScomplexesat
a rate of less than 60 bpm; and AVdissociation (Chou, 1986; Conover, 1986;
Catalano, 1993). ~" ~..
Patients with third;degree AVblock and a high hear~ rate, resulting in
sufficient cardiac output, do not have symptoms.However,these patients usually
cannot tolerate exercise. Most patients experience symptoms related to low
cardiac output, including dizziness, weakness, syncope, pressure and pain in the
chest, shormess of breath, and low blood pressure. Stokes~-Adamssyndrome is
caused by intermittent third-degree AVblock. This syndrome is marked by
transient :fainting spells with low blood pressure. It is aseful to be able to monitor
these epiSodesin spite of their transient nature (Catalano, I993). ~..
Third-degree AVblock is considered a cardiac emergencyunless the patient
is tolerating the arrhythmia well. Even in the latter case, the patient should be
monitored. Medication maybe prescribed to increase the SA rate or ~increase
conduction through the AVnode and reduce the degree of the block. If the block
is transient a, temporary pacemaker is prescribed, otherwise a permanent
pacemaker is warranted (Catalano, 1993; Conover, :1986).
4.6 BUNDLE BRANCH BLOCK
The .,el~ctric~ impulse normally, generated at the SAnode, travels through the AV
~o.de, ~His bundle, and then through.th e fight and left bundle branches, which
sp~ad~0ut into the Purkinje system.. The left bundle branch divides into the
~a~rior ~ ~and superior, subdivisions called fascicles. If these pathways behave
no~ail~, i~e fight and left ventricles are activated at the same time, resulting in
a Synchronous contraction of both ventricles. During right (or left) bundle
branch block, RBBB(or LBBB),there is an abnormal conduction of the impulse
through the fight (or left) bundle. The impulse can also be blocked in the anterior
or (and) posterior fascicle resulting.in anterior hemiblock, posterior hemiblock,
bifascicular, or trifascicu!~ bl0~k. Figure 4.13 describes someof the features of
the surfaceECGUsed in di~ignosing bundle branch block.
T~e,
N .: QRS>120ms R’ in right: PCL
Broad S
aVL,V6.~Delay in
¯ deflection.in right
PCL > 50 ms ¯
LBBB N QRS>120 ms Broad, notched, R in
NoQ:~ I, V6 I, V5, V6. Broad,
negative QRSin ~V6.
N QRS: (N/> LAD of QRS axis
by 20 ms) .
QRS: (N/> ;RAD of QRS axis
by 20 ms)
Figure4.13 Diagnosticcriteria for differentiatingbetweenarrhythmias of bundlebranchblock.

Thediagnosticcriteria maydiffer if concurringwithanotherarrhy~-nia.HR:heart rote; N:normal;
PCL:precordialleads; LADf
left axis deviation;RAD:fight axis deviation;l: or:
4.6.1 Right bundle branch block
In RBBBthe impulse is blocked in the fight bundle branch resulting in a delayed

activation of the right ventricle (RV). The ~ft ventricle (LV) is depolarized
normal manner via the normal left bundle branch. The RVis depolarized later
than :the LV due to the impulse propagated from the LV through the
myocardium. ~
The .dclayedactivationof the RV is manifestedby a broaderQRS
(->120ms)~ Theearlypartof theQRScomplex is thesameas thatin thenormal
morphology. TheRV scptumandfrccwallsthcn beginto depolarize because of
theearlier occurring LV depolarization, resulting in theQRScardiac vector
being directed anteriorly and rightward. The cardiac vector during the delaye~
RVcontraction phase is unopposed by left ventricular forces. Thus a prominen
secondary R wave, R’, in right precordial leads (V1 and V2) is recorded. The let
precordial leads (V5 and V6) as well as lead I record a slurred S wave. The
wave is slurred because of the slower conduction through the cardiac muscl~
during the abnormal spread of the impulse to the RV. V1 is usually the mos
important lead for diagnosis of RBBB(Chou, 1986; Bennett, 89). Figure 4.14(a
shows an ECGpattern manifesting R.BBB.
Diagnostic Criteria: A QRSwidth greater than 120 ms; ~an R’ in righ
precordial leads with rsR’ or rSR’ morphology; delay in deflection in righ
precordial leads greater than 50 ms; and wide S wavein I, V5, and V6; the rate it
normal; rhythm is normal; P-R interval is normal; in leads I, aVL, and V6 thert
is a broad S wave; or secondary T-wave morphology changes (Chou~ 1986
III aVR aVL aVF
V
3 V
4
III aVR aVL
Figure4.14 (a) Right bundlebranchblock, manifestedby a wideS wavein leads I, V5,and

V6.(b) Left bundlebranchblock, manifestedby an absenceof a q wavein leads I, V5,andV6.
FromChou,T. C. 1986.Electrocardiography
in clinicalpractice.2ndEd. Grune&Stratton.
Variations of the diagnostic criteria exist. The S wave may be small o~

absent. The initial R wavemaybe absent or the R’ maybe smaller than the initial
R wave but remains to be wide in V 1. The T wave is in an opposite deflection as
compared to the abnormal deflection in the QRScomplex. The T wave ~s uprigh!
in leads I, V5, and V6 and inverted in the right precordial leads (the normal
morphology). A diphasic T wave is also possible. RBBBmay be transient o~
intermittent, usually occurring during a faster heart rate. A partial RBBBresults
in a similar morphology but the QRSwidth is between 80 and 110 ms (Chou,
1986).
::~!~:.,,Patients with RBBBhave cardiac output that is minimally compromised.

.~ere are. no symptomsassociated with RBBB,however, in the setting of acute
anteroseptal myocardial infarction, a pacemaker may be warranted (Catalano,
1’993~ C0nover, 1986).
4.6~2 Left bundle branch block

A block in the left bundle branch results in a delayed activation of the L¥ due to
electrical activity from the normallydepolarized right ventricle. Activation of the
interventricular septum is initiated by impulses arising from the fight bundle
branch and is therefore in the opposite direction to that of normal. The LV
begins d~poladzing from the right sepmm,apex; and ventricular free wall.
The electrical forces from the right septum and ventdcular free wall oppose
each othfr and are thus mostly canceled. The activation of the apex, however,
r~sults in’h depolarization from the endocardium (inner Cardia~ muscle) to the
epica~dium(outer cardiac muscle). The cardiac vector during this initial phase
thus oriented leftward, anteriorly, and inferiorly. Thus the small q wave seen
u~ualiy’ in lead I and the left precordial leads is absent.
¯ The"activation continues to spread from the right to the left in the septum
r~sulting in a net cardiac vector oriented leftward, posteriorly, and inferiorly.
Thus leads.V5, V6, and I continue to record an upwardR wave: In addition, since
the c0nduetion is abnormal and does not follow the Purkinje network, the R wave
is notched: and slurred. The asynchronous depolarization of the left and: right
ventdcle~ result in a prolonged QRSduration o:f 120 ms or more.
The abnormaldfpflarization of the LVis associated With an ~alteration of the
rgpolarization phase: The.electrical forces du~ing the repolari’zation phase are
6pposite in polarity to those generated during de~ladzation. If ~e repolarization
proceeds in the same right-to-left direction as the LBBB depolarization phase, the
cardiac vectors during the S-T segment and T wave are opposite to that of the
QRS(Chou, 1986). Thus S-T segment depression and a T-wave inversion are
recorded on leads I, V5, and V6. Figure 4.14(b) Shows an ECGpattern
manifesting LBBB.
Diagnostic criteria: QRSduration _~ 120 ms; broad’mOnophasic R wave in
leads I, V5, and V6, which is usually notched or slurred; absence of Q wave in
leads I, V5, and V6; displacement of S~T segment and T wave ina direction
opposite to the major QRSdeflection; rate, rhythm and P-R interval are normal;
broad and mostly negative QRSin v6; in leads I, aVL, and V6 there is an R
wave, no q wave, and no S wave (Chou, 1986; C0nover, 1986):
P~a] LBBBhas a similar morphology as 6omplete LBBB, but QRSwidth
is between 100 or 110 ms. The time of the intrinsic depolarization is prolonged to
60 ms or longer in the precordial leads. TheQ wave is absent in the left
precordial leads. The R wavein the left precordial leads is notched and/or slurred
(Chou, 1986; Bennett, 1989).
In a patient with complete ~ right or left bundle branch block, the H-V
interval of the His bundle electrogram represents the conduction time through the
functional conduction branch. If the H-V interval is prolortged, this would
further indicate that the functional portions of the conduction system are
abnormal. Lesions which occur at the origins of either or both of the bundle
branches mayaffect the His bundle. Of patie~its with RBB~,23%manifested H-V
prolongation, but 8I% of patients with LBBBmanifested H-V prolongation,
implying first-degree block of the fight bundle branch. The His bundle itself may
have lesions which result in various degrees of heart block, i.e. intra-His bundle
block. These are manifested as a split H wave, H and H’, separated by 10 to 20 ms
or more (Helfant, 1974).
Patients with LBBBhave no symptoms that are associated with the block
itself. If the arrhythmia has developed recently in association with acute
myocardial infarction, there is an increased probability of complete block and a
higher mortality rate, and these patients should be monitored closely and
prescribed a temporary pacemaker (Catalano, 1993; Conover, 1986).
4.6.3 Left anterior hemiblock
The anterior division of the left bundle branch conducts impulses to the
anterosuperior (frontwards and upwards) region of the LV, and a block in this
pathway results in left anterior hemiblock (LAH). LAHresults in a delay in the
activation of the anterosuperior portion of the LV, but activation of the
posteroinferior portion (caused by the posterior division of the left bundle)
unaffected.
In LAH,the impulse initially spreads inferiorly through the posterior
division of the left bundlebrancli.. ~his results in an initial positive deflection in
infedor!y oriented leads (II, III, and aVF)and in an initial negative deflection
the lateral leads (I and aVL)..The excitation then begins to spread from the
posterior region of the LV t0"~the anterosuperior region, The cardiac vector
during this phase Will thus be superiorly directed resulting in an R wavein I and
aVL~mdan S wavein leads II, liI, and ~VF. The forces during this phase are also
very prominent and result in the meanQRSto be shifted leftward and superiorly,
i.e. a left axis deviation.
The conduction through Ordinary, slow conducting myocardiumrather than
specialized conducting tissues results in delayed activation of the anterosupedor
region and consequently unopposed electrical activity from the rest of the
ventdcles~ Thus the superiorly directed waveis larger than the initial inferiorly
directed waves. To diagnose LAH,two criteria must be satisfied: there must be
left axis deviation, and the inidal direction of ventricular activation must be
inferior and to the right, i.e. there must be an initial r wavein leads II, III, and
aVF. Figure 4.15(a) ~hows an ECGmorphology during LAH.
Dh~gnostic criterM: The rhte is normal; rhythm is normal;. P-R interval is
normal; QRScomplex is normal (or lengthens by 20 ms); left axis deviation
the QRSaxis in the frontal plane between -30* and -90*; qR or R waves in leads
I and AVL; rS complex in leads II, HI, and aYF; terminal R wave in aVRand
aVL; increased QRSvoltage in the limb leads (Chou, 1986; Conover, 1986).
4.6.4 Left posterior hemiblock
In left posterior hemiblock, LPH,the posterior division of the left bundle branch,
which conducts impulses to the posteroinfedor regions of the LV, is blocked.
The situation with LPHis opposite to that with LAH.The activation in the
posteroinferior region of the LVis delayed. The electrical forces during the
delayed activation results in a cardiac vector directed inferiorly and rightward.
The delayed forces, as in LAH,are unopposed, and this results in a rightward
displacement of the mean QRSaxis, i.e. right axis deviation RAD.Since the
anterolateral region of the LVis activated early there is an initial R wavein leads
I and aVL and a q wave in the inferior leads (II, III, and aVF) (Chou, 1986;
Bennett, 1989). Figure 4.15(b) shows the ECGmorphology during LPH.
I II III aVR aVL aVF
(a) V
1 V
2 V
3 V
4 V
5 V
6
LeadI LeadII LeadIII aVR aVL aVF

""~.~
"" " :. ¯.......
:"U~! ’ - -
(a)
V
I V
2 V
3 V
4 V
5 V
6
Figure4.15 (a) Left axis deviationduringleft anterior hemiblock.(b)Rightaxis deviation

.duringright Posteriorhemibloek.
in clinicalpractice.
2ndEd. Grune&Stratton.
Diagnostic criteria: The rate is normal; rhythm is normal; right"axis

devihtion, +90° to 180°; P-R interval is normal; a normal or slightly prolonged
(20 ms) QRSwidth; lead I has a rS complex; the inferior leads have a
complex; or an r wave in aVL(Chou, 1986; Conovet, 1986).
The phenomenonof~RBBBwith fight axis deviation is not verycornmon. It
suggests complete block of the right bundle and left posterior division. In this
situation the ~H±vinterval on the His bundle electrograrh measuresthe conduction
through the anterior division of the left bundle. Fewcases of RBBBand fight
axis deviation have been studied and the majbdty have shownH-V prolongation.
A normal His-Purkinje conduction time has been noted occasionally (Helfant,
1974).
4.6.5 BifasCicular block
If conduction is blocked in only two of the three fascicles (among the right
bundle’ branch, anterior fascicle, and posterior fascicle), tile functional fascicle
.will cbnduct ~itrial impulses to the ventricles and maintain sinus rhythm. A block
m the remaining third fascicle will lead to complete AVblock.
The most common type of bifascicular block is RBBBwith LAH. The

posterior fascicle of the LBBis a stouter structure and has a better blood supply
than the anterior fascicle and is therefore less vulnerable. Thus RBBBwith LPH
is less common. When RBBBand LAHare present, activation begins in the
posteroinferior region of the LV. Then the activation spreads abnormally to the
anterolateral region of the LVand through the septum to the right ventricle. The
first part of QRSmorphologyis similar to that of LAHand the last part similar
to that of a RBBB.Patients with acute myocardial infarction and this type of
bifascicular block maydevelop complete heart block.
An ECGmorphology of RBBBwith marked left axis deviation is common.
This pattern has aroused interest since several studies indicate that it is the most
commonpattern antedating the development of compJete heart block. According
to the tdfascicular structure of the conduction system, the RBBBwith marked
left axis deviation indicates complete block of the right bundle and anterior
fascicle of the left bundle. The H-Vinterval in the His bundle electrogram then
represents the conduction time ~through the posterior fascicle, If this interval is
also prolonged, it wouldindicate a first degree block of the. posterior left bundle.
The H-V interval measured from the His bundleelectrogram helps differentiate
whether a patient has in addition to RBBBand left axis deviation, first degree
block of the posterior left bundle. This diagnosis can be clinically significant
since it mayherald the developmentof complete heart block (Helfant, 1974).
D~agnosttc criteria for RBBBw~th LAH::QRS duraUon _ 120 ms; an RSR~n
lead V1, with the R’,. wavebroad and slurred; wide and slurred S waves in leads I,
VS,.and V.6.. The first 60 ms of the QRScomplexhasa frontal plane ~QRSin
-30 to -90 ; an initial rlwave in the inferior leads (Ch0u, 1986).
Diagnostic criteria for RBBBwith LPH:QRSduration > 120 ms; an RSR’ in
lead V 1, with the R’ wavebroad and slurred; wide and slurred S waves in leads I,
VS, and V6. The first 60 ms of the QRScomplex has a frontal plane AQRSin
+90*or more to the right; an rS wave in lead I; and a qR wave in leads II, III,
and aVF (Chou, 1986).
Block in anterior and posterior fascicles of the left bundle branch causes
complete LBBB.The combination of LBBBand LADmay indicate more disease
of conduction tissues than LBBBwith a normal frontal axis. P-R interval
prolongation is usually due to impaired AVnode conduction, but in the context of
bifascicular block it is more likely to reflect abnormal conduction in the
functioning fascicle (Bennett, 1989).
4.6.6 Trifascicular block
A trifascicular block, which results in complete AVblock, is a block in the right

bundle branch and the two divisions of the left bundle branch. The inherent
ventricular escape rhythm has a slower rate and a wide QRScomplex since the
intrinsic pacer is located at the peripheral part of the conduction system, far from
the sites of the block. A change in the morphology of the QRScomplex from a
previous knownbifascicular pattern is indicative of a tdfascicular origin of the
compete AVblock. A recording from the His bundle is required.to make a
conclusive diagnosis.
If the block in one of the three fascicles is incomplete the ECGwill display a
bifascicular block with first Or seCond-degree AX/ block. Thus thep0ssible
morphology of the ECGis that Of RBBBwith LAHor LPH, divisional LI~BBand
P-R prolongation, or second-degree AVblock. The cause of the P-R delay needs
tO be determined.: The long P-R interval maybe due to a proximal lesion of the
bundle of His. Studies of the His bundle electrogram are needed to determine if it
is a true :trifascicular block (Luna, 93; Chou, 1986). For example, Figure 4.16
shows: how, the His bundle electrogram is used to differentiate in the case of first
degree heart block associated with RBBBor LBBBand determine if the
conduction abnormality lies in the AVnode or the His-Purkinje system. Figure
4.16 shows situations of two patients with a prolonged P-R interval. Patient 1 has
an abnormal His-Purkinje conduction time (H-Q = 92 ms), and a normal P-H
time (115 ms). Patient 2 has a normal H-Q~time (39 ms) with an abnormal
nodal conduction time (P-H = 175 ms) (Helfant, 1974).
P-R (ms) ..P-H (ms) H-Q (ms)

Patient 1 210 ~ 115 92
Patient 2 220 175 ’ 39:
Figure 4.16 Measurementsfrom the His bundleelectrogramhelp diagnosebetweenabnormal

conductionin His-Purkinjesystem(increasedHQinterval in patient 1) andabnormalAVnode
conduction
time(increasedP-Hintervalin patient2) (Helfant,1974).
4.7 PREEXCITATION ARRHYTHMIAS
Preexcitation arrhythmias result when the impulses ~0f the SA node reach the
ventricles earlier than ~normal. The enhanced conduction may be due to
conductive muscle (beside the normal conduction pathway) anywherebetween the
atria, and.ventricles (Wolff-Parkinson-White.syndrome), a seg, .mem:. -ofthe-AV
node which conducts the impulse faster than usual (Lown-Ganong-Levine
syndrome), or Mahaim fibers which are abnormal pathways.between the AV
node~ His bun~e, or bundle branches and the ventricles.
4~7.1 Wolff-Parkinson-White syndrome
The a~normal pathways in the Wo.lff-Parkinson-White (Wp~W) syndrome Consist

of cardiac muscle between the atria and ventricles, which Cpnductfaster than the
AVnode. ~These accessory .pathways, oneon each side of the he~, arb!c0ngenital
and arecalled the bundles of Kent. In patiems with wPWone’or both of these
bundles 0fKent c~ conduct impulse~s from the SA nod~ ito the ve~cles.
An~ata-ial impulse that~avels through the accessorYpathway~,:~sults in early
excitation of the ventricles. The early activation of the ventricles is manifested on
the surface ECGas a short P-R interval and a slurred initial portion of the, QRS
complex, i.e. a delta wave. The P-R interval is shortened because the intrinsic
deia~ of the AVnode is avoided. The .delta waveresults f~omthe preexcitation
traveling through the slow-conducting myocardiuminstead of, the. speciMized
system.
Type, A wPW.r esults whenthe Kent bundle, o~n the le~ side of~the he acts
m
as the accessorY pathway, Thus the left ventricle begios to depolarize before the
right ven~cle/(si~milar t~ a right bundle:broth bi~)~ Iii type A,the delta wave
and the QRSc~mplexare up~ight in all th6. precordial leads. Vishows either’a
notched R .wave or Rs or R~r’ ~norphology~ In type B WPW the bundle of Kent
on the fight side of the heart conducts impulses prematurely to the right
ventricle. The fight ventricle thus depolarizes before the left ventricle (similar to
a left bundle branch block). The delta wave and the QRSare negative in V 1 and
V2 but are upright in the left precordial leads (Chou, 1986; Catalano, 1993).
Figure 4.17 shows the ECGmanifesting type B WPW syndrome.
~LeoclT ~ "rrr oVR ¢ZVL OVF
Figure 4.17 Type B WPWsyndromeresembles the morphologyof left bundle branch block.
in clinicalpractice.2ndEd. Grune&Stratton.
The delay of impulses in the AVnode serves to protect the ventricles from
rapid electrical activity due to atrial fibrillation (350 to 600 bpm). The bundle
Kent howeverprovides a route for high rate impulses to activate the ventricles.
Thus patients with atrial fibfillati0n and preexcitation can have a ventdcular
response, thatean lead toheart failure or shock and ventricular fibrillation.
If an ectopic beat in the atria occurs~dufing-normal Sinus rhythm~reenla’y
tachycardia cotdd ’.result due to the accessory pathway and AVn6de~ having
different refractory periods. This arrhythmia is an example of paroxysmal
supraventricular tachycardia; PSVT, and is manifested on the surface ECGas
narrow ventricular complexes in rapid, regular succession. There are no delta
wavesin this situation. Treatment of this situation is directed at incre~a~ng the
refractory period of the AVnode and includes medication and cardioversion, the
latter resulting in the refractoriness of the entire myocardium.
Somepatients"with PSVTdo not present any evidence of pre~xcitation on the
surface ECi3.:In thesesituations inVasive~ electr~physiologic studies mayreveal a
concealed bundle of Kent~ This accessory path~ does no~ conduct impulses
from the SAnode either because of its distance fro~nthe SAnode, the length of
the bundle; ~ direction of conduction possible, o~’~onducti~An~timeinvolved.
Hbwever,impulses :from the ventdcles ~an~ be~con~lUctedretr0grad~ to the atria,
throug h the concealed pathway. Thus there is no delta wave or ~P.-qR interval
shotterling in the normal sinus rhythmof the,an-hythmia. A patient with a normal
ECGmorphology during sinus rhythm¢ and an inverted P wave between QRS
complexes during tachycardia, should be suspected for concealed preexcitation
(Bennett, 1989).
inti:acavitary electrophysiologi~ studies-that include pacing the atria at
different rates~’~fid recording theletect~o~i!am help to 10~ai~ize the ~site’ of the
anomalous pathway (Luna, 1993~ Maefaflane and Lawrie; 1989)? Right atrial
pacing results ~n greater Prc~citation for ~ type B~Wsyndrorn6 tha~.,ifor ~ type
AW-PW. Similarly it is possible to see inore preexcitation in patients with type A
WPW syndromeif the left atrium is paced, suggesting that the accessory pathway
is on the left. Electrogramsfrom the left ventricle record activity coinciding with
the delta wave on:the ECGfor type. A WPW syndrome. Recording activity from
the right and left atria simultaneously helps determine the location of the
retrograde ventricle-atria conduction in patients with WPW and supraventricular
tachycardia (Chou, 1986).
,Diagnostic criteria for typical WPW syndrome: the:.rate is normal;, the
rhythm is regular; P-R interval is less than 120 ms; QRScomplex width is
greater than 110 ms; distinguishing features include a short P~-R, broadQRS,
delta wave, and a tendency towards PSVT, and atrial fibrillation or flutter;
Secondary T waves may be present.
Diagnostic criteria for concealed WPW syndrome: the~rate is normal; the
rhythm is regular; P-R interval normal; QRScomplex normal; the distinguishing
features include normal P-R, normal QRS, and a tendency to PSVTand atrial
fibrillation or flutter.
WPW by itself does not produce any symptoms on patients. However, if
supraventricular tachycardia is present with rapid rates,then symptomspresent
are due to low cardiac output. The patient mayfeel weak; dizzy, palpitations in
the chest, pressure or pain in thechest, or shortness of breath (Catalano; 1993).
Treatment for induced PSVTwould involve use of vagal maneuver, and if
this is unsuccessful, cardioversion or medication is administered based on the
hemodynamicstatus of the patient. Treatment of atrial fibrillation and a rapid
~,entricular rate:would include cardioversion and avoiding digitalis (Conover,
1986).
4;7.2 I~own-Ganong-Levine syndrome ¯ -~
In the Lown--Ganong-Le~ine (LGL) syndrome impulses:from the ~SA node

bypass the AVnode as they travel accessory pathways. The accessory pathways,
James fibers, are extensions of the normal intranodal pathways from the SAnode,
and these terminate below the AVnode on the bundle of His.
The delay of the AVnode is bypassed so there is a shor~eningof the P-R
interval on the surface ECG.Since the impulse after bypassing the AVnode
travels through the bundle of His, i.e. the natural conduction system, the
ventricleS’are depolarized normally, and ~the QRScpmplex has a normal
morphology.Thus there is no delta Wavebecause the impulse travels through’ the
normal conduction system of the heart after the bundle of His. Figure 4.18 shows
the ECGmanifesting LGL.
HI aVR aVL aVF
I II
Vl V
2 V
3
.......... : ......... ~.
F|g~re4.111TlaeP-Rinterval is short, andno del~Wave is presentin the LGLabnormality.

in clinicalpractice.2ndEd.Grune& Stratton.
96 DESIGN OF CA~IAC PACEMAKERS
Diagnostic criteria: the rate is ~normal; the rhythm .is regular; the P-R
interval is < 120 ms; QRScomplex normal; distinguishing features include a
short P-R, normal QRS,and tendency to PSVTand atrial fibrillation or flutter;
no delta waveis present.
The patient does not have any symptoms due to LGL syndrome itself.
However, if LGLsyndrome is associated with supraventricular tachycardia,
symptomsof low. cardiac output are present. Treatment is crucial in ~ the case of
associated atrial arrhythmias or supraventricular tachycardia. LGLsyndrome is
treated well with cardiac medications and surgical intervention is dangerous and
not often effective (Catalano, 1993).
4.7.3 Mahaim-type preexcitation
Mahaimfibers from ,the base of the AVnode, or top of the His bundle, to the
ventricles conduct impulses originating from the SA node and traveling via the
AVnode directly to the ventricles.
These Mahaim fibers may :originate in the AVnode, a nodoventricular
connection; or in the~.,His bundle or bundle branches, a fasciculoventricular
connection. The impulse from the SA node is thus delayed normally at the AV
node and then .directly travels.to, the base of the ventricles via the Mahaim
fibers.
The surface ECGthus manifests anormal P-Rinterval and the delta wave due to
slow.conduction via the accessory pathway.
Diagnostic criteria: The rate is normal; the rhythm is regular; P-R interval
may be short or normal; QRScomplex varies in morphology; distinguishing
features include a tendency to PSVTand atrial fibrillation or flutter. The ECG
morphologydepends on the origin and insertion of the extra fiber, as well as:its
length.
Treatment is same as for the situation of supraventricular tachycardia with
WPWsyndrome.
4.8 SUPRAVENTRICULAR ECTOPICS
Supraventricular arrhythmias originate above ~the His bundle, due to impulses

generated outside the SA node. Some of these abnormalities may be due to a
premature impulse or enhanced automatiejty~of sites in the atria and include
premature atrial contraction, atrial tachycardia, atrial, flutter, or atrial
fibrillation.
4.8.1 Premature atrial contractions ~ ,- ~
An ectopic site in the atriummaygenerate an impulse that prematurely results in

a heart beat. This premature atrial contraction (PAC) is caused by regions
atria whichalso have the same intrinsic rate as the SAnode.
The ectopic
focus. The have as in
normal is in the right :atrium, theP wave’saxis is
directed ~us P waves in the limb leads
appear normal, while those in V1 through V4 are inverted (Chou, 1986). The
ventricles are activated via the normal fonduction system, and thus the QRShasa
normal morphology.
The premature ectopic beat may occur very early in the cardiac cycle and
overlap with the T wave of the preceding cycle or it mayoccur just before the
normal sinus P wave and result in a fused beat. Ectopic beats generated from the
same ectopic site have intervals between them that are approximately the same.
Most PACsare followed by an incomplete compensatory pause. The interval
containing the PACis shorter than twice the basic sinus interval because the
ectopic beat depolarizes and resets the SA node. Figure 4.19 shows an ECG
tracing of the PACabnormality.
Figure 4.19 The-PAC appears as a Pwavethat is not so smooth.Thefirst PACis blocked,

~hile the second PAC
ctrocardiography results in ventricular
in clinicalpractice. depolarization.
ZndEd.Grune&
Stratton. FromChou, T. C. 1986.
Diagnostic ~criteria: The rate is that of the intrinsic rhythm; the rhythmis
irregular because of the PAC; the P-R interval is normal; the P waves are
up~gtit and ha#e the same shape in leads I, II, aVF, and V4 to V6; the P’-R
interval maybe no~, longer, or shorter than the P-R interval (where P’ is the
atrial depolarization due to the ectopic beat); the P’ maynot be conducted to the
ventricles; distinguishing features include a normal QRSand a P’ wave that is
premature and has a different morphology than the normal sinus P wave
(Catalano, 1.993; Conover,_!~86). -
Most patientswitth~this abnormality do not havelany symptoms.Howeverfew
patients mayfeel skipped beats if the PACsare frequent. The cardiac output is
not significantly compromisedbecause the ventricles contract normally. The
abnor~aality is t~eated’:~ith ~medicationif the PACsare frequent:
4.&2 Atrial tachycardia
Dufing.~atrial tachycardia, a certain area of the atria generates impulses at a rate

higher ~than that from.the SAnode. This is similar to PACsoccurring one after
the other.
The ectopic site generates impulses resulting in the depolarization of the
atria, and this is manifested on the surface ECGas abnormally shaped P waves.
There is no sawtooth pattern in the~ECG.The AVnode usually conducts all the
impulses generated by, theectopic site, but someimpulses maybe blocked. During
intermittent ,atrial tachycardia,~ the atrial rate is usually higher than during atrial
taehyeardia, and. the episode begins and ends abruptly.
Diagnostic~criteria: The rateis 140-250 bpm; the QRScomplex rate depends
on ratio of beats conducted; the P waves are ectopic and have different shapes
than normal; P waves may be hidden in the preceding QRSor T waves; the QRS
complexes are normal although other pathologies may prolong them; the P-R
intervals are normal (Catalano, 1993; Conover, 1986), .....
Patients have symptomswhich depend on the rate of the arrhythmia. If the
cardiac output is ’significantly compromisedpatients-have symptomssuch as
dizziness, syncope, chest pain or pressure, shortness, of breath, or chest
palpitations. Treatment is prescribed based on the patient’s clinical status and is
dependent on howwell the arrhythmia is tolerated. Medication that increases the

blood pressure, blocks or slows the impulses, and sedates the patient may be
prescribed. Cardioversion is administered whenother modes of treatment have
failed, and hopefully results in only the SAnode taking over as pacemakerof the
heart (Catalano, 1993).
4.8.3 Atrial flutter
Whena single area of the atria discharges spontaneously at rates greater than
250/min,then atrial flutter results.
Atrial flutter is manifested on the Surface ECGas rapid and regular F waves,
i.e. a sawtooth morphology.This pattern is best Seen in .leads II, III, aVF, and
V1. In most situations, the F-waveaxis is directed superiorly, andthe F waves
are thus inverted in leads II, III, and aVF. The downwarddeflection of the F
wave has a small slope, while that of the upward deflection has a higher slope,
The F waves may not be noticeable on leads perpendicular to the F whve axis,
e.g. lead I. Variations of these criteria are possible (Chou, 1986).
The ventricles cannot contract at rates as high as that possible in the atria.
The AVnode helps prevent high rate impulses of the atria stimulating the
ventricles by blocking someof the excessive impulses generated in the atria in
ratios such as 2: 1, (i.e. one out of every two atriallimpuises are c~nducted)~~3:
and 4:1. Figure 4.20 shows an ECGpattern manifesting atrial flutter.
igure 4.20 Atrial flutter is manifestedby F wavesbetweenQRScomplexes.SomeP waves~re

blockedin orderto protectth~ ventriclesfroma highdepolarizationrat6. FromChou;
T. C. 198(i.
Electrocardiography
in clinicalpractice.2ndEd.G-rune&Stratton.
Diagnostic criteria: The atrial rate is 250-300 bpm; and that of the QRS
complexes 125-150 bpm; the QRScomplex is normal; theT’-R intervalis 260-
460 ms, where P’ is a nonconductedP wave; distinguishing characteristics .include
a sawtoothpattern in leads II, III, and aVFi a sharp, positive P’ in V1(Catalano,
1993; Conover, 1986).
Most patients do not have any~ or have very insignificant/symptoms, The
symptomsinclude a rapid fluttering feeling, palpitations ~ in the chest, or-~the
feeling of skipped beatsJ If the arrhythmia has just d6veloped¢then~ medication is
used to convert it to normal sinus rhythm. If medications are:trot effeCti:ve then
cardioversion is administered. If the arrhythmia’ is persistent due ~to~a cardiac
disease, ~then medication is usually prescribed to keep the ventricular rate,below
100 bpm (Catalano, 1993):
4.8.4 Atrial fibrillation
Multiple areas of the atria .may .~generate impulses at random,~ .depolariZing

different regions of the atria at different times. These impulses resultin an
erratic quiveringof the atria, i.e~ atrial fibrillation.
This arrhythmia maybe caused by multiple reentry circuits within the atria
and results in the atria not filling up during the cardiac cycle. All the impulses
from the atria, generated at a rate of 300-650/min, are not conducted to the
ventricles because the AVnode cannot conduct during its recovery period. Thus
the ventricles have an irregular depolarizing rate.
The rapid atrial activity is manifested on the ECGby ’f’ waves, which are
irregular in amplitude, and frequency. These waves are not detectable in all leads
but are best .seen in lead V1.. If these wavesare not detectable, then the irregular
ventricular depolarizing rate is indicative of atrial fibrillation: Atrial fibrillation
can exist with other abnormalities such as WPW syndrome and bundle branch
blocks, and this will result in additional changes to the morphologyof the ECG
(Chou~1986). Figure 4.21. shows the ECGmorphologyduring atrial fibrillation.
Figure4.21 In atrial fibrillation the ventricular depolarizingrate maybe irregular, and

fibrillatory wavesaxe usually seen in lead V1.FromChou,T. C. 1986.EleCtrocardiographyin
clinical practice.2ndEd. Grune&Stratton.
Diagnostic ~criteria: The atrial activity’~iis:m~ifested ~s wa~e~Sof varying

amplitude, duration,, and shape; the ventdcular rate maybe a controlled rate, 70-
80 bpm, or an unc0ntrolledrate, greater than 100 bpm; the P .waves may be
abscnt,,jagged, or erratic; the QRScomplexis normal (Conover, 1986).
’,~.~ t~i~lano (1993) reports on/sympt0msof patients with atrial fibrillati0n~ The
a~i~ contraction normally fills ~e ~entricles to capacity before systole. If atrial
contraction is lost, then the cardiac output is reduced by about 10%.This is not a
compromisein cardiac output for healthy individuals, however manypatients do
experience symptomsassociated with low cardiac o~tput. A main risk is that clots
ma¥~form in the left atrium and result in strokes. It is also possible for patients to
have s~ptoms of pulmonary emboli and congestive heart failure. Whenthe atria
are contracting irregularly, blood in the atria remains static and begins to clot
andthis results,in pulmonaryemboli. These clots-may travel ~to the lungs via the
pulmonary artery. , .If cardiac output is reduced ~for~a long period of time,
congestive heart failure results, and associated symptomsinclude lung congestion.
.... ~reatment is, directed towards ,converting the atrial fibrillation to’normal
sinuS, rhythm. Medication is used ~if the abnormality is persistent, otherwise
eardioversion mayalso be indicated (Catalano, 1993). -
4.9 V NXaICULAR
i CXOI’ICS
A ventricular ectopic beat results whenan area of the ventricle captures a heart
beat due to enhanced activation, reent ~, ~r naturally. Someof the ventdcular
ectopics arrhythmias are manifested on the ECGas premature ventricular
cont~aetions~.ve~tricular tachycardia and flutter, ventricular fibrillation, and
vet~ ~ "¢ular, escape:.
4.9.1 Premature ventricular contractions
An area of the ventricle, below the His bundle, may discharge spontaneously
before the impulse from the sinus node has captured the heart. The result is a
premature ventricular contraction (PVC), and the basic rhythm of the cardiac
cycle is disrupted.
The ectopic beat is triggered by a location in the ventricles, and thus
conduction will be abnormal. This abnormal conduction is manifested on the
ECGas a wide QRScomplex. If the ectopic area is in~.the ~left ventricle,, the
impulse spreads towards the right ventricle, and the leads oriented ~in the
direction of the.spread of this impulse will show a positive deflection. The
repolarization phase, is also altered, resulting in changes in the S-T segment and
T wave. The S-T segment is depressed and the T wave inverted if the major QRS
deflectionis itp right,
A PVCis as u~ lly followed by a compensatorypause, i.e. the R-R interval
containing the PVCis approximately equal to twice that .of the normal sinus
rhythm. This is usually observed if the sinus node is not..affected by impulses
from the ectopic site (Chou 1:986). Figure 4.22 shows an exampletff ia PVC.
Figure.4~2--The-eompensatory
pauseis present after the prematureventricul~rContraction,The
R-Rinterval containingthe PVCis greater than the normalR-Rinterval.FromChou;
T. C. 1986.
in "clinicalpractice.2ndEd:-Cimne
Electrocardiography &-Stratton.
PVCswith the same shape and interval~ between them are ~ssumed~to arise
from the same ectopic site, The R on T phenomenon occurs when .a PVC
coincides with the T wave of the previous cycle. Manypresentations of PVCsare
possible (Chou, 1986; Catalano 1993).
Diagnostic criteria: The rate is that of the intrinsic.sinns rhythm; the rhythm
is irregular because of the ,PVC; the P-R interval is measured from the normal
beat and not the PVC; the QRScomplex of the PVCis broadand premature, and
that of the normal cardiac cycleis normal; there is no P wave associated with the
PVC;the T waveof the PVChas an opposite polarity .to ~that of. the QRS;there
are variations in the frequency and distribution of,the PVCs;there is a. full
compensatory pause following a PVC(Chou, 1986; Conover, 1986).
Most patients do not have any symptoms. However, with frequent PVCs,
patients mayfeel skipped beats or palpitations in the che~t.’lsolate ] ~ncidents of
PVCsare not dangerous, but medication is prescribed if the patient has frequent
PVCsor has myocardial infarction (Conover, 1986; Catalano, 1993).
4,9.2 Ventricular tachycardia and flutter
In ventricular tachycardia (VT), thereis a ~rapid sequence of three or more

ectopic ventricular beats, i.e. similar to a sequence of PVCs.Ventricutar flutter
results whenthere is an area of the ventricles that takes over as the pacemakerof
the heart.
During sustained VT, the abnormality lasts longerthan 30 s. The onset of the
VTprovides prognostic information, and thus it is important to classify the VT
according to howlong it lasts. Mechanismsfor sustained VT include reentry and
aneetopic focus (Luna, 1993).
During ventricular flutter, only one area of the ventricle is spontaneously
discharging pulses spontaneously and activating the heart. During ventricular
fltitter,.the heart beats faster-than in VT, and thus can be:differentiated by the sine
Wavem0rphology of the’ECG; The ECGis rounded on the.top and the bottom in
ventricular flutter, as compared to in VT where a sharp angular configuration
due to ventricular depolarization is noticeable, as shownin Figure 4.23.
(a)
(b)
Figure4.23(a)Ventrieulartaehycardia,whichis different fromventrieularflutter, (b), in

the ventricular complex has~a sharp angular morphology. FromChou, T. C. 1986.
Ele~troc~t?diography
in clinicalpractice.2ndEd.Grune&~tratton.
Diagnostic.criteria for VT: The rate is 100-170 bpm; the rhythmis regular
m0~t of~the-time; the P-R interval cannot be measured; the QRS~complexis
greater than 120 ms; distinguishing characteristics include left axis deviation and
a monophasic R, QR, qR; or RS morphology in lead V1; AVdissociation may be
present; there is an abrupt onset and termination of theabnormality(Chou, 1986;
Conover~ 1986). -
Diagnostic criteria for ventricular flutter: The rate is faster than 250 bpm;
the P-R interval cannot be measured; the QRScomplex is broad aiad not
presented well; the morphologyof the ECGresembles a sine wave, i.e. without
d~finedQRS complexes; it is not possible to differentiate T ware’from QRS
complexes; tlie ventricular complex is not recognizable in this situation as
e0~pated to in VT (Catalano, 1993; Conover, 1986). * -\ -~i
" ’ Patients with VT have symptomsthat mayor not be tolerated~depending on
the h~’ rate. Patients with-heart rates of 100-125 bpmcan tolsrate~ it for along
time:They eXperience fluttering in the chest, shortness of breath,, intolerance to
activi~, low blood: pressure, and a low pulse. Treatment is based on whether the
patiei~’ean tolerate the symptoms or not..Medication may be preSCribed.
Cardi0~efsion is administered for a rapid termination of ~/T. Patients with
v~ntri~ular flutter have the. same symptomsas: those ~with VT. However,these
symptomsare not tolerated well and are often treated with a tiered implantable
cardft~erter-defibrillator. Ventricular flutter could progress to ventricular
fibrillation if not treated quickly (Catalano 1993).
I02 DESIGN OF CARDIAC PACEMAKERS
4.9.3 Ventricular fibrillation
Whenthe electrical activity in the ventricles is unsynchronized,the cardiac output

is significantly compromised and this abnormality is known as ventricular
fibrillation.
Ventricular fibrillation is caused by reentry or a multiple of ectopic sites.
Patients with ischemic heart disease are at a greater risk of having ventricular
fibrillation.
The.rhythm~dudngthis abnormality is irregular and chaotic. Figure ~ 4.24
shows that, during ventdcular fibrillation, the ECGmanifests deflections of
varying amplitude and shape with no well defined P, QRS,or T waves.
Figure4.24 Duringventricular fibrillation, the ECG

trace is erratic witchno discernibleQRS
complexes.FromChou,T. C. 1986.Electrocardiography in clinical practice. 2nd Ed. Grune&
Stratton.
Late with sustained and

inducible VT. Late with sustained VT
than those with ventricular fibrillation and has a good sensitivity and specificity
for detecting patients at high riskof malignant ventricular arrhythmias,
Diagnostic criteria: The rat~, rhythm, P-R interval, and QRScomplek are
not defined well on the ECG; the distinguishing feature includes a chaotic
morphology without any QRScomplexes.
Patients with ventricular fibrillation have no circulation of the blood. There
is no blood pressure, no respiration, and no pulse is detectable. The patient’s skin
becomes cold, and the pupils remain fixed and dilated. Immediate treatment is
crucial or the patient will die. The patient should be administered
cardiopulmonaryresuscitation as soon as possible. Electrical defibrillation.and
medication should be administered immediately (Luna, 1993; Catalano~ 1993).
4.9.4 Ventrieular escape beats
Whenthe pacemakersites in the region above the ventricles fail to trigger, or ~in
the presence of a conduction block, i there maybe an interval Of time ~hat i’s
grea~er than the intrinsic firing rate of the natural pacemakersin the v~ntdcieS,
whenthere is no ventricular depolarization. A natural pacemakerin the ventricle
theninitiates theheart to beat, resulting in a ventr~cular escape beat, (VEB)..
The impulses from the higher sites in the conduction system do not activate
the ventricles. Thus the ECGshows the VEBwithout a P wave before it..It~-i~
possible to have a P wave dissociated with the.following VEBor a retrograde one
after the VEB. The QRS complex has a morphology similar to that of a
ventricular ectopic beat. ~ Figure 4,25 shows an example of an ECGtracing with
VEBs.
Diagnostic criteria: The rate is normal ~but usually slower ~.than usual; the P-
R interval is measured from the normal cardiac, cycle because .the VEBdoes not
DIA(;NOSING ARRHYTHMIAS 103
have an associated wave before it; the QRScomplex of the escape beat is broad; a
distinguishing feature is a broad QRS complex followed by a long pause; the
escape beat has an attached T wave in a direction opposite to that of the QRS
complex (Catalano, 1993; Conover, 1986).
Figure 4,25 A blocked premature atrial contraction results in a ventriculareseape beat. From
Chou,T. C. t986. Electrocardiographyin clinical practice. 2nd Ed. Grune&Stratton.
Patients with VEBsdo not have any specific symptoms but may feel skipped
beats during the long pause before the escape beat. The cardiac output is reduced
because of the slower ventficular rate, and thus patients also have symptoms
resulting from low cardiac output. Treatment of VEBs involves increasing the
rate of the basic rhythm by prescribing medication (Catalano, 1993).
4.10 REFERENCES
Bennett, D. H. 1989. Cardiacarrhythmias:practical notes on interpretation andtreatment. 3rd Ed.

Bristol: John Wright&Sons.
Buraek, B., and Furman, S. 1969. Transesophageal cardiac pacing. Am. J. CardioL, 32: 469-
472.
Catalano, J. T. 1993. Guideto ECGanalysis. Philadelphia: J. B. Lippincott.
Chou, T. C. 1986. Electrocardiography in clinical practice. 2nd Ed. Orlando, FL: Grune &
Stratton.
Conover,M. B. 1986. Pocket nurse guide to electrocardiography.St. Louis: C. V. Mosby.
Greenspon, A. J., and Waxman,H. L. (eds.) 1992. Contemporarymanagementof ventricular
’arrhythmias.Philadelphia:F. A. Davis.
Heger4J. W., Roth, R. F., Niemann,J. T., and Cdley, J. M. 1993. Cardiology. Baltimore, MD:
Williams and Wilkins.
Helfant, R. H., and Scherlag, B. J. 1974. His bundle electrocardiography. NewYork: Medcom
Press.
Luna,A. B. 1993. Clinical electrocardiography:a textbook. NewYork: Futura Publishing.
Macfarlane, P. W. and Lawfie, T. D. (eds.) 1989. Comprehensiveelectrocardiology: Theoryand
practice in health and disease. NewYork: Pergamon.
Pan, L and Tompkins,W. J. 1985. A real-time QRSdetection algorithm. IEEETrans. Biomed.
Eng., BME-32:230-236.
Roberts, N. K 1975. The cardiac conducting system and the His bundle electrogram. NewYork:
Appleton-Century -Crofts.
Scherlag, B. J., Lau, S. H., Helfant R. H., Berkowitz, W. D., Stein, E., and Damato,A. N.
1969. Cathetertechniquefor recordingHis brindle activity in man.Circulation, 39: 13-18.
T0mpkins, W. J. (ed.) 1993. Biomedical digital signal processing. EnglewoodCliffs, NJ:
Prentice-Hall.
Neuman, M. R. 1992. Biopotential amplifiers. In J. G. Webster (ed.) 1992. Medical
instrumentation:application and design. 2ndEd. Boston:HoughtonMifflin.
Weisner, S. J., Tompkins,W.J., and Tompkins,B. M. 1982. Microprocessor-based, portable
anesthesiology ST segmentanalyzer. Proc. Northeast Bioeng. Conf., 222-226.
4,11 INSTRUCTIONAL OBJECTIVES
4.1 Explainthe function of an electrocardiograph.~

4.2 Describe the generation of the instantaneous cardiac vector and the useof different lead
systemsin measuringit.
4.3 Describe the morphologyof any lead of the standard 12-lead ECG,given the instantaneous
cardiacvector.
4.4 Describenonnaicharacteristics of the ECG.
4.5 Justify the use of Holter monitoringand explainits t .~hnique.
4.6 Describethe utility and :techniqueof s~ss testing in diagnosingarrhythmias.
4.7 Explain the automated~aiySis of the S~Tse~at.: :~. -
4.8 Describethe techniqueused in acquiringthe electrograrafr0mthe left atrium.
4.9 Describethe intracavitary electrophysiologictechniqueusedto study sinus nodefunction.
4.10 Describethe arrhythmiasassociated with the sinus node, and for each. describe the features
on the 12-lead EC~and I-IBEand symptoms of the patient that are diagnostic.
4.11 Describe the arrhythmiasassociated with atrioventdcular block, and for each describe the
features on the 12-lead ECGand HBE and sympt0ms of the patient that are diagnostic,
4.12 Describe the arrhythmias associated with.bundlebranchblock, and fo~ each describe the
features on the 12-lead ECGand HBEand symptoms of the patient that are diagnostic,
4.13 Describethe arrhytluniasassociatedwith preexcitation, and for each describe the features on
the 12-lead ECGand HBEand symptoms of the patient that are diagnostic.
4.14 Describethe arrhythmiasassociated with supraventricularectopics and for each describe the
features on the 12-lead ECG and symptoms of the patient that ate diagnostic.
4.15 Describe the arrhythmias associated with ventricular ectopics and for each describe the
features on the 12-leadECGand symptoms of the patient that are diagnostic.
5
Artificial Pacing
Mohammad H. Asgarian
The previous chapters described how cardiac pathology may affect the patient.
After diagnosis, the patient seeks proper therapy. The first avenue of therapy is
to use .~ ~drugs. Manyofthe abnorm]~lit]es~of the heart, can be treated bydrugs. If
drugs alone are not sufficient, then temporary(artificial) pacing is considered.
the disease is not chronic, in manycases,, acOmbinatioii of temporary pacing and
drugs-helps the patient. But if temporary pacing is inconvenient and the patient
needs, regular pacing, an (artificial) permanent pacemaker is eonsiderod. This
option involves a surgical operation and the related cost.
Implantable pacemakersimprove the quality of life and give the patients near
normal life functionality. This chapter considers general considerations for
artificial pacing. Section 5.1 reviews basic componentsof an artificial pacemaker,
the lead and pulse generator. Section 5.2 describes different types of pacing
(synchronous, asynchronous, and rate-adaptive). Section 5.3 describes temporary
pacemakers. Section 5.4 reviews indications for pacing (whether tem~rary o~
pe~anen0. Sectipn 5.5 defines the methods of designating pacemaker modes.
~ecfion 5Ji defines Several functional pacing modes and ~inally section 5.7
eons~d~ ,the criteria for selection of proper pacemakers. .
5.1~.~:ARTIFICIAL PACEMAKERUNIT
The pacemaker unit delivers an electrical pu~e with the proper intensity to the
prolTer location in, the :heart to stimulate the heart at a desired rate and~ thus
the patient with a functional heart. Figure 5.1 shows a functional
of an artificial pacemaker, which requires a pulse generator and a lead.
The p~ generator .houses electrical components responsible for generating be
pulse, .(~a-output circ~ts) at the proper time (via (timing)control circuits) base,
on events sensed (via sensing circuits). It also contains the power supply and may
include other elements such as telemetry for testability and programmability and
ROM or RAMto store data for diagnostic purposes. The lead contains a wire to
deliver the pulse to its destination in the heart and to sense and carry back
info~tion tO the sensing u~ts in the pulse generator.~ ,This ~ section~ reviews
major c~mp~entsof an arZtficial pacemaker.
5.1.1
~e,!ea d electrically connects the pulse generator to the myocardiumof choice.

The lead delivers the pulse from the pulse generator unit to the site of excitation.
In addition, it carries the myocardialpotentials back to the sensing portion of the

pulse generator. The lead consists of three portions: a connecting portion to the
pulse generator, an electrode for attachment to the myocardium and a wire
connecting the two connectors. Chapter 6 discusses the lead and electrode as well
as the biocompatibility.
Sensing
unit
Lead
Powersoume
Control
unit
Pulsegenerator
Figure5.1 Afunctional diagramof heart andpacemaker.~
5.L2 Power source
The power source provides.the energy required for the 0perafi0 ~ Of the’ circuitry
of a pacemaker, which includes the control, ~ensing and puls~:gener~tting units:
For implantable pacemaker~at present the p6We~s~0ur~e is usually’ a ~aemical
battery. Several other sources (such as a nuclear battery and a biological battery)
have been developed, but their use~ in pacemakersis considered, less practical.
Modempacemakers typically use batteries with lithium as the anode element and
iodine as the cathode. These form a battery that does not produce gas and can be
hermetically Sealed,to prote~t’the~battery-from body’ti~sues (Monde"1983~: ’A
main concern in Using a battery ~ is itslongevity. Longevity of a battery can’,be
determined"knoWingbattery :capacity antt~current drain. Battery
usually defined in term of ampere-hour~~while’ ei~r~ent drain isin ~ terms 6f
microamperes.The ~Ui’tSnt drain:.is~depend~nton tlae typ’e::0f electrode as Well~ as
the ciret~itry and typeofpulse getieration ofthe pacemaker: Chapter 7 discusses
power,supplies.
5.1.3 ¯ ’Sensing
,The- sensing unit ,amplifies. and filters the information.received via the electrode
and lead from activities inside the heart. To avoid attenuation.of signals,~Op~amps
with a high input impedance amplify the signal. Bandpass filtering remgves
unwanted signals. A comparator determines whether the QRSis detdetedqn 6rdet
to reset a timing circuit. Modem pacemakersalso include noise reversion circuits
tO Change the pulse generator tb ~’an:asynelironoi~s paeitlgmode :when ~e~nc~i~
ARTIFICIAL PACING 107
level surpasses the noise reversion threshold. This prevents inhibition of pacing in
the presence of noise. The sensing circuits also include circuits for protection of
the electronic, circuitry of the pulse generator in the clinical situations where
excessive voltage maybe applied to the sensing circuit. Such a case would happen
in the presence of defibdllation,~ensing is explained in Chapter 8. The sensing
element relays the processed information to the control unit where it is analyzed
and decisions are made.
5A.4 Codtroi
The control unit is responsible for determining whento send a pulse for pacing,
to change the mode, and to save data. The control unit for the most.part is ,a
timing device. The first control units were simple timers madeof resistors and
capacitors. Presently the timing circuit is madeof a crystal oscillator, which
generates accurate signals. Using the clock pulses, the control logic determines
whento trigger the output pacing pulse, the °blanking and the refractory intervals
and the AVdelay and to reset the escape interVals of an inhibited pacing system
or~ trigger initiation, of ~ AVdelay for triggered pacing modes, The control also
contains a rate-limiting circuit: that sets. an upper,limit ,(runawayrate) for pacing
in~case of a failure. ~Chapter 9-discusses the timing logic.. Chapter 10 covers_
CMOS.,technology used for implementation of control. In,-.many of today,s
pacemakers telemetry, circuits are available :to allow programmingthe control
functions and transfer of collected information(if any) for diagnosis purposes.
addition, a magnetic field detector is .included to~ intentionally, interrupv the
normal’ functions of :a pacemaker tot test purposes, Chapter 12 covers
programmingand telemetry. ~
5.1.5 Pulse-generating unit
The pulse-generatingcircuitry (referred to as the output circuit) is responsible

for generating a voltage pu!se to create an electric field..of adequate: inten~ity,_to
stimulate the myocardiumand create a wave of action potentials, The.minima!
energy.to create such a waveformis called stimulation thresholds. AS~.the duration
of a pulse is increased~ the voltage magnitude . required to exceed stimulation
threshold decreases and as .the duration of a pulse, is.decreased, the voltage
magnitude needed to exceed that stimulation threshold in~.reases. The ,pulse
generating unit charges up a capacitor and the capacitor!is discharged whenthe
control (timing) circuitry requires the delivery of a pdse.~The unit uses pump,up
capacitors to~de!~i,~er pulses of larg~r~ magnitudethan the potential of the batteries.
The purnp’up.: capaCitors are charged inparallel .and disehargedinto the.output
capacitor in~edes. Chapter 11 discusses pulse~generation~ . ~ -~
5.2 PACING SYNCHRONY
Operation of a pacemakercan be~divided into 3 classes.: (1) asynchronous.(fixed)

(2) synchronous (demand)(3) rate, adaptive.
5.2.1 Asynchronous ....
In asynchronous(fixed-rate) pacing, the paced chamberis paced at a constant rate

irrespective of events in the heart or physiological needs of an individual. This is
the simplest of all operational routines for a pacemaker and requires minimal
circuitry and logic implementation. However, this type of operation causes
serious problems in patients. Since no event is sensed, the synchrony between the
atria and the ventricles maybe lost and thus the pumpingefficiency of heart
would decrease about 15%.As a result, the patient maynot get enough nutrients
and oxygen and mayfeel dizzy or have palpitations. Fibrillation mffy result (in
somepatients) if the pulse is delivered within the vulnerable period. Further, the
patient’s heart is paced at a rate that maybetoo rapid during sleep or rest and too
slow during exercise.
5.2.2 Synchronous
In synchronous (demand) pacing, theheart is paced based on an event in the

heart. In.response to the sensed event within a base period, a synchronous
pacemaker may trigger orinhibit a pacing pulse; The triggered:pulse may occur
immediately after sensing the event (for examplei wbenaventricle is paced based
on the R wave) or after some ~delay (for example, whenthe ventricle is paced
based on a P wave).~ This avoids the probability~ of pacing the heart during the
vulnerable period and minimizes hemodynamicdeficiencies~ If the searched-after
event is not sensed within the base period, a synchronous pacemaker delivers a
pacing-pulse. Figure 5.2 shows examples of ventricular inhibited and ventrieular
triggered synchronousmodes. As with asynchronous pacing; the ,patient’s heart at
rest would be paced at the base rate, which maybe too fast and continue at the
base rate even though a higher rate is needed (as while running).
5.2.3 Rate-adaptive
Despite the fact that the normal sinus node is the ideal rate-adaptive generator,
the. occurrence of sinus node dysfunction and atrial fibrillation in many
individuals limits the use of atrial sensing for rate adaptation(Kay, 1992). Rate~
adaptive pacing refers to the case whenthe base rate of pacing is influenced by
events occurring outside the heart. Modulation of the pacing rate based on these
events, whichcorrelate indirectly or directly with the level-of :metabolic ~demand,
satisfies the metabolic .needs of a-patient as the situation changes (e.g. ~from
resting to exercise). These : events ’. include changes in mechanical vibration,
ventilation, right ventrieular stroke volume and systolic time, intervals,
temperature, paced depolarization integral, and mixed venous oxygen saturation.
Chapter 13 explains rate-adaptive pacemakers.:. Chapters 14, 15, and 16 cover
motion-based rate-adaptive pacemakers, temperature-based rate-adaptive
pacemakers, and fight ventdcular stroke volumeand systolic time intervals-based
rate-adaptive pacemakers;
5.3 TEMPORARY PACING
A temporary :pacemaker, like an implantabie pacemaker;, e0asists of-tw0 ~maj6r

parts: the pulse generator and the lead. However; unlike~ in implantable
pacemakers,the size of pulse .generator is not a major issue and no major surgery
is involved, It can be used for diagnostic purposes as well as in therapeutic
applications where artificial pacing is needed immediately or temporarily.
Therapeutic uses of temporary pacing include any transient and reversible
situation such as tachyarrhythmias due to effects of antibradyarrhythmia drugs,
temporary symptomatic arrhythmias, open heart surgery, or while a patient is
waiting for.:~an iimplantable pacemaker. Diagnostic ap,p_lications of temporary
pacing inchide amongothers the assessment of a patient s tolerahee to stress -and
assessment of coronary artery diseases by increasing the heart rate artificially.
This section describes different techniques in applying temporary pacing. The
techniques differ in the delivery of the pacing pulse and include transcutaneous
cardiac pacing, transvenous pacing, transthoracic pacing, and transesophageal
pacing.
interval
<c,A A I :A
Figure5.2 Diagramshowjag-ventricular triggered and inhibited synchronousmode.(a)
representsa naturallyoccurringbea~tbeatsituation,(b) representsthe ventriculartriggeredpacing,
while(c) indicatesventrieular
inhibitedpa~.ing:,’,
5.3.1 Transcutaneous paf~hg
In transcutaneous pacing, the pacing pulse is delivered at the surface of a patient’s

chest wall through surface electrodes. The electrodes can be positioned anteriorly
and posteriorly on the chest wall or both anteriorly (Figure 5.3). However,the
cathodal (negative) electrode must be placed only anteriorly or otherwise
thresholds maybe unobtainable or painft{i"(Wood et al., 1992). This pacing
easy and can be done quickly and with little training; however, it challenges
patient tolerance and suffers from variable capture. Only ventricles can be paced
~tsyhchi:onousiy; and it is used mainly for cardiac arrest ~ndprOphylactic pa~ing.
110 DESIGN OF CA~C PACEMAKERS
Back
Figure5.3 Positionof transcutaneouselectrodes. Circularelectrode(the cathode)is placed

the anterior of thorax. Therectangularelectrode(the anode)can be placedon the anterior
posteriorof the thorax.
5.3.2 Transvenous pacing
¯
In transvenous endq~ardial pacing, pacing leads are usually "lnserted~htravenously
under fluoroscopy !~nd local anesthesia to b~ " "
posmoned safely, a~d accurately
(Figure 5.4). This methodof pacing is the most reliable of all temporary methods
and can be used for a long time; however, it is time-consuming and has some
complications (such:i as venous spasm and chance of lead displacement with body
position changes). Both atria and ventricles can be paced (asynchmnously and
synchronously) aadi~t is used mainly for cardiac arrest and prophylactic pacing.
Pulse generator
Atrial
ball tip
cathode
Ventricular
cathode
Figure 5.4 TemporarytransVenouspacing. The 16ads ~are passed throtigh Veins under
fluoroscopy.
5.3.3 Transthoracic pacing
In transthoracic pacing, pacing leads are inserted into ventricles directly through
percutaneous cardiac needles inserted into the chest wall. This method is the
fastest and simplest of all temporary pacing ’methods; however, placement of the
needle’can cause coronary vessel laceration leading to cardiac tamponade(Purcell
et al., 1986) and its efficacy is unproved(Woodet al., 1992). Only ventricles
easily be paced, and it is used mainly for cardiac arrest.
5.3.4 Transesophageal pacing
In transes0phageal pacing, pacing leads are placed into the esophagus; which.is in
the proximity of the left atrium. This methodis simple and safe whenpacing the
atrium and allows reliable atrial capture; however, it provides poor ventricular
capture and maybecomeintolerable (when the output current is high). It is used
mainly in prophylactic atrial pacing, diagnostics and termination of
sui~raventricular tachycardias (Woodet al.; 1992).
5.4 PACING INDICATION
Indications for pacing are constantly evolving and it is difficult to define absolute
indications for pacing. Further, pacing, in particular permanentpacing, is costly
and overuse of pacemakersmustbe avoided. To address .these issues and to design
a standard for pacing indications, the American College of Cardiology and the
American Heart Association collectively developed and published guidelines of
indications for permanent pacemakers, antitachy pacemakers, and implantable
defibrillators in 1984. The guidelines also included the recommendedpacing
modes and were accepted widely, .In 1991,~the guidelines were revised to
incorporate new developmentsin artificial pacing.
The guidelines classify indications of pacing for different groups of
arrhythmias based on the degree of their acceptabilities and lack of
contraindications. Figure 5.5 shows the three classes defined by ACC/AHA for
permanent p~cing: This section discusses indications’for antibradycardia
permanent and’~temporary.pacing. SUbsections 5.2t.1 to 5.4.6 address indications
of permanent pacing while 5.4.7 summarizes indications of temporary pacing.
Chapter 17 covers indications for antitachyarrhythmia pacing and Chapter 18
addresses indications for implantable cardioverter defibrillators.
Classification of indications for permanentpacemakers

Class I: Conditiohsfor whichthere is general agreementthat permanentpacemakersrOt
. antitachycardia
devicesshouldbe implanted. -~ .
ClassII: Conditionsfor whichpermanent pacemakers or antitachycardiadevicesare frequently
usedbm~tbereisdiverl~ence
of opinionwithrespectto the necessit~of,their.insertion:. ~.
Class I~: Conditionsfor whichthere is generalagreement that pacemakers or antitachycardia
Figure ~’$.5 1991ACC/AHAdassifieations of indications for permanentpacemakers.From

Dt~ifUS,L.- S, Fisch, C., Griffin, J; C.,Gillette, P. C., Mason,
J. W.;andParsonnet,V. 1991~
Guidelinesfor implantationof cardiacpacemakers andantiarrhythmia
devices.JACC
18: 1-13.
5.4.1 Indications for permanent pacing in acquired AV block in

adults
AVblock is classified electrocardiographically as first degree, second degree’ or

third degree (or complete) heart block¯ It is anatomically defined as supra-His,
intra-His and infra-His. Second degree heart block with and without progressive
prolongation of P-R interval before a blocked ~beat is called type i and type II,
respectively. Patients with abnormalities of AV conduction may be asymptomatic
or symptomatic. Presence or absence of symptoms that are directly related to
bradycardia influence the decision as to whether permanent pacing is needed¯
The mere presence of supraventricular tachyarrhythmia in AV block does not
indicate the need for permanent pacing unless it is specifically indicated¯ Figure
5.6 shows the indications for permanent pacing in acquired AVblocks in adults.
Class I
A. Completeheart block, permanentor intermittent, at.any anatomiclevel, associated with. any
one of the followingcomplications:
1. Symptomaticbradycardia. In the presence of complete heart block, symptomsmust be
presumedto be due to the heart block unless provedtobe otherwise.
2. Congestiveheart failure.
3. Ectopic rhythms and other medical conditions that require drugs that suppress the
automaticity of escape pacemakers and result in symptomaticbradycardia.
4. Documented periods of asystole _> 3.0 s or any escape rate < 40 beats/rain in symptom-free
patients.
5. Confusionalstates that clear with temporarypacing.
6. Post AVjunction ablation, myotonicdystrophy.
B. Seconddegree AVblock, permanentor int~rmittent,~ regardless of the type or the site of
~lock, with symptomaticbradycardia
¯ Atrial fibrillation, atrial flutter or rare cases of supraventricdartachycardiawith complete
heart block or advancedAVblock, bradycardia and any of the conditions described under IA.
Thebradycardiamustbe unrelated to di[i~alis or druids known’tO impair AVconduction.
Class lI ¯
A. Asymptomatic completeheart, block, permanentor intermittent, at any anatomicsite, with
V~ntdcular rates of 40 beats/rain or faster.
B. Asymptomatic type II seconddegree AVblock, permanen t or intermittent.
l
C. Asymptomatic type I secondd%,reeAVblock at intra-His Or infra-HiS levels.
A. First degree AVblock.
B. Asymptomatic
Class llI
type I second de~ree AVblock at the supra-His (AVnode) level. ,
Figure 5.6 1991 ACC/AHA guidelines for permanent pacing in acquired AVblock in adults.
FromDreifus, L. S., Fisch, C., Griffin, J. C.~ Gillette, P. C., Mason,J. W., ahd Pars0nnet, V.
1991. Guidelinesfor implantation of cardiac pacemakersand :antiarrhythmia devices. JACC18: 1-
13.
5.4.2 Indications for permanent pacing AV: block, associated with

myocardial infarction
A variety of AV and intraventdcular conduction disturbances follow myocardial

infarction.. The disturbances are mostly related to the site of infarction.
Supraventricular arrhythmias, .such as sinus bradycardia, sinus arrest, atrial
fibrillation, atrial flutter, and first and second degree type II AVblocks, associate
with an inferior myocardial infarction. Intraventricula~ ~onduction defects and/o~
AVblock associate with anterior myocardial infarction.
The presence of intraventricular conduction defects mainly indicates the need

for permanent pacing after myocardial infarction in patients with AVblock. The
criteria in patients with myocardial infarction and AVblock do not necessarily
depend on the presence of symptoms. Figure 5.7 shows widely accepted
ACC/AHAguidelines for permanent pacing in AV block associated with
myocardial infarction. The three classes of indications for permanent pacing AV
block associated with myocardial infarction are asfollows:
Class I
A. Persistent advancedseconddegreeAVblockor completeheart blockafter acute myocardial
infarctionwithblockin His-Purkinje system(bilateral bundlebranchblock).
B., Patientswithtransient advanced AV,block andassociatedbundlebranchblock.
: CI.ass
~II
A.Patientswithpersistentadvanced blockat the AVnode.
Class III
A. TransientAVconduction disturbances in the absenceof intraventficularconduction
defects.
B. TransientAVblockin the presenceof isolatedleft anteriorhemiblock.
C. Acquiredleft anteriorhemiblock in the absenceof AVblock.
D, Patieot~:,with persistent first degreeAVblockin the presenceof bundlebranchblocknot
dbmonstr~it~ed’previougly.
Figure5.7 1991ACC/AHA guidelines for permanentpacingafter myocardial:infarction. From

Dreifu$,L. S., Fisch, C., Griffin, J. C., Gillette, P, C., Mason,
J. W.,andParsonnet,V: 1991.
Guidelinesfor hnplantationof cardiacpacemakers andantiarrhythmiadevices.JACC
18: 1-13.
5.4.3 Indications for pacing in bifascicular and trifascicular block

(chronic)
Bifascicular and trifascicular blocks refer to impaired conduction below the AV

node in two or three fascicles of the right and left bundle. A high death rate and a
significant incidence of sudden death have been-associated with bifascicular or
tfifascicular block. Syncopeis common in patients with bifascicular block.
Measurements of P-R and H-V intervals are considered as Vogsible
predictors of complete heart block and sudden death. P-R interval prolongation is
a sign of bifascicular block. Someinvestigators consider permanent pacing for
bifascicular block accompanied with a prolonged H-V interval of greater than
100 ms and others have advocated pacing for an H-V interval of greater than
70 ms. Figure5.8 shows commonly accepted ACC/AHA guidelines for pacing
in bifascicnlar and trifascicular block.
5.4.4 Indications for pacing in sinus node dysfunction
Sinus node dysfunction includes cardiac arrhythmias such as sinus bradycardia,

sinus arrest, sinoatrial block, and paroxysmal supraventricular taci~Ycardia
alternating with periods of bradycardia or asystole. For permanent pacing, only
Cases.of bradycardia accompanied with symptomsare considered suited. Use.of
drugs to control tachycardia may induce symptomsof bradycardla. Treatment of
tachycardia may then substantiate the use of ’an antibradycardia pacemaker.
Figure ~5.9 show~the ACC/AHA guidelines for pacing in sinu~ node d~sfunction~
Class I
A. Bifascicular block with intermittent complete heart block associated with symptomatic
bradyeardia(as defined).
B. Bifaseicular or trifascicular block with intermittent type II seconddegree AVblock without
symptoms attributable to the heart block.
Class II
A. Bifascicular or trifascicular block with syncopethat is not provedto he due to completeheart
block, but other possiblecausesfor syncopeare not identifiable.
B. Markedly-prolonged HV(>100 ms).
C. Pacin$-inducedinfra-His block.
Class III
A. Fascicular block without AVblock or symptoms.
B. Fascicular block with fkrst de~ree AVblock without symptoms.
Figure 5.8 1991 ACC/AHA guidelines for.pacing in bifascicular and trifascicular block
(chronic). FromDreifus, L. S., Fisch, C., Griffin, J. C., Gillette, P. C., Mason,J. W., and
Parsonnet, V. 1991. Guidelines for implantation of cardiac pacemakersand antiarrhythmia
devices. JACC18: 1-13.
5.4.5 Indications for pacing in hypersensitive carotid sinus and

neurovascular syndromes
A syncope resulting from an extreme reflex response to carotid sinus stimulation

is defined as the hypersensitive carotid syndrome. Cardioinhibition and
vasodepression are two components of the reflex. The cardioinhibitory reflex
results from an increased parasympathetic tone and is manifested by slowing of
the sinus rate or prolongation of the P-R interval and advanced AVblock. The
vasodepressor reflex follows a reduction in sympathetic activity resulting in
hypotension. Hyperactive response to a carotid sinus stimulation is defined as
asystole due to sinus arrest or AV block of more than 3 s or a substantial
symptomatic decrease in systolic blood pressure, or both. Permanent pacing for
patients with pure excessive cardioinhibitory response to carotid stimulation is
effective in relieving symptoms. In patients whose reflex response includes both
cardioinhibitory and vasodepressor components; attention to the latter is essential
for effective therapy in patients undergoing permanent pacing. Figure 5.10
shows ACC/AHAguidelines for pacing in hypersensitive carotid sinus and
neurovascular syndrome.
Class I
A. Sinus node dysfunctionwith documentedsYmptomatic bradycardia. In somepatients this will
occur as a consequenceof long-term(essential) drug therapy of a type and dose for whichthere
are no acceptablealternatives.
Class II
A. Sinus node dysfunction, occurring spontaneouslyor as a result of necessary drug therapy,
with heart rates < 40 beats/minwhena clear association betweensignificant symptoms consistent
with bradycardiaand the actual presenceof bradycardiahas not beendocumented.
Class III
A. Sinus node dysfunctionin asymptomaticpatients, including those in whomsubstantial sinus
bradyeardia(heart rate< 40 beats/rain) is a consequenceOf long-termdrug treatment.
B. Sinus node dysfunction in patients in whomsymptomssuggestive of bradycardia are clearly
documented not tohe associated with a slow heart rate.
Figure 5.9 1991 ACC/AHA guidelines for permanent pacing in sinus node dysfunction. From
Dreifus, L. S., Fisch, C., Griffin, J. C., Gillette, P. C., MasS,a,J. w., and Pa~sonnet,V. 1991.
Guidelinesfor implantation of cardiac pacemakersand antiarrhythmiadevices. JACC18: 1-13.
Class I
A. Recurremsyncopeassociated with clear, spontaneousevents provokedby carotid sinus
stimulation;minimalcarotidsinus pressureincludesasystoleof > 3 s durationin the absenceof
_anymedicationthat depressesthe sinus nodeor AVconduction.
Class II
A. Recurrent syncope without clear, provocative events and with a hypersensitive
cardioinhibitory
response:
B. Syncopewith associated bradycardia reproducedby a head-up tilt with or without
isoproterenolor other formsof provocativemaneuversand in whicha temporarypacemaker.and
a secondprovocative
test canestablishthe likely benefitsof a permanent
pacemaker.
Class III
A. A hyperactivecardioinhibitoryresponseto carotid sinus stimulation in the absenceof
symptoms.
B. Vaguesymptoms,such as dizziness or light-headedness, or both, with a hyperactive
cardioinhibitory
responseto carotidsinus stimulation.
C. Recurrentsyncope,light-headednessor dizziness in the absenceof a eardioinhibitory
~response.
Figure 5.10 1991ACC/AHA guidelines for permanentpacing in hypersensitive carotid sinus
andneurovascularsyndromes.FromDreifus,L. S:, Fisch, C., Griffin, J. C., Gillette, P, C.,
Mason.J. W., andParsonnet,V. 1991.Guidelinesfor implantationof cardiac pacemakers and
antiarrhythmiadevices.JACC18: 1-13.
5.4.6 Indications for permanent pacing in children
There are special considerations whenconsidering permanent pacing in children.

Fig~¢~i.l’l sho~s these conditions and the variations from pacing in adults: ~
5.4.7 Indications for temporary cardiac pacing
Temporarycardiac pacingis used a~ a therapeutic means in treating transient and

reversible situations. The transient examplesof pacing include whenthe patient is
waiting for a permanent pacemaker or after surgery~ An example of reversible
situations is a~ute myocardialinfarction. Figure 5~ 12 incliides several common
indications for temporary cardiac pacing. ~"
5.5 PACING DESIGNATION
ASdifferent kinds Of pacemakersbecameavailable, it becamehecessary to. find a

simple way to class.ify:pacem,akers. Parsonnet, Furman~and s~yth developed a
three-letter pacemakercoding system based on the functionality’ Of paeem.akers.
In 1974 the Inter-Society Commission for Heart Disease Resources (ICHD)
recommended it and it became widely accepted (Figure 5.13). The letters
correspond to the chmnber(s) paced, chamber(s) sensed, and mt~cle of response(s).
As more complex pacemakers (such as programmable pacemakers, noninvasively
activated pacemakersand antitachypacemakers) becameavailable, the three-letter
code :became inadequate, and, thus in 1981, ICHDrecommended a revised (by the
original at~ors) version of,the 1974 code. The new.code had :an additi0nal,mode
of responses (for tachycardia :managementcalled Reverse in position III), and
letter positions four and five corresponded to programmable functions and
special tachyarrhythmia functions, respectively (Figure 5.14).
Class I
A. Secondor third degree AVblock with symptomaticbradycardia, as defined.
B. Advancedsecondor third degree AVblock with moderateto markedexercise intolerance.
C. External ophthalmoplegia with bifascicular block.
D. Sinus node dysfunction with symptomaticbradycardia, as defined.
E. Congenital AVblock with wide QRSescape rhythmor with block below the His bundle.
F. Advanced secondor third de~,e AVblock persistin[ 10 to 14 days after cardiac surgery.
Class II
A. Bradycardia-tachycardiasyndromewith needfor an antiarrhythmic drug other than digitalis
or phenytoin.
B. Secondor third degree AVblock within the bundleof His in an asymptomatic patient.
C. Prolongedsubsidiary pacemakerrecovery time.
D. Transientsurgical secondor third degreeAVblock that reverts to bifascicular block.
E~ Asymptomaticsecond or third degree AVblock and a ventricular rate < 45 beats/min when
awake.CompleteAVblock whenawake,with an average ventricular rate < 50 beats/rain.
F. CompleteAVblock with double or triple rest cycle length pauses or minimal, heart rate
variability.
G. Asymptomatic neonate with congenital completeheart block and bradycardia in relation to
age.
H. Complexventricular arrhythmiasassociated with gecondor third degree AVblock or sinus
bradycardia.
I. Long QT syndrome.
Class III
A. Asym_ptomatic postoperativebifascicular block.
B. Asymptomatie postoperativebifascicular block with first degree AVblock.
C. Transientsurgical AVblock that returns to normalconductionin < I week.
D. Asymptomatic type I seconddegree AVblock.
E. Asymptomatie congenital heart block without profoundbradycardiain relation to age.
Figure $.11 1991 ACC/AHA guidelines for permanentpacing in children. FromDreifus, L. S.,
Fiseh, C., Griffin, J. C., Gillette, P. C., Mason,J. W., and Parsonnet, V. 1991. Guidelines for
implantation of cardiac pacemakersand antiarthythmia devices. JACC18: 1-13.
Indications for temporary pacing

Third degree AVblock
A. Congenital (AVnodal), symptomatic
B. Acquired(His-Purkinje), symptomatic
C. Postoperative, symptomatic(and asymptomatic(Bartecchi, 1987))
Second degree AVblock, symptomatic
(Resulting from)acute myocardialinfarction
A. Symptomaticbradycardia
B. Third degree AVblock
C. Alternating bundle branch block
D. Newbundlebranch block with transient completeheart block
E. Acutebifascicular or trifascicular block
Symptomatic sinusnodebradyarrh~hmia
Symptomatic digitalis=induced bradyarthythmias
Ventricular cctopicarrhythmia ~elated tobradycardia
anddm~-unresponsive
Prio~ to implantation of permanentpacemaker
Durinl~or after heart surgery
Figure 5.12 Common

indications for temporary cardiac pacing. Compiled from multiple
sources.
In 1983, North American Society of Pacing and Electrophysiology (NASPE)

adopted a ratio-format code (NASPEspecific code) based on a specific code
proposed by Brownlee, Shimmel and Del Marco in 1981. This code was
developed to describe clearly and accurately the most complicated modes of
paci,ng~ This code, however, was not intended to replace the generic code. In
1987~ NASPE.and the British Pacing and Electrophysiology Group (BPEG)
ad0pted a generic code for pacemakers based on the two earlier recommended
versions of pacemaker codes (1974 and 1981 ICHDcodes). This new generic
code called NASPE/BPEG Generic Pacemaker (NBG) Code allowed inclusion
additional features such as rate-adaptive (in whichthe escape rate is controlled by
events other ~than that of heart) and antitachyarrhythmia devices including
eardio~;erters and defibrillators. The generic code is used for conversational tasks
and th, e~:specific code is used whenthe generic code can.not provide enough
ilnf0~tiOn (such as the case in some dual pacemakers). In effect; the NBGcode
is a ebaci~e code andthe NASPE Specific code is a precise code.
~ Three-letter pacemakercode ICHD
-! . ":Position I H m
-~ Cate$or~
¯ " Chamber(s) paced Chamber(s)sensed Modeofresponse(s)
’ V= Ventricle V= Ventricle T = Triggered
’ A = Atrium A = Atrium I = Inhibited
D = Double D = Double D = Double*
’,.......L:~: - , . . O = None. ..... O =,None
~Atrialtriggeredandventricular
inhibited,
Figure 5.13 Thethree-letter pacemakercodingsystemwasrecommended by ICHD in 1974and

becamethe first widelyadoptedpacemakercode. It wassimple and easy to use and it only
conta~.edthree letters. Thefirst letter designatesthe chamber(s)
paced:ventricle(V), atrium
or bo~(D for double)~Thesecondletter designatesthe chamber(s)sensedi"Thethird letter
designotes the modeof response(s). The Codewas revised in 198! to ~ accommodate new
fun~9~alitiesof pacemakers, i " .
As the capabilities and complexities of implantable cardioverter

defibrillators (ICD) increased, a generic code for cardioverter defibrillators was
t~doptgd in 1993 by NASPEand BPEGand is called NASPE/BPEG Defibrillator
(~l]~D).c0de. The code describesthe capability and operation of ICDs and comes
in.two long and short versions, This section describes the :NBGcode, the NASPE
specific code, and the NBDcode, in addition to somecomb’mationof these codes.
5.5.1 NASPE/BPEGgeneric pacemaker code
Figure 5.15 shows that the NBGcode is composedof five letters: The first letter
corresp6nds to the chamber(s) paced. In this position, O refers, to :no bradycardia
pacing, V refers to pacing the ventricle while A denotes pacing the Atrium and D
corresponds to Dual whenpacing both chambers.
The second letter corresponds to chamber(s) sensed.~ The lettei~s are the same
as for the first position.
The. third letter corresponds to the response to sensing: An O is used when
there is no ’r6spons~ to the sensed event. A ~T is used Whenthe sensed evem
triggers the paced event and an I whenthe sensed event inhibits the paced event.
A D i s used if in responseto the sensedevent(s), pacing in chamber(s) is inhibited
orltriggere d basedonsensed eVent(s). D in this’position stands for Dual (T +
""The fourth letter corresponds to programmability and rate modulatiom An
O in this’ position indicates :the lack of programmability-andrate modulatiori. A’ P
stands f6~ simple programmable, in which case one or two features can be
programmed: Usually, however, it indicates the programmability in rate and
output. An Min this position stands for Multiprogrammable. A C in this position

indicates telemetry capability and stands for communicating (the use of T was
avoided to prevent confusion between triggered and telemetry). An R in this
position stands for rate modulation and .indicates a pacemaker whose escape rate
may change from beat to beat in response to a physiological variable.
, , Five-letter pacemaker code ICHDi ¯ , .

Position I III .W,. V
Category Chamber(s) Chamber(s) Modes of Programm- ~ Special
paced s~nse response(s) able functions tachyarrhyth-
d ~ mia ~uncti0ns
l_~tters used V-Ventricle V-Ventdcle T-Triggered P-Programm- B-Bursts
able (rate and
/or output)
A-Atrium A-Atdum I-Inhibited M-Multipro- N-Normal
grammab[e Rate Com-
’ petition ¯
D--Double D-Double eD-DoublC S-Scanning
O-None ’
O-None R-Reverse O-None E-Extea’nal
Manufacturer’s S-Sing[~ ’ S-Single
designation chamber chamber
,only
A~altriggeredand ventdcular inhibited.
Figure 5.14 The revised five-letter version of the 1974 ICHDcode, was,recommended in 1981.
In the first twoletters, there wasno change.In the third position an additional, letter wasaddedto
indicate pacemakerswhich start pacing when-the heart beats becometoo fast. This modeof
response was designated by R for Reverse. Letter position four correspondedto programmable
functions and containedthree letters: P for (simple) programmable (either rate or output or both
can be programmed),Mfor multiprogrammable (capable of changing morethan two features)
Ofor no functions. Letter position five eorrespoudedto special tachyarrhythmiafunctions. In this
position, O stands for none, B for bursts of impulses, N for normal-rate competition(such as .in
dualrdemandpacemaker),S for scanning response (such as timed extrasystoles, etc.), and E
external control (pacemakeractivated by a magn,~tof by radiofrequenc)/)~ Telemetricf_~nctions
were not’included: in the code as they did not involve pacing or s~nsing,modalities i From
Parsonnet, V., Furman, S., and Smyth, N. P. D. 1981. A revised code for pacemaker
identification. PACE 4: 400-402.
The fifth letter denotes antitachyarrhythmia function(s). O denotes the case

where no antitachyarrhythmia function is available, P stands for pacing
antitachyarrhythmia, S stands for shock, and D stands for. dual in which both
pacing and shock are used.
5.5.2 The NASPE specific code
The NASPEspecific code was designed to supplement the generic code. It is a

ratio-format code in which information pertaining to pacing in atrium is placed
in the numerator of the ratio and information regarding the pacing in ventricle is
placed in the denominator. A P is used to indicate pacing in a chamber, an S is
used to indica.te sensing in a chamber, and when no sensing 0r pacing js done in a
chamber, an~ 0 is used. Pacing may be inhibitory (I)or triggering (T). A lower
case letter following either I or T ~dicates what ~veht influences ~h~ mechanism
of pacing. For a pacing mechanism based on sensing an event in the atrium,
ventticld,, or other than these two, the lower case letter is a or v or e,
respectively. Figure 5116 shows the NASPEspecific Code.
ARTIFICIAL ’ PACING 119
T~PE - generic (:- -G)l~acemaker code

~ Position I~ II HI W
~Category Chamber(s) Chamber(s) Response to Programm- Antitachy-
’ paced sensed ’
sensing ability rate arrhythmia
~ ~
:~ " : modulation function(s)-
~- 0=- None O= None O= None O= None O= None
~ : A=Atrium A= Atdum T=Triggered P= Simple P= Pacing
programmable (antitachy-
arrhythmia)
V=Ventricle V=Ventricle I=Inhibited M=Muldpro- S= Shock
grammable
D=-~Dual D=Dual D=Dual C=Commun- D=Dual
(A + V) (A + V) (T + I) icating (P + S)
R = Rate
¯ modulation
Manufacturer’s S = single S = single "¯
designation (A or V) (A or V) ¯
only
-Note: Positions I throughllI are exclusivelyfor antibradyarrhythmia
function
Figure 5.15 The NBGpacemakercode; internationally accepted and adopted Since 1987. From
Bernstein, A. D., Camm,A. J., Fletcher, R. D., Gold, R. D., Richards, A. F., Smyth,N. P. D.,
Spielman, S. R., and Sutton, R. 1987. The NASPE/BPEG generic pacemaker code for
antibradyarrhythmia and adaptive-rate pacing and antitachyarrhythmia devices. PACE 10: 794-
799.
NASPEspecific code
General format Atrial-channelfunctions/ ventricle,channelfunctions
a-c abef (a-c ate f) / v-c abef (v-cate
Antibradycardiafunctions Antitachycardiafunctions
.Basic functions O=-none U=underdrive
pacing B=burst
S=sensing ¯ 0R=ramp
I--inhibited X=extrastimulus
T--triggered¯ l C=cardioversion
D=defibrillation
Source of sensing a=atrium. a=atrium~
~--ventdcle v=ventricle
e=extemal e=extemal
~igu~ 5.16 NASPE specific code. The code ¯provides a detailed -description of functions of a
ember,a-c: atrial~hannel; v-c: ventricle-channel;abe: antibradycardia;ate: antita¢~ycardia;f:
funeti0hS~ FromBernstein, A~ D.,’C~ A. J., Fletehef~ R. D., G01d,R. D., Ridhardg~A. F.,
Smyth~N. P. D., Spielman, S. R:, and Sutton, R. 1987. The NASPE/BPEG generic pacemaker
code for~antibradyarrhythmiaand adaptive-rate pacing and antitachyarrhythmiadevices. PACE 10:
794-799.
Antitachyarrhythmia pacing functions can also be specified in this format.

The capital letters for antitachyarrhythmias are U or underdrive, in which the
chamberis paced at a rate lower than that of the tachyarrhythmia; B: or..burst
(Mso o~erdrive), in which case the chamber is paced at a fixed rate Of limited
d~r~fi0n at a rate greater than that of the.tachyarrhythmi¢; R or ramp, in "which
ease ~: chamber is paced at a fixed rate with limited duration and systematically
varying~ rate, both chosen by the user; X or extrastimulus, in which case a
stirh{fl~8 6r stimuli synchronous with a previous event sensed by the device, with
fixed or variable coupling and/or interstimulus intervals are delivered to the
corresponding chamber; C or cardioversion, in which case a synchronized shock

of preselected energy is delivered, and D or defibrillation, in which case an
asynchronous shock of preselected energy is delivered to the corresponding
chamber. The lower case modifiers as for bradyarrhythmia are a, v, and e. The
portion of code corresponding to antitachyarrhythmia modesin each chamber is
placed within parentheses. Figure 5.17 presents several examples of the general
code and specific code.
Examples
NBGcode NASPEspecific code
VOO O/P
O/PSIv
O/PSIv
VVIC O/PSIv
O/PSIv
PSla/O
DVIM PIv/PSIv
S/PSIvTa
PS~aIv/PSIvTa
DDDM PSTaIv/PSIvTa
DDDR PSTaIv/PSIvTa
DDDMS PSIaIv/PSIvTa
DI)IX~ PSIaIv/PSIvTa(D)
VVIMP O/PSIv(Bv)
OOOOP
DDDCP PSIv(BaBvUv)/PSIvTa(Uv)
Figure 5.17 Examplesof NBG and NASPE specific code. NASPE explains the functionality of
a pacingmodewith a greater degreeof precision.However, it doesnot holdinformationsuchas
programmability,
telemetry,or rate-adaptation.Thusin the NBG examples,the fourthpositionhas
no bearingon the NASPE specific code. Theabsenceof the fifth letter indicates the absenceof
antitachycardiafunctions. Unlikethe NBG code, NASPEspecific codespecifies antitachycardia
functionsandthe chamberin whichantitaehyarrhythmia functionsexist. FromBemstein,A. D.,
Carom,A. J., Fletcher, R. D., Gold,R. D., Riehards,A. F., Smyth,N. P. D., Spielman,S. R.,
and Sutton, R, 1987.TheNASPF_,/BPEG generic pacemakercodefor antibradyarrhythmiaand
adaptive-ratepacingandanfitachyarrhythmia devices.PACE 10: 794--799.
The official NASPEspecific code does not include adaptive pacing

(including rate-adaptation). However, a mech~smhas been suggested to include
adaptive pacing features (Bernstein, 1991). In this mechanism,’adaptive features
of antibradyarrhythmia pacing are appended to _~he antibradyarrhythmia portion
of the code (Figure 5.18). The adaptive features are appended to the
corresponding part of the code using a hyphen to separate the adaptive features
from unadaptive. Capital letters are used to indicate pacing parameters and
lower-case letters to indicate the controlling variables~ Pacing parameters include
escape interval (E), refractory period (R), and :atrioventdcular interval (AV).
Controlling variables include stimulus-to~T wave interval (qt), activity
mechanicalvibration (act), temperature ~(t), respiration (r), pace or sense
and ventricular premature depolarization (vpb). A VVI pacemaker , with rate
hysteresis is then represented by O/PSIv-Eps, a motion-sensing VVIRpacemaker
by O/PSIv~Eact and an inhibited Ventricular pacemaker with temperature-
controlled rate modulation and externally initiated antitachyarrhythmia burst plus
extrastimulus VVIRPby O/PSIv-Et(BXe);
Pacing E=escapeinterval
parameters: R=refi’actoryperiod
AV=atdoventricularinterval
Controlling
variables: ps---pace or sense . ~
qt=stimulus-to-Twaveinterval
r=respiration
t=temperature ¯
vpb=ventricularprematuredepolarization
Figure 5.18 Rate-adaptive parameters suggested by Bemstein in 1991 tobe added to NASPE
specific code for inclusion of rate:adaptivity in the code. From Bernstein, A. D: 1991.
Classification of cardiac pacemakers.In EI-Sherif, N., and SametP. (eds.) Cardiacpacing and
electrophysiology. 3rd Ed. Saunders.
5.5.3 Defibrillator code
Figure 5.19 shows the NASPE/BPEGdefibrillator code, NBD, which is a four~

letter Code. The first position corresponds to the shock chamber. An O indicates
that no defibrillation function is present, an A stands for atrium, a V stands for
ventricle, and a D (dual) in this position indicates that both chambers can
shocked, The presence of antitachycardia pacing capability in a pacemaker
implicitly includes the capability of tiered therapy in which antitachycardia
pacing may befollowe d by ashock if necessary.
The second position indicates the antitachycardia pacing chamber. An O
indicates the absence of any antitachycardia pacing while A, V, and D indicate
which chamber(s) can be paced to stop or prevent tachycardia.
The third position indicatesthe means oftachycardia detection. An E stands
for electrogram and indicates that detection is, done only on the basis of
electrogram signal processing while anH stands for hemodynamic~ and indicates
that the device senses one or more hemodynamics-related variables, such as
transthoracic impedance or blood pressure in’ addition to electrogram signal
processing.
The NASPE/BPEGDefibrillator NBD) Code’

I Shockchamber II Antitachycardia lH Tachycardia IV Antibradycardia ’
pacinl~ chamber detection pacing chamber
0"’= None - 0 = None E = Electrogram O = None
A = Atrium A = Atrium H = Hemodynarnic A = Atrium
V= Ventricle V = Ventricle V= Ventricle
D = Dual(A+ V) D = Dual (A+ V) ’ D =Dual (A + V)
Figure 5d9 The NASPE/BPEG Defibrillator Code (long version). From Bemstein, A. D.,
Carom,A. J., Fisher, J. D., Fletcher, R. D., Mead,R. H., Nathan, A. W., Parsonnet, V.,
Richards, A. F., Smyth, N. P. D., Sutton, R., and Tarjan, P. P. 1993. The NASPE/BPEG
defibrillator code. PACE16:1776~1780.
The:fourth position indicates the antibradycardia pacing-chamber. If .no

antibradycardia is present, an 0 stands in that position: If antibradycardia pacing
present, A, V, or D are used to indicate the chamber paced.
Positions I and II are needed in all cases. Position III should be included if
antibradycardia function is present or hemodynamic sensing is present. For
device labeling and record keeping, when antibradycardia pacing is present, the
fourth letter is replaced with a hyphen followed by the 4 letter NBGcode
corresponding to that antibradycardia pacing mode. For example, a ventricular
hemodynamic defibrillator with rate-adaptive ventdcular antibradycardia pacing
could be labeled VOH-VVIR.
Figure 5.20 shows a version of the NBDcode, called the short form, which
is intended for conversational usage.~ This code allows distinguishing among
devices that are cardioverters or defibrillators only and the ones that incorporate
antitachycardia and antibradycardia pacing as well. Figure 5.21 provides a few
examples of short and long forms of the NBDcode.
The short form of the NASPE/BPEG defibrillator (NBD) code

ICD-S= ICDwith shock capability only
ICD-B= ICDwith bradyeardia pacing as well as shock
ICD-T= ICDWithtach~cardia (and bradycardia) pacin~ as well as shock
Figure 5.20 The NASPE/BPEG defibrillator code (short form). From Bemstein, A. D., Carom,
A. J., Fisher, J. D., Fletcher, R. D., Mead,R. H., Nathan, A. W., Parsonnet, V., Richards, A.
F., Smyth, N. P. D., Sutton, R., and Tarjan, P. P. 1993. The NASPE/BPEG defibrillator code.
PACE16: 1776-1780.
Examples of defibrillator designation

Short Form Lonl~ Form Label
ICD-S VO, VO~
ICD-S VOEO’ " VO~
ICD-S DOH DOI-I~VVIR
ICD-S
ICD-B VO VOE-VVIR
ICD-B VOEV
ICD-T" DDE-DDDC
ICD-T DDE-DDDC
ICD-T DDED DDE-DDDC
Figure 5.21 Examples of defibrillator code (NBD). From Bernstein, A. D., Camm,A. J.,
Fisher, J. D., Fletcher, R. D., Mead,R. H., Nathan, A. W., Parsonnet, V., Richards, A. F.,
Smyth, N. P. D., Sutton, R., and Tarjan, P. P. ¯1993. The NASPE/BPEG defibrillator code.
PACE16: 1776-1780.
5.6 PACING MODE
Manufacturers use the NBGcode to give the description of pacemakers. The five
letters designate the mode and capabilities of a pacemaker. At least the first four
letters are needed to give product descriptions; however, in clinical usage, only
three are needed if the fourth letter does not indicate a rate-adaptive pacemaker
(Bernstein et al., 1987). Each different pacing mode can be indicated for certain
abnormalities and may ’be harmful for , some others. (Improvements in
implementations may change the view.) This section reviews different modes of
pacing, their usage, and their contraindications.
5.6.1 VOOor O/P ventricular asynchronous
In ventricular asynchronous(also called ventricular fixed rate and ventricular set

rate) mode, the ventricle is paced at a constant rate irrespective of any event
affecting the cardiac activity. This modecan be used in patients with no intrinsic
cardiac rhythm. As long as the natural ventricular rhythm is not present or
normal rhythm is below the preset rate, VOOmode can help the patient.
However, if the naturally occurring rhythm returns (which is the case when the
natural rate is above the preset rate), ventricular activation is disturbed causing
degradation of hemodynamicswith serious consequences in some patients. In
patients withmyocardial ischemias and/or irritable myocardia, the occurrence of
an artificial pulse during the vulnerable period of the heart maycauseventdcular
fibrillation. As a result, VOOis not used as a .single-mode implantable
pacemaker. However, VOOcan be used temporarily to underdrive or overdrive
the ventricles for reversion of tachyarrhythmias (where occurrence of pacer
pulsesbetween ectopic ~QRScomplexes may stop tachyarrhythmia)(Mond, 1983),
severe bradycardia/asystole due to oversensing, and routine end-of-life checks of
pulse generator (Purcell and Burrows, 1986). In patients with no competitive
rhythm and myocardial ischemia, VOOpulse generators can also be used when
pacemaker inhibition is interrupted due to skeletal myopotential and/or other
extracorporeal interference. Thus, VOOis inclt~ded ih ’ programmable
pacemakers. It is important to understand VOOsince pacemakers revert to VOO
as a result ot~ failed sensing. The patient mayfeel dizziness and/or palpitation if
this occ~s,
5~6.2 AOOor P/O atrial asynchronous ~
In.atrial async~onous(also called atrial fixed rate) mode,the atrium is paced at

constant rate irrespective of any event affecting the cardiac activity. It induces a P
wave which is followed by a QRS,This modecan be used in patients with,severe
stable sinus bradycardia and inadequate sinus response to exercise" who: have a
normal His Purkinje system and no evidence of atrial fibrillation,
tachyarrhythmia or ectopic rhythm (Mond, 1983). AOOis also used for the
reversion of supraventricular tachyarrhythmia. Since the occurrence of naturally
occurring P waves at a rate greater than that of the pacemakermayinduce atrial
fibrillation and would waste the battery, the modeis rarely used in single,mode
imp!antable pacemakers .... mode, however, is included in many
multiprogrammable pacemakers to be used.when the need arises.
5.6.3 DOOor P/P atrioventricular asynchronous sequential
In AVasynchronous sequential (also called AVfixed-rate sequential) mode, the

ventricle is paced with a delay (equal to a set interval called the AVsequential
interval) after the atdumqs paced at a constant rate~,irrespective of any event
affecting the cardiacactivity. As with VOOand AOO.DOOalone isnot used
any more. In a multiprogrammable pacemaker, however, it may be used to test
the battery capacity. It has also been used to reverse and control atrial reentry
tachyarrhythmias using very short AVsequential intervals (Mond,1983).
5.6.4 VVI or O/PSIv ventricular inhibited
In ventricnlar inhibited (also called R-waveinhibited, R-inhibited, R-blocking, R-

suppressed, noncompetitive inhibited, demand (USA), and standby) mode,
ventricle is paced only if a naturally occurring R wave does not occur within a
certain interval. If a naturally occurring pulse occurs within the interval, the
pacemaker pulse is inhibited. As a result, as compared to asynchronous
pacemakers, it conserves power source energy when no pacemaker pulse is
needed and thus extends the pulse generator longevity. Further, it avoids the
occurrence of competitive rhythms. It is indicated for atrial fibrillation with
symptomatic bradycardia in the chronotropically competent patients and for
complete heart block with recurrent Stokes-Adams’ attacks. VVI does not
provide AVsynchrony and as a result, the cardiac output may be low. This
condition is referred to as pacemaker syndrome. In addition, it does not change
the pacing rate as the need arises. The use of this modein patients whobenefit
from rate response and who are knownto have encountered pacemaker syndrome
or hemodynamicdeterioration with ventricular pacing should be avoided (Hayes,
1991).
5.6.5 DVI or PIv/PSlv atrioventricular sequential
In atdoventricular sequential (also called sequential demand) mode, only the

ventricle is sensed but both chambers are paced. Both chambers are paced at the
same rate separated by a fixed AVsequential interval and both are inhibited by
ventricular events. It is indicated where previously documented pacemaker
syndromes exist and/or where there is a need for synchronous AVcontraction in
symptomaticbradycardia with a slow atrial rate (Dreifus et al., 1993). Lack
atrial pacing prevents the rate responsiveness in the chronotropically competent
patients and maylead to competitive atrial pacing. It has also been contraindicated
where frequent supraventricular tachyarrhythmias, including atrial fibrillation
an~flutter exist.
5.6.6 VVTor O/PSTv ventricular triggered
Ventricular triggered (also called R’wave synchronous, R-wave triggered,

triggered, R-wavestimulus, demandin Europe and Australia, and standby) mode,
the pacemaker delivers a pulse not only when no ventdcular event has been
sensed within a preset interval but also paces over any naturally occurring
ventricular event sensed within the preset interval. The mode was invented to
overcome difficnlties that the earlier VVIpacemaker encountered whenexposed
to magnetic interference in which case the pacemaker would falsely inhibit the
delivery of pacing pulses. As the casing material and noise filters were improved,
the VVI pacemaker became more resistant to magnetic interference. VVTis used
only whena patient is routinely exposed to electromagnetic interference and
where symptomatic tachycardia can not be prevented by sensitivity programming
adjustments. VVTis generally not used as it-may cause tachyarrhythmias up to
the rate limit whenoversensing occurs, in which case ventricular fibrillation may
result.
5,6.7 VVIR~or O/PSIv rate-adaptive ventricular inhibited
In this mode, the occurrence of a naturally occurring R wave within a certain

interval inhibits the pacemakerimpulse. The pacemaker paces a new pulse at the
end of the interval if no pulse is encountered and enters a new interval. The
length of the interval is influenced by physiological factors. Thus it overcomes
the limitation of VVIin which VVI is not responding to the metabolic changes.
VVIRis used for fixed atrial arrhythmias with symptomatic bradycardia in
chronotropically incompetent patients. It is contraindicated if ventricular pacing
results in retrograde (VA) conduction and/or a fall in blood pressure (Hayes,
1991) and whencongestive failure or angina pectods is aggravated by fast rates
(Dreifus et al., 1993).
5.~6,8 AAI or PSla/O atrial inhibited
In.atrial inhibited (also called P-waveinhibited, P blocking, and P suppressed)

mode, the atrium is paced if a-P wave does not occur within-a certain interval,
otherwise the pacemaker pulse is inhibited. This modeis used for sick sinus
syndrome’withoutperiods of atrial fibrillation (i.e. AVconduction is adequate)
With symptomatic bradycardia in the chronotropically competent patient. Use of
KAI mast be avoided whenadequate atrial sensing can not be attained and with
sinus node dysfunction with associated A.V block either demonstrated
spontaneously or during preimplant testing (Hayes, 1991).
5.6.9 AATor PSTa/O atrial triggered
In-atrial triggered (also called P triggered, P stimulated, or ~P synchronous) the

atrium is paced immediately after a P wave or when no P wave occurs withiti a
preset interval. In theory, this modeis used whendue to symptomatic skeletal
muscle sensing, the AAI mode can not be used. AATis preferred to AOOas it
does r/ot induceatrial fibrillation.
5~6:10. AAIRor PSIa/O rate-adaptive atrial inhibited
In’this mode, the atrium is paced if a P wave does not occur within a certain
interval. The occurrence of a naturally occurring P-wave will inhibit the
pacemakerpulse..In addition, the length oft he interval is changed in response to
physiological events. AAIRis used in treatment of symptomaticbradyeardia as a
result of sinus node dysfunction in the chronotropically incompetent patient and a
predicted high level of physical activity and whenAVconduction can be proven
normal. This mode will restore rate responsiveness and maintain AVs~nchrony.
AAIRhas been contraindicated whenadequate atrial sensing can not be attained
and with sinus node dysfunction with associated AVblock eider demonstrated
spontaneously or during preimplant testing (Hayes, 1991), .....
5.6.11 VATor S/PIa atrial synchronous
In atrial synchronous (also called P-wavesynchronous, atrial triggere d and AV

synchronous) mode, the ventricle is paced after a set period (which corresponds
to P-R interval) following the recognition of a P wave. This mode attempts to
reestablish AVsynchrony and responds to the physiological ,needs of the patient
as the atrial rate adapts. This modecan be used in patients with complete heart
block with normal sinus and atrial electrical function, but it should be avoided
whenan abnormality of sinus or atrial function is present. Due to the atrial
sensing refractory period, the maximal ventricular rate is limited (to
approximately 125 beats/min), which is disadvantageous in young patients but is
protective in situations whereatrial sensing mayoceursuch as in supraventricular
tachycardia and atrial flutter. Whena unidirecti’onal AVblock with slow
retrograde conduction is present, it may result in taehyarrhythmias (Mond,
1983).
5.6.12 VDDor S/PSIvTa atrial synchronous ventricular inhibited
In this mode (abbreviated as ASVIP and also called P-wave synchronous

ventricular inhibited), the ventricle is paced after a set period (which corresponds
to the P-R interval) following the recognition of a P wave unless an R wave
occurs before expiration of the interval. This mode is used for complete .AV
block with normal sinus node function and for congenital A.V block (Furman,
1991). It also permits variable ventricular pacing at the rate of P waves and
ventricular sensing prevents pacing of ventricles during the vulnerable period
(Purcell and Burrews, 1986). VDDis contraindicated when AVnode and distal
conducting .systems are intact, since it may cause retrograde conduction with
sensing of P waves leading to reentry tachyeardia (Mond, 1983), If
synchronyis lost due to cessation of atrial activity or malfunction in atrial lead,
pacing becomes VVI which may become symptomatic in patients dependent on
AVsynchrony as a result of inadequate cardiac output (Drei~s, 1986).
5.6.13 DDI or PSIaIv/PSIv AV sequential, atrial, ~ and ventricular

inhibited
In this mode, occurrence of certain events (P or R wave) start cycles. Since only
ventricular activity is tracked in pacing ventricles, its rate of pacing never
exceeds the programmedrate. This mode is used in patients with Pa.roxysmal
supraventricular tachycardias that could result in rapid ventricular pacing if the
patient were programmedto the DDDmode (Hayes, 1991), It is also used with
chronotropically competent patients with AVblock and sinus node dysfunction in
the presence of significant PSVT.It has .been contraindicated, in chronotropically
incompetent patients with a demonstrated need or improvement with rate
responsiveness (Hayes, 1991).
5.6.14 DDIR or PSlaIv/PSIv rate-adaptive DDI
DDIR,the rate-adaptive DDI, is used in chronotropically incompetent patients

with AVblock and sinus node dysfunction when a high level of activity is
anticipated and frequent supraventricular tachyarrhythmias are present. It is
controversial in the absence of AVblock (Hayes, 1991).
5.6.15 DDDor PSlaIv/PSIvTa AV universal
In DDD,both chambers are paced and sensed: Pacing is inhibited in atrium by a

sensed ventricular or atrial activity and is inhibited in ventricle by a ventricnlar
~ ~ :~ARTIFICI~LTACING;~ ii? 127
~ctivity but triggered by sensing an atrial.activity. :DDDis indicated for

chronotropically competent patients with normal~ Sinus node function and AV
block and for patients in need of AVsynchrony to achieve maximal cardiac
output: as well as in patients where previous pacemaker syndrome has been
observed. It has been contraindicated in situations where frequent
supraventricular tachyarrhythmias, including atrial fibrillation or flutter, exist
and whereatrial sensing is inadequate.
5.6.16 DDDRor PSlalv/PSIvTa Rate-adaptive AV universal
DDDR,the rate-adaptive DDD,is used in chronotropically incompetents with AV

block and sinus node dysfunction whena high level of activity is anticipated but
atrial rhythm is stable (Dreifus et al., 1993). DDDR pacing in these patients
restores rate responsiveness and AVsynchrony. In patients with paroxysmal
atrial rhythm, DDDR allows tracking of any rapid pathological rhythm (unlike
DDIR,for example) (Hayes, 1991). DDDR is particularly suited for patients with
persistent VAconduction. It has been contraindicated when chronic atrial
fibrillation, atrialflutter, giant inexcitable atrium, or other frequent paroxysmal
Supraventricular tachyarrhythmias are present and whenad~tlat~ atrial sen~ing is
not achieved (Hayes, 1991).
5.7 PACING SELECTION
After the patient has been diagnosed properly and the need for permanent .pacing
has been confirmed, the proper pacemakerrnustbe identified.~ I,~ selecting the
p..roper~pacing mode, whether synchronous,~Or~rate~adapti,~e (asynchronous mode
is obsolete as an implant time mode), severalfactors must: be considered. These
factors include the patient’s physical condition (Hayes, 1991), the presence
coronary heart disease and angina pectoris (Dreifus et al., 1993), the anticipated
level of activity, exercise capacity, chronotropic response to exercise, and the
cost. For example, in th~ absence Of chronotr~pic i/~crmpetence, one may not
need a rate-adaptive pacemaker, which (at present) costs more than a synchronous
pacemaker.
Somebelieve that single chamberrate-adaptive pacemakers can replace dual
chamberpacemakers in terms of physiological effectiveness. However,the single
chamber rate-adaptive pacemakers do not maintain AVsynchroriy~ This may not
be an issue at fast heart rates, but at slow heart rates, maintaining AVsynchrony
is desired. Absence of AVsynchrony may lead to atrial fibrillation and stroke
and reduces patient life expectancy,.,especially !f impaired ventricular functions
are present. Figure 5.22 shows whe~ier pacing ~aodes .listed preserve. AV
synchronyand are rate-responsive to exercise.
Finally, in selecting the proper pacemaker, one needsto have a:’ complete
knowledge of advantages and disadvantages Of using a pacing mode an’d be
fa~iiiar with abnormalities and ~eir cfffiseq~ences~ Figure 5.23 shows an
example of an algorithm for selecting the ~roper pacemaker for a patient
possessing symptomatic bradycardia while FigureS.24 shows a logic diagram for
selecting the proper pacing mode~
Mode Preserves AV Rate-responsive to Rate-response

synchrony exercise? accurate in
presence of atrial
arrhythmias?
VVI no no N/A
AAI yes* yes** ¸ no
DVI yes no N/A
DDI no N/A
VDD yes*** yes** no
DDD yes yes** no
VVIR no yes yes
DDDR yes yes ???
Figure 5.22 Hemodynamic effects of pacing mode. N/A: not applicable; *: only if AV
conduction is preserved; **: only if sinus response to exertion is, preserved; ***: unless sinus
bradycardia is present. From Naccarelli, G. V. 1991. Cardiac arrhythmias: a practical approach.
Mount Kisco, NY: Futura Publishing,
Can the atrium be sensed and paced reliably?

If no, use VVIRor VVI.
If yes,
Is AVconduction adequate?
If yes:
Is there chronotropic competence?
If yes, use one of these: AAI, DDI, AAIR,DDDR
If no, use AAIRor DDDR
If not:
is flaere ~hronotropi~.competence?
If yes, use DDDor DDDR
If no, use DDDRor DDIR
Figure5.23 Alogical sequencein selecting the ~proper pacing modefor a patient with
symptomatic bradycardia.FromBenditt, D. G. 1993.Current pacing, modes:a brief reviewof
their features andindications. In Benditt, D. G. (ed.) Rate-ad~ptivepacing.Cambridge,
MA:
BlackwellScientific.
5.8 REFERENCES
Bartecchi,C. E. 1987.Temporary cardiacpacing.Clfieag6:P~ptPress.

Benditt, D. G.1993.Currentpacingmodes:a ~irief reviewof their features andindications. In
Benditt,D. G. (ed.) Rate-adaptivepacing,Cambridge, MA:,Blaekwell
Scientific.
Bemstein,A, D. 1991.Classification ofc~acpac~emakers, h EI-Sherif, N,, andSametP. (eds.)
Cardiacpacingand electrophysiology.3rd Ed. ~d.e)pMa:W.B. Saunders.
Bemstein,A.D., Brownlee,R. k., Fletcher, R.~ C~KI,R. :D.; Smyth~ N. P~ D., and Spielman,
S. R.: 1984. Report on the NASPEmode codeco~ttee~PACE7: 395-402.
Bernstein;. A.. D., Carom,A. J., Fisher, J. D., Fletcher, R. D., Mead,R. H., Nathan;A. W,
Parsonnet,V.,. Richards~A. F.,’ Smyth,N, P2 D., Sutton, R., and Tarjan, P. P. 1993.The
NASPF_./BPEG defibrillator code. PACE16: 1776--1780.
DDDR I
DDIR ]
DDD I
Figure 5.24 A logical diagram of relationship between rhythm disturbances and therapeutic
opfacing modesBedim
the heart. for selecting the proper" pacing mode.FromSchaldach, M. M. 1992. Electrotherapy
Springer-Vedag.
Bernstein, A. D., Cairn, A. L, Fletcher, R. D., Gold, R. D., Richards, A. F., Smyth, N. P. D.,
Spie!man., S. R., and Sutton, R. 1987. The NASPE/BPEG generic pacemaker code for
" at~til~rad#arrhy~a and adaptive-rate pacing and antitachyarrhythmiadevices. PACE 10: 794-
799.
Brownlee, R. R., Shimmel, J. B., and Dcl Marco, C. J. 1981. A new code for pacemaker
Operating modes. PACE4: 396-399.
Dreifus, L. S., Fisch, C., Griffin, ]. C., Gillette, P. C., Mason,]. W., and Parsonnet, V. 1991.
Guidelines for implantation of cardiac pacemakersand andarrhythmiadevices. JACC18: 1-
Ell~n-bogen, ~K. A., and Peters, R. w~1992. Indications for permanentand temporarycardiac
i ~ pacing. In Ellenbogen,K. A. (ed.) Card’~.~pacing:
BoSton:BlackwellScientific.
Furman, S. 1993. Pacemakercodes. In Furman, S., Hayes, D: L.; and Holmes, D, R: (eds.)
’ ’p/a~tice Of cardiacpaci~lg3rd Ed. MountKisco, NY:ilutura Publishing.
Eurman,S., ,Hayes, D. L.,~imd Holmes,D. R. Jr. 1993~A practice of cardiac pacing. 3rd Ed.
MountKisco, NY:Futura Pul~lishing;
Garrett, A. E., and Adams,V. 1986. Common cardiac arrhythmias, recognition and treatment.
Pl~i,~’ladelphia:
J. B.Lippincott.
Griffin, C;IIG{1993. Indications for the use of implantedarrhythmia devices: comments on the
i991 ACC/AHA Task Force report. In Barold, S. S. and Mugica,J..(eds.) Newperspectives
in carcl~.,~ pacing.3. MountKisko, NY:Futura publishing~ . ,, ,
Hayes;D~E.~ 1993. Indications for permanentpacing. In F~an, S., Hayes, D. L., and rtonnes,
. D.R. A practice of cardiac pacing 3rd Ed. MountKisco, NY:Futura Publishing.
Hhy~s,D. L., and Holmes,D. R. 1993. Temporarycardiac pacing. In Furman,S., Hayes, D. L.,
and Holmes, D. R. (eds.)A practi~e of cardiac piecing 3rd Ed. MountKisco, lqY: Futura
Publishing, ""
~.~.#,’G. N; !992. Basic aspects ofciirdiac pacing. In Ellenbogen,K. A.
~ (ed.) Cardiac pacing.
~ ,>"B~stoniBlackwellScientific; " .... . " " "
M6~id~H. G~ 1983. The cardiaC pace~r,’function and raalfunction: 1st Ed, NewYork: Grune
and S~atton. ’ ’ ......
Naccarelli~ G. V. 1991. Cardiacarrhythmias: a practical approach~MountKiaco, NY:Futura
Publishing.
Parsonnet, V., Furman, S., and Smyth, N. P. D. 1981. A revised code for pacemaker
identification. PACE 4: 400-402.
Purcell, L A., and Burrous, S. G. 1986. Fundamentalsof pacing. In Riegel, B., Purcell, J. A.,
Brest, A. N., and Dreifus, L. S. (eds.) Dreifus" pacemakertherapy: an interprofessional
approach?Salem, MA:F.A. Davis.
Purcell, J. A., Kloosterman,N. D., and Miller, L. K. 1986. Care of the hospitalized patient
undergoingpacemakertherapy. In Riegel, B., Purcell, J. A., Brest, A. N., and Dreifus, L. S.
(eds.) Dreifus’ pacemakertherapy: an interprofessional approach.Salem,MA:F. A. Davis.
Reynolds, D. W. 1992. Hemodynamics of cardiac pacing. In Ellenbogen, K. A. (ed.) Cardiac
pacing. Boston:BlackwellScientific.
Schaldach,M. M. 1992. Electrotherapyof the heart. Berlin: Spdnger-Verlag.
Wood,M., Ellenbogen, IC, and Haines,D. 1992. Temporarycardiac pacing. In Ellenbogen, K.
A. (ed.) Cardiacpacing. Boston:BlackwellScientific.
5.1 Describethe operationof an artificial pacemaker andits functionalunits.

5.2 Describe asynchronousand inhibited synchronouspacings. Describe what happens when
AVsynchronyis lost. List the advantagesof rote-adaptive pacing.
5.3 List the diagnostic and therapeutic uses of temporarypaei, ng. List the advantages and
disadvantagesof each of the four temporarypacing techniques discussed in section 5.3.
Explaintranscutaneous and transesophagealtemporarypacing.
5.4 Describethe ~lasses of indications for permanentpacing.
5.5 State the abnormal conditions of acquired AVblock for which permanent pacing is
necessary.
5.6 Determinethe class of each of these abnormalities:(1) first-degree heart~ block (2) second-
degree AVblock with symptomatic bradycardia (3) sec0nd-degr~e AVblock with
asymptomaticbradyeardia (4) complete heart block with ventrieutar rates of at least
40 beats/rain.
5.7 Describethe indications for permanentpacingafter myocardialinfarction in patients with AV
block. List five intraventricular conductiondisturbancesand indicate whetherthey associate
with an infedor or antedor myocardialinfarction.
5.8 List bifasCicular blocks wherePacing is necess.ary or maybenecessary. Describethe Sinus
node dygfunctiousfor whichpe~anentpacing iS not required.
5.9 State the abnormalitiesthat necessitate permanentpacing in a child.
5.10 For a pacemaker made between 1981 and ’1987 and designated as AAR,ON,give its
5.11 ~ esignation in both NBG and NASPE specific codes if it were madetoday.
xplain cardioversion~defibrillation, underdfive,and burst.
5.12 Write the code for each of the following pacing mOdesin both NBG arid NASPE specific
codes: (I) ventricular pacing inhibited by sensing in ventricle and tachycardia detee~on
ventriclesresults in bta:sts in ~/entriele(2) pacingin ventricleinhibited~); sensingin ventricle
and includes these anfitachyarrhythmia functions: burst, underdri~,e, ~amlJ, b~t plus
ex_tr;astimulus, extrastimulusin ventricle aeti~,ated externally (3) pacing of b~th’eh~bers
alter an event sensed in the atrium’(andinclude multiprogran~iJility).
5.13 De~cribeeach of these pacing mOdes:(1) PSIalv/PSIv’~a(D),(2) O(Ua)/O;(3) P/O
PIv/S’. .... ’ ....
5.14 Describethe operation of each DDD modelisted ~ Figure 5.17.
5.15 Write the cOdefor these VVIRpace.makers using NASPE specific code and Suggest~drate-
adaptiveaddition: (1) varies e~eapeiiiterval in responseto the changesin (a) te~ra~
ventricular prematuredepolarization(e) ventilation, (2) varies refi’dctory pedodm response
to changesin (a) activity level(b) stimulus’to-Twaveinterval, and (3) varies atfioventdeu!ar
interval in responseto.(a) temperature(b) ventilation.
5.16 Write the code.for aDDD pacemakerWhoseAVinterval differs after paced and sensed
events and whose atrial refractory period is extended after a Vent~ular premature
.d.e.polarizatiOn. Givethe advantages~f ~sing this p~maker.
5.17 write the code in NBD format (short form,~long form and label) for the followingdevices:
(1) ventricle-only ICD wlthVVIR~antibrad}e~dla pacing, (2yICD with ventri~ular
cardioversiorddefibdllation, dual chamberantitaehyca~y~din paein~~1. DDDR antibt;ady~dia
pacing, and (3) ICDwith X;entrieular cardi0Ve~sion/defibrillafion, AFconversion,
hemodynamic sensing, and WIRantibradyeardia pacing. Note that, in each Case, more than
one long form mayb~ p6ssible.
5.18 Describe each of the following NBDcodes, indicate whetherthe correspondingcode is for
general description, for conversational purposes, or for book-keepingpurposes and give
each code in its conversational format if not already in that form: (1) VOEO (2)
(3) AAEA (4) DDED(5) DDE-DDDC(6) DDH-DDDR (7) AAE-AAICICD- T
.(9) ICD-S(10) ICD-B.
5.19 List the potential problemswhenusing VOO mode.Describe howa failed pacemakersensor
wouldaffect the patiem. Identify the groupof patients for whichAOO maybe used. Identify
the modethat preserves AVsy~Chrony. "
5.20 Explain the pacemakersyndrome.Give the indications for VVIpacing. List the conditions
for which the use of DVImodecan be beneficial. Identify the modethat preserves AV
¯ synchrony.
5.2i Identify the situations in whichAATor VVTmaybe used. List the disadvantages of using
these modes.Identify the modethat preserves AVsynchrony.
5.22 DiStinguishwhich of these pacemakersmaybe used in chronotropieally competentpatients
and which in ehronotropically incompetent patients: VVI, VVIR,DVI, AAI, AAIR,DDI,
~d DDDR. List the modesthat preserve AVsynchrony.
5.23 Comment on the rate responsiveness to exercise of each modementionedin section 5.6 and
, hot listed in Figure 5.22. Comment on whether ornot the rate-response can be considered ¯
~’ ~te in the presence of atrial arrhythinias in each case. ’ ~ ’
52~4 E~pihin~/htth~r or not dual chamberpacemakerscan replace single chamberrate,adaptive
: .: ,’ pacemakers,ExplainwhyAVsynchronyis important.
5.25 S~gest th~ proper.pacingmode,for the following patients using,Figure 5.24: (1) a patient
! : ,, Wi~often ~ ~uare~lia,b.le atrialrhythms(2) a patientwitli sometimesumllab!eatrial rhythSmsbut
’~ Witii no n~ for atrial syn~hrony(3) a patient with unreliable atrialrhythmsin needof rate
~ - ~dapt3vepaeihg. Ifmor6than one modeis possible~ select only one as the proper modeand
. , ?~justify your;answerassumingthat you have a programmablepacemaker.Whatwouldhave
youselectedif cost werea factor in determiningthe propermode..’?Justify youranswer.
6
Electrodes, Leads, and Biocompatibility

Brian K. Wagner
A pacemaker system applies electrical stimuli to induce cardiac muscle

contraction. Pacemakerresearchers apply principles of enginee .ring and materials
science to interface technology with body systems. Materials used in manyother
engineering applications are often not acceptable in the human body; We
therefore find or develop biocompatible materials and shape them into ’useful
pacemaker components. We must understand the body’s biochemical and
pathological systems to minimize foreign body reactions. Reducing interactions
between the pacemakerand body contributes to longevity of therapy. A patient’s
safety, livelihood, and comfort rely uponsuccessful adaptation of technology into
his or her body. Successful pacing therapy depends upon the ability of an
electrode to safely, effectively, and efficiently stimulate excitable heart tissue and
sense intracardiac signals. Pacemaker leads deliver electrical signals to and
receive signals from the heart. Lastly, the reaction of the body to the materials
and device, or biocompatibility, must be acceptable.
6.1 PACEMAKER ELECTRODES
Overall efficiency and efficacy of a pacemakersystem depend upon an electrode’s

ability to interface between the two realms of physiology and electronics. The
utility of pacing technologyis diminishedor lost entirely if an effective interface
cannot be established between these two systems. This section investigates roles
and applications of pacemaker electrodes and how engineers, physicians, and
scientists improve cardiac pacing via evolving electrode technology.
6.1.1 Electrode roles in pacemaker systems
The modempacemaker electrode often fulfills two major roles. The first is the
introduction of cathodal stimuli, produced by the pulse.generator, into excitable
myocardial muscle. If implemented, the second role is to optimally sense
intracardiac electrocardiograms and conduct them back to the pulse generator for
signal processing and algorithm control (Sinnaeve et al., 1987).
Figure 6.1 shows an example of a modemporous steroid eluting electrode.
The implementation of porous electrodes began in the late 1970s at Cardiac
Pacemakers, Inc. [CPI, St. Paul, MNU.S.A.] (Mugica et al., 1988). Various
porous and steroid eluting electrodes have provided significant advances in the
pacemakerindustry. Porosity utilizes the principle .that the ratio of the electrode
ELECTRODES, LEADS, AND BIOCOMPATIBILITY 133
tip’s electrically active surface area to the tip’s overall size should be large
(Mugica et al., 1988; Schaldach, 1992). Steroid elution designs increase pacing
efficiency and sensing sensitivity by reducing encapsulation of the electrode tip.
Figure~6AA modem pacemakerelectrode. The Medtronie[Medtronie, Ine~, Minneapolis,MN

U.S.A~]model4003CapSure® unipolartined porouselectrodeis an.example~of a poroussteroid
elution electrode. Behindthe poroustip surface is a silicone rubberplug filled with an
inflammation suppressingsteroid. Thesecretionof this drugthroughthe tip s~ffacedecreases
inflammation andresultmgencapsulation.Th~sincreasesthe electrode s pacingefficiency and
efficacy andsensingsensitivity FromMond,H., Stokes,K. B., Helland,J., ~gg,L., Kertes,
P., Pate, B., andHunt,D. 1988.Theporoustitaniumsteroid eluting electrode: a doubleblind
studyassessingthe stimulationthresholdeffects of steroid. PACE,
11: 214-219.
The primary design criterion for electrode design is safe cardiac stimulation.
A patient’s safety is of utmost importance. Mini~zing energy loss from a small
pulse generator battery source is another~important electrode design
consideration. Charge consumption from_, the.battery is reduced, to provide
extended life. Electrodes used with today s du~. ghamber and rate-responsive
pacemakers, which inherently draw increased c~,urrent from the power source,
must especially reduce current drain. Because the heart beats an average
exceeding 85,000 times a day, the potential existsi~at a relatively large amountof
energy could be inefficiently used. During paci~gi~:--the pulse generator acts as a
power source while the heart acts as anelectriCal lo~’d. Wl~enthe pacemaker
operates in sensing mode, the heart becomesthe source of electrical~energy~and
the pacemakersensing circuit becomesthe load. These differing and alternating
roles sometimesrequire different design considerations.
Other-important electrode design criteria include: biocompatibility,
biostability, electrode size, invasiveness to cardiac and circulatory functions,
fixation! into heart tissue, and ease of clinical manipulation(implantation and if
necessary removal). While overall system biocompatibility i~s addressed
specifically in section 6.3, electrode tip biocompatibility is of special concern
becauseit directly correlates to electrode efficiency.
6.1.2 Electrode-myocardium interface
This section explores the electrochemical, ionic, and electrical current

characteristics existing at the boundary layer between an electrode tip and heart
tissue.
The primary reason a pacing electrode is introduced into the heart is to
electrically stimulate excitable heart tissue and induce muscular contraction. To
accomplish this, adequate electrical stimuli must first be .applied to ekc~mble
cardiac ~ells, or myocardium. An artificial pacemaker SUl~lies an’ electrical
potential difference to myocardiamvia an electrode. The electrode and tissue
interface is a complex one. Electrical engineering applications (such as pulse
generator circuits) utilize electronic conductidn while biological systems
implement ionic conduction. The interface where these two different Charge
ear’tying systems cometogether is knownas an electrochemical phase boundary.
Electrochemical phase boundary
The humanbody is often modeled as

H+, Na÷, K÷, CI-, and others. These ions fulfill
in electrochtmical reactions sustaining cellular life.
primarily of W~ter, are electrolytes d~e tO their s ions
within solution.
Figure6.2
heart tissue prior
tissue layers are not electrically active; they are protective cellular membranes.
An electrical field introduced by an electrode must pass through these two thin
layers to influence the nearest membraneof an excitable myocardial tissue cell.
Endothelium
Figure6.2 Electrode-tissue phase boundaryprior to encapsulation~VoltageVTstimulates

myocardial
actionpotential.
Figure ~6.3(a) shows a first order approximationof .the electronic and ionic
interactions occurring at the stimulating cathodal electrode-electrolyte interface.
More complex, models can and havebeen developed. An electrical phase
boundaryis defined as an interface whereon one side electrical charge is .carried
by electrons, while on the other, side charge is carried by ions, Electrons in the
electrode are drawn to the interface surface by their attraction to positive ions
present in the bodily electrolyte (Na+ and H+, for example). Electrolyte cations
are drawnto the interface surface by their attraction to the electrode’s electrons.
Equal and opposite charge concentrations arise on each side of the electrode-
electrolyte interface and an electrical field is thus established (Deconinck,1992).
Primary water Secondary water

layer,-J
w ~ --layer
Interface particles
’Cation
Electron
M-O ~ Metal-oxide
J i complex .
-~: i ~ Helmholtzdoublelayer
C-H ÷
Figure6.3 (a) First order approximation

of stimulatingcathodalelectrode-electrolyteiaterface.
Primaryandsecondarywater layers comprisea simpleinterface-modelknown as the~ Helmholtz
dtublelayer.Notecation--electronmutualattractions.toone.another;Watershells surrounding ions
~ ~..,~owncol, lectively!ashydratedions. Metal,oxidecomplexesOndiqa~ted as M-O)are yaluable
constituentsin sustainingreversible interface reactioos. Reversiblereactions, as opposedto
irre~et~ible’reactior/s, limit cellular damageandi~t~l’am~tion in nearby:endotheliUm and
~ndocardium. Electrodetips implementing metal0xidematerials help prevent chemical~tions
anddatlslimit corrosion.(b) TheHelrnholtz
double-layer
physicallyexhibitscharacteristicsof plate
e~apaci[orCtl dueto surfacearea of interface, dielectric constantof primarywaterlayer, and
distancebetweenelectronsandcations. Increasingthe 9apacitanceof Ctt increasesreversible
eh~rg6transfer (RCT)and thus reduces destructive F~radiccurrent, Resistancea~buted
electrolyte is.shownby RE.Thisinterface approximatio~ is thus commonly modeledas-a parallel
RCnetworkin series with resistive elementREFromSchaldach,M.M. 1992.Electrotherapyof
theheart.Berlin: Springer-Verlag.
Figure 6.3(a) shows a primary layer of water molecules nearest the electrode
~surface, ,More complex models may incorpgrate many more primary layers.
~i]aese’i~d~ary layer water molecules neariy C0nii~leteiy co~ter the e!ec~0d~tip’s
~ufface. N0td that dipoled water moleculds tehd~tp ’ align themselves
~ Under.the
influence Of the inducedelectric field (Waltonet al.,"1987).
Figure 6.3(a) also shows the attraction of positively charged cations to the
electrode tip’s surface. Electric fields exerted by these cations are sufficient
enough to draw dipoled water molecules around them. Thus, these ions develop
hydration shells (Schaldach, 1992; Walton et al., 1987). These ion-water shell
complexes are knownas hydrated ions. Positive hydrated ions are drawn towards
the electrode-electrolyte interface. Together the hydrated ions comprise the
secondary water layer. The primary and secondary water layers comprise the
Helmholtz double layer, as proposed by.Helmholtz in 1879 (Schaldach, 1992;
Waltonet al., 1987).
Figure 6.3(b) shows that a simple Helmholtz double layer approximation
corresponds to a plate capacitor schematically represented byCH.The value of
this Helmholtzcapacitance is determined by three physical factors: the dielectric
constant of the primary water layer er; the active surface*area of the electrode tip
a; and the distance d betweenthe electrode’s charge and the electrolyte’s ions:
CH = e°era - (6.1)
d
where~ is the permittivity of free space.

Electrical current from the stimulating cathode into the tissue occurs as
electrons pass from the electrode tip into the electrolyte. This type of current,
known as Faradic current, is undesirable. We prefer instead to minimize
electrochemical reactions as a means of charge transfer to reduce biological
destruction.
Theconcentration of electrons present in thestimulating electrode exceeds
by orders of magnitude theconcentration of ionsin theelectrolyte (Bockris and
Drazic,1972;Schaldach, 1992).Resistance of electrons to flowfromthe
electrode intotheelectrolyte is knownas reaction inhibition an~is shownin
Figure 6.3(b)as RF, the Faradic resistan~ Current flowing th~bugh Faradic
resistance depends largely upon the tip’s stimulating potential. Faradic current
induces irreversible reactions in the electrolyte and would thus ideally be
negligible.
Instead of destructive irreversible reactions induced by Faradic currents,
reversible reactions are much more desirable. Reversible charge transfer (RCT)
can be achieved in two ways.
Note in Figure 6.3(a) the rel,a, tionship betweenthe particles indicated by the
’MY and ’O. ’~ Platinum and ~idmm~two metals eommonl,y implemented as
electrode tip surfacesmare represented collectively by the ’M’ indicating ’,m6tal."
’O’ represents oxygen. It is ~lieved: that p!atim~m~iddium,and rda~ed metals
absorb oxygenat an electrode-electrolyte interface (Waltonet al., 1987). If true,
a metal oxide (M-O)complexis most likely created as detailed in the following
reduction-oxidation reactions. Platinum is used as’ the electrode material in the
following example (Dymond, 1976):
4e- + 02 + 4H+ ¢:~ 2H20 (6.2)

2Pt + 2H20 ¢~ 2PrO + 4H+ + 4e- (6.3)
Thus, the first, way to achieve. RCTis by successful implementation of

reversible reduction-oxidation,reactions at the elec~ode-elect~oly~ interface.
However,this charge t, ran~fer reversibility is l~ted by implementedelectrode
materials which maybe Contaminatedby blood constituents.
The second method to obtain RCTis simply charging and discharging the
Helmholtz capacitance shown in Figure 6.3(a) as CH. In order to improve the
reversible charge transfer by means of CH, the capacitance must be increased.
Accordingto Equation 6.1, this can be achieved by increasing the active electrical
surface area a. Section 6.1.4 discusses howa can be madesubstantially large by
implementing surface porosity.
Overall pacing system electrical model
Figure 6.4 shows a simple electrical model of a typical pacemakersystem.
Pulse Cathode ~ssue

generator
-i.
Anode :
Figure 6.4 Simplepacing system electrical modelascorrelated with exhibited~ physical

~’h~aet¢fifties of: device,materials,tissue, andelectrochemicalcomponents.
Thismodelis based
~nly uponmeasurablesystem components and excludes eiilpirieal assumptions.Components
include:the pulsegenerator,stimulatingcathode,anode,andtissue. FromBolz,A., Frthlich, R.,
andSehaldaeh, M.1993.Elek/xoehemisehe aspekteder elektrostimulation--ein
beitrag zur senktmg
des energiebedarfs.In M.Hubmarm and R. Hardt(eds.) Schrittmachertherapie undhamodynamik.
M~ehen:MMVverlag.
Four major model components are shownin Figure 6.4: the pulse generator,
cathode, anode, and tissue. VBrepresents the pulse generator’s stimulation
votfage. CRis the pulse generator’s reservoir capacity. Cc is the coupling capacity
t~etween the pulse generator and the leads. Switches S1 through $3 represent
~ous switching elements designed in many pacemakers to permit charging and
¯ ~harging of various system ,capacitances.
The lead resistances for the cathode and anode are shown by RCand RA,
f~Sp~ectively. The cathode and anode specific Helmholtz capacitances CHCand
~, le~tie~tive ly, multiplied by their respective ~leetrode ~a~a andai result in
each individual electrode’s Helmholtz capacitance. The Faradic resistances RFC

and RFAvary with the stimulating voltage.
In the tissue, RE represents the resistance comprised by electrolytes. RS
designates the shunt capacitance in which current is able to pass through non-
excitable tissue and blood outside the desired current path. The cellular
membranespecific capacitance Cmmultiplied by the cathode’s area divided by
two sides is assumed as being proportional to the number of ceils directly
surrounding the cathode. Nonexcitable cells within the cth-rent path contribute to
the tissue resistance Rt.
A stimulation ~pdse is considered effective if it charges a myocardial cell’s
membrane above its stimulation threshold voltage VT. Using Laplace
transformation analysis and knowing typical values for model components shown
in Figure 6.5 enables calculation of this stimulation threshold.
Parameter~ symbol Typical value

Reservoir capacity, CR 10 ~F
’ Coupling capacity, Ce 10 IxF.
Specific Helmholtz capacity, Smooth 20.2 [xF/mm
Cac, Porous/ 40/.tF/mm2
Fractal
Total lead resistance, RE= RC -!: RA 50 f~ ,
Surface area of cathode, a 10 mm2 ,.
Surface area of anode, ai Unipolar 10 cm2 ~ ,
Bipolar 250 mm
Pulse width, T ~ 0.5 ms
Cell membrane,capacity, Cm/~ 0.01 #F/ram2
Tissue/electrolyte resistance, ¯ .Initial 40k~
R = RE + Rt ~. Chronic 70 k£~
Shunt resi.stance, RS 600t2
Depolarization voltage, VD 30 mV
Figure6,5 Typicalvalues of pacingsystemelectrical modelcomponents shownin Figure6.4.

FromBolz, A., Fr6hlieh, R., and Sehaldaeh, M. 1993. Elek.trocbemisehe aspekt¢ der
elektrostimulation-einbeitrag zur senkungdes energie~bedarfs.In M.~Hi~bmann
an~[
¯ R~~ardt
(eds.) Schrittmachertherapie und ~. M~neheniMMVverla~,
The following simplifications can be madefrom Figure 6.4:
R = RE + Rt (6~4)
RL = RC + RA (6.5)
(6.6)
.K,t~R ~’c aCHc
C2 = Cma (6.7)
Laplace transformation s’~m~plificafion results inthe following expression for

the stimulation threshold ~voltage VT!’
2VD fy2 -4X

(6.8)
where the poles Pl andp2 are def’med as:
y_~y2 -4x
Pl =- (6.9)
2x
P2 = _y÷__2~ (6.10)
2x
atid variables x ~d y are determined by:
(RLRS
+ RLe+&R)qC2 (6.11)
y (6.12)
F_xluation 6.13 shows that CI andC2are significant.factors in reducing the

amount’ofcharge required to raise the excitable cell’s membranepast stimulation
threshold:-Figure ~6.5 shows~ that fractal, or other porous tip surfaces clearly
provide higher specifie:Helmholtz capacitances to more efficiently utilize
available charge from the battery source.
The charge required for a single stimulation pulse QTis thus calculated:by:
(6.13)
[e p2T -I~(RLp2 + R)C2P2+ 1]]
Note a two dimensional representation of a

pacemaker , .two lead resistors
and resistive
tissues current is
physically complex
modeling element
techniques.
This excludes
empirical
Inflammation, encapsulation, and stimulation threshold change
The introduction of a foreign body into humantissue often triggers a complicated

process !¢nown as inflammation: During inflammation¢ ~the body attempts ~.to
ehcapsul~Re and isolate:~;a foreign obje~L Wemust compreheiad~the~proc6~es
~
associated wi~h tissue inflamn~atio~ and encapsulatio~ toexplain .~lecfrode
performance changes due to foreign body reactions.
As an electrode is implanted, it is often placed against the endocardiumor

into the myocardium.Proteins are absorbed to the electrode surface, where they
change in structure, desorb, and induce an immunesystem reaction. Local
capillary dilation then occurs. Phagocytic cells, including monocytes and
macrophages, infiltrate the region and release lysosomal inflammatory mediators
(various oxidants, hydrolytic enzymes, and chemotactic agents). In a more mature
inflammation stage, this phagocytic activity occurs at both the electrode-
electrolyte interface and in the surrounding myocardium,eventually resulting in
the death of nearby myocytes and local necrosis (Henson, 1971; Henson, 1980;
Salthouse, 1984; Stokes and Anderson, 1991). Additionally, the lysosomally
released inflammatory mediators may dissolve the collagen structure holding
nearby myocyticceils in their orderly fashion (Robinsonet al., 1983). A collagen
capsule then forms around the electrode tip (Mondand Stokes, 1991). Between
the collagen capsule and the electrode exist one or more layers of remaining
macrophages and foreign body giant cells, which become the interface between
the electrode and the heart tissue (Stokes and Anderson, 1991).
Inflammation begins immediately upon electrode implantation (Schaldach,
1992; Stokes and Anderson, 1991). : During inflammation, the required
stimulation voltage required to induce myocardiumcontraction can increase.
Somemodemelectrodes significantly suppress inflammation by using steroid
elution techniques, or. relatively biocompatible materials. Muchof the required
.stimulation voltage increase, if any, can be .attributed to inflammation,and the
collagen network ~developing between the electrode and myocardium.
Figure 6.6 showsencapsulation of a vitreous (or glassy) carbon electrode tip.
To some degree or another, this typeof growth is typical for many pacemaker
electrodes.
Figure6,6 Resultingencapsulationof a vitreouscarbonelectrodetip (magnification:x250).The

capsule,eomprisedprimarily of collagen,addsa resistive elementbetweenthe electrOdeandthe
electrolyteandincreases.the~ effectivesize of :the electrOdetip (the lighter area onthe left).
Myocardium is shownon the far right. FromBeyersdorf,F., Schneider,M., Kreuzer,J., Falk,
S., Zegelman, M.; andSattef, P. 1988.Studies bf the tissue reaction inducedby transvenous
pacemaker~electrodes:I. microscopicexaminationofthe extent of connectivetissue aroundthe
electrodetip in the humanright ventricle. PACE,11: ~1753-1759.
Macrophagesand foreign body giant cells migrate into the pores, cracks, or
grooves of an electrode tip’s surface. In addition to the collagen capsule
surroundingthe tip, these cells increase the effective electrically active size of the
electrode. Indeed, an extremely small tip can be potentially biologically
destructive due to Faradic current. Yet, too large an electrode size results in a
decreased electric field density at the myocardium. Electric field density
decreases as a function of the square of the distance between the electrode’s
surface and the myocardium(Irnich, 1973; Irnich, 1975).
6.1.3 Ideal characteristics of electrode tip for pacing and sensing
electrode tip criteria are important electrically for pacing and

polarization characteristics (dynamic interface impedance) and
electric field density, Figure 6.7 shows ideal electrode tip design
forefficient paci.ng and optimal sensing,
Pacing Sensing
Electrode polarization
Microscopic
surface area
Electdc field density
Macroscopic
geometric size
Figu~16.7 Ideal electrical designcriteria for intracardiacelectrodetips. Forboth pacing~d

~e~si~g;~energylossa~ociatedwith electrodepolarizationis mii~imized byincreasingthe tip’s
mic~opic-surface~ a. Decreasingthe geometriC.Sizeof the electrodetip inf~ases electric fi~ld
densi’ty’requiredto inducemyocardialmusclecontractionduringpacing.Thfis, a high rati6 of
microscopicsurfacearea to macroscopic
geometricsize is desirablefor tip implementations.
Pacing efficacy and efficiency
The g6al,Of pacing is to safely introduce effective cathodal stimuli to myocardial

tissue via th~ electrod6tip. Figure 6.7 shows that to most efficiently-accomplish
this; electric field density is increased while polarization 10ss at, the el~ctrode-
el~t~olyte interface is mi~zed. , -
Figures 6.8fa) and (b) showthat as tip encapsulation increases, the resultant
effective size of the tip increases radially, :increasing the" geometric tip Size
disperses the electrode’s inducedelectrical field, and thus decreases the:~ efficacy of
thd~dect~ode. This reduction in field density decrehse~elec~Cal influence ~n any
one myocardial cell, More charge must therefore be supplied by thepulse
geherator t6-induce the same ~ effect prior to encapsulation:: To reduce radial
of the induced electrical field, the tip’s geometric size should be
polarization ~ losses can be decreased.

One way to decrease charge loss is described as successful implementation Of
re#ersible reactions at the electrode-electrolyte interface. The second method
describes increasing the reversible charge transfer by increasing the Helmholtz
capacitance CH. This second method requires that .the electrode tip’s active
surface area a be increased. Both methodsincrease pacing efficiency.
(a) (b)
Figure6.8 Electricalfield inducedbyan elec[r0detip. (a) In this ideal case, noencapsulation
the electrodetip has yet 0¢eurred.(b) In re~, h0~ever;p~ss .of encapsulationre~ultff in,a
collagenousnetworksU/’rounding tip’s surf/lee area. This effecfi~Veeiilargementof the tip s
geon~triCsize re, stilts in a r~aldi~r~of dn~ttedelectric field aadd~pacingefficacy.
Detection sensitivity
The same electrode used to pace myocardial tissue is commonlyalso designed to
sense, or detect, an electrogramsignal from’: within the herbert and deliver itto the
pulse generator. Somepacemakersutilize this natural cardiac signaLin algorithm
control for demandand/or rate,adapfve.pacing systems,
Because pacing and detection applications shar~e ~e same electrode-
electrolyte inteffa.ce~:electrode pola~rizati~n losses ~or,sensi~g are, reducedin the
same mannerthey are for pa~ii~g, ~Methodsav~lable for reducing these interface
losses are described in section 6,1.2~
Chapter 8 discU,s~s.eS methods6g enhancingdetection sensitivity by utilization
of sophisticated amplifier designs. Combinedwith highly selective filters, these
amplifiers commonlyhave both extremely high input resistances and gains, ~They
often provide high fidelity: reproductions of carc[iac signals to the p, ulse
generator. A major criteria for electrode design is minimizingcharge loss. from a
small battery source to increase dewce longewty. Muchof.a pacemakeg,.SYStem
charge loss is attributed to pacing. Enhanceddetection circuitry internal to the
pulse generator provides ~design flexibility for increasing:pacing efficiency and
extending device longevity,
6.L4 Modern electrode design
In addition to conservation of battery charge, there are other electrode design

considerations. Some of these include: (1)tip size, shape, and porosity;
(2) electrode bodyand tip materials; (3) steroid elution techniques; (4) electrode
implantation and fixation; and (5) cost reduction. Generally accepted guidelines
for electrode design include: small size (although not too small to limit Faradic
currents), high active surface area, biocompatibility, and relatively inert,
noncorrosive materials.
Tip size, shape, and porosity
For traditional design, the electrdde tip’s radius should be less than or equal to
of that will i
2A= 2 n’r (6.14)
If the thickness of the expected encapsulation layer is between 0.80 and 1.4 mm,
the surface area of the tip is calculated to be between 4.0 and 12 mm 2 as the
optimal, i: .tip ., : radius is assumedto be 0.80 to 1.4 mm,respectively. Effective
traditional .pacing cathodes commonlyexhibit geometric sizes within this range.
Not6 that as an encapsulation layer accumulates on the surface of the tip, the
effective radiu~ and size of the electric field emitting active surface increases.
This.reduces pacing efficiency. ~
Somemore contemporary designs have tip sizes smaller than 4.0 mm 2 due to
suppressed inflammation and reduced encapsulation techniques. The next two
sections will discuss how different tip materials and steroid eluUon techmques
provide ~e capability to design smaller, more efficient,electrodes.
" In addition to size, the evolution of pacemakerelectrodes has also included
several types of tips not having simple rounded surface~i During the past decade
electrode designers have developed electrode tips having a wide variety of
different geometric shapes. Sometips are nearly spherical or hemispherical.
Other tips are flat, annular, ring-shaped, or barbed (similar to that of
fishhook), lntermedics [Intermedics, Inc, Angleton, TXU.S.A.] has introduced
an IROX®model electrode implementing sharp edges and points for.l, ocalized
concentration of current. Debate still continues to whether any of-these designs
alone contribute to increased pacing efficacy (Adler et al., 1990;
Djordjevic et al., 1986; Karpawichet al., 1992; Mugicaet al., 1988; Pioger and
Rip:art, 1986).
To reduce electrode polarization losses_for pacing and ..sensing, the active
microscopic surface area of an electrode tip Canbe increased without necessarily
increasing thefip’s geometric size. The active s.urface ~ea can be greatly
increased if the tip’ s surface is designedto be conducivefor bodily electrolytes to
flow into any surface microcavities. Collectively knownas being porous, ~several
industrial processes have been developed to produce high active surface areas.
Figures 6.9(a) through (e) show electron microscope scans of five different
porous surfaces. Note that in all of the different porous surfaces shownin Figure
6.9 that microscopic grooves, crevices, or pores exist for electrolyte to flow into
or between. The microscopic ridges and edges generated by these various surface
processes increase the tip surface area. In modemporous electrodes, microscopic
surface areas have been reported to exceed macroscopic surface areas by factors
sometimes exceeding 1,000 (Schaldach, 1992). Other methods of creating porous
surfaces not sbown in Figure 6.9 include- sintedng--where metallic powder is
partially welded together by application of nonmelting beat--and chemical vapor
deposition (CVD)(Schaldach, 1992).
(a) (b) (c) (d) (e)
Figure6.9 Scannedelectron micrographs of variousporoussurfaces. (a) Fractal coating(From

Biotronik[Biotronik, Inc., Berlin, Germany]),(b) Meshed CPImodel4116.FromMugiea,
Henry,L., Atchia,B., Lazarus,B., andDueonge, B. 1988.Clinical experiencewith newleads.
PACE,11: 1745-1752,(c) Activatedcoating Sorin modelS100. FromMugi~ca~ J., Henry,L.,
Atehia, B., Lazarus, B., and Duconge,B. 1988. Clinical experiencewith new!cads.P~4CE,
11: 1745-1752,(d) Physical vapor deposited (PVD)coating. FromSchaldach,M. M::1992.
Electrotherapyof the heart. Berlin: Spfinger-Verlag,and(e) Vitreous(DeadSeaScroll,
Institute of PhysicalandChemicalResearch,Saitama,Japan. FromKatsumoto, IC, Niibori, T.,
Takamatsu, T., andKaibara,M.1986.. Development of glassy carbonelectrode(deadsea scroll)
for lowenergycardiac pacing. PACE,9: 1220-1229.
Figure 6.10 shows how pacing voltage loss can be reduced using a porous
electrode tip surface as opposedto a relatively smoothtip surface.
Electrode materials
There are generally two different components comprising a standard electrode:

the electrically active tip aiad the electrode bodyhousing. Both must be blood and
tissue compatible.
While general biocompatibility is discussed in section 6.3, electrode, tip
biocompatibility is especially important. Wall chosen tip materials potentially
reduce inflammation. In addition to being tissue compatible, the electrode tip
must also be blood compatible. This means that the material must have a low
affinity for protein binding and not induce thrombosesand embolisms.
.Materials commonly used for electrode tips include: titanium and its alloys,
platinum and its alloys, iridium¢ carbon and metallic activated glass (commonly
referred to as being vitreous), and Elgiloy®. Titanium or its alloys used as
electrode tips are often Coated with platinum and/or iridium to prevent
nonconductive layers from developing.
ELECTRODES, LEADS, AND BIOCOMPATIBILLIT¥ 145
¯ " L " ¯ ¯ " .L_’ "

J I
¯ I I I I
I
Smoothelectrode surface - _ .
0 I I " I " " i

1 10 100 1000 10,000
Frequencyof stimulation, f(Hz)
Figure 6,10 Pacing voltage loss at the myocardium-electtodeinterface is reduced by

implementing
aporousas opposedto relativelysmoothtippedelectrode.Decrease in voltagelo_ss is
largelycontributedto bydecreasedelectrodepolarizationassociatedwithincreasedactive surtace
area. FromSchaldach,M.M.1992.Electrotherapy of the heart. Berlin: Springer-Verlag.
Electrode housings are typically comprised of silicone rubbers or

polyurethanes~All of these materials are discussed in detail in section 6.3.
Steroid elution techniques
The application of pharmacological antiinflammatory agents at the interface

between myocardiumand an electrode can significantly reduce both acute and
chronic increase in stimulation threshold. Acute inflammation can contribute
significantly to energy loss during the first one to four weeks following
implantation. Various drug-eluting electrodes haye been extremely successful in
maintaining low-energy losses for both pacing and .sensing by reducing
postimplantation inflammation (Mondet al., .1~988; Mondand Stokes, 1991;
Stokes, 1988; Stokes and Church, 1987).
Figure 6.11 showsa steroid-elufing electrode~ It is a cross-sectional view of
the same Medtronic CapSure electrode shownin Figure 6.1. Note that while this
is~indeed a steroid-eluting design, it also exhibits traditional designcharacteristics
discussed in the preceding three sections. Its tip is nearly hemispherical, and has a
geometric area of approximately 8 mm2.In addition, it usesa porous, platinum-
coated titanium surface to increase the active surface area while reducing tip
incompatibility. While steroid elution is an important advancementin electrode
~ ~
c[?4ao!ogy, previously discussed design criteria are still important (Mondand
to’kes; i991).
shown in Figure 6.11 has behind its porous tip a silicone
~ ~(~ownas the monolithic controlled release device) filled with
s~ghtly less than 1 mg of dexamethasone sodium phosphate (DSP) (Mond
Stokes, 1991). Whenexposed to tissue, the drug elutes through the porous surface
into the surrounding electrode-myocardial interface. DSPis a memberof the

potent antiinflammatory pharmacological family knownas glucocorticosteroids.
Manyglucocorticosteroids are knownto suppress inflammation (Mond et al.,
1988; Mondand Stokes, 1991).
Porous, platinum
Electrode
body coatedtitanium tip
Silicon rubber
plug (impregnated
with DSPsteroid)
Figure6.11 Cross-sectional viewof a steroid-eluting intracardiac electrode (Medtronic

CapSure® electrode, model4003). Notesilicone rubber plug with impregnatedsteroid DSP.
Steroidelutes throughthe poroustip into surroundingtissue, thus reducinginflammation.
From
Mond,H., and Stokes, K. B. 1991.Theelectrode-tissueinterface: the revolutionaryrole of
steroid elution.PACE,15: 95-107.
While glucocorticosteroid chemical mechanisms are not yet completely

understood, their success is theorized to be the result of suppression of early and
late stages of inflammation (Stokes and Bomzin,1985)..~.Reeall from section 6.1:2
that phagocytic cell activity around the electrode tip causes release of lysosomal
inflammatory mediators. DSP is believed to stabilize the membranes of
phagocytes by altering theirpermeability, thus decreasing their tendency to
release lysosomal inflammatory mediators (Henson, 1971; Henson, 1980; Preston
and Judge, 1969). Reduction of inflammatory mediator release can ’therefore
reduce inflammation.
Other implementations of steroid-eluting intracardiac electrodes have also
been developed. Several companies such as Medtronic and Telectronics and
Cordis Pacing Systems [Telectronics and Cordis Pacing Systems, Sydney,
Australia] have implementedexternal drug-releasing ceramic collars around some
electrode tips. As discussed in the next section, atrial pacemakerelectrodes are
commonlyactively fixed to the heart’s surface. Modernactive fixation methods
often use methodswherea helical corkscrew tip is twisted into the atrial wall. By
placing a permeable, drug-releasing collar around the hdical screw, steroid is
able to flow into the tissue directly surrounding the screw tip. Decrease in
stimulation thresholds exhibited by collar steroid-eluting electrodes--which also
commonlyimplement the DSPsteroid----concur strongly with those found in
other drug-eluting designs (Brewer et al., 1988).
Steroid-during designs implemented in several modern pacemaker electrodes
provide an effective method of maintaining low acute and chronic stimulation
thresholds. While technology is relatively new, glucocorticosteroid elution into
tissue surrounding the electrode tip-has already proven to be successful.
Electrode implantation and fixation
Reliable: electrode fixation near or into myocardiumis critical to effectively

interface the pulse generator and the heart. Implantation of a permanempacing
electrode is generally desired to endure the lifetime of the patient. In rare cases,
cardiologists consider withdrawal~ of the electrode due to infection, thrombosis,
or cardiac :dysfunction. While fixation should withstand the natural mechanical
and chemical.conditions within the heart, reasonable ease of removal is desirable
if theelectrode induces morecomplications than it resolves.
~ ~ere ~.:are three general categories of electrode fixation. The first group
consists of floating leads. Electrodes on these leads are not actually attached to
heart tissue at all. Instead, they float inside the heart’s cha~-bers. Complications
attributed .to lead movementand straying stimulation current makefloating lead
implementations less chronically desirable than electrodes having direct or near
contact with :myocardium. Floating leads are therefore most often utilized in
temporary pacing systems.
~-.A.more .reliable method of attaching pacemaker electrodes is via active
fixation. There are currently three types of active fixation: sutured, barbed, and
helical:Sutured fixation commonlyrequires open-heart surgery. An ~epicardial
electrode suture pad-often having an active electrode at its.center--is actually
sewn directly onto the epicardial tissue. This procedure, although not common,is
prescribed most typically :for children, whose physical growth increases lead
tension and tugs at implanted electrodes (Gillette et.al., 1985; Karpawichetal,,
1.992;- Williams et al., 1986). Barbedfixation is analogous to afishhook and also
requires~an open-heart procedure for implantation. A barbed, metal electrode tip
initially~placed against the endocardiumis pulled or pushed into the tissue, thus
rendering it immobile. It mayor maynot be surgically sutured further in place.
Helical active fixation electrodes incorporate one or more helical screws at
the tip that are rotated into the myocardialtissue: Electrodes .using helical fixation
can be implanted transvenously and have therefore becomeclinically popular for
active fixation (Charles et al., 1977; Gillette et al:, 1985; Stokes and
Stephenson, 1982). In addition, if the lead must be clinically removed,
physician is able to simply unscrew the lead from the myocardiumand withdraw
it. The screw mayor may not be implemented as the electrode’s pacing/sensing
region. Helical fixation electrodes are commonlyused for atrial implantation
procedures to accommodatethe lead bending required for introduction into the
right atrial wall. Such fixation into myocardiumdecreases the opportunity for
lateral force exerted by the lead to dislodge the implant.
However, transvenously passing sharp helical tips during implantation
procedures sometimescauses inherent clinical implications such as slicing veins
or excessively puncturing heart tissue. Problemsassociated with fixed helical tip
implantation have led to the developmentof both retractable and coated helical
fixation electrodes (Charles et al., 1977; Gillette et al., 1985; Ormerodet al.,
1988). Retractable helical tips have rotational mechanismswithin the lead to
permit rotation of a pin external to the incision site to retract the fixation screw.
The lead is then able to be safely passed transvenously into the heart. Oncein the
heart and ready ~t 0 be implanted, a physician is able to re-extend the screw and
twist it into place. ¯
There are two disadvantages associated with manyretractable tip designs.
The first is the increased lead diameter required to accommodaterotational
apparatus and protection of lead filament coils. In addition, lead flexibility is also
decreased (Cameronet al., 1990; Ormerodet al., 1988). Section 6.2 discusses the
physiological implications of both of these design disadvantages. Coated helical
tips, however, permit less hazardous transvenous passage without having
rotational apparatus incorporated into the lead (Ormerod et al., 1988).
nonretractable helical screw is encapsulated with a biocompatible gel that
dissolves after implantation, thus making insertion and handling muchsimpler
and less dangerous than other nonretractable models (Ormerodet al., 1988).
All-three active fixation methods result in extremely low dislodgement rates
(often lower than 1% of the total numberof implantations). However,invasively
puncturing heart tissue via active fixation, is theorized to induce increased
inflammation. It has already been determined that such an increase reduces pacing
efficiency.
A third method of implanting pacemaker electrodes has:also been developed:
passive fixation. Passively f’~xated electrodes utilize natural tissue encapsulation of
their physiologically foreign materials to anchor the devices in place. They do not
puncture the myocardium--theygently lie against the endocardium very near the
myocardium. This reduces inflammation. Several mechanisms have been
developed .to promote tissue passive fLxation, including: wings, crowns, flanges,
bristles, projecting wires, and tines. Often these fixation devices are comprisedof
polymers due to their relative biocompatibility and flexibility. While active
fixation methods still-exhibit lower dislodgment rates, improving technology
contributes significantly to increasing passive fixation reliability (Mondand
Sloman, 1980). Various tined fixation implementations currently exhibit the most
passive fixation clinical success, exhibiting dislodgement rates averaging between
3~4%. These designs typically ~include three or more tines in a variety of
configurations such as helically woundaround the electrode body, symmetrically
spaced in one or more rows spanning the length of the electrode body,, and
others.
.Figure 6.12 showsvarious examplesof active and passive f’Lxation electrodes.
(a) (b) (c) (d)
Pigure6,12 Examples of active andpassivefixation electrodes.(a) Epicardialsuturepadactive

fixation withdisk-shaped,steroid eltiting platinized porousplatinum~lectrode.in center~rom
Medtronic,Inc.); (b) Barbedepicardial polishedplatinum"fish-hook"electrode(Medtronic model
6917A, FromMedtroaie,Inc.); (C) Hdliealactive fLxationelectrode; (d) Tinedpassive’fixation
electrode (BIOTRONIC, Inc. modelDJP/JP, FromBIOTRONIC, Inc.).
6.2 LEADS
Leads are an important component of a pacemaker system. While commonly

addressed simultaneously with electrodes, manylead design criteria differ from
those of electrodes. Permanentpacemaker electrodes are designed to remain in a
fixed position once implanted. The lead, however, must be able to flex and
possibly growwith the patient.
Leads are often threaded through vessels of the .upper venous system into the
heart.~ to avoid open-heart procedures~ They must therefore have diameters that do
not occlude and be comprised of materials biocompatible with the cardiovascular
system. Similar to electrodes, leads are usually intended to last the remainder of a
patient.~s.life. Device longevity requires, durable design which maycompromise
invasiveness and .biocompatibility criter.ia. Recent advancements in lead
technology have incorporated manyeffective compromises between flexibility,
biocompatibility, and durability. .
6.2.1 .Lead roles .in pacing system
Th~ pacemaker lead often fulfills two roles: (1) delive~ng stimulation pukes
from the pulse generator to the electrode and, if implelndnted, (2) delivering
electrogram signals sensed by the electrode.to the pulse generator ....
Figure 6.13 shows two general types of modempacemaker leads: unlpoiar
and bipo!ar.~ Unipolar designs only require one lead conductor (knownas a coil).
The stimulating cathode is attached to the distal end of the lead. The pacemaker
casing is often utilized as the anode. An advantage of unipolar implementations
includes simple, single coil technology less prone to clinical and manufacturing
difficulties. In addition, unipolar leads are typically thinner than bipolar designs
(because they have only one coil as opposed to bipolar’s two coils). Unipolar
leads sometimesappear to ,induce less inflammation .than bipolar models because
bipolar leads are stiffer and result in increased pressure on cardiac tissue
(Cameronet al., 1990; Jacobs et al., 1993). In addition, lead compression damage
attributed.to medial subclavian caudal traction is commonlyreduced in unlpolar
leads because of increased flexibility(Cameron et al., 1990; Jacobs et al., 1993;
Magneyet al., 1993).
Atrial J-shaped Atdal J-shaped
Ventdcular Ventdcular
Unipolar Bipolar
Figure6.13 Unipolarandbipolar implementationsof both J-shapedandnonpreshaped leads.
All modelshavedistal cathode.Bipolardesignstypically havea ring anodeproximal10-15nun
onthe lead.
Bipolar leads also have distal cathodal electrodes. In addition, each also
typically has a ring anode that floats in the heart cavity proximal on the lead. The
distance between these two electrodes varies by lead model from approximately
10-15’ram. Bipolar leads offer several potential advantages compared to
unipolar designs; including: reduction of far-field potential amplitudes (Aubert et
al., 1986; DeCaprioet al., 1977; Gdff’m, 1983), relative immunityto external
interference and myopotentials (Antoniucci et al., 1981; Breivik et al., 1983;
Daley and White, 1982; Levine et al., 1982; Levine and Klein, 1983; Secemskyet
al., 1982), signal-to-noise ratio improvement(Aubertet al., 1986; DeCaprio
al., 1977; Griffin, 1983), and decreased skeletal muscle stimulation (Cameron
al., 1990).
A physician typically decides whichtype of lead is, inthe best clinical interest
ofhis’or her patient (Hayes, 1992). Due to lifestyle variances, different lead
configurations are implanted in different people. Clinical advantages of bipolar
leads commonlyoutweigh the advantages offered by unipolar designs~(Hayes,
1992). Bipolar leads have been made even more clinically desirable as
technological advancements have madethem thinner and more flexible. In 1989,
76% of nonsurgeons and 60% of surgeons preferred bipolar configurations
(Bernstein and Parsonnet, 1989). However, pacing and sensing differences
between the two do not dramatically differ. ~
6.2.2 Lead implementation characteristics
There are several characteristics important to successful implementation~ of

pacemakerleads. Froman electrical perspective, lead conductance directly affects
both the system’s pacing efficiency and ability to accurately sense electrogram
signals. The material, thicknes~a; and the length of lead conduit contribute to
resistance induced losses. In addition, durability of the leads is important to
overall’ device reliability. Stiffness of a lead is importantfor two reasons:- ease of
implantation and electrode efficiency. Stiffness iS generally determined by the
insulation material, coil materials, and coil configuration (unipolar ’versus
bipolar). Lead insulation must be biocompatible to reduce pathological effects
that could possibly induce thrombi, emboli, or. infection of the cardiovascular
system. Lastly, to avoid increase in lead resistance due to corrosion, insulation
material must be both durable and flexible; it cannot wear away in the
bloodstream or crack under repeated flexion.
Reducing lead voltage loss
Voltage loss in a lead is reduced by decreasing coil resistance.. Coil resistance is

determined by the expression:
RL = pL (6.15)
ac
wherep is the coil material’s resistiVity, L the coil filament’s total length, and ac
the coil filament’s cross-sectional area. Onewaylead resistance can be lowered is
by shortening its length. However, lead length is determined primarily by the
physical characteristics of the patient, Especially in children, extra lead length
must be coiled somewhere to accommodate both bodily ~ flexion and physical
growth. In child implantation cases, researchers are nowable to determine within
95%accuracy howtall a child patient will become. Thus, excess lead allocation
can be made(O’Sullivan et al., 1993). For both children and. adults, patients are
conimonly requested to maximally inhale, exhale, and exertbodily movements
typical, to their lifestyles. Fromboth expected height information and allowance
required for physical movement,required lead length can be determined. While
extra length can be coiled behind the pulse generator itself, considerable bulk
added tothe implant resulting in decreased cosmetic desirability and increased
risk of lead extrusion make,this a less attractive option (O’Sullivan et al.. 1993).
Excess lead .length is now commonly looped in the right atrium
(O’Sullivan et al., 1993).
Another method of lowering lead resistance is by choosing coil material
having low resistivity. Lead coils are commonlymanufactured from cobalt-based
alloys such as MP35N(35% Co, 35% Ni, 20%Cr, 10%Mo) having silver-filled
cores due to theirextreme flexibilities and low resistivities. - In .addition, they are
not difficult to manufactureor consistently coil (Cameronet al., 1990).
to200
no
the
In addition to providing flexibility and elongation capabilities, various lead coil

configurations also provide a lumen for ,insertion and extraction of devices
knownas a stylets. Firm stylets are used in implanting and removing pacemaker
ieads. In some designs, the lead is already preshaped to accommodate the location
into which it will be introduced (often J-shapedfor upside-down introduction of
electrode into right atrium). In such a preshaped!ead, a straight stylet mustbe
inserted through the coil lumen to allow venous transversal during the
implantation procedure. In other leads, the lead itself is not preshaped and passed
directly through a vein into the heart. If required, a preshaped stylet maythen be
inserted to permit and maintain the desired lead shape for effective electrode
enlodgmentuntil it is removed,if ever.
Lead testing
Common.measurementsof lead durability include: general lead reliability, flex

fatigue~ stylet insertion and extraction, vibration -testing, and leak testing. General
lead reliability is usually determinedby the ability of the lead to tolerate normal
stresses induced by handling and implantation. Flexural testing determines how
well a lead performsboth electrically, and physically after repeated flexing and
elongation. Stylet insertion and extraction tests determineira lead is physically or
electrically damaged by multiple stylet insertions and removals. Vibr~ions
attributed to,manufacturing, shipping, and handing processes mayalso. contribute
to lead deficiencies. Various vibration tests are often performedon multiple axes
to determine if a lead can withstand such conditions. Leak testing is important to
determine if lead insulation and joints can withstand chemical conditions similar
to those found in the body.
After most lead tests have been performed, electron microscope scans (EMS)
are routinely performed to determine coil integrity. Figure 6.14 shows two
examples of coil deformation commonlyattributed to compression induced by the
scissoring effect betweena patient’s clavicle and first fib upon an implanted lead
(Brinker et al., 1991; Stokes and McVenes, 1988; Stokes et al., 1987). The
procedure used to implant leads experiencing such deformations is. knownas the
percutaneous subclavian vein approach. This procedure has recently accounted
for between 75-95%of pacemaker lead implantations (Bernstcin and.Parsonnet,
1989). While clinical ease and speed of implantation have. accounted for the
popularity of this procedure (Hess et al., 1982; Jacobs et al., 1993), increase
coil fracture occurrence, attributed to repeated scissoring compression have
required evaluation of b0th the implantation procedure and lead design (Alt et al.,
1987; Luck and Pae, 1991).
(a) (b)
Figure 6,14 Examplesof compressed leads. (a) Compression
damageto soft wire coil after
single applicationof compression
in medialsubclavianimplantation,(b) Coilfracture morphology
associatedwithrepetitive andcompressivescissoringbetween
a patientYsclavicle andfirst fib.
FromJacobs, D. l~I., Fink, A. S., Miller~R. P., Anderson,
W.R., McVen~s, R. D., Lessar, J.
F., Cobian,K. E., Staffanson,D. B., Upton,J. E., andBubrick,M. P. 1993.Anatomicaland
morphological evaluationof pacemaker lead compression.PACE,16: 434-444.
Lead stiffness
Lead stiffness is important to both ease of clinical insertion and electrode

efficiency. If a lead is too stiff, transversal of its length is madedifficult as the
physician attempts to run it through one of several upper venous system veins.
Although rare, clinical cases have been reported of electrodes piercing vessel
walls due to overly stiff leads. Additionally, once an electrode has been implanted
(whether actively or passively), minimal pressure should be exerted against the
endo- and myocardium. This minimizes mechanically induced inflammation. If a
bent lead excessively pushes its electrode against the heart tissue, increased
inflammation results in reduced pacing efficiency. If a lead is extremely stiff or
improperly implanted in a patient with deficient myocardial tissue, the patient
may experience more severe conditions such as high ~threshold exit block,
myocardial ischemia, or ventficular perforation (Cameronet al., 1990).
Bipolar leads are traditionally known to be stiffer than unipolar
implementations (Cameron et al.; 1990). While the distal length between the
anode and cathode is structurally the same as with a unipolar lead, abipolar lead
ELECTRODES( LEADS, AND BIOCOMPATIBILITY 153
often has a pair of coaxial coils comprising the remainder of its proximal length.
This increased bulk can significantly increase lead stiffness. Intermedics has
introduced a thin bipolar lead having greater flexibility than observed in many
other bipolar designs (Adler et al., 1992). Figure 6.15 shows both traditional
coaxial and Intermedics ThinLine®lead models.
O~or.~ O~thode~ . _ Int~grld
~igure 6,1Si Comparison

of traditional coaxialbipolar~oi~~0nfiguration
nLinedesign.Notethat the ThinLine
withIntermedics,Inc.
lead is si~nifi~tly thinnerthana ~tandardbip61arlead.
ThisresUltsin increasedlead flexibility andless invasiveness.FromAdler,S. C., Foster~A.J.,
Sanders,R: S., andWuu,E. 1992.Thinbipolarleads:;a solutionto problems with coaxialbipolar
designs. PACE,15: 1986-1990.
Lead insulation
Anotherlead consideration is insulation material.’ important criteria: to selecting

these materials include~ electrical insulation propertieS, stiffness, durability, and
biocompatibility. Two Classes of modern materialg have been found to
Satisfactorily exhibit most Of these characteristics: polyurethanes and silicone
rubbers. Both are excellent electrical insulators, very d~able, and are relatively
biocompatible. Manypolyurethanes used as lead insulation are less flexible than
silicon~ rubbers and tlitJs can cOntribute to.the ov~rali stiffness: of the lead
(Cameronet al., 1990).~ In’ addition~ gtudies in recen~ years .denioristrate higher
rates of insulationcracking for leads using polyurethanes than those
implementing siliCCne rubber~. Howevei:, poiyuretlaaheS have.lower friction
coefficients ~han silicone rubbers and are therefore easier to implant. The
advantages and disadvantages of polyurethanes and silicon rubber as lead
insulation have been a source of debate for years.
6.3- BIOCOMPATIBILITY
It is important that anything implanted in the patient not compromiseotherwise

previous healthy body systems. Protecting the patient from adverse material side-
effects is the primarygoal of biocompatibility.
A secondary goal is protecting pacemaker operation from the body’s hostile

environment. This is known as biostability. The human body exerts multiple
processes to either destroy or isolate foreign materials from its otherwise normaJ
physiologic operation. If materials are chosen poorly or not manufactured
properly, foreign body processes mayenter and possibly corrupt the integrity of
any or all pacemaker components. To maintain effective pacing therapy,
therefore, body fluids must be kept from entering any component, joint, or seal
in the entire system.
6.3.1 Characteristics of pacemaker biomaterials
There are no known entirely biocompatible .materials. Whenimplanted, all

materials undergo various types and-de~rees of chemical interactions with bodily
solutions. It is important, therefore, to find suitable materials for specific
biological applications. Such materials arC defined by the following:
me that does not lead to an acute

or chronic inflammatory response ~nd that does not prevent a proper
differentiation of implant-surrounding tissues (Williams, 1987).
The tissues affected by the three pacemaker components--the pacemaker,

lead, an.d, .electrode---all dif~’e~ Thepacemakeritself is usually pocketedb~rtween
a patient s skin and pectoral musel~,~Alead typically transverses the subclavian or
cephalic vein into the superior vena~cava.~ The electrode is implanted into the
right atrium or ventricle. It is important to select or develop materials compatible
with the respective implant locations’ characteristics.
From these three locations (skin/muscle, venous, and inner heart), two
different pacemaker material groups are distinguishable: soft tissue and blood
compatible materials. For each,, several characteristics need to be considered for
implantation: physical, mechanical, chemical, dectrociaemical, physiological,
pathological, and biological. Manufacturability, quality control, and cost
reduction are also criteri~ i~p0rtant for mass production. Compromisesmade
between physical and production criteria determine a pacemaker system’s
biocompatibility success.
Physical and mechanical material characteristics include: density, hardness,
flexibility, tensile strength, gas permeability, shear modulus, electrical and
thermal conductivity, thermal coefficient of expansion, and surface roughness
(Billmeyer, 1984; Brown, 1988; Fraker and Griffin, 1985; Mohtashemi and
Hines, 1983; Rembaumand Shen; 1971; Schaldach.and Bolz, 1991; Shalaby,
1988; Szycher, 1983; Williams, 1987). Pacemaker materials must be able to
withstand various physical, mechanical, and chemical elements for decades.
Generally, the body is chemically modeledas a salin~ reservoir comprisedof
manydifferent ions. It is also comprised of electrolytes. These characteristics
make the pacemaker system vulnerable to a variety of chemical and
electrochemical interactions. Reducing opportunity ~ for ~ pacemaker system
materials to negatively affect the body and vice versa requires several chemical
parameter considerations. These include: corrosion resistance, chemical stability,
resistance to chemical solvents~ sterilizability, water absorption, and surface
tension characteristics (Billmeyer, 1984; Mohtashemiand Hines, 1983; Rembaum
and Shen, 1971; Schaldach and Bolz, 1991; Szycher, 1983; Williams, 1987).
ELECTRODES, LEADS, AND BIOCOMPATIBILITY
Chemical and electrochemical reactions occurring at ~material-tissue

interfaces often induce physiologic, pathologic, and biologic changes. Clinical
consequencesof these interactions require that pacemakerdesigners also consider
material criteria directly relevant to patient health. These clinical considerations
include: carcinogenicity, toxicity, thrombogenicity, immunalresponses, infection
affinity, and allergic and inflammatory reactions (Mohtashemiand Hines, 1983;
Schaldach, 1992; Schaldach andBolz, 199I).
Common complications attributed to pacemaker materials and improvements
requiredto for complication reduction are shownin Figure 6.I6.
Complications Future development

action items
Throiribosis "- AntithrombogeniCsurface
Blood traumatizatior,--.~_ ~’- Blood compatible materials

Tissue reaction ~~ Improved(~onsiruction
¯
----~
Fibrosis~
Corrosion and degradation ~
Inert, noncorrosive
Products of abrasion~ v materials .~
Infectioti~~ Atoxic matei’ials
-’’-~s.........../
Metabolicchange " ¯
Figure 6.16 Common

complicationsattributed to pacemakermaterials and goals for future
development.FromSchaldach,
M.M.1992,Electrotherapyof the heart. ~erlin::Springer-Verlag~
6~3.2 ’Summary of pacemaker biomaterials
There are fo~ general classes of biornaterials: metals, polymers, gl~ses, and
cei~cs. There are also composites of these materialS. All are knownas b~ing
al,10plastic, meaning not biologicalin origin. The chemical bonds holding each
ni~t~dal together geiiera!ly dete~e implantation Utility. - ~
Metals
Me~ls typically exhibit bonds characterized by free eleCtronS in a l~ttice o.f

ptsitiX, e atomic cores. These bonds and their free electrtns Contribute to the
electrical conductivity of manymetals (Brown, 1988; Fraker and Griffin, 1985;
seiialdach, 1992; Szycher, 1983; Williams, 1987). Ittadditi0n, metal lattices
e0ntribute to their relative strength, flexibility, and hardness compared:tO.other
~atefi~S. Titanium and two 0fits alloys, niobium and ~talum, are especially
bi~0~patible because they Spontaneously form nonconducting oxide layers at
their ~ surface (such as Ti02) ~. This provides a protective Surface preVenting
exchange of charge carders across the phase boundary :(Fraker et at., 1980;
Zitter and Plenk, 1987). Platinum and/or iridium coated electrode tips have
exhibited low chronic stimulation thresholds due to reduced local inflammation

(Mondet al., 1988; Rubin et al., 1991; Schaldach et al., 1990). Titanium and its
alloys also exhibit physical and mechanical properties equivalent or superior to
manyother metals (Schaldach, 1992). The modulusof elasticity of titanium and
its alloys range between 100-120 GPa. Extreme resistance to corrosion and
durability maketitanium and its alloys ideal materials for hermetically sealed
pulse generator cases (Schaldach, 1992; Tar jan. and Gold, 1988). These cases are
nowcommonlylaser welded together.
Other metals implemented in pacemaker components have included various
stainless steels (such as type 316L), cobalt and chromiumalloys, platinum and
some of its alloys, nonferrous alloys such as MP35N® [Standard Pressed Steel],
Elgiloy [American Gage and Machine], and Tinel®/Nitinol® [Raychem], and
iridium (Bittence, 1983; Boretos and Eden, 1984). In addition to titanium and its
alloys, various stainless steels have also been used for. both pacemakercases and
lead coils. Cobalt, chromium, silver, and nonferrous alloys are also commonly
implemented as lead coil conduit due to electrical and flexural properties.
Platinum, iridium, and Elgiloy are commonlyused for electrode tips due to high
biocompatibility.-While these materials are generally not as biocompatible as
titanium and its alloys, they suitably fulfill requirements of their respective
biological implantation sites.
Polymers
Polymers, or plastics, are commonlyused as lead insulation, electrode housings,

electrode case sealants, and for bonding lead components. In addition, they are
also used foi? electrode fixation apparatus and forming the connector block
between the pulse generator and the lead. Polymers are characterized by
elongated molecular structures containing large quantities of covalently bonded
carbon groups. Due to bonding covalency, many polymers exhibit very little
chemical interaction with the body. However, because of the length of some of
their molecular chains and the bonds that hold them together, polymer
mechanical properties are often dependent upon temperature (Billmeyer, 1984;
Rembaumand Shen, 1971; Schaldach, 1992; Szycher, 1983). Thus, properties
such as: hardness, flexibility, and thermal coefficient of expansion are specifically
of concern. Additionally, due to petroleum-based manufacturing processing,
polymer materials often have carcinogenicity and toxicity considerations. Despite
these possible disadvantages, polymer materials are generally cheaper and
available in forms more easily’~aanufacturable than most biocompatible metals.
Polymers are commonlyavailable in granules, pellets, or films. These forms are
easily adapted to manufacturing processes such as extrusion, injection molding, or
vacuumcasting. Metal processes such as cutting, grinding, and polishing are less
cost and time effective.
Commonpolymers used in pacemaker applications include various
polyurethanes and silicone rubbers. Polydimethyls, siloxanes, and various
polyurethanes are flexible, nonconductive, and abrasion resistant. They are also
easily manufactured by injection molding and extrusion processes. All of these
characteristics contribute to successful implementation as lead insulation and
electrode housing materials: (Llewellyn et al., 1988). Epoxyresins and silicone
rubbers exhibit five advantageous pacemakermaterial characteristics, inclu~ding
being chemically resistant, exhibiting low shrinkage in warm, aqueous
environments, strong adherence to metals, extremely flexible, and easily
ELECTRODES; LEADS, AND BIOCOMPATIBILITY 157
tfi~nufacturable in molding processes. Such resins are thus .commonly used in

p:~fi~maker system jointsand connectors, especially the pulse generator connector
~i~tk (Billmeyer, 1984; Rembauin and Shen, 1971; Schaldach, 1992!
SZycher, 1983).
Glasses and ceramics
Glasses and ceramics are extremely hard and exhibit desirable properties relevant
to~,~hermal, coefficients of expansion, specific heats, insulation, and smoothness.
Tl!e~e ~e several pacemaker uses for glasses and ceramics.i One use includes
ee~c encapsulauon of the pulse generator for protection. Th~s sealant layer ~s
ex~mely smooth and very soft tissue biocompatible. Ceramics or glasses are. also
sometimes activated with metals or vitreous carbon to produce high active surface
areas desirable for electrode tips (Katsumoto et al., 1986; Mundet al, I986;
geti~d~ich, 1992). Due to absorption characteristics, eerie collars surrounding
electrode tips have been used for containment.and elution.of steroids into
surrounding tissue to minimize inflammation and collagenous accumulation
~iii:i~rson et aL, 1990; Anderson et al., 1991; Mathivatlar et al., 1990;
~i~sky et al., 1990; Wilson et al., 199I)~ Lastly, glass is commonlyused to both
seal=pulse generator can entry and comprise the connector block where lead
eon~eetion occurs.
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r ELECTRODES, LEADS, AND BIOCOMPATIBILITY 159
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:,::leads~with a reduced doseofDSP.(abstract) RBM,12:62.
Mohtashemi, M.,andHines, G. L.1983.Tissue response to permanently implanted pacemaker
¯ generators andelectrodes. In L.R.Rubin(ed.)Biomaterials inreconstructive surgery,
London: TheC. V. Mosby.
Mon&H.~andSloman, G. 1980.Thesmalltinedpa~cemaker lead-absence of dislodgement,
PACE, 3: 171-177. -
Mond,H., and Stokes, K. B. 1991. The electrode-tissue interface: the revolutionary role Of
’~.~Steroid elution. PACE,15: 95-107.
Mond,H., Stokes, K. B., Helland, J., Grigg, L., Kertes, P., Pate, B., and Hunt, D. 1988: The
porous titanium steroid eluting electrode: a double blind study assessing the stimulation
~eshold effects of steroid. PACE,11: 214-219.
Mugica,J., Henry, L., Atchia, B., Lazarus, B., and Duconge,B. 1988. Clinical experience with
new leads. PACE,11: 1745-1752.
Mund,K., Richter, G., Wiedlich, E., and Falhstrtm, U, 1986. Electrochemical properties of
platinum, glassy carbon, and pyrographiteas stimulating electrodes. PACE,9: 1225-1229.
Ormerod,D., Walgren,S., Berglund,J., and H¢il, R., Jr. ~1988.De~s!gnand evaluation of a low
threshold, porous tip lead with a Mannitol Coated screw-in tip ( SWEET TIP" m). PA
11: 1784-1790.
O°Sulliv.,an, J. J., Jameson,S., Gold, R. G., and Wren,C. 1993. Endocardial pacemakersin
’ ’itl~ct/en: lead length and allowancefox growth.. PACE,16: 267-27~L
Pioger, G., and Ripart, A. 1986~.Clinical results of low energy unipolar or bipolar activated
. ~.~.earbontip leads. PACE,9: 1243L1248.
Preston, T. A., and Judge, R.: D. 1969; Alteration :of pacemaker threshold by drug and
physiologicalfactors. Ann. ~N. Y. Acad. Sci., 167: 686.
Rembaum, A., attd Shen, M. 1971. Biomedicalpolymer~.NewYork: Dekker;
Robinson,T. F., Cohen-G0uld,.L., and Factor, ’S: M. 1983; Skeletal frameworkof mammalian
heartmuscle:arrangementof inter- and pericellular connectivetissue structures. Lab. Invest.,
29,." 482-498.
Rubin, L., Rosenberg, D., Parsonnet, V., Villaneuva, A., and Ferrara-Ryan, M, 1991.
Comparison of titanium-meshand porousdisc electrodes .for epicardial defibrillation. PACE;.
~ 14:1860-1864. ~
Salthot~se, T.N. 1984; Someaspects of macrophage behaviorat theimplant surface. J.Biomed.
Mater. Res.,18:395-401.
Schaldach, M.M;1992. Electrotherapy oftheheart. Berlin: Springer-Verlag.
Schaldach, M.M.,andBolz, M, A,1991.Biocompatibifity optimization:of materials byhybrid
"~structthdng. Medicalengineeringand computing~ 29: 134:
Schaldach, M. M.,Hubmann, M.,Weild,A.,andHardt,.R.1990.Sputter-deposited TiN
electrode coatings forsuperior sensing andpacing, performance. PACE, 13:1891-1895.
Secemsky, S.,Hauser, R,.andDenes, P.1982.Unipolar sensing abnormalities: incidence and
clinical significance ofskeletal muscle interference andundersensingin 228patients, PACE~
5: 10. -
Shalaby, S. W.~988. Polymeric materials. In J.~ G. Webster (ed.) Encyclopedia of medical
ddvices and instrumentation. NewYork: John Wiley,&Sons. ’ .
Sinna~Ve,A., Willems, R., Backers, J., Holovoet, G~, and,Stroobandt, R.-t987. Pacing-and
sensing: howcan one electrode fulfill both requirements.?PACE,10: 546.
Skalsky, M., Mathivanar, R., andAnderson,N. 1990: :Threshold’performance’ofbipolar leads
with a drug eluting,cotlar (DEC).(abstract) RBM,12: 108~
Stokes, K. B. 1988. Preliminary studies on a newsteroid eluting epicardial elec.trode~ PACE,
11: 1797-1803.
Stokes, K. B., and Anderson,J. A. 1991. Lowthreshold leads: the effect of steroid elution.
Proceedingsof the second international symposiumon cardiac pacing leads. Amsterdam,The
Netherlands:Elsevier SciencePublishers.
Stokes, K. B., and Bornzin, G. 1985. The electrode:-biointerface: stimulation. In S. S. Barold
(ed.) Modemcardiac pacing. MountKisco, NY:Futura Publishing Co., Inc.
Stokes, K. B., and Church,T. 1987. The elimination of exit block as a pacing complicationusing
a transvenonssteroid eluting lead. (abstract) PACE,10: 748.
Stokes, K. B., and McVenes,R. 1988. Pacing lead fracture, a previously unknown complication
of subclavianstick. (abstract) PACE,11: 855.
Stokes, K. B., Staffanson, D., Lessar, J., and Sahni, A. 1987. A possible newcomplication of
subclavianstick: conductorfracture. (abstract) PACE,10: 748.
Stokes, K. B., and Stephenson, N. 1982. The implantable cardiac pacing lead--just a simple
wire? In S. S. Barold and J. Mugica (eds.) The third decade of cardiac pacing.
Mount Kisco, NY: Futura Publishing.
Szycher, M. 1983. Biocompatible polymers, metals, and composites. Lancaster: Technomic
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Tarjan, P. P., and Gold, R. D. 1988. Implantable medical electrical devices. In J. Kline (ed.)
Handbookof biomedical engineering. NewYork: AcademicPress.
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Williams,D. F. 1987. Definitions in biomaterials. Oxford:Elsevier SciencePublishers.
Williams, W.G., Hesslien, P. S., and Kormos,R. 1986. Exit block in children with pacemakers.
Clin. Prog. Electrophysiol. Pacing,4(5): 478-489.
Wilson, A., Kay, N., Padeletti, L., Michelucci, A., Ferri, F., Baird, D., Mathivanar, R., and
Skalsky, M. 1991. A multicentre study of steroid eluting collar leads. (abstract) PACE,
14: 629.
Zeidler, D. E. 1977. Stress fractures in pacing leads. Medtronicnews, 7:8-11.
6,5 INSTRUCTIONAL OBJECTIVES
6.1 State the twomost common electrical roles of a pacemakerelectrode. Explainbriefly which
is mostimportant~to extendingpacemakerduration of service and why.
6.2 Excludingelectrical roles requestedin Instructional Objective6.1, list six considerations
importantto electrode designphysically. Explainbriefly whyeachis important~
6.3 Sketch the fwst order approximationof the Helmholtzdouble layer formedby metal being
submersedin electrolyte. Includeelectrical schematicmodelcorrelated to ~xhibitedphysical
characteristics of this doublelayer~ Whyis metal-oxideformationdesirable?
6.4 Explainwhyreversible reactions are preferable to irreversible.reactions at the electrode-
electrolyte interface. Explainbriefly twopossiblq waysthat reversible chargetransfer (RCT)
is obtainedat this interface. .
6.5 Discussthe.origin of Faradiccurrent. Whyis Faradiccurrent undesirableS.
6.6 Explain whythe suppression of electrode induced inflammationis important to decreasing
both acute and chronic stimulation threshold change. Explain briefly howsteroid-eluting
designsare theorizedto accomplishthis.
6.7 Describethe difference betweenelectrode tip macroscopic size andmicroscopicsurface area~
Explainwhythe difference is importantto electrode tip design.
6.8 Explain whyporosity is important to electrode tip design. Discuss the theory behind its
Success.
6.9 List two general advantagesto active helical fixation,, methods.Withrespect to pacing
efficiency, state a disadvantageassociatedwith general active fixation methods.
6.10 For a general ventricular electrode implantation, explain whyapassive tined electrode may
be preferableto an active hefical tip implantation.
6.11 Sketchboth unlpolar and bipolar types of leads. List twoadvantagesfor each.
6.12 Whatis the difference betweenbiocompafibilityand biostability? Whyis each important?
6.13 List four uses for metals in pacemakertechnology.Explain whytitanium and its alloys are
so effectivein their respectiveapplications.
6.14 Discuss two primary concerns associated with implanting polymersin the body. List the
advantages polymershave over other biomaterials. List two. polymerscommonly used in
pacemaker technologyand their respective uses.
Battery
!0~ G. Webster
~ ~acemaker demands a very small power. A stimulus pulse of 5-19 mAat 1-

[*~’V ~,ith ’a duration of 0.25-1.0 ms is delivered at’a rate of 30"150 bpm. The
average current drain is 30 #W. Thus a 2 A-h battery would last 21 years. Early
batteries were rechargeable, followed by the zinc-mercury battery. Since 1972, the
lithium battery has been the principal power source. Present batteries~last more
than, 10 years.
7,1 MATERIALS
~l!l’Early development
Nic’kel cadmiumrechargeable battery
The first implant in 1958 was, designed by Elmquist and used a rechargeable
(secondary) nickel-cadmium battery. It was inductively recharged by the
transmissionof energy to the implanted receiver. The cell.voltage was 1.25 V and
the capacity was 190 mAh.It was unsatisfactory because thefifetime was not. long
enough compared to a (primary) nonrechargeable battery. Also, it was not
satisfactory to place the responsibility for recharging in the hands of patients~ who
in manycases were senile.
Z~n~c~.~mercu~,
batteries
In 1958-1960, the zinc-mercury battery ~ was modified for longer shelf life for Use
in electric watches. For pacemakers,three to six cells in series provided 4-8 V. It
became widely used in pacemakers, typically cast in epoxy, which was porous to
the evolved hydrogen and permitted its dissipation. However, even with
improvements,by 1970, longevity was only about two years.
Biological batteries
The concept of using power from within the body is attractive, Somehave tri~
biogalvanic cells in whichdissimilar electrodes and the body’s electrolytes yield
power. Others have tried fuel cell’s that utilize oxygenfrom the blood and hydrogen
from body proteins or glucose from the blood. Still others have converted body
movementthrough piezoelectric generators or self-winding watch escarpments.
Noneof these has proved practical.
Nuclear batteries
Practical nuclear batteries use plutonium(238pu). It has a half-life of 87 years

the output degrades only 11%in 10 years. Howeverit is highly toxic and 1 l.tgin
the blood stream could be fatal. While early pacemakersused metallic plutonium,
recent pacemakers use the ceramic plutonium oxide, which would reduce the
possibility of spillage in case of the accidental impact of a rifle bullet. Patients
receive less radiation than a control patient in Denver, CO,wheresolar radiation is
poorly faltered (Greatbatch and Sdigman,1988).
The plutonium emits o~ particles, which .impact upon the container and
generate heat. Thermopiles of dissimilar p- or n-doped bismuth telludde generate
the electricity for the pacemakercircuits.
7.1.2 Lithium batteries
Fabrication
Since 1972, a variety of lithium batteries have been used. These include Li/SOCI2,
Li/Ag2CrO4, Li/CuS, Li/I2-Polyvinylpyridine (PVP), and, in more limited use,
Li/LiI(A12)3/PbI2,PbS, Pb. The Li/I2-PVP is the principal pacemaker b.a~e~: and
yields 2.8 V (Schaldach, 1992).
The cathode is a complexof iodine and poly-2-vinyl pyridine (P2VP). Neither
conducts electricity, but whenmixed and heated at 1497Cfor 3 days, they react
into a black viscous paste that conducts electricity. This is poured into the battery
whenmolten and cools to form a solid. Whenthis paste contacts metallic lithium, a
monomolecular layer ~of crystalline lithium iodine forms. It is a molecular
semiconductorthat passes lithium ions, as required, for current flow, but not iodine
molecules (Greatbatch and Seligman, 1988).
Reactions
Figure 7.1 shows that conventional current flows through a device from anode to
cathode. For a battery, the current flows from the negative~anode,~through~the
batte~, to the positive cathode. Oxidation of metal occurs at the anode,
Li --> Li+ + e- (7.1)
and reduction of halide occurs at the cathode,
12 + 2 e- --) 2 I-. (7.2)
The combinedreaction is,
2 Li + 12 --) 2 LiI (7.3)

BATTERY 163
Internal,resistance Battery cathode

Battery anode _.= ~.
t
12 + 2e- -~ 21-
R.~.uction
Load anode
Current
Figure7.1 Conventionalcmrentflowsfromanodeto cathode.Thelithiumreacts with the iodine

to formlithium-iodide,whichgrowsin volume
andincreasesthe resistance.
Resistance
The se~formingLiI discharge product is not a perfect barrier to iodine diffusion.

Small cracks and grain boundaries may permit the iodine to diffuse along these
interfaces and react directly with the lithium. This self-discharge reaction decreases
the capacity.
The battery resistance builds up as the solid LiI dectrolyte accumulates as in
Figure 72,.The anode is precoated with a solution of PVPto lower the,resistance.
The solvent evaporates, leaving a contiguous, film of pure PVPon the entire anode
surface. Later developmentswere the use of a cast film of PVPor impregnation of
an inert substrate with a solution of PVP, drying the solvent, and cutting the
material into the appropriate shape for pressing onto the anode (Greatbatch and
Holmes,~1992).
~’ UNCOATEO
/
160OO
/
12OOO / /
8OOO
4OOO
0
o 200 600 ~10001400’1800 ’2200 26003000
Capacity(mAh)
, Figure. 7.3, phase I showsthat the voltage starts to decrease. In phase lI, th
dathode becomes S~ed .of iodine and de~elops a~ higher impedancb’tli~/he.,LiI
electrolyte, Causing the shoulder region of Figure 7.3. During phase"III; He
concentration of available iodine is so low that the voltage drops dramatically--a

region well beyond the designed end of life (EOL).
VDC
3.0V
2.8V
iodine in P2VP
matrix
3 Ah
Figure7.3 Typicallow-rate,triple-phaserundownpattern of lithium-iodinebattery for phaseL

phaseII, and, phaselII. FromGreatbatch,W.,and Seligman,L. I. 1988.Pacemakers. In J. G.
Webster(ed.) Encyclopediaof medicaldevices andinstrumentation.JohnWiley&Sons.
7.2 MANUFACTURING
7.2.1 Construction
Figure 7.4 shows the internal construction of a central anode/case grounded cell
with corrugated anode. Lithium is easily formedinto sheets that can be cut to the
required sizes. It is easily pressed ~to specific anode shapes. The lithium anode is
coated three times with a solution of PVP. The solvent is evaporated to leave a
contiguous film of pure PVPon the anode surface. The precoated central lithium
anode is corrugated to increase its area ~and lower battery impedance. To obtain
lower impedance, newer designs use more concentrated active materials and larger
~n_heodesurface
complex ~as~,. Multiple
ofi0dine anode surfaces
and l~ly-2-vinyl pyritemay:be:used
~P2VP)is~t0pod
lower.~b_e
into theimpedance.
cath6de
c~e to cool
..... " dohe
bye fe through
or ceramicinsulator.
BAT~RY 165
GONNEGTION
TO CATHODE GLASS-TO-METAL
SEAL
(CASE)
CENTRAL
ANOOE
CATHOOE
Figure7.4 Internal constructionof central anode/case-grounded

cell with corrugatedanode.
FromSchaldach,M.1992.Electrotherapy of the heart. Springer-Veflag.
7.2.1 Testing
To maintain high reliability’, cells are designed conservatively. They are

manufactured under stringent, quality controls, as" demanded by the Good
Manufacturing Practices (GMP) issu~ by the Food and Drug Administration
~A). Figure 7.5 shows that qualification testing is performed under accelerated
test con&dons(Schaldach, 1992).
Nondestructive examinations
Thermal cycling
High pressure
Mechanio.~lvibration
Temperature/humidity
Mechanical shock
Voltage/temperature
Seal terminal strength
Elevated temperature discharge
Destructive analysis
Solvent resistance
Figure7.5 Qualific~itionlist for Li/I2-PVP

cells (Shaldach,1992).
7~3 END OF LIFE
As :the~battery depletes, we need a,means of determining that the~endof life, is

approaching, so wecan plan replacement of the battery on a scheduled, rather than
an emergency~basis,
73;~ Ratechanges
As the battery of, a pacemakerprog ~ressively discharges, the internal resistance can
increase to the point that inadequate charg~gof the ou~ut capacitor occurs, If the
capacitor fails to store enough charge between pulses, then there is the chance a
stimulus pulse delivered could fail to cause contraction of the heart. Therefore, it is
wise to ensure that the stimulus amplitude is always above threshold.
Figure 11.6 shows one method for assuring adequate output amplitude
Elmovist (1984). This circuit releases stimulation pulses only if a specific minimal
voltage Vminis reached. Every pulse delivered will be above threshold, and the
heart is certain to be stimulated.
Battery
I
I Vb
i Monostable
one
t~0.8 ms
Mt~,OonOStable
t~,O.5,~
~,,~
ms ~ i -..--.I
7 J’-°
"
Ana!£gor, I ’, "" I
I cD~gimt~la~ator ~ivmin ~ "
(b)
Ri
Figure7.6 Lowpoweroperating circuit. (a) Aschematicof the system.Monostable two is not

allowedto fire unless the output capacitor has reached a minimal,voltage Vmin.(b) The
frequencyof stimulation,internal battery resistance,andoutputvoltagecharacteristicsovertime.
WhenRi is great enoughthat the outputvoltage doesn’treach.Vnanin 0.8 s, the frequencyof
stimulationbeginsto decrease.FromEimovist(1984).
Figure 11.6(a) shows that starting with both monostables low, the capacitor
charges from the battery through battery resistance Ri and a,~f~ed r, esis~tor. The
output capacitor is connected to a comparator which compares the capacitor
voltage value with a set minimalvoltage Vmin.If the voltage at the capacitor is
below Vmin,the comparator output is_ high and a logic J is delivered to the~:~OR
gate, resulting in an output from the NORgate whichis low. Oncethe, voltage .at
the output capacitor is greater than Vmin,the comparator output goes ~low;:.which
delivers a logic 0 to the NORgate. Assumingmonostable one is already low, the
output of the NORgate becomeshigh. This activates monostable two’,~,whi6hYliff
active for approximately 500 Its, and subsequently switches the transistor into its
through ~ the heart to, grO~nd~’~Aetivation of monostable two a|~o-actiqates

BATTERY 167
monostable one. A logic 1 is supplied by monostable one to the NORgate, which

changes the NORoutput back to low, for a minimumof 0.8 s.
The base frequency of the circuit is set by the timing of monostable one.
Whenthe internal resistance of the battery is low enoughto allow the capacitor to
reach Vminbefore monostable one becomes low, then output pulses will occur
every 0.8 s. Figure 11.6(b) showsthat whenthe internal resistance Ri increases
the point that the output capacitor does not charge adequately in 0.8 s, the
frequency of stimulation begins to drop. This frequency drop can be used as an
indication of battery end of life. The stimulation frequency will continue to
decreaseas the internal battery resistance increases. It is possible to adapt this basic
idea to more sophisticated pacing schemes. For instance, monostables one and two
could be replaced by, logic circuitry that allows for triggered and inhibited pacing,
and different pulse durations. Other modifications can be madeon this design as
well.
7.3.2 Capacitor chargeup
Frost (1986) designed a circuit that indicates depletion of the battery prior to rate
changes. It momentarilyswitches the battery to a test capacitor. Figure 7,7 shows
that pacemaker 12is normally powered£rom battery, VC. Switch S1 is opened
momentarily and the pacemaker continues to be powered by filter capacitor CB,
Switch $3 has discharged test capacitor CTand opens. Switch $2 closes and CT
~hearges wi~’,from
termined a time constant z = RCT,
the Charging ,The internal
charaCteriStics resistance of the battery
shown in Figure 17.8 andR is
is
telemetered from the body.
Figure7.7 This circuit measuresinternal.battery resistance. SwitchS1 that powerspacemaker

12 is opened.Switch$2 is closed so test cap~acitorCTcharges, up ~roughbattery internal
resistanceR (Frost, 1986).
7.3.3 Marking pulse ;~
Moberg(1987) designed a circu~ that Calculates the batter~ charge consumed

microampere-hou~rs and creates a marking pulse that can be read by the external
ECG.It counts,the numberof stimulation pulses and uses pulse amplitude, pulse
duration, and electrode impedance. Figure 7.9 shows that it generates a marking
pulse whos~timingdepends on the remaining battery capacity, ~Figure 7,10 shows
that n0fmal!~U!Sts~ave in’creased voltage by chhrging two Capacitors’in p~al!el
and discharging~emin Series. The:smaller subthreshold marking pulse is ii~Se~d
by a single capacitor.
VOLTAGE
AT
VBA VDD
T
VREF
St CLOSED
S2 OPEN
$3 CLOSE{
TIME
S3 OPENS
SI OPENS $2 OPENS
SI CLOSES
sz cLos~"
COMPARATOR
OUTPUT VDD
TIME
vssI
~.i~, ~ 7.8 VDDis common.When$3 opens, VBATgoes tO -Vc because voltage drop throughR
decreases to zero. When$2 closes, VBATis clamped to VDD,then exponentially charges through
R toward ~-Vc. Comparator14 detects time toxeach VREF,~whichis a function of R (Frost, 1986).
6
LI
["-,~X-lO0 ms -I
Figure 7.9 After a stimulating pulse, a smaller nonstimulating marking pulse is placed at time
X. 100 ms, where X is remaining battery capacity in years (Moherg, 1987)..
Fi~ur4~ 7.10. Circuit foT~voltage doubling ~a~._dgenerating ~g PUlSe. Through resistors 43

~ !~ ~ ~th~.~ battery charges ~the capacitors with switch posi~ons shown..Then switches 29 and 30
~c ~c!~s~d .an d Switc, h 31 is open~, which genei~teS a normal vol~ge’ doubled pulse by
(liSc~mgthe capacitors through the heartat 32~ For generatin~’asmall~ ~g pulse, switch
27 is closed for I ms (Moberg, 1987).
BATTERY 169
7.4 POWERPRIORITY
Pless and Stotts (1986) designed a priority switching circuit for extending
pacemakerlife while providing a minimalvoltage to a voltage-sensitive load. The
pa~makeroutput circuit requires a large current to recharge the output capacitor
between pulses~ This current flows through the battery internal resistance and
~reases the battery output voltage. This temporary decreased voltage can cause
~b~eiitially dangerous intermittent malfunction of the control circuit and
corresponding erratic operation of the pacemaker.
Figure 7.11 showsa powerdistribution controller that selectively switches the
battery betweenthe output circuit and the control circuit. A hold-up capacitor Chold
is connected in parallel with the control circuit in order to maintain at least a
minimal operating voltage Vminwhenthebattery is disconnected fromthecontrol
circuit andconnected topower theoutput circuit.
Figure 7.12shows thatwhenthebattery isnearendoflifeandRbatt
the.power distributioncontroller mostefficiently distributes thepower~ to maintain
controller voltagc~Figure7.13gives typical d~...ta fora power prioritysystem.
CONTROL
CIRCUITRY !
Figure
7.11
Whenvoltageon
theholdcapacitor
decreases
totheminimum,
switch
S1isclosed
torecharge
itandswitch
$2opened.
Tocharge
thepulse
output
capacitor,
switch
S I isopened
andswitch
$2closed
(Pless
andStotts,
1986).
7.5 REFERENCES
Elmovist,H. 1984.Implantableheart pacemaker.USpatent 4,463,706.J

Frost, J. G. 1986.Pacemaker battery impedance test circuit andmethodof operation.USpatent
4,606,350.
Greatbatch,W., andHolmes,C. F~~i992.Thelithium/i~nebattery::a historical perspective.
PACE, 15:2034-2036 .................. ~ .
Greatbatch,W., andSelignmn,L. }~ 19881Padcmakers, In L’G.:ilWebs~r(ed.)Encyclopediaof
medicaldevicesandinstrumentation.New ~ York:~:JohnWil~Y &’~0ng. ~~
.
Moberg, L. 1987.Batterytest circ~t for a heart pa .~maker.USpa~4,686,990. i
Pless, B. D., andStotts, L. J. 1986.Powerpfiori~;System.USp/trent 4,599;523.
~cha~dach, M. i992. E~ectrotherapy of the heart, e~rUn:Sp~[er:Veiiag.
R~B~t’~IK
A
¯" ~ R~tt "!OK
TI =Tim COlitroi Circuitry
Tl-l"iml
Figure7.12 When voltage on the hold Capaelt0fdecreasmto the minimum,

switchS l is closed
to rechargeit and!switch$2opened(Plessand<Stotts,1986).
Typical circuit values

Battery open circuit vol~ge 2.8
Control circuit minimalvoltage 2.2 V
Controlcircuit current drain 10
EOLbattery resistance ,+ 10 k~
Chold 10 ~F
Discharge times 1 ms, 5 ms
Oscillator frequency 167 Hz
Duty cycle 16.7%
Figure7.13 Typicalcircuit valuesfor the powerpriority system(Pless
andStotts, 1986).
7.1 Explainwhyreehargeablebatteries are unsatisfactory.

7.2 Describethe possible bi01o~calbatteries. ’ . ’
7.3 Explainhowthelithium-iodine15atteryis manufaCtUred.
7.4 Describethe three phase,~of rundown for a lithium~
7.5+ EXplainh0w
~ end-of-lifecircl~ii can"Cause rf~l~ ~iodine
elia~ge +.
’--s
battery.
7.6 ,,+~xplainhow +endoflife. ....
7.7 " EX~Iain + " r +
7.8
7.9 Describea
7.10Calculate is drawnfroma
PacemakerSense Amplifiers
David M. Beams
Early artificial pacemaker devices were asynchronous pulse generators which

delivered stimulus pulses at a fixed rate, regardless of natural cardiac electrical
activity oriphysiplogical state of the patient. The idea of a pacemak6rresponsive to
cardiac electrical activity was attractive for conservingthe limited energyavailable
in the pacemaker batteries and for avoiding competition between artificial
pacemaker ,stimulus and natural .stimulus. Su~li ~responsive-pacemakers would
require the ability to not only deliver stimulus to the heart musclebut also to sense
cardiac electrical events. Pacemakerswhichsense cardiac electricalactivity require
somesort of sense-amplifier circuits to amplify and detect that activity.
Fig~e 5.15 summarizes pacemaker types as designated by the NASPE/NBEG
gene~C~p~e.maker c0de, The second~haracter of th6code gi~ves information about
whi~:~hamber(s)Of the heart is (~)~ensed. Atrial; ventfieular,,~d dual-chamber
sensing categories exist (as well :as a category for asynchronouspacemakerswhich
donot:sensecardiac activity), Somemultiprogrammable pacemaker models (such
as the Medtronie Thera) maybe programmedto supportany of these possibi~ties:
Figure 8.1 gi~es a ~:rspe, cti~e of the coinp6si~i~nof the sense~ahiplifier block
of a, sensing pacemaker. This figure ,shows only one~ amplifier; a pacemaker
capable of dual-chamber sensing would have two such amplifiers’:~The common
sensing/pacing electrode is normally connected through the block markedblanking
to the variable-gain amplifier and bandpass filter; the connection is temporarily
openedwheneither a sensing or a pacing event occurs. Digital control lines from a
microcontroller select the. gai~of the~plifier; a windowcomparator, capable of
detecting sign~-exc~;sioos~abo~e,~r below the thresholds w~chare fixed by an
internal vOltag6 reference. The unfiltered intracardiac electr0gram mayalso be
madeavailable for tel6me~try p~ses. "
8.1 REQUIREMENTS
8.1.1 Unipolar and bipolar sensing
Figure 8.2 illustrates unipolar and bipolar sensing and unipolar and bipolar
electrode systems,~ The.unipolar ~ease-utilizes a~ single-ended-amplifier whose
reference-is~thepacemaker case and a single dectrode lead.~hich~terminates in the
electrode tip ~whiehisin.eleetfiCal contact, with the~myocardium~Thebipolar
system utilizes a differential amplifier and a dual-conductor lead which terminates
in the tip and ring electrodes. The unipolar pacemakersense amplifier responds to
electrical potential differences whichappear betweenthe tip electrode and the case
of the pacemaker; the bipolar pacemaker responds to electrical potential
differences betweenthe tip and ring electrodes.
Blanking
Gaincontrol
Variable gain
Window ~
amplifier and comparator
bandpass filter
, -sense
Blanking
circuits Voltage
reference
’ " Telemetry [._~
To telemetry circuits
I~ amplifier /
Pacing/s
lead(s)
Figure 8,1 Theprincipal components of the analog:sensingsystemare a ban@assfilter and

variablergain amplifier stage, a bl~g ei~uit to prevent amplifier overloadduring pacing
stimuli, anda window comparator (whichcan be triggeredby asignal of sufficient amplitudeof
either positiveor negativepolarity)to createa digital signalcorresponding
to detectionof cardiac
electrical activity. Avoltagereferenceis usedtoset the switchingthresholdsof the comparator.
Unfilteredendocardialsignals maybeprovidedfor telemetry,purposesby meansof an a~uxiliary
telemetryamplifier. Notshownin this diagramare the volt~g~-lihdting~omponents at the poitit
wherethe sensing/pacinglead enterSthe.pacemaker circuitry; these are used to prote~t the
pacemaker fromdamage fromelectrical overstressin the case of external defibrillation of the
pacemaker patient.
¯ Ring
Tip c
Lead [- I ’~
Case~’~"( ~_~~
Unipolar Bipolar
Figure8.2 Illustration of tmipolarandbipolarsensing.
8.1.2 Time-domaincharacteristics of the intracardia¢ electrogram

The study of~the, design, of pacemaker~sensing
circuits begins:with-a consideration.
of the characteristics of the intraeardiac electrogram. The morphologyof the
intracardiac electrogram_is considerably different from the familiar~ surface
electrocardiogram (ECG), but the nomenclature which pertains to the surface ECG
"
r PACEMAKERSENSE ~AMPLIFIERS 173
labeled the R wave). This difference in morphologyarises from the difference in

the sources which produce the intracardiac electrogram and the surface ECG;the
surface ECGis produced by the entire heart while the intracardiac electrogram
results from the spread of electrical activity throughout a small volumeof heart
tissue in close proximity to the sensing electrode (Olson, 1994a).
Furmanet al. (1977b) listed three types of signals which maybe seen in the
intracardiac electrogram: the intrinsic deflection arising from depolarization of the
muscle adjacent to the electrode; far field potentials (such as contralateral
ventricular activation, skeletal:muscle potentials, externally-generated
electromagnetic interference, and ventricular activity appearing in the atrial
electrogram); and current of injury. Far:field potentials and current of injury
constitute forms of extraneous signals and should not be considered normal
constituents of the intracardiac electrogram. Figure 8.3 is an exampleof an acute
intraventricular electrogram (recorded from a recently-implanted lead). This
waveformshows the ~rapid transition of the intrinsic deflection followed by an
elevated S-T segmentwhichis characteristic of the current of injury. Note that the
T wave in Figure 8.3 is almost masked by the S-T segment elevation. Olson
(1994a) notes that the electrogram of Figure 8.3 manifests an unusually large
current of injury whichwas probably the resdt of the use of a screw-in endocardial
~iectrode instead of a tined electrode. Fig. 8.4 is an example of a cl~onic
iittraventricular electrogram; this waveform does, not manifest S-T segment
~i~/ation and the T wave is rounded and negati_vely inflected ~ The waveformsof
Figs. 8.3 and 8.4 are right-ventricular waveformsrecorded with a unipolar lead
configuration.
/3 IIII s-r
III
-4"
II
-6" I
0 200 400 800
Time, ms
~i.gure 8.3 ACuteunipolar fight-ventricular intracardiac electrogrammanifestingcurrent of

injury. (Adaptedfrom Furman,S., Hurzeler, P., and DeCaprio,V, 1977a.~Theventricular
6~ido~ar~lialeleetrogramandpdcemaker sensing. J.Cardiovasc.Thorac.Surg.’ 73: 258-266.
CopyrightMosby YearBookInc. Usedby permission).
¯ Ne
I atlvel ,-intleC :eo I t lave
2
~ o
-2
-6
0 200 .400 600 800
Time,ms....
Figure 8.4 Chronic unipolar right-ventficular intracardiae electrogram. Note the absence of
current of injury. (Adapted from Furman, S., et al., 1977a. The ventricular endocardial
Mosby Year Book Inc. Used by permission).
,electrogram and pacemaker sensing. J, Cardiovasc. Thorac. Surg. 73: 258-266. Copyright
. ~
The electrograms of Figures 8.3 and 8.4 are of the biphasic type (the intrinsic
deflection excursions are both positive and negative with respect to the isoelectric
baseline), but considerable variation exists in polarity and morphology.Furmanet
al. (1977b) state that 58%of acute unipolar ventricular electrograms are biphasic,
while 30% are monophasic negative and 12%are monophasic positive. The same
reference gives the characteristics of the chronic ventricular electrogram as 68%
biphasic and 32% monophasic negative with no S-T segment elevation. The
chronic electrogram shows amplitudes comparable to those of the acute
electrogram but somedecrease in slew rate (the rate of maximalvoltage change in
the intrinsic deflection) was noted as the tissue-electrode interface aged. A later
study by Furman(1993) reports Similar data.
The unipolar atrial electrogram is morphologicallysimilar to the ventricular
electrogram; 89%of atrial electrograms were found to be biphasic and 11%were
monophasicnegative with little change in the intraatrial signal as the electrode
matured (Furmanet al., 1977b). Furman(1993) states that 14%of acute intraatrial
electrograms showcurrent of injury. An exampleof the atrial electrogram is shown
in Figure 8.5.
The studies of Furmanet al. (1977a, 1977b) found wide variations in the
characteristics of the intracardiac electrogram. The amplitudes of the acute
intraventricular electrograms ranged from 2.0 mVto 36.4 mVwith a mean of
12.4 mV. Chronic intraventricular el~dtr0grams ranged from 1.2 mVto 26 mV
with a meanof 10.5 inV. Meanslew rates for intraventricular electrograms were
1;5 mVlms,for acute:,electrograms and 0.9 mV/ms:for chronic electrograms;
Amplitudes: of intraatrial elec~rograms were typically smaller than th6se of the
intr~ventricular electrogram (a meanvalue of 4.8i mVwasl,reportea). ¯
PACEMAKER SENSE AMPLIFIERS 175
O 0 ~ ""-’~ ~
Ventrl:ular( ~pola~
~zatioi~
~ 0 200 400 600 800

~T Time, me
s~er than~that of theventricular electrograms of Figures 8:2 and 8.3. The crosstalk from the
far-field = ventricular potential is also apparent. (Adapted from Furman, S., Hurzeler, P., and
DeCaprio, V. 1977b. Cardiac pacing and pacemakers HI. Sensing the cardiac electrogrmn. Am.
Heart J. 93:794-801. Copyright MosbyYear Book Inc. Used by permission).
Myers,et al. (1978) studied of the effects of load reSiStance ,(simulating

input impedanceof a pacemakeramplifier) and electrode size on intraventricular
u~ipolar electrograms in 30 human subjects involving both pulse generator
replacement and new pacemaker implantation. Their result~ ~lemonstrated a
posi~y¢ correlation betw~n R-wave amplitude ,and electrode area which bec~e
more pronounced as the load resistance Was ’decreased. MeanR:w=tve amplitude
with large (>20 ram2) electrodes was 17.8 mVfor a 100 k~ 10adresistance,
decreasing to 14.8 mVfor small (8 ram2 + 10%)electrodes. The corresponding
figures for a load resistance of 10 k~Qwere 15mVand 10.6 inV.:Slew rates in the
range of 2.03 mV/ms(with a load resistance oflO0 kf4 and large electrodes)
1.29 mV/ms(with a load resistance of 10 ,k~ and s~ electrodes) were reported.
Kleinert et al, (1979) studied umpolar intraventricuiar and intraatrial
electrograms. They reported that intraventricular R waves ranged fro m 3 mVto
24 mVwith slew rates from 1 mV/msto 6 mV/ms.Most of the data presented in
this study were obtained from patients.receiving newpacemakers;this, is reflected
in the ~ oi~servation that most of the intraventricula~ electrog~ams showed S’T
se~ent elevation. The few chronic cases incorporated in ~s,,,study showed
,negatively-inflated T waves with rounded morphologies and amplitudes of 3 inV.
Int~aatrial P waves ranged from 1.2 mVto 11 n~Vwi~h slew rate~ from 0.3 mV/ms
to 3 mV/ms;intraatrial pickup of ventricular QRScomplexes ranged from 0.2 mV
to.3 ~V with slew rates of a~proximately 0.05 mV/ms.Ventricui~r T waves wire
ess~e~ally undetectable in ~e intraatr[al electr0gram. Kleinert et al. reported
studying 15, ventricular and 16 atrial electrodes, air’tough one atrial electroiJe .Was
exclude~ifrom the study due to inconsistent results attribeted to electrode flotation;
Parsonnet et al, (1980) reported results of studies of intraatrial unipolar
. electrograms utilizing various load resistances (100 k~, 20 k.Q, 10 k.Q, and 2 k~)
with electrodes of fLxed area (11 ram2). The P waves were mostly biphasic (similar
to Figure 8.5); an unusually-long duration P wave was recorded from a patient
manifesting complete atrial-ventricular dissociation. The Pwavesrecorded in this
study ranged from a mean of 4.92 mV(representing 20 cases spanning a range
from 3.1 mVto 8.1 mV)with a terminating resistance Of 100 k.Q to a meanof
3.3 mV(representing 5 cases spanning a range from 1.8 mVto 4.9 mV)with
terminating resistance of 2 k.Q. The meanslew rates were observed to fall with
decreasing terminating resistance (from 0.915 mV/msfor a terminating resistance
of 100 k.Q to 0.63 mV/msfor a load resistance of 2 k.Q).
Irnich (1985) presented a modelfor the genesis of the intracardiac electrogram
in which the spread of depolarization in the myocardiumis viewed as the uniform
linear motion along the myocardial wall of a pair of orthogonal electric dipoles.
The longitudinal dipole is oriented parallel to the myocardial wall while the
transverse dipole is normal to the myocardial wall. The total potential at any
intracardiac observation point is the superposition of the potentials due to each
individual dipole. The unipolar intracardiac electrogram is represented as the time-
varying potential recorded at an intracardiac observation point relative to a
reference (presumedto beat infinite distance) as the dipole pair movesalong the
myocardial wall. The bipolar electrogram is represented as the difference between
the time-varying potential at two intr~icardiac observation points. This simple
model successfully explains the clinical observation that some intracardiac
electrograms exhibit .monophasic morphology while others exhibit biphasic
morphology;the motion of the longitudinal dipole past the observation point will
result in a biphasic morphology,whereas the motion of the transverse dipole will
result in a monophasic morphology. The observed morphology depends upon
which dipole is predominant. The model is somewhatless successful in predicting
signal amplitude as a function of electrode area; the modelpredicts a reduction in
signal with increasing electrode area, whereas Myers et ai. (1978) found the
converse. Experimental results cited in this study found 60% of 133 acute
intraventrieular electrograms were~biphasic while 30% of 20 chronic
intraventricular ~Iectrogra~ns were biphasic. MonophasiC positive intra~;entricular
morphologieswere not~xt only in case~ in which myocardial injury was present. All
acute intraatrial electrograms(7 cases) were biphasie.
Someof the studies previously cited also examined bipolar electrograms.
Furman et al. (1977b) compared the tip unipolar signals and bipolar signals
obtained simultaneously from the same intraventricular lead and found little
difference in either meanintrinsic deflection amplitude or slew rate. This study
found that 51%of the bipolar electrogram intrinsic deflections were smaller than
those of the simultaneous unipolar electrograms; the bipolar electrogram
amplitudes exceeded their simultaneous unipolar amplitudes i~ 43%of the cases.
Unipolar and bipolar amplitudes were found to be equivalent’ in the remainder of
the cases. It was reported that 2%of the cases manifested bipolar electrograms too
small to be sensed while the simultaneous unipolar electrogram was of adequate
amplitude for sensing. This finding appears to confirm the theoretical possibility
that the spreading myocardial depolarization could produce similar potentials at
each electrode of .a bipolar .electrode pair, .resulting in little or no po[ential
difference. Irnich (1985), however, claimed to have never encountered inadequate
bipolar sensing in Clinical practice; this agrees with the experience of Det~viler
(1 ~94). ’Parsonnet t al. ( 19~0)presented bipolar intraatrial .d ecti:ogram data fr
two cases with load resistances of 100 k.Q and 20 k~. The amplitudes were 4.4 mV
and 9.1 mVfora load resistance of’l~ k~; the figures for a terminating resistance
PACEMAKERSENSE AMPLIFIERS 177
of 20 1~ were 4.3 mVand 6.2 mV. Measured slew rates were 0.92 mV/msand
1.9 mV/ms for a terminating resistance of 100 kf~ and 0.82 mV/ms and
1.31 mV/msfor 20 1~. The principal benefit of bipolar sensing was the reduction
in the effect of far-field signal sources; Parsonnet et al. (1980) noted that
ventdcular crosstalk in the intraatrial electrogram was completely attenuated by
bipolar sensing without concomitantsacrifice in atrial signal. Furmanet al. (1977b)
reported that canine studies had shown’thatthe atrial bipolar endocardial electrodes
reduced ventricular potentials sensed in the atrium by 80%relative to the
corresponding simultaneous unipolar electrogram.
The results cited in the preceding paragraphs were obtained with endocardial
electrodes. Furmanet al. (1977b) reported observations of chronic right- and left-
ventricular epicardial electrograms; the meanleft-ventricular amplitude in 9 cases
was 18.0 mVwith a meanslew rate of 1.85 mV/ms,while the corresponding right-
ventricular results in 14 cases were 11.24 mVand 1.09 mV/ms.
Wesee from the studies cited above that intracardiac e!ectrograms exhibit
wide variation in amplitude, slew rate, and morphology;successful sensing over
such a wide range of signal characteristics represents a significant design
challenge. The desirability of pacemaker.devices whosesensing functions maybe
programmed in situ (to customize the pacemakerto the patient) is apparent.
8.1.3 Frequency-domaincharacteristics of intracardiac electrograms
Irnich (1984, 1985) indicated that widely-reported data concerning the spectral
.c09tent of signals encounteredby pacemakerswere erroneous..~Th,e figures cited by
Irnic’h indicate that T waves contain energy at frequencies beloW 10 HZ while
R waves contain components eXtending from 20 Hz to 45;Hz; the frequency
content of P waves extends from 50 Hz to 90 Hz, while that of electromyographic
signals extends from 80Hzto 1 kHz. Schaldach (1992) appears-to confirm these
figures, citing design frequencies of maximalresponse of 70 Hz fo~’atdal sensing
and 40 Hz for ventricular sensiag with asymmetric 10w- and high-frequency
responses (four poles of high-pass faltering and two poles of low-pass filtering,
providing a sharp rolloff at low frequencies to reject repolarization potentials).
Other studies, however, confirm lrnich’s claim that these data are incorrect.
Kleinert et al. (1979) analyzed the spectral energy density of intracardiac signals
and found maximaof approximately 30 Hz for the intraatrial sigaal and 20 Hz for
the intraventricular signal. The frequency of maximalT wave energy density was
below 3 Hz. The maximal energy density of the P wave was less than the maximal
energy density of the R wave by a factor of approximately 10, This study
concludedthat ventricular and atrial spectra are sufficiently similar that sensing
circuits of similar frequency response maybe used for both, a finding confirmed by
Olson,(1994a), Parsonnet et al. (1980) noted that the frequencies of P wavespectral
maximawere inversely related to pacemakeramplifier input resistance (rising from
approximately 25 Hz at a resistance of 100 k~ to 30 Hz with a resistance of
20 kf~). Ohmet al. (1977) concluded that the spectra of myopotential signals
endocardial signals have a significant degree of overlap.
The Fourier transform of the chronic ventricular electrogram of Figure 8.4 is
shown in..~Figure 8.6. The most prominent spectral peak is associated with
ventricular repoladzation (T wave); the next-larger spectral peak is associated with
ventricular depolarization (R wave).
wave
0 20 40 60 80 100
Freq., Hz
Figure8.6 Fouriertransformof the unipolar chronicventricular intracardiac electrogramof

Figure 8.3 as computedby PSpice 5.2 (MicroSimCorp., Irvine, CA). Thespectral peaks
associatedwith the T waveandR waveare readily apparent.
Figure 8.6 gives someidea of the requisite frequency response characteristics

of pacemakersensing circuits; in particdar, the necessity of a steep low-frequency
rolloff to avoid T-wavesensing is apparent.
8.1.4 Test signals
Ex-vivo specification and measurementof pacemaker sensing-circuit sensitivity

cannot be discussed apart from the nature of the test signal. The problem of
generation of a test signal with physiological fidelity is not easily solved; wehave
already seen that wide variations in amplitude and morphology exist among
individuals. Among those factors whichcontribute to the shape of the intracardiac
electrogram are lead’placement within the heart, lead type, and the ,health of the
heart tissue; amplitudes vary from patient to patient (as wehave already seen) and,
withtime and health, within a given patient (Anonymous,1975).
Various test signals have been used or proposed; amongthose which have
been used are rectangular pulses, half cycles of a sine wave,and the haversine (sine
squared) waveform. Irnich (1985) proposed an alternative test .signal which
consists of an asymmetrical negative-going triangle wave, but this waveformhas
not earned acceptance. The sine squared waveform appears to offer the best
compromisebetween physiological fidelity and ease of generation.
8.1.5 Other requirements
Pacemakersense amplifiers must be light and compact to fit within the massand
size constraints imposed by the pacemaker package. They must operate correctly
with battery voltages as low as 1.5 V and must be tolerant of battery-voltage drop
as the battery ages; and they must consumeas little eloctdcal energy as possible.
The ~wide range of possible intracardiac signals ,which the pacemaker may
encounter highlights the desirability of being able tochangethe detection threshold
(sensitivity) through external programming.
8.2 CONTINUOUS TIME CIRCUITS
8.2.1: Discrete component

circuit designs
Early pacemakersense-amplifier designs were realized with discrete, components

utilizing printed circuit board or hybrid circuit techniques; spaeeand power-
consumption constraints imposed limits on the complexity of the circuits. This
section is intended to provide someinsight into the creativity with which design
engine¢~ have approached the unique problems of pacemaker sense-amplifier
design while working within the constraints of availabletechnology.
Figure 8.7 shows a ventricular sense amplifier described by Greatbatch (19~2,
1~94). JFETQ1, bipolar transistors Q2 and Q3, and associated passive components
f6ma~,,,,a de,coupled amplifier whoseoutput voltage is developedat ,the emitter of
Q3. Let the output voltage be designated V3; the small-signal gain of the amplifier
is:
~--i ~-- T($) -- gra(1 + hfe2Xl+ hfe3)R6($- zt )
+ + p,)($-p2) (8.1a)
WhereT(s)is the transfer function of the twin-T notch filter comprised of R1-R3
aiad~(1,7-C3; gin is the transconductance of JFETQi; hie2iS the common-emitter
input impedanceof Q2; hfe2and hfe3 are the small-signal current gains of Q2 and
Q3, respectively; and the zero and two poles are given by:
e c,
~is-c~cuit ~splays design ingenui~ w~ch desexes ad~fion~ co~enU ~e use

of P~ bipol~ ~sistor Q2 in conjunction wi~ ~T Qt smb~zes ~e de g~ of
¯ e circuit at approximately -R~R5 reg~dless of unit-to-unit v~afions,in the
~ansconductance of Q1. The location of ~e. zero at s =-11R5C4is fix~ by
component v~ues, wh~e ~e l~ations of ~e ~o poles ~e subj~t to some. u~t-to-
u~t v~ability due to ~e dependence upon p~eters of bipol~ ~sistors Q2
~d Q3,
~e ~ansfer ~nction of ~e tw~-T notch fdter, T(s), can ~ ~deVeloped ~er
S~ghffo~d (al~ough somewhat tedious) circuit ~ysis w~ch Will riot
included her6. ~t us ch~se R1 and R2 to be equ~ ~d set ~e~~ v~ue to R ; let us
~so fix the v~ue of C2 to be C. ~t us choose R3 = R/2 ~d C1 = C3 = C/2, If we
180 DESIGN OF CARDIAC PACE~KERS
do so, we find that the twinoT notch filter has equal numbersof poles and zeros
with a pair of zeros at s = .+_jl2RC.The twin-Tcircuit exhibits unity gain for both de
and high frequencies while having a notch at a frequency of II4~RC. With the
values used by Greatbatch (R = 3001~ and-C = 0.02 ILtF), the notch frequency
approximately53 Hz. Theinclusion of the notch filter is particularly noteworthyin
that it demonstratesthat the possibility of interference from power-line sources was
being considered in pacemakeramplifier design as early as the late 1960s.
Figure8.7 Ventricularsense amplifier describedby Greatbatch(1972). Noteparticularly the

discrete-cir¢~uit implementation andthe twin-Tnotchfilter for 60-Hzrejection. Components in
this figure withoutcomponent designationscomprisethe outputstage whichis not part of the
linearamplifier. Thelinearamplifieroutputvoltageappears
at the emitterof Q~andis designated
V3in
the text andin this figure:TheoutputVoproducesan outputpulsewitheachventriculardepolarization;
this pulseinhibitsthe stimulus
pulsegenerator.
Figure 8.8 shows the results of SPICEanalysis of the circuit of Figure 8.7
using generic JFET and bipolar transistors models for Q I-Q3. The predicted
maximal gain of 36.5 dB occurs at approximately 10 Hz. Note the low-frequency
gain is approximately2.8 (9 dB), whichis close to the ratio of R6to R5. Theeffects
of the zero and the poles of the active amplifier circuit are evident, as is the notch
inserted by the twin-T network.
The linear amplifier of Figure 8.7 supplies its output voltage to a passive RC
differentiator connected to the base of a. 2N2450transistor normally biased in
cutoff. A ventricular depolarization wouldresult ina biphasic pulse at the base of
this output transistor; the negative-going portion of this pulse would turn on the
output transistor and provide a positive~going pulse at output Vo. This pulse would
inhibit the otherwise free-running oscillator whichproducesventricular-stimulation
pulses.
Schaldach and Furman (1975) give other examples of pacemaker-amplifier
design techniques in the early 1970s with diagrams of amplifier circuits from
instruments produced by Medtronic Inc., American.Optical Company,and Cordis
CorPoration, all of which utilized discrete circuit techniques like the circuit of
Figure 8.7.
20
-2 -1 0 1 2 3 4 5
~og(f),
Figure8.8 Frequency
responseof the ventricular-sensingamplifierof Figure8.7 as calculated
by SPICEusing generic modelsfor QI-Q3.
The circuit of Figure 8.7 operates with fixed gain and sensing threshold. Later
developmentsincorporate circuit variations which permit adjnsmaentof sensitivity
by meansof variable-gain amplifiers or adjustable-threshold voltage comparators.
DeCote(1988) provides an example of the latter approach. A fixed-gain amplifier
provides an amplified and f’dtered cardiac signal to a pair of voltage comparators,
the ratio _of whosethreshold voltages is determinedby a resistive voltage divider. A
DAre’operating under microprocessor control sets the voltage across the divider
si~e~~the rhore sensitive comparatoris-triggeredby car~ae activity while the
less sensitive comparatoris not. A significant change in cardiac-signal amplitude
will,,ca~s e both comparators to trigger or neither to trigger, in which case the
~p~ocessor can take the appropriate corrective acti6n to fmda new s~ensing
~~:~igiire 8!9 showsa published circuit of a less~elaborate meansof achfg~,ing the

s.~a~e ~nd (optimum sensing)~ by means of a gain:control amplifier. MOSFET
s~itches s i~’and $2 comm~tate at a~rate whicli" is ’deter~ned by ~xternal
~i¢~0proces~0rcontrol; depei~dinguponthe.duty cycle Of the switches tii6 average
g~tte:to-source Voltage may be varied betweeh "0: and-(Vdd-Ve)? This rmiiS
control of the channel resistance of Q 1 and thus the voltage gain of th~~ entire
circuit. A gain range of 30:1 is claimedfor the circuit of Figure 8.9. This circuit
was utilized as part of a~cardioverter/paCer system whichCoulddistinguish the low-
level ventricular electrical activity characteristic of ventricalar fibrillation fi:om the
absenceof activity characteristic of asystole or the slow activity of bradycardia and
thus,to apply the appropriate electrical therapy (cardioversion or pacing).
: The space, weight, and power restrictions of cardiaccpacemakers place a
p~miumon ci~uit performance with a minimal number of components. ~Fignre
8~ 10 is~ a notable exampleof simplicity and economyofdesign.. It, is .~also notable
for its use of operational transconductance amplifiers (OTAs),devices: that differ
from traditional operational amplifiers in that they act as voltage-controlled current
sources instead of voltage-controlled voltage sources. The ~ansconductance(ratio

of output current to differential-input voltage) of the LM3080 OTAsused in this
circuit maybe controlled by adjusting the amplifier bias current (/b in Figure 8.10).
Vd(
Figure8.9 Gain-controlamplifier (Menken;1989). SwitchesS1 and S2arecontrolled by

digital microcontroller;the :duty cycleof the switchesdeterminesthe gate-to-sourcevoltageof
JFETQ1, whichis utilized as a voltage-controlled resistance.Again rangeof 30:1isclaimedfor
this circuit.
JFETQ1and sturce resistor R9 form aconstant current source which~ drives

the voltage-divider string consisting of R2; R4, and the parallel combinationof R5,
R7, andR8. The current source thus establishes the quiescent operating point of U1
(the Volt~ige at the junction of R2 and R4) and two voltage levelg used
comparator thresholds, oneabove and on~ below ~quiescent point of U1. The
curr~nt delivered by al splits three waysat the no~it’~bmmont~ R5~, R7, andR8
aiad thus supplies equal bias currents to each OTA.UI is ~ised as, a linear amplifier
with transfer function:
v°= SCl(1-grnR6)’~ --- :~C1R6~ forgmR6 andgmR1 >>1 (8.2)

Vi sCl(l+gmR1)+gm sqRl +1
If the conditions of Eq. (8,2) are satisfied, the OTAused for U1 gives the same
performance~asa traditional operational amplifier. OTAsU2 and U3 .are employed
as high-gain voltage comparators; they-are operated~ open:loop anti’their outputs,
used to drive .the gates d f MOS
switch ~ansistors, ~are operating into virtually open
circuits. Threshold ~voltages for these eomparators are derived from the output
current Of Q 1 flowing through R2 and R4. Thus a commoncurrent source sets the
operating point of U1, establishes the comparator thresholds, and provides bias
currents to the three OTAdevices.
+V
U2
R4 ,R5 I Ib
C2
R8
F~ 8.10 Amp!ifier/comparatorcombination(Renirie et al., 1976). This circuit is

pa~cularlynoteworthyexample0.f Simplicityandeconomy of design~Integrated.c.’,~.c~uitsU.I~U3
~re LM3080 Operational ~sconductanceamplifiers (OTAs).Outputsof U2ana U3,are ShOWn
as voltagesinsteadof currei~tssince the, loadresistancesdriVen.bythese devicesare extremely
high, causingthemto operatein a voltage-outputsaturationregimeinstead of a current-output
linear ~egime.
8,2;2 Monofithi¢circuit techniques
Pacemakertechnology has been driven toward monolithic-circuit implementations

to satisfy demands:for ittcreasiiig flexibility and functionality ’within the cons~ts
of ~tcd space and battery power. The integration of sense-amplifier circuits on
the, Samesilicon die as the digital circuits is a natural consequenceof this technical
evolution. Someof the’ techniques used in ,monolithic fabrication of cardiac-
pacemakeranalog circuits and the limitations of those techniques will be discussed
in the section to follow.
8.2.3 CMOS
operational amplifiers
Micropower operation of MOSFETs is achievable by exploiting the subthreshold

regime. Unlike the saturation region in whichdrain current is ,a;,function of the
square of the gate-to-source voltage, subthreshold or wcak-inve.rsion operation
demonstratesan exponential relationship between drain currem and gate-to-source
voltage (Stotts, 1989):
Id=/doW
tu_ v_~..
T eq~,~_,T//nk (8.3)
L
in which I d is the drain current, /do is a process-dependent leakage current, W/L

is the MOSFET gate-width-to-channel-length ratio, VG is the gate voltage, VT is
the MOSFET threshold voltage, n is the weak-inversion slope factor (always 1 or
greater), k is Boltzmann’s constant, q is the charge of an electron, and T is
temperature in K. Equation (8.3) incorporates simplifications :which maybe made
whenthe source-substrate voltage is zero and the drain-to-source voltage is greater
than 3kT/q (about 81 mVat 310 K).
Wemay compute the transconductance of the MOSFET by differentiating Id
with respect to Va:
gm-- ~9-~Gold = nk---fq /do ~eq(Vo-VT)lnkT

= n~ Id (8.4)
Stone et al. (1984) report room-temperature(300 K) values~of nkT/q of 54 mVfor

n-channel and 41 mVforp-channel devices that they fabricated; since kT/q has a
value of 26 mVat 300 K, we find that n has a value of 1.6 to 2.0. This is also a
process-related parameter, but we maytake it to be indicative of the range of
values which n may take. An n-channel device like those cited above would, by
Eq. (8.4), exhibit a transconductanee of 1.85 flS at a drain current of 100 nA.
Eq. (8.4) demonstrates that the transconductance of the MOSFETin weak
inversion is directly proportional to its drain current. The designer of micropower
MOSlinear circuits faces a tradeoff between transconductance and power
consumption; higher transconductance comes at the expense of higher drain
current. Operation of the MOSFET in weak inve~rsi0n i s ~alogous to the bipolar
transistor in which small,signal transconductance. is directly proportional to
collector current. Comparedto bipolar transistors, MOSFETs .present both
advantagesand disadvantages for linear-circuit applications. The bipolar transistor
has greater transconductance and lower 1If flicker noise (which is the dominant
noise component at frequencies of interest in biomedical applications); the
MOSFET has advantages for monolithic implementatipn since monolithic MOS
circuits do not require the isolation diffusions betweendevices necessary in bipolar
monolithic circuits. Since CMOS is the technology of choice for the micropower
digital circuits of the pacemaker, the use of CMOS in the linear portions of the
pacemakeris natural.
Successful application of MOSFETs in low-voltage applications requires
careful control of threshold ~voltage. Metal-gate technology may be used to
manufacture n-channel devices with low threshold voltages, but aluminum-gate p-
channel devices will exhibit threshold voltages of -2 V or less (Swanson and
Meindl, 1972), requiring silicon-gate technology for low-threshold p-channel
devices. Control of threshold voltage may be effected by ion implantation
(Streetman, 1980).
8.2.4 Operational amplifiers
Figure 8.11 shows a simple two-stage CMOS operational amplifier 0f the type
analyzed at length by Gray and Meyer(1982).
Vdd
Fi~i~"8;11Simpletwo-stageCMOS operational amplifier similar to’ circuits described by

Stonebt al~ (1984)and Grayand Meyer(1982). Thecurrent sourcesmaybe madewith.a simple
NMOScurrent mirrorcircuit.
~..~.~, Figure 8.12 shows a small-signal model thereof, Analysis of the model of
Figure 8.12 yields the ,following transfer function:
(8.5)
gmi (gm2- sC1 ).

s 2 (ColCI+ Col Co2+ Co2C1) + s(gol (C! + Co2) + go2 + Col) + gm2C1 ) + golgo2
wheregml is the transconductance of the first stage (differential pair Q1and Q2);
gin2 is the transconductan~e of the output stage (Q5); gol and Col are the output
condiictance.and capacitance, ,respectively, of thefirst stage; go2 and Co2ar e the
Output condfictance and capacttance (including 10ad conductance and capacit~ce)
ofth~ ~ec0nd ~tage; and ~t is the con~pensating (or pole-splitting) capaci~ce
Figurf 8..1!. Equation (8.5) shows the existence of a rightrhalf-plane zero, which
may pose a problem of excess phase shift for micropowerMOScircuits operating
at low .transconductances. In a similar two-stage bipolar amplifier, the higher
transconductance of the second stage wouldmovethe zero further from the s-plane
origin and thus diminish its effect. Gray and Meyer(1982) show that the voltage
gain of a common-source MOStransistor under open-circuit condi’tions is inversely
related to drain ~urrent until the drain ~urrent is redaged to.the point at whichth~
weak-inversion regime b~gins; the voltage gain then remains relatively constant at
a value .similar to that attainable.with a bipolar transistor. This wouldap~ar t0 b9
a~omalous, given that we have already se~n that the transconductance of an MOS
device~n wd~inversion is directly proportional to ~ain current (see Eq. (8.4)).
C1
gml(Vi) go1 =t go2
gm2(Va) CoZ
Figure8.12 Small-signal modelof two-stageMOS amplifier. Thedifferential input of the

circuit in Figure8.11 maybe convertedto the single-endedconfigurationaboveby connecting
the invertinginputto signal(ac) ground.
The open-circuit voltage gain of a common-source MOStransistor amplifier is

gin/go, where gm is the FET transconductance and go is the FET output shunt
conductance (def’med as 691d/JVds, where I d is the drain current and Vds is the
drain-to-source voltage). The decrease in transconductance with decreasing drain
current in weak inversion is compensated by a decrease in output conductance,
causing the open-circuit voltage gain in weakinversion to be relatively constant. If
a fixed external load resistance RLwere applied to the output of the FET, however,
the available voltage gain wouldbe gmRLif RL<< 1/go; in the case of such a fixed
external load resistance, we wouldexpect tosee the available voltage gain decrease
with decreasing dc .drain current. Even though the simple two-stage CMOS
amplifier is seen to be quite sensitive to loading of its output (both capacitive and
resistive), it is nevertheless useful in monolithic pacemakerdesign in which its
output drives only internal (high-impedance) circuit nodes; ’~ does notneed th e
output-drive capacity of a general-purpose operational amplifier.
Figure 8.13 shows a design of a MOSFET-based OTA based upon a
differential pair (Q3 and Q4) and simple current-mirror circuits; this amplifier
similar to circuits described by Stotts (1989) and Laker and Sansen (1994).
topology resembles that of the amplifier of Figure 8.11 from which Figure 8.13
differs in that Figure 8.13 lacks both the common-sourceoutput stage and the
compensationcapacitor of Figure 8.11.
8.2.5 Monolithic low-frequency filters
Monolithicfilters with critical frequencies in the range of interest for biomedical

applications are difficult to fabricate. Active RCfilters require prex~ise control of
their constituent resistances and capacitances if the design frequency,response
characteristics are to be realized, and such precise control requires that the
resistances and capacitances be implementedby discrete componentsinstead of by
monolithic fabrication techniques. The frequencies of interest in cardiac
pacemakingare well below100 Hz, requiring that active filters be madewith fairly
long time constants (for example, a single-pole RClow-pass filter witha comer
frequency of 70 Hz requires a time constant of 2.27 ms). Stotts (1989) e~timates
the largest practicable value of monolithic capacitance at 20 pF per pole; direct
realization of this time constant with such a capacitor wouldrequire a resistance of
113 IVLO,which wouldbe impracticable in monolithic fabrication.
One technique for achieving long time constants while using small values of
capacitance is capacitance multiplication, illustrated inFigure 8.14: This circuit
differs from traditional operational-amplifier circuits in that the output voltage of
the operational amplifier is not used directly but is utilized to cause specific
terminal characteristics (in this case, a virtual capacitor). Therelationship of input

voltage~to:input current of the capacitance-multiplier is given by:
Vi = 1 = 1 (8.6)
Vdd
Q6
Vss~ Vss
Fibre 8;13 CMOS ~operational transconductaneeamplifier. ’Q3 and Q4form, adifferential

NMOSpairTthedrain~et~rrent
of Q3drivesPMOS
.eu_~e.nt
mi.rr.orQ5-6.,~. e~ou~
tp~u.teur~e._.nt..i.s the
differencebetween the drain currentsof Q4andQ5.Ibis .the.bias-.currentinput. ~d~ana~z iorm
an NMOS current mirrorcircuit.
R2
C(I+RI/R2)
tobea
Thu~the input of the network appears to be a capacitor multipliSd by a factor

of (1 +R 1,/R2): Stotts (1989) reports that successful monolithic continuous-time
filter circuits with comer frequencies in tl’/e range of 10 Hzto 500 Hzhave been
built utilizing capacitance multiplication in conjunction with the technique of

transconductancereduction. These monolithic falter circuits are particularly useful
as anti-aliasing filters for discrete-time circuits which are the subject of the
following section.
8.3 DISCRETE-TIME (SWITCHED-CAPACITOR) CIRCUITS
Switched-capacitor networks offer an alternative to R C active and passive

networks and have significant advantages for implanted medical device
applications:
1. A switched-capacitor network has crfical frequencies which are functions of

the ratios of capacitors, not the absolute values of capacitors and resistors.
2. A switched-capacitor filter’s critical frequencies are also determined by an
external clock; a sufficiently low clock frequency can be used with a switched-
capacitor filter to program frequency-response characteristics suitable for
processing signals of biomedical origin without having to incorporate large values
of resistance or capacitance.
3. Monolithic switched-capacitor technology is compatible with the monolithic
fabrication techniques used to manufactureCMOS digital circuits.
These advantages are balanced by disadvantages of the switched-capacitor

technique relative to continuous-time techniques:
1. Switched-capacitor filters are discrete-time systems and are thus subject to

aliasing unless steps are taken to band,limit the signals reachingthe filter.
2. Switched-capacitor filters are subject to clock feedthrough, which manifests
itsdf as a source of both noise and of dc offset. The dynamicrange (definexl as the
range of output amplitudes bounded by saturation at one extreme and the noise
floor on the other) of switehed~capacitor networks is less than that of their
continuous-time counterparts.
The advantages of switched-capacitor techniques outweigh the disadvantages;

in particular, the ~bility to switched-capacitor tecl~no|0gy to synthesize monolithic
low-frequencyfilters in a technologycompatiblewith digital-circuit fabrication is
of great importance.
8.3.1 Switched-capacitor network fundamentals
Refer to Figure 8.15. A capacitorof capacitance C is connected to a matrix of four

switches activated by a two-phase clock whosephases are ¢1 and ¢2. Note that the
two clock signals are nonoverlapping(i.e., ¢1 and ¢2 are never both low or high at
the same time). It is not important whether these switches are active-high (as will
be assumedin the illustrations to follow) or active-low; what is important is that
switches controlled by ~1 and those controlled by ¢2 never be simu! ~tan~eouslyON.
If it is assumedthat Vi and Vomayvary at rates muchless than the frequencyof the
clock signals, capacitor C charges to (Vi- Vo ) whenclock ¢2 is active and
discharged whenclock phase ¢~1 is active. Since both clock phaseswill be,active
once during the course of one clock cycle, the capacitor thus passes a charge of
C (Vi - Vo ) between the input and output voltages with each clock cycle. If the
clock frequency is f, the charge transferred per second isfC(Vi - Vo). The
switched capacitor appears tobe an effective resistance whosevalue is given by:
Reff=(V i-Vo)= (V i-Vo) =1 (8.7)

I fC(Vi-V o) fC
The effective resistanceof the switched capacitor is thus inversely proportional m

both the capacitance and the switch frequency. Small capacitors suitable for
monolithic fabrication can manifest very large values of effective resistance; for
example a 2-pF capacitor switched at 10 kHzwill have an effective resistance of
50 M~.
~)2 C ~2
~2
Figure ~8.I5 Switched--capacitoranalog of a resistor. Switebeslabeled "¢1" are ONwhen

Controllingwaveform ¢1 is high and OFFwhen¢1 is low; switcheslabeled"¢2"are likewise ON
whenwaveform 02 is high andOFFwhen¢2 is low. Notethat the two phasesof the clock are
non0v~.~rlapping~ preventingthe twosets of switchesfrombeingONat’the same~time.Charge:is
transfet’redbetweetiVi 9nd~Vo at arate of fC(Vi-Vo)C/s, makingthe switchedfapacitor appear
to l~e an effeetiveresisUinee
equalto 1/fC.
Switdhed-capacitor integrators
The effective resistance of a switched capacitor maybe combinedwith operational

~tmplifiers and nonswitchedcapacitors to makeintegrators which are core building
l~ks of filter synthesis. Figure 8.16 shows an implemer~tation of an integrator
with a differential input. Switchedcapacitor Ci is charged to (V1 - V2) whenclock
phase ¢1 is active; whenclock phase ¢2 is active, Ci is connected betweenphysical
ground.and ’the inverting iinpur of the operational amplifier. ’Presumingthat the op
amphas-high’open-loop gain and very high input ~impedances, all of (he. charge
stored on Ci during ¢1 will be transferred tothe nonswitched feedback capacitorCf
during ¢2.~ Assumethat the point at which one clock cycle is presumedtoend and
~.~. 9~er t0 begin is the point at which¢2’s active state :is ending. At the time that
clock cycle n is ending, the total charge on Cfwill be that which Wastransferred
from Ci during cycle n in addition to that which was present at the beginning of
cycle n. The charge transferred from Ci to Cfduring phase ¢2 of cycle n is that
transferred to Ci during dock phase ¢1 of that same cycle. A difference equation
maybe written to reflect the charge stored on Cf at the end of switching cycle n:
CfVo(nT)= CfVo(nT- T)+ CiAVi(~T-~) (8.8)
where AVi= V1 - V 2 and T is the sample period given by T = 1/f. The notation
AVi(nT- T/2) denotes the differential voltage AVi whichexisted across Ci at one-
half-switching period before time nT, i.e., at the time at which¢1 was active.
I ~ n T- T/2
nT-T..-..-....~I I I.,~---nT
Figure$.16 Lossiessdifferential,inputswitched-capacitorintlgrat;r. ~0te~thefimingigf~hetwo

tm~r0verlappi~ng clocksignals; cycle nTendsat ~e point at, ~vhieh;e!0ck phase,¢2!makes its
transition fromtile ONtothe OFFstate. Theillustration above,assumesthat switchesdosewhen
their controllingclocksignalsare high,althoughactive-lowswitchesare equallysuitable.
Applicationof the z-transformto Eq. (8.8) and algeb.r,,~c m, ,an~.’~pdati0n,giv~the

domaintransfer function of the circuit in Figure 8.16:
= (8.9)
To lind the. steady-state ae response of theswitched-eapacitor integrator, we

mayevaluate the transfer,function abovewith the substit~tion:~z = eJ~r: if,toT <<n:
(which is implied by the condition imposed above that Vii ~and V2 varyslowly
compared ~to. the clock frequency), we may make-the, approximation
e-j~r ~ 1 - jtoT..Thus the transfer function approximates that bfa continuous-~
lossless integrator: ’ ’ : ~ " " "
~ V I ~"’ ,-": " ~
o . (8,!,0)
,:
aV
i
~,~,., ~,.’ B.l? ~Ssy,,~ffe~nfi~input.

inte~ator(single-~ielow-p~sfdteO.
-:~"~ ~’~¢ lossless i~te~to~ i~ a ~e~usefuI building bloc~ fori~plCme~do~of

~S filter m~logies; for ex~ple~ ,two lossless ,integrators-. may ~ combined
~~One s~ng ope~fi~ ~plffier to re~ a s~fe-v~le filter from w~ch
~ be simul~usly derived high-pass, low-pass, ~d ~b~dpass ou~uts. ~e
l~ssy~integrator (single-~Ie low-p~s filter) is si~l~lya use~ buil~ng block
~r syn~esis.,~e lossless switch~-capacitor i~e~tor may ~ m~fied by ~e
~ddifioa of ~o~er switch,capacitor Cx to p~vide a leakage pa~ for ch~ge
g6~don ~e~f~baek capacit~ Cf. Ch~ge stor~ on Cxd~g clock ph~e ol
is returned to ~e op-~p suing node d~g cI~k pha~ ~2 ~ Such a way ~ to
~duce ~e ch~ge stor~ on Cf. Were ~ere no dffferenfi~ input vol~ge present
0.e., were AVi = 0 ), the pa~ provided by Cx would eventu~ly completely
~sch~ge feedback capaci~¢e Cf ~n a m~er ~ogous to ~at of a physic~
resis~ce in p~lel wi~ ~f. ’ ~: : " ~
~e ~ff~ence equadon governing ~e lossy integrator is a mo~fication of
~at gove~ng ~e lossless integrator; ~e o~y ch~ge involved ~ is ~e addidon of
Se te~ involv~g Cx: ".
The transfer function of the lossy integrator is likewiS~ similar t6’ its lossless
counterpart except for an addi~onal denominator term which shows the effect of
Cx:
V°-= Ciz’0"5 (8.12)
z-0.5
AVi " Cf(l_z-l)+Cx
Makingthe substitution z = eJ°~rgives the freqUency-domaintransfer function of

the lossy integrator:
.......... = (8.13)
, -AVi Cf(1--e -jc°T) e-
+ jc°T/2
Cx
If we again make the approximation, that coT is small, e -jt°T = 1- jcoT and
e-Jf°TI2 __. 1; the frequencyresponseof the lossy integrator is then:
(8.14)
AVi jo)TCf + x
This is the transfer function of a single-pole low-pass filter with dc gain Ci/Cx and
(radian) comer frequency CxiTCf. One of the previously,mentioned advantages of
switched-capacitor networks is. nowmadeevident; both the d~ gain and the cutoff
frequency of the lossy integrator are determined by the ratios of capacitors, not
their absolute values. This makes possible the implementation of monolithic
switched-capacitor networks with capacitors in the picofarad range which are
nevertheless usable as filters at frequbncies characteristic of cardiac electrical
activity. A switched-capacitor low-pass filter utilizing Cx = ! pF, Cf = 8 pF,
Ci = 10 pF, and a~switch frequency of 2 kHz will manifest a de gain of 10.and a
comer frequency of 40 Hz; Figure 8.18 below compares, this circuit with its
continuous-time counterpart. Note the differences in the responses of the two
networks are virtually .identical for frequencies below300 Hz,~but that they begin
to diverge as the signal frequency rises. Also note that the response of the
switched-capacitor network between signal frequencies of 1 kHz and 2 kHz is the
mirror image of the response between de and 1 kHz; this symmetry, about half the
switch frequency is characteristic of sampled-datasystems.
Gain resp )nse of Iossy ~tegrator , "
2O
~hed-oapaeitor/
10
-10¯
1000 2000 3000

Frequency, Hz
F’.~u.re8.18Comparis.on. of the gainvs. frequency

characteristicsof a switched-capacitorsingle-
polelow-passfilter ana ~ts continuous-time equivalent.Thecontinuous-time filter has a de gain
of 20 dBanda comerfrequency0f 40I-lz; the switched-capacitor circuit is clockedat 2 kHzand
utilizes the topologyof Figure8.17withCx= 1 pF, Cf= 8 pF, andCi = 10pF.
Parasitic-insensitive switched-capacitor networks
~:~ f~i,]ossless and lossy integrators shownabove are adequately described in the
pr~ing equations only if the effects of the parasitic capacitances shown in
iTi~e~ 8.19 are ignored. Leakage capacitor Cx is assumedto have an associated
p~ificcapacitance to ground designated Cpx. Floating input capacitor Ci has two
~SO~.:i~d parasitic capacitances to ground designated Cpl and Cp2. Note that Cpx
has,~e effect of increasing the value of Cx, reducing the gain of the circuit and
increasing the. corner frequency. The role of.the parasitic capacitances associated
v~ith-;fl0ating input capacitor Ci is somewhat Lmore complex. The parasitic
capacitance Cpl charges to V1 on clock phase ¢1, but this capacitor is simply
discharged during ¢2 and none of the charge stored on this parasitic.capacitor
during~.~l is transferred-to integrating capacitor Cf. The presence of this particular
parasitic capacitance is thus seen to be benign insofar as operation of the circuit is
concerned.
Cpx
(~ ~~
Cx+
Cf
Ci :
Cpl
Figure8.19 Differential-inputlossy switched-capacitor intekratorwith parasitic capacitances.

Capac,i~ance
s connectedwith dashedfines are parasitic capacitances;those connected withsolid
linesa/e explicitcapacitances.
Parasitic capacitance Cp2 iS~:charged to V2 d~g clock phase ¢1 and is discharged

by’connection~to the virtual ground at the inverting input of the Operational
amplifier during clock ,phase ¢2, transferring ~this charge to the, feedback
cap~c~,tance Cf. ’~he difference equationof the di~erential-ini~ut lossy iate~atorof
Fi~e K 19 iS given by: ....
Cf Vo(nT) = Cf o ( nT- T) +
CiVI(nT_:~).,(Ci+C#2)V2(nT_~).(Cx . ). ( x Vo nT_~: ( 8A5,

Common-mode rejection of the differential-input lossy integrator depends upon the

gain with respect to VI being equal in magnitudeand opposite in sign to the gain
with respect to V2. Eq. (8.15) shows that this balance is upset bythe presence
parasitic capacitance Cp2 (the coefficients of V l and V2 are no longer equal),
degrading common-mode rejection.
The problem of parasitic capacitances in networks such as that shown in
Figure 8.19 may be tolerable in implementations using discrete components in
which the explicit capacitances maybe manytens, hundreds, or even thousands of
picofarads while the parasitic capacitances may’be on the order of a few
picofarads. Monolithic implementations, however, use capacitances of a few
picofarads or, at most, somefew tens of picofarads; parasitic capacitances of even
0.5 pF cause: significant gain and frequency response errors. Estimates of parasitic
capacitances arising from multiple ~sources--wiring, capacitor plate-to-substrate,
junction capacitancesinthe MOSFET’sswitches--range from 10%to 20%:of the
intended value of a capacitor implementedin monolithic form.
Figure8.20Differential-input
lossyintegratorin parasitic-insensitive
topologywithimplicitparasitic
capacitances.
Notethe topologicalchangesbetween this circuit andthat of Figure8.19.
The difficulties posed by parasitic capacitances can be largely overc~omeby

use of parasitic-insensitive topologies in which parasitic Capacitances are eider
prevented from charging or, if they are permitted to charge during the switching
cycle, are discharged without pe~itting their ch~ge to be transfer, red to the
nonswitch~ifee~tback capacitance. Figure 8.20 sho~,g the differential-input lossy
integrator reconfiguredas a isarasitic-in~enaitiV6circtiit.
~’ Th6~parasidc~insensitiv~ topology of th~ circuit of Figur~ ’8.20 can be
qualitatively understood by visualizin~ khe Chai~gingand discharging of parasitic
capacitances Cpl-Cp4. Note that the topology of Figure 8.20 hag made~cx into a
floating capacitor and, as such, it nowhas tW~parasitic capacitances to ground
instead of the one shownin Figure 8.19. Parasld~C’capacitanc~Cpl is charged to V!
dutifig clock :pha,se ¢1 and to V2 during 02, cau~ngCol to appear as a floating
resistance between Vi and~ V2. The effect of Cpl ~sto lower the d~fferenaal ~nput
impedanceof the circuit, but it has no effect on the output voltage of the circuit.
PACEMAKERSENSE AMPLIFIERS. 195
p.,.~asitic capacitor Cp2is switched to physical ground dufingclock phase Ol and is

8~witehedto virtual ground during clock phase ¢2..Cp2 is therefore prevented from
~itrging or discharging, effectively removing it from the circuit. A similar
explanation attaches to parasitic capacitor Cp3. Parasitic capacitance Cp4is charged
tO, iV,0 during ¢2 but is simply ~discharged to ground during Ol. This parasitic
~ai~iCitance acts only as a load on the output of the operational amlMifier and has
no ~effect on the chargeon the nonswitchedfeedback capacitor Cf.
*-~., :.~e rearrangementof the ’circuit causes its output-to:input relationship to
dif~ei~,s0inewhatfrom’that of the original circuit. Application .of charge balance to
(i.e,,nonparasitiC) capacitors of the circuit ’in Figure 8:20 gives the
or~ in terms of the z-transform,
(8.17)
The sequential (instead of simultaneous) sampling of V1 and V2 cause this to not

a true differential-input,circuit, but it approximatesa true differential-input circuit
if oJT is small. Figure 8.21 shows the degradation of common-mode rejection ratio
with respect to signal :frequency as computedfrom Eq. (8.~7) for a parasitic-
insensitive differential-input lossy integrator with Cx = 1 pF, Cf~ 8 pF, Ci = 10 pF,
and a clock frequency of 2 kHz. :~
6O
CMRRof differential.’i~put parm;itic-insen-
ve differen i~l integralor
¸5O
4O
30"¸
~oglf),
~t!z
wi~ Cx
2 kHz.Notethat the abscissais logarithmic
insteadof linear as wasthe casein Figure8.1
Parasitic capacitances ~Cp2and Cp3 of Hgure 8.20 were effectively removed

from the circuit by being commutatedbetween physical ground and the inverting
input of the operational amplifier which is presumedto be a virtual ground. The
effective removalof these parasitic capacitances will not take place, however, if
any signal voltage is present at the noninverting input of.the operational amplifier,
The operational amplifier must,have sufficient open-loop gain that its inverting
input behavesas a virtual groundi~ the circuit of Figure 8.20 is to be insensitive to
parasitic capacitances. Switched-capacitor circuits als0~ cannot, be used to
synthesize single-amplifier second-order networks (such as ~Sallen and Key VCVS
topologies) without sacrificing insensitivity to parasitic capacitances. Higher-order
parasitic-insensitive filters may be realized by cascading suitable first-order
sections or by using a parasitic-insensitive biquad topology.
Parasitic.insensitive filter
bandpass
Figure 8.22 shows a typical switched-capacitor biquad circuit consisting of a

lossless inverting integrator (the upper branchof the circuit) and a lossy integrator
which is noninverting with respect to the upper branch and inverting with respect
to the input voltage Vi. This circuit hasa single-ended input and has a z-domain
transfer function given by:
Figure 8.22 Switched-capacitorbiquadbandpassfilter. Thelower branch of the circuit,

consistingof U1,CI-C3,andassociatedswitches,is a parasitic-insensitivelossy integrator;the
upperbranchis a parasitic-insensitivelossle~s i~tegrator. Notethat C3andC1share a common
circuit nodeand a common pair of switchesin this topologysince both capacitors havea
te~al conn,to grounddufing,~t aiidt0 the inverting i~put ~f~the operational amp~iiier
during 02. -Comparethis with the ~uivalent nonmiuimu~ s~itch~ ~ang~mentof the iossy
integrator.of Figure 8:20. -
PACEMA~R SENSE AMPLIFIERS 197
(8.18)
A~.few qualitative observations maybe madeabout this transfer function. This

dr¢~uit hasa zero at z=l, whichcorrespondsto o~ = 0; its dc response is thus zero.
~ote~that if either C4 or C6 is set to zero, the connection between the lossless
in~t~grator and ~the lossy integrator is broken, and the circuit become
s simplya los~y
integrator. Figure 8.23 shows the frequency response for the. switched-capacitor
bi~uad filter of Figure 8.22 for capacitor values and switch frequency as shown.
Wenote that Eq. (8.18) depends upon capacitor ratios, as did the first-order
circuits (lossless and lossyintegrators) which were previously discussed; were all
capacitor values multiplied by a constant, Eq. (8.18) would remain unchanged.
C2:20 pF
C3:1 pF
10’ C,4:1.5 oF
C5:5pF, ~=
C6:1.5pF i
-10
¯ . LL=2.4
Switchfreq~=ency= 2 kHz
2
log(f), Hz
~in
Figure8.23 Typicalfrequencyresponseof biquadswitched-capacitor filterofthe tTpe~ho~n
Fi~: 8it7. Thei~spon~b~ gins to deviate from~at of a c0ntinuous~fim~filter
for frequencies
~ is mo~tevident~in tbe~phaseresponse;~a~ntinuous-time
~b~approximately 100 Hz,~This
ne(v/brk’s phase response wouldasymptoticallyapproach~-90~for frequencies beyondthe
respon~pe, ak,~
Switches
The Switches
appro~a.tes~ that~Ofideal switches.

is ~h0~n in Figuie 8~24. NMOS~Sistor~ the
series-pass elements; they are switched ONor OFFsimultaneously by the voltage

applied to both the gate of Q1 and the inverter pair Q3and Q4. The control voltage
directly commutates Q1, and the inverted output of Q3 and Q4 switches Q2
simultaneously with Q 1. A single transistor such as Q 1 could serve as the pass
element, but the ONresistance of such a switch would be more dependent upon the
applied signal~level than wouldthe resistance of the complementarypair. Note that
the Vi and Vo signal levels-of the inverter .in Figure 8.24 should be constrained to
between Vddand Vss. The use of complementarypass transistors also provides a
measure-of clock-feedthrough cancellation; the gate signals of Q1; and Q2 are
opposed in phase ~ charge injection via the gate-to-source capacitances of Q1
and Q2 tends to be Self-canceling.
+Vdd
Clock signal
Q1
+Vdd OIil~
Vo
Q2 ,~
-Vss
Figure 8.24 CMOSswitch implementation.
Figure 8.25 illustrates three of the possibilities for makin~monolithic c,apacitors.

Fi ~gtu~~ 18.25(a) shgWS~a ~ Capacitoriti ~ hich ~ ~tallizatibn is ~plied to
met~-0ver-/~
a ~gionof ~ o~Jde directly abo~ea’p-~ weH’.iFi~~e. 8~2~(b)iSi~a,~,ariatic~on the
stmeturein (a)in that dopedpolycrystalline silicon is utilized as. the matedal~ofthe
upper plate of the capacitor. Both structures assumethat the n-substrate will be
connectedto the most-positive point in the circuit in order to reverse-bias the p + n
junction whichthe well forms with ~ substrate. The w~ellrtorsubstrate capacitance
will constitute a voltage-varihble pdr~sitic c~apacitan~e; ~d:~the’ dophig Of the/7+
well must be sufficiently heavy that the MOScapacitor structure remains in
accumulation over all possible signal voltages which may be applied to the
capacitor; if this is not the case, the capacitor itself will be voltage-variable~d
’01tage
ion and
PACEMA~R SENSE AMPLIFIERS 199
~e,,,same authors report a capacitance of 0.56 pF for a poly-over-p+capacitor

~hoseplate dimensionswere 47/.tin X47/Jm.,Giventhat the dielectric constant
6f silicondioxide is 3.9, we can find that the thin oxide layer whichformsthe
dielectric of the capacitor had a thicknessof approximately
136nm.
~/_ Metal /
P÷ wo,, ’ I ’ ~ ¯
~
"~( n-substrate Thin°xlde! ’ (a)
Metal
Oxide Metal Oxide
Polysilicon
p-I-
(b)
~
"~ Oxide. Polysilicon .......
~
Metal -,~
’ Thin oxide- ~
~ substrate ~:
.....
,- . ,(c)
Figure 8.25 Typical MOS capacitor structures. The capacitors in (a) and,(b)Use_a buffed
we!l,¢oform~0n¢iplate of the capacitor; the structure in (c) !utilizes twodopedpolysilieonlayers
t~.formthe capacitor plates. ~ _~,-,
~of
~n but capac ~s
200 DESIGN OFCARDIAC PACEMAKERS
considerably more repeatable. Ratiometric capacitors maybe directly synthesized

by fixing the ratios of the areas of the capacitors, but.more precise control of the
ratios of capacitors is achieved by forming each capacitor by the parallel
connection of several unit capacitors. Fringing of the electric flux at the edges of
the capacitor plates and possible photolithographic imperfections should have
equal effects on the value of each unit capacitor. The 0.56-pF MOScapacitor
described by Stone et al. (1984) was such a unit capacitor.
Operational amplifiers
The operational amplifiers described in section 8.3 are suitable for monolithic
switched-capacitor networks, including the operational t~ransconductanceamplifier.
It is importantthat the amplifier be able to deliver sufficient output current to re-
distribute the charge stored on switched capacitors to non-switched capacitors
during clock phase ¢2. Gray and Meyer(1982) state that the minimal open-loop
voltage gain required of an operational amplifier in a switched-capacitor networkis
on the order of several thousand. Stone et al. (1984) report that simple two-stage
CMOS operational amplifiers like that of Figure 8.11 have been used with success
in two-poleswitched-capacitor~filter circuits.
8.3.3 Examplesof switched-capacitor circuits
Figure 8.26 reproduces a part ofthe switched-capacitor networks described by

Morgan(1991). The circuit in figure 8.26(a) will be recognized as a cascade
lossy integrators (single-pole low-passfilters), the first of whichhas a differential
input. Thedifferential stage has a de gain of 17 as set by the ratio of C3(4.7 nF)
C4 (270 pF); the de gain of the second stage is selectable meansof the gain-select
switches (which are MOSswitches, like those described ebxlier) and mayrange
from a minimumof 1 (when only C6, which has a Value of 270 pF, is connected)
a maximumof 15 (when C6-C9 areall colmected)..The leakage capacitor C11 of
the second stage has a value of 270 pF2CapaeitorC-~ is’540 pF; C8is 1080 pF; and
C9is 2160pF. The clock frequencyis gi~,en ~.as 2 kHz; at that rate, capacitors C4
and C ll act as effective resistances of 1.85 Mr2, which--paralleled by
nonswitched capacitances of 1 nF (C5 and C10 )--give each stage a low-pass
corner frequency of 85.9 Hz. The cascade of the two will give a corner frequency
of 55.3 Hz. Passive RC low-pass networks RI:C1 and R2-C2 have corner
frequencies of approximately 120 Hz, providing bandlimiting to avoid potential
aliasing problems.
Figure 8.26(/~) showsa high-pass filter, a cirenit topology which,hadnot been
previously considered, although extending the analysis of earlier circuits to the
highrpass case is not difficult. The high-frequency gain of the circuit is given by
the ratio of C12toC14 if C13 is not connee~ed’tr, if C13 is inthe ekcui~, by the
r~ti,o of (C12 + C13) to C14JC12, C13, and C14~ali have identical~.values (2~2 nF),
giving possible ga~s of l ~ or 2 for this stagel Switthed capdeitor’C15~ias a ~value
of 2~i~ pF; switched at 2 kHz, it manifests ~ effectiVe rtgistance of 2.27 Mr2
which, in conjunction with nonswitehed feedback capacitor C14,~i~vesa’~gh-pass
corner frequency of 31.4 Hz. Twosubsequent cascaded high:pas~ ~stagts with the
same eorii~r f~uency were also shown; ~e Seeond~tage~ad a’ifigh~pass ’ gain of
1.5 ~whiie thethird stake had a high~p~tssgain Of 3. The ~h-p~g~,c~f frex~uency
of a cascade of ~hree such filter~ w~ibe61~5 Hz. C0mpa~ihk this ~Viththe eo.m.e~r
frequency of the cascaded low-p~s filter (55~3H~); we see that the highpa s
comer frequency is above the low-pass,comer frequency, leading to a passband

with,.a peak at about 58 Hz and with asymptotic slopes of -40 dB/decade for
~equencies above the passband and -60 riB/decade for frequencies below the
passband.
~2 ~)1
R1
-I c~
(a) Differential-inputamplifierandlow-pass
filter
C13
V/
C12
(b) Adjustable-gainhigh-passfilter
Figure8.26,Swi,tehed-eapaeitor
circuitsdescribedby,Morgan(1991). Part(a) is the diff.e .re.ntiai-
input amplifierandlow-passfilter; part (b) representsoneof three high-passstages wnienare
cascadedafter the low=pass
sectionabove.Onlyoneof the three high-passfilters has switchable
gain.Vbis a bias-voltage
bus.
~.Th. ~ alert reader will have already realized that somethingis not fight in the
description of th~ Circuits in Figure 8:26. ~e circuits as described by ~Morgan
C6~d~zotbe redu~ed~o monolithic fonni ~thb ca~it0~v~u~’,..are .mucli.tooia~ge
for ~stic monolithic implementation.and .th~ filter top010giesehosen are not
parasitic-insensitive. In addition, Morganshowspower-supplyvoltages of :E5 V for
the operational~ amplifiers in his circuit; these voltages ~are:,not available in the
typical implantable pacemaker. This .e~uit can nevertheless give someinsight into
the,frequeney-responsecharacteristies of a typie~ pacemakerand can allow ~us~to
practice-some of the analysis teehniquespreviously explored; for these reasons, it
is worth mentioning.
Stotts ~(1990, 1992) describes switched,capacitor amplifiers~similar to the
circuit of Figure 8~26(b), Switched-capacitor biquad topologies were employed
Castello et al; (1990) to build a sixth-order bandpassfilter~ for implantable-device
202 DESIGN OF CARDIAC PACE~KERS
applications: They present a filter fabricated in 2-pro CMOS technology which has
a’centerfrequency of 50 Hz, a bandwidth of 60 Hz, and draws only 500 nA from a
+1.2 V battery while being capable of’driving capacitive.loads of 30 pF. This
implementation utilized a 2-kHz clock and multiplexed two operational amplifiers
amongthe three biquadratic calls (the operational amplifiers are necessary during
the clock phases whencharge is being redistributed but not whenthe charges on
the nonswitchedcapacitors are simply being held). The oper.ating voltage range is
given as +1 V to +1,8 V. The total silicon area occupiedby the filter was given as
2.
2200 mils
The battery specifications cited by Castello et al. (1990) andthe use of a
bias-voltage bus in Figure 8.26 leads to the tentative conclusion that circuit ground
is defined at the midpointbetweenthe terminal voltages of the 2,8 V lithium-iodine
battery. The ground,potentialshown
in, preceding~
switched-capac~or;~~ ,.~ circuits need
not necessarily be identical with the potential of one end or tile other of the battery.
8.4 BLANKING CIRCUITS
Blanking is necessary during periods of pacing to prevent saturation of the

pacemaker sensing amplifier(s). In pacemakers whiCh sense and pace both
chambers, blanking is also used to prevent crosstalk between channels, i.e., to
prevent the stimulation of one chamberfrom being interpreted as cardiac activity in
the other. ¯
Figure 8.27 shows a commonblhnking m¢~o~]~ ,:.. Ananalogswitch (similar to
those seen earlier in the discussion of switched-capacitorn¢~t3vorks)is controlled by
the appropriate blanking output of the digital ~Toeotatroller and simply connects
the amplifier input through a low impedance ~ to circuit ground during pacing
stimuli. The blanking pulse will generally last for someperiod of time (5-10 ms)
after the end of stimulus.
To sensing/pacinglead To senseamplifier
’ control
~ signal
Figure &2~Blanking:network describe’by Morg~an (1991). The ~bla~kingcontrol ,signal

actiVatesth~ analog~vitch and~sh6rt-eircu~ts ihe :sense-ampl’ifie~ihpiitto ground"when
appropi’iate~i~ prevetit~sa~turatitn6fthe ~n~;amplifierbyapds~’ontheleb~bnsensing/pacing
lead or erosst~~,’ from pacing of the bther chamber.~ ~ ~: .... !~, , :
Herscovici et al: .(1984)and Shonlder(1990) disclose ,another method

bl~g:. In these.:cases, an~electronic switch turns of£ the battery voltage~to the
sense amplifiers during blanking, Both descriptions expl~n~thf actions of,these
circuits in terms of elimination of crosstalk from Onechannel to the other-ina dual-
chamber sensing, dual-chamber pacing pacemaker. ~ ...... ,~ ~
De~0te¢Jr. (1987)~ takes yet another approaeh;,toi,~the ,question of saturation
during pacing ,transients; ~s particular ;circuit utiliz-~ £our operational~amplifiers,
three of which form aeonventionalcoiatinuous-time instrumentation amplifier. The
,PACEMAKER SENSE AMPLIFIE~RS 2O3
~ax~’,mal differential voltage which mayappear at the instrumentation amplifier

~als is limited by a pair of back-to-back silicon diodes and the gain of the
instrumentation amplifier is calculated such that a transient whichcauses one or the
other diode to conduct will still be of insufficient amplitude to saturate the
ins ~_~ mcntafionamplifier. Thestage following the instrumentation amplifier has an
oUtpUtvoltage that~is limited by a pair of series-connected Zener diodes to a
maxim~,al output voltage within the output-voltage capabi~tyof that stage.
8.5 OTHERCIRCUITS
8.5.1 Switched-capacitor voltage comparator
Figure 8,28 is an exampleof a switched,capacitor voltage comparatorsimilar,to the

one shownby Stotts et al. (1989). Included in that figure is,a state, ruble for the
activation of the switches. This circuit is novel for its dual use of the operational
amplifier; the closure of $5 during phases 1 and 3 utilizes the operational amplifier
~ .~ yoltage follower to maintain a VirtuaFgroundat its inverting input. Switch $5
bp~ils during phases 2 and 4, allowing the operational amplifier to operate in an
open-loop configuration.
Vs
$4
¯ ;Switchandclo~ksignalstatetable ~ CIkA
~ ,I
~l [ n 0 1 2 ~
3: J ~
~,. 1’ CIk B
4 3 4 3 ~: ~
5 Clk A 5 ClkB
Figure8.28 Switched-capacitor voltage comparator.Theswitchesandflip-flop clock signals

eycl~t~,o.ugha pattem~offour st~es; the ta,,ble aboveAndieateswhiek switches~ closed~,a~/d
whichflip-~opdocksignals ar~, ~tive duringwhic~states. If.the, input sighai is mo~re negatiye
tllan the negatl~,e~thresh~ld
given~in flip-flop ~ Wi!l’be driver] high
F-xl. (8:20), the/QnO,cUt.of
d~g~phase 1: If the input signal4s .morepositive than e thresholdgivenin Eq~(8:21)~the
output of flipflop F~ will bedriveapositive durin~pliase~. . " ,. .~, ,
. " . During phase 1, capacitor C2is charged,to Vddand, Cl,is,charged to ~Vs, the
signaL voltage from~the output, of,the switched-capacitor bandpass filter. During
phase 2~~C2is switched from. Vdd,tOVrefand~Cl:is switched from Vs to ground;~the
voltage at the inverting input of the operational:amplifier becomes:~. ,,
204 DESIGN OFCARDIAC PACEMAKERS
Va=C2( (Ci+C2)
Vref-Vd, )_C1
’- +c2) (8.19)
(q
whereVais the voltage at the inverting input of the comparatorand Vs is the signal
voltage at the bandpassfilter output. Hip-flop F1 is clocked during phase 1, and its
/Q output will be driven high if the output of the comparatoris low. This occurs if
Va> 0, whichrequires that:
Vs < C2 (Vdd - Vref) (8.20)

CI
Capacitors C1 and C2 are charged in phase 2 as they were in phase 0 with the
exception that: C2 isinitially charged to Vref instead of Vdd. The output of the
voltage comparatorwill go high during phase 3 if:
Vs >~C2(V~dd~ Vref) (8.21)

c1
Hip-flop F2 is clocked by Clk A during phase 3; the Q output of F2 will be driven

high if the bandpass filter ~ output voltage is greater than,,,threshold given in
Eq. (8.21). This circuit is especialhy noteworthyfor?itslow powerconsumption(it
does not use a wasteful resistive! voltage~ divider to set its sensing, thresholds and
makesvery efficient use of the operational amplifier as both a linear amplifier and
as a voltage eomparator.
8.5.2 Bipolar/uuipolar sensing/pacing circuit
Figure 8.29 shows circuits which are used to select either bipolar or unipolar
sensing or stimulation and to permit such selection to ’be madeautomatically. The
table in Figure 8.29 describes what combination of switch, FETsQ1-Q3is used for
each pacing and sensing mode.FETQ4is activated briefly after a stimulus pulse to
permit rapid repolarization of the electrode and discharging of the capacitor which
couples the pacing stimulus to the lead.
8.5.3 Voltage reference
The switched~capaeitor voltage comparatorof ~FigureS,28 requires a reference

voltage which operates at a fixeddisplacement f~om the Vdd supply (see Eqs.
(8.20) and (8.21)j., Figure 8.30 showsi:sucha V01tagereference~
"i~ais circuit utilizes
a differential pair of silicon-gate p-channel MOSFETs, Q1 and Q2, whosegate-to-
substrate electrostatic potentials are madeto be different by differential doping of
the polysilicon,gates: The gate of Q1 is p÷ polysilicon; while thatof Q2 is n+
polysilicon; the difference:in gate dopants causes a~displacementin the threshold
voltages of ,the two FETs which is approximately equal tothe silicon bandgap
voltage. The drain currents of Q1 and Q2 in weakinversion are given by:
~ ~PACEMAKER
SENSE AMPLIFIERS 205
~d~= ldo W~e-(V~wVr)/~kT

L1
(8.22)
Id2=/doL2
W2-e-(V~2-Vr+Vnv)/nkT
in which VT is the threshold voltage of Q1; VG1 and VG2are the gate-to-source
voltages of Q1 and Q2, respectively; Wl and L1 are the channel width and gate
length of Q 1; W2and L2 are the channel width and gate length of Q2; and VBGis
the bandgap voltage of silicon (1.11 V @300 K). Other parameters of Eq. (8.22)
were previously defined (see Eq. (8.3)). If we compareEq. (8.22) with Eq.
we will note the introduction of negative exponents in Eq. (8.22); this sign change
accounts for the fact that p-channel devices Q I and Q2 show increasing drain
currents with increasing negativ e gate-to,source voltages. The current mirror
formed by Q3 and Q4 forces the drain currents of Q 1 and Q2 to be equal; by
equating the two relations in Eq. (8.22), wehave:
Vre f = VBG +nkT tn[(WilL1)/(W2/~)

] (8.23)
+V
04
+V
Transistors Bipolar Bipolar Unipolar " Unipolar

.... ,~ sense pace ¯ . sense pace
q~ "OFF . ON OFF , OFF
q2 OFF , OFF ON OFF
Q3 ON . OFF ON ON
Figure 8.29 Circuit permitting multiple sensing/pacingmodes.This’particular embodiment
consideredthe battery positiveterminalto be the referencepotential of the pacemaker
(Barreras
and Martucci,198~),
Temperature compensataonof Vref can be obtained by proper choice of the width-

t0qength ratios of the,differential-pair transistors. Tsividis and Antognetti,(1985)
descrthe a mmllarclrctut that generates a reference voltage relatave to ground; they
cite a temperature coefficient of + 30 ppm/*Cwith an unadjusted accuracy of

+ 50 mVfor their device. Circuits like that of Figure 8.30 can be used to generate
reference voltages while drawing operating currents in the range of tens of
nanoamperes.
+ n+ gate
Vref / Ibias
Q3
Vss o
Figure8.30 Micropowervoltage reference circuit whoseoutput voltage is at a fixed

displacement
fromthe positive power-supply
voltage.
The circuit of Figure 8.30 develops a reference voltage by exploiting known

differences in the drain current vs. gate-to-source voltage characteristics of two
nonidentical FETsforced to operate as a differential pair and conducting identical
drain currents. Other implementations are possible; Ong(1984), for example,
describes a similar circuit which utilizes an enhancement-mode FET and a
depletion-modeFETin the differential pair.
8.5.4 Current reference
Circuits previously described have often had current sources that were integral
parts thereof. The circuit of Figure 8.31 shows howsuch current sources maybe
constructed. It depends upon the availability of a moderately-large resistance,
which may be implemented in high sheet-resistivity polysilicon as described by
Stone et al. (1984). Identical p-channel devices Q3and Q4 cause the drain currents
Vdd c Q~
Isouree ¯ ]
Isink
Vss c -
Figure8.31Micropower
currentreferencecircuit. Thiscircuit is :~apableOf prtvidingbothsink
and go~ ~urrents.
of asymmetric n-channel devices Qland Q2 to be equal. Assumingthat Q1 and Q2

Operate in weakinversion, we maywrite:
Idl = e(V~l-Vr)/nkT
Ido
(8.24)
Id2 = Ido
e(Vo2-Vr)/nkr"
Wealso note that:
VGI = VG2 +/d2Rs (8.25)
By<e6mbining
Eqs. (8.24)and Eq. (8~25), we find that the drain currents of Q 1
Q~ ~ given by:
ld =-~-~" L~J ~ (8.26)
These are ~the drain currents of Q3 and Q4 as well; the drain current of Q5 maybe
usedas a current source whosevalue is given by Eq. (8.26)if weassumethat Q5
identical; Thedrain current of Q6maybe similarly utilized as a ~cu_rrent sink; this
sink current will be described by Eq. (8.26) if Q6is identical to Q3: Notice that the
output currents of the circuit of Figure 8;31 are directly~proportional ,to
temperature. Werecall from Eq. (8.4) ~ ,that ~the transconductance of an FET
operating in the weak-inversionregime is directly proportional to’ drain current ’and
inversely proportional to temperature. ~Theuse of a current reference like that of
Figure 8.31 to determine the operating currents of FETs operating in weak
inversion can compensatetheir transconductances~ for variations in temperature.
V~ry small reference currents may be/generated With moderate-.values, of RS.
Assumethat nkTIq is 54 mVand that the width=to-length ratios ofboth Q1 and Q2
are equal; a resistance of 75 k,Q will produce reference Currents of. 720 hA. This
could be further reduced by increasing the width-to-length ratio of Q 1 or reducing
that, of Q2.
8,6 PACEMAKERS AND ELECTROMAGNETIC INTERFERENCE
The question of pacemaker response to interference from electric and

electromagnetic sources is one of great interest to physicians, pacemakerdesigners,
and patients alike. It is also an area of considerable confusion, partof whicharises
from nomenclature. The terms electromagnetic and interference used
independently or ~in conjunction appear in multiple contexts. Furman(1982) uses
the phrase electromagnetic interference to denote skeletal,muscle myopotentials;
Belott et al, (1984) use it in the context of electrosurgery., Others use similar
terminology to denote radio-frequency interference (Bossert and Dahme,1988;
Smith and Aasen, 1992). This section will follow the example of Hanser~(1994)
and Irnich (1984) in which the term interference is meant in its broadest sense,
incorporating ~ both endogenous(internal to the body) and exogenous(external
the body) sources of unwanted potentials to which the implanted pacemaker may
be exposed. Exposure of pacemakers to potential sources of interference is
unavoidable. Electrotechnology in various forms is widespread in industrialized
society, and pacemaker implantation is common;Sowton (1982) estimated that one
person in 800 in the United States and one person in 2000 in the United Kingdom
had an implanted pacemaker, with implantation rates in other western European
nations and in Canada being comparable to that in the US. Later figures give a
worldwidetotal of 1.5 million implanted pacemakers, of which 700,000 were in the
US (Smith and Aasen, 1992).
8.6.1 Endogenousinterference
Myopotential inhibition of demandpacemakers implanted in the pectoral region

has been recognized for sometime as a significant problem; Vrints et al. (1981)
summarizedata from previous studies of the prevalence of inhibition of unipolar
demandpacemakers by myopotentials, finding episodes of inhibition in as few as
11%to as manyas 69%of cases surveyed. The authors then disclosed results of
their ownstudies. One study consisted of 34 unipolar pacemakerpatients and 11
bipolar pacemaker patients who were asked to perform simultaneous isometric
contraction of both pectoral muscles by forcefully pressing the palms of the hands
against each other. Evidenceof interruption of pacing was provided by an external
ECG. Unipolar pacemakers manifested inhibition in _15 cases; no cases of
inhibition were .found amongthe bipolar pacemakers. Symptomsof inhibition
(dizziness or syncope) were reported by 3 subjects. The second study involved the
subcutaneous implantation in the fight pectoral region of 40 unipolar pacemakers
that had been fitted with an insulating silicone rubber sheath that coveredthe entire
surface of the pacemakercase except for a small window.~Thiswindowwas turned
toward the subcutaneous side of the implant site, insulating the pacemaker case
from direct contact with muscle. No cases of myopotential inhibition were found
amongthose unipolar pacemakersfitted with the sheath.
Irnich (1984) confirms the superiority of bipolar sensing .to unipolar-sensing
insofar as rejection of myopotentials is concerned. Hauser(1994) states that bipolar
sensing is the best technique for dealing with clinical cases of myopotential
inhibition. The possibility of pectoral n,/yopotential inhibition of a unipolar
pacemaker can be reduced by implantation in a more medial site in the pectoral
region; lateral implantation in the deltopectoral groove is associated with greater
incidence of myopotential inhibition.
Irnich (1984) mentions myocardial repolarizati0n and charging of the
pacemakeroutput capacitor(s) as potential sources of endogenousinterference but
states that such occurrences imply a mismatch amongsensitivity, frequency
response, and refractory periods.
8.6.2 Exogenousinterference
This category includes all types of extracorporeal signal sources, encompassinga

broad range of methodsfor creating potentials which mayinterfere with pacemaker
operation. Certain types Of potential sources of interference are discussed below.
Low.frequency interference
The frequencies used in ac power transmission (50 Hz and" 60 Hz) lie close to the
ranges of frequencies characteristic of P and R waves(see section 8.1); it is natural
that there be concernover the possibility that high voltage powertransmission lines
might cause interference with pacemakers.~ Butrons et al. (1982) described a series
of~xperiments in which volunteer subjects fitted with Medtronic 5985 Spectrax
unipolar pacemakers were exposed to 50 Hz electric fields with intensities of
20!kg/m, resulting incorporeal displacement currents of up to 300/zA: No
inhibition nor other abnormal pacemaker responses were noted. A follow-up study
0f~35 unipolar demand pacemakers (representing 16 pacemaker models from
different manufacturers) gavedifferent results (Butrous et al., 1983). No noticeable
effects, were seen ,in 11 units; 18 units revertedto asynchronous mode. The
remainder manifested irregular or inappropriately slow pacing. The corporeal
currents necessary to provoke reversion to asynchronous modewere found to range
fftm 18.4/zA to 250 ,uA.
~ Kaye et al. (1988) found similar results by utilizing 50 Hz current injection
into:the bodies of 18 subjects with implanted unipolar WI pacemakers. These
~pacemakers represented 12models from 6 manufaCturers; eleven pacemakers were
implanted in a left prepectoral ~ position~and,four, were implanted ina right
prOpectoral position. The remaining three devices were implanted in the abdomen.
bIormal pacing was seen in~ all pacemakersat low values of corporeal :~current.
~ents~ above~acertain threshold caused inappropriate pacing, erratic sensing, and
intermittent inhibition in most of~the pacemakers-used in this study; currents
beyonda second (higher) threshold caused the susceptible pacemakersto revert
asynchronous mode.,The three Medtronic units utilized in this study maintained
normalpacing up m corporeal currents of 600 gA(the limit of the current-injection
d~viee); units producedby Telectronics were found to be the most susceptible.
~,~:~:~.~stridge et al,~(1993)performed a similar study utilizing dual-chamber
p~cemakers with programmable lead configuration. Reversion to asynchronous
mixie~withbipolar lead configurations occurred at relatively high currents (170
to~550/~A); the onset of malsensing and~inappropriate function was found robe in
th~range of 80 #A to 500/~A~ Unipolar sensing was much more susceptible to
cbrporeal current; unipolar atrial sensing manifested the onset of malsensing at
currents between 10/~Aand 80/~A, while ventricular~ malsensing with inhibition
was found to occur at 40/~Ato 120/JA. No significant differences in susceptibility
were found among models produced by Siemens Pacesetter, Intermedics, and
Telectronics. Malsensing in bipolar modewas not observed in either of the two
Medtronic models which were tested; one model showed no abnormalities in
unipolar modeat - the maximal current of 600 #A, while the other reverted from
normal operation to asynchronous pacing at currents ex~g 120
.... Lrnich (1984) describes mechanisms, of magnetically-coupled interference.
Thearea subtended by a unipolar pacemakerand its lead arranged in a semicircle is
estimated at 570 cm2; a magnetic~field intensity of 21 gT ~rms) at 50 Hz:or
1,7,:5/~T (rms) at-60 Hz normal to that semicircle would produce a potential,
l~mV~peak to peak, a value Irnich takes to be the critical value at whichmalsensing
maybegin. These kinds of magnetic field intensities’may be found in the vicinity
of devices which draw large ~currents (such as arc welders and electric steel
furnaces). Bipolar sensing should prove muchless susceptible to magnetically-
coupled interference.
Radio-frequency interference
Early pacemakers were encapsulated in nonconductive epoxy resin and had few
interference-rejection components; as a result, the literature of pacemaker
electromagnetic interference was rich with reports of interference from sources

such as microwave ovens (Olson, 1994b). Pacemakers of modemdesign are
enclosed in sealed titanium cases which act as Faraday cages, leaving the lead
system as the only meansof entry for:radio frequency signals. Effective capacitive
bypassing of the leads to the case renders modempacemakers remarkably
impervious to radio-frequency interference.
Radio-frequency interference maybe generated by intentional sources (such
as radio transmitters, electrosurgery and diathermy units, and,microwaveovens) or
by unintentional sources (such as electrical equipment which creates arcs in its
operation). Microwave ovens .are the source with which a typical pacemaker
patient may be most likely ,to come into contact. Sowton (1982) reports that
rmcrowaveovens can occasionally affect pacemakers, especially in the event of a
degraded door seal; O’Bfien (1982) also names microwave ovens as potential
sources of interference which would cause demand pacers to revert to
asynchronous mode. Irnich (1984), however, reports experiments which showed-
that microwaveovens do not influence pacemakers by their microwaveradiation
even whenrunning at full powerwith.the door open (which is only possible if the
door interlock has been defeated). Irnieh states that the penetration depth of
2.45 GHzmicrowaves is only about 6 mmin the humanbody and thatmost of the
energy is dissipated superficially. Hanser (1994) concurs with Irnich,s judgment
concerning the lack of hazard posed by microwaveovens.
Smith and Aasen (1992) assessed the safety of pacemakers in the vicinity
high-powered short-wave and medium-wave broadcast transmitters. They state that
effects of electromagnetic interference in pacemakerswould not occur tmtil:,the
electric field intensity exceeded 200 Vim.or until the~magnetie fidd intensity
exceeded 1 roT. This dectric .fidd intensity is round,in only a few specific
locations in a typical VOA,.(Voiee of America) relay station (such as
transmission lines, short-wave and medium, wave .transmitting antennas, and
microwaveand satellite-link transmitting antennas), and magnetic~field intensities
greater than 1 mTmight be found around some power transformers. One of.the
authors (Smith) had an-implanted pacemaker and showedno adverse effects of her
exposure to electromagnetic fields of two VOA relay stations.
Bossert and Dahme(1989) performed laboratory tests on 34 different types
cardiac pacemakersand found their radio-frequency interference susceptibility to
vary considerably from manufacturer to manufacturer; they suggest simple circuit
modifications which would decrease the susceptibility of pacemakers then
available. These modifications include the shunting of pacemakerlead(s) to the
case by suitable capacitors of at least 1 nF, a passive low-pass filter betweenthe
lead(s) and the sense amplifier input(s), and modification to permit lead-to-case
potentials of 10 V to 20 V before clipping begins. The test waveformto which the
pacemakers were subjected was pulsed AMin which a period of unmodulated
carrier of 600 ms was followed by 100 ms of 100% sinusoidal amplitude
modulation. A modulating frequency of 100 Hz was used.
Hanser (1994)and Grant (1993) concur ~that little risk attends the use
Citizens’ Band or amateur-radio equipment by pacemaker patients. Hanser stated
that both are "generally safe."
Medical electromagnetic sources
Belott et al. (1984) report cases of resetting of DDDpacemakersto backup mode

by electrosurgery, including cases of pacemakers which were damaged by the
~tocedu~ and which could not be restored to their original programmedsettings.

G~(i993) outlines potential risks ’in electrosurgery in the pacfmaker patient
ngthe conduction of electrosurgery current through the pacemaker lead to
tllei~i~yo~ardium with the attendant risk of ventricularfibrillation; Sowton(1982)
~f~n~nsthat there have been reports of fatal episodes of ven ~tricular fibrillation
g"ftom electrosurgical procedures on pacemaker patients. Hayes (1993)
de~es.the risks of electrosurgery as inhibition, reprog~ng to backup mode,
~ssible circuit damage.
~:~!~~~,~:~ ~:.. ¯. equipment.,i~a rather uniquehazard~n"thatthe atatie magneticfield of
~li~i~.~Strumentis of sufficient strength to close the pacemakerreed switch. This
w?0otd place the pacemaker in an asynchronous modeand remove one normal level
0f~tection against unintentional reprogramming.Hayes (t993) cites animal tests
~ .~hich it was found that certain pacemakerscould be madeto pace ~at the pulse
~ition ,rate of the MRIequipment. Hayes also states that radio~fre,quency
~rmy apparatus mayproduce circuit damage, or inhibition of both unip61ar and
bipO[.ar pacemakersand that electroshock therapy (electroconvulsive therapy) may
~’~§~ inhibition or temporary reversion to asynchronous pacing; unintentional
~ptp~ng may also be~ possible. Hauser (1994) places electroshock therapy
~6n~ the unlikely sources of pacemaker interference. Sowton (1-982), Hauser
(1~,94), ~d Hayes (1993) cite potential risks of TENS(transcutaneous electrical
nb~ sfi~ulation) devices. Hauser lists these risks as inliibition, reversion to
~Chrpnous mode, and c0mpetitive pacing; Hayes also includes ~reprog~ng
~k a potential dsk but asserts that these effects fromTENSa~paratus are.rare.
Sowton~Simply. recommends that pacemaker patients avoid the use of TENS
apparatus altogether. There appears to be~ widespread agrecnient that
.c.~0wersig~defibdllation ~arries the risk of CircUit damage(H~tyes, ~.1993;
~ interference sources
O~e~r
Th~hazardsof 0ther:potential sources of electromagnetic inteffe~nce~.with, which

theipacemaker patient maycomeinto contact in the course of daily life appear:to
be minimal. Office equipment, light shop equipment, video games, and dental
equipment are all listed as unlikely sources of interference by HauseL(1994),~
assessment with which Hayes (1993) appears to agree, although Hayesdoes cite
hazards of inhibition or reversion to asynchronousoperation associated with .arc
welding and Grant (1993) stated that arc welding is contraindicated for pacemaker
pafl~’nts.. Sowton(1982) advised that pacemaker patients avoid, airport metal-
detector equipment, Hauser, however, viewed such security devices as unlikely to
cause interference. Hayes saw airport-security equipment as carrying the risk for
one-beat inhibition while the passenger is traversing the security apparam.s; Hayes
also reported that this same risk of one-beat inhibition mayoccur with retail
antitheft devices.
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8.8 INSTRUCTION~ OBJECTIVES
8.1 List and explain the constraints whichpacemakerapplications imposeon electronic design.
8,2 Explain the difficulties encountered in makingcontinuous-time circuits with frequency
responsessuitable for cardiac-sensingapplications.
8.3 Explain someof the difficulties encounteredin utilizing MOS devices as linear-amplifier
elementsoperating in weakinversion.
8.4 DeriveEq. (8.6) (capacitancemultiplication).
8.5 List the advantages and disadvantages of switched-capacitor technology for cardiac-
pacemakerapplications.
8.6 Calculatethe effective resistance of a 20-pFcapacitor switchedat a rate of 20 kHz.
8.7 Describe the operation of a noninvertinglossless switched-capacitorintegrator and derive
its charge-balanceequation.
8.8 Explainhowparasitic-insensitive switched-capacitortopologies differ from those whichare

not parasitic-insensitive. Explain whyparasitic-insensitive topologies-are crucial to
successful monolithicimplementationof switched-capacitorfilters.
8.9 Explainwhetheror not the switched-capacitorcircuits of Figure 8.21 wouldbe suitable for
monolithic implementationand explain whyor whynot
8.10 Describethe operation of the switched-capacitorvoltage comparatorof Figure 8.23.
8.11 Describethe operationof the circuit of Figure 8.24 whichpermits both unipolar and bipolar
sensing and pacing.
8.12 Explain whyblanking circuits are necessary and howthe- blanking function is usually
accomplished.
Logic Flow and Timing Diagrams
Be~jahn A. Afsari
Tht:main goal of cardiac pacing is to artificially stimulate a dysfunctional heart

tomimic a normal heart. In normal hearts there is a specific sequence of
excitation, as described in section 1,.6. Whenthis sequence breaks down
(abnormal conduction, blocks, etc.) the pacemaker should intervene and perform
the appropriate action at the appropriate time.
~. ~.This.chapter presents some of the basic timing cycles of pacemakers. The
approach taken is to start ~with the simplest pacemakerand use that as a building
block. Logic flow diagrams are given in preparation for the following chapter on
pacemaker hardware.
9.1 SINGLECHAMBER PACEMAKERS
In single chamber pacemakers, all timing cycles begin and end by pacing or
sensing’one chamber, In a ventricular based pacemaker (VO0, VVI, VVT), .the
Vent~ele detem~~’nes ~alltiming events. ~ Similarly, in an atrial based pacemaker
(AO0, AAI~AAT)the atrium determines all timing events. "
9.1.1 Definitions
Lower.rate interval (LRI)
Fi~ re 9,1 shows that the LRI (also known as the automaticinterval) is the
lo~ngest period be~tween consecutive paced or sensed events occurring in the
relevant chamberl. The pacemaker keeps track of t_he LRI by u~izing a timer. If
thefimer expires, before an event is sensed, the pacemaker will stimulate the
Figure9.1 In a ventrieular basedsingle chamberpacemaker the LRIis definedas the longest

periodbetweenconsecutivepacedor sensedventricularevents.Theshadedbar representstime.
chamber and reset the timer. The programmed LRI value defines the minimal
number of beats per minute (bpm) as #bpm= 60/LRI (s). For example, if
LRI were equal to 600 ms, the minimal number of bpm would be 100. The LI~I
is determined by the physician and is based on the patient’s age, fitness level,
activity level andlifestyle.
Upper rate interval (URI)
Figure 9.2 shows that the URIis the shortest period allowable between paced or
sensed events, while still maintaining one-to-one (1:1) atrioventricular (AV)
synchrony. 1:1 AVsynchrony means that for every atrial beat there is a
corresponding ventricular beat. Once the URI is reached, 1:1 AVsynchrony can
no longer be maintained. At this point special algorithms are used in order to
pace efficiently. These algorithms are discussed in section 9.2.4. For sensor
driven modes (VVIR, AAIR) and dual chamber tracking modes (DDDR, DDD,
VDD), the URI is used to limit the maximal rate at which the pacemaker can
pace. This rate is also determined by the physician and depends on the patient’s
age, activity level, fitness level, and lifestyle.
The URI becomes a factor when ventrieular activity begins to occur too
rapidly. The ,URI, based on the VRPis: upper rate (bpm) = 60/VRP (s).
numberof algorithms for dealing with the URIare discussed in section 9.2.4.
URI ~
Figure9,2 In a sensordrivenor dual chambertrackingmodepacemaker, the upperrate interval

GIRl)is defrayedas the shortestallowableperiodbetweenpacedor sensedventrieularactivities. In
comparingthis figure to Figure9.1 above,the differenceis that the distancebetweenthe QRSs is
longerin Figure9.1. Thissymbolizes a longertimeinterval.
Refractory period
A pacemaker refractory period is distinguished from the natural physiologic

cardiac refractory period. A pacemaker refractory period is a period during
which a channel’s sensing mechanismis blanked to incoming electrical signals.
Refractory periods are essential in pacemakersfor the following reasons: (1) the
output pulse of the pacemaker must be prevented from reentering the input
amplifying system; (2) the pacemaker should not be disturbed by a QRSsignal
emanating from a paced ventricular beat; and (3) to avoid the sensing of after-
potentials (Barold, 1971).
Youmay recall from Chapter 8, that the input amplifiers are blanked for a
period of time to avoid sensing during paced events. The difference between the
blanking period and the refractory period is that the refractory period is greater
than or equal to the blanking period. Obviously nothing can be sensed whenthe
amplifiers are blanked, however, through software or hardware, the blanked
interval can be extended to provide a longer refractory period.
Refractory periods can be lengthened or shortened through programming. A
physician may lengthen the refractory period in order to avoid sensing the
LOGIC ~OW AND TIMING DIAGRAMS 217
preceding QRScomplex, T wave, or the after-potential of.. a paced beat. On the

other hand, a physician mayshorten the refractory period to allow sensing of
premature ventdcular contractions that are not being sensed because they fall
within the current, long, refractory period. Whendealing with dual chamber
pacemakers (VDDor DDD),lengthening of the atrial refractory period can help
avoid endless loop pacemaker-mediatedarrhythmias (Moses, 1991).
Ventricular refractory period (VRP)
Figure 9.3 shows that in a ventricular-based~ single chamberpacemaker, the VRP

is defined as the period following a paced or sensed ventricular activity during
which no sensing occurs. The pacemake(, is rendered insensitive to incoming
signals. More advanced, modern pacemakers may sense during this period and
use the information gathered to dictate somefuture activity.
The VRPcan either be programmedor set at the factory. Typical values for
the VRPare 200-350 ms.
VRP ~
Figure 9.3 TheVRPbeginswhen a ventficular event is paced or sensed. It lasts for a set
amountof time, typically 200-350
ms.
Noise sampling interval
The noise sampling interval has been integrated into the ventdcular refractory
period (VRP) of modern pacemakers. During the noise sampling interval, if
significant amountof electromagnetic interference is sensed, the pacemakerwill
pace the ventricle regardless. This is done because if there is a lot of EMI,the
true ventricular signal will be difficult to sense.
9.1.2 Modes
In discussing the ~.various modesof tingle chamberpacemakers, we will focus on

ventricular based systems. Atrial based systems operate exactly the same as their
ventrieular counterparts, except that they sense and pace Be atrium as opposed to
Be ventricle. The goal of this section is not to comprehensivelyexamineall single
chamber pacemaker modes. Instead, it is to examine specific modes and study
their timing cycles.
VO0 and AO0 modes
The VOOpacemaker is the most basic. This pacemaker paces the heart at a fixed
rate with no regard for underlying cardiac activities. Pacing at a constant, preset
rate is referred .to as asynchrq,nous pacing (also knownas fixed rate pacing),
single timing interval is employed in these relatively simple pacemakers. Each
time a pulse is delivered, the internal timer is reset. While the pacemakeris in
218 DESIGN ~ OF CARDIAC PACEMAKERS
this mode,if there does happen:to be underlying spontaneous heart ,activity, the
stimuli will be effective only outside of the cardiac refractory period, as the
cardiac tissue is.unresponsive to stimuli during the cardiac refractory period.
Figure 9.4 is a logical flowchart, representing a VOOpacemaker. The
diagram uses a counter to keep track of time, however, any circuitry capable of
tracking time could be used (i.e. a simple RCcircuit). Suppose a pulse has just
been delivered. The counter is reset and counting begins anew. The counter is
continually incremented until the LRI is reached. The LRI corresponds to the
programmed(or factory specified) lower rate interval. Oncethe LRI is reached,
the pacer delivers a pulse and the cycle is :repeated.
]I Resetcounter
~--Jl,cre~:nt
coun,er
J
Deliverpulse
Figure 9.4 Flowchart of events in a VOOpacemaker. Upon delivering a pulse, the counter is
reset, and a new timing interval begins. The counter is continually incremented until the count
value is greater than the LRI. At this point a pulse is delivered and the cycle is repeated.
Pacemakers of this type were popular in the early days of pacemaker

technology because they worked well and were electronically simple. In today’s
market place, pacemakerswithout sensing abilities are obsolete.
VVI and AAI modes
The VVI mode of pacing delivers a ventdcUlar stimulus whenever the heart
neglects to do so. This pacemaker employs two timing cycles, the lower rate
interval (LRI) and the ventricular refractory period (VRP).
Figure 9.5 shows that a VVI pacemaker’s timing cycle always begins and
ends with either a paced or sensed ventricular event. Supposethat the pacemaker
has just delivered a pulse, its internal counters are reset and the pacemakerwaits,
continually incrementing its internal counters. The pacemaker monitors the
ventricular channd for a QRScomplex. If a QRScomplex is sensed, and the
ventricular refractory period expires, the counter is reset, and the cycle begins
again. If the LRI expires before an event is sensed, a pulse is delivered by the
pacemaker,and then the counter is reset.
VVIR and AAIR
In rate-adaptive single chamberpacemakers, the rate-adaptive circuitry adjusts

the length of certain timing intervals. For example, at any given time, the lower
rate interval can either be the basic programmedlower rate interval (LRI) or the
constantly changing, sensor-controlled LRI (Singer and Kupersmith, 1993). The
shortest possibleLRI is equal to We pacemaker’s programmedURI. The rate of
change atwhich the intervals are adjusted depends on the software algorithm
LOGIC FLOW AND TIMING DIAGRAMS 219
which processes the sensor’s data. These details are covered in Chapters 14, 15~
16, and 17.
No
" No
~ DeliverpulseJ
Figure 9.5 Logical flow diagramrepresenting ,the WImodeof a single chamberpacemaker.

All, timingcycles beginandendwith either a pacedor sensedventricularevent. Assume that a
pulsehasjust beendelivered,all counters.arereset, an~dcounting~0~~,rt~ .~ees. If the pa~make_r.
~ie~.a/ventricularevent,andtlie VRP hasnot exPired,it is treateda~n.o~ise andthe VRP reset. It
/~0eventis detectedpriorto the expirationof the LRI,a p~seis delivered.
9.2 DUAL CHAMBER PACEMAKERS
The dual chamberpacemakerhas the ability to sense and pace both the atrium and
the ventricle. Ever since the late 1970s, the use of the dual chamberpacemaker
has been steadily growing. As of 19.86, an estimated 50-70%of all permanent
pacemakers implanted were dual Chamber. One probable explanation for their
adoption is that they most closely mimicthe function of the physiologic heart.
9.2.1 Definitions
Because of their increased complexity, dual chamberpacemakers require several

additional definitions.
Atrioventricular interval (AVI)
Figure 9.6 shows that the ,AVI is the electronic analog to the P-R interval. The
AVI is the programmed~~nterval from a paced or sensed ~ atrial event to the
following paced or sensed ventricular event.
The importance of the AVIis thatjt gives the ventricle time to fill following
an atrial contraction. An optimal A~I, which is necessary for maximal
he~Odynamic benefit, may cause up to a 40% increase in ventricular end
di~/st61i’c volume~ri patients with~ sinu~~ rhythm (Benchim6i~eta!., 1965). If
p/i~e’itlaker has ~ ~p~grammableAVLand~ the physician has ~ equipment to
~oninv~/si~cely meaningcardiad output (i.e. puisea’ boppler); ~ai/6pti~al AVI
could be determined by pacing at a fixed rate~ varying the AVI, andmeasuring
220 DESIGN OF CARDIAC PACEMA~RS
cardiac output. However, if the above experiment can not be performed, it has
been found that an AVI of 150 or 200 ms provides a patient with maximal
cardiac output, whenpaced at 80 and 110 bpm(Haskell and French, 1986).
Figure 9.6 TheAVIis the programmed interval froma paced or sensed atrial event to the
followingpacedor sensedventrieularevent.
Ventriculoatrial interval (VAI)
Figure 9.7 .shows that ther ventriculoatrial interval (VAI)--also knownas the
atrial escape interval (AEI)---iS the time between apaced or sensed ventdcular
event to the next atrial event. The VAI can be derived by subtracting the AVI
from the LRI (Barold, 1988). The VAI is important in that it provides li nk
between the atrium and the ventricle.
VAI
Figure9.7 TheVAIis definedas the time betweena pacedor sensedventricular event to the
nextconsecutive
atrial event.It canbe derivedbysubtractingthe-AVl
fromthe LRI.
Postventricular atrial refractory period (PVARP)
The PVARP,as shownin Figure 9.8, is an atrial refractory period following a

paced or sensed ventricular event. The PVARP is designed ,to prevent the atrial
channel from falsely sensing a ventricular signal and inte~reting it as an atrial
signal. The PVARP’sprogrammed interval is usually s~t longer than the
retrograde ventriculoatrial conduction,time in order, to prevent the ~trial channel
from sensing retrograde a~ial depolarization (Barold, 1988). This interVal Can
either be s6t at the factory or p~ogrammedby the physician and is typically
300-350 ms.
PVARP ~
Fi~9.8 The PVARP

is an atrial refractory period following a paced or sensed ventricular
~v~nC
Total atrial refractory period (TARP)
T~e TARPrepresents the total amount of time that the. atrial channel is
r~fract0ry. It Consists of two separate timing intervals previously discussed: The
TARPbegins witha paced or sensedatrial event and extends through the AVI.
¯ The atrial sensing amplifier is always refractory for the duration of the AVI.
Finally, ~the TARPends with the completion of the PVARP.Therefore, Figure
919 shows that the TARPis equal to the sum of.the AVI and the PVARP.The
d~u’ation of the TARPdefines the shortest possible upper rate limit.
PVARP ~
Figure9.9 TheTARP is the sumof the AVIand the PVARP.

It represents’the total amountof
ti/~. that tl~ atrial channel
is refractory.
Summary
Figure 9.10 summarizesall of the timing intervals that have been covered in the
chapter.
9.2.2 DDD pacemakers
A DDDpacemaker senses and paces both the atrium and the v~ntricle. A simple
DDDpacemaker can be made by taking a VVI pacemaker and adding an atrial
channel (Bernstein et al., 1987). Indoing so the simple DDDpacemaker possesses
six timing intervals: the LRI, the VRP, the URI, the AVI, the VAI, and the
PVARP.
_:/~ ..~e. atrial, .and ventricular channels ofa DDDpacemaker are, intimately
fifiked and ~the events in.one channel influence theother (Barold et .al.,. 1989). For
example, suppose the ~trial channel has just paced theatrium or sensed an atrial
event. Nowthe AVI begins. Whenthe AVI timer expires, ifno~QRS complex has
been sensed, the pacemaker will deliver a ventricular pulse. Following

ventricular activity, the VAI begins. If no P wave is detected before the
completion of the VAI, the pacemaker will deliver a pulse. Otherwise, if a P
wavewere detected, the atrial channel iS inhibited. Figure 9.11 shows the basic
flow of events in a DDDpacemaker. Figure 9.12 shows all the intervals of a
DDDpacemaker.
The VRP and the TARPare employed to prevent timers from resetting
incorrectly. If a pacemaker does not have a separately programmable URI, the
TARPwill function as the URI.
Interval Abbr. Starts Ends with: Purpose ....

with:
Lower rate I LRI PotS ¯ Next P or S Sets the minimal
interval ventricular ventricular numberof. beats per
event event minute ,
Upper rate URI P ors Next P or S Sets the max,.:’real
interval ventricu!ar ventdcular numberof. beats per
event event minute.:
Ventricular VRP P ~or.S Timed out Prevents crosstalk,
refractory ventricular oversensing, and
period event undersensing
Atdoventricular AVI P or S atrial Either a S Mimics AVconduction,
interval event QRS complex analogous to P-R
oraP ¯ interval. Provides dme
ventricular for ventricle to fill
beat. .~ following an atrial
contraction.
Ventdculoatrial VAI P or S P or S atrial . Ensures an atrial pulse
interval ventricular event following a ventricular
eveiat~ r pulse.
Postventricular PVARP’Pt~rS"..... ’ ’ Timed ou~ Ensures atrium doesn’t
atria,1 refractory ventricular ~ ~ falsely sense
period " event ’ .~ ventrieular activity
Total atrial TARP P or S atrial Completion Ensures atrium doesn’t
refractory event of PVARP falsely sense
period ventricular .activity
Figure9.10Thistable lists all the timingintervals fromthe chapter.’:P"= paced,"S"= sensed

and’q’imedout" = intervalis a fixedamount
of timeandexpiresonlyafter the timeelapses.
9.2,3 Additional features of DDDpacemakers
Ventricular blanking period (VBP) and ventricular,safety pacing

(VSP)
The VBPand theVSP are two dining intervals used-to help prevent crosstalk and
are incorporated into-the current atdoventdcular interval (AVI). ~Grosstalk’-in
electromagnetics is the ,influence-of one signal onanother. Similarly, in cardiac
pacing, crosstalkis the incorrect:sensing 0fone channel by another, Thisoccurs
LOGIC FLOW AND TIMING DUGRAMS 223
whenthe pacemakerstimulates the atrium and the ventricular channel incorrectly

senses this signal as a spontaneousventricular pulse.
Figure 9.13 shows that the VBPis a bd.ef 10--60-ms interval that begins with
the release of the atrial stimulus and continues for a brief period after the atrial
output pulse. The ventricular blanking period can be thought of as an absolute
ventricular refractory perio& In some more sophisticated pacemakers, the
ventricular blanking period automatically adjusts based on the .programmedatrial
output levels and ventricular sensitivity.
Atdum
sensed
expired
Figure 9.11 Flowchartof events in a DDD pacemakerexcludingrefractory periods. Suppose

thgt ~a ycntricle pulse has just beendelivered,the pacemakerwatchesthe atrial channelfor a
~[ibnt/a/ebus~P’~wav~? ’if, the VAI~imes"out,the p~eer~ei|~)ers’~ paei~ng-p/d~to ~th~a~m~
0therviis~;,~the atrial ’ou~tput’is inhibi~ed.The i~ac~m~/’no=w:ffatch~si?theventricle ft~a
spontaneousQRScomplex,If it is detectedthe ventrieular outputis inlfi~ited; otherwisethe
pacemakerderiversa pacingpulse.
AS VS AP VS AS VP AP VP
AVI
PVARP
TARP I I I I I ’t i
VAI I I ~\\\\%~ I I I
VRP
URI I I i "i I ,1 I
LRI
Figure 9.12 AS= atrium sensed; VS= ventricle sensed; AP= atrium paced; VP= ventricle
paced;stripedboxes= interval terminated earlydueto spontaneous
cardiacactivity. Aninve.rted.P.
waveor QRScomplex symbolizesthat it wasinitiated by the pacemaker. Thefirst sensedatrial
eventinitiates the first AVI.Sincethe first QRScomplexis spontaneous,
it causesthe first AVI to
be prematurelyterminated,andit also causesthe first VAIto begin.Atthe completion of the first
VAI,an atrial pulse is delivered.Dueto the spontaneous secondQRScomplex,the secondAVIis
prematurelyterminated.ThesecondVAIbegins; It is terminatedearly dueto the spontaneous P
wave(the third P waveabove).At the endof the third AVI,a QRScomplex is paced,since none
weredetected. Thethird VAItimesout, anda P waveis paced.At the completionof the AVI,a
QRScomplex is paced,since noneweredetected.
Following the VBP comes the VSP period. It encompasses the next
60-120-ms of the AVI. During the VSP period, any signal (crosstalk, QRS
complex, etc.) sensed by the ventricular channel will not inhibit the pacemaker.
Instead, the sensed signal will initiate a pulse to be delivered by the pacemaker.If
the sensed signal were a QRS-complex,the delivered pulse will fall in the
refractory period. If the sensed signal were indeed crosstalk, the AVI.will be
abbreviated due to the early release of the QRScomplex. Once the VSPperiod is
complete, any subsequent sensed signals will inhibit the pacemaker’soutput.
Figure9.13 TheVBP.and the VSP~~a~e..~wo timingintervalsincorpo~a.te~l,into the A.~LT.he

VBPi~ an absolutebl~ngperiodin’:~e first half Of the AVI,T!3eVSP~s tnc0rporatexlinto me
secondhalfofthe AVI. ’,
The advantages of using a VBPand a VSP, as opposed to a long VBP, are

that it helps alleviate undersensing by the ventricular channel. Therefore, the VSP
optimizes the ventricular sensing by keeping the VBPshort.
Hysteresis
Hysteresis is not a feature exclusive to DDDpacemakers, it can be incorporated

into any pac~makermode.Hysteresis occurs whenthe heart’s spontaneous rhythm
is greater than the LRLIn other words, as the spontaneous rate drops below a
preset limit, the pacemakerbegins pacing at a defined higher rate until the heart’s
spontaneous rhythm is at that rate; at Which point the pacemaker stops
stimulation. For example~ if the heart drops below 50 bpm, the pacemaker will
kick in and begin pacing at 70 bpm~Once the heart star/s pacing at 70 bpm, the
pacemaker’s output will again be inhibited,
~. One potential danger is that if the pace’d beat were to .travel retrograde
through the AV’nodeandconsistently capture the atriumethe rpatient would tend
to be locked into th~ relatively rapid pace.
Separately programmable URI
Another additional feature of the DDDpacemaker is a separately programmable

U.P,,L :In l~t.,cemakers without this feature, _the TARP
functions as the upper rate
i~erval (URI), The advantage of having a separately programmable URI,
provided that the URIis longer than the_ TARP,is that more sophisticated upper
rate response algorithms are available. These are .discussed inthe following
s~tion. ~.
9.2~4 Upper rate response of DDDpacemakers
Sincei:~arly~iin .the chapter, the upper rate, interval has been an integral timing
interval in many pacemakers. Brat, how does the pacemaker respond wben ~e
atrium beats faster than the programmed upper rate? There are a number of
algorithms used, none of which are ideal.
The two methods discussed here depend on the complexity and sophistication
of the pacemaker. The fixed ratio block method uses the AVI and the PVARP,to
define the upper rate li~i’t. The Wenekebach method has a separately
programmableupper rate limit, which gives these pacemakers a more desirable
upper rate response.
zxed~ratla ,.block
The fixed-ratio block method is the simplest way fora DDDpacemaker to

control the upper rate limit. As the atrial rate continues to increase, P waves
occurring within the TARP(remember that the TARPis equal to the PVARP
plus the AVI)are ignored or blocked. The degree of block depends=onthe atrial
rate and where the P wave occurs in the pacemaker timing Cycle (Barol~, 1988).
Figure 9.14 is a simplified diagram illustrating 2:1 fixed ratio block. Note that
~ r every, two spontaneous atrial events a single ventricle beat is paced. As. ~e
al raie tongues ~tO incre~e, moreand niobe P waves ~get bi0ck~d, even~y
leading to n:l fixed ratio block.
AS VP AU AS VP AU
~ AVI ~ PVARP
Figure 9.14 S = sensed; P = paced; U = unsensed; inverted QRScomplex= QRScomplex

i~tiated bythe pacemaker.In’this diagram,the sinus nodeis pacingat a constant,rapid rate. The
first P waveis sensed,this eventinitiates an AVL Atthe completion of the AVIthe ventricleis
paced.ThesecondP wavegoesundetected,or is blocked,since it fallswithin the PVARP. The
third P waveis thendetected.Notethat the ventricle beats oncefor everytwOatrial beats, this
represents2:1fixedratio block.
Wenckebach pacemaker response
Figure 9.15 shows that in order for’a ~paeemaker to implement th6 Wenckebaeh
type of an upper rate response, a sep~ately programmableURI is necessary. In
addition, the URI must be programmed longer than the TARP. In these
pacemakers,as the atrial rate increases; the AVIis lengthened so as not to yield a
ventricular pacing pulse prior to the end of the upper rate limit. As atrial rate
increases further, and P waves begin to fall within the PVARP,fLXed-ratio block
then occurs. The amount of time that the AVI is lengthened is equal to the URI
minus the TARP. ¯ ~
The advantage with the Wenckebachresponse is that it avoids the sudden
reduction of ventricular rate (which commonlyoccurs in fixed ratio block).
addition, this methodalso helps maintain some degree of AVsynchrony at higher
atrial rates.
AS VP AS VP AS VP
~ b.\\\\’l k\\\\\xl k’NL~\’ %N.~

V/~/A,"/////////////////A
~ AVI ~ URI
~ PVARP ~ Wait
Flgu 9A5S = sensed; P = paced, ExampleofWenekebach t~pper rate response. Note that
as the atriumbeginsto speedup, the AVIis extended~so
that aventficularpulseis not delivered
beforethe expirationof the URI.
9.3 REFERENCES
Barold, S. S. 1990. Management of patients with dual chamberpacemakers:central role of the

pacemaker atrial refractory period. Am~CollegeCardiol. 5(4):
Barold, S. S. 1971. Clinical significance of pacemakerrefractory periods. Am.J. Cardiol. 28:
237.
Barold, S. S. 1988. NewPerspectives in CardiacPacing. Mt. Kisco, NY:Futura Publishing.
Barold, S. S., Falkoff, M. D., Ong,L. S., et al.. 1989. Function and electrocardiography of DDD
pacemakers. In S. S. Barold (ed.): ModernCardiac Pacing. Mt~ Kisc0, ~Y! Fut~ira
publishing.
Barold, S. S., Belott, P. H. 1987. Behavior of the ventricular triggering period of DDD
pacemakers. PACE.10: 1237.
Barold, S. S., Carrol, M. 1972. "DoubleReset" of demandpacemakers.Am.Heart J. 84: 276.
Benchimol,A., Ellis, J. G., and Dimond,E. G. 1965. Hemodynamic consequencesof atrial and
ventricular pacing in patients with normaland abnormalhearts. Am.. J. Med.39:911.
Bemstein, A. D., Carmen,A. J., Fletcher R., et al. 1987. The NASPE/BPEG generic pacemaker
code for antibradyarrhythmiasand adaptive-rate pacing and antitachy-arthythmia devices.
¯ ,~ACE. 10:794.- ¯
F~ S., Hayes, D. L., Holmes~D. R. i993. A pra¢iice of cardiac" pacing. ~3rd Ed. Mt. Kisco,
~’, NY: Futu/aPublishing. ........ ¯ ~ ....
H~kell, R. J.,/ilid:Freneh, W.J. 1986. OptimumAVinterval in dual chamber pacemakers.
PACE~°9:" ~670..
Le~ine, .P.A. ~198,5. Normaland abnormalrhythmassociated with dual-chamberpacemakers.
Cardiol. C[in. 3:595
Levi~p.A. 1983. P0stveritricular atrial refractory periods and pacemakermediatedtachycardia.
: ’~:ChTi.~Prog.
Moses;H::W.19~91-.A Practical Guideto CardiacPacing.Boston:Little, Brown.
Ol~on~W.H.~Goldrey~¢r, R. N., and Goldreyer, B. N. 1987. Computer-generateddiagnostic
diagram~for pacemakerrhythmanalysis/rod pacing systemevaluation. J. Electrophy~li~1:
¯ 376=38%
~inger; L, Kupersmitli, J: (eds.)1993. Clinical Manualof Electrophysiology. Baltimore’:
i~Williams&Wilkins:
9.4~ INSTRUCTIONAL OBJECTIVES
9.1~ i ~fine and illustrate the followingterms: LRI, URI,and VRP.

9.2 E~plainthe significanceof the refractory period.
9.3 Define and illustrate the following terms: AVI,VAI,PVARP, and TARP.
9.4 Withoutlooking at Figure 9.11, drawa flowchart for a simple DDD pacemaker.
9.5 Give someadvantages ~ ~’sing a VBPanda NSPas opposed to a long VBP.
9.6 Explain whenthe AVIis prematurelyterminated.
9.7 Give an advantageto having a separately programmable URI.
9.8 Explainthe differences betweenfixed-ratio block and Wenckebach response.
10
Logic Implementation
Surekha Palreddy
A variety of implantable devices supplement or replace impaired body functions.

Artificial pacemakers are the devices used to stimulate an impaired heart to
maintain the steady pumpingaction needed to sustain life. Such devices can be
implanted in patients for ten or more years and function from a single battery.
The failures of early pulse generators indicated a need for reducing the
number of manually soldered electronic interconnections. Size was also a
constraint, limiting the number of discrete components that could be used.
Functions such as programmability could not be implemented and :high power
consumptionof the discrete componentswas another limitation that shortened the
life of the pulse generator battery. These problems were overcome with the
developmentof miniature highly sophisticated integrated circuits. All ~the present
day pulse generator circuits are composedof miniature integrated circuits and a
small mix of discrete components.
The microelectronie tec.hnology that has revolutionized the computer
industry has also revolutionized the pacemaker industry. The semiconductors
used in pacemakers allow handling of complex information in a small space at a
relatively low cost with little expenditure of energy, a high degree of reliability,
and little generation of heat.
10.1 MICROPROCESSOR-BASED PACEMAKER UNIT
Microprocessors are the devices which incorporate necessary electronic

components to perform arithmetic calculations with the small size needed for
implantable devices. Someof the microprocessor chips which are designed for a
specific application differ from standard microprocessors to someextent and are
referred to as microcontrollers. However, the distinction between the
microprocessors and microcontrollers is not very clear and a microprocessor-
based pacemaker is often referred to as a microcontroller. Microprocessors are
designed with the capability to accept data from various body sensors, analyze the
data, and generate a response appropriate for that particular analysis. This
property greatly erthances the capabilities of microprocessor-based implantable
devices. But the relatively large power consumption required to operate such
devices makeit impossible to use them for battery-operated implantable devices.
This problem is solved by using custom digital designs implemented in CMOS
technology, which has a very low current demand.
LOGIC IMPLEMENTATION 229
Control
Unit
Programmability I
~xternal
&telemetry programmer
~ 10.1 Functional block diagram of a microprocessor-based pacemaker. RAM and ROM

~te :the memory
units to store the parameters
andprograms to be executed~
Analogsignals fromthe
~nsorsare conyertedinto digital formby the ,ADCs.DACs generate a stimulationpulse. The
~ropro~essor
is ~sointerfacedwith the telemetryunit to provideflexibility in programming
the
~~ execution algorithw~.
.... ~ This :chapter describes the logic implementationof a microprocessor-based
~actn!aker. DDD,the most versatile modeof the pacemakers, is ’selected as an
~ple to explain the concepts. The components identified as the digital unit in
~igure 10..1 will be discussed in greater detail here. Theconcepts of certain safety
~tures ~that are essential for a pacemakerare also presented.
PACEMAKER REQUIREMENTS
The basic requirement of a pacemaker isto pace the heart when needed. Other
functions "include~. the ability to sense-the cardiac signals. Multiprogrammability
adds flexibility in-choosing parameters of the pacing pulse and also to ~.monitor the
dat~ storage; Somepacemakersare provided with diagnostic capabilities that can
be’~sed for".therapy. VLSI technology makes it feasible to integrate alLthese
features of the pacemakeronto a small chip. Someof the basic requirements .of a
pacemaker are:
Basic funct.io~:-.Pace, sense, programmable,diagnostic, interactive
High ~eliabil~i ~O.~5%failures/month "
Adequate lon~ty:i’7=lO years . .
Snu!~ ![ si~: i O:~.thick, 25750 g "
Simple to be p~. grammedb~y a physician ~:
The functions of a pacemaker depend completely on the electroifie eonttol
system. Therefore, selection of electronic.technology that provides the pacemaker
requirements forms the basis~to pacemakertherapy.
10.3 CHOICE OF ELECTRONIC TECHNOLOGY
The electronic control of an implantable pacemakercan be designed using custom

integrated circuits -designed ~specifically for pacemakers,or: microp~essor-based
circuits with custom software, or some combination of these two, This section
discusses the several aspects of these different combinations of electronic

technologies (Hartlaub, 1982).
There are two types of customintegrated circuits: digital (control) circuits
and analog (sensing) circuits. Comparisonof technologies is based only on digital
circuits used for the control. Analog circuits are used for amplification and
sensing functions in pacemakers,but they do not provide flexibility in controlling
the functions such as pulse rate, width, mode,etc.
A customcircuit is described as a digital integrated_ circuit, designed for a
specific application and composedof a collection of logic elements connected in a
unique fashion. The circuit is put together with tens of thousandsof transistors on
a small chip with VLSI teelmiques. The development of a large scale integrated
custom circuit is very time-consuming and expensive. However, these custom
circuits provide multiprogrammability and complex pacing modaiities with
adequate low current drain and excellent reliability.
A microprocessor-based pacemaker .has more flexibility and added
capabilities. Capabilities such as monitoring or storing data~ data processing, and
increased flexibility in functional changes of the software-based system are added
advantages of a microprocessor-based system. Additional functions suCli as rate-
responsive pacing can be madeavailable with inputs from physiological sensors.
While these additional functions are achievable using CustomCircuits, there is
more flexibility and ,:~apacity for future growth in a microprocessor-based
system.
The four alternative combinations of above electronic iechnologies for
implementing a pacemaker have some advantages and disadvantages, as
summarized in Figure 10.2. Custom, random logic-based design has the
advantage of being a knowntechnology~ wit h, adequate reliability, and the
capability to provide both multiprogrammableand physiological pacing systems.
The disadvantages include little or no capability to monitor and process data and
limited flexibility for modifyingexisting designs.
~Thecombination of custom random, logic to control pacing fu~nctions and a
commercially available microprocessor to monitor and process data would give
adequate reliability but is severely limited with excessive current drain and
complexity. Also, there is limited pacing flexibility as the pacing,control:resides
in the customcircuits.
Alternatives Advantases Disgdvantages ¯ ~

Customrandom Knowntechnology Minimal p~ssing
lo~iecircuit Adequatel~¢reliable IAmi~’ted .... ¯ ’ ,,
flexibilit~
Combination Monitoringand Limitedaddedfunctions.
customrandomlogic data processing , for.adde.d.guL’~.m, , i
~a.cing functions) Basicpacing Complex,mi~ltlpl.eChips
A~’~lable’microprocessor functionsreliable " ~. ,. Lirm’tedpacingflexibility
(monitor/dataprocess)
Available Hardwareconstant Needssomecustomcircuits
microprocessor ’ Highcurrent drain (short:
pacemaker longevity)
Custom All functionspossible , ~ Reliable~
microprocessor ’ (Atlowcur~etit ’~’~’’~B~g~expens~ve’
&ain) " ~::: d~mgn"
..... ’ ’:
Hardwareconstant program
Figure10.2 ~e advantagesanddisadvantagesof the four different:combinations

of electronic
technologiesfor implementing
a pacemaker;
A commercially available microprocessor with no custom digital circuits is

impractical with high current drain makingit impractical to operate for a battery
operated implantable device. However, the current-day technology is providing
the meansto manufacture low current drain microprocessors to some extent.
A custom microprocessor designed specifically for a cardiac pacemaker
would have an optimized architecture as well as an optimized instruction set to
maximize the computational power in the pacemaker application. The advantage
of this method includes the maximal computational power with minimal current
drain, and the detailed architectural knowledgehelps in simulating the operations
to demonstratereliability.
10.4 PACEMAKER~SYSTEM ARCHITECTURE
The digital portion of an integrated circuit-based pacemakerperforms the timing,

memory, and analQg interface functions and logi~ decisions of the pacemaker
system. For a technologically .advanced pace~~er these-functions are of
sufficient complexity.to ~equire, if not demand, a micr0p~essor-based system in
order to be consistent with a practical design concept. An advanced pacemaker
system derived from a fixed, hardwired logic concept is likely to have the
complexity of a microprocessor-based system and the disadvantages of an
infl~xlble, noiaprogrammabledesign concept.
10.4.1 A state machine,based pacemaker
A ~pacemakeris basically a timer that changes its functional states in response to

elapsed intervals or sensed signals. This operation suggests-the application, of a
known~conceptsuch as a state machine, in which the processor movesfrom one
state to the next in response to time,out signals or an externally-sensed signal.
Eaeh~state~ has its ownconditional set of rules that will steer the processor to its
next :state based on the inputs. Figure 10~3 .shows a simple state machine
pacemaker:Each node in the figure.-represents a state of the pacemaker, The pace
timing cycle starts at state 0 which is "Start", The state of the pacemaker is
changedto either state 1 or state 2, dependingon the sensed wave. If a P waveis
sensed, the state of the pacemakerchanges to statel inhibiting atrial stimulation
pulse, and if an R waveis sensed whenin state 1, the processor moves~tostate 2~
inhibiting .the ventrieular stimulation pulse. If the R waveis not sensed~instate 1,
the processor will provide a stimulus to the heart after the "ventdcular0refractory
period exeeeded’~, signal is set and movesto state 3. Similarly, - atrium is paced
whenP waveis not sensed and atrial refractory period is expired.
~, This state machine can be~ implemented: wittha programmablelogic :array
(PLA). A PLAcan be visualized~as a device that will enable the programmer
force.any desired ~set of output, conditions in responseto any set ofdefined iaput
conditions. ~
I0.4~2 :Microprocessor.based system architecture
Atypical microprocessor,based pacemaker has a CPUas the cOrer of the system to

control the overall operations~ of .the. pacemaker~system~ :The coded program
instructions are stored in ROM (read-.only memory), ~while the temporary data
used during system operation are Stored in RAM(random access memory).
Initialize refractory
periodtimers
P-wave
sensed R-wave
refractory
period exceeded
Figure10.3 Asimplified state-machinepacemaker.Theprocessorchangesstate in responseto

elapsedintervals andsensedsignals. Eachnodein the diagramrepresentsa state,andeverystate
has its uniqueset of rules to steer the processorfromonestate to anotherbasedon the inputs.
FromSchaldach,M.1992.Electrotherapy of the Heart,Berlin: Spfinger-Verlag.
A microprocessor controls the response of a pacemaker to various external

physiological events and internal timer events. It is customized for use with the
limited energy supply available from a battery by activating internal logic
componentsof the processor only in. response to selected .events .and rtO perform
an operating routine corresponding to the "wakeup" event. External events are
sensed to derive signals to indicate occurrences such as atrial or ventricnlar.beats.
Internal timers may awake the processor to generate output pnlse commandsand
to sense external events during selected physiological intervals.
Figure 10.4 shows the general componentsof an 8-bit microprocessor-based
pacemaker. It comprises a ROM to store the instructions of the l~rogram :to be
executed and various programmable parameters, a RAMto store ~the various
intermediate parameters, timers to track-the elapsed intervals, a register file to
hold intermediate values, an ALUto perforfla.the arithmetic calculations, and
other auxiliary units that enhance the performance of a mieroprocessor~based
pacing system.
The.size of ROMand RAMunits are selected based.~on the~reqnirements of
the algorithms and the parameters, to be stored. The.numberof registers in the
register file are decided based upon the complexity of computation and the
required numberof intermediate values. Timers of different precision are used to
measurethe elapsed intervals.
The two main componentsof a microprocessor are the datapath and control:
The datapath performs the arithmetic operations and the control directs the
datapath, memory, and I/O devices to execute the instructions of the program.
The hardware componentsof the mieroprocess0r are designed to execute a set of
simple instrnetions. The complexity of the in’struction set determines the
complexity of.datapath elements and controls of the microprocessor.
LOGIC ~ IMPLEMENTATION 233
I watchdOg
timell I Interrupt handle~
I~
I Flags
ROMi
I Wakeup
I Pa~
II
I I Register
file
. ;amcounter
~!I InstrUctionregister IIntemalI-3..
~
clock ~1
I’ [Clock
. . control
I Backup ’I Extema
controller
. _ I II Digttall/O
I c’°c.l I r,sI
I
/ / tiiillll~
. ’ I Sens~rsll
Figure~ 10.4 Functional block diagramofa micml~rocessor-baSed pacemaker.Memory unit:
ROM i~ Usedto store the instructions of the program,~ to store the various programmabIe
parameters,
timersto keeptrackof the elapsed)ntervals,
registerfile to Store~ntermediate
values,
an ALU to performthe arithmetic calculations, and’otherauxiliary units that enhanc~the
performanceof a microprocessor-basedpacingsystem.
A microprocessor may be provided with a fixed operating r~0utine or maybe

~rovided with the cal~ability of actually introducing program changes in the
l~|~,ante d device. Th ~ instruction set of the microproces~6r, the size of the
~gi~tef files, RAMandROMare selected based onthe performance needed and
the’~of the algori .thms" used. For the applications such as p~cemakers,in which
~6ye~hi algorithms ean. be loaded and modified, ~Red~ed ihstruction Set
Co~uter (RISC) architecture’ is: useful. RISCarchitecture offers advantages
~S¢ it can be opt~iled to r~duce the instruction cycle which: in turn reduces
~li~/~indme of the program and hence the current drain. The simple instruction
~&~ehitectur e of RISCand its simple hardware can be u~d t6 implement"any
~
~fithmwithout much difficulty. Since ~ize is also amajor considetation,~an8
flit ~croproce~sor is used for the purpose. As most of th~ arithmetic Calculations
are based on a few parameters and are rather simple, an accumulht0r architecture
is used to save bits from specifying registers. Each instruction is executed in
multiple clock cycles, and the clock cycles are broadly classified into five ~tages:
~i~ally,:an~opfimal instruction set ~c~tectui~e is sel~tedbase, don th6aigofi~

t6 be implemented~d also taking into Consideration the special needs:Of a
234 DESIGN OF ~CARDIAC PACEMAKERS
microprocessor based pacemaker. Figure 10.5 shows that for RISCarchitecture,

the instructions are broadlyclassified into Load/store instructions, Arithmetic and
logic instructions(ALU), control instructions, and special purpose instructions.
Load/storeinstructions
Load re$ addr Loadsa valuefromRAM into a resister
Load immediate Loadsa number specifiedinto the accumulator
Loadtimerre$ timer ~LOads a ~valuefroma:re~sterinto a timer
Store re[ addr Storesthe valuein a resister into RAM
Storetimer re$ timer Storesthe valuein timerfoa resister ¯ .
ALU instructions
Add Addavaluefroma resister to accumulato, r
Sub re$ Subtracta contentsof a resister fro.~ accumulator
Mult re$ Multipliesthe valuein a resister withaccumulator
Increment re$ increl~entsthe valuein regis~r by one: :
Decrement rel~ Decrements the valuein a resister byone
~ontrolinstructions
BGErel~l re$2 Branchwhen(re$1)>_(re$2)
BLEregl reg2 Branchwhen(regl) ~ (reg2)
8LT regl reg2 Branch,when(re$1) < (re~2)
lump addr lump,to ’~e.~ s~eih~laddress
~pecialinstruction
~LEEP : - Puts, the microprocessorto sleep
Figure10.5. Asimpleinstruction~et: for:RISCmachines.
Instruction format.
The instruction format is decided based upon the total numberof instructioiis in
~e instruction set. ~:Th, e instructions fetched from memory,are 8 bits long, Each
instruction ha~ an Op~odefield(2 hits),, a register~ specifie~field (3-bits), a~nda
bit immediate,field."The opcodefield indicates ~e ~ype ofthe inst/’ucti0n that was
fetched. The’ ~egister specifier indicates. ~e ~add~es6of the reglsterin the r~gister
file on which the operations are pefformed~ The, immediate field i~: Shift~and
sign extended t6 0~tain :the address, of the memory.location in load/store
instructions, Similarly, in branch ~and jumpinstructions; the Offset field i8 hsedto
calculate the address~of the memoryi~ahbt(the,.9ontrol needs to. be transfe.rr~ ed
tO. ~e fgrmat of the instruction, set., ,chosen to implementthe AViate-respotlsi~ee
pacemakers is discussed in the Al~ndix~,, ’ .... ~
Register file , , .
A regf~er fde is a collection of r~isters in which any register can be read from
or written tO by s~ecffying the tiiJrnber of the register inth6 tilde. Base.d ~on’the
requirements of the design, the, s~ze of the register file is d¢¢ide~.’ Fgr the
purposeg of implementation ofa phce~aker algorithms, a registe/fi|~ of eight
registers is sufficien~t, with~ three .~pecial:purposeiegisters (0-2) ~d. fig~ ge,fi’era!
purpose registers (3-7), as showii in Figure’ 10.6. Register "0" always holds the
value "zero". Register ’T’ is dedicated to the sensed/paced flags. Register "2" is
an accumulator in which all the arithmetic calculations are p~rf~ed~.T~e
read/write address port provides a 3-bit address to identify the rel~i~ter:being
r~ or written into, The ~write ~ta PO~provides. 8.-bit data to he written into ~
registerseitherfrom ROM/R~or ~rs~ Read.~e.n~bie.~0ntr61~ .when assert6d
LOGIC- IMPLEMENTATION 2 35
enables the register file toprovide data at the read data port. Write enable control
enables writing of.data being provided at the write-data port into a ~register
specified by the read/write address.
ROM Read/write Registerfile

Instructions Instruction
Programmable Zero
~meters PaceFlag
~RAM ~
Intermediate -
Read
AVtimer
Pacetimer
Clock Write
enable enable
Figure 10.6 A sebelii’atie diagram of the register file,.timers and ROM/RAM. Three registers of
the register file ~ dedicated for Special purposes and the Test are general purpose registers. An
instruction register is used to load the instruction fetched ~frommemory.
Timers
Generally, two or more timersare required to implement any algorithm for a

pacemaker. For example, ~e~~day-be used to measure the AVinterval and the
other for the pacing interval~ ~e timers are read and written into just as any
other memorylocation. The timers ~re provided with read and write enable
controls.
Arithmetic logic unit ~(ALU) , , ..

The arithmetic logic unit is an important componentof the microprocessor. It
performs the arithmetic operations such as addition, subtraction and logical
operations such as ANDand OR. The instruction format of ALUinstructions
consists of an opcode field (2 bits), a function field (2 bits) to indicate
function that needs to be performed, and a register specifier (3 bits) or
immediate field (4bits) to provide an operand. ~,
Datapath, ,
The hardware components discussedabove constitute~: the impo~’tant components

of a datapath, There~ are,some, special,,, purpose registers such~a~r~agramcounter
(PC) ,to: hold .the~0addressof,~the instruetioni,being~,~fetch~d~£rom ROM ~and
instruction register(IR) to hold the ins~ction,that is fetched ~for fu~rther decoding
and execution. ThePCis incre~mented in each instmetion~fetch stage to ~feteh
236 DESIGN OF ~CARDIAC PACEMAKERS
sequential instructions from memory, In the case of a branch or jump

instructions, the PC multiplexer allows to choose from the incremented PC value
or the branch or jump address calculated. The opcode of the instruction
fetched(IR) is provided to the control unit to generate the appropriate sequence
control signals, enabling data flow through the data path. The register
specification field of the instruction is given as read/write address to the register
file, whichprovides data from the specified field on the read data port. One port
of the ALUis always provided-with the contents of the accumulator and the other
with the read data port. This design is therefore referred to as accumulator-based
architecture. The sign-extended offset is used for address calculation in branch
and jump instructions. The .timers are used to measure the elapsed interval and
are enabled to count downon a low-frequency clock. The timers are read and
written into, just as any other memorylocation. Figure 10.7 shows-the datapath.
Clocks Pulse
1 MHz Control¯ I/O portsI Atdalsensed/
100 Hz
ventriclesensed
Program
counter Register
file
Read Wdte
enableenable
Zeroflag
PaceInterval
timer
Wdte
Clock
Figure 10.7 Datapath and control of a custom-designedmicroprocessor-basedpacemaker

implementingAVrate-responsivealgorithm.
Control=
In a multicycle implementation, each stage of instruction execution takes one

dock cycle. Since the datapath takes multiple clock cycles per instruction, the
control must specify the signals to be asserted in each stage and also the next step
in the sequence. This can be easily implementedas a finite state machinethat is
represented graphically in Figure 10.8,
A finite state ,maehine~eonsistsof a;set ofstates and directions on howto
change states.~. The~direetions:are defined by a ne~t-state function;which mapsthe
current stateand the !inputs to a newstate. Each stage also indicates.the control
signals that need to be asserted. Everystate inthe finite state machinetakes one
clock cycle. Since the instruction fetch and decode stages-are commonto.all the
instructions, the initial two states are commonto all the instructions. Step 3 to
step 5 differ dependingupon the opcode. After the execution of the last step, the
finite state machinereturns to the fetch state.
State0 State1
Jump
Bmnoh
State State State
address
Fi~r~ t0.8 Finite state machine diagram indicating various states:of instruction types. Load
in~h3~cfign:takes 5 clock cycles whereas store-and A~.~ instm_ ctions take 4 clock cycles. Branch
instructionsare the shortestandare completed
in 3 clockcyc|e~. .
:A finite state machine can be implemented with a register ’that holds the
Current stage ~ind a block of eombinationaI16gicSuch as a PLA~it determines the
datapath sign’s that need t,o be aS~6rted as well as the next state. A PLAis
des6dbed as an array of ANDgates f~llbwedby an array of ORgates.. Since any
function can be computedin two levels of lo~ic, the two-level logic 0f PLAis
~s~~fot generating e~ntml signals. ’ ’ ~"~ ~:~ i ’’ " * ’ ¯ ~ .
~:’!,~ ,~e occurrence of a w~ehp event initiates a sfor~doperating routine
e~Sponding to the e~nt; In the time imervailbetw~n a~completed operating
r6~ne and a next wakeupevent; the~ internal logic components of the pr0ces~b~
ar~;’lieactivated and no energ~is being expended:in l~efforming an operating
r6iatine.
10.5 DUAL CLOCK CONTROL OF MICR(~PROCESSOR
Artificial pacemakers, implanted in patients for long periods of time, are

required to function from a single finite source of energy, usually a battery.
Microprocessors can greatly enhance the capabilities of implantable
pacemakers at the expense of po~er requirements. Even though the low current
drain demands of CMOS technology has made .it possible to implement custom
designed pacemakersusing microprocessors, the current consumption increases as
the frequency of the circuit operation incre~ses~ Therefore. the ~gher frequency
portions of the circuits must be kept to a minimumand made active only when
required.
A microprocessor controls the response of a pacemaker to ~arious external
physiological events and internal timer events. Itis often desirable to provide
different " clock frequencies to various timers, to control the resolution of the
timers. A single clock signal cannot i pro~ide an. optimal frequency for the
microprocessor operation and also the individual timers, The clock frequency
used in such systems is usually too high :for the time~s and too low for the
microprocessor, makingit slow. Typically~ a single external clock, of 100 kHz is
used for such systems, with a clock divider t0 generate flocks of different lower
frequencies for various timing signals. ~iSf~equency division of the external
clock signal is a waste of power. Also, ~e microprocessor operating atthe
frequency of the external clock would be sl0w and introduce delay in responding
to external stimuli. Often a frequency multiplier is used to generate a higher
frequency clock from the external clock to Operate the microprocessor.
.~ In order to develop a ~croprocessor-based pacem~aker with maximal
processing capability and minimal power requirements, a dual clock control is
employed (Russie, 1991). In a dual clock control system, a free running low-
powered clock is employed to perform the basic timing functions using timers;
and a secondhigh power clock is turned on andoff when required t0 ~perform
complex computational :functions 6f~&e :microprocessor as shownin Fi~e 10.9.
Since the events of interest in a cardiac cycle occur at a low frequency, the
~croprocessor can be deactivated dufi~ ~i~e phases. The dual clock control has
a~apt~d the miC~oprocess0r,bas~ ~ac~er fo~ use with~the limited energy
Supply~available from a batter~ by activating internal logic comptnents of the
processor only in response to sele~t~ ev~n~andto perform an operating routine
corre~p6nding to the "wakeup"eg~nt~ ~:’ ~ ~’~ ~ ~ ~ ~ ’~
The dual clock,controlled microprocessor has two Clock,s operating at
different frequencies and a clock c~ontrol unit to ~Synchroni~ethei~ activation. An
external cl6ck of kHZ di~,ided by g ci~ck divider int6 severai lower
frequencies "iS"used as requir6d by! thetimer~ A seabed dock of I’MHz is
c0~eCied betwe~fi the cld~k ~6nt~ol unit ~nd mic-r0pi0~essor~’ f0r providing a
dock signal to the microprocessor in the "wake up" ~state. ’This improves the
response ttme of the pacemaker to external events by ten ttmes. Typically, th
events that turn on the clock of the micrbprocessor include timing ot/i of one of
the timersl Sensing a ~ardiac 6we~t, or telemetry inte~pts provided b~ the
intemipt !ogi~ unit: The ~Cr0pro~esSor in th6 ,’wake up!~ Stgt~6 e~fite~ the
nece§s~ functions based 0n the inl~uts from timers and several oth~ri~xtemal
~nputs, ~fter proper execu~on of ~e functions required, the m~croprocessor
completed operating routine arid ~ next iWakeupevent, the internal logic

componentsof the processor are deactivated and no energy is being expended in

performing an operating routine.
R~M _I /
ROM ~ Microprocessor
~ Pacemaker [
External Defibrillator
clock
32 kHz
1MHzclock with Sleep"
ON/OFFand
Clockdivider intemalinhibit
~ Intermpt,wakeup
~ i control logic
Sense/telemetry
andother inputs
Figure 10.9 A schematic block diagram showing the microprocessor-based pace ~n~. r system
with dual clockcontrol. Anexternal low-frequency clock(32 kHz)dividedinto requi ~redlower
frequenciesfor timers. Ahigh-frequency
internal clock(I MHz)is activatedin the "Wakeup"
state
of the microprocessor
(Russie,1991).
Russie (1991) described a modified ring oscillator circuit’withinstant 0n/off

control and the capability of maintaining a high state for a preset period of time,
preventing the microprocessor from entering the "wake up, state when the
external timers are being updated.
Figure 10.10 showsthe clock control circuitry. This circuit has three D flip-
flops; and a control gate. The control signals shownare AS (Ad&essStrobe),
STOP-CLK,DS (Data Strobe), START,MCLR,and 8 ms. The 8-ms clock signal
is derived from the 32-kHz clock that has a pulse width of 15/ts, and AS is
derived from the 1-MHzclock of the microprocessor. AS-is connected to FF1 and
FF2 via an inverter. The STOP-CLK and DS signals are connected to the clock if
FF0 via a NAND gate. STARTand MCLR are connected to the reset t~rtninal of
FF0 via a NORgate. The 8-ms and MCLRsignals are connected to the reset
terminals of FF1 and FF2 via a NORgate. The control gate inhibits the clock
wheneither input of the gate goes high. The MCLR is the master clear signal
which goes high whenthe system is reset. The 8-ms signal is a clock which is fed
to the system timer to clock: them at 128 Hz. The clock ctntrol ~eircuit respbCd~
to signals from the microprocessor such as "data strobe DS", "address strobe AS’
and "STOP-CLOCK" and externally generated signals such as "START","8 ms"
and ’~Master Clock - MCLR".
The . "START"signal is turned on when an interrupt occurS. The ’~STOP-
~CK"signal .is generated by the microprocessor after the:sucCeSsful operation
of required functions to turn off the clock:Figure 10,11 sh0wa~the response of
the ring oseillation-based clock of the microprocessor to "START"~and~"STOP2
~LOCK"signals. The 1-MHzclock signal corresponds to the output clock. As
240 DESIGN OF CA~IAC PACE~KERS
shownin the figure, the output of the clock is terminated whenthe "STOP-CLK"
signal goes fromhigh to low.
~ J Jstabl~RCoscillator
ii [ start (in_hibit)
Stop C_J-KDs ~F
To microprocessor
Figure10.10Aschematicdiagram illustrating the clockcontrolcircuit with"Start" and"Inhibit"

control (Russie, 1991). Theflip-flops FFI andFF2providesynchronizationbetweenthe 8-ms
clockandthe addressstrobeAS.
Stop CLKinhibit
Ds I I
Stop CLK \~
Start /
Figure10.11Atimingdiagramillustrating the correlation in the stop clock inhibit, mode

(Russie, 1991). Theou~ut cl~bkis terminatedwhenthe "STOP-CLK"signal goes fromhigh
low.
Figure 10.12 shows the "clock inhibit" mode employed to prevent the
microprocessor from reading the value of the timers while they are being clocked
by a 128-Hzclock. The 8:ms clock is the primary dock to the timers. This signal
is a pulse~one-half, the; width of the 32-kHz clock cycle which occurs every
7.8125 ms, The timers are .clocked onthe failing edge of the 8,ms iclock and the
inhibit circuit is inactive as long as the 8 ms is low. This: is accomplished by
holding FF1 and FF2 in reset states. Whenthe 8-ms signal goes high, the reset is
released. At the trailing edge of the first pulse of ASfollowing the transition
from 0 to 1 of the 8-ms clock, FF1 is clocked triggering Q1. to logic 1. Thus, a
logic 1 is applied to the date input of F’F2. At the second ASpulse~ the output of
FF2 (Q2) goes high, which holds the microprocessor in the address decode state
until the 8-ms clock goes to low. Thus, it is guaranteed that 3 gs will be provided
from the time the timers are clocked until the first .high-to-low transition of the
DS, when the data is written or read. FF1 and FF2 provide synchronization
between the 8-ms signal derived from the 32-kHz external clock and ASderived
from the 1-MHzclock of the microprocessol;
8 msinhibit
1 MHz
AS
8 ms /1/fill//
Inhibit
Figure10.12Atimingdiagramillustrating the correlation in the predetermined

time interval
inhibit mode(Russie,1991).
This dual clock control mechanism in a microprocessor-based pacemaker

offers optimal processing ,capabilities with little power consumption. Also, the
clock divider requires less power to generate low-frequency timing signals from
the relatively-low-frequency external clock.
10.6 ANALOG-TO-DIGITAL CONVERTER
A microproc¢ssor-based pacemaker operates on several analog and digital, inputs

accessed under the control Of the microprocessor and stored~in ~e memoryor
~egisters. The analog signals to be pro¢. essed by the microprocessor need to be
onverted into an~:~appr~priate digital form using analog2to-~digital cof~verters
(ADCs). Several .circuit designs of ADCsusing differeiit technologies are
patented. An,ADC.c0nverter optimized for use in battery-p0wered im~lantable
~levices such as a pacemaker is ciescdbed here. .,~ ’ : ~ , . ~
The ADC6onverteris ,implemented in CMOStedh991ogy to take adV~ge
of its minimalcurrent drain:The circuitry is configured .such that the. Output
signal from the ADCconverter ~presents the analog ihput signal., independeni of
th~ applied clock frequency (Dug~an, 1992). ~ . ~~
Various analo~ inputs ~e sequentially ~Selected and steered to the
microproceSSo/’~bya multiplexer through an~plifier ~dan ADC.Multiplexing
is rinsed to reduce the haiidware required foi’ pr0eeS~ing of ~altg sign’s and
minimize the power requirements. Figure 10.13 sh0w’s the futietional~diagram of
the ADCconverter.
Accumulator
VCO counter
Up ~ f ~ Zero
count
I D~
In
Reset Up Down
V(x)
Eref ~7
CIk
Strobe NDcomplete
In "N"’output
counter
N(x)
Fig 10.13Functionalblock diagramof an ADC

as incorporatedwithin a pacemaker
(Duggan,
1992).
An analog voltage V(x)to be converted into digital form is connected

input Vin to the voltage-controlled oscillator "VCO"through the switch "S 1"
whenit is in the "up" position. The output of.the oscillator is applied to the input
of an accumulator counter, capable of counting "up" or "down". A clock signal is
applied to the "divide by n" circuit in the control logic, whoseoutput is coupled
to throw switch "SI" to the "down" pogition. At the same instant, signals are
applied to the accurfiulator switching it to counting downmodeand reset the "N"
output counter.
This ADCconverter operates in the followingfashion: The unknownvoltage
V(x) is applied to the VCOfor a fixed period of time, Tu,~. During this time, the
accumulator counter is counting up the :output of me VCO~much like an
integrator. The accumulator count builds up at a linear rate for a given voltage
V(x). Tup is dependent upon the clock ’frequency applied and the ’’ counter. At
the end of Tup, the switch "S 1" is movedto the ’down’ position to connect the
input of the VCOto the reference voltage Eref. At the same instant, the
accumulator is switched’~0 the counting downmodeand the ’:~N" output Counter is
reset. The zero flag of the accumulator is set whenthe count reaches zero. The
time required to count the reference voltage back tO zero is proportional to the
average value of the input voltage V(x). While the accumulator is Ctunting back
to zero, the Clk frequency is counted by the "N, output cdunter. Counts
accumulated in the "N" ctt~nter am in ~ digital form and are dimctl~~ proportional
to the initial unknownvoi~age V(x). ~
Since the up count and downcount of an accumulator are equal,
¯ LOGIC ’ IMPLEMENTATION 243
Aup = Adown (10.1)
where the accumulator count is a function of the input "Vin" and the length of the
time this voltage is applied to the VCO.
Aup = Cvco x V(x) x Tup (10.2)
Adown= Cvco x Eref x Tx (10.3)
The effect of constant of scaling of VCOon .~A/D conversion is eliminated by

equaiing Aupand adown. Tii6 ~ total count of the ."N" output counter is given by
the clock frequency Folk and the time taken to count back the accumulator to zero
N(x)= Fcll~ Tx (10.4)
Tupis determinedby the input clock frequency as a function of ~’n," i.e.
n
Tup - Folk (10.5)
From. the above equalities,
- V(x)
N(x) = X Eref (10.6)
The digital output N(x) is independent of the clock frequency, strobe

frequency, and the VCOscale factor. Since .a single VCOis used for both the
analog input and Eref, the effect of the scaling factor of VCOis eliminated. Since
the Sa~neclock is used to clock the accumulatorcounter during the 6otiriting down
m0~e", and the "N,: output, counter forthe Same peri0d,, the effect o.f clock
fre~.~uencyon the digital output of the. Counterindic~tive.6f.~the ampllmde.,of the
inf~iit ~signal is eliminated, Therefore, the Clock used need not :be~of:~high
precision, and can be optimally selected to minimize the drain on ~ the power
spurce of the pacemaker. The key point of implementation of the control logic of
~i~,~C is based on the four:i~it ring counter; which~ :foi~ces the ADCinto one
~d ~hly one of the four p6~sible modescorresponding~tofoui~6utput states: (t)
w~t((2) preset; ~up Count; and (4) downcount: in th e wait modeof th
th~ VCOis turned off by disconnecting the unknownanff reference VoltageS.~ :The
Converterremains in the wait modeuntil a strobe pulse is received to drive it into
#e~t mode. The accumulator counters are preset during the preset mod~¢,Which
one-half of a clock period..
incorporation into implantable devices. ’ The
as minimalcurrent draln and insensitivity to’clock
’. of the ADCd~scribed here, makes it a preferable choice for
10.7 SAFETY FEATURES
Pacemakers are designed with several safety features to enhance :their

performance and improve reliability. Some of the safety concepts such as a
watchdog timer, interrupt handler and battery life estimation circuits are
discussed here.
10.7.1 Watchdog timer
The operating system of a computer controlsthe, various activities of the system.

The main program is usually thoroughly debugged before introducing it into a
system. However,it is not possible to check alternative paths i~ossible under all
operating conditions. :Consequently, potential logi~ faults in the less traversed
paths of the main system might prevent the execution sequence from returning to
the main program. These faults could prove to be fatal if they happened in a
microprocessor-based pacemaker. To guard ag~nst these fatal faults and allow
the system to recover, a hardware timer called the watchdog timer is
implemented in some systems as shown in Figure 10.14. The principle of
operation of a watchdogtimer is discussed here.
Reset time JBegin
II0
interrupt
Figure 10.14 Watchdog timer operation. The~operating system performsvarious tasks in

sequenceandresetthe timerat the endOf eachCycle.When a software/hardware
fault occurs,the
timeout~ignalfromthe timerrequestsa reinitialization of the system.Markers
are updatedwhen
traversedthroughandare usedby the systemto diagnosefaults~ FromKraft, G; D.~andToy,W.
N. 1981,Microprogramraed control and reliable designof smallcomputers,Englewood Cliffs,
NJ:PrenticeHall.
A hardware timer is run continuously, and reset by the maln program

periodically if no unusual event occurs to deflect the main program from the
normal sequence of execution. Whena hardware or software fault occurs, the
~ontrol cannot return to the main program and the timer is notreset. After a
preset period of time, the timed out signal from the watchdogtimerissues a high
priority interrupt ~signal tO reinitialize the system. Theinte~r~, pt¯ enables execution
of the program from a preestablished checkpoint. ’
Even though, the principle of operation of a watehd0gtimer is quite, simple,
considerable attention should be given for: careful integration of the~ timer~ with
the software structure of the system~ The timer should always’be reset during the
normal operation of the program, and a time out signal from the timer should
request reinitialization. The time required for execution of one complete cycle of
the program depends on the number of active tasks on the system and the time
taken for each task. The timer is usually initialized to the maximalcycle time
possibly required by all the defined active systems. In order to check whether a
program.’ segment is being executed at all, markers are introduced into those
segments that get set whentraversed. The main program studies the behavior of
the markers and takes diagnostic measuresto identify if a problem is suspected.
:~.~ The regulations of the Food and Drug Administration require that, whenthe
watchdogdetects a major failure, the implantable device be set in a state that is
safe for the patient. If necessary, that state can be nonfunctional.
10.7.2 Redundant pacemaker system
Redundantbackup systems are essential in any life-saving devices. The redundant
pacemaker system is a simple pacing circuit, which operates in a VVI mode
(Schaldach, 1992). In this mode, the ventricle is sensed and a pulse is applied
whenthe signal is not detected. The redundant circuit is activated, simultaneously
deactivating the microprocessor circuit, whena fault is detected in the operation
of the microprocessorcircuit.~ This circuit provides stimulation pulses at a fixed
predetermined rate.
10.7.3 Interrupt handler
The microprocessors designed to perform several complex operations in a

pacemakerexecute various functions based on the inputs provided under different
conditions and the controls enabled. To prevent the possibility of providing more
than one request to the microprocessor at a time, an interrupt-handling system is
essential to prioritize the requests. Interrupts caused by conditions such as
initiation of the telemetric process and low battery conditions are appropriately
prioritized and served in that order.
In a simple interrupt-handling system there are two interrupt modes in
which the processor can run: an interrupt-enabled modein which if an interrupt
requestreaches the processor it is accepted immediately after the execution of~e
present instruction; and an interrupt=disabled modein which no interrupt requests
are accepted by the processor.
Usually the processor is run in. the enabled mode. Whenan interrupt occurs,
the processor automatically switches to disabled mode and enters an interrupt
service routine. The interrupt service routine is a sequence of instructions
starting at a predetermined location in the memory.The processorexeeutes the
specified routine and returns to resume the interrupted process, simultaneously
switching the processor to interrupt-enable mode. In order’to enablethe ~return of
e0ntf01 after servicing the interrupt to the interrupted procesS; the address of the
instruction thatWasinterrupted is saved in a predetermined~register.
-In the simple two-level interrupt system, the process wilFnot accept any
interrupt signals-While already servicing an interrupt until the ~ serviCe routine is
completed~This might result in losing information about transient interrupts.
If the processor is in interruptable mode, when an ,interrupt occurs, the
response time depends on the maximal execution time of the instruction ~being
~¢ectited (during which the interrupt cannotbe accepted). However, if a second
interrupt occurs, when the processor is already servicing an ~interrupt; the
response fimeis the maximalexecution time of the interrupt service.routine.
246 DESIGN OF CARD~C PACE~KERS
¯ An interrupt service handler is a process that enables the less-critical

condition to be interrupted by an interrupt signal from a more critical condition.
This processor on entry into an interrupt service routine will enable or disable
individual interrupt conditions or groups of conditions, either by hardware or
software. The disabled interrupt signals are held pending until the condition is
enabled, This interrupt priority structure helps in serving the high priority
interrupts as quickly as possible. , ¯
In the hardware implementation of a multilevel interrupt system, each
interrupt signal is assigned one of the possible interrupt priority .levels. If the
interrupt signal is at a priority level lower than or the same as the running
process, it remains pending. If not, the interrupt is serviced as soon as the current
instruction is executed as shownin Figure 10.15. This implement(t_tion maintains
stack allowing interrupt routines to be interrupted only by higher priority
interrupts.
Process LoWpdodty High pdodty
.level level level
Highpriodty interrupt i i~ .
Lowpdodtyinterrupt "
Lowpriority interrupt
Highpdod~interrupt
Figure10.15Amultilevelinterrupt systemin whichahighlevel priority signal.hadprecedence

over lowerpriority signals. Theprocessesof lowerpriority are interruptedw~e
n a ~gh priority
interrupt o~curs. Onthe other hand, the lowpdority interruptg are kept pendiiig until the
completionof higher priority interrupt service routines. FromGarside, i~: G~"1980.The
architectureofdigitalcomputers. NewYork:OxfordUniversityPt~ss~ -~
10.7.4 Battery life.estimation system -
In an artificial pacemakerit is essential to have the circuitry to identif~y the

remaining useful life of battery in a simple and reliable manner. In many
pacemakersystems, circuits are provided to measurethe internal resistance of the
battery to deduce the remaining life, ,With this circuit, the p, acemakeris first
switched to "test mode"and a resistive load is applied-to the battery to measure
the voltage drop. The status of the battery is indicated.by generating a series of
test pulses. Depending on the internal voltage drop, and thus the internal
resistance, the:frequency of the.stimulation pulse is changed, which is measured
externally. However,this circuit can only-be used for batteries with increasing
internal resistance as the battery discharges.
To overcome the limitations of the previous teqhnique and to measure the
life expectancy of a battery with constant internal resistance, another technique
was proposed. The battery test circuit is provided :with a pulse counter and input
logic to measure the consumed charge from the operating parameters of the
pacemaker and the number of pulses delivered over a period of time. During
each test, the charge delivered since the last battery test is calculated based on the
count ,in the pulse counter, which is then summedto the contents of the charge
counter in memoryas shown in Figure 10.16. The content of the:charge counter
is a measure of the total charge consumed and provides information about the
remaining life of the battery (Moberg,1987).
Pulse parameters
cou~ter i ~1 1
I Input logic It,~l~ Moderegister
~1
I Charge counter
Figure10.16Batterystatus test circuit. Chargedeliveredby the battery is ~sdmatedby keeping

track of the numberof pulsesdeliveredby the pacemakerandthe modeof operation.Aninternal
chargecounteris updatedduringeachtest modeto readthe total chargedelivered.Thisinformation
aboutbattery status is readfromthe pacemaker
by telemetry(Moberg,1987).
The circuit is implemented internally in the implantabledevice and a~means

is provided to report the valuetof the charge counter when interrogatedby
te!emetric methods. The advantage of this methodis that there is no need to alter
thefrequency of stimulation pulses while testing the battery. ¯
10.8WHY CMOS?
Pacemakercircuits include digital and analog unitS. In digital units, information

iS :p¢ocessed by turning switches on or off: This technique is reliable; energy-
efferent, and used in the timing circuit and programmingcircuits, In analog
units, information is processed by regulating the amountof current or voltage in
asystem; for example, thesen,sing circuit uses analog technology to senSe the P
Waveand R wave of thepatient s ECG.
’~ A semiconductor is a crystal (usually silicon, Which is n6rmally ~a
none0nductor) that has had its crystal strue~re deliberatel~ Contaminated with
o~hei atoms (referred to as doping). These atoms replace silicon atoms in the
g~c~re of the crystal but have one valence electron more or less than the ~four
in’silicon that are necessary for proper binding. As a result, the doped crystal
trnd~ to accept or donate electrons easily from an added atom. Th.e. arrangement
0f.s~miconductors and metals separated by an insulating silicon 6xide forms a
transistor.
~i~~. Very large scale integration (VLSI) is a nonspecific term referring to the
t~e~]anol0gy that produces high:density circuits With"the capacity’of having
thousands of transistors in an area of a few square millimeters.
The abbreviation CMOSis used often, in pacemaker advertisements to

describe the unit’s circuitry and stands for "Complementary Metallic Oxide
Semiconductor," Whenan area in a semiconductor that tends to accept electrons
is next to an area that tends to donate electrons, they are complementary;
electrons can flow in a unidirectional current at very low voltage with little
generation of heat. The complex CMOStechnology is extremely compact and
operates at low energy.
Vdd
Figure10.17CMOS
inverter configuration.When
In = Vdd,Ptran is openandNtranis closed,
so out = 0 V and vice versa .... ¯
Digital designs for pacemakers are implemented in the CMOS technology in

order ’to take advantage of the very low current demandsof the process. Since
virtually no current flows through a logic gate in a steady-state condition, low
current drain is achieved in this process. The reason behind low current drain can
be understood by analyzing an inverter, implemented in CMOS technology shown
in Figure 10.17. In an inverter, the n-channel MOStransistor and a p-channel
MOStransistor are connected in series between the terminals of a source (Vdd)
and ground, and their input on gates are connected together. Whenthe input of
the inverter is high the p transistor will be switched off and the n transistor will
,be turned on, connecting the Gndto the output and p~rforming inversion of the
input. Whenthe inverter input is low,~the p ~sistor ~vill be turned on and the n
transistor off, again creating the inversion operation. In any state, one of the
series transistors is off, preventing the existence of current flow between Vddand
Gnd. Thoughit might appear that the CMOS concept requires no current at all
since no current flows in both the states of the inverter, there are several current
flow mechanismsthat exist. During switching from high to low at the inverter
input, both transistors maybe on slightly at the same time, and a small amountof
current flows. In addition, small electrical capacitances exist that transfer charge
during the high-to-low transition and result in small current flows. These two
effects explain whycurrent consumptiongoes up as the frequency of the circuit
increases, and therefore the higher frequency portions of the circuits must be
kept to a minimum.Small .leakage currents also eas t for all CMOS processes
resulting in a small static current drain. The principi~s used to construct the basic
inverter ~of complementary, p-and n-type transistors from metal, oxide, and
semicondiJctor la~ers (CMOg)can be expanded ~o configur~ more complex type
of logic functions.
LOGIC ~IMPLEMENTATION 249
Other types of semiconductor technology may be used in pacemakers in the

future. There is a growing demand for still denser, mixed signal circuitry that
operates at lower power. A concurrent trend in chip lithography is
submicrometer features, which easily overheat and therefore also must be
operated at low power.
As for lower power, reducing the power supply voltage from today’s 5 V to
3 V can lop two-thirds off power consumption, extending the battery life. More
fundamentally, as minimal chip geometries edge below 0.5 #m, 3 V becomes a
necessity; lines as naxrow as that would be overheated by high-frequency signals,
and .if used on a 5rV chip with a high gate count, would downgrade reliability.
There are several engineering issues that need to be considered with 3-V mixed-
signal design.
410.9 REFERENCES
Amado,J. B., Belaza, J., Diaz, A., and Tur, J. B. 1985. Technologyof pacemakerselectronic
circuitry. In F. P. Gomes et al. (eds.) Cardiacpacing: Electrophysioiogy.Tachyarrhythmias.
Mt. Kisco, NY:Futura Publishing. " ~
Baker, R. G., Jr. 1989. A-Vresponsive rate adaptive pacemaker,USPatent 4,856,524.
Buffet, J., Gautier, J. P., and Jacquet, J. P. 1982. The software pacemaker.In G. A. Feruglio
(ed.) Cardiacpacing: electrophysiology and pacemakertechnology. Padova, Italy: Piccin
Medical Books.
Buffet, J., Gautier, J. P., and Jacquet, J. P. 1982. The software pacemaker- Feasibility of
recording pacemaker.In S. S. Barold and J. Mugiea(eds.)The third decodeof cardiac pacing:
advancesin technologyandclinical applications. MountKisco, NY:Futura Publishing.
Buffet, J., Meunier,J. F., Gautler, J..P., and Jacquet, J. P. 1982. Technology and reliability of
microprocessorsused in pacemaking,In S. S. Barold and J. Mugiea(eds.)The third decadeof
cardiac pacing: advancesin technology and clinical applications. MountKisco, NY:Futura
PuMishing.
Dassen, W. R. M., Dulk, K. D., and Wellens, H. J. J. 1988. Modem pacemakers: Implantable
artificial intelligence? PACE,11:2114-2120.
Dassen, W.R. M., Steld, A. V., Braam, W. V., Dulk, K. D., Gorgels, A. P. M., Bmgada,P.,
and Wellens, H. J. J. 1985. PACTOT: A repmgrammable software pacing system. PACE,8:
574-578.
Dassen, W., Steld, A. V., Dulk, K. D., Brugada,P., and Wellens, H. 1984. The soft pacemaker:
A new approach in pacemakerdesign? Computersin cardiology, 4: 529-532.
~uggan, S. R. 1992. Analogto digital converter, USPatent: 5,092,330.
inspruch, N. G, and Gold, R. D. 1989. VLSIelectronics microstructure science, VLSI in
medicine :17, Orlando, FL: AcademicPress.
Fromer, M., Shenasa, M., Kus, T., and Pag6, P. 1987. Management of a patient with recurrent
sustained ventricular tachycardia with a newsoftware-based antitachyeardia pacemaker.J.
ElectrophysioL, 1: 133-139.
Gaggini, G., Garberoglio, B., and Silvestri, L. 1992. Mixedmicroprocessor-randomlogic
approach for innovative pacing systems. PACE,15: 1858-1861.
Garside, R. G. 1980. The architecture Of digital computers.NewYork:OxfordUniversity Press.
Harrigal, C. E., and Walter, R. A. 1990. The development of a microprocessor controlled
implantable device. Proc. IEEENortheast BioengineeringConf. 3: 137-138.
Hartla{~b, J. 1982. Pacemakerof the future: Microprocessorba~ed or customcircuit? In S; S.
Barold and J. Mugica(eds.)The third decode of’cardiac pacing: advancesin technologyand
clinical applications. MountKisco, NY:Futura Publishing.
Kraft, G. D., and Toy, W. N. 1981. Microprogrammed control and reliable design of small
computers,Englewood Cliffs, NJ: Prentice Hall.
J. L., and Patterson, D. A. 1993. Computer organization & design: The
hardware/softwareinterface. San Mateo, CA:MorganKaufmann.
, L. 1987. Battery test circuit for a heart pacemaker.USpatent 4,715,381.
Russie, R. J. 1991. Implantable cardiac device with dual clock control of microprocessor. US
Patent 5,022,395.
250 DESIGN OF;CARDIAC PACEMAKERS
Schaldach, M. 1992. Electrotherapyof the Hea~.Berlin: Springer-Vedag.

Stotts, L. J., Infinger, K. R., Babka, J., and Genzer, D. 1989. An 8-bit microcomputerwith
analog subsystemsfor implantable biomedicalapplication. IEEEJ. Solid-state Circuits,
292-300. " ~"
Wittkampf, F. H. M., Candelon, B., and Arragon, G. W. 1984. The importance of software
programmablepacemakers:In vivo programmingof a prototype device. PACE,7: 1207-1212.
10.1 Explainthe differences betweena microprocessorand a customrandom circuit ~aCemaker.

10.2 Explain the design of a state machine-basedpacemaker.’ .... ~ ~ ’,.
10.3 Explain howa microprocessor-basedpacemakerdiffers from a state machine.
10.4 List the basic components
of a microprocessorand briefly explain the functions of each.
10.5 Summarizethe design process of a microprocessor-based pacemaker and the issues
involved in o~g the performance of the system.
10.6 Explainthe advantagesin using a dual clock control rneehanismin~ microprocessor-based
pacemakerand drawthe block diagram.
10.7 Briefly explain the designof a low-poweranalog-to-digital converter.
10.8 Explainthe function and advantagesof a watchdogtimer.
10.9 Explainthe advantageof a w, dundantpacemakerand,wbenit is used.
10,10 Explainthe functions of an interrupt handleritia microprocessor-based pacemaker.
10.11 Explain whyCMOS technology is an ideal Choice for a pa~maker.
Pulseoutput
Michael K. I~udon
Thefunction .of the output circuit is to deliver periodic voltage pulses to the heart
muscle. High standards of quality and durability are required for the design and
implementationof the circuitry. A patient’s quality of life, and sometimeshis/her
life itself, dependupon the proper operation of the pacemaker.Malfunction of the
anit~generallyresults in an unhealthy and Unhappycustomer.
~Design of the output circuit has evolved since the first pacemaker was
implanted. Manyearly Units had RCoscillators and transformer-coupled outputs.
Quite a few of these devices were also constant current output sources. As time has
progressed, these units have fallen out of favor and been replaced by devices with
constant voltage capacitor discharge outputs and crystal oscillators. Other advances
in pacemaker design, such as triggered and inhibited sensing, have created new
problems which require solving. Someof these problems and their corresponding
solutions are addressed in this chapter, along ,with the basic fundamentals for
designingoutput circuitry ........ ~ ....
11.1 CONSIDERATIONS F0R OUTPUT DESIGN
C~diac pacemakersare required to deliver a stimuhs pulse of sufficient magnitude

and ~duration to :cause heart.muscle, contraction. A typical stimulus pulse has a
ch~gein ther~,a,n~e of 0.1 to 50/.tC anda duration of~0Ato 2-ms (Ryan, 1989).
achieve ~a~ sufficient stimulati0n ValUeland ~aximiZe the ~ battery longevity, a
pa’c~e~:idquites~utPutip~ise pro~abiiity ~f abom’ten amplitud6 and ten
duration values (Ryan, 1989). All new implantable pacemakers are constant
voltage sources, designed for a typical load impedances between 400 and 1000 fl
(Furman .et al.,: 1993): Whendesigning an output circuit¢ it is important
understand the basics ofheart stimulation in order to moreeffectively address the
problem of maximal stimulation with minimal use of pacemaker energy. The
following sections explain someof these basic concepts concerning pacemakers.~. ~
ll,IA Strength,~uration curve .,,
Vary~g the pulse duration is a commonand effective method of controlling the

pacemaker output.. Understanding the relation between the pacemaker pulse
voltage amplitude and duration required for effective heart sti.mulation can help
increase the pacemakerlifespan. In order to gain an understanding of what occurs
during the output pulse, it is necessary to understand the strength-duration curve,

shownin Figure 11. l(b).
Figure 11. l(a) showsa stimulation device (the pacemaker)in series with a
membrane.Depolarizing (i.e. achieving a voltage drop of 20 mVacross Rm)the
membranewith differem current values results in the strength-duration curve of
Figure 11.1 (b). In reality, while the load seen by a pacemaker, is more complex
than a simple membrane, the resulting strength-duration curve has the same
characteristics as a cell membrane,with different current and voltage values. Thus,
for the sake of simplicity, the membranemodelwill be used to explain the response
of the heart to electrical stimulation.
Cell
(a) Membrane
S
(b)
u
r
r
e
n ~eobase
t
chronaxie time / Log Pulse DurStion
Figure11.1(a) Asimplifiedversionof a pacemaker stimulatinga load. In this case, the load

simplya cell membrane.(b) Thestrength-duration curveassociated,with the circuit in part (a).
Whilethis specific curverelates:to the depolarizationof a single cell membrane,the strength-
durationcurvefor stimulationof the heart has the sameshapeandcharacteristics. Therheobase
is the minimalcurrent that will causethe membrane to depo!a~ize..The~hronaxie time iS the
pulsedurationrequiredto causedepolarizationWhen the stimulatingdurrentmagnitude is (wice
the rlleobase. ~
The stimulus threshold curve is explained with reference to Figure .I 1.1(b).

The pulse amplitude is shownas the log of current versus the log of the pulse
duration, This strength-duration curve can be plotted either as a voltage
characteristic or as a current characteristic. The correspondingvoltage curve is the
same shape as the current curve, with current replaced by voltage. It is possible to
show that the amountof charge used during pacing is minimized as the stimulus
pulse amplitude is increased.
Assume,that we model many parallel cell membranes, by the single Celt
membranein Figure 1 Ll(a) and that wechoose componentvalues of 1 ~tFfor the
capacitor and 1 ~for the resistance. Depolarization of the cell membraneis
achieved by providing enough current to cause the voltage drop across the
PULSE OUTPUT 253
membraneto change by approximately 20mV.The stimulus current I is the sum of

the current through the capacitance, ic, and the current through the resistance,/R,
t=ic +iR=C(aV
/ dt)+ V / (11.1)
The voltage drop across the membranedue to current flow can be found with the
equation
V = IR(1 - -t/Rc) (11.2)
(Geddes, 1984). To depolarize the cell, V must equal -20 mV.With R equaling
1 f~, the minimalcurrent whichwill achieve this is
I = 20 mV/ 1 ~ = 20 mA. (11.3)
’minimal current Value is the rheobase of the curve. The rheobase value is
depe,ndentupon the characteristics of the load (in this case the membrane).
.T0ill~s~ate the Cli~ge saved by increasing ~e amplitude, and shortening the
dBi~afipn of the.stimulus pulse; we Will use current levels of~25 mAand 40 mA
(rem~,-,~..ber that, ~ese values haveno ,relatioti to actual pacemaker-indue~xl
currents
~,heart). With a 25 mAcurrent mplittlde, the mininial dUrati~ia of the square
~av~ stimulus is
20mV = 25 inA x 1 fl(1 -t/10-6
~ e ~ ). (1L4)
This results ina stimulus time t of 1.60 ~s. Thetotal charge tised (current x time)
at tlfis’-stimulus amplitude is’ 40nQ.Now,if thb~40 mACurrent pulse is used, the
stimulus duration required to achieve depolarization is
;.-~
.: 20 mV= 40 mAx 1 £2(1 ~ e-~/i0-6 (11.5)
with t equaling 0.69//s. The .amount of charge used is,only 28 nC. Therefore, the
charge dissipated during excitation with the 40 mAstimulus amplitude is only 70%
of~that consumedwhenthe stimulus is25 mA.Itis easy to see that shortening the
duration of the stimulus pulse is effective in reducing charge consumption.
Although charge consumption is,minimized when the pulse duration is
shortened, energy is not. Assumingthe pacemakerload (i.e. the heart) is a fixed
value; energy usage can be shownby the: following equation
W = 12Zt (11.6)
whereZ is the entire load impedance. The minimalproduct of voltage (or current)
and duration is described by
l= lo(l +t¢ It) (11.7)
WhereI0 =,voltage rheobase,, tc~is the chronaxie time, t is the duration.of stimulus,
and~I,is the, amplitude,of ,the..~stimuluslcurrent.~The,chronaxie,time,is,. the stimulus
dttration:when, the stimulus current magnitudeistwice the rheobase,~andis near the
point of minimal energy consumptiomCombiningEqs~ (11.6). and (11.7) results
the energy use at the chronaxie time tc being .~
I = I 0 (1 +tc / te) = 210 (11.8)
W= (2I 0 )2Ztc = 4Io2Ztc (11.9)

If the stimulus duration is changed from the chronaxie time, then energy.
consumption goes up. For instance, with durations of one-fifthand twice tc the
amountof energy used is
-W=7.2I~Zt¢ (t=O.2tc) (11.10)
W = 4.5IgZt~ (t = Zt e ) (11.11)
The energy used with t = 0.2 tc and t= 2tc is 180%and 113%, respectively, more
than what is used whent is equal to the chronaxie time. This energy consumption
definitely influences the longevity of the pacemaker.
The stimulus threshold curve results from the interaction of the pacemaker
patient’s heart and the electrod6 and i~ influeheed by ~any factors~Th~se include
the size and nature of the stimulating electrode, the nature Of the’ heart, the
placement of~e lead; epinephrine leyels in’~e body, etc’. ~ Since nunierou~’~actors
affect the threshold for cardiac padhg,a 100%safety margiia i~~ genelally set
(Furmanet al., 1993). This meansthat the energy delivered while pacing should
100%higher than the minimalamountof energy necessary to excite the heart. This
can be easily determined using the strength-duration curve and energy equations
previously mentioned..Thethreshold:for excitation increases by: a factor of two to
three after imp!antatio, n due to inflammationandthe deve~lopmentof scar tissue but
then stabilizes after a monthor so. ~.
Changing nowfrom working with current to voltage, the chron~xie time can
be found by determining the stimulus threshold at two fixed voltages VI and V2.
The stimulus threshold at fixed" voltages call Be found by varying the pulse width
until cardiac activity in response to pacing is barely present. The pulse widths
associated with V1 and V2are tland t2 respdetively; In equation form
V1= Vo(l + tc I tl (11.12)
V2 = Vo(l + t~/ t2 ), (11.13)
with V0 being the voltage rheobase (the minimalvoltage, required for stimulation).
Manipulating Eqs. (11.11) and (11.12)~ we can fmd the chronaxie
t c = (V1 - V2)(tit2) / (V2t2 -Vlt1 ). (11.14)
The chronaxie time approximates the most efficient stimulation pulse duration
(Furmanet al., 1993). Thus, including the 100%safety factor, a preferable stimulus
would have an amplitude of twice VOand a ’duration of twice the chronaxie time.
The duration is lengthened to twice the chronaxie time to achieve the safety
margin. Such anadjustment is generally~easierthan changing thevoltage level,
since the timing,circuit and pulse width,seleetor:can-:be more easily: designed to
deliver a plurality of pulse widths than,are a~cailable from~oltageeonverters: Note
that the chronaxie.time calculations .in,thiS paragraph were done with voltages, as
all new cardiac pacemakersare constant voltage sources, -
PULSE OUTPUT 255
11.1.2 Unipolar and bipolar stimulation
In a unipolar stimulating device, the electrode tip stimulates the heart, while the
pacemakerunit serves, as the reference. In a bipolar ~device, the lead has both a
Stimulating tip, the cathode, and a ring, the anode. The ring generally has a much
larger surface area. The separation of the ring and tip are 2-3 cm, dependingon the
pacemakermodel (Furmanet al., 1993).
.The current threshold of stimulation is the samefor both unipolar and bipolar
l~adS. The voltage threshold, however,is slightly higher for a bipolar lead because
of~the4ncreased lead resistance (Furmanet al.,.1993); :For instance, with a pulse
duration ~of 0.1 ~ms, the impedance of a unipolar lead was found to be around
489 ~2, while the bipolar impedance was 600 f~ (Furman et al., 1993). This
increased resistance during bipolar pacing is due to the ring area being much
smaller than the pacemaker case area..(which is the anode in unipolar pacing).
Since resistance is a function of condueiionpath area, the anode in bipolar pacing
has moreresistance than in unipolar pacing. The extra tissue betweenthe electrode
and can in unipolar pacing can be neglected becametissue is a good conductor.
A benefit of a bipolar lead configuration is that the signal-to-noise ratio of the
sensed heart signals is better.than that found with unipolar leads. The bipolar
sensing configuration eliminates muchof the noise resulting from nearby muscle
movement.However,as will be seen in the next section, bipolar stimulation can
also have its drawbacks. Most modemde;cites can be changed from unipolar to
bipolar configuration, and vice-versa, through telemetry (see Figure 8.23).
11.1.3 Cathodalvs. anodal stimulation
Figure11.2 Stimulationof a cell with the anOdeandthe cathOde.Thecell I~omesdepo~l~

whenthe potential drop across the cell membrane is approximately-70 inV. Theeathtdal
stimulation of magnitude-20 mVcausesthe potential drop across the membrane to reach the
depolarizationthresh0l~.~However; anodalstimulation’cauSesa hyperpolanzation~ot~ the cell,
forcingthe cell membrane potential oppositethe ~desireddirection. If the~anodalstimdl~sis
",increasedto a larg~enoughvaluethe ce~lLwilleven[ual!y~e, but the ano&d,,stimulusmagnitude
rcqu~f0r d..epolatizationcanbe fromtWoto three timesas muchas the 6athodalvalue.
In all stimulation occurs at while anodal

situated in
or on the myoeardiumof the heart, ~ ~e anode is located.~stally near’the heart
(b~ipol~aeing); or remotely as ~ p~ ~’ ~ p~!se:ge~or f ~i~6iar p acin’g).
"Fi~t~r6 il.2 shows that th~:~timui~s ~u~reti~f0r eeu ~xei~fibn is leas with
Cathodai simulation than with anodfl Stinli~lati0n. The. pot~iitial drop from th~
256 DESIGN OF C~IAC PACEMAKERS
interior to exterior of a heart cell is about -90 mVwhenthe cell is in its resting
state. Loweringthis potential drop to approximately -70 mVwill cause to cell to
exhibit an action potential. In the case of cathodal stimulation, direct application of
-20 mVlowers the extracellular potential to -20 mV,and the entire potential drop
across the cell membraneis now-70 mV.This results in the cell firing an action
potential. Onthe other hand, if cathodal stimulus is used the extracellular potential
is raised in the positive direction, and the resulting drop across the cell membrane
isnow around -110 mV.This large voltag e drop results in hyperpolarization of the
cell, and no action potentials occur: Note that increasing the anodal stimulus level
will eventually result in the cell firing. However, the magnitude of stimulus
required from the anode can be two to three times what is required from the
cathode.
Threshold
(v)
Anodal
I
Cathodal
i
0 ms 200 ms 400 ms
Delay Time
Figure11.3 Thecatbodalandanodalexcitationthresholdsduringthe cardiaccycle, or strength-

interval curves. TheECG abovethe strength-intervalcurveillustrates timesduringthe cardiac
cycle whenstimulationcanhaveadverseaffects. Theventricularfibrillation (VF)periodoccurs
duringthe first part of the T wave,whilea multipleresponse(MR)period occursduringthe
secondhalf of the T wave.Stimulationof the heart duringthe VFperiodmaycausethe heart to
fibrillate, Whilestimulationduringthe MRperiodwill causethe heart to havemultipleresponses
to a single stimulation.Thetime after the T waveis the nonvulnerableperiod(NVP),wherethe
heart can be successfullystimulatedwithoutcomplications.FromFurman,S., Hurzeler, P.,
Mehra,R. 1977.Cardiacpacingand pacemakers IV. Thresholdof cardiac stimulation. Am.Heart
J., 94: 115-124.
Note also the myocardial response to stimulation during the refractory period.
In early bipolar devices, the anode and cathode were nearly equal in size (Furman
et al:, 1977). It was found the anode of bipolar electrodes may have been
responsible for someoccurrencesof ~,entricular fibrillation. In fact, Stevensonet al.
(1986) found that anodal excitation can occur during bipolar stimulation, producing
changesin local myocardialactivation,-potentially causing initiation of Ventricular
This can be demonstrated witha strength,interval curve, shownin Figure

11.3. Sensitivity to anodal stimulation o~cu~searlier than eathodal senSitiVity,
shown by the earlier threshold drop of the anodal curve. Shown above the
PULSE OUTPUT 257
strength-interval curve is the corresponding ECGof the heart. During the T wave,
the anode can easily cause stimulation. Dueto this, multiple response (MR), which
is morethan one response to a single stimulation, and ventricular fibrillation (VF)
conditions are more sensitive to anodal stimulation than they ever are to stimulus
from the cathode (Furmanet al. 1977). Other factors also contribute to the heartrs
susceptibility toward MRand VF. The ratio of the surface area of the cathode to
the anode is one factor, and another is the proximity of the anode to stimulatable
tissue. One solution used to eliminate VFand MRis to increase the size of the
anode, while keeping the cathode small. Another solution is to movethe anode
further awayfrom the heart. Whilemovingthe anode helps to solve ~the problem of
anodal stimulation, it also decreases the signal-to-noise ratio of the evokedheart
responses, whichare sometimes; sensed to allow more effective stimulation of the
heart.
11,1,4 Output waveformcharacteristics
Pacemakers should ideally deliver a square wave pulse from the cathode with
characteristics similar to Figure 11.4(a). The duration andamplitudeof,the pulse
should be adjustable. All modempacemakers are of the constant voltage output
type. Thus, the load impedancehas a large efftct on the stimulus current. A load
withhigh impedance will have an excessivelyhigh threshold ofstimulafion, while
a 10wimpedancewilt result in large.currents and premature battery drain. Furman
et al. (1993)-describes the four different pacemaker output designs which have
been or areiavailable~
(a) Ideal I--T~ (b) Actual I---T~I
Vdd
Figure 11.4 (a) A representation of an ideal stimulation pulse from a constant voltage
stimulator.Thevoltageis measured fromthe stimulatingtipto.the reference’. (either the ring or
the pacemaker can). Vdd Can either be a fixed value, as in single ~voltagede~iees, or. a
programmable value, with variability dependentuponthe pacemakermodel. The period of
stimulationT is variablein all devices.(b) Arealistic depictionof a waveform appearingacross
the heart emittedfroma capacitordischargeoutputcirc~t. Nolethat the drop.in Prise voltage
magnitude is dependentuponthe size bf the ttitput capacitor:’ Alarger’eap~ito~~vill :havea
waveformwhichmore closely resembles an ideal constant voltage. The small rise and
exponentialdecayafter the stimduspulseis an afterpotenfial,whichis discussedin section11.3.
Single voltage-multiple pulse durations
These devices ha~,e .a fixed output voltage, while ~Pe~Odof stimulatio n is

variable. Most of these devices .have an oqtput voltage of 5.QV~The pulse duration
is commonlyfrom 0.05 to 2.0 ms. The threshold of stimulation can be deterp3jn~d
by successively decreasing the pulse duration until cardiac stimulation is barely
existent.
Dual voltage-multiple pulse durations
Devices with this designation have two output voltage-levels, 2.5 and 5.0 V. The
period of stimulation Tis also variable similar to single voltage devices. Formerly,
the 5.0 V setting was regularly used, and the 2.5 V setting was used in special cases
whenextremely low (at the time) thresholds of stimulation occurred. Now,with the
advent ofnewlow threshold electrodes, the 2.5 V setting is regularly used, and the
5.0 V setting used only in situatons where2.5 V is insufficient for stimulation.
Quad voltage-multiple pulse durations

The-voltages available to these devices are generally 2.5, 5.0, 7.5-8.2, and 10 V.
Some generators in this category allow for only four pulse durations,
corresponding to times wherechanging the pulse duration has the most effect (i.e.
0.25 to 1.0 ms). The 7.5 and 10.0 V settings should be used only for short term
expediency. At these high voltages, battery energy is consumedrapidly.
Multiple voltage-multiple pulse durations
ModemCMOScircuits allow. 0~1 V voltage .steps, and 0.01 ms steps in pulse

duration, These multiple voltage output devices are becomingprogressively more
common.Oneconsideration when,designing devices with~morevariability is that a
point is reached wherethe steps are too fine to have any practical benefit~ Creating
pacemakers with outrageous numbersof voltage steps and pulse durations is not
actually necessary to improvetheir operation
11.1.5 Automatic output adjustment
To minimize energy drain, it is desirable to pace at a safety margin above the

pacing threshold. Frthlich et al. (1994) developed an Automatic Amplitude
Adjustment (AAA), which is based on the measurement of the ventricular evoked
response (VER). After’each pulse is released, the VERis measuredand analyzed.
Because VERshave a longer duration than the intrinsic ECG,the pacing pulse is
defined as capture if all measurementstaken in a 60-ms windoware higher than a
programmedreference value. The algorithm avoids problems with fusion beats.
Electrodes are shorted for 50 ms after pacing to minimizepolarization, problems. If
no capture occurs, the pulse amplitude is increased until capture, occurs, then a
safety margin added.
11.2 DESCRIPTION OFOUTPUT CIRCUITRY
The constraints involved whenworking with pacemakerslimit the liberties which

can be taken designing the circuitry. One major constraint of pacemakers is the
actual physical size of the unit. Minimizingthe, size of the unit while maximizing
its effectiveness is a major concern. Capacitances must be kept as small as
possible,~as, they req~a large p0ifion of the hybrid circuit space., Redundancy~0f
critical components,Used in devices wheresize is not as important a corisideration,
caiintfbe-practiced iii p~teemaker§::Thus, it is crUcial that ~ design, be ragged
enough’to last the ~ 10 to:iS years which cardiac pacemakers are nowexpected to
function.
PUI~E OUTPUT 259
Another limitation is the low voltage values available from the pacemaker
battery. The voltage of a modernpacer battery is about 2.8 V, which is below the
functional range of many standard componentsused in electronics. While the
voltage in pacemakerscan be stepped up, this should be avoided wheneverpossible
due to the losses incurred whenusing voltage multipliers. The circuit must also
function over a range of supply voltage values. As the lithium-iodine battery
depletes, the magnitudeof current whichit can effectively supply decreases as the
internal resistance of the battery increases. Since replacing or recharging the
battery is out of the question, the pacemakershould still be able to operate under
low battery conditions.
11.2.1 Voltage multipliers
Multiplying the voltage is necessary in situations where the battery voltage of

2.8 V is not sufficient for the needs of the pacemaker,such as whenmultiple output
voltages are desired. Stotts (1989), describes a method which is used
implantable devices requiring higher voltage levels.
Figure 11.5 shows the battery voltage Vbat, the battery resistance Rbat, the
pumpcapacitor Cp, and the ~utpu~,capacitor Co, which is driving a load with load
current IL. With a small battery resistance, Cp is charged to the battery voltage
during Phase I. At the same time, the output capacitor is supplying charge to
maintain the load current. During Phase II, the circuit is switched, as shownin
Figure 11.5(b). Because the pumpcapacitor is inseries with the battery voltage
this configuration, the entire voltage drop across capacitor C~is the battery voltage
plus the voltage across Cp, whichsums to twice the battery voltage. Since Phase II
is the only time Cois supplied with charge, the average current from Cp, is
(11.!5)
wli6re T is the s~itehing period, fi~ the frequeoCy0fswitching,and V is’ithe peak-
t0~peak ripple v~ltage o~ Cp.. Since,the ch,~rge Supplied froth Cp .to Coisin turn
supplied to the load,
(11:. 16)
Defining the average output resistance of the voltage multiplier, Rm, to be

VilL, then "
Rra =VlCpVf~i:]Cpf ~~ ...... (11.i7)
The average current from the battery is equal to the sum of the charge
supplied during both phases. During Phase I, the battery supplies the pump
capacitor with ~pV. ’During Phase :II, ~ the pumpcapacitor supplie~Co with CpV;
while the battery is still supplying CpV.The average battery current iS then
Iba t = 2CpVf = 21L (11.18)
.The energy transfer effieienqy r/is defined~
r/,~ ILVout/ IbatVbat (11.!9)

(a)
:Cp Co=r Vout
PhaseI
(b) +Vbat
¯ ""Vbat Cp Co lVout ¯
PhaseII
Figure 11,$ Circuit diagram of a voltage doubler. (a) Phase I. During this time, the pump
capacitor Cpis chargedto Vbat alld the output.capacitorCosupplies charge to the load. (b) Phase
II. Thepumpcapacitorcharge.sthe outputcapacitor,which.,iss, till supply,!ngt~,.e lo~a.dc,u ~. nt.
Note the voltage drop across the output capacitor is twice meoattery volu~ge (Le. meoagery
voltageplusthedropacross~ which alsoequalsthe.batteryv.ol~ge):
If .hi.’ghe.rm.u.l~ples,
of ~e
battery~oltageareneeded,tiffs doubling
circuitcanbec..asc.a~d~d,with
o~_r~o,,u~un.g
~h-~cm.is.
FromStotts, L. J. 1989.Introductionto implantible
biomedica~~ aes~gn.11~’~t, wcuztsuemces
Magazine,~ (1): 12-18.
In the ideal case that the battery current is exactly twice the load current (Eq.
(11.17)), ~ is exactly100%(i.e. Vout/(2Vbat)= 1). In reality, the energyefficiency
is actually very clos~to 100%with lowvaluesof ripple.
Whenthe battery resistance gets large, the pumpcapacitor does not fully
chargeduring PhaseI, and do~snot dischargeto the steady-state value in PhaseII.
This results in the pumpcapacitor chargingto an averagevoltage of
Vpum (11.20)
p = Vba
t -t 2 lL Rba
Theoutputvoltage is the result of, load resistance RLin series with voltagesource
2Vpump,and the output resistance Rm.Thus,
. Vout= 2 Vpump- I L Rm (11.21)
You (11.22)
t = 2Vicar "4RbatlL ~ I~ ICpf
When
the battery resistance is high, the outputresistance of the multiplier is
PUI~E OUTPUT 261
Rm=4Rb
t +l/Cpf (11.23)
In general, Rmcan be approximated by
Rm p= (n - 1) / Cpf f << 1 / RbatC (11.24)
Rm = n2Rbat +(n-l)/Cpf
p f>>I/RbatC (11.25)
wheren is the numberof multiplication stages used.
11.2.2 Basic circuit
Figure 11.6 shows an example of a simple capacitor discharge’system. The

capacitor is periodically discharged across the load resistance (the pacemakerlead
and heart) to stimulate the heart muscle. Duringoperation, if the voltage at the base
of the transistor is low, then the transistor will be in its nonconductive
(off) state,
this situation, the capacitor charges to Vddthrough the pull-up resistor. Upon
reception of a signal at its base, the transistor goes into its conductive state, and
gro~d voltage appears at the collector. Since the collector is nowat ground, the
voltage drop across the capacitor causes a voltage of-Vdd to appear at the load
resistance. This causes stimulation and subsequent contraction of the heart muscle.
~er the pulse signal is removedfrom the base of the transistor, the transistor turns
off, and the output capacitor recharges to Vdd. . .
(a) Circuit (b) Output

Vdd
Voltage
~.Time
F|giire 11.6 Asimpleversionof thecapacitordischargeOutpufCircuit, TheCapacitorinitially

eli~ges to the voltage Vdd.Uponreception of a signal fromeither the mieropr0cessoror a
separateoscillator,the transistoris switchedinto its. conductive
state.: This-causes
groundvoltage
to appearat the collector,. Sincethe outputcapacitoris alreadychargedwitkvol~ag~:Vdd,~
andthe
load resistance is eormeetedto ground, a negative Voltage2Vddappe~a6r6ss the output
resistance. This voltageinducescurrent flowwhichstimulatesthe heart muscleto contract. (b)
Theoutputwhichappearsacrossthe heart.
H.2;3 Unipolar stimulating circuit :
Blaser (1980) designed a slightly more sophisticated circuit shownin,Figure 11.7,

To unde~tandthe functionof the circuit, assumethat it is initially at:steady state:
all three capacitors have acharge of Vdd across them(noting that the 3.3~//F
electrolytic capacitor has a polarity opposite that of the + sign), and both transistors
are not in the conductingstate.
Vdd
Zener 8.2 V
~_lJ+/ _~ Output
:~t.3:lx F " to heart
(c)
Micro- I
I
processor~~_ ,,
Figure 11.7 Abasic unipolar output circuit. A commandfromthemicroprocessorcauses an

outputofr2Vddto appearat the output. Adapted
fromBlaser(1980).
If a pulse is applied at the base of Q1, with sufficient magnitudem place the
transistor in the conductive state, then the. voltage at the e011ector of Q1 will
effectively go to ground. Since capacitor A cannot discharge immediately, this
forces the emitter voltage of Q2 to be shifted below the ground potential of the
circuit. The base of Q2 is connected through the 15-162 resistance ~to groundand is
switched into the conductive state whenthe emitter voltage drops~ This changes the
voltage at the collector of Q2 toward -Vdd. Just prior to Q2 being switched, the
3.3-/.tF capacitor has a charge of positive Vddappearing at the negative side of the
capacitor. Whenthe collector voltage of Q2 is abruptly changed toward -Vdd, the
3.3-pF capacitor already has a voltage drop of Vddacross it. This causes a voltage
close to -2Vddto appear at the output electrode. The circuit acts as a voltage
doubler. The zener diode is in place to limit the output voltage fluctuations, while
the 33-/zF deeoupling capacitor B connected from the supply rail to ground is in
place to stabilize Vddwhena pulse is being delivered.
The duration of the output pulse can be controlled by adjusting the length of
time that Q1 is in the conductive state. A controller attached to the base of the
transistor could suP ply ......
pulses with the , duration
. .,. ~Jad’usted
.... internall b some1~ ic
¯ . ,Y Y
implementation, or externally through telemetry. As an even more basic design,
attachmentof a fixed rate oscillator to,Q 1 and the battery directly to the supply line
Vdd, would provide an output With a fixed voltage andfixed duration.
11.2.3 Bipolar output circuit
A bipolar stimulating circuit is shownin Figure 11.8. The methodof operation is

similar to the basic circuit, but there is the addedavai~bility of two voltage levels~
While primitive compared to some modern pacemakers which have as many as ten
or more;.v01tage levds, itis a distinct improvemento~er the single output voltage
most early pacemakershad: It is also possible; ~with the use of :voltage dividers or
multipliers, to alter Vdd,giving addedvoltage selectivity tothe device.
PULSE OUTPUT 263
Vdd
TA
Switch ~Switch
Network~,,O__ ~2
Sensing
Vdd
Amps.
S
S
o
I
|
Figure1L8Abipolar stimulatingcircuit. This devicehas the ability !to:select twodifferent

voltage setti ags, withoutchangingthe value of Vdd.Witha logic 1 ~iacedan line C, switch
networkonecloses and switchnetwork2 opens, allowingpacingof the heart. Logic1 on line A
andlogio~;atline B results in a pulseof Vddacrossthe heart. Logic1 onbothAandB results in
2 Vddacrossthe heart. FromSfindt andWright(1981).
Assumeinitially the output capacitor is chargedto Vdd.If the Controller place6

a high output on line C, switch network one will be placed in the conductive state.
The inverting gate inverts and delivers a~ low signal to switch :network two,
blanking the sensing amplifiers. This co~afigurationiallows pacing of the heart.
If the controller places a high signal on line A, transistor Q 1 will remain off
while Q2 is placed in its conductive state. A low signal on line B results in the
NAND gate emitting a high output, turning on Q4 and leaving Q3 off. 6, path of
conduction is opened from ground, through Q4, thi~ough the output capacitor,
through switch network one, through the heart, back through switch network one,
and through Q2 to ground. This allows the output capacitor to deliver a stimulus
with amplitudeVddto the heart. If Vddisthe battery voltage, then the output would
have a magnitudeof 2.8 V, ideally. "~ " "
If the basic battery voltage is not adequate for stimulation, then, the amplitude
can be doubled. Withline C high, ~the controilerl, generates high sigiaflS on both
lines A and B. Transistors Q2 and Q3 will be condt~cting,’ ~hile Q1. a~dQ4will be
in their high impedancestate. This permits a conduction path fr0in Vddthrough Q3,
through the switches and heart, and finally through Q2 to ground. When~, ,~sistor
Q3 conducts, the side of the capacitor that is connected to Q3 goes to Vdd.With-the
addition of the voltage drop already across the .capacitOif; the Output stimulus
amplitude is doub!edto 2Vddor 5.6 V whenVddis the battery voltage.
! ’": Ai~tet ~timt/ius has been applied to the ~ heart; the ogtputcapacitor :mu~t be
~har~ed. Settiiig both A and B lo w reSu!t~:iri QI andQ4’6~nducfing~~iS all0~
recharging of the output capacitor to Occur through the same path ~tSstimulus
occurs. Thenet current flow throughthe leads is zero, leaving no opportunityfor

metallic ions to migrateinto the heart muscle(iontophoresis).
Figure 11,9 showsa slightly different methodfor bipolar pacing. This design
eliminatesthe needfor outputcapacitors. Sincecapacitorsrequire relatively large
volumesand can have long term reliability problems, a functional pacemaker
design minimizingthe numberof capacitors used is desirable. However,this device
is mostlikely not used exactly in this form, since the ring has the possibility of
stimulatingthe heart duringthe first half of the stimulusphase. Anotherpotential
problemis that the output electrode is connecteddirectly to the battery voltage.
Unless there is a large decoupling capacitor, the supply voltage will drop
drastically whenVddis delivereddirectly to the load,
(a)
Ring Vdd
enable
Paceinput ~2
signal I
_ Ring
Vdd
Pac(
enable
Tip
enable
(b) Pace input-.-[TL--J-~
(differential from II " I!

tip to dng).
Figure11.9(a) Adevicewhichdeliversa biphasicstimulation:
Thedeviceis uniquein that
doesnot requirean outputcapacitor.(b) Thewaveforms
appearingonthe Paceinputline’and
the electrodes.FromDuggan(1983).
Whenpacing, the circuit delivers~.a biphasi¢output pulse a~rossthe. ring and
tip of the dec~. ~a lo~cl is placed at the ~g en~ le, then Q4is switched on,
and the inverter delivers a logic zero ’to Q1, whichis also switchedon. Thus,Vdd
PULSE OUTPUT 265
appears at Q2 and ground appears at Q3. A logic 1 applied to the tip enable
similarly results in Vddbeing connected to Q6 and ground connecting to Q7.
Setting the pace enable to logic zero allows the flip-flop to be clocked by the
pace input signal. Everypulse from the pace input will invert the values of the flip-
flop outputs. For instance, a pace input of logic 1 results in a logic 1 at Q (of the
flip-flop) and will place logic 0 at Q2andQ3.This sameinput, resulting in logic
at Q prime, places logic 1 at Q6 and Q%The final result of the pace input is that
Q2 and Q7are on, and Q3 and Q6 are off. With both ring andfip enablesat logic 1,
the,voltage Vddappears at the ring, and groundappears at the tip of the electrode.
A second logic 1 appearing at the pace input, signal will result in the flip-flop
outputs inverting. Thus, logic 1 is placed at Q2 undQ3and logic 0 is placed at Q6
and Q7. The end result is Vddconnecting to the tip and ground appearing at the
ring. A stimulus has been applied across the heart, as shownby the differential
electrode output in Figure 11.9.
11.3 ELECTRODE RECOVERYTIME
After the pacemakerdelivers a pulse to the heart, there is a period of time where
sensing cannot occur. This effect is due to what is called the post-stimulus potential
or afterpotential. In order to sense signals accurately, it is first necessaryto remove
~ e afterpotential whicharises from charge stored at the electrode interface. ’Figure
L i0 qualitatively shows what occurs near the electrodes ~dudn’g and after a
stimulus pulse. ~i ~
- Measuring:" the re~sponse’of the heart to a.;stimulu~ pulse is:’desirable for a
nu~r’~of reasons. T~ackingthe threshold 0f stimulation, for. i6~sfance, requires
distinctionbetween an effective pulse (one whichcauses the lieartt~ contract~ and
a subthreshold pulse. Reliable sensing is impossible until the .charges resulting
from the stimulus dissipate sufficiently ~because the poststimulus potentialS are
muchlarger than those resulting from a heartbeat. In the case of a dual-chambered
pacemaker,whenan atrial stimulus occurs, detection of events in the ventricle is
necessary for the microprocessor to operate the pacemaker efficiently. The
stimulus at the atrium generally results in potentials appearing at the ventricle
sensing electrode, whichis called "cross,talk". Cross,talk must also be minimized
to allow effective sensing of intrinsic signals.
11.3.1 Electrode polarization
Within the metal electrode, current is canopied by electroCs,.~ while outside ~e

eledtrode; it is mainly ions which causeOeurrer~t. A~, the electrode interfaCe~
electrons and ions interact and-forman electrical ~ double layer called :th~Helmholtz
layer (see Figure 6.3). Introducing an electrical field across this layer decreases the
membranepotential of cells nearby, and subsequently causes depolarization (if the
field is of sUfficie’nt magnitude).Waltonet al.(1985) state that the majority of
reactive portion of the load impedanceresults from this electrode interface.
! n order to understand the el~ct!~0chemica! prope~i~es of the interface, a
simplified model can be used. The model consists of the lead resistance in series
with the parallel Faraday resistance and Helmh01tzcapacit/tnceshown in Figure
11.11. Figure 11.12 gives the,typical resistance and.capacitance Values for the
interface model. The eapacih~ce of the double layer is
DESIGN OF C~C PACEMAKERS
(a)
Ring
Tip
(b)
®
0
(c)
Figure1L10Qualitativeexplan~ti0nOf afterpotentialcteation. (a) At the onset of a stimulus

pulse, the:ions ~s~ntin the~tissue near,the ring and tip are randomlydispersed.’ (b) Upon
applicationof the stimulus,the ions movetowardtheir respectivecounterparts(i.o positiveions
movetowardthe negativecathode,andvice-ve~a);(c) Immediately after stimulation,the ions
mustreturn tO th~ei~quiescentstate. Thedelayrevolvedinthe ion dissipation
~ increaseS;is whatcreates
aflerpotentials.~ Thepolariz~increasesas~lie lengthof stimulation resulting in a
rising 4oadimpedance duringstimulation:~This~is anotherreasonwhystimuluspulse durations
shouldbe keptas short as possible;FromMoses,H.W.,Taylor,G;.J., Schneider,J.~ A,Dove,J.
T.. 198~LA practicalguideto cardiacpacing,lAttle, Brown.
Ch
RI
Rf
Figure’llA1Asimplifiedm6delof the:electr0de inteff~e. Rl is the~leadresistance, Ch~the

Helmholtz ,resistance ’of the interface. Theinterface Of,the
capacitance,and, Rfis the~Faraday
electrode and heart tissue results in Rf~and Ch~ ....
PULSE OUTPUT 267
Ch = er x e0 x A / d (11.26)
whereA = surface area, d = thickness, and er = relative dielectric constant (whichis

between-5 and, 80 depending on the thickness of the double layer) (Schaldach,
1990). The impedanceof the system is
Z = R1 + Rf / (1 + ja~ChR
1) (11.27)
Neglecting the Faradic resistance, Schaldach (1992) describes the voltage,drop

across the Helmholtzcapacitance as
Vc(t < T) = a ×(1- e(-t/RICh)) (11.28)
where Va is the constant’amplitude voltage applied to the Helmholtz capacitance

(i.e. the stimulus voltage), vc the voltage drop across the capacitor, and T is the
period o~pplied stimulus. The afterpotential is
Vc(t > T) = a ×(1- e-r/e~c~) x (e (- t-T)/R~Chi (11.29)
Equation (11.29) shows that an increase in either resistance RI or capacitance

will decrease the magnitudeof the afterpotentials. An increase in R 1, however, is
not acceptable because this causes an increase in energy consumption, and impairs
sensing of evokedresponses. Thus, an increase in the Helmholtzcapacitance is the
most acceptable solution. Since the relative dielectric constant ~0 and thickness d
are .basically unaffected by electrode construction, the area, is~ the only
cha~rhctefistic of the electrode-which Can be altered. Increasing the area of the
e~de.in~creases the Helmholtz capacitance. However, measurements done with
diffJ~dntsized stimulating electrodes have shownthat increasing electrode size
increases the !charge required for stimulation (Schaldach t992).~ Thus, simply
in~Creasi~ngthe electrode tip size is not a s01ution.~Thetip.must"remainsmall while
the active surface area is increased through othermeans. Using different electrode
constructions such as porous tip and TiN coated have proVlded Workablesolutions
(Schaldach, 1990). Chapter 6 presents other methodsused to increase the tip area.
V~hile increasing the Helmholtz capacitance decreases the magnitude of
afterpotentials, it increases the dissipation timer constant. Thus, while the
m~gnitudeof.~the~afterpotentials will be less initially with~ a large Helmholtz
capacitance, they will remain for a muchlonger peri ~lof time~ However, if the
sense amplifiers are sensitive enough,the initial afterpotential~ value ,with large.Ch
maybe small enoughthat ~t does not matter ~howlong/he diss~pauonperiod is,~ ~
Methods~to, avoid, or diminish afterpotentials other than altering-electrode
sin-faces .are also available. Standardpractice calls for blankingthe sense ~amp!ifier
¢0nneeted to .the pacing lead for many milliseconds while the afterpotenfial
dissipates. It ia~a, goal of pacemakingdesign t0~ shorten, the blanking-period by
speeding the charge dissipation process. Speeding the dissipation can be achieved
using methodswhich actively recharge the output amplifier.
One’ method~ ~
Of active recharg6used to shorten the electrode recovery time ~is
referred to as charge dumping. Figure 11.12(a) shows an example 0fa charge
dumpcircuit. This methodallows a low-impedancepath for current to flow back

into the stimulating lead. Large reverse currents flow through the lead system,
dissipating the charge stored at the electrode interface. Charge dumping is
generally done for about 10 ms immediately after an output pulse (Ryan, 1989).
Figure 11.13(a) showsthat a pulse is delivered to the heart in the usual fashion
by turning on Q2. After Q2 is turned off, Q1 is turned on, resulting in a low-
impedancerecharge path. It should be pointed out that Q1 is left off for a short
time between the stimulus and recharge. This is done to avoid a short circuit from
the battery to ground. In addition to decreasing the blanking period, charge
dumpingincreases the efficiency of the output stage by eliminating _the power
dissipation whichoccurs in the recharge resistor.
(a) Vdd (b)
(~°WinttCrh°ii ~-~ll---’~0.4 ms~"
Figure11.13(a)Aaexampleof a chargedumpcircuit. Theswitchcontrol turns on either QI or

Q2,but bothtransistorsare neveronat the sametime.If a stimuluspulseis required,thenQ2is
activatedwhileQ1is inactive. After the stimuluspulseis delivered,Q1is activatedto ~lowa
low-impedancere.chargeof the circuit. Thepositiv~rechargepulseis delayedfor approxi/nately
0.4 msto avoidshort circuitingthe battery to ground~Notethat the rechargepulseoccursduring
the nonexcitableperiodof the heart, to avoidanycomplications
involvinganodalstimulation.(b)
Theoutput waveform with chargedump.Thefirst pulse stimulates the heart, while the second
rechargesthe capacitoranddissipates afterpotentials.FromSutton,R. andBurgeos,L 1991.The
foundationsof cardiacpacing,pt i~" an illustrated practical guide to basi~ p~cing.Futura
Publishing.
Applying a .biphasic stimulus has also been found effectivein reducing the
afterpotentials associated with cardiac stimulation. Figure 11.14 shows a method
for providing a biphasic stimulation. ’ Thecircuit consists of three transistors that
are used as switches; an-output capacitor Cout, a charge capacitor B, and capacitor
A which is a power-supply decoupling capacitor. Figure: l l.14(b) shows the
voltage that appears at the outputelectrode.
Assumeas an initial condition that the output capacitor and Capacitor B are
charged to Vdd/2. At time tl (see Figure 11.14(b)), Q3is turned on, and the output
capacitor is charged for .the period TI until the voltage across it is nearly Vdd.At
the same time, Q1 is turned on, and capacitor B discharges (its charge going into
the output capacitor) undl both sides are at Vdd. At time t2, QI and Q3are turned
off, and Q2 is turned on. This delivers a stimulation pulse of length Tst to the
myocardiumof the heart. At time t3, Q2 is turned off, and Q1 is ~ed on. for
period T2. The output capacitor and capacitor B recharge tt: Vdd/21Th~is prt’~ides
the second positive recharge pulse. The switches are left open until the next
stimulation is to occur.
PULSE OUTPUT 269
(a)
[Timing ]
Circultry
I
T~ T~
--
(b)
I IV I
I I I I
I T1 ITsd T2 1
Figui’e1i.14, Abiphasicstimulationcircuit. (a) Devicewhichemitsa positive pulseof Vdd/2,

followed:by a negative pulse of -Vdd,followedby anotherpositive pulse of Vdd/2.(b) The
voltageappearingat the output. PeriodsTI, T2, andTst correspondwithpulses fromthe timing
circuitry shown
in part (a). Adapted
fromCalset al. (1982).
Figure l 1.15 shows a different proposed method of quickly reducing the

charge stored between the stimulating electrode and the reference electrode, Note
that this was referenced from a bench model and mayor maynot currently be in
use.: At .the end of an (atrial or ventricular) stimulus pulse, the stored charge
monitored, and short duration pulses are applied to the stimulating dectrode to
quickly reduce this charge. . -
The~outputcapacitor of Figure’l 1.15 is charged by the reference source, ’ and
whena pulse is supplied to Q1, a stimulus pulse occurs at the electrode. The
s~mulus width and amplitude are both variable. The width is changed by adjusting
the.time that Q1 is conducting, and the amplitude can be adjusted by changing the
tapping of Pot 1.
:i The reference voltage source, Vrefi and node A are connected to the inputs of
instrumentation amplifier, Amp1. Amp1 subtracts the voltage appearing at node
A ..from the reference voltage. Theresult is amplified and added to an offset equal
in .magnitude to the reference voltage. The output of Amp1 is ~ connected through
S~to a capacitor, whichacts as a sample and hold circuit. The capacitor should be
a~10~:l¢~ak~ age polyester type capacitor. .
~.....Iii i~e~ation, immediately after a sdmuluspulse, S1 is closed and $2 opened
for a preset period. The output of Amp1 is sampled and held in the capacitor.
Switch S 1 is then openedand $2 closed for a preset period. This supplies a voltage
pulse to node A, with the sample-and-holdcapacitor located at the input of Amp2
determining the magnitude and polarity of the pulse. Application of these
poststimulus pulses speeds the dissipation of the stored charge at the electrode
interface. Repeating the cycle a predetermined numberof times returns the voltage
at node A to a value close to Vref and the voltage at the stimulating electrode near
ground. This then allows sensing of evoked responses to occur with the same
electrodes used for stimulation.
~ ..... _ll
I
I
I
I Vref
lAmp 2 I I
Vdd
)ll I I
I
/
Node A
Hold Pt
Figure11,!5Acircuit whichdeliversshort durationpulsesto:eliminatethe chargebtdf~dat the

electrodeinterface. Vddis the batteryvoltage,andVssthe negativebatteryVoltage.Addpted
from
F, eonomides
et al. (1989).
PULSE OUTPUT 271
11.4 LEAD MEASUREMENT
During implantation, the pacemaker lead can receive damage which affects the
electrical insulation. This damagecan go undetected and not affect the system until
later:in the service life of the unit. Whenthe insulation is damaged,there can be a
logs of sensing or a loss of capture due to less energy reaching the heart muscle.
Since all new pacemakersare constant voltage output generators, changes in the
lead resistance will have a large effect on current flo~ through the load (Furmanet
al., 1993).
Other things mayoccur to alter the impedance characteristics of pacemaker
leads. Fracture in a conduction coil can affect operation by increasing lead
resistance. A complete fracture wouldresult in no energy reaching the heart due to
an infinite lead impedance.Impropercontact of the electrode tip with the heart wall
wouldalso result in a high impedance.
Measuringthe lead impedancecan indicate if any of the previously mentioned
problems have occurred. In some situations, whena pacemakeris being replaced,
the lead will be left in the patient, and only the pacemakerunit will be changed. In
this~case; it is importantto knowfit.he entire unit has failed or if the pacemakeris
working, but the impedanceof the lead(s) has risen to a level that prohibits proper
function ofthe unit. The physician should be able todetermine if the lead being left
in ~tli~ ’patient is in satisfactory conditioti{ Kn0w!edgeof the lead impedance~ght
alS0 possibly allow logic circuitry to. alter,the output voltage in response tO a
change in impedance. For example, the output voltage amplitude could be
increased if a high-impedance situation occurs, ensuring that enough energy
reaches the heart to provide stimulation. ~
1~.4.1 Lead-impedancemeasurementcircuit
Figure 11.16 shows an abbreviated output circuit with lead-impedance

measurement. T~e impedan6e may be measured at periodic predetermined
intervals, Or by an external telemetered command~. ’ When~ ~easurementoccurs, the
outpfat capacitor is charged tOVddand switches twOand four are closed, allowing
the capacitor to discharge through the knownresistance Rknownwhile the counter
is enabled and starts counting clock pulses. Whenthe voltage across the output
capacitor reaches Vdd/2, the counter stops and the time is stored as tknown. Then,
the same operation is done again, except switcheS-twoand three are closed, which
allows the output path to go through th,e lead and heart impedances,Rlead. The time
for the voltage across the capacitor tt~:reach Vd~/2is measuredagain, this period
being denotedas tlead. Rkno~,~is constant’ ~,mdShouldbe a precision resistor with a
value between 1"3 1~. Since Via is relatiwly constant (until very near the end of
the battery life), the only componentswhich~an change o~,er time are the switches
and the output capacitor. ThiS necessitates that tknownbe taken every time the lead
impedance is measured. Otherwise, if all component v~ues remained the same
ov6r~time, tknown could be measured once and stoied in memory.Si~ch isnot the
ease though, and t~6wn is measured, every time a lead:impedance measurement
Because: Vf = Vi exp(tknown/RC) (11.30)

(a) Vdd
I-clock
Counter~
~----Enable
(b)
~.-time
tknown tlead
Figure 11.16 (a)A lead-impedance measureme.nt circuit. Closing $2 and $4 allows

measurement of the capacitor dischargeacross a. knownresistance. Closing$2 and $3 allows
measurement of dischargeacross the lead resistance. Thetime required for the capacitor to
dischargeto Vdd/2is usedto calculate the lead resistancevalue. (b) Anexampleof the output
capacitorvoltageversustime for the twoimpedances. Measured
timestknownandtlead are used
in Eq. 11.33forcalculatingthe lead resistance. FromKuehn.1993.
the relationship between the capacitance and theresistances Rknownand Rlead are
shown by
C = tknown / ln(0.5)Rknow
n (11.31)
C = tlead / ln(O.5)Rlead (11.32)
The value of Rknownis already known,so it can be used as a constant. The variable
lead resistance is then found by setting Eqs. (11.31) and (11.32) equal to each other
tlead / ln(0.5)Rlead = tknown/ ln(0.5)Rknown (11.33)
Rlead = Rknow
n (tlead / tknown ) (11.34)
The impedancesof the switches will generally be insignificant and can be ignored,
or they can be subtracted if their impedancevalue is known.
Figure 11.17 shows a different methodto measure the lead impedance using a
current mirror. This device consists of two transistors connected to the output after
the load (heart). Neglecting the effect of finite fl, the output current through the
load will be equal to the reference current. If the reference current is measured,
with our ___kn, owledgeof the output voltage wecan find the impedancevery simply
using Ohms Law. The equation for finding the reference voltage is
Iref = (Vou
t - VBE) / Rload . (11.35)
PULSE OUTPUT 273
Vout
iref
lout
I
Figure 11.17Currentmirrorusedto measurethe outputcurrent. Measuring

the referencecurrent
allowsthe lead impedance
to be calculatedusingOhm’sLaw.
1L5 OUTPUT CIRCUIT PROTECTION
It is possible for individuals with implanted cardiac pacemakersto comein contact

with high voltages. These voltages can severely.damage inadequately protected
circuitry in the pacemaker. Such damagewould be deleterious t~ the health of an
individual relying on the damaged pacemaker. For instance, in the case of
ventricular fibrillation, large voltages are applied across the heart in an attempt to
revert the heart to normal rhythmicpulsation. The voltage used whendefibrillating
runs into the thousands, subsequently causing high currents toappear in the heart
region. Electrosurgical units can also deliver high voltages to a patient. Open
circuit voltages of these devices can range from 300 to 2000 V, with power into
500 f2 loads ranging from 80 to 200 W(Neuman, 1992). There are also many
natural situations whereshock hazards can occur. In all of these situations, current
tends to go through the pacemaker and associated electrode because they offer a
path which is more conductive than the surrounding body tissue:Steps must be
taken to remedythis situation.
Early protection circuitry involved placing one or more zener diodes between
the output terrain_, al and ground of the pacemaker. This eliminates the threat to
pacer circuitry by opening a path for current that bypasses the pacemakercircuits,
and limits the voltage whichappears at the pacemakeritself. Pacing will continue
to occur even in the event that cardioversion or someother high voltage event has
occ~ed.
11.5,1 Pacemakerunit and lead protection
While the zener diode arrangementprotects the pacemakercircuitry, high currents

can still flow through the electrode tip and lead assembly: These high currents have
:" been found to. cause myocardial damage(Hauser, 1994). High currents can also
i~9~ase the threshold.0f stimulation by causing .fibrosis of the tissue near the
d~t~odetip, whichincreases:the separation of the tip and excitable tissue:
~. Figure 11.18 shows prot orion devices that protect the umt and also hrmt the
~Ui~ent flow through’the lead(s)~Figure 11.18(a) shows the block diagram of
protection circuitry, while Figure 11.18(b) and (c) are two current-limiting devices
.which can be placed in the box labeled Current Limiting, Device in part (a). Figure
11.18(d) showsthe current vs. voltage characteristics of the devices in parts (b)
(c).
The current-limiting device in Figure ll.18(b) is a symmetrical depletion
modedevice. The device is basically two field effect transistors connected in
series. The gate and drain of each FETare shorted to each other by a conductor.
Whenthe voltage increases at the drain, it also increases at the gate. This causes a
self-limiting effect wherethe current cannot becomegreater .than a certain value.
Referring to the current vs. voltage characteristics, whenthe drain voltage (i.e. the
voltage received by the electrode) is small, the device acts as a resistor. This
resistance should be minimalwhenin the linear range, in order to keep the load
resistance low. Increasing the drain voltage causes the depletion regions to pinch
off betweenthe gates. The current then levels off, since the gate voltage increases
in conjunction with the drain voltage. As the voltage increases, the current flowing
through the electrode stays at a maximum of 20 mA.If the voltage occurring at the
electrode is greater than +1500V, then breakdownoccurs, and the current limiter
fails. In this situation, large currents will flow through the lead. The pacemaker
circuitry is still safe though,as the zener diode will limit the voltage that app¢~ars.at
the output capacitor and shunt the current flow to ground. But the lead(s) ~nay
damagedwhenvoltages of such large magnitudes occur (in which case the patient
will probably also be damaged).
(a)
..--~ Electrode
Current
Limiting
Device ~
Generator~
(b)
(c) (d)
10 ~ 2KQ ~ 15~X)
Figure11.18Apacemaker unitandlead protection device. (a)Blockdiagramof the device. (b)

Acurrent limitingdevicewhich.can be placedin the boxlabeledcurrentlimiting devicein part
(a). Theequivalent
circuit of the sy ~stemis shown.(c) Adifferentcurrentlimitingdevice.(d)
eun~ntvs. voltagecharacteristics of current limiting devices(b) and(c). AdaptedfromMoney
(1982).
PULSE OUTPUT 275
The device in Figure 11.18(c) is a different method for achieving Current

limitation. If a large positive voltage appears at the electrode, current flow will be
limited by the BJT. Because the base of the transistor is tied to ground and the
transistor is not in the conducting mode, current flow through the transistor will be
minimal. If a large negative voltage were to appear at ~e electrode, the diode
connected to the collector of the BJT would limit the flow~ of current. Thus, for
~ osidve voltages, the transistor is the current limiter, and for negative voltages, the
iode limits the current. Both devices should be able to withstand voltage
magnitudes of 1500 V. Note that for this circuit to be effective, the pacemaker
cannot be emitting a stimulus pulse, This pulse would cause, the voltage~ at the
emitter of the transistor to go negative, and as a result, the BJT. would be in its
con~ctive state an allow large currents to flow. Thus, reception of large voltages
at the electrode should cause inhibition of the pacemaker in order for this setup to
be..effective.
IrOn"REFERENCES
Blaser, R. 1980. Cardiac pacemakercircuit with variable operation. USpatent 4,202,341.

Cals, G. L. M., Wittkampf,F. H. M., Mensink,IC A., Brouwer, H. L. 1982. Pacemakeroutput
Circuit. USpatent 4,343,312.
Duggan,S. R. 1983. Pacer output circuit. USpatent 4,402,322.
Economides,A. P., Gergely, S., Walton, C. 1989. Cardiac pacemakerwith fast stored charge
reduction. USpatent 4,811,738.
Elmovist, H. 1984. lmplantible heart pacemaker.USpatent 4,463,760.
Fr~hlieh, R., Bolz, A., Hardt, R., Hubmann,M., and Schaldaeh, M. 1994. Automaticamplitude
adjustment of the pacemakeroutput voltage. Proc. Annu. Int. Conf. IEEEEng. Med. Biol.
Soc. 16: 55-56.
Furman, S., Hayes, D. L., Holmes, D. R. 1993. A practice of cardiac pacing. 3rd Ed. Mount
Kisco, NY:Futura Publishing.
Furman, S., Hurzeler, P., Mehra, R. 1977. Cardiac pacing and pacemakersIV. Threshold of
cardiac stimulation. Am,Heart Z, 94:115-124.
Geddes, L. A. 1984. Cardiovasculardevices and their applications. NewYork: John Wiley &
Sons.
Hauser, R. G. 1994. Interference in modernpacemakers:status report. MedtronicNews,22(1):
12-20.
Kuelm,IC P. 1993. Medicallead impedancemeasurementsystem. USpatent 5,201,865.
Money,D. 1982. Protection device for pacemakerimplantees. USpatent 4,320,763.
Moses, H. W., Taylor, G. J., Schneider, J. A., Dove, J. T. 1987. A practical guide to cardiac
pacing. Boston:Little, Brown.
Ryan, T. G. 1989. Cardiac pacemakers. In N. G. Einspruch and R. D. Gold (eds.). VLSI in
medicine. Vol. 17. San Diego: AcademicPress.
Schaldach, M., Hubmann,M., Weikl, A., Hardt, R. 1990. Sputter-deposited TiN electrode
coatings for superior sensing and pacing performance.PACE,13: 1891-1895.
Schaldach,M. 1992. Electrotherapyof the heart. Berlin: Springer-Verlag.
Stevenson, W. G., Wiener, I., Weiss, J. N. 1986. Contribution of the anode to ventricular
excitation during bipolar programmed electrical stimulation. Am.J. CardioL,57: 582-586.
Stindt, R. E. and T. C. Wright.1981. Cardiacpacer circuit. USpatent 4,300,566.
Stotts, L. J. 1989. Introduction to implantible biomedical IC design. IEEECircuits Devices
Magazine,5 (1): 12-18.
Sutton, R. and Burgeos,I. 1991. The foundationsof cardiac pacing, pt 1: an illustrated practical
guide to basic pacing. MountKisco, NY:Futura Publishing.
Walton, C., Gergely, S., Economides,A. 1987. Platinum pacemakerelectrodes: Origins and
effects of the electrode-tissue interface impedance.PACE,10: 87-99.
Neuman,M. R. 1992. Therapeutic and prosthetic devices. In J. G. Webster (ed.). Medical
instrumentation: application and design. 2nd Ed. Boston: HoughtonMifflin.
11.1 For Figure ll.!(a), with the membraneresistance and capacitance 1 f~ and 1 RF,
respectively, calculate the time required to depolarize the membrane "with an applied
current of g0 mA.
11.2 Describewhyanodal stimulation of a cell requires a larger stimulus amplitudethan does
cathodal stimulation.
11.3 Explainwhyanodal stimulation has a greater ~hanceof causing ventricular fibrillation
than cathodalstimulation.
11.4 List twoconstraints involvedin output circuitry design.
11.5 Giveabrief; qualitative description of voltage multiplication using apumpcapacitor and
switching network.
11.6 Briefly explain whythe waveformdelivered by the circuit in Figure 11.9 maybe
considered undesirable.
11.7 Show,with a figure, the ion movements whichcreate afterpotentials.
11.8 Explainwhyan increase in the lead resistance is not a desirable methodfor speedingthe
dissipation of aftevpotentials.
11.9 Explainqualitatively howthe lead impedancemeasurement circuit in Figure 11.15 works.
For Rknown I kf2, tlead 0.5 ms, and tknown0.7 ms, calculate the lead resistance.
ll.lO Describe howthe device in Figure ll.18(b) can limit lead current during cardia~
defibriliation.
ll.ll Designan output circuit that includes deviceprotection and output voltage variability.
External Programming
Kevin M. Hugo
Sinceeventhe ~mostsophisticated pacemakerscannotperfectly adapt to changesin

their operating.conditionsover the devices’lifetimes, it’ is advantageousto allow
th~ physician to changetheperformanceof the device noninvasivel~,This process
is knownas programming.The first programmablepacemakerwas introduced by
Medtronic,Inc. in the early 1950sand used triangular transcutaneousneedles.tO
adju~st.two potentiometers that controlled the rate, Later pacemakersused
~agaetic"’reed ~witchesto temporarily adjust the sensitivity, rate ~, and pulse
ma~nitud6 (Sehoenfeld, 1993). M~dern programmable pacemakers use
ele~tr0magnetic~coils and digital codes to programparameters. Electromagnetic
ffbils ~so permit the pacemakerto transmit i~ormation out of the device:This
6an be us~fu!~forverifying parameters. - ¯ ~~ ’ ’ .....
~’ Such a bidirectiohal ~ ~ommunicationslink can also be used t6~relay data
coll6cted from sensors in the patient or pacemaker.Thi~~’proe~ssis called
telemetry. Although. programmingand telemetry are d~fferent pacemaker
fu0~ions~putting dat~ in versus getting data out--they share muchof their
h~dWareand th~ of operation.
12.1 HARDWAREINTERFACE
Figure 12.1 shows the block diagram of the pacemaker programming and
telemetry interface Theleft half of the figure is the programmer--an external
device which communicatesprogrammingand teler~etr~ information with the
pacemaker. The sections of the pacemaker associated with programmingand
telemetry are shownon the right. The programmingsequence is initiated by
bringing ~i permanentmagnetin the proximity of the pacemaker,whichdoses a
reed switch in the latter. Information is then encodedinto a special error-
correcting pulse sequenceand transmitted electromagnetically through a set of
coils. Thereceived messageis decoded,checked.for errors, and passed on to the
unit’s logic circuitry. Modernpacemakersinclude the capability of bidirectional
communication.
Reed switch
reeds normallyspring apart whenno magneticfield is present. Whena field is

28O DESIGN OF CARDIAC PACEMAKERS
Oscillator---
~t~~ ~ ~.~Enable =+~ , ~Psh~i~tedetector ~

, Vref
Datato I
I
transmit
Pacemaker
Figure12.4 Programmer
headpositioningcircuit. AdaptedfromBaltina and White(1985).
A programmingmessage is comprised of five parts (Figure 12.5(a)).

start bit indicates the beginning of the message and is used to synchronize the
timing of the rest of the message. The parameter number specifies which
parameter (e.g., mode, AVdelay, pulse width) is to be programmed. In the
example in Figure 12.5(a), the number 10010000specifies the pulse rate to
specified. The parameter value represents the valu~ that the parameter should be
set to. This value maybe an index into a table of possible values; for example,the
value 00101100represents a heart rate of 80 beats/rain. The access code is a fixed
number based on the pacemaker model which must be matched exactly for the
message to succeed. It acts as a security mechanismagainst use of the wrong
Start bit I Parameter no. Parametervalue I AccesscodeI Padty
I
. (a) 1 bit
1
8 bits
10010000
MSB LRB
8 bits
00101100 10010111I
M~B LRB I MRB 8L~B
8 b~ts
10111100
bits I[ M~B LSB
2.2 ms 1.0 ms 0.35 ms
Start
fl
175kHzcarrier
Figure 12.2 Typical encodingand modulationof programming messages.(a)~Parts ofthe

message.
(b) Encodingof the first five binarydigits of (a) into pulses.(c) Moduiated
signal.
Signalafter receptionanddemodulation.
EXTERNAL PROGRAMMING 281
programmer, errors in the message, or spurious programming from

environmental noise. It can also potentially allow more than one programmable
implant in the patient. Finally, the parity field is the bitwise exclusive-or of the
parameter~number and value fidds. It is one of several error-detection
mechanisms.
All of the bits are then encoded as a sequence of pulses of 0.35-ms duration
(Figure 12.5(b)). The-start bit is a single pulse; the remaining bits are delayed
from.their previous bit according to, their bit value. If the bit isa zero, the delay
is short (1.Ores); if it is a one, the delay is long (2.2 ms). This technique, called
puIseposition coding, makesdetection of errors easier.
The serial pulse sequence is then amplitude modulated for transmission
(Figure 12.5(c)). The carder frequency is the resonant frequency of .the coils.
This signal is,transmitted from one set of coils to the other and then demodulated
back into a pulse sequence (Figure 12.5(d)). Each manufacturer, uses a different
set of frequencies.
Figure 12.6 shows how each bit of the pulse sequenceis decoded from the
demodulated signal. As soon as each bit is received, a timer begins timing the
d6Iay to the next pulse. If the pulse occurs within a specific early interval, it is
counted as a zero bit ~ (Figure 12.6(b)). Ifit otherwise occurs within a later
interval, it is considered to be a One bit (Figure 12.6(d). Pulses that come
early, t00~late, or between the two intervals are considered to be errors and the
enfi~e message is discarded(Figure 12.6(a, c, e)). Each bit begins the ~timing
the. bit that followsit. Thestart bit is used only to time the first bit.
Risingedge
Of previous bit ....
I Invalid Valid zero Invalid Valid one ~ Inv~iid
/interval , interval interval interval, inteival
(a) ~ Invalid
(b) --~ Zero

N
(e) I-"-I ~ Invalid

I--’]
(d) ~ One
’~’~
(e) I~l I--L_---~ Invalid
Figure12.6 Decoding onebit of the signal fromFigure12.6. Thetimingbeginsfromthe rising

~g e, of the bit that precededit. (a) Pulseoccurstoo earlyandis invalid.(b) Avalidzerobit.
se whichis invalidbecauseit occursbetween
Pulseoccurstoolate andis invalid.
the zeroandoneintervals. (d) Avalid onebit. (e)
Telemetry data may be either analog or digital. Digital signals are first
stream using an encoding such as shown in Figure
stream or the analog data is then frequency modulated for
An advantage of this and other encodings is that they provide multiple forms
of error detection. The coils and receiver circuitry are tuned to the modulation
frequency, eliminating noise at other frequencies. Pulse-position coding can
detect errors by accepting pulses only within narrowly-defined intervals. The
access code acts as a security key to prevent programmingby spurious noise or
other equipment. Finally, the parity field and other checksumsprovides a final
verification that the messageis valid. At any time, if an error is detected, the
entire messageis discarded (Gordonet al., 1982).
In order to increase the ~bit transmission rate, manypacing systems use a
more sophisticated type of pulse position modulation. In these, the position of a
pulse within a frame is encoded into one of a finite numberof values, e.g. 16. A
special synchronizingbit is transmitted to signal the start of the frame. Typically,
the frame contains a code which specifies the type of data contained in the
remainder of the frame.
12.1.4 ,Output drivers
Programming and telemetry typically use different modulation methods;

therefore, different circuits are used to drive the coil. The driving circuitry in
the programmerconsists of an amplifier which drives the coil in parallel with a
capacitor (see Figure 12.5) using pulsed amplitude modulation. Eigure 12.7
shows the circuit for driving the telemetry coil using frequency modulation.
Analog data or serial digital data are frequency modulated using a voltage-
controlled oscillator (VCO). An increase to the input voltage of the VCOwill
increase the frequency of the output signal. This signal drives an analog switch,
which alternately charges capacitor C1 and discharges it through the coil. Since
the analog switch has an undesirably high impedance, a field-effect transistor is
also used to lower the impedance. The parallel combination of capacitors C1 and
C2 plus the coil create a resonant frequency which should be matched to the
carder frequency of the VCO.The circuit can be turned off to conserve power.
Enable
Digital or_l Voltage-

analog--~1 controlled
signal / oscillator
Figure12.7 Circuit for drivingtelemetrycoil. AdaptedfromDuggan

(1981).
12.1.5 Input amplifiers
The pacemakercoil, in parallel with capacitor C2 in Figure 12.7, creates a tuned

circuit for receiving data. Figure I2.8 showsthat the signal is band-pass f’dtered
and envelope detected to create the pulsed signal in Figure 12.6(d). After’
decoding, the parameter value is placed in a RAM,at the location specified by the
parameter number. Some pacemakers have two copies of the RAMma permanent
set and a, temporary set---which make it easy for the physician ,to set the
pacemakerto a:temporary configuration and later reprogram it back to the usual
settings.
Decoder RAM
detector
Figu~12.8 Diagramof receivinganddecodingcircuitry for programming

data.
Figure 12.9 shows the basic circuit used to receive telemetry data from the
cir~uit Of Figure 12,7. The coil, and Capacitor create a resonant .~ircuit tunedto
the!~,c~irrier frequency. :The signal ~,furthe¢~ hand-paSS fll~t~red and then
fre~ ueacy-demodulate~!using a phase-locked loop.
Band-pass Phase-
filter locked
loop
Figure12.9. Diagramof receiving and decodingcircuitry for telemetry data. Adaptedfrom

Dti~gan(1981).
12.1.6 Inter~pt and CPU interface
As stated earlier, the closure of the reed switch by the progra~mming, magnet
causes a nonmaskable interrupt to the pacemaker processor. The processor
suspends its normal operation and reverts to an asynchronous pacing mode. It
then waits for an incoming message and dispatches it. Programmingparameters
replace old valueS:in the paramete~ RAM:Telemetry can be started and st6pped
by speciat pro~ng instructions~;When the magnet ~ is removed, the process.or
restarts pacing ¢¢ith the~newparameters. ~
12.2, ’ SOFTWARE.INTERFACE
Because of the complexity involved in interpreting the parameters in a modern

pacemaker, it is handled by software, The following sections. :describe ,various
parameters used in programmingand telemetry.
12.2.1 Configurable parameters
Modern pacemakers use complex algorithms requiting numerous parameters.

Many of these values can be programmed after implantation. Figure 12.10
summarizes many of the commonly-usedparameters.
Parameter Allowable value(s) Typical Units

value
Mode VVQ, DDDR,Off, etc. DDD None "
Lower rate 0 to 140 60 pulses/rain
(pore)
Hysteresis rate 30 to 140., Off Off ppm
Upper rate 80 to 185 160
Upper rate Wenckebach,f’LXed - None
response ratio, automatic mode
Refractory 200 to 775 400 (A), ms
period* 300(v)
¯ AVdelay, sense 15 to 300 180
AV
delay,pace 15 to 300, Dynamic Dynamic "ms
~DynamieAV Low, Medium, High, Medium None
delay Off
Safety AVdelay 100 to 150
Sensitivity* 0.5 to 7.5 1.5 (A), mV
2.5
Ventricular 24 : .ms
blanking period
Electrode Unipolar, bipolar Unipolar i None
polarity, sense*
Electrode Unipolar, bipolar Unipolar None
polarity, pace*
Pulse amplitude* 0.1 to 9r6 4.8 V
Pulse width* 0.05 to 1.5 0.5 ms
Downloadable CPUinstructions
code
Telemetry On, Off None
Figure12.10Typicalprogrammable
parameters.Items denotedwith asterisks (*) haveseparate
atrial
andventricular
settings.
The pacing modeis the basic operating mode for the pacemaker, as defined
by the NBGcode. In the absence of sensed beats, the pacer outputs at the sensor-
indicated rate or the lower rate, whichever is greater. The unit will not begin
pacing until the natural rate falls belowthe hysteresis rate. The upper rate is the
fastest rate that the pacemakerwill output; special options are sometimesavailable
to handle tachycardia. The refractory periodis the period after the last sense or
pace during which a new pace will not occur. The AVdelay is the interval after
an atrial sense or pace that the ventricle must be sensed; otherwise, a ventficular
pace may occur. It may be reduced with increasing heart .rate by setting the
dynamic AVdelay(Biotronik, 1993.). Chapter .9 gives further descriptions
these parameters.
-,~.,- Inorder to detect an atrial or ventricular event, the voltage received by the
sense,amplifier of that channel must exceed its sensitivity value. After an atrial
pace;~the ventricnlar sense amplifier is blocked for a given, duration to avoid its
m
sensing-of the atrial pulse. The polarity of the leads during,sensing and pacing
whether the voltage applied or measured is relative to ~he pacemaker case or
across a bipolar ,lead---can also be configured. See Chapter 8 for more
irfformation. Whena pace occurs, its peak amplitude and duration is determined
bythe~ pulse~width and pulse-height.parameters (Chapter. 11).
Additional functions can ,be enabled via programming. Some
microprocessor-based pacemakers allow executable code to be downloadedinto a
RAM.This allows the physician to patch the built-in code or provide a different
algorithm. This capability is-generally implementedonly in prototype or research
pacemakers (Ripart et al., 1984). The uploading of telemetry data is also
e0n~olled using special start and stop commands.
.... "Many pacemakers now have the capability of performing programmed
~finllilation through the pacemaker. The procedure spares the patient the trauma
~ Qejated with electrophysiological (EP) catheterization, and in most cases

S Cost. original implementations operated the pacemaker in VVT.or AAT
~eg"and used Cbest wall stimulation to trigger the pacemaker. Newel~ designs
hiapiement n0ninvasive pulse stimulation (NIPS) either’in the pacemakeritself
in the programmer.
12.2.2 Telemetry of biomedical signals
On~e~tf the advantages of a bidirectional communicationlinkis the ability of the

p~emaker to communicate ~:the status of the patient and ’pacer ’back to the
"p~i~ie~ani Figure i2:11 summ~zestypical data that are commonlytelemetered~
Parameter Units ~
Prog~g parameter status Read back value "
B,atte~. vol~ge
Battery’impedance
Battery current
Low battery True/False
Lead impedance
Pulse voltase V -
Pulse current
Pulse width
Pulse charge
Pulse ener~
Sensed events
Paced events Count
Histogramof events vs. pulse rate Counts
Electr0gram . mV
Rate-adaptive sensor reading Varies
H~12.11.Typical telemetrydata and their respective units.
All of ~the parameters that can be programmedcan also be ,read back, or

interrogated. This allows the physician to confirm the programming of the
pacemaker. The voltage, current, and internal impedance of the pacemaker

battery can be measured to estimate the remaining battery life. A low battery
indicator is also available; it is latched on if the battery voltage falls belowa
certain reference voltage and can be reset through programming. The impedance
of the leads and the voltage, current, width, output charge, and energy of the
output pulse can be reported in real-time. Counts of the number of sensed and
paced events can be measured, as well as a statistical report of the number of
events in particular ranges of the heart rate. Finally, the physician can acquire the
electrogram and signals from any other sensors in the pacemakerin real time.
12.3 PACEMAKER FOLLOW-UP AND CARE
Although modempacemakers are self-contained units which require no daily

maintenan.ce, it is important for the physician to perform regular checkups to
assess ,~ condition of the patient and pacemaker as well as perform any
corrective actions. There are also conditions from which the patient should be
restricted becanse of possible damageto or malfunctioning ,of the pacer. The
following sections detail the follow-up procedure and pacemakercare.
12.3.1 Office visits and telephonic monitoring
The pacemaker should be monitored closely during the first~few months after
implantation. In the U.S., Medicare Guideline I specifies coverage for pacing
systems with less than five years of clinical data, It provides for transtelephonic
follow-up once amonthfor the first six months, then e’(ery other monthuntil the
end of the third year after implantation, and monthlythereafter. Manyphysicians
use this schedule (Biotronik, 1993).
The visit begins by placing the programmer head--containing the reed
switch magnet and the programmer coils---over the pacem.aker l~ody (Figure
12.12). LEDs on the programmer head indicate when thehead ~and pacer are
within the proper range.
aker-(implanted)
Programmerhead
Figure 12.12Positioning of the programmer

head over the pacemakerfor programming.
Several tests are routinely performed during these visits. The programming
parameters are verified and the battery status is checked. Real-time telemetry of
the electrogram and other sensor signals is acquired; a normal rhythmshOddbe
observed: Finally, the pacemaker should exhibit the normal operation of sensing
and pacing: Because programmers are often used by persons without engineering
of eoniput~r backgrounds,it is especiallyimportant to makeit easy to use.
~ ,’ Pacemakermanufacturers sell programmersthat are compatible with. their
ownpacers, but are rarely compatible with other pacemakers due to proprietary
modulation and encoding schemes. Programmers which are compatible with a
variety of pacemaker brands are also available. Multiprogrammerseaninterface
with, more than one manufacturerrs proprietary protocol. A single protocol for
all pacemakershas been proposed but not accepted; in that case, we could use a
single universal prograrntner to program any pacemaker. An emergency
programtner~has also been proposed which could :revert any pacemaker into a
basic VOOmodewith 70 beats/min at maximal output (Schoenfeld, 1993).
,~.~:Instead of makingan office visit for a check-up, a patient maysave time and
~oney by using :a telephone link from homeor a local Clinic to the physician’s
office:, The patient, with prior training, uses a portable programmingunit that
has the entry and display hardware replaced by a computer modem.Another
modemcgnnects the physician’s computer via local or long-distance telephone
(lrhakor et al., 1982).
i2~3.2 ~Restrictions-to other therapies
Ma~0ydiagno,stic and therapeutic procedures create conditions that maydamage

~6 ~geemaktr (physically or eiectribally)or can mimic the nodal or abnormal
~fidti~ari of th~ he ~ar~.( Malfunctionsmayoccur immediatelyo~: at a later time.~
~y paceniake.r manufacturers suggest the following restriction~ ~
’.i ’Diathermy’i~s the use of higl~frequency electro fields to hea~ tissue for
~. B~ause of heating ~ff~cts in the pulse generator, this therapy should ¯ be
a¢isided (M~dtronic, 1990; Biotronik, 1993).
Electrosurgery and electrocautery use electricity during surgery to cauterize
tissues. The currents can cause the pacemaker to fail, change mode and
parameters, or exhibit low-battery settings. If electrosurgery is necessary, steps
should be taken to preprogram the pacemaker into VOOmode, place~ theground
plate under the buttocks or legs, choose a bipolar electrocautery system, use low
energy levels and short duration bursts, and keep the scalpel at least 15 cm from
the pacemaker~In addition, a temporary pacing system and a defibrillator.should
be~available as a backup (Medtronic, 1990; Biotronik, 1993).~ -
Manypacemakersare protected against defibdllation;,~nonetheless, several
pi?eeautionsshould be obServed~.’ The paddle~ should plac~¢d along a line i~at is
perpendiculars,to that, t,~of the pacemakerand the implanted lead and shouldb~ no
less than 10 cm from the pacemakeror electrodes. After applying a pulse of the
lowegt necessary energy setting¢~the pacemaker should be checked for proper
operafion~(Biotronik, 1~93)~. ’ ~? ¯ .~ ~’ ¯ i ~ , ~ ~
~agt~ti~ resonance imaging (MRi) is a medical imaging t~hnique that uses
strong magnetic and RF fields. The static magnetic field can cause movementof
the pacemakerunit and leads Or closure of the reed switch, even whenthe titlit is
not scanning. Whenscanning, the RF field can cause improper triggering and
Pacing, tissue damage, or. pacemakermalfunction (Holmeset.:al., 1986). Because~
of .the:danger involved, MRIshould be used~only in extreme, circumstances
(Medtronic, 1990;~Bi0tronik, 1993). " .
* Transcutaneoug"~6iectrical nerve stimulation (TENS)is th6 application
electric.currents to relieve pain. It isnot widely clinically accepted ahd shbuldnot
be .used on pacemakerpatients (Biotronik, 1993).
288 DESIGN OF~ CARDIAC PACEMAKERS
Lithotripsy is the use of shock waves to disintegrate calcifications in the

body. It can interfere electrically or mechanically with :the pacemaker(Biotronik,
1993). If treatment is necessary, the pacemaker should be preprogrammedinto
VOO mode, placed at least 5 cm from the focal point of the lithotripsy be ~am, and
checked for proper operation after treatment (Medtronic, 1990).
X ray and fluoroscopy can be used with pacemakers. All pacemakers have a
radiopaque label which can be used for identification of the device. The levds of
ionizing radiation used in radiation therapy, however, may permanently damage
the pacemaker (Medtronic, 1990; Biotronik, 1993). If therapy is necessary, the
pacer.should be shielded from the radiation and checked for proper function after
treatment (Muller-Runkelet al., 1990).
Finally, additional factors in home and work environments are often cause
for concern for pacemaker patients. Electromagnetic interference (EMI)from
power lines has been shownto have little effect on the operation of pacemakers;
careful selection of lead placementand sensitivity levels will reduce susceptibility
under even extreme circumstances (Toivonen et al.,~ 1991). However, electrogram
artifacts have been noted in the vicinity of occupational electric equipmentsuch as
arc welders (Embil et al., 1993) and degaussing coils (Marco et al., 1992). Other
hazards have also been reported from metal detector~ security gates (Copperman
et al., 1988), retail antitheft devices (Dodinot et al., 1993), and radio2controlled
toys (Manet al., 1993).
In conclusion, telemetry and programmingenable the physician to monitor
the patient and provide changes to the operational parameters of the pacemaker.
The hardware provides encoding, modulation, and ’error checking in order to
reduce the risk of spurious programming. Many,parame~ters may be .set and/or
measured depending on the type of pacemaker.. Finally, successful therapy
depends on good-foll0w~up ~nd car~ of the patient b.nd pacemaker after
implantation.
12.4, REFERENCES
Baltina, W.P. andWhite,R. M.1985.Acquisitioncircuit for cardiacpacer. USpatent 4,550,731.

Biotronik, Inc. 1991. PMS600 Programming and MonitoringSystem.for Biotronik Heart
Pacemakers OperatingInstructions. LakeOswego, OR.
Biotronik,Inc. 1993(.Genmos 04, 04-AUnipolar/B’ipolar MultiprogrammableIraplantablePulse
Generator Techm’calManual.LakeOswego,OR. "
Copperman, Y; Zaffati, D.,’andLaniado,S. 1988.Theeffect of metaldetector gates on implanted
permanent pacemakers. PacingClin. Electrophysiol.,11: 1386-1387.
Dodinot,B., Godenir,J. P. andCosta,A. B. 1993.Electronic.article surveillance:a possible
dangerfor pacemaker patients. PacingClin. Eiectrophysiol.,i6: 46,
Duggan, S. R., 1981,Implantabletelemetrytransmissionsystemfor analoganddigital data. US
patent 4,281,664,
Embil,J. M., C_wAdes, J. S., Foster, D., andSandeman,J..1993. Returnto axe weldingfollowing
defibrillator implantation.PacingClin. ElectrophysioL,16: 2313.
Fyke,F~E., IR 1963.Maleficentmagnetsandmangledn~egabytes.PacingClin. Electrophysiol.
16: 1231~
Gordon, P. L., Calfee, R. V., and Baker, R. G. 1982. Multiprogrammablepacemaker
technology.In S. S. BaroldandL Mugiea (eds.) Thethird decadeof cardiacpacing:advances
in techniqueandclinical applications.Mount Kiseo,NY:.FuturaPublishing.
Hartlgub, J. :T., McDonald,R. S., and Shearon, L. W. 1981. Temporaryand permanent
pro~le digital cardiac pacemaker.USpatent 4,253;466.
Holmes,D. R.; Jr.; Hayes,D. L., Gray,J. E~, and Meddeth,|.1986. The-effectsof magnetic
resonanceimagingon implantablepulse generators.PacingClin. ElectrophysioL, 9: 360-365.
EXTERNAL PROGRAMMING 2 89
Man, K. C., Davidson, T., Langberg, J. J., Morady, F., and Kalbfleisch, S. J. 1993.
~-Interference from a hand held radiofrequency remote control causing discharge of an
"~ implantabledefibrillator. PacingClin. Electrophysiol.,16: 1756-1758.
Marco, D., Eisinger, G., and Hayes, D. L. 1992. Testing of work environments for
electromagneticinterference. PacingClin. ElectrophysioL,15: 2016-2022.
l~exl~nie, inc. 1990. Minix Multiprogrammable PacemakerTechnical Manual.Minneapolis, MN.
Muller-Runkel,R., Orsolini, G., and Kalokhe, U. P. 1990. Monitoring tbe radiation dose toa
multiprogrammable pacemaker during radiation therapy: a cash~ report. Pacing Clin.
ElectrophysioL, 13: 1466-1470.
Ripart, A., Fontaine, G., and Mugiea, J. 1984. Howshould the software pacemaker be
programmed during manufacturingand after implantation? PacingClin. Electrophysiol., 7:
1202-1206.
Schoenfeld, M. H. 1993. A primer on pacemakerprogrammers.Pacing Clin. ElectrophysioL, 16:
~ 2044-2052.
Thakor, N. V., Webster,J. G., and Tompkins,W. J. 1982. A battery-powereddigital modemfor
telephone transmission of ECGdata. IEEETrans. Biomed. Eng., BME-29:355-359.
Toivonen, L., Valjus, L, Hongisto, M., and Metso, R. 1991. The influence of elevated 50 Hz
dectric andmagneticfields on impl,,ml, te~ cardiacpacemakers:the role of lead configurationand
;!~: prOgramming ~ensitivity: PacingChn. Electrophysiol., 14:’ 2t14-2122.
INSTRUCTIONAL OBJECTIVES
l~2A Descdbethe difference betweenpaeemakerprogramming and telemetry.

1~,2~ .Sketchthe reed switchdebouncing circuit andekplain its Ol~’ration.
12~3 Explainwhythe reed switch is no longer used to receive cx~mmunieation pulses.
i2~4,~ Describe thb parts of a programmingmessage. ’
1,2:5 Givenaparticular bitsequence, such as 001011, sketch the encoded(but not modulated)
signal using the encodingteclmiquein the text.
12,6 Describethe methodsused to detect commtmieation errors.
12.7 Describe five programming parameters.
12;8 Descdbefive telemetrydata.
12.9 Explain the difference betweenuniversal programmers,multiprogrammers,and emergency
programmers.
12.10 Describe five medicalproceduresthat mayadversely affect pacemakeroperation.
13
Rate-Adaptive Pacemakers
Timothy Harvey
Rate-adaptive pacemakers use information from a sensor to Change the rate of

stimulation. In situations like complete heart block, whenthere is a naturally
stable atrial signal, pacemakers can synchronize the heart beat to that signal.
Pacemakers like DDDand VAI sense the atrium. However, about 50% of all
pacemaker patients have symptomaticsinus node dysfunction. Other patients have
unreliable atrial signals due to atrial flutter or other possible disorders. For these
patients there is no adequate frequency commandsignal to .the heart for the
pacemaker to measure. Therefore, the heart rates for about half the people that
get pacemakers are determined solely by the pacemaker, The ~major focus of this
chapter is the sensors, other than the atrial sensor, that can help pacemakersknow
whenand howto change the heart rate.
13.1 INTRODUCTION
Cardiac output is determined by two factors, the volume of blood pumpedout per
beat and the heart rate. Normally,the heart rate is the major factor in controlling
cardiac output. During strenuous exercise, heart rate can increase by 250%over
its resting rate, comparedto about 50%for stroke volume.If the heart rate is set
at a constant rate, for example by a VVI pacemaker, then the body will have to
adjust stroke volumein order to adjust cardiac output. A fixed heart rate places a
serious limitation on the ability of the body to adjust cardiac output to the
demandsof exercise or other physical activity. This abnormal situation puts a
heavy strain on the heart muscle. If there is insufficient cardiac output, the patient
maybecomefatigued and maynot be able to continue exercise. It is clear that,
especially for active patients, rate adaptation will increase the quality of life,
comparedto fixed rate pacemakers.
One way to determine if rate-adaptive pacemakers will help a patient is to
look at their heart rate reserves (Furmanet al., 1993). Generally, chronotropic
incompetenceis classified as whenthe range of heart rate is less than 80%of the
theoretical value. The theoretical maximal heart rate (MR) and the heart rate
range are determined from the patient’s age and resting heart rate (RR).
MR= 220 - age (13.1)
Range = MR- RR (13.2)

~TE.ADAPTIVE PACEMAKERS 291
, To calculate the border ’of chronotropic incompetence (BCI)~ ,multiply the

heart rate range by 80%and add it to the resting heart rate.
BCI = RR+ 0.8 x range (13.3)
Putting Eqs. (13.1) through (13.3) together,
BCI = 176 + 0.2RR - 0.8 x age (13.4)
For example, consider a 70 year old patient with a resting heart rate of 65
bpm. Using Eq. (13.1), his maximalheart rate should
220 - 70 = 150 bpm (I3.5)

~ FromEq. (13.2), his theoretical heart rate range
150 - 65 = 85 bpm (13.6)
~,:~:~ The border of chronotropic incompetenceis calctilated from Eq’. (13.3)

(13,4)
"~’. BCI= 65 + 0~8..× 85 =133 bpm = (13.7)
:i Using exercise testing~ the patient’s maximalheart rate is found. If it is less

tlian 133-bpm he would .be a good Candidate for a rate-adaptive pacemaker.
HOwever,t~s is0nly an approximation, and does not allow for the fitness of the
’~,<~’~This ’chapt~r~gives"the~ reader a general understanding of rate-adaptive

p~ieemakers.. First, it.d, scribes the various sensors used. Then it discusses
different control strategies. Finally~ it gives a summaryof.rate, adaptive
13.2 SENSORS
This section summarizes the different sensing techniques Used by rate-adaptive

pacemakers.It .des~cribes~ what each sensor measures, and .why. It also discusses,
howthe signal ~lS measured.This includes the sensor type and locauon. Finally, it
gives someadv~antagesand disadvimtages for each of the sensors.
There are !a-few special considerations ~hen evaluating different sensors.
Somesensors require extra leads, other than the pacing lead. An extra lead may
movearound over time, increasing the likelihood of irritation. Other sensors can
use the pacing lead.witha few specialized-modifications. Specialized leads ha~e
the sensorbuilt into the lead. This requires more wiresin the 1cad, makingthe
lead bigger and less flexible. If special or extra leads are needed the system will
be more difficnlt to implant, and it will be more expensive. During pacemaker
upgrades;~the Old leads are~leftin if possible. If the.new sensor needs a special
lead, .it might not, be~possible touse the old leads. ~- ~.: ~
Plaeingdeads in~ the bloodstream causes other problems, First~:to correctly
place the electrode intheheart, x-ray fluoroscopy is commonlyused. This adds
cost, complexity and perhaps some radiation side effects. Electrodes in the
bloodstream may also experience more motion artifacts during heart beats.
Sensors which do not need to be placed in the bloodstream are attached to the
outside of the heart. Typically these are implanted during open heart surgery,
which also adds trauma. In the body, some sensors and electrodes get coated with
more fibrotic tissue, makingthem less sensitive and perhaps less useful; Also,
some sensors require more power than others. This will lead to shorter
pacemakerlifetimes.
13.2.1 Impedance measurements
Many of the sensing techniques use impedance measurements to get their

information (Alt et al., 1993; Benditt; 1993). This section will describe three
different impedance measuring systems which the following sections may refer
back to. There are other methods and configurations, some are mentioned in
section 16.4. However these three systems cover the main ideas of impedance
measurements.
Common impedance measurements use three electrodes, with the pacemaker
case serving as one of the electrodes. Twoof these electrodes are used to emit a
signal, whichis typically either a low-amplitude high-frequency signal, or a low-
amplitude pulse train. The amplitude is typically 1-10%of the threshold required
for mnsele stimdation to save energy. A different pair of the electrodes is used to
pick up the signal. One method (Figur e 13.1(a)) uses a unipolar pacing lead
an extra unipolar lead~ with the pacemakerease as. the ground. The extra lead is
placed in the subcutaneous tissue across the anterior chest wall. Unipolar leads
can become inhibited by myopotentials. Another similar method uses a standard
bipolar pacing lead as shownin Figure 13.1(b). The i’ing electrode takes the place
of the auxiliary electrode in the previous system. These two systems have durable
sensors, However,even though the emitted signal has a small amplitude, they add
up. These two measurements require additional power consumption. Also, the
signal generator used to measure impedance may be an annoyance to
electrocardiographers, and may interfere with transtelephonic pacemaker
monitoring (Benditt, 1993).
(a) (b) (c)
Figure13.1 Impedance measurement systems.(a) Extra lead configuration. Theextra lead

placedin the subcutaneous
tissue acrossthe anteriorchestwall. (b) Bipolarlead configuration.
(c)
Two-electrode configuration.
The final impedance measuring technique is in the experimental stage.

Impedance can be measured using a single unipolar pacing lead as in Figure
13.1(c). Actually; a bipolar lead similar to Figure 13.1(b) can be used with
emitter and measurementtaken between the ring and tip electrodes. A voltage is
RATE-ADAPTIVE PACEMAKERS 293
applied betweentwo electrodes and the current is measured.UsingOhm’s~law the

impedancecan be obtained. Theobvioussignalto use is the pacing,pulse(Chifife,
1991), whichwill yield the right ventricle end-diastolic volume.Us’mgrthepacing
pulses meansthat this methoddoes not require any more power, except for
processor power.r Aproblemwith this methodisthat it maynot proyide adequate
samplingrates for certain signals. For example,if an inhibited pacemakermode
is~iused, and no stimulusis neededfor a fewbeats, the pacemaker will not be able
to measureventilation rate. Also, the samplingrate wouldbe dependenton heart
rate; : makingcalculations more complicated. Dueto-these problems, this
techniqueis not very useful for slower signals like ventilation.. Properlytimed
pulses other than the pacing pulse can yield specific cardiac information. One
such measurementis end systolic volume,obtained,by a~ second, smaller~ pulse
emittedat the endof systole.
13~2~2 Atrial sensing ~r~
I~ patients ~wherethere is adequateatrial stimulaUon,a sensor can be used to

~t~t.the sign~i (Funla~ et ’a]., 1993). Oncean atrial signal is detectedi
.,~i~cle Can be sfi-muiated with the proper AVdelay. TOmeasurethe atrial
~!g~ial~twodifferent methodscan be used. Thecommon wayto meamrethe atrial
si~iial is tO use an extra, s[andard lead placed in contact with the ~trial wall
~ternative|y, a speci~ lead. used to Stimulate the ventricle can be used that can
~o detect the atrial s~gnal. ~ " " .... . - ~
~If the atrial signal can be properlymeasured,then this’type .of pacemakercan
p~perlycontrol the heart rate followingtheSAnode signal. Thi~’~pacemakerwin
~yfie~0iiize ~ with the SAnode and needs no-tuning after~installation, and
e]~fe~&ivelybridges AVblocks. However,this methodcan not ’be used in cases
wherethere is no reliable atrial signal. If a second lead is used to sense the
~tim, it adds e~penseand complexityto installation. Also:-for Youngerpatients,
the se~0ndlead ~ay add discomfortas they grow. The’ atrial lead can alwaysbe
a~ldrd later, during a pacemakerupgrade. Sinus node dysfunction¢ atrial
fibrillation; flutter’, and other arrhythmias,makethis sensorUseless/ACcording to
Ftmnanet al, (1993)aboutone third of USpatients use atrial sensing. ~ ....
13.2.3 Direct metabolic sensors
Car~acoutput shouldincrease with an increase in the metabolicrate. This helps

traneport mor~ oxygen tO the, body and remove more waste products. The
followingtwo~sensors, in eff~t,, measurethe metabolicrate of the body, Using
either oLthesetwo sensors would, ,allow, the, pacemakerto. use a closed, loop
controller. ~Thesesensors are theoretically appealing, but not very practical so
far.
Central venous pH
One~of the first sensors studied for use in rate. adaptation ,was ~e pHsensor
(Benditt, 1~993)~ASthe exercise level incre~s, the l~ood bec0me~m~reacidiC.
The system Consisted of a reference Ag-AgCI electrode placed in the pacemaker
case :hnd a pH-~sensitive Ir~IrO2 electrode placedin the right atrium. ~These
e|ectrodes co-ulaldetect a change.in the bl~pHdue to exe~reiS~or disbase. Once
a’ ~hangewasde~ected, the pa~ingrate could be changedaccordingly~Usingthis
system like a closed-loop controller essentially let the pacemakeradjust the heart
rate to keep the pH constant.
The system would-not require any additional power consumption. However,
there are manyproblems with this system. First, there is a complexrelationship
between pH and heart rate. The electrodes are even more of a problem. The lack
of long-term pH reliability and stability in the body have led to problems. Also,
the specialized pacing lead with the pH sensor in it is a drawback. The electrode
gets covered with fibrotic tissue and maybecomeless sensitive to pH. The pH-
monitoringsystemswere unsuccessful in their initial clinical applications and are
not currently available.
Mixed venous 02 saturation

The other sensor that directly measures metabolic rate is the oxygen, saturation
(SO2) sensor (Alt et al., 1993; Benditt, 1993). One of the major roles of
cardiac system is to deliver oxygen to the body. If theheart is not providing
enough blood to the body, the SO2 decreases. To compensate for this, the body
should increase the cardiac output in order to get more oxygenfrom the lungs. It
is onlynatural to try to use SO2 in a rate-adaptiVe pacemaker. One .way to
m~ast~re~SO2~is tO us~ two LEDs ~d a photodetector to measure.the blood’s
reflectivity in the right ventricle. Ti~e photodetector is most likely:a
phot~tmnsistorl that i~ ~ensitive to both of the LI~Ds’ frequencies, however
photodi~des and photoresistors could also be used. One of the LEDSis red
(660 nm), while the other is in the infrared region (805 nm). The reflectivity
the blood in the red wavelengths depends on the hemoglobin. This can be
understood when. you consider that oxygenated blood looks ~r,e~_ and deoxygenated
blood io0~s bluish. Since the lungs will replenish ~the blood s oxygenlevels, the
measurements should be taken on the. venous side of the cardiac system, where
there are greater variations in SO2.
,.Oxygen rich red blood will reflect the red LEDlight much better than
deoxygenated blood and will cause a higher detector current. If SO2drops, the
photodetector-currenl: will decrease and:the pacemaker will speed up the heart
rate;in order to increase ~SO2. The infrared_ LEDis not affected by SO2and is
therefore used as a reference value, In the blood, this window, can become
covered with fibrotic tissue. This wouldchange the amountof reflected red light.
The sensor may also move around inside the ventricle over time. The measured
signal maybe very different if the windowis facing across the ventricle Or if it is
up against a wall. For all these disturbances, the infrared signal wouldbe changed
similar:~to the red-signaL The’pacemaker can use the infrared signal to
compensatefor these disturbances. If both thered and infrared signals ~ drop by
the same~ amount, then the pacemakerwill ignore~it: .if thered signal increases
and the infrared signal doesti’t, then SO2is increasing. Since both-LEDsuse the
same detector, the t~/o LEDsare time multiplexed~so that only 0ne LED.is on at a
time. Typically the LEDsare pulsed for 2 to 10 ms every 4 s or so. Over a five
year period, the LEDswill be on for about 100 h.
An SO2 sensor w~ill allow closed loop control that can react to stress and
emotionl ~Th~reare:~rdbleins with thi~ system. First a special lead, with the LED
an~: photode[eet6~’:!n;~it, is needed... Thislead needs to’have the LED’and
pti6todetect0r~iri~ide ofih ~ind6w, aa’ showninFigure 13.2. The~Sensorneeds to
be Oiacedin thefi~ht ~,~ntrlcle.’Therei~’aig~i~a lag in the systemd~eto the time it
takes the blood toretUrn to tlie hehrt from the ~us~les. Thomain~problem is that
th6 LEDsare:veryinefficient light sources and requi~e a lot of power, which will
de~ease the battery life of the pacemaker. Benditt (1993) estimated that these.
sensors will shorten the pacemaker life by six months. There is no SO2_sensor-
based, pacemaker available today, However, due to rapid progress with these
senators; they maybe important rate-adaptive sensors in the f~ture.
’~ ’ =~Oxygenated
~-~ ,.,~ ~’, J H~moglobin
III = ,Deoxygenated
~ ~: 1 ~ ~lemoglobin
l~ig~ire ,1~ Oxygen saturation sensor. Oxygenated hemoglobin m the right ventriclereflects the
red LED s ~ght. Conversely the dex~xygenated hemoglobi~ absorbs it. Both ~flect infrared light. ~
~3;2,4 Indirect metabolic sensors
Indirect,metabolic signals allow the pacemaker,to estimate the metabolic ,rate.

With~goodestimations, near closed-loop~ control can be implemented.~~
Venalation.~ rate
Since: effective SO2sensors: are not available yet, another ~me~odis to estimate
the oxygen, intake: Perhaps the most obvious parameter to estimate~oxygenintake
is~e ventilation rate (,Alt et al., 1993;~Benditt~,1993; ,Furmar~;etal., 1993). Since
~9156,ventilation rate has, been considered= for use ;with rate-adaptive pacemakers.
I~,has been shown~expedmentallythat.there ~is a good correlation: between heart
rate, ventilation rate, and oxygenintake. This is in both normalpatients and those
with~respiratory, diseases.
Ventilation~ rate can ;be measured by analyzing, the:imPedance between ~e
pacemaker electrode ,and the paeemaker,’s~=body. The, impedance measurement;
conlfigurations in Eigure 1,3;l(a~ b) are the techniques used for measuring
ve~i!lation~rate, with the extra lead ,method more eommon:,,As ,the patient
b~athes, the chest impedance changes. From~ichanges~,~i~, this-me~s,ured.
impedance,:ventilation rate,can !no,derived: The ventilation :sign~ has a relatively
low; frequency,= comparedto ~heartbeats and noise. The pacemaker~must select and
measure .the proper signal.component. Since .,the range of ventilation rate :and
ttem, rate :ovedap,, just simple bandpassf’dters cannot be used, Therange of heart~,
rates is ~normally 60-200 bpm, so the, pacemaker must be able,.to h~andle ~a
ventilation rate above 60,breaths/min~ Typieal~ly, the pacemakerwould filter o~!t
s~gnals,, above,60~eycles/min, ~ thus= losing~tra~k of~~the ,ventil,ation rate~ The
pacemakerwill hold the ~ensor , signal; to that correspondingtoga ventilation rate
of 60 breathslmin, until the rate. drops into the:readable range;,.,~, :
A final~,~way~todetect ~ventilation rate,is to use, envelopedetection o~ other
sensor signals (Chirife, 1991). Manysignals like the intracardiac,,ven~icular
electrogram fluctuate with ventilation. Therefore it is possible to extract

ventilation rate information from them. Envelope detection seems to suffer less
from arm-movementartifacts. This method is useful in multiple sensor designs,
whichwill be discussed later. Envelopedetection is still in the experimental stage.
An advantage of the ventilation rate system is the durable sensors. However,
just ventilation rate does not track all physiological changes well. If the auxiliary
lead is used, it adds expense and can lead to more irritation, and other problems.
Armswinging and coughing change the chest size ahd can be detected by these
sensors. This can cause erroneous heart rates. Ventilation rate systems cannot
distinguish between shallow and deep breathing. Not much work has been done
on ventilation rate sensors, since minute ventilation seems more promising.
Howeverventilation rate pacemakers have been successfully used in Europe for
years.
To see howwell ventilation rate approximates SO2sensors, consider the task
of breath holding. For a SO2 sensor, as the SO2 decreases, the heart rate
increases. Eventually, the.rate mayreach the maximalvalue. A ventilation rate
sensor decreases the heart rate, eventually to the resting heart rate. These will be
the results regardless of the activity. It makesno difference whetherthe patient is
swimmingor resting.
Minute ventilation
A better approximation of the SO2sensor is the minute ventilation sensor (Alt et
al., 1993; Benditt, 1993) (see Chapter 17). Minute ventilation is the product
ventilation rate and tidal volume.This effectively measuresthe amountof air that
is being inhaled. Minute ventilation has been found to be an excellent parameter
for estimating metabolic .rate, and can detect some changes due. to stress and
fever. Minute ventilation ranges from about 6 L/min at rest to about 150 L/rain
for an athlete at maximal exertion. TO measure minute ventilation, impedance
measurementsof the chest, like those used by ventilation rate,, are used~ Envelope
detection of other sensor signals (like pressure~ and electrograms) can also
usedto obtain ventilation inftrmation in multiple-sensor systems, The frequency
of the ventilatory signal gives the ventilation rate, .and the amplitude gives tidal
volume. The bipolar lead in Figure 13.1(b) is the most commonimpedance
sensor.
The signal received by the sensor contains a lot of information and has to be
prbcessed. First, the signal will have in it a higher frequency componentdue to
the beartbeats. To alleviate this problem a signal-averaging process with a 30-s
averaging windowis used (Alt et al:, :.1993). This workslike a low,pass f’flter.
The system should also track~slow changes in minute ventilation, due. to things
like circadian rhythm and sickness. To dothiS a reference value is determined by
a second signal-averaging process, wi~.an-averaging~windowof about one hour.
The difference between the two averagers is the change in minute, ventilation that
is sent to the controller. This setup~allows the system :to track slow changes, as
designed, but can present a problem. If the ~patient participates-in prolonged
exercise, approaching one hour or more, the reference value will slide up to the
current,value. This would, canse the difference between the two averagers to
decrease eventually to zero. If the pacemaker was~allowedto do this, the heart
rate would erroneously decrease~: .To keep this from happening, minute
ventilation pacers of this-type freeze the long~ermaverager when.-the short term
value is above 50%its maximal value. Oncethe short.term value ~drops below
50%, both ~registers resume theiraveraging~. -,
Experimentally, minute ventilation pacemakers have proven~ to have very

successful rate~ response at rest and during exercise. Minute-ventilation systems
can use the standard bipolar pacing leads. Also, the system tracks many
physiological changes well. Unlike activity sensors, minute ventilation sensors
increase heart rate while ascending stairs and decrease heart rate while
descending them. However, the impedance measurements consume power, which
Shortens the battery life. Just like ventilation rate, minute ventilation pacemakers
w:ill~.slow the heart,rate while breath holding., Motion artifacts due to the
eteC~ode .moving or upper body movementcan be picked, up, causing possible
false detection. Armswinging can be picked up since it may have .a frequency.
~ery, si:milar to ventilation.~This maycause an increase in the heart rate. Talking-
during exercise will decrease the heart rate,, Finally, there is a lag incorporated in
the, ~controller, since the measurement does not measure the instantaneous
ventilation rate but the average rate over the last breath or so. Another problem
is due to the overlap of ventilation rate and heart rate..If ventilation rate exceeds
60 breaths/min, the rate-adaptive algorithm is suspended. For this reason these
sensors should not be used in young children or in patients prone to
hyperventilation.
, if:Because of its ease of implantation and" Setup, one application for minute
~/en~ilati0n sensors is for pregnant ’women(Lau et’al., 1990). Not wanting
dxpb~e an unborn’baby to x Pays, a minute ventilation pacemaker can be put in
d~ing a left subclavian puncture, with ECGand ultrasotind for guidance. Studies
Showthat minute ventilation works ~,ell dudng pregnancy and Cesarean section.
Mixed venous temperature

As~,~met.abolic rate increases, body temperaihr~ ’ and subsequently. blood
temperature, also increases (see Chapter 15). The lungs normally tend to cool, Off
the ~blood as it passes through the. alveoli. For the best temperature measurement,
v~n0us temperatures should be used, Measuring blood venous temperature can be
~.,gfod indicator, of metabolic rate, Putting a small.ceramic thermistor in the
pacing lead and positioning the lead so the thermistor-is, in the right ventricle lets
the blood temperature be measured. A thermistor is a temperature-dependent
resistor, so it is a simple sensor to use. Also, temperature changes are only a few
degrees, so the thermistor can be assumed to be linear. Blood temperature
i~r ~eases with exercise and ~ever.
i’~:~:~One advan~ageoftemperature sensing is that blood temperature is a good
indicator of m~/al~oli6 need. Also, the :~ensfr is qu~durable:’ However,a’~ial
p~fingle~/d is ~needed: Encapsulation 6f the
s~iisor over time~ The ~ig~als of interest are smaffandslow, So the: p~eernaker’s
response may’be ~16wer~ than desirable, ~ Short sprintsi~may "ti~t ~~ raise ~ the
ten~perature-etiough to be~deteeted~Finally; any heat sinkg near the body-may
e~e.ct the response. Temperature-based pacemakers are available, as Chapter 15
will elaborate oh.
13.2.5 Nonmetabolic physiological sensors
Nonmetabolic physiological sensors attempt to measure physiological changes

which indicate a change in heartxate is.in order. All but the ~pressure. sensor
measurechanges, causeddirectly ~bythe body, If it is sensed,that’ the bodyis trying
to increase cardiac, output, the pacemakercan help by increasing the heart rate.
298 DESIGN OF CARDIAC-PACEMAKERS
Q-T interval
The most successful physiological sensor for rate adaptation has been the Q-T
interval sensor (see Chapter 16). The Q-T interval is the same as the Stim-T
interval and is the time between the onset of the QRSwavet o the T wave. When
the body tries to increase the heart rate, not. only is the SA node frequency
increased, but catecholamines are also injected into the heart muscle. These
hormones shorten the contraction duration. ~During exercise or stressjthe Q-T
interval decreases. An appropriate heart rate response can then be implemented.
To measure these signals, the pacing leads used for stimulation can be used to
pick up the intracardiac ventficular electrogram:
Since this system has been successful, there isa good basis of clinical support
for it. This system also uses the standard lead, whichdoes notneed to be placed
inside the heart, They do not require any more power, except for the extra
processing, Q-T measurements respond to physiological changes~ in about one
minute. Onelimitation is that there are problemsdetecting repolarization signals.
Ventricular depolarization gradient

Ventricular depol~ization gradient (VDG)sensors are very similar tO Q-T
interval sensors (Beiiditt, 19~3). Instead Of measuring the time intervals, VDG
sensors measure the area under the paced intracardia~ ventricular electrogram’s
QRSwave~Other namesfor ~his. signal, are evqked:.v~ntdCtdarpotential and paced
depolarization integral~ ~The area isaffeeted by .hgart rate and sympathetic
neuroendocdne activity in oppositedirections. As exercise increases, the VDG
decreases. As heart rate increases, so does the VDG.
This system uses the standard pacing electrodes, not necessarily inside the
heart. This variable is a very good one for closed:loop control., It does not
require additional power and responds ~ quickly. VDGsensors can also detect
emotion and ,stress. However electrode polarization and some drugs make the
sehsing of precise local ventdcular, electrtgrams difficult. There .is no available
VDG-basedpacemaker, but there is a,multiple-sensor pacemaker that combines
VDGand minute ventilation sensors: ¯
Systolic indices ¯ . i ~ ~ ~.
S~stolic indices include stroke volumeand pre-ejecfion phase (see Chapter 16).
The pre-ejection pha~se (PEP) is the time bet~veen_~e ~oh~i ~0f ventricular
depolarization and. the opening of the ’abtedc. v~qe~ Sys[61iC indices are good
indicators f0r"rate adaptation. Impedance mea§t!re~ents ~ f¢om the p~cing
electro’de to the~.~acemak~r body c~tn-be used to mt~s~ 9hang~.,in blood pool
volume. S~roke’ vtlume will increase, and.the PEP will:decreast~ith exercise.
The pacem ~aker .can ~n adapt the heart rate to minimize the change in stroke
volume.
These pacemakers can use sta~dard:0r ;~i~hfly mbdified leads. They should
respond qtfickly to changes. However,like all impedancemeasuring systems, they
require more power and therefore shorten the battery life. These systems may
also pick up motion artifacts, " ~’
Pregsure " - ’
The cardiovaseula~ colati~0l system works to.keep,the mean. arterial blood
pressure (MABP)e0mtant (Air et al.,:1993;’Ber~ditt, 1993; Furmanet, al., 1993).
Therefore it is only natural totry to makea pacemaker that does the same. Both
RATE-ADAPTIVE ,!PACEMAKERS 299
magnitude and rate of change of pressure increase with exercise. A-piezoelectric

sensor is placed in the right ventricle. Because it cannot measure meanpressure,
it measures dPIdt, and from this infers ~meanpressure. A silicon strain gage
pressure sensor could measure meanpressure,
dP/dt
Piezo
Figure 13.3 Bloodp~essurederivatiye sensor. :As the: bloodpressure changesaroundthe

sensor,the walldeflectionwill change.Defleeti0nsof the wallapplya forceon the piez~element,
whichcreatesan el~trical signal.
¯ ,~s ~system. would ~o theoretically appealing since a ctos d-ioop¯ controller

~ ’si nde
eouid be used to keep the ~tessure constant: The sensor would, react quickly,
the blood pressure, should ehangequiekly with exercise: However, no system has
yet been adequately tested.which inco/porates pressure sensors. ’ The sensor would
13~2,6 Direct activity sensors
Because the major reason for changing the heart rate is exertion, th6 most
commonrate-adaptive pacemaker is the motion-detecting pacemaker (see Chapter
14). In these systems, either an accelerometer or a vibration sensor is used to
estimate activity. These elements are placed, inside, the pacemak~ercase. These
sensors detect motionand vibrations in the upper chest. After the level of actlwty
is estimated, the heart rate is adjusted according to an algorithm.
The prime advantage of activity sensors is the experience and confidence
people have in ,tbem, Furtber, placing~the rugged sensors inside ,~,e pacemaker
case makesimplanting, a rate-adapfive~pacemaker~.ofthis type no differe~t~ than a
normalpacemaker.This also protects the sensor, providing long-~termtell.ability.
Also, very little additional poweris needed to run these sensors. Activity sensors
are very fast and therefore can allow for very responsive- pacemakers,, ~e m~n
disadvantage of these sensors are their specificity. They may pick up some
undesirable,signals and~.miss other desirab|¢~ones. Imagine. a task ofwalking
staixs-~ Goings,up is harder~workthan~going~.down~!but~the,latter causes heavier
footsteps andthus stronger pressure~waves in:the cbest. ~ An activity sensor may
very well cause a higher heart rate going downstairs, comparedto going up~
300 DESIGN OF CARDIAC-PACEMAKERS
13.2.7 Other sensors
There are many other sensor techniques that may prove useful after more
research. Manyof these can be obtained from standard leads (Chirife, 1991).
Other possible cardiac indices which can be obtained by impedance measurements
are end-diastolic volume, end-systolic volume, ejection fraction dVIdt, and
ejection time. Someother possible signals that can be obtained from intracardiac
electrograms are T-waveslope, pacing threshold, and depolarization.
13.2.8 Multiple sensors
Manyof the sensors discussed above have good attributes and work-well, but
none is perfect (/kit et al., 1993; Furmanet al., 1993). The obvious solution is
combinemore than one of them. In almost all available single-chamber multiple-
sensor systems a fast activity sensor are combinedwith a slower, more accurate
sensor. Activity sensors have been combined wi~ .Q-T and minute ventilation
sensors. One available system that does not use. the activity sensor is a minute
ventilation and a ventricular depolarization gradient system. Here, minute
ventilation provides the prolonged response while vtntricular depolarization
gradient provides the quick response.
Activity, minute ventilation, and PEPare each used along with atrial sensors
in rate,adaptive dual-chamberedpacemakers. The first two are available, and the
PEPsystem is under investigation~
With one set of leads, manydifferent signals can be obtained (Chirife, 1991).
Sensor techniques such as intracardiac ventficular electrograms and impedance
measurements,along with. envelope detection, can. yield manydifferent signals.
Manyof these are listed in the previous section..Actually, a standard bipolar lead
could be used for both impedance measurements and electrograms. With
increasing processor power and speed, it~may.be possible that many more
combinations of sensors will be used in one pacemaker-in order to help eliminate
artifact. Artifact is erroneous signals that the pacemakerdetects and acts on. The
algorithm that runs the pacemaker may check the signals to see if they are
corrupted with motion artifact or other artifact. For example, .if the pacemaker
saw both Q-T and stroke volume decrease, something is wrong. Signal processing
could then be used to resolve the contradiction.
13.3 CONTROL STRATEGIES
The information received by :the sensors needs to be applied to a control

algorithm. There are two basic types of control algorithms closed loop and
disturbance feedforward.
13.3.1 Control architectures
Different controllers use their inputs-in different~ways. Closed. lOOprand

disturbance feedforward (open-loop) controllers are r the, two.basic control
architectures. Somepacemakers like the minute-ventilation are a combination of
the two. ~
Closed loop controllers

The.mostappealing control strategy is the use of: a dosed-loop controller (Alt et
al.i 1993; Furmanet al., 1993; Schaldach, 1992). Closed-loop control can be used
whenit is desirable to keep the sensor output,-or a modification of it, atsome set
value. Figure 13.4 showsthat in closed-loop control, the signal is comparedto the
reference. The difference is then put into a control algorithm, which determines
the!~heart: rate. Thecontroller will continue to increase, or decrease the heart rate
until a limit is reached or the~sensor output matchesthe reference value,
Refe~ence
Control Cardiac
algeritlnn Paeemake !~..~1 ~ systei~
" Sii~oe I "
I
Sensorsignal
Figure13.4 Closed-loop control system.Thecontrol strategy computes

a heart rate to keepthe
~nsorsignal equalto the referencevalue~
Disturbance feedforward ::(open~,. loop) , controllers

Figure 13.5 shows, that disturbance feedforward is an open-loop control strategy
designed to cancel the effect of disturbances on the system (Schaldach, 1992). The
way it works is that the disturbance is estimated by a sensor. Then, with
knowledgeof the system the, effect of~ the disturbance is:,e~timated. Finally an
input to the system is applied that should cancel the effect of the disturbance. The
disturbance can be either physical activity or metabolic demand.
Physiological
disturbances
Figure13.5 Disturbance
feedforward
controller. It calculatesa heart rate to cancelthe effect of
physiological disturbances. ,
All ~of,th~ ’different sensors~can be used with adisturbance feedforward

system, HoWever it must,be kept in ma’ndthat iti~ still possible to get positive
feedbackqfthe sensor signal~ is~dependent on heart rate.: For, an example of
positive open-loop feedback, consider a very responsive Q-T pacemaker with no
allowance for heart rate. If the Q-T interval shortens due to exercise the
pacemakerwill increase the heart rate. ,~As heart.rate increases, the Q--T interval
shortens even more, causing the pacemakerto falsely detect more activity. If the
pacemakeris responsive enough this could yield anunstable system.
Combination controllers
There are somecontrollers that do not fiteither of the previous, categories. They
seem to fit somewherein between the two. For example, the minute ventilation
sensors use the sensor signal and a reference value to obtain the change in minute
ventilation, which resembles a closed-loop controller. Howeverthe algorithm
used, as shownin Figure 13.6, is an open-loop type algorithm. For any given
change in minut~ vei~tilation,, the algorithm yields one heart rate. A closed-loop
controller would .try to adjust the heart rate to keep the change in minute
ventilation value equal to zero. Ventilation rate, minute ventilation, and systolic
indices all fit in betweenclosed loop and disturbance ~feedforward.
13.3.2 Control algoi~ithms
The pacemakercontrol algorithm is the heart of the rate-adaptive pacemaker(Alt

et al., 1993; Benditt, 1993). It is the mathematical function that calculates the
pacemaker’srate. The x axis is the’~sensOr signal, aiad ~e y axis isthe Calculated
heart rate: ~With modern mieroprocess0rs, the control functions can be very
elaborate. HoWever, an important factor in’implementing rate-adaptive
pacemakers~ is set/ip:~After implanting thepacemaket, the doctOrm~Stset various
parameters to ~ fit ’~ patient. The more complicated the algofithini the harder it
is to set up; ~This wotiid meanlonger hosp.ltal ws~tg; and more costi Manyof the
rate-adaptive Curves’ eah be appro~at&l ~bya s~ght line: connecting ~a ~mal
and maximalheart rate.
Mtfltiple ¯ Slope Control Function
Heart
Rate
(bpm)
Min
Change in MinuteVentilation
(impedance)
Figure13.6 Anexampleof a multiple slope control function used for a minuteventilation

pacemaker.
Theminimalandmaximal heart rates are specifiedby the physician,along with the
numbercorrespondingto the desired preprogrammed curve. "
Figure 13.6 shows a multiple slope control function that;is similar tothose
used in minute ventilation pacemakers. The algorithm has about 60 different
preprogrammedslopes~ Tbe pacemakers, only need three parameters to be. set by
the physician ortechnician: ~These parameters. ~e the.~al and.maximal heart
rate, and the numberof the.desired slope. Somevariations of this-algorithm are
to have three levels, or different attack and decay slopes. Other control
alg0tithms are presented in the following four chapters.
13.3,3 Setting parameters
Once a control algorithm is chosen, it needs to be custom fit to the patient

(Furmanet al., 1993). The~first parameter that is separate from the algorithm
the’sensitivity. The sensitivity is the gain of the sensor amplifiers. It determines
how small a signal can affect the algorithm. The parameters that customize the
algorithm then~ need to be chosen. The more complicated the algorithm, the
greater numberlof parameters. However, as in Figure 13.6; the main three basic
parameters, are ~the minimal and maximal heart rate and the responsiveness. A
very responsive algorithm is one which makes drastic changes in the heart rate
for Small changes in the sensor output~ Tlie more ,responsive the pacemaker, the
greater the exercise capacity. Patients with undertuned pacemakers tend to
complain about being tired and short of breath. However a more responsive
pacemaker is not necessarily better (Sulke et al., 1990). A very responsive
pacemaker tends to react to noise. For example, a very responsive activity
pacemaker may begin to race during a car ride. Patients with overtuned
pacemakers complain about palpitations and find the~ settings unaecept~tble.
Patients prefer properly tuned pacemakersand can live with undertuned ones, but
most demand,thaf an overtuned pacemaker be changed. In order to properly set
the parameters, e~ercise tests (Zegelmanet al., 1988) and/or Holter mo~t0rs are
typically used along with trial,and error.
~ ~ Newermodels of rate-adaptive pacemakers incorporate automatic parameter
setting modes (Alt et al., 1993; Bcn~tt, 1993; Furman et al:,. 1993).Various
rri~ltiparameter op’fimization techrht~ues are used to automatically set the
parametersat their., optimal values. Theytypically ,take about four monthsto settle
;downto a final value but are close even after one month. If they are preset with a
good estimate, it ,may .take muchless time to settle down. Automatic setting is
pro~ably’~e. Wayof tlie future. ThSy,allow for fewer clinical visits and more
accuracy. They also let the pacemakerget tuned in the patient’s natural habitat,
doing what they normally do. Automatic setting also lets more complexfunctions
be used, si,nce it~.won’t dependon an operator selecting the best settings~ As far as
the op~ation routines are concerned, another paratTneter is easily added. It just
takes a little longer to settle down.
13.4 CONCLUSION
Frommany clinical studies, rate-adaptive pacers have been shownto allow the
recipient the potential for greater exercise capacity. For example, a Q-T sensor
can provide, twice the cardiac output as comparedto a fixed-ratepacer ~ Further
research into sensors like the SO2will provide:~Ore yiable ~ensb~r’ 0iJtions. The
future of rate-adaptive pacemakersis multiple sen~or, niore advanced algorithms,
and automatically tuning systems~
Several sensor techniques have been mentioned. Figure 13.7 summarizes
someof the key aspects of the different techniques.
304 DESIGN, OF CARD~C PACEMAKERS
.... Long Excess Closed Type of Senses . Speed Ease to Avail-~

Sensor type term powe
r loop leads emo- of re- implant able &
stability drain con- used tion & sp0nse well
sensors trol stress tested
Atrium Yes No No Extra Yes Fast Difficult Yes -
pH . No No Yes Special Yes Slow Diffionlt No
SO2 Yes Yes Yes Special Yes ¯ Slow Medium No
Ventilationrate ’Yes Yes No Extra No Slow Difficult : Some
Minuteventilation..... Yes Yes No Standard Yes Slow Easy ¯ Yes
Temperature Yes. Some Yes , Special Little Slow Medium Yes
Q-Tinterval , Yes No ¯ No Standard ~ Yes Slow Easy Yes
VDG -. Yes No Yes Standard eyes : Fast Easy, No
Systolic indices Yes Yes ’ No Standard Some : Fast
Pressure N/A No Yes ~ Special: Yes- ~
Fast No
Activity Yes No ’ No ~ None, No Fast ¯ F_~y
Figure 13.7 Typical characteristics ofdifferent rate-adaptive pacemakers.Standardleads can be

either unip01aror bipOlar pacingleads. Special leads are modifiedpacing leadg. Extra leads mean
that a lead other than the pacinglead is used. Fast responsemeanssignal changesare on the order
of a heart heat.
13.5 REFERENCES ~:~:,.

~
Alt, E., Barold, S. S., and Stangl, K. 1993. -Rate adaptive cardiac pa~cin.g. Berlin! ~ Springer
Verlag.
Benditt, D. G. 1993. Rate-adaptivepacing. Boston:BlackwellSelentifiePublications.
Chirife, R. 1991, Acquisition of hemodynamie data and sensor signals for rate control from
standard pacing electrodes. PACE,14: 1563~-1566.
Furman,S., Hayes,D., Holmes,D..Jr. 1993. A prd¢tiCe of cardiac pacing. 3rd Ed.’Motmt Kisco,
NY:Futura Publishing. ~"
:":~
Lan, C., Antoniou, A., Ward,D. and Camm,A. 1988. Initial clinical experience ~with a minute
ventilation sensing rate modulated pacemaker:improvementsin. e~ercise..capacity and
symptomology. PACE,11: 1815-1822.
Lau, C., Lee, C., Wong,C., Chong, C. and Leung, W. 1990. Rate ~potisive pacing with a
minute ventilation sensing pacemakerduring pregnancyand delivery. PACE,I3~ 158-163.
Schaldach,M. 1992. Electrotherapyof the Heart. Bedim"Springe~,Verlag.
Sulke, N., Dritsas, A., Chamhers,L, Sowton,E. 1990. Is accuraterate response programming
necessary? PACE,13: 1031-1044.
Zegelman, M., Creslinski, G., Kreuzer, L 1988. Rate response during submaximalexercise:
comparisonofthree different sensors. PACE,11: 1886-1895~¯
13.6 INSTRUCTIONALOBJECTIVES
13.1 Explainwhyit is importantto control heart rate.

13.2 Determineif a 26-year-oldpatient with a maximalheart rate of 167bpmand a resting heart
rate of 65 bpmhas chronotropicincompetence.
13.3 List somereasons whyatrial sensing mightnot be used in somepatients.
13.4 List somereasons whypHsensing is not very practical.
13.5 Explain howSO2can be measured.
13.6 Explainhowdigital averagersare used in minuteventilationrsensing pacemakers.
13.7 List the signals.that can be obtained ~ standard bipolar leads, ,
13.8 List the available multiplesensor ~makerg.~ "
13.9 Explainwhat kind of signals ean be.u~ ~Vitha eloged-loopcontroller.
13.10 Disonss the pros and cons of a moreresponsive pacemaker.. ~..
13.11 Describewhichavailablerate, adaptivepacemake.,
rs canquic,kly.react to emotion., andstress.
Rate-Adaptation by Motion
Kevin T. Ousdigian
;~¢ most widely used method for rate-adaptive pacemakers is to sense body
~ovements. This approach has been met with clinical success because it does not
require additional leads (sensor is-inside the pacemakercan) so the system is easy
to implant, is relatively simple to program, and, as we will see later, rapidly
adjusts the pacing rate. A motion sensor inside the pacemaker senses body
movementswhichare primarily due to the ~patients’ foot ~fall. The pacemakeruses
this sensor signal to determine the appropriate pacing rate. Bodymotion sensing
does not directly sense metabolic changes such as anxiety, fever, or circadian
laeart rate-changes.
The motiowbasedrate-adaptive pacing rate accuracyis based on:
~’1: Sensitivity: modifying.the sensor, signal to makeit proportional to patient
~o exertion. ~
2~ .~- Specificity: pacing rate should be specific to activities that. normallyincrease
...... heart rate, in other words, pacing should not changedue.to~ activities that
normally do not cause heart rate increases (nonactivities); environmental
-factors such as vehicular travel, or other noise inputs.
3."- Rate of increase~decrease (speed of response):-appropriate pacing rate
;. in~tease/decrease following activity-changes~
To meet these requirements the motion-based pacemaker designer ~must
¢arefully~choose (Figure 14.1):
1~: A sensor that detects activity and uses nanoamperesof power~
2. ~ Signalprocessing that distinguishes between activities and nonactivities.
3~- An algorithm for generating an appropriate pacing rate based on the
Progf~ammable
rateof
increase
Programmable and decrease
Parameters
Activities Pacing
Noi3-activit|es rate
Noise signal
Figure 14,1 Ram-adaptive pacemaker basic blo~kdiagram.Therawsensor!signal is converted

~o~ activityestimatewith,si.gn~pr0~.,..essing(i-.,e.~ filtering, ampli£ying,thresholddetectors).
Designers
are ehalienged
to make tii~ activityestimatepro~portional to the patientactivity level. A
pacingrate is determinedbasedon tlie ~ty estimateandi~rogrammed pabameterS~
processed activity level and is adjustable to meet the needs of various

patients.
Clinicians typically program the adjustable parameters through telemetry
after the pacemaker is implanted. These commonlyprogrammedparameters are
(1) minimalactivity level required to increase pacing rate, (2) the rate of pacing
rate increase/decrease, and (3) the ~maximal pacing rate. Typically the
programmable parameters are optimized by having the patient simulate daily
exercises such as walking or climbing steps.
There are three sensors currently used for detecting body motion:
piezoelectric, piezoresistive, and piezocapacitive. Also there are two methodsare
used for mountingthese sensors:
1. A piezoelectric crystal is bonded to the inside of the pacemaker can. This
detects pressures caused by the movingbody.
2. An accelerometer mounted on the circuit board.
This chapter discusses motion sensing, the sensing elements, and it discusses
the designs of commercial rate responsive pacemakers. Finally, it presents
comparisofis of the various devices.
14.1 HUMAN ACTIVITY AND HEART RATE
Original pacemakers maintained a minimumheart rate so that patients did not

become dizzy and faint during a cardiac conduction block. This was a great
advancement, but during patient activity.this minimumheartrate would limit
cardiac output, since cardiac output equals the product of stroke volumeand heart
rate. During exercise a person with a normal heart rate triples cardiac output,
with the increase mainly due to heart rate and a smaller portion to enhanced
contractility and stroke volume.
The first solution (introduced in the 1970s and still used today) is the use
atrial synchronous pacing. In this modean electrode senses atrial depolarization
(P wave) and then uses a second electrode to stimulate-the ventricles, the main
pumping chamber in the heart. This :bypasses the.~ dysfunctional ’ AVnode;
however, 30-50%of paced patients have a dysfunctional atrium, classified as sick
sinus syndrome-(Anderson~ 1986). :Therefore, in the .late 1970s researchers
started in,vestigating techniques to emulate a normal, v.,ariable heart rate of a
normal sinus. In the past few years, clinicians have routinely used rate-adaptive
pacemakerswhich produce a pacing rate responsive to the body’s needs.
14.1.1 Correlation basis
The relationship betweenhumanactivity and heart rate is based on the correlation

that body activity requires energy expenditure which increases the oxygen
consumption. The body increases blood circulation by increasing the cardiac
output to meet this energy expenditure rise in oxygen consumption. The
contractility change is limited so the:primary cardiac output increase is due to a
heart rate increase. Therefore, body activity is accompan.i~d’ by a heart rate
increase.
The degree of the correlation between sensed body activity and heart rate is
dependent on the ability ~to ,distinguiSh between varying exertion levels of
different activities while excluding nonactivities (aCtivities whichdo not cause
heart rate increase). This distinguishability depis~ds on’the relative magnitudes
RATE,ADAPTATION BY MOTION 307
and r~frequencies of activities and nonactivities. Nonactivities include things like

vehicular travel vibrations, a vacuumcleaner, or an electric, knife. Different
levels of exertion need to be distinguished to adjust heart rate; for example
climbing stairs should produce a higher rate than descending stairs. The same
exertion level for different activities should require the same rate such as walking
or biking at 100 Wof expenditure.
14.1,2 Power expenditure research
Motion-based rate-adaptive pacemakers try to measure the power generatedby

the body to adjust the heart rate appropriately. The power (W) integrated With
respect to time is energy (W.s): Physics reveals that for a free-moving
frictionless bodyof massm starting at rest, the energy Wrequired to accelerate it
to velocity v is
W = mv2
2 = 2 (14:1)
Thus,~energyis proportional to the integral of acceleration ~uared.

0~ Cotes and Meade: (1950) studied human ambulation-theoretically and
experimentally. They found three relationships on walki~’ng/~nning:
L . Lift height per~ minute is proportio~nal~tothe squareof the velocity.
2.~ Energy~penditure is proportional to the square.of the velocity,
3. Energy expenditure is proportional to the lift work.
Therefore, either lift height per minute or forward velocity can be used to
measure walking energy.
Montoye ~andEpstein (!965) studied energy: expenditure for correlating
diseases with in~etiveor sedentary life-styles,
Ismail et al: (1971) reliably predictedoxygen consumption using force
platform measurements which measure the three orthogonal components of a
force acting on a rigid platform. For a rigid body, acceleration componentsare
proportional to force based on the relationship f= ma. Therefore acceleration
can be used to predict oxygen consumption._An ~accelerometer is ,:a device~ that
measures acceleration..Reswicket.al. (t978) found the integral of absolute value
of the acceleration divided by~time yields oxygen consumption.. The result
obtained using the absolute value of acceleration,is a goodestimate if the subject
is-not involved in high force activities: with short movementssuekas weight
lifting orisometric exercises,
Wongetal. (1981) designed and tested a portable accelerometerwhich could
be worn by a subject as a measure of energy expenditure. The absolute value of
acceleration is .integrated and scaled .to produce: an energy ,expenditure estimate.
Servais et al. (1984) redesigned this device to improvethe transducer and display
resolution and reduce the power consumption and size. This device measured
accelerations in the vertical axis~ of the subject. These devices had good
reproducibility~ and produced good energy expenditure estimates.
~ These researchers showed ~at-it is possible to measure body:~ activity and
estimate~energy~expenditureand found it possible to correlate :these with oxygen
consumptionand heart rate.
14.1.3 Acceleration sensing of various exertion levels, activities,

nonactivities, and noise
Alt et al. (1989) used tfiaxial external accelerometers strapped onto the pectoral
region of twelve subjects (six healthy volunteers and six pacemakerpatients)
emulate accelerometers inside a pacemaker can implanted in the pectoral region.
Mianulli et al. (1989) and Benditt et al. (1991) found strap-on acceleration-sensed
rate-adaptive pacemakers are valid representations of implanted .rate-adaptive
pacemaker response when standardized techniques are used. Vertical (up and
down for a standing human), horizontal (forward and backward), and lateral
(side to side) accelerations were recorded for a variety of exertion levels,
activities, and noise sources. The piezoresistive acederometers from Endevco
(2262 CA-200) had a measuring range of +~00 g, a much.wider range than they
measured (:~2 g).
The following sections describe the results from the study performed by Alt
et al. They performed a Fast-Fourier Transform on the data to provide
frequency and amplitude information. The subjects had a wide variability in age
(22-78), height (154-196 cm), and weight (58-100 kg) however, the
showedno direct influence due to these parameters.
Walking
For various exertion levels walking on a treadmill, the acceleration frequency for
each axis was linearly related~to the step:frequency (numberof times the foot hits
the surface per second) ~ The frequency of the higbest:aceeleration amplitude was
found to be in the range from 1 to 4. Hz for speeds varying from 3.2 km/h
(0% grade) [a normal walk] to 5.6 km/h" (16% grade) [a near run] (Alt et
1989).
Harmonics
The peak amplitude occurred at the step frequency: Harmonics of the step
frequency are also significant, but less than the fundamental step frequency. For
instance, the horizontal axis, acceleration third harmonic for a Walkingspeed of
4,2 km/h is about 40%of the p~ value, while the componentat 1.0 Hz is about
20%of the peak (Alt et al. 1989).
Stationary bicycling and axis comparisons

Bicycling does not :have the foot impacts that other activities do and therefore it is
harder to determine the activity level. The vertical axis ,has ~the largest walking
signal for .all exertion levels, but it also has the smallest,bicycling signal for all
levels: The vertical mean acceleration signal changes byabout 100%over the
range of exertion levels for walking but has negligible change during biking. The
lateral axis signal is at least twice the horizontal or vertical axis signals for all
exertion levels. The lateral and horizontal meanacceleration signals change by
about 40%over the range of exertion levels for biking and 100%for walking
(Air et al. 1989).
Stair ascent~descent and axis comparisons

The average age of a bradycardia pacemaker patient is 72 years :old (Medtronic,
1993). A commonactivity which requires a pacing rate inerease is climbing
flight of stairs, The acceleration going up stairs is very low, but the need for a
pacing rate increase may be high depending on the patient condition. Three
RATE-ADAPTATION BY MOTION 309
speeds were tested for ascending and descending a flight of stairs. Acceleration
variation with speed of ascent or descent was insignificant for the lateral and
horizontal axis: The horizontal axis showedsimilar meanacceleration levels for
ascent and descent, The lateral axis mean acceleration ascending was almost
dbuble that of descent. The vertical axis meanacceleration had a variation with
speed, but mean acceleration levels were similar during ascent and descent
~Alt et at. 1989).
Gomparing low ~and higher frequencies for walking and noise

T~wofourth-orderButterworth filters were ~constrncted to show the relative
strength of the activity data. The low-pass filterhad a corner~frequency at3 Hz
and the high-pass filter had a corner frequency at 8 Hz. The low-passed data
were about five times greater ~in amplitude than .the high-passed data for each
w~ng level tested. Both sets doubled in amplitude from the lowest walking
I~vel to the highest,
~,,-Tests on acceleration levels for various noise sources were presented for the
hbrizontal axis. Household duties such as vacuuming, cleaning windows, or
cutting with an electric knife had meanacceleration values at similar levels both
below 3 Hz and above 8 Hz. Hitting the chest produced strong noise signals at the
frequency of excitation as well as at the harmonics. (Alt et al. 1989).
I4~i.4 Pressure sensing of various exertion levels, activities,

nonactivities, and noise
Re fn’st rate-adaptive Sensing techn~ique used a piezoelectric sensor which is

~nded tO the inner surface (Figure 14.2)of the pacemaker housing (or can)
sense acceleration pressures. A pacemaker is normally implanted so that the
sensor faces inward. Body movementcauses pressures which bend the can and
thus the sensor. An intimate bond between the sensor and can is required for
transducing the pressure exerted on the can to the sensor. A piezoelectric bender
element is used to convert this bending action into a generated voltage, which is
amplified and filtered as mentionedin section 14.2.1.
Viewfrom Viewfrom Viewfromfront

right shoulder abovepatient of patient’s
chest
Ribs
i,~J ~-"Skin ~ ,Sensor
Ribs I ’ " I l Skin

Back can geedge .
facing inside Electrgnics!
of body Battery
Figure 14.2 Piezoelectric elementbondedto the inside of the pacemaker can. Bodymotion
causespressurefluctuationswhich~ausethe can to deflect whichbendsthe sensorto.producea
voltage.Theleads fromthe piezoelectricsensorare connected
to the pacemaker
electr0ni~s.Thisis
onepossiblelayoutfor the pacemaker components.
The body acts like a mass-damper system with a resonance around 10 Hz.
According to Deickmann(1957), the mechanical energy originating from the feet
propagates through the bodyas pressure waves, especially if the energy is in the 5
to 40 Hz region.
Wehave not found published raw data on the crystal bonded to the can like
the study done by Alt et al. (1989) on accelerometers. Manystudies have tested
the heart rate performance of piezoelectric-based pacemakersbut did not measure
raw sensor output. The studies will be presented later in the chapter. Anderson
and Brumwelt.(1984) reported that "data has been collected which shows that the
response of the typical human body which results from mechanicalactivity
related to the physical activity of the patient such as pedal impacts from walking
or running are centered around approximately 10 Hz."
The noise components, similar to the signals from the accelerometer, occur
at a variety of frequencies and amplitudes. A piezoelectric sensor does not
respond to de signals; however, direct pressure on the body around the can will
increase the effective mass of the can which will magnify signals. For instance,
the cardiac signals from the heart (-- 1 Hz) mayappear~ as an activity whenthe
patient is lying prone (i.e. sleeping).
The piezoelectric sensors like classical accelerometers should have a stronger
signal descending stairs than ascending because the feet are hitting the ground
harder. An activity like biking should produce amplitudes less than walking or
running because very little impact is present. However,there is body movement
and signals will be produced.
The type of footwear mayaffect the amplitude of crystal and accelerometer
signals because some shoes (i.e. running) mayabsorb the foot impact more than
other shoes. However,the step frequency is not affected by changes in footwear.
14.2 SENSORS CURRENTLY USED
Piezoelectric, piezoresistive, and piezocapacitive are three different sensing

techniques whichare used in various configurations to sense accelerations.
14.2.1 Piezoelectric sensors
Piezoelectric transducers are used to sense various mechanicalproperties because,

when they are bent or deformed, an electric charge is produced. They produce
strong signals (several millivolts) when defl~cted~only a few nanometers.
Mechanical strain produces the dectric potehfiai 6eeause ah~ asymm~calcrystal
lattice is distorted causing a charge reorientation which yields a relative
displacement of negative and positive charges. These internal charges induce
surface charges of opposite polarity on opposite sides of the crystal, whichcan be
measured by the voltage between electrodes attached to the surfaces. They are
different from most other sensors because their effect is reversible; they deflect
mechanically whensubjected to an applied voltage.
The Curie family discovered the piezoelectric effect in natural quartz around
1880: Moderntransducers often use artificially grown quartz (SiO2) crystals,
elim~n~tting impurities and crystal imperfections, but man-madepiezoelectric
ceramic materials are more common.
Piezoelectric sensors can be configured to sense a variety of mechanical

variables including: force, displacement, vibration, pressure, or acceleration.
These modes are implemented using certain materials and crystallographic
orientation of the plates and the method of fixation. Longitudinal compression
mode induces a voltage across the electrodes when the thickness is changed.
Thickness-shear action is the commonmode for piezoelectric sensors in
pacemakers. Figure 14.3 shows the bender configuration which has two layers of
crystalline material laminated together with a brass center layer. Whenan
external force is applied to the lower part of the sensor, the top ~expandsand the
lower part is compressed. Charge outputs of like polarity ,are produced because
the two layers are polarized in opposite directions. ,The charge,q produces an
output voltage Vo= qlCs. This charge generator is equivalent to a current
generator because i = dqidt.
Tension
+ V
0
~
Compression1
Fome
Figure 14.3 A piezoelectric bender element induces a voltage (several millivolts) when
mech~.
~a~ically
deflected.
Accelerometers use piezoelements and a seismic mass and/or a cantilever
beam. It is analogous to a weight on a spring which is connected to a frame. As
the frame moves, the mass will tend to stay at rest until the spring, being
stretched, can exert enough force on the mass to makeit move. The piezoelectric
bender element is one example of a sensor used in accelerometers to measure
displacement changes of the base. A beam 6f piezoelectric or piezoceramic
material ig attached to the seismic mass as shownin Figure 14.4. Electrical
contact is madeto electrodes on the top and bottom of the beam. The base of the
accelerometer is attached to the test object whosemovement,say, is perpendicular
to the bender and will exert a force on the mass of the beam. The mass’s inertia
will resist movement,;causing the beamto bend. The electrodes detect the electric
signal which can be conveyedto an amplifier.
Cantilever beam
Brass
Sensed
Base accelerations
Piezoceramic
material
Figure14.4 Accelerationsperpendicularto the base massare sensedby a piezoelectricelement

whichproduces
an electricalsignalacrossthe electrodes.
The advantage of a piezoelectric accelerometer is that it produces a voltage

while the two other acceleration sensors (piezoresistive and piezocapacitive)
consume some power for sensing. Often a custom-designed sensor is used for
pacemaker applications because a small size and range (:~.2 g) is required.

Manufacturers of piezoelectric accelerometers include IC Sensors and Endevco.
One piezoelectric accelerometer suitable for implementation in a pacemaker
is the ENDEVCO Model 12 Picochip®. This model uses a bimorph sensing
element with a cantilever beam to generate a high charge output for its
size (3.82 × 4.57 × 1.53 mm)and mass (85 mg). The device can be mounted
to the pacemaker can or used as a surface mount chip component. The frequency
response is 1-2000 Hz (_+_5%). The charge sensitivity is 2.0 pC/g with a sensor
capacitance of 550 pF. The voltage sensitivity is about 3,6 mVIgwhen:cabling
capacitance is low. The maximal vibration~ is 500 g. A charge amplifier is used
for converting the charge into a usable voltage signal.. An exampleof a switched-
capacitor charge amplifier is now presented. The fundamentals of switched-
capacitor amplifiers are covered in Chapter 8.
Figure 14.5 shows a two-stage amplifier with bandpass filtering. The first-
stage converts charge to voltage with high-pass filtering while the second-stage
provides low-pass filtering. Both stages have ddjustable gain. The high-pass
comer frequency is
1 ACsl
fcH - 2/i:CflReffl - 2/1:C~ (14.1)
where, Reffl = llfsCsl,fs = the clock switching frequency, and Csl = leakage
capacitance.
Csl
Figure14.5Thefirst-stage is a chargeamplifierandhigh-passfilter whilethe secondstage is a

low-pass
filter. Theswitched
capacitorsact like a resistance.]’his circuit is a parasiticinsensitive
topology.
The charge sensitivity for the Picochip accelerometer determines the charge
induced by an acceleration (g), and then the amplifier first stage converts charge
to voltage. The gain of the trust.stage charge amplifier is
GI = Cfl ~ (14.2)
RATE’ADAPTATION BY MOTION 313
The low-pass filter comer frequency and gain are
1 fsCs2
feL- 2~’Cf2Reff2- 2~’Cf2 (14.3)
Ci V
G2 -- Cs2 V (14.4)
EXample for charge amplifier in Figure 14.5:

Design a circuit for the Picochip by Endevcowhich passes frequencies from
1:5 Hz. For an acceleration of 2 g the circuit’s output should be 5 V. The clock
frequency range is 1-5 kHz and capacitors’ values must range from 0.25-50 pF.
Solution: ~
The charge produced by the Picochip for an acceleration of 2 g is
2pC 2g = 4pC
g
For the high-pass filter, given fell = 1 Hz, choose fs =1000 Hz and
Csl = 0.25 pF to minimize Cfl so G1 is maximized.
Solving for Cfl in Eq. (14.1): "Cfl = 40 pF and
1 - V
G1- 40 pF = 0.025~
First stage output = 0.025 ~ Umes4 pC = 0.1 V. Wewant second-stage gain
-5V V
G2-0.1 V - -50~
For the low-pass filter, given fcL = 5 Hz, choose Cs2= 0.25 pF and
fs =1000 Hz. Solving for Cf2 in Eq. (14.3): Cf2 = 8.0 pF.
Solving for Ci in Eq. (14.4): Ci = 12.5 pF.
14.2.2 Piezoresistive sensors
A piezoresistive sensor is based on the property that electrical resistance changes

whenthe material is mechanically deformed. They ~e often called strain gages
begause the deformation causes strain. The first strain gages used metal filaments
on a backing film of electrically isolating material (Pall~is-Areny and Webster,
1991). Currently, they are often madefrom copper/nickel alloy (constantan) or
single crystal semiconductor material such as silicon with boron impudties~
Stressing semiconductormaterials causes resistivity changes. The semiconductor’s
variation with strain is approximately 50 to: 70 times that of the metals. This
larger variation is desirable because less amplification~is needed. The
seniiconductor resistive changes from mechanical stress are dependent on the type
of material and the doping dose. A p-type .material increases resistance with strain
while an.n-type material decreases resistance from strain (P(dlas-Areny and
Webster, 1991). The strain sensitivity is temperature dependent, but the

temperature of a sensor in a pacemaker implanted in the b~ly only changes a few
degrees centigrade whichhas very little effect on the sensor materials. If there is
temperature sensitivity, either additional temperature compensationcircuitry is
used or an expandable backing material is used which causes the backing
resistance to decrease and offset the semiconductorresistivity increase.
Piezoresistive accelerometers use a mass suspended by four semiconductor
strain gages (Figure 14.6) that act like legs of a table. As the massis accelerated
perpendicular to its surface a strain occurs on the g~ges which changes their
resistance proportional to the acceleration. Manufaci~ers include Endevco and
IC Sensors.
Silicon
substrate
Sideview
Accelerations
I ~
~ ~.T°P view
Srees~n:.~O
rnsdu ct ° rMass
~
Integrated Semiconductor
Accelerations signal resistors
~J in and out ~ndlioning
of page
(a) (b)
(c)
Figure14.6 (a) Topviewof a piezoresistiveaccelerometer.Accelerationsin or out of the page

cause the massto movein or out whichstretches or compressesthesemiconductor resistive
elements.(b) Side view.Accelerationsup or downcausethe strain gagesto stretch or compress.
(c) Astrain gagebridgewhichoutputsa voltageproportionalto smallresistancechangesdue
acceleration.Thedifferential amplifier(Figure8.18(a))convertsthe signal into a usablevoltage
level.
A strain gage bridge with a differential amplifier is used to convert small

resistive changes to accelerations (Figure 14.6(c)). The resistance of
semiconductor is on the order of several kilohms. The bridge is balanced by
makingR l/R2 = R31R4so that the output is 0 V, but under strain the resistance
changes makingthe output voltage
R2
Vo= RI +R2 (14.5)
14.2.3 Capacitive sensors
Capacitive sensors have grown in popularity due to the application of

photolitliography teclmiques used in the semiconductor industry. The advantages
of the capacitive sensor include their high stability, reproducibility, and
resolution. Th~se sensors can be applied to the measurementof any quantity that
can be converted to a displacement, such as pressure, force, torque, and
acceleration:
A capacitor is madefrom two electric conductors separated by a dielectric,
often air or vacuum. The difference in voltage between the conductors is V =
Q/C, whereQ is the charge and C is the capacitance. The capacitance is a function
of the plate area, dielectric material, and the distance between the plates.
Therefore, different capacitor arrangements can be used to build capacitive
sensors whose output varies as a function of plate area, plate separation, or
dielectric. The change in dielectric is rarely used due to the mechanical problems
during~manufactudng and operation~ The variation of area is commonlyused for
medium range displacement measurements (!-10 cm). The commonarrangement
for small and large displacements is based on the variation of distance between
plates (Pall~s-Areny and Webster, 1991).
Capacitive accelerometers utilize a varying distance between plates as a
function of acceleration. These sensors usually have one plate stationary
(connected to the housing) and another plate is attached to the movingmass.
compensatefor interference and drift a third (upper) plate is added in the same
structure and is also connected to the housing (Figure 14.7). One capacitor
formed between the bottom and middle capacitor and the other between the
middle and top plate. Figure 14.7(a) shows a micromachined silicon,
piezocapacitive accelerometer cross section where an internal mass is supported
by four silico~ springs in between the upper and lower caps. The outside plates
are.:dgidly-held in place and-the center mass (plate) moves proportional
accelerations perpendicular to the substrate. Whenthe mass (center plate)
disiflaced a distance x towards the upper plate, the upper plate spacing decreases
by x. The amountof decrease is equal to the force acting on the mass divided by
the spring constant of the silicon springs. Therefore, the capacitors vary
proportional to acceleration whenthe electrostatic forces do not affect the mass
position. If d is the plate distance for the top Ct and bottomCb capacitandes arrest
then after movement,
e0 erA and Cb - e0 er A
Ct-d-x d+x (14.6)
The difference between the top and bottom capacitor voltages is proportional
to the acceleration. Therefore, two capacitors can be used as the input impedances
to~a-differential switched-capacitor~amplifier (Figure 14J6(b)) whose~output
proportional~to acceleration.
:~ Piezocapacitive accelerometers, in the +_2 g range change capacitance by
about. 2-5%:with a total displacement around one 1 #m. This makes .the sensors
difficult to mountbecause a small change in the thin ceramic walls will produce
capacitive offsets. Piezocapacitive accelerometer signal conditioning is also more
difficult than for piezoresistive and piezoelectric accelerometers. Manufacturers

of these sensors include Silicon. Designs, Inc., Endevco, Analog Devices,
Motorola, and Kistler.
~xI Accelerations
Siliconsprings
SwiChing
netwock
Ct
Switd
Vo o¢(Ct - Cb)/Cf= acceleration
Cb
(b)
Figure14.7 (a) Apiezoeapaeitiveaecelerometerwherean internal massis suppot~,.dby four
silicon springsin betweenthe upperandlowercapacitors.Thecapacitancesof the upperandlower
plate vary as a functionof acceleration.(b) Aswitched-capacitor
differential amplifierwhose
outputvoltageis proportional
to acceleration.
14.3 PRESSURE-BASED APPROACHES
This section discusses pacemaker implantation issues for detecting pressures

resulting from accelerations~ Then, it presents the signal processing and rate-
adaptive algorithms for commonpacemakers or patents from Medtronic, Inc.,
Biotronik, Inc, and Pacesetter Systems(St. Jude).
All the pacemakers have programmable minimal and maximal heart rates. A
programmablethreshold is also commonto most designs. The threshold sets the
minimallevel of activity which must occur for an activity to be processed by the
rate-adaptive algorithm and also allows for sensor-to,sensor manufacturing
variation. Loweringthe threshold allows lower levels of ,activity to be detected.
For instance, ,an~ older~person maymoveslower than an athletic person, but the
older person will probably need a pacing rate increase with minimal activity.
Therefore, the. threshold should be set low. Present pacemakers also have
programmablecurves that mapactivity levels to target pacing rates. The rate of

pacing rate increase and rate of pacing rate decrease as a function of time are
often programmable.
ill 14.3.1 Issues of detecting pressure
Chevalier (1985) reported clinical studies which suggested that the sensor could
be placed in either the pectoral or abdominal region. Andersonand Moore(1986)
performed a couple of activities with the sensor located at both locations. They
found a slightly larger signal from the abdominal location than the pectoral
region, but both were within the range of the threshold programming.
Pacemakermanufacturers are constantly trying to reduce the size and weight
of the pacemaker and its can. The size of the pacemaker can may vary the
coupling (how the can transmits movement)between the patient, sensor, and can.
Therefore, each modelwill be built with a slightly different internal gain so that
heart rate response does not change. The Coupling mayalso be affected by the
patient’s upper body structure or how the pacemaker rests in the patient
(pacemaker may movearound after implanted).
14.3.2 Medtronic, Inc.
This section describes the first motion-based rate-adaptive pacer patent to show
the basic operation of a rate-responsive pacemaker. Then, the operation of
Medtronic’s various rate-adaptive motion-based pacemaker models are discussed.
In 1992, rate-adaptivepacing systems accounted for more than 60%of Medtronic
pacemaker units sold around the world (Medtronic, 1992);
First rate-adaptation by motion patent

Anderson and Brumwell(1984), from Medtronic, Inc., patented the first rate-
adaptive pacer. Figure 14.8 is a functional block diagram of Anderson and
Brnmwell’s rate adaptive pacer. These functions were used in Medtronic’s first
rate adaptive pacemaker, the Activitrax. The following paragraph discussesthe
operation of the patent.
Body accelerations produce pressure,, which bends the piezoelectric sensor
producing a signal in the millivolt range. A bandpass filter removesrespiratory,
cardiac, and other low.frequency noise from the raw sensor signal. The
eomparator produces.an activity estimate .-An activity estimate is usually
geiierated after filtering, amplifying, and using threshold.levels on the-raw sensor
signal: Designers are challenged to makethe activity estimate proportional to the
patientactivity level: The activityestimate is a series of variable-spaced pulses of
constant height and width: Next; the activity estimate is integrated to produce, a
voltage signal which in turn causes a proportional pacing rate. The integrator has
a programmable~curvethat determines the heart rate increase/decrease: The rate
of increase/decrease is a programmableparameter between the activity estimate
and pacing rate. Most manufacturers use linear curves, however some have
exponential shapes. The pacing rate decrease, operation is not-described in this
patent,, however, the techniques implemented by Medtronic’s pacemakers are
discussed in the following sections. Theterm voltage-controlled oscillator (VCO)
iw.med; a ‘VCOproduces constant height pulses which causes a pacing rate
p~oportional to their occurrence per unit of time. This signal is used.by the
pacemaker’sescape timer to generate a stimulation rate.
Programmable
S!opes]
Piezo- [Bandpass
H Comparator~ Integrator I
st electric -"-’[ 1< f< 20 Hz
Activitie sensor Activity
Non-activities estimate I Voltage
noise
output
bandpass Threshold
~al
Pacing
I I\/Vl I\. t Time rate
output
comp-
arator
.I- .... Dashedline
output
integrator I I,. _ _ _ J,- I hashigher
!~3-’---" programmed
minimal ~ slope
pacing Time
rate
Figure14;8 Thesignalis bandpassfiltered to re, duceUnwanted signals. Acomparatorproduces

activity estimates whichar~ pulses with.widthsproportionalto,the~area abovea programmed
threshold.Theintegratoruses programmable slopes to producea voltagesignal whichproducesa
pacingrate proportionalto that signal.is. TheVCOgeneratespulseswhosefrequencyis the pacing
rate.
Activitrax ® "
Activitrax was released in 1984 as the first rate-adaptive motion-based
pacemaker. The motion-based rate, adaptive technology has been used by over
100,000 patients between 1984 and 1989 (Medtronic, 1989). Similar to the patent
by Anderson and Brumwell (1984), accelerations produce pressure to bend the
piezoelectric sensor which produces a voltage. The programmer selects .from
three minimal pacing rates ~(60,~ .70, or 80ppm),.and three’maximal: rates (100,
1~25, 150 ppm). A bandpass filter removes ventilatory, cardiac, and other tow-
frequency noise componentsfrom the raw, sensor, signal. A.threshold, detector and
counter eotmts excursions per second above a programmable threshold (Figure
14.9): Zero counts/sis no detected activity above the threshold and 15 counts/s is
the heaviest ~activity. The programmerhas the choice, of three threshold levels.
The counts/s are mappedto a target pacing,rate using one of ten.programmable
curves that mapan activity estimate (level) to~ a target pacing rate. The target
pacing rate is ~ the pacing rate that should be obtained for the-present activity
estimate (level),~ Thetarget rate~ is updated,everytwo seconds,: but the pacing rate
does not change as rapidly because the~pacing rate,is smoothedby the pacingrate
time constants,-which are,diseussed~in the following paragraphs. The activity
estimateto :target pacing rate.mapping could be implemented with a 4ook-up
table. Figure 14.10 showsthe shape of five rate-response curves.
Programmable
thresholds
Threshold , J Determine|
electric I [ Bandpass detector
nmssurel----’t 7 < f < 45 Mapping~ pacing
and rate
’ I /
A ~ensor [ ! (Hz) counter Activity
N0n-activies estimate Stimulations
noise (counts/s) per minute
Thresholds:
Outputof ~ .... _Threshold
level counts/s
bandpass". high 3
filter l’~/" ~-t’~- ~-I’~-7- Low 7
v ~- "~-tr - - - Medium medium
~_~V~i~ "f~"
low 9
V VV ~V~S time
Figure 14.9 Activitrax rate-adaptation block diagram.Countercounts activities abovea
programmablethresholdsetting. Rateresponsecurvesconvertthe activity estimate(counts/s)to
target pacingrate. Thepacingrate is calculatedbasedon presentrate, target rate andrate of
increase/decrease
whichdetermines howfast the pacingrate shouldchange.
The next pacing rate is calculated based0n the present pacing rate, target
pacing rate, and the rate of increase/decrease. The rate of increase/decrease is
howfast/slow the pacing rate can change as a function of rime. The~Acdvitraxhas
set acceleration and deceleration times, which determine the rate of
increase/decrease as a function of rime. The acceleration and deceleration times
vary the rate of pacing rate change as a ftmcdon of time (how fast/slow does the
pacing rate Change).’ The,acceleration/deceleration time is the time it takes to
achieve 90%of the difference betweenthe present rate and the sensor-iiidicated
target rate. The 90%difference is calculated using pacing intervals and not by the
pacing rate.
Target I Curve#
; pacing .150t
rate . - .... ~-~
~
;.=.=T-. ~-=---~: Maximal
(ppm) 140.]- 9f ~.~"~ 7 ~)
~ pacingrates
/ / .... j_25_ (selected by
120 - ..... , ..... -.--’Z: ....... physician)
110
100"
80"
-0 3 6 9 12 15 Activity
~ .¯ -: estimate
,. (counts/s)
~’,.’.gurei4.10Five of the~tenprogrammable
rate response
Curves. Thecurvesmapthe activity
ebtimate(c0ums/s)io a target pacingrate.: Reprintedwith p~rmissionfromM6dtronic,Inc.
©Medtronic, Inc. 1986.
After an increase in the activity estimate, the rate increase curve resembles a
relatively fast (smaller time constant) first-order system step response, while
after an activity decrease the pacing decrease curve resembles a slowly decaying
response. If activity level stabilizes, the pacing rate maintainsits steady state value
until the activity level changes. Equations (14.7) and (14.8) showthe response
dependent on the present pacing rate (ppr), target ,pacing rate (tpr) and the
constants. The time constants are proportional to the acceleration/deceleration
time and determine the. rate of increase/decrease. The increase (,i) and decrease
(~d) time constants are nonprogrammable for the Activitrax but have
programmable values for other Medtronic pacemakers such as the Legend®.
Figure 14.11 shows a first-order response to a step change in activity level. The
actual pacing rate is updated once per second and therefore would be constant
over the one second interval.
Targetrate
Pacing .dudngincrease,
rate
(ppm) _ Jp.resent rate
._._~w..-Present
rate dunngdecrease
dudngincrease
Time(s)
Figure14.11Anincrease in the actiVity~estimatecausesthe pacingrate to slewtowardsthe

target pacingrate that is determinedfromthe mappingcurves.Anactivity estimatedecreasecauses
the pacingrate to decayto a lowertargetpacingrate.
npr = ppr + (tpr - ppr) (1 - e-t/~i) (14.7)
npr = tpr + (ppr - tpr) (e-tied) (14.8)
where
npr = next p~acing rate
ppr = present pacing rate
tpr = target pacing rate
*i = rate of increase time constant
*d = rate of decrease time constant
One disadvantage of a device depicted in Figure 14.10 is that, for maximum
activities along some curves, the rate can not reach the programmedmaximal
rate. An example of this is: curve #5 is programmed along with a maximal
pacing rate of 150 bpm. The maximal rate is not achievable because the maximal
curve flattens out at 140 bpm. The inability of the Activitrax to achieve the
maximal rate was confirmed in several studies including Mond(1993) and Lau
(1989). ~,h_is disadvantage was fixed by using~linear mapping curves
Medtronic s next gener~0h pacemakers.
Toff et al. (1987) tested the Activitrax with typical settings aboard
aircraft. They found that pacing rates were not unduly affected by travel in fixed
wing aircraft although large rate increases did occur transiently in the smaller
aircraft. Sustained rates were observed in rotary wing aircraft and hovercraft.
These rates are often well tolerated and often unnoticed as long as the patient is
awake.
Kubischet al. tested the Sensologi n a sports plane and reported that jostling
from turbulences causes rate increases. The affect is highly dependent on the
chosen programmingparameters. Further investigation of air travel with respect
to the programmedparameters Should be carried out.
Medtronic’s present rate-adaptive pacemakersdo not distinguish the intensity
of activities once they are over the minimal threshold. The amountof activity is
indicated by counting activity occurrences, even though one count may have a
muchhigher intensity over the threshold than another count. The effect on the
pacing rate may be minimal for most exercises because as the activity level
increases, so does the cyclic frequency. This was shownby Coates and Meadein
1960. Lau et al. (1988b) showedthat a better correlation ~betweenpacemakerand
sinus rates could be achieved by-using the strength of vibration rather than a
process of peak counting. However, an accelerometerwas used to determine the
strength ~ of vibration and this was compared to the Activitrax’s heart rate
response. Therefore, this study is somewhatinconclusive because two different
variables were sensed and different signal processing is used in the devices.
Lau et al. (1988a) found that the Activitrax responds rapidly and accurately
to variations in walking speed on a constant slope, but whenthe treadmill slope
~ increased the pacing rate did not change even though the energy level was
~gher.~:This ~effect is, similar to stair ascension and will probably be ~xperienced
by all motion sensing pacemakers because the impact frequency and magnitude do
n~t changeproportional to grade levels so the heart rate will’ not be dependenton
grade.
Synergyst ®
The Synergyst line uses Activitrax’s rate-adaptive technology, but is a dual
chamberpacemaker,pacing both the atrium and ventricle in resp9, nse to activity.
Legend® and Elite®

This next generation rate-adaptive pacemaker ~provides the user with more
programmingfeatures and the ability to record and report cardiac events, It was,
introduced in the:United States during Medtronic’s fiscal year 1,990~ The Legend,
asingle chamber pacemaker, keeps the fundamental-operation of rate-adaptive
pacing ~e same but adds more programming features for improved sensitivity;
specificity, and rate response, The Elite line uses :the Legend technology.
However,it is a dual chamberdevice.
This pacemaker has six programmable lower rates (40-90 ppm) and seven
programmable upper rates (100-170 ppm) (Medtronic, 1990); A new pacing
is determined every two seconds ::as follows. A bandpass~filter removes
ventilatory, cardiac, and other low,frequency noise from the raw sensor-signal.
The bandpass filter has a ~range from 7--45. Hz. The activity estimate is generated
’by counting,peaks/2 s exceeding one of:five programmed, threshold windows
(Figure 14~. 12)instead of counting activities ~ abovea positive .threshold like the
Activitrax. For one count to occur.~the.signal must exceed both-the positive and
negative levels of the window.The numberof counts per 2 s is truncated at 24,
Programmable
Programmable rateof
thresholds increase/decrease
IPiezo- Bandpass
HThreshOlddetector
electric , I Determine/
, ,~ pressure 7 < f < 45 ._~-~
MappingS] pacing I
and rate
Activitiesl sensor (Hz) =
counter Activity ’l /
Nonactivites estimate Pacing
noise (counts/2s) rate
(ppm)
Outputof -’
bandpass.
~.. ~: V ~_ _ ,Jwindow
’~Sh~dedareais
lowthreshold
window
Figure 14.12 Legend®and Elite® rate-adaptive block diagrams. The activity estimate
(counts/2 s) is producedby counting the numberof peaks outside a programmed threshold
window.Theactivity estimate is mapped to a target pacingrate througha programmable rate
responselinear curve. Thepacingrate is determinedusingthe presentrate, target rate andthe
pro~ammablerate Of increa,~e/decrease
settings.
The activity estimate (counts/2 s) is converted into target pacing rate li ke

the Activitrax With one of ten programmable rate response curves (Figure
14.13). Unlike the Activitrax, these curves do not flatten out, and therefore the
patient’s upper pacing rate can be reached from any of the rate-response settings,
provided abe/she can produce enough counts. Each curve’s slope varies depending
on the lower and upper rate settings, therefore they are relative curves and not
set slopes. Curve#1 is always the least responsive to activity and curve #10 is the
most responsive so it has the greatest incremental rate Change. The pacing rate is
determined using the present pacing rate~ target pacing rate, and the
programmablerate of increase/decrease (time response) settings. The Legend has
three programmablerate of increase/decrease settings called the acceleration and
deceleration times. The programmedtime should be programmedto emulate the
normal heart. The programmableacceleration times are 0.25, 0.5, oral min and
deceleration.times are 2.5, 5, or 10 rain. (Medtronic, 1990).
Since the Legend and Elite, Medtronic has developed several other motion-
based .rate-adaptive pacemakers with~ an operation commonto the Legend; but
with additional features. The Legend :Plusis a dual-sensor pacemaker that uses
minute ventilation and activity sensing. The Thera line are Medtronic’s first
microprocessor’ based pacemakers that use activity sensors and provide many
added therapeutic and diagnostic features,
Target Curve#
pacing
rate 150’ Maximal
(ppm) 140- pacingrates
120-
100-
80
60
I I I I I
0 3 6 9 12 15 Activity
estimate
(counts/s)
Figure14,13Five of the ten linear programmable rate responsecurvesused to mapan activity

estimateto a target pacingrate. Notethat eachcurvestarts at the programmedminimal
rate and
increasesto the programmed maximalheart rate. Reprintedwith permissionfromMedtronic,Inc.
©Medtronic, Inc. 1990. ’ - " - - ,
14;3.3 Biotronik ’- Erg0s®
Figure 14.14 shows that the Biotronik Ergos operates similarto Anderson and
Brtlmwell (198~t) because it uses a pressure sensor, bandpass filter, comparator
and integrator. The raw signal is filtered .with a second-order bandpas~ filter
centered at 4Hz. Figure 14.I5 shows two of three programmable thresholds;
which determine the level of a cornparator which outputs an’activity estimate.
This is a fixed height pulse width proportional to the area"of the filtered signal
above the programmedthreshold. Then, the activity estimate is integrated .to
produce a signal proportional to the pacing rate. The slope of integration is set by
a programmablerate of increase gain. In the absence of pulses, the pacing rate
d,~creases proportional to the Programmedrate 0f decrease. The programmerhas
a’ehoice of three decay’time Settings (30, 50, Or 100 s); which determine how
long it takes for the pacing rate-to de~rease downto the target pacing rate.
Programmable
Programmable ratesof
thresholds increase/decrease
electric Bandpass " H ’’ H

preSSure i.ifcenter =~ 4 Hz Comparator Integrator
~Pac ing
Activitiesl sensor Activity rate
Non-activies estimate
noise
Figure14.14Thevibration--inducedsignal is bandpassfiltered to reduceunwanted signals. A

comparatorproducesactivity estimates, whichare pulses with widthsproportionalto the area
~abovea progra0maedthreshold~Theintegratoruses programmable slopesto produc¢,a signal t~t
is proportional
to pacingrate.
output ~L/~- - High

_/j__1\_ ../~_
bandpa,~ hresh°Id~
T
" ;"~"" i~ "~’ ......... =Low
comp-output---~ dark= highthreshold

arator ~ !.~-. H ¯ time
output ~’ ’ ’ ’ thresholdlow
inte- ~ate increase: low and high (dark)
grator
(pacing
rate) time
~rate decrease: medium
Figure 14.15Theprogrammed thresholdchangesthe widthof the comparatoroutput. Therate
of increase/decrease
settingsvaryhowfast the pacingrate canchangeas a functionof time.
I4.3.4 Pacesetter Systems, Inc. (St. Jude)
Pacesetter Systems has developed several rate-adaptive pacemakers using a

motion sensor. One of the patents will be discussed and then three different
pacemakers’ operations will be described from the pacemaker manuals.
Smith and Jones (1990) describe a Pacesetter. rate-adaptive pacemakerwhere
a piezoelectric sensor raw signal is amplified and then rectified. The rectification
could be either a half-wave rectifier~or a full-wave bridge. Then ~the signal is
integrated to generate an average amplitude signal. It is claimed that this
technique does not lose any useful information Whichtechniques like filtering and
threshold detection do. However,this is also prone to letting noise or low-level
nonactivities, contribute to the false activity sensing.
Sensolog III®
The piezoelectric sensor, signal is first multiplie d by a programmable gain
(Figure~ 14.16) (Pacesetter,,1990). A bandpass filter~ with a range from 2-50
(Stangl et al., 1989) is used .after the gain, and then an actiwity estimate
produced after a programmablethreshold (choice of 5)i~ Used tO reject any low-
level signals. The activity estimate is mappedto a target rate using one of eight
Programmable
rate of increase
Programmableand decrease
Pro-rammable
~1 slopes ! I
IP
Piezo- I threshold. ~ I’ ~ /~ |
,~ ’ I- ¯ ,/ ! Determine/
I--~ Threshold ~ Mappingl’~-~I pacing ~
Activities] sensorI ’ I
/~ctivitv I Irate I Pa.cing
Target rate
Non-activities estimate
noise [
,ressure pacing
,rate
Figure14;16SensologHI uses a piezoelectric sensor, a thresholddetector, anda target rate

mapping.
programmablelinear curves. Next, the target rate is converted to a pacing rate

using one of five different reaction/recovery times. These times determine the
rate of increase/decrease as a function of time. This pacemakercan also generate
histograms through telemetry, which indicate the numberof times paced in certain
heart rate intervals.
Solus® and Synchrony®

These pacemakers add a little more programmability, but the rate-adaptive
algorithm is similar to the Sensolog III. Also, the user can choose an automatic
threshold level or program one of seven. Another change is that the threshold
level is subtracted from the raw signal, and this difference is used as the activity
estimate, which is a number from 1-31, The Sensolog’s programmable features
include 16 activity-estimate-to-target-rate-mapping curves, 4rate-of-increase
curves, and 3 rate-of-decrease curves..These pacemakers can also generate
pacing histograms.
14.4 ACCELEROMETER-BASED _APPROACHES
14,4,1 Issues for acceleration detection
Accelerometers can be madetodetect accelerations up to 2000 g and frequencies

from dc to 3 kHz. Patient accelerations are usually within the :L2 g range. A
pacemaker accelerometer can be integrated onto the same circuit board as the
signal ’conditioning ~.and the unit may~ be tested before putting the unit into the
pacemaker can~. All present devices sense acceleration in the horizontal-axis
(Figure 14,17)of the body (anterior-posterior, forward-backward).: Section
14.1.3 presents someadvantages and disadvantages regarding signal specificity of
each axis. Mountingthe sensor to detect anterior-posterior~ accelerations is much
more compatible with the can design and the other electronics. In general: the
piezoelectric accelerometers are about-. 10 to 20 times more expensive than the
piezoelectric elements, although the sensor is a small part of the :pacemakercost.
Viewfromfront
Viewfrom of patient,s,
right shoulder c~e~ ’ ~ r
~- Skin -, = Battery
/ =
Ribs
~ ~ Accelerations
Accelerometer
Acce~erometer
~
(senses
accelerations
intoor
out ,of pagb)
Figure14,17Accelerometers
detect upperbodyaccelerationsin the horizontalaXis(antefior~
posterior, forward-backwarddirection).
14.4.2 Cardiac Pacemaker, Inc.
Cardiac Pacemakeruses a piezoresistive accelerometer with a bandwidth from 0--

300 Hz.. The following description of Figure 1’4.18 is from Meyerson et al.
(1993). A technique similar to this is believed to be used in the Excel rate-
adaptive pacemaker.
DC
offset .Modulation, I ~a<np<~is(~ ~__.
.I Accel- Amplification, I kl
-I e rati°n ~ Filtering Modulationl--- ~ H
Activities ! Sensor Harmonics,,and I ’
Non-activities Demodulation |
noise
Activity
estimate Arate
~ Targe
(~ ~ + I Rate I _ rate t Oeterminel
~l ’’’~J
mean t-*~ response I-T’*~ pacing" ~ ’rat~
~__1’- Inumber |~ .]+ Irate . /
Threshold Basel]
rate,
level ,~ ~" Rateof
increase
and decrease
Figure14.18Thepiezoresistive accelerometer,signalis modulated/demodulated to removede

offse~,~Thedemodulated,signal is bandpassfiltered andthen an activity.estimateis producedby
taking the root meansquareandsubtr,actingthe programmed threshold.Atarget rate is produced
aftermapping the activity estim~tteto a changeinrate andaddingtlcbase rate. Thepacingrate is
detei’minedfromthe presentrate; ’targetrate, andtheprOgrarnmed
rat6 of increase/dec/ease.
The -aecelerometer,signal~ (+30 #Vp_p/g) has a de offset added to it from

diode drop’~ Therefore, a modulation/demodulation technique is used to extract
the acceleration signal, Another technique is used to eliminate dc offsets.
Meyersonetal. (1993) show ~the detailwof these techniques: After demodulation
the signal is proportional to acceleration and the bandwidth is still 300 Hz. The
patent claims a distinguishability of 0.01 g. A low-pass filter with a comer
frequency of 10 Hzis ~ ased to filter out unwantednonactivities and noise. Next, a
high-pass filter with a-6omer frequency of 1 Hz is used to filter out very low-
frequency components. Tti~n a programmablegain is used to amplify the signal
before samplingthe analog signal at 2,738 Hz to convert it .to a digital signal. A
programmable threshold is subtracted from the root mean squarq to produce an
activity estimat¢’~:~Thi~ estimate is mappedto a bli~gein pacihg rate using a
programmablegain.. Thenthe base rate is added to produce~thetatgbt pacing rate.
The next pacing :rate is determined from the present rate, target rate, and the
programmedrate of increase (reaction time) and rate of decrease (recovery
time).
14.4.3 Intermedics, Inc.
Intermedics was assigned dual sensor patents, (Alt (1991); Adkins anti Baker
(1989)) that incorporate a piezoresistive accelerometer. Alt (1991) describes
use of a piezoresistive accelerometer and Adldns and Baker’s (1989) describe the
use of a piezoelectric accelerometer. Section 14.1.3 describes AltOs (1989) work
on the basis for detecting humanactivities with an accelerometer. Alt (1991) also
shows some time domain accelerometer raw data during walking, running, hitting
thorax, coughing, laughing, and during a car stopping. Frequency domain data
are also included during walking.
Both patents show the use ofa bandpass filter to isolate frequencies between
0.3-4 Hz. Various long algorithms to incorporate dual sensors have been
described in the patents. The acceleration algorithm relies’only on. acceleration
changes and not on absolute acceleration values (Alt etal. 1988). Alt (1991)
explains the details of this algorithm. ~ ~¯
Intermedics Dash® and Relay® pacemakers use accelerometers and pass
accelerations between 1 and. 4 Hz (Figure 14.19(a)). Then the signal is integrated
to produce an’ activity estimate. The activity estimate is mappedto a pacing rate
response using a triphasic curve (Figure 14.19(b)) (Intermedics, 1990).
curves have a steep slope at the onset of activity, level off, then have a steep slope
again during high levels of activity. Accordingto Lau eval. (1992) this maintains
rate stability during ordinary workloads. The programmercan .choose between
several onset slopes, ordinary workloadlevels, and ten high-activity-level:slopes.
"~Programmable
low and high
rate ,of increase
IAccel- Band
--
. --
. ~
ass I I =, IDi~terminel
P _, ,]-"llntegrator I’--’tpai~iiag -I
sensor ~1erati°n , ~ .Actlvitylrates.~ iva~!ng
ActivitiesI
.Nonractivities
:estimate 17ate
noise
(a)
Pacingrate
of increase
Tailoredrate
lowerrate of increas
e : _.,~:
.. . activity estimate
(b) -~ ~
Pigure14,19Theactivityestimateis convertedto a p~cingrate.ruinga td’phasic~qu~w~,e (b). This

e has a. moresensitive acceleration/pacing
~triv
~0ads
ity, .with a less sensitiVeintermediate’
rate re!afipnshipduringlowand.hiila levels of
slope tb mainta~:~.~,~m, ~bi|~ ~u/~:0~
14,5 STUDIES ON MOTION-BASED RATE-ADAPTIVE

PACEMAKERS
Extensive clinical studies have been performed on motion-based rate-adaptive

pacemakers. A number of factors may affect the outcome of these studies and
specific features are rarely isolated. For instance, manystudies conclude that
accelerometers are better than pressure sensing, but the’study compares the
pacing rates from the pacemaker and not the .raw sensor data. The signal
processing, algorithms, and programmed features influence the outcome
therefore, the conclusions from he study maybe inaccurate.
Mianulli et al. (1989) and Benditt et.al. (1989) found strap-on acceleration-
sensed rate-adaptive pacemakers are valid representations of implanted rate-
adaptive pacemakerresponse whenstandardized techniques are used. Matula et al.
(1992) strapped external pacemaker~~onto ten patients with implanted pressure-
sensed devices. There was little difference between the external and internal
pacemakersduring various treadmill .exercises.
For studies comparingdifferent pacemakers, we must always be aware of the
interindividual Variability; the selection of programmedparameters, as well as
the factors mentioned above. Often studies set the programmedparameters at the
nominal values while performing tests but, the pacemakers are intended to be
programmedfor each specific patient. With these factors in mind, the conclusions
from several studies are presented.
14.5.1 Cardiac performance
Humenet al. (1985) showed that the Medtronic’s early motion-based pacemakers
significantly, improved cardiac performance and increased exercise tolerance.
This was confirmed by Faerestrand et ,al. (1987) and Beyersdoff et al. (1986).
Candinaset al. (1991) studied the patient well being during routine daily exercise
for patients with e~ther ma Activitrax or Sens~10gpacemaker. The conclusion was
that patients who were fully dependent on pacemakers showed greater benefit
from rate response pacing compared to those who only intermittently required
pacing.
14.5.2 Stair ascent/descent
A pressure or acceleration, sensed systems will not generate proportional

responses during stair ascent/descent because foot impact is harder (and pressure
signals are larger) during descent than during ascent. This is confirmedin studies
by Candinas (1991) and Lau (1989). Acceleraiion sensor systems have shown
little better response than pressure sensed systems, but the response still does not
have a proportional response. Alt (1989) Showed that horizontal axis
accelerations exhibit a very small difference betweenstair ascent and descent.
Matula (1993) tested the second-generation accelerometer-based pacemakers
from Intermedics (Relay®,Stride®, and Dart®). The pacemakers tracked the
actual heart rate change at 90 steps/min, but at 120 steps/rain the pacing rate
increase from descent to ascent was about one-third of the actual heart rate’s
increase.
Bacharaehet al. (1992) tested Excel® VRby CPI (acceleration-sensed)
the Legerid’by Medtronic (preS~e-~,ensed). The Study showed thepacing rate
the acCeleratiOn-sensed pa~make~ii~ereased during a~cent However, the change
was significantly less than the intrinsic heart rate. At 100 steps/min, the pacing
rate change was about one-tenth the intrinsic heart rate change. This test also
showedthat the pressure-sensed pacemaker inaccurately had higher pacing rates
descendingthan ascendingstairs for rates of 80 and 100 steps/re_in.
14.5.3 Studies comparing pacemakers using pressure sensing
Res and de Boer (1990) compared the Ergos 2® and the Activitrax pacemakers
during a multiphase protocol. This study showed that the Ergos 2 followed the
intrinsic rate much better than the Activitrax. The Ergos 2 did perform much
better during bicycling. However, the Activitrax’s performance may have been
improved by programming the pacemaker better because it is biased about
25 beats/rain belowthe Ergos 2 and the intrinsic heart rate. The poor pacing rate
during bicycling and lower rate increases may have been improved by lowering
the Activitrax activity threshold or by choosinga quicker activity response.
Stangl .et al. (1989) compared the Sensolog and Activitrax pacemakers
during bench tests and in patients during various activities.~ The Sensolog
pacemaker increased its pacing rate for a constant speed, increasing slope test
performed on a treadmill. The Activitrax did not discriminate between slope
levels. This could be due to the Activitrax’s ~ algorithm of counting steps/s and
disregarding the intensity information over the set threshold. Sensolog’s
algorithm includes integrating the signal over’ the set threshold so that intensity
information is included. A disadvantage to this technique, as supported in this
Study, is that the pacing rate increases more whenthe patient is lying in a prone
~sition. Various noise sources from travel were found tO ~!Jave~e same minimal
effect on both devices. ~ ~
In contrast to’ Stangl et al. (1989), Kubischet al. (1988) did not find a
increase of the Sensolog during treadmill exercise ~with an-increasing gradient
while keeping the same speed. Kubisch et al. chose the same rate responsive
parameters found useful in the patients’ daily life while Stangl et al. did not
report the l~rogrammingparameters chosen.
Lau et al. (1992c) studied the effect of footwear on these two devices. The
Sensolog’s signal integration is more susceptible to the type of footwear because
the impact intensity over the threshold changes the pacing rate. Medtronie’s
threshold:, detection method is not used for amplitude.iiiformationbut.-to 1)
~
distinguish betweennoise and activities and 2) correlatethe activity frequency to
heart rate.
14.5.4 Studies comparing pressure-sensed and acceleration-sensed

pacemakers
Bacharach et al. (1992) compared the Legend (pressure sensed) and Excel
(accelerat.i0n sensed)~during various activities using nominal ~programmed
settings. Excel’s pacing rates were Closer to the ii~tr~nsic heart rate than the
Legend’s rates du~ng treadmill walking, bicycle erg~¢try, and stair ~nsi0n.
Lau et al. (1992b) found that acceleration-sensed pacemakersrespond better
than pressure-sensed pacemakersduring walking, jogging, and standing..
Matula et al. (1992) comparedpacing reSgQa~Sof the Relay (accelerometer-
sensed), Sensolog, and Activitrax (pressure,sensed) during a ~ead~l!exercise
with changing speeds and slopes (Fibre 14.20). The basic rate for all pacemakers
was set at 70 bpm, and the pacemakerswere calibrated to yield a pacing rate of
95 bpmwhenthe subjects were walking on a treadmill with a speed of 3.2 km/hr

and a 0% grade. The resting rate of subjects was 90 bpm, but for an unknown
reason, the experimenters programmedthe-devices, to 70 bpm. The heart rates
and pacemaker rates were plotted as a function of workload. The Relay’s pacing
rates and slopes most closely correlated with the intrinsic heart rate.
Figure 14.20Acomparisonof the Relayaccelerometer:sensedpacemaker with the Activitrax

andSensolog vibratiun-sens~ed
pacemakers andthe intrinsic heart rate, Theplots are basedonthe
averagefroifi 20subjects. The,startingintrinsic rate was90bpmwhilethe pacemakers basic rate
wasSet to 70 bpm.TheXaxis i~ the walkingspeedin kin/h" andthe slope of th~.treadmill(%).
FromAlt, E. 1993. Advancesin sensor technologyfor activity rate=adaptive pacemakers:
traditional piezoelectriccrystal versusaccelerometer.~ Barold,S. S. andMugica,J. (eds.) New
perspectivesin cardiacpacing.MountKisco,NY:FuturaPublishing.
14.6 SUMMARY OF SENSING TECHNIQUES AND DESIGNS
Motionsensing is the most widely used methodfor rate-adaptive pacemakers.It is

clinically successful becatlse this methoddoes ngt.require, additional leads so the
system is easy to implant, i,s ~latively simp!e to program, and rapidly adjusts the
pacing rate. Acceleration and pressure sensors produce activity signals primarily
due to the acceleration forces working on the pacemaker mass. Body motion
sensing does not directly sense metabolic changes such as for anxiety, fever, or
circadi~ heart ~ate Ch~ges. Dd~l~enso~ designs should include ~h activity
sensor for a fast rate response at the onset of exercise and a metabolic sensor to
improve the physiological response.
The designer must consider the following:
1. Sensor, signal processing, and algorithms to produce~anaccurate pacing rate.
2. Pacemakermass and Candesign because they affect the sensor output.
3. Minimizing power rgqnirements to extend pacemaker-life.
14.6.1 Sensing methods
The advantages of acceleration ~nsing over pressure sensing include:

1. ~ The acdeleration signal produced’ during-stair descent is not’ incorrectly
larger than stair ascent, while the~ vibration signal during stair descent ,is’
RATE-ADAPTATION ~BY MOTION 331
inappropriately larger than stair ascent. However,the acceleration Signal is

not l~roportional to activity level during stair ascent or descent.(Alt, 1989).
Manufacturability: the acceleration sensor can be flow soldered to a surface
mount hybrid chip with an automatic assembly, while a piezoelectric
vibration sensor is bonded to the can and usually manually soldered to the
electronics.
DCpressure (i.e. lying prone) maylargely increase the sensor coupling for
pressure sensing so that cardiac signals could be detected as activity. Note
that somepressure-based designs filter out these 10w-frequencyeomponents~
~DCpressure does not produce ~an activity signal in acceleration sensors, but
,tight clothing above the pacemakermaydecrease an accelerometer’s_output.
Vibration sensing advantages include:

1. The piezoelectric element initial cost is about an order of magnitude lower
than for an accelerometers. ~
2. The Vibration sensor produces an activity signal without consuming power,
which is Of vital importance in a p~cemaker. The amplification for
~ac~cele~rometers is also about 100 times greater than vibration sensors..
3. -The pressure sensor signal to noise ratio is less than the ~acceleration sensor
signal to noise ratio. Therefore, the designer has a greater challenge to
extract the acceleration signal with rninimal.power requirements.
.... Alt et al. (1989) showedthat acceleration signals from about.l-4 Hz should
be used for activity sensing, but a slightly higher cut-off Couldbe used effectively
because this would incorporate higher frequency activity signals~ The horizontal-
axis (anterior-posterior) accelerations are currently sensed. The lateral-axis also
shows distinguishable acceleration variations during biking and large variations
during stair ascent/descent and walking. The lateral and vertical axis has probably
not been used because it maybe harder to mount the sensor inside the pacemaker
s~eways and also if the pacemaker rotates inside the body the detected signal
levels maychange.
14.6.2 Motion-based rate-adaptive pacemaker designs
Figure 14.21 summarizes some of the pacemakers produ’C~d.~This ’does not

include dual-sensor designs. ~
14.7 REFE~NCES ~ ~
Adkinsand Baker,1989.Rateresponsivetarmacpacemaker.USpatent 4,922,930,

A!t, E. 1991. Rate responsive cardiac pacemaker..USpatent 5,014,700. ~ .... ¯
AI..~t, E, 1993.Advances in sensortechnology
.for activity rate-adaptivepace~akersg
~traditional
piezoelectric crystal versus accelerometer.In Barold, S. S. and Mugiea,J. (eds,) New
..perspectives in cardiacpacing.MountKiseo,NY:FuturaPublishing
Alt, E., Matula,M.,Theres,H., et al. 1989.Anewrate-modulated pacemaker,s3~st~raoptimized
::~ bYcombination of, two. sensors. PACE,
11=1119-1129:
Alt, E., Matula,M., Theres,H., et al. 1989.Thebasis for activity controlledrate variable
~ pace.makers:An. analysis of mechanicalforces on :humanbodyinducedby exercise, and
environment.PACE,12: 1667-1680.
,Mt,. E.~Matula,M,Theres,H., 1989~..Thebasis for activity controlled~rate variablecardiac
~. pacemakers~ an analysis of mechanicalforces on the~human bodyinducedby, exercise and
environment.PACE,12: 1667-1680.
¯"1
Manufacturer Sensing method Approximate Thresh-

A = acceleration bandpass . olds~
P = pressure filter ~utoff
and type of sensor:. °frequencies
piezo- (Hz)
E = electric
R = resistive
C = capacitive Incr Decr
Num ~er of programmable
settin ;s
Medtronic
Activitrak/Synergyst P,E <f<45 3 10 !i 1
<f<45 5 10 3 3
8<f< I00 5 . I0 3 3
Biotronik
P,E =4
f~.~r 3 ~0 3 .3
Siemens
Sensolog IH P,E 2<f<50 5 "~ 8 5
Solus & Synchrony P,E 2<f<50
lntermedics 0.3<f<4 ? I0 I0
Dash, Relay
Cardiac
Pacemakers l<f<10 8 16 6 8
Excel
Figure 14.21 Properties of motion-basedrate=adaptive pacemakers’. The ban@assfilter and

thresholdstry to spatially separateactivities, nonactivities, and noise. Themappingcurvesconvert
an activity estimate to a targetpacingrate. Therate of increase/decreasecurves determinehowfast
the pacingrate changesas a functionof time. The.9 indicate uncertainty.
Analog Devices, One Technology Way, P.O. Box 9106, Norwood,MA02062-9106. 1-800-262-
5645.
Anderson, K. 1986. Sensor pacing - research leads to major breakthrough in rate-responsive
pacem__aking. MedicalElectronics, 10:. 89-93..
Anderson,IC and Brumwell,D. 1984. Rate adaptive pacer. USpatent 4;428,3781
Anderson, IL and Moore,A. 1986. Sensors in pacing. PACE,9: 954-959. . .
Bacharach,D, I-tilden, R. Millerhngen,J:, et ’hi. 1992. Activity-ba~edpacing: comparisonof a
device using an aceelerometerversus a piezoelectric crystal. PACE,15:,188-196.
Barold, S., S. and Mugiea, J. 1993. Newperspectives in cardiac pacing. MountKisco, NY:
Futura Publishing.
Benditt, D. G., Mianulli, M., Fetter, J., etal. 1991. Anoffice based exercise protocol for
predicting chronotropie response of activity-triggered rate-variable’ pacemakers.Am.
CardioL, 64: 27-32.
Beyersdorf, K. 1986 Increase in eardiac output with rate-responsive pacemaker.Ann. Thoracic
Surg., 42: 201-205.’
Candinas, A., Gloor, H., Franz, W, et aI. 1991. Activity-sensing rate responsive versus
conventional freed-rate pacing: a comparisonof rate behavior and patient well-being during
routine dallyexereise. PACE,14: 205-213.
Chevalier, P. 1985. Improvedheart rate and exercise performance with an activity sensing
pacemaker.(abstract) PACE,8: 22.
Coates, J. E., and Meade,F. 1960. The energy expenditure and mechanical energy demandin
walking. Ergonomics 21~97-119,
Deiekmann, D; 1957. Ein fluss ventikaler maeehanisehen swingungen auf den:~Meneh.
Arbeitsphysiol, 16.
Faerestrand, S.;Breirik, K.,andOhm,O. 1987:Assessment of theworkcapa~eity and
relationship betweenrateresponseand ’exercise: tolerance associatedwithactivity-sensing rate
responsive ventricular pacing. PACE,10: 1277-1290.
Humen,D. P., Kostuk, W. J., Klein, G. J. 1985. ,Activity-sensing, rate-respOnsive pacing:

improvementin myocardialperformancewith exercise. PACE,8: 53-59.
IC Sensors, 1994. Micromachined silicon sensors product catalog, 1701McCarthyBlvd. Milpias,
CA95035-74!6. 1-800-767-1888
Intermedics. 1990. Cardiac pulse generator physician’s manual:Relay Model29403.
Ismail, A. H., Barany, L W., and Smith, C. B. 1971. Relationships betweenmechanical force
and physiological costduring gait in adult man.M.Cooper(ed.). Biomechanics,Chicago,The
A~ti~ hstitute.
Kubisch,K., Peters,.W., Chiladakis, I., et al. 1988. Clinical experiencewith the rate responsive
pacemaker Sensolog 703. PACE,11: 1829-1833.
Lau~C., Stott, J.,~ Toff, W~,et al. 1988b.Selective vibration sensing:A newconceptfor activity
sensing rate responsive pacing. PACE,11: 1299-1309.
Lau C., Tai, Y., Fong, P., et al. 1992b. Clinical experience with an activity sensing DDDR
pacemakerusing an accelerometer sensor. PACE15: 334-343.
Lan, C., Mehta,D., Toff, W., et al. 1988a.Limitations of rate responseof an activity-sensing
rate-responsive pacemakerto different formsof activity. PACE,11: 141-150.
Lau~C., Wong,C., Leung, W,et al. 1989. A comparative evaluation of a minute ventilation
sensing.and activity sensing adaptive-rate pacemakersduring daily activities. PACE,I2:
1514-1521.
Lau, C., Tai, Y., Fong, P., et al. 1992a. The use of implantable sensors for the Control of
pacemaker~ated tachycardias: a comparativeevaluation betweenminute.lventilati0n sensing
" ~mdacceleration sensing dual ch~ber rate adaptive pacemakers.PACE,15: 342-44.
Lau, C., 1992c. The range ofsensorsand algofitht~ used in rate adaptive cardia~ pacing. PACE,
~ lS: 1177-1211. " "
Matula, M.,Aft,E.,Schrepf, R.,et.al. 1993:Therateadaptation ofanaccelerometer controlled
pacemaker during stairwalking. (abstract) PACE,16:1195~ .
Matula, M.,Aft,E.,Schrepf, R.,Holzer, K.1992. Responseofactivity pacemakers controlled by
different motionsensors totreadmill testingwith variedslopes. (abstract) PACE, 15:523.
Medtronic. 1986.Activitrax Technical Manual, 7000Central Ave.NE,Minneapolis, MN55432.
Medtronic. 1989.Annual Report, 7000Central Ave.NE,Minneapolis, MN55432.
Medtronic. 1990.Legend Technical Manual, 7000Central Ave.NE,Minneapolis, MN55432.
Medtronic. 1992.Annual Report, 7000Central Ave.NE,Minneapolis, IvlN55432.
Medtronic. 1993.Annual Repo~7000Central Ave.N’E,Minneapolis, MN 55432.
Meyerson, S.J.,Linder, W.J.,Maile K.R.1993. Acceleration-sensitive cardiac pacemaker and
method of operation. USpatent 5,179,947.
Mianulli etal.1989A comparison ofstrap-on versus implanted activity-based rate-responsive
pacemakers: Arestrap-on studies valid? (abstract)PACE, 14:742.
Montoye, H. J.andEpstein, F.H. Tecmnseh community healthstudy: aninvestigation ofhealth
anddisease inanentire community. J.Sports Med.5:127-131.
Motorola. 5005E. McDowell Rd.,Phoenix, AZ 85008. 800-521-6274.
Pacesetter. 1990.Sensolog HImanual. 12884Bradley Avenue, Sylmar, CA91342.
Pacesetter. 1990.Solnsmanual. 12884Bradley Avenue, Sylmar, CA91342.
Pacesetter. 1990.Synchrony IImanual. 12884Bradley Avenue, Sylmar, CA 91342.
Pall~is-Areny, R.,Webster, L G.1991.Sensors andsignal conditioning, NewYork: JohnWiley
& Sons.
Re.s, L. and de Boer, T. J. M. 1990. Evaluation of a newbody motion sensing rate response
sensor (Ergos 2), using a multiphaseexercise protocol. PACE,13: 1207.
Reswick,J., Perry, J., and Antonelli, D. 1978. Preliminaryevaluation of the vertical acceleration
gait analyzer (VAGA). Proc. 6th Annu. Syrup. External Control Human Extremities, Aug28-
Sept. 1, 305-314.
Servais, S. B., Webster, L G., and Montoye,H. J. 1984. Estimating humanenergy expenditure
using an accelerometerdevice../. Clin. Eng., 9: 159-171.
Silicon Designs. 1445NWMall Street, Issaquah, WA98027-5344.206-391-8329.
Stangl, K., Wirtzfeld, A.,.Lochschmidt,O., et al. 1986. Activitrax pacemaker:Physiological rate
response with a nonphysiological sensor? Symposiumof Progress in Clinical Pacing, Rome,
124.
Stangl K., Wirtzfeld, A., Lochschmidt,O., et al. 1989. Physical movement sensitive pacing:
comparisonof two "activity"-triggered pacing systems. PACE,12:102-110.
Toff, W. D., Leeks, C., Joy, M. et aL 1987. Activity-sensing pacemakerfunction during air
travel Br. HeartJ. (abstract) 57: 573.
Wong,T. C., Webster, J. G., Montoye,H. J., and Washburn,R. 1981. Portable accelerometer
device for measuring humanenergy expenditure. IEEE Trans. Biomed~Eng. BME-28:467-
471.
14.1 List the three pacing rate accuracy factors for a rate-adaptive pacemakerwith a motion
sensor and give an exampleo~ each.
14.2 Givethe frequencyrange that shouldbe used for accelerationsensingaccordingto/kit et al.
(1989). State whetheror not the hodzontalaxis acceleration can distinguish betweenstair
ascent/descent.Repeatfor different exertionlevels duringbiking.
14.3 Designa switched-capacitoramplifier with a total gain >400and a baiidpass falter topass
the frequency range from 0.5-4 Hz for the Picochip piezoe[e_c.tric acceierometer by
Endevco:The clock frequency ’range is 1’5 kHz and capacitors values must range from
0.25-50 pF.
14.4 Describethe operationof a piezoresistive accelemmeter.
14.5 Describethe operationof a piezoeapacifiveaccelerometer.
14.6 Describeand illustrate howa piezoelectric cry~stal is used to sense vibration andpressures
in pacemakers.Explainhowthis configuration is diff,’rent fro musing an ac;cel~rometer.
List two advantage~and give two examplesofinapp~priate pacing respot~ses:
14.7 Explainwhatthe threshold levels are used for. Giveah examplefor whyone patient’s level
wouldbe set lowand anotherpatient’s level high.
14.8 ~De,scribehowa disadvantageof the ActiviWax~ Wasfixed in the next:generafignLegend.
14.9 Explainthe,differences betwe~,~nthe methods~ised~to.~nerateaft activity estimate for the
MddtronicLegend, Bidtrotfik Erg0s, and P ,a~settet Seiisolog llIi ~ .. ~ ¯
14.10 Explain tl/e differences betweenthe meth&lsus&l io generate an activity estimate for
Car~acPacemakerand Intermedics pacemakers.
14.11 List three factors that dete~ne the pacing rate for the MedtrOnie’Legend pacemakerand
explain howthe factors are determined.
15
Rate Adaptation by Temperature

Mark J. Mayotte
Chapter 13 notes that patients whosuffer from atrial flutter or,fibrillation, SSS
(sick sinus syndrome)~:sinus bradycardia, .or other types of sinus node disease are
incapable of benefiting from atrial-sensed rate-responsive pacing,:;Although
according to Starling’s law, cardiac output can vary dueto an increase in stroke
volume,L sueh~ehanges are limited to a maximal increase of less than 50%,
whereas metabolic demandsmayrequire a four to fivefold increase (Houdas and
Ring,~ 1982; Furman,1990). Therefore, in order, for such patients’ heart rates to
vary, their pacemakers should be able to make,accurate and reliable changes in
pacing rate in response to direct or indirect metabolic indicators which parallel
normal heart rate (HR) modulation., One of these, indicators is eentrat venous
blood temperature (CVT).
In order to understand howCVTis used as a measurand for rate adaptation,
it is both useful and important to understand how the body produces heat and
regulates temperature.
15.1 BODY TEMPERATURE PRODUCTION AND REGULATION
Under normal resting conditions, the average humanCVTis approximately 37"C.

The CVTis best represented as--and for the purpose of this chapter is ass.6med
to be~--the temperature of the blood in the right ventricle because the blood in the
ht ventricle is a mixture of the venous return from all parts of the body. The
~dy produces heat as a-byproduct of metabolism: 78+4%of the energy produced
during metabolism is in ~the form of heat, while only 22+4%is released in the
form of mechanical energy (Alt et al., 1986). If this heat were not regulated, the
body temperature would rise approximately l*C/h (Rhoades and Pflanzer, 1992).
The body dissipates heat through the peripheral circulation.-~-20% by
evaporation, 25%by conduction, and 45%by radiation--aud through respiration
---8% by evaporation, and 2%by radiation (Rhoades and Pflanzer, 1992),
15.1.1 Regulating temperature: the hypothalamus
Mthoughthere are several thermore~latory structures, mainly in the brain stem

~d spinal ~ cord, the hypothalamus iZmsthe main control over thermoregulati0n.
The hypothalamuscontains three main types of neurons that participate in either
thermosensitivity or thermoregulation. Like the cold and warmreceptors in the

skin, which modulate their firing rate under most circumstances as a linear
function of temperature, the hypothalamusalso contains its ownthermosensitive
neurons, which change their firing rates based on local changes in temperature.
In addition to having cold and warmreceptors, it also contains interneurons,
which change their firing rate in response to local temperature change, but unlike
the warmand cold receptors, the change is not linearly related with temperature
(Houdas and Ring, 1982).
Although both the warm and cold neurons and the interneurons do not
produce thermal effector reactions, they maytransmit a signal related to this
temperature change as well as provide a pathway to the third type of neuron in
the hypothalainus. The hypothalamus receives electrical stimulation from
thermoreceptors in the body and responds with thermal effectors, which cause
such reactions as "skin vasodilation, vasoconstriction, shivering, increased heat
production by metabolism, and possibly a link with the sympathetic nervous
system, which results in an increase in HRduring periods of extreme external
heating (Houdas and Ring, 1982).
Interlinked between the affector and effector signals is some form of
integrator which compares the affector signals with a set point or reference
temperature to determine the required effector stimulus. The set point changes
due to such conditions as exercise, at whichthe set point, increases, or sleep,, at
which the set point decreases. The exact method by which the hypothalamus
processes the information, determines the effector stimulus, and sets the
temperature reference is uncertain (Morgane and Panksepp, 1980; Houdas and
Ring, 1982). Figure 15.1 shows a modification of the thermoregulatory loop
diagram (Houdas and Ring, 1982).
Endocrineand
otherinfluences I I Brai~ I
I
rl d:tT:!a mlus I ~and
Therm°sens°rs Craerd:Op~na~e~lar
]I I
constriction dilationVaS°"
[ I
I Shvedngand
metabolicheat
production
I
Swe
ringI
Body
temperature 12
I
I
I Respiration Environmenti
Figure 15.1 The basic components of the negative feedback thermoregulatory loop Tset
represents the hypothalamus’s changing thermostat. From Houdas, Y., and Ring, E. F. J. 1982.
RATE ADAPTATION BY TEMPERATURE 337
15.1.2 Temperature fluctuations and their relationship to heart rate
Becausethe CVTdoes not.stay at a constant 370Cbut varies in response to .several

factors, it is .necessary to understand these factors and howthey relate with HR.
Circadian variation~
CVThas a circadian (diumal)~ fluctuation: the CVTfluctuates, approximately
x~0.25,C around the baseline, reachinga minimumat night and amaximal peak
during the day. The increase _ in HRduring the dayis at.least partially due to the
increased~ metabolic need while awake. Floweret, the CVTreaches a maximal
peak generally during mid to late afternoon whether or not a person is active or
resting. This peak has been shownto occur continually even during experiments
where the, subject was completely isolated from factors such as light, time, and
noise. Thus the circadian variation is not o~y a function of increased activity but
also seems to be an intrinsic property of the bod~ (Houdas and Ring, 1982).
~2imilarly, HRalso varies in paralle l, ,with CVT(Sellers,. 1987), approximately
O bea~s/min (~pm), reaching a minimumat ~ght, a rise during W~inghouri,
and a maximal peak during late afternoon. BothHRand CVThave a direct
correlation with metabolic rate (Hanser, 1984; Berggren.and Christensen, 1950;
Altet al, 1986). Figure 15.2 shows the circadian C~I" and FIR fluctuations over
a 24-h period with periods of exercise supedmpesed.
Exercise . " .
Aithoughcircadian variations in HRa~e significant, the .need for an in,reded HR
d~fig exercise in the~absen~e .of normal sinus function initiated. ~e development
0f.rat~-adapfive p~cemakers~HRs can increase between 25 and 90 bpm at ~owto
moderate exercise levels (20-150 W), which corresponds to exercises such
bicycle ergometry at approximately 50-60 revolutions/rain or trea ~dm.ill tests at
approximately, 2-5 km/h.. ~is value, of course~ can .vary depending on the
physical condition, of the individual. At a given workload, th~ increase in HRas a
~unCtion of time is linear to exponential in shape until a point at whichthe FIR
plateaus (Laczkovics, 1984; Fearnot, 1988). The rate of increase in FIR as well
the level of the plateau is dependent on the individual’s oxygenuptake at. that
workload relative to the maximaloxygen uptake (relative workload) (Aft et al.,
1986; Munteanu, 1986).
0.75--
~- 0.0 ~
~ O0 l: O0 ~: O0 S: O0 ~5:O0
TIHE (HOURS) ¯
Figure 15.2 Thecircadian fluctuations of CVT and HRof one subject, averagedover 10-rain
intervals, with periodsof exercisesuperimposed. TheHRandCVT are at a minimalvalueduring
the night andat a maximal
valueduringperiodsof exerciseandin the midafternoon.FromSellers,
T. D., Fearnot,N. E., Smith,H.J., DiLurenzo, D.~ M.,Knight,J. A., andSchmaltz,M.J. 1987.
Rightventricularbloodtemperature profiles for rate responsivepacing.PACE,10: ,467-479.
338 DESIGN OF. CARDIAC PACEMAKERS
The need for an increased HR.is not only to compensate for increased
metabolic demand,but it is also required in order to increase circulation to allow
for cooling of the body as suggested by abnormally elevated CVTsin persons
during exercise who have impaired cardiac output (Nielsen, 1966). Although the
need for an increased HRmaybe clear, the mechanismby which it changes is not.
The increase in HR,according to available evidence, is due to the activation of the
sympathetic nervous system by reflexes in the contracting muscle; and not due to
either a perceived drop in blood pressure due to vasodilation of the blood vessels
in the muscle or due to a drop in concentration .or partial pressure of 02 or
increase in concentration or partial pressure of CO2(Berne, 1981). In fact, the
baroreceptive reflex, which responds to changes in blood pressure, is reduced
during exercise (Berne, 1981). "
CVTalso increases during exercise. Due to ~e increase in metabolic rate,
additional ~heat is produced. This additional heat causes the CVTto rise. CVTs
can increase between 0.4"C and 1.4’C from an initial exercise-evoked dip at low
to moderate exercise levels’(20-100 W). Similar to HR, at a given workloadthe
inc.rease in CVTas a function of time is linear to’ exponential in shape
(Laczk0vics, 1984; Cook, 1984) until a point where heat production is balanced
by heat loss at which it plateaus. The rate of increase in CVTaswell as the point
at which it plateaus is set’according to the relative workloadof the individual~
The CVTrate of increase and its plateau at a sustained workload also correlate
with HR. Meantypical HRrate increases (d(bpm)ldt) and CVTrate rises (dT/dt)
for exercise levels described previously are approximately 10-15 (bpm)/min and
0.05:-0.11 C/rain, respecuvely (Sellers, 1985, ’Griffin, 1986). Studies companng
HRch~geto CVTchange during exercise at levels described above have shown
correlation coefficients between 0.95 and 0.9864 for both healthy and pacemaker
patients (Munteanu,1986; Alt et al., 1986).
Although the correlation between the CVTand HR is very good, it is
necessary to investigate the correlation further. Figure 15.3 shows a healthy
individual’s CVTand HRvariations during moderate exercise (Alt et al, 1993).
~ knvh
~ k~n~h
l S%
..o- HR(1/ndn) ’38,3S
120 37.60
1011
37.10
36.60
Time
Figure15.3 A healthy individual’s CVTand HRduring moderateexercise. FromAlt, E.,

Barold,S. S., andStangl,K.(eAs.)1993.Rateadaptivecardiacpacing:Berlin: Springer-Vedag.
There is also strong correlation between HRand CVTduring less strenuous

exercises, such as walking (Alt et al., 1986), and during heavier treadmill
exercises (12 km/h) (Behrenbecket al., 1985).
- The graph shows that there is a strong correlation between CVTand HR.
Closer investigation of the graph shows an interesting phenomenon:an initial
decrease in CVTupon initiation of exercise followed by a later increase in CVT.
The. initial decrease in CVT,whichusually occurs at the onset of exercise, is due
to sudden vasodilation, which can occur either just prior to exercise due ~to
a~nficipation of exercise, or as an initial and suddenresponse to exercise (Sellers,
1987; Fearnot, 1988; Cook Pacemaker, 1992). The dip is caused by a heat
trari~sfer between the cooler surroundings and the greater volume of blood
flowing through the periphery due to the vasodilation. The magnitude of the
decrease ranges approximately between 0.15-0.5"C with low to.moderate
exercise levels with a meanaround 0.25"C and reaches the minimal peak during
the first 1-2 min (Sellers, 1985; Sellers, 1987). This value was determined from
studies that included both healthy and cardiac patients, the .latter whotypically
have lower than normal cardiac output. During periods of repeated exercise
followed by-brief periods of rest, the exercise-evoked dip reduces in magnitude
(Sellers, 1987). At 10wexercise levels (10--30 W), the temperature increase after
the initial dip maynot increase above the resting CVT(Zegelmanet al., 1990).
The HR,on the other hand, increases rapidly at the onset of exercise. Both
the HR and CVTrise rate and increases in magnitude at a given absolute
workload are higher for cardiac patients than in normal; tiealthy subjects (Alt et
al., 1986). In general," the rate of CVTand HRrise during exercise is less than
the rate of decline in CVTand HRafter exercise. Both CVTand HRusually have
:a steeper initial slope followed by a gradually decreasing slope .a~t higher and
lbw~r CVTtemperatures-tothe exercise and baseline rate~ respectively.
Following exercise, CVThas a latency of about l min befor6 it begins to
fall r while the HRbegins to fall immediately. This value was estimated and
averaged fr0m values taken from available graphs containing HRand CVTcurves
from both cardiac patients and normal subjects. There is also a latency associated
with the rise in CVTof approximately 1 min; that is, the CVTcontinues to
increase for a period of about 1 min after the HRhas either plateaued or has
begunto decrease upon cessation of exercise.
Fever ~
In.general, an increase of 10-15 bpm/*Cis associated with fever along with an
increase in metabolism(Alt et al., 1986). In addition to CVTincreases, often
times fevers have periods of chills. Studies involving such effects on HRand CVT
have not been reported.
Anxiety
EmOtionalanxiety, which is Sometimesexperienced before many Of the exercise
protocols, has :been shownto cause both initial HRincreases and CVTvariations
similar to the onset of exercise (dips followed by increases) (Fearnot, 1987;
Sellers, 1987; Feamotet al., 1989).
Ettvironment
A decrease in the ambient temperature, which initially decreases the CVT,will
trigger an effector response from the hypothalamuswhich will cause an increase
in thermal metabolism and/or vasoconstriction. If the effector is solely
vasoconstriction, the HRwill decrease as a result of the baroreceptive reflex to an

increased MABP.At temperatures colder than 15"C (Houdas and Ring, 1982),
increase in thermal metabolism also results. This corresponds to an increase in
HR. Similarly, an increase in ambient temperature causes an initial increase in the
CVT. This will result in vasodilation causing MABP to decrease, thus causing the
HRto increase.
Although there are a limited number of studies relating HR and CVTwith
taking showers or baths, these will most likely follow the trends of ambient
temperature albeit probably with a steeper rate of change of both HR and
temperature. Studies by Sellers et al. (1985, 1987), Alt et al. (1993), and Fearnot
et al. (1989) have shown that hot baths have caused an increase in CVT
approximately 0.2-0.5"C over a period of about 10 min after initial CVTdrops
concomitant withstanding, bathing preparation, and movement into the bath tub.
Eating-and drinking
Studies "by Sellers et al. (1985, 1987) reported that eating causes transient
increases in CVTbetween 0.13-0.48"C. These studies reported that ~ drinking cold
liquids caused transient CVTdrops between 0.08-0.15°C over periods less than a
minute. Hot-liquids had no-effect on CVT. The effects on HRwere not reported.
Figure 15.4 summarizes the.effects of temperature change on heart rate.
Effector CVT Chanse (’C) Effect on HR(bpm)

Circadian Magnitude:..~+0.25 Magnitude: AHR= + 20
Rate: slow; dependenton activity. Rate: slow; parallels CVT.
Temperaturelow during sleep and higher
dm~n~
day.
Exercise Dip magnitude: 0.15-0.5 Magnitude: AHR= 25-90
D/pdurat/on:’ 1-2 rain. Rise slope: 7-15/min,parallel to
Rise magnitude:0.4-1.4 from dip for slow
to mode~tetreadmill/cycle exerc|ses. Fall slope: -20-28/min,parallel to
Rise slope: approximately+0.I/rain,
dependenton activity.
Fall slope: approximately-0.15/min
Fever Magnitude: <3.0 "MagNitude: z~-IR= +I0-15/’C.
Rate: in general, slowbut occasionalchills
can be experienced.
Similar to exerciseonset Heart rate parallels CVT
Food intake Hot liquids: none Eating changescorrespondto an
Cold:-0.1 (< I rain) increasein metaboficactivity
Eat/n$: 0.4 eausin$ HRto increase.
Environment AffeCtedby environment;however, Cardiacoutput reachesa lowat
hypothalamus vasoconstriction and dilation 15°C(4.8 L/rain) and increases
help regulate. otherwisewitha steeper slope at
hisher ambienttemperatures.
Hot tub Magnitude: 0.2-0.5 (after initial dip) Mostlikely mirrors environment
Rate: 0.025-0.05/rain heading
Figure 15.4 A summary

of effectors of CVTchange and their relationship to HR.
Heart rate
Studies have shown that an increase in pacing rate does not cause the CVTto rise
(Jolgren, 1984; Laczkovics, 1984), Thus pacemakers using this technology have
negative feedback. Increased pacing rate, as mentioned earlier, will help regulate
the body temperature as a healthy person’s would.
15.2 HARDWARE .REQUIREMENTS
In.addition to having a measurand which indicates metabolic activity, and

~erefore a need for an increased or decreased heart rate, a viable pacemaker
System must have a sensor that can accurately and reliably detect the measurand
as.well as a means by which the sensed measurand is interpreted and introduced
to the pacing control algorithm. In addition, the necessary sensor should be
relatively small, easily and reliably placed, and require minimal changes or
additions to the pacing lead(s)..Figure 15.5, showsthe general system diagram
a CVTrate-adaptive pacemaker.
Stimulator
Endocardium
~at~piing
igure 15.5’ The;CVT ~ate-adaptive pacemakersystem. The microprocessorcontrols the
rate of the CVT.
In addition,the microprocessor
maycause~th~
powerto be ttirned off to
th~ evaluationcircuit wben~the~
temperature is not beingsampled.Also,in pacemaker
Systems
such
as~the IntermedicsCircadia® (see Figure15.6) the microprocessormayadjust the reference
temperatureof the amplifier/evaluation
circuit dueto component
tolerancesordrift.
15.2.1 The thermistor
Althoughother types of temperature sensors exist,,,,tbe thermistor is used because

it is by far the, most sensitive. Most thermistors are made of semiconductive
materials, have negative temperature coefficients, and have resistances with an
exponential relationship ,w.ith temperature; although for blood temperature swings
(t~pieally between36S40C) the relationship is very nearly ,linear. In addition
sensitivity, a thermistor has long term stability, can be very small (necessary to
fit inside of lead), and can be chosen to have a low energy consumption. Typical
characteristics are shownbelow.
1. Type: sealed glas~ bead,

2. Size: 0.4 mmdiameter.
3. Nominal resistanff: 75 162~@25°C.
4. Temperaturecoefficient:,~-3 kD,/*C(-4%/*C),
5. Accuracy: _+0.004-0.01"C,
6. Thermal time constant: 1-5 s (fast enough, limitation due to covering).

7. Lowdrift: 0.001-0.002"C per year.
8. Coveting: high-strength Silastic ® or polyurethane tubing which is necessary
for isolating thermistor from blood environment, which would shunt the
thermistor leads. In addition, the thermistor leads should be coated with a liquid-.
proof polymer to avoid bridging of the leads which could otherwise occur due to
the intrusion of liquid ’through micropores in the pacing/sensing lead (Sneed,
1994).
The thermistor, due to its tiny size, can be placed inside the pacing lead
between 3-7 cm from the end in the fight ventricle (see Figure 15.6).
Electrode
3 to 7 cml
Figure15.6 Pacing/sensingelectrode with integrated thermistor Adapt,#from:C00k
etal.
(1985).
15.2.2 Amplifier and ADC
Basic circuit
In order to determine whether or not the present pacing.r~te ’sho.~ld be changed,
the change in resistant6 of the thermistor must be~c0~tedt0 a voltage that
relates to temperature.-In order to eliminate unnecessary processor floating point
operations, it is useful to first lineafize the temperature/voltage relationship over
the entire range of the ADCbefore converting the analog representation to
digital. Figure 15.7 showssuch a circuit. Note that this Circuit is only shownfor
functional purposes, and that in practice it maybe done differently.
5/:/
1.2V~
R
Fo ADC
-1.2 V Rth
Figure15.7 Functionalrepresentationof temperature/voltage

lineadzationamplifier.
The inputs of the circuit, shownwith values of 1:2 V and -L2 V, are below
the battery’s voltage becauseit will gradually decrease ovtr ~time.
The thermistor, which is assumedto have anegative temperature coefficient
of -4%/*C, assumed to be linear over the temperature range 35-40°C, and
assumed to have a nominal resistance of 1.786R @25"C, in Figure 15.6 is the
RATE ADAPTATION B~ TEMPERATURE 343
resistor with the value Rth. Thus the resistance will change by -0.0714R/*C,
which corresponds to a 0.286R swing (between R and 0.714R) over the
temperature range of interest (36--40°C).
Equation (15.1) relates the output of the amplifier,
(15.1)
Thus the output voltage will vary linearly with CVTbetween 0 V (36°C) and
2.4 V (400C).
The ADCfollowing this Circuit is assumed to’be an 8-bit ADCwith a
reference voltage of 2.4 V. The resulting resolution is 0.02*C/bit, which is a
co,only reported value.
An improved approach
Because resistors have imprecise values and both the resistor’s and the
thermistor’s values maydrift over time, circuit compensation is desirable. The
circuit of Figure 15.8, which has been slightly modified from the corresponding
figure in Calfee et al. (1989), has.the ability to adjust for the aforementioned
tolerances: This circuit is used in the Intermedics Circadia pacemaker.
" I ladderl I J
~
~ Vl R! ~ V2 R~.. 2R1 (k~ /~th
/ Micropressor I l l Tomicro
rocessor
i at a ro s usI , ,,,
Fibre 15,8 A mo~ adv~ced tem~rat~e/voltag¢ line~izafion ~C u~d in ~e Inte~edics
Cima~a pacem~erw~ch ~lows for adjus~ent due to resistor tolerates ~d com~nent &i~.
The 8-bit R-~ ladder DACis us~ to dete~ne ~e cu~nt C~ while the 4-bit R-2R ladder
DACis ~ to adj~t for resistor tole~ ~d~. A~dfrom C~f~ et ~. (1989).
According to Ca~.ret al. (1989), ~1 ~e componentsshownin Figure 15.8,

with ~e exception of Rth ~d Rt, ~e located on a single IC. Al~ough it is
¯ ~cult tO fabhcate resisto~ wi~ absolute v~ues on ~: [C, it ~S~sy to fabricate
multiples of avalue on such a eircuit.~(~f~ et al. (1989) give ~e no~v~ue
ofR ~ 5~kO. In addition, ~e ~e~stor is given ~,the ~e~ome~cs~Model
BR16 w~ch has a no~nal~resis~ce of 75 k~ at 37.0"C ~d..a ~mperature
~fficient of ~%/*C: Rt, w~ch.bo~ line~zes ~e ~e~stor as we~ as matches
¯ e ~e~stor,s tem~rature response wi~ ~e r~ge of the 8-bit DAC,is given
as 71.5 k~ (Calfee et al., 1989). Thesupply voltage, Vs, of the circuit is also the
reference voltage of the DACs.
For ease in analysis, the voltage outputs of the 8-bit and 4-bit DACshave
been labeled V1and V2, respectively.
Using superposition, Eq. (15.2) describes the voltage, Vn, of the
noninverting terminal of the comparator
v. = + v2 + 8Vs (15.2)
18
V1 and V2 are given by Eqs. (15.3) and (15.4), respectively
1 7
(15.3)
(15.4)
~ \ n=O
where
Vs is the reference voltage of the DAC
n is the bit placement
an is the value 0 or 1 of the individual bit of the 8-bit DAC
bn is the value 0 or 1 of the individual bit of the 4-bit DAC
CombiningEqs. (!5.2), (15.3), and (15.4)
Vn = 8 +=Zan 2n + ~.~bn2nl (15.5)
Equation (15.6) describes the voltage, Vth, of the noninverting terminal

the comparator
Vth = Vs( 71"5x103 (15.6)
Assumingthe thermistor has a linear relationship with temperature, the

thermistor’s resistance will decrease by 3000 D,/*C.
Before describing the 4-bit and 8-bit DACs’relationship with temperature,
which does not have an absolute correlation with temperature, it is necessary to
first describe the purpose of each of the DACs. The 8-bit DACis used to
increment or decrement the noninverting voltage VI until it causes the
comparator to toggle (meaningthat the value is within one bit of Vth). The 8-bit
value just prior to toggling is taken as the present CVTtemperature. The 4-bit
DACis for calibration of the circuit, both initially toaccount for resistance
tolerances and as time passes to account for drift. Once the circuit has been
calibrated, this 4-bit value is kept constant until a future calibration is required.
Calfee et al. (1989) chose a nominal temperature range of 36--40’C;

therefore a value between 40-50H was chosen as the basal 8-bit DACvalue, This
is one-fourth of the maximal8~bit value and thus reflects the temperature 37"C,
which is one fourth of the way through the nominal temperature range.
Using the above information, we calculated _values of 72H and 8H for the
8-bit and 4-bit DACvalues, respectively, corresponding to 37"C (assuming all
resistor values are absolute).
15.3 SOFTWARE REQUIREMENTS: THE ALGORITHM
Up .until now we have shown that the CVThas a strong correlation w~th heart
rate and that the additional hardware changes to nonrate-adaptive pacemakersare
minimal and easily implemented, Perhaps be most important--and developing--
aspect of the. CVTrate-adaptive ~pacemaker is the algorithm by which, the
pgcemaker changes its rate ba~d on CVT.
The best algorithm is. one which exactly, mimics the function of a normal
person’s heart. Any algoritllm relating CVTwith HRmust have programmable
parameters because of individual differences in CVT,HR, ,and rate-adaptive
needs. Some of the factors which need to be considered when developing an
algorithm include the magnitude of the temperature Change (both for the
e~ercise-evoked dip as well as for the increase in temperature during exercise),
file.rate of changein temperature (both positive and negative), the .rate of change
in HRfor a given magnitude or rate of temperature Changeduring both exercise
and circadian (slow) cycles, the length of time at an elevated pacing HR,and the
maximaland minimal pacing rates (commonin all types of pacemakers).
In addition, it is necessary to have an algorithm that will distinguish
exercise-evoked CVTchanges with those occurring due to other factors such as
circadian cycles or periods of fever. Also, during periods of exercise the
algorithm should provide a pacing rate adjustment that is as quick, accurate, and
smoothas possible.
This section describes four algorithms that have,been,used in CVTrate-
adaptive pacemakers. The first two algorithms give a general understanding of
how the aforementioned parameters are implemented in an algorithm. The last
two algorithms, which are more advanced, show the latest algorithms and how
they offer an improved pacing~response when compared to the two former
algorithms. Due to limited public iriformation, all aspects of the following
algorithms are true in their description insofar as information allows.
15.3.1 Cook Model Kelvin ® 500 series
One of the first CVTrate-adaptive pacemakers was the Cook Model Kelvin 500
series (available in both unipolar and bipolar models). This type ~of pacemaker
bases itsrate,adaptation strategy on the following algorithm which~wasdeveloped
from tests on canines (Cooket al., 1985).
HR = A + B(T - 0) ÷Cs ign(aT/dt) (15,7)

where
HRis the instantaneous HR(bpm)
A is the resting heart rate (bpm)
B is the slope of the HRversus temperature curve during exercise
T is the smoothedor f’dtered instantaneous CVT
TOis the resting CVT
C is the initial rise in HR(bpm) divided by the slope of the temperature-
versus-time curve during exercise
sign(dTIdt) is the sign (+) of the derivative of temperature with respect
time
Equation (15.7), however, is only a basis of the algorithm, not the actual
algorithm that is used. The algorithm present in the Kelvin 500 series pacemaker
not only modulates the heart rate according to the factors affecting Eq. (15.7),
but it also takes into account the initial dip in temperature as well as adjusts its
baseline HRand CVTthroughout the day (Sellerset al:, 1987; Fearnot and Evans,
1991; Bixler, 1994). Figure 15.9 lists a description of the symbolsused in Figure
I5.10, whichgives hysteresis curves (a and b) and a flowchart representation (c),
which describes the algorithm during each sample period, which happens once
every 10 s (Bixler, 1994). In addition to the instantaneous temperature, the rate
of temperature Changeversus tithe is needed for determining the required pacing
rate. This is calculated by taking the average of the six most recent CVTvalues
and subtracting it from the average ofthe six CVTvalues which preceded.
Therefore, a total of 12 CVTvalues (2 re.in) are neededto determine dTIdt. Both
Figures 15.9 and 15.10 were developed from available information (Cook et al.,
1984, 1985; Sellers et al., 1987; Volosin et al., 1989f Heggset al.,~ 1990; Fearnot
and Evans; 1991).
Using Figures 15~9 and 15.10, we can simplify Eq. (15.7) by the following:
HR(t ) = HR(t_I) + AHR (15.8)
where ....
HR(t) is the current
HR(t-1) is the previously determined
AHRis a positive~or negative transient rate increase
Although this equation appears to allow the HRto assume many different
values~ most of these values are only transient rates whichallow the HRto adjust
to one of the three distinct rates (Hr, Hi, He). The algorithm changes the pacing
rate based on both the difference in C, VTfrom the baseline temperature as wall as
the rate of change in the CVTversus time. The former of which decides which of
the two hysteresis curves (Figure 15(a) and (b)) the algorithm follows.
maximal and minimal decision point~ (Ln, Hx, Lx, Hn) of the two curves are set
in such a wayas to makeit more difficult for the HRto adjust to the exercising
rate, He, whenthe CVTis below Th and easier for HRto adjust to the resting
heart rate, Hr, whenthe CVTis below Th than to adjust to the intermediate rate
when the CVTis above Th.-These set points help reduce the possibility of an
unnecessary adjustment of the pacing rate from Hr to He as well as reduce the
required CVTversus time slope required to adjust the HRfrom Hi to He. This
reflects the natural HRand CVTrelationship at higher CVTs(see section 15.1.2).
-Parameter Description Commonvalue

Current CVT(*C) See Fi~.ure 15.4
dT/dt Derivative of smoothed CVTversus time (*C/s) See Figure 15.4
determined by taking the difference between two
successive 1-mintemperatureaverages’
Resting CVTconstant (*C) 37"C
Temperature constant which .represents Tr plus a *
constant whichis less than the difference in the basal

and sustained exercise CVT¯.
**
Zn Lowheart rate minimalset point constant (*C/s)
**
Lowheart rate maximalset point constant (*C/s) ,~
Highheart rate minimalset ~oint constant (*C/s)
H lgh heart rate maximalset point constant(’c/s)
Twoprogrammablerate ramps (+, -) which provide 1-20 bpmevery 5 or
transient rate changesto changethe heart rate to one of 10 s (programmable)
the following3 pacing rates (bpm)
Pro~mamableresting HRconstant (bpm) ° 70bpm
Pro~unmableintermediate HRconstant (bpm) 85 bpm
Programmableexercise HRconstant (bpm) 120 bpm
Pro~amedmaximal.time at Hi 2,4,6,8, 10, 12rain
2rid lowest CVTvalue out of 8 values sampled at variable
evenly spacedinterv~s over a period of 2 h
HR Current pacing rate (bpm) " ’
Figure 15.9 Parameters used in Figure 15.10, which describes the algorithm by which the
Kelvin500series pacemakeradjusts the stimulation rate. ¯ Note that all of the parameterslisted
abovewere.notspecifically namedas such but are providedhere for clarification of the algorithm.
*Valuenot given, but is probably less than Tr + 1 C. Values not g~venbut are probably a
function of the remaining programmableparameter called Kelvin. set~w~ieh ffetermines the
sensitivity of the algorithmto temperaturechanges(Adaptedfrom Cooket al., 1984~1985;B0alet
al., 1987;Sellers et al., 1987;Volosinet al., 1989;Heggset al., 1990;Feamotand Evans,1991).
In addition, the exercise-evoked CVTdip (see s~ction 15.1.2) is accounted

for by an incremental increase in HR. It is important to select the dip-detection
rate threshold value in such a way that it is less than the slope typically
experienced by the patient at the onset of exercise but greater than the. slope Of
temperature drops associated with circadian fluctuations. This holds true for all
algorithms using a dip-detected rate criterion. In addition, it is aJs0 imi~grtant.to
select the programmedmaximal time at Hi (ti) in such a way that it is longer than
the duration of the typical temperature drop. A further a~pect of ihis algorithm
adjusts the baseline temperature value Tr, which corresponds to,-the programmed
baseline rate. The reason for this adjustment is to allow for a more-optimal
response to exercise regardless of the circadian cycle: In addition, this may also
help account for the temperature sensing circuit tolerances and drift. It is
important to realize that the baseline temperature reference is adjusted and not
the corresponding programmed baseline pacing rate Hr.
Example using the Kelvin 500 series pacemaker algorithm

In order to understand the algorithm, it is useful to pace through hypothetical
exercise situations. First, assume that the patient, equipped with the Kelvin 500
series pacemaker, is initially at rest ( CVT= 37"C, HR= 70). This corresponds
a CVTthat is below Th (see Figures 15.9, 15.10(a), 15.8(c)) The patient
begins to exercise, causing his CVT~to change at a rate below Ln. The HRwill
then increase by the programmed rate, AHR, every 5 orl0 s - (depending on
which is programmed). Because the CVTsampling rate of the KelvinS00 series
is 1 sample/10 s, there will either be 1 or 2 transientrate adjustments .between
CVTsampling times. Assuming that Hi (the intermediate rate) = Hr (70 bpm)

15 bpm, and +AHR= 10 bpm, it will take 2 transient rate adjustments for HRto
reach 85 bpm (see dotted line of Figure 15:10). Note that the HRdoes not
increase to 90 bpm,but levels off at Hi.
dT/dt
(a) (b)
no
yes no yes ye~ no
SetTr
yes Set HR= Hr Set HR= Hr
yes lies
I~et ~-IH = I
IDOSI(IVe
rate
no
Set &FIR=
negativerote
negative
rate Remove
oldest temperature
valuefrombuffer andshift valuesup negativerate
c)
Figure15.10CookKelvin500series rate-adaptivealgorithmbasedon CVT.(a, b) Hysteresis

curveswhichdeterminethe pacingrate. (c) Algorithm
flowchart.(Adapted
fromCooket al., 1984,
1985;Sellersetal., 1987;Volosinet al., 1989;Heggs
et al., 1990;Fearnot
andEvans,1991).
Nowassumethat the patient continues to exercise, eventually causing dTIdt >

Hx. The HR will continue to increase by +AHRuntil it reaches He (120 bpm).
After a period of 10 rain, and a Tc > Th (see Figure 15.10(b)), the patient stops
exercising. The subjects CVTbegins a steep drop (dTIdt < Lx). After a period of
3 rate adjustments (-AHR= 30 bpm), the HRadjusts to the Hi. Soon after, the
< Th and the slope of the dTIdt ramp decreases but is still less than Ln. The HR
will then begin to drop again according to the rate -AHR,eventually reaching Hr2
Nowassumethat the patient stops exercise instead of continuing (once again
at Hi on the dotted line of Figure 15.10(a)). The subject’s HRwould stay at
until ti has ’elapsed. After this time, the subject’s HRwould be decremented by
-AHRuntil it reached Hr. The purpose of such a limit is to ensure that the pacing
rate, HR, does not stay at an elevated rate for an extended period of time in case
the patient suddenly Stops exercising after inidaily Starting (which’ wouldcause
Sl0w return to baseline CVT)or in case thealgorithm mistakenly interprets
drop in CVT(due to circumstances other than exercise) as an exercise~evoked
dip.
Nowlet’s assume that rather than stop exercising, the patient continues to
exercise for’a period of 2 h. Usingthe left half of Figure 15:10(c), wesee ~that,
the HRstays at anyof the three HRlevels for more than 2 h, the Tr is ~ adjusted to
be..the second min~al temperature of 8 equally spaced samples over the 2-hour
period (T2m)..The algorithm correspondingly adjusts to Hr, the programmed,base
~acing late. PresumablyTh, Hi, He arealso adjusted. This of Coursg is ’aot the
~lesired physiological~e~ponse.If the patient cohtinues to extrci~e, h0wever, i~tis
likely that the cvT will rise in such a way to at least adjust for pacing/i/the
intermediate rate because of the resulting increase in CVTdue to the relationship
between HRand temperature regulation (see section 15.1.2).
Adi, antages and disadvantages to the .KelVin 500 series pk~cemaker
Although this algorithm offers a great improvementto a need for increased heart
rate during exercise for patients who cannot benefit from the. traditional AV
synchronous pacemaker, its implementation is suboptimal because it.responds in a
stepwise fashion with only three distinct pacing rates. Also; the transitions
between the three pacing rates are abrupt, which does not correspond to the
naturally smoothtransition of the HRand also allows for high~levels.of~ unde~Sired
tachycardia in the event of false exercise detection. In addition, ,a!thougti: the
algorithm adjusts to circuit and circadian CVTfluctuations ~y adjt!sting the.
baseline rate) to allow for an improved response to exercise regardless of the
circadian cycle, this also allows for an unnatural respons~dudnglong periods of
sustained exercise. Asimilar undesirable response can occur during fever, which
is more.likely to last more than 2 h. Finally, this algorithm has a latency.~between
the algorithm’s response and the natural response as shownin studies by Sellers et
ilc (e :!~ !cheem~k~

~ i nme~t
esde nt- aeCshuY
:~do’l: r W;aSc
~rte~ ~ 1 oas~1
During a routine arm ergometer stress test while leaning over, .the ~subject
experienced intermittent chest wall twitches. Further ’examination revealed-that
while the subject was in this position, his diaphragm muscles were being
s~ulated by the paeemaker:This stimulation caused an inereaseff metabolize rate,
which in turn in,eased CVTat a rate high enough to trigger th6 algorithm to
~,’..~e at theUppei~rate. If the patient remainedat this position¢~tl-ie paCemaker-
niediated taeh’ydardia persisted. Later the pulse wi~d~, which’bad’beenat 0.55ms;
was decreased to 0.31 ms. Following thiS; the patient experienced nff"further
episodes of pacemaker~mediated ~hycardia.
350 ~DESIGN OF CARDIAC PACEMAKERS
15.3.2 Intermedics Nova MR®
Another one of the first CVTrate-adaptive pacemakers was the Intermedics Nova
MR(both unipolar and bipolar models), which differs from the Kelvin 500 series
in that its pacing algorithm has a more dynamic HRresponse. Like the Kelvin
500 series,pacemake r , the Nova MRnot only modulates the heart rate according
to the derivative of the CVTversus time curve as well as the instantaneous CVT,
but it also takes into account the initial dip in temperature. It does this, however,
using an algorithm with a response that is more natural. Figure 15.11 gives the
parameters for Figure 15.12, which gives HRand CVTcurve relation (a) and (b)
and a flowchart representation (c) that describes the algorithm based upon which
curve the algorithm is currently working on. Figure 15.12(a) shows a series
curves (3 are shown)that are referred to as the:,exercisf curves and are used to
adjust the heart rat e as a linear function 0f CVTduring exergise. The. algorithm
uses two curves that have a linear relationship ~betweenC~Tand pacing rate, The
nrst ofthese curves,,~e basic curve orfever curve, has an ’adj/~stable slope of 6,
12, 18, or 24 beats/C increase. This curve follows teinpe~ture changes that
occur" more s, lowly such as those due to circadi~ fluctuations and ~fe~er. The
slope ~f thesecurves is programmableand is t,.yl~ic~lly aroui~dS0bpm/,Cinitially
followed by a decreasing slope (about 25 bpm/~C)at higher HRS(Alt ~ al., 19 86;
AI~, 1987; Alt et al., 1993).
Parameter Description "~~ "Common value

HR Currentpacingrate 50-180 bpm
dT/dt Similarto the CookModelKelvin500series See Figure15.4
~KI --Thepro~’ammedexerci~ curves,~ ~"
.......
~,’.’: K2+40to 12Obpm/°C
K2 Theprogrammed basic
curve 70,bpm (37"C) :~5-25
*C
: Te *Current CVT . 36-40 °C
ATb **CVTdip masnitudefromthe basic curve ’I see Figure 15.4
AT~ PrO~amn~le ~VTdip mal~aim.dethreSholacodstant ’ -. 0.12-0.25°c
Tdr :’ CVTcltop rate threshold eonstani . ’ ........ . ’ 0.!2--0.20°C/min
HIi ’ Intermediate-HR limit (bpm) ’ ¯ ’ ~ .,. ¯ ~ ...... 85 bpm
.Pro~rammableHRinerease from K2 to Hi .. ::~ ;.~ , :: , 15bpm
Intermediate HR, .....
. ~Pro~ammable
ba~ierate thresholdconstant ***-0.08*C/rain
Prol~ammable ~ time at HI
Maximaltime on an exercisecurve.... 30 rain’ ....
Figure15.11Parameters
usi~dinFigure15,12whichdescribes
thealgorithmbywhichthe
Intermedics
NovaMRpacemaker
adjust
thestimulation
rate.
Notethatall.of
theparameters
listed
abovewere
notspecifically
namedassuch,butareprovided
here
forclarification
ofthealgorithm.
¯ This**
vdue~
ismost
likely~
an....
average
ofa number
ofthe
mos,[
rec~nt
CVT
sawn..pl,e
s (ap~x~mat.ely"
8).Themethodbyw~chthisvalueisdetermined
isnotglven;’h0wever,
zt~smost hkely
taken
asthedifference
betweenthe
maximal
andminimalCVTfr6ma set~fthemostt’e~entiy
stored
samples.-***Value
notgiven;
estimated~from
available
information
(Adapte,
xlfrom Altetal.,
1986~
Alt~1987;
Aftetal.,1988;
Aftetal.,
1993).
,.sampii
gratgiven
as,
eve.:
ilis,
cos,or
scond
,Calt,
1988)
.b_.ut !~ reported to ~ every 4 or8 pacemaker.cycles (Siaeed, 1994,. The period at
hicn;’i, ~e. pacemak.e.radjusts the ~ac~ag’rate is identical, (Sn~<19,94),~Like; the
dK, ,~l, vih~i0~ns~dT’"~,thve N~)vaMR,~oa~hinalso. use;’k~yd..set; ’of CyT"~alues, fo¢
tete,rm.i iig th;,, CTrate.of 3hage, alt iSugh .the,atlmb r..of temperature
sam~"pies im;olved in th’si dete~nation is n0~ ind~ted~ in addition,the ~,+aMR
RATE ADAPTATION ~ BY TEMPERATURE 351
algorithmalso limits the mountof time at an intermediateHR,HI, as well as ,the

amountof time the rate is regulated by the exercise curve, K1. It does so,
however, in a moredesirable way.
Increase HR
Transition
to HI
threshold
threshold
TransitiontoK1
~.~ HR (HR) ~ith clip algorithm, exerdse

.... HR(H/~ without dip a~ dthm, exercise
Exercisediscontinued.
~ CVT
b)
Figure15.12 IntermedicsNovaMRalgorithmbasedon~CVT (Adaptedfrom-hitet al., 1986;

hit, 1987;hit et al., 1988),(a) Basic(K2)andexercise(K1)curves.(b) CVT
dipresponse
(c) AlgorithtnflO~chart.
~a~ple using:the ~oV, ]MR pacemaker, aig~th~:. . . ;

Inorder to unders ,~t~.:;,d the algorithm,, it is u~e,~ to,pace thr0ug! .,,hypothe~cal
e~erci§e situations. F~st, as iimethat e:p/fie f,. qulpp he Nova
~
paeemfikdr,,iSinitialIy a~ re, slt~ "ASthe ~ati~nt~bh~uesto rest,
huetuateSlightly as w611as b6 affected by eiieadiah ~hanges. Durin this dme,"th~
patient’s pacing rate is modulated by the K2 curve (see Figure 15.12(a))

705:15 bpm/°C. Nowassume that the subject’s CVT, Te, and HR are 37°C and
70 bpm, respectively, and that the subject is at rest. Duringthe day, the subject’s
CVTfluctuates according to the circadian rhythm discussed in section 15.1.2.
Thus the pacing rate will follow the curve K2 (see Figure 15.12(a)). Assuming
that his Tc has risen to 37.2"C in such a matter, the corresponding pacing rate,
with K2’s slope being 15 bpm/*C, will be 73.0 bpm. At this time the subject
begins to exercise, eventually causing his Te to decrease by 0.4°C, followed by a
rise in Tc accompanyingcontinuing exercise~ As soon as the patient’s Tc drops by
a value greater than ATdand a rate value less than Tdr (meaningthat the slope is
steeper in the negative direction), the HRwill increase through a rapid transition
phase to HI. Note that before the required drop threshold value is reached, the
pacing rate will experience a transient initial decrease because curve K2 is
controlling the pacing rate (see Figure 15.12(b)). Assuminga ATdof 0.2"C,
resulting intermediate heart rate, HI, will be 85 bpm. Nowassume that the CVT
begins to rise by a rate greater than Er. The HRwill rise by a curve, K1, which
has an initial slope of 80bpm/°C(see Figure 15.11).
Assumethat the patient continues to exercise until his HRand CVTplateau at
125 bpmand 37.5"C, respectively. Soon after, the patient ceases exercise, and his
HRcontinues to follow the exercise curve, KI, which he is currently on until his
dTIdt is greater than Br (meaning that the temperature is not decreasing as fast
over time) and the time spent on this curve is greater than tt (approximately
30 min). At this time, the control of the pacing rate, HR, will shift from the K1
curve to the basic curve, K2, through a smooth but rapid transition between the
two curves at the present Te.
Thenecessity of the time criterion, tt, isas follows. If this criterion were left
out, then the HRwould immediately be shifted to the K2 curve as soon as the Te
started to plateau. As stated in section 15.1.2, at a given level of exercise, the
CVT(and HR)will eventually plateau.
Nowassume that the patient stops exercise instead of continuing (once again
at HI). The subject’s HR.would stay at HI until ti has elapsed. After this time, the
subject’s ~HRwould be decremented to the basic curve, K2, through a smooth but
rapid transition between the two curves. The purpose of such a limit is the same
as that in the Kelvin 500 series pacemakeralgorithm.
Nowassumethat rather than stop exercising, the patient continues to exercise
for a period greater than tt. The algorithm would, through a smooth and rapid
transition, adjust the HRto the basic curve, K2. Uponreturning to K2the patient,
whocontinues to undergo significant levels of physical stress, will experience a
sudden increase in his CVT.The pacing rate will therefore shift as before from
curve K2 to K1. Figure 15.13 shows the pacing HRand the CVTin a 63-year-old
man with an implanted Nova MRrate-adaptive pacemaker in an atrial position
(AAI-R)during various activities.
Advantages and disadvantages to the Nova MR pacemaker algorithm

The Nova MRpacemaker algorithm is more optimal than the Kelvin 500 series
pacemaker algorithm in that it is more dynamic. Such an algorithm allows for
both circadian and exercise HR~increases which are closer to the natural HR
response. However,this alg0rithm:is less than optimal because its Tc (CVT)-vs.-
pacing rate is linear in shape,~hen the natural response is exponential as the CVT
approaches the exercise plate~au from below and approaches the baseline CVT
RATE ~ ADAPTATION ~BY TEMPERATURE 353
from above. In addition, the patient will experience an initial brief decrease in the
pacing rate at the onset of exercise until the dip meets, the rate and magnitude
threshold criteria. Also during periods of sustained exercise longer than tt, the
pacing rate initially shifts from K1 to K2 when the natural response would
assume the higher rate. Also, transition between curves KI and K2 can often be
unnaturally abrupt.
"
110
~.e.
37.5
70
20 40 6~ 80,, 100 Time
Figure 15,13 PacingHRand the CVTin a 63-year-old man.with an implantedNovaMRrate-

adaptivepacemaker in an a~al position (AAI~R)
duringvariousactivities. FromAlt, E., Barold,
S. ~., andStangl,IC (eds.)1993.Rateadaptivecard’~tcpacing.Bedin:Springer-Veflag.
A study of 21 patients by Zegelmanet al. (]990) showeda meanincrease

exercise capacity of 33%while using the Nova MRin the rate-responsive mode
compared to the nonra~e~responsive SSI mode. It did, however, ~ report the
~
fo~6wingsuboptimal results:
1.~ .The mean response time (time ~o ~ the HR to increase 5 bpm) was
~ .9qnin? One factor that~mayha~/e lengthened thistime interval is the fact. that
e themaistor Was10c~ited ii~ the apex ~f the right atrium in someOf the patients.
At least one study has suggested that such a placement mayresult in a delayed
response due to inadequate mixing of the blood ~n the right atrium (Alt et al.,
19~6). !n~ addition, some pa~ents mayshow a Slo~r and ~p~olong6d CVT.Thisis
commonwxth patients suffering from chromc heart dxsease and xs caused by
constriction of the peripheral blood vessels that service the limbs uponinitiation
0fexercise (Sneed, 1994). This causes a slower CVTdip. The dip is prol6nged
d~ie to the decreased blood fl0w t0 ~e i~uscleS,~whicli~i~eresponsil~le for the~ heat
production.during exercise. This ~oo w6u!dincreaa~the ni~t~ response time.
2. ~After’ ~i~edenenig theqntermediat6 ~pacing ~a~e i~ncr~ase after the dip was
detected, son~¢patients experienced adecrease (after the 22thin’time ~imit at the
intermediate) d~Je to’the previously described prolohged dip.
15.3.3 Intermed~cs Orcad~a®
The Intermedics Circadia pacemaker (unipolar)’ algorithm incorporated most

the basic principles applied to the Nova MRpacemaker along ~ with several
impr6vements which include: ¯
1. An algorithm that adjusts the pacing rate in a way whichbetter simulates the
rate of a normal, healthy heart under conditions such as rest, circadian
rhythm, exercise, and fever.
2. An algorithm that provides an improved detection of the beginning of
physical activity.
3. An algorithm that controls the slew rate of the calculated pacing rate to
avoid abrupt increases or decrease in HR.
4. An algorithm that provides a more optimal response after saturation of the
pacing rate whichcan occur during periods of strenuous activity.
5. An algorithm that, in addition to performing the above, will automatically
adjust the reference temperature used by the rate response algorithm.
The algorithm bases its pacing rate, which is calculated every 4 or 8 beats
(programmable), on Eq. (15.9) (Calfee et al., 1989; Sneed, 1994). The Circadia
pacemaker samples the CVTevery beat.
Rate = Reference Rate + Natural Rate Response + DynamicRate Response (15.9)

+ Step Rate Response
where
Reference Rate is the desired base pacing rate.
Natural Rate Response is the desired change in resting pacing rate with a
CVTchange due to natural causes such as fever and circadian cycles.
Dynamic Rate Response is desired change in the pacing rate due to CVT
changes associated with exercise.
Step Rate Response is desired incremental change in pacing rate associated
with the exercise-evoked dip in CVT.
The Reference Rate is the desired resting pacing rate and is initially
programmed by a physician (typically around 70 bpm). The ~remaining
parameters will be explained using applicable equationS’, ~t~bies, and pseudocode.
Figure 15.14 displays a general flowchart of this algorithm while Figure 15.15
illustrates somecharacteristic curves of the af~ementioned parameters (Calfee et
al., 1989).
Circadia Natural Rate Response

Figure 15.16 describes the pseudocode governing theNaturOl RateResponse.
where
KNATPis a programmablepositive natural rate coefficient with a typical
value of 12 bpm/*C(see Figure 15.15(b)).
KNATNis a programmablenegative natural rate coefficient with a typical
value of 6,bpnd*C. ~’
TAVGis the current average CVT(°C) calculated from’ the 4 or
(programmable) most recent temperature samples.
REFTMPis the weighted average reference t,e~perature which initially is
programmedby the physician (typically 37 C)~ but after implantation
modulated by Eqs. (15.10) -(15.12),
REFTMPis periodically calculated by REFTMP.=AN, where AN is

determined by Eqs. (15.10) - (15.12), to account for any miscalculation in
initially programmedreference temperature as well as to allow the reference

temperature to adjust over time due to seasonal or other long term fluctuations in
the resting temperature.
Find current
Start temperature
End ~.~ calculation ~ ~ yes

~ cycle /
Calculate new step
rate response
term averaging Adjust rampback
Calculate & apply Test and,,~pply

current ste~,r~sponsel~
naturalrate ’response
Calculate & apply / Perform slew

rate test
Idynamic
[ rate resPonse
limit test
I Perform rate I
End
Figure15.14Basicalgorithmof the IntermedicsCircadiapacemaker

AdaptedfromCalfeeet al.
(1989).
AN = K*.SN-1. (15.10)
DN = TA VG ÷ AN (15.11)
SN = SN-1 + DN (15.12)
where
AN is the current weighted average reference temperature over a
predetermined time period.
K is a constant coefficient, (1/2)n wheren is an integer between8 and 24.
DNis the difference between the current and weighted average temperatures.
SN is the current=sum.of the previous :. average~ weighted sum and the
difference between the current average, temperature and the weighted
average temperature; initially programmed with a value of
2n(REFTMP).
SN-1is the previous average weighted sum.
~ The value chosen for n determines how much reference temperature,

!~P, is adjus.~ for~-the predetermined time period,= Three programmable
~es, slow, medi~, andfast; are p~0vt~ded to"~i~w for weightedaverage time
constants of >14 days, 7"14 days, and 1-7 days (Sneed, 1994).
’~:, The~NaturalRate Response’~ways contributes tothe pacing rate value unleSS
TAVG = REFTMP.
356 DESIGN OF CARDIAC ~PACEMAKERS
Tern)erature Naturalrate
72
response(bpm)
KNATP
-~FTMP
Time TAVG(’C)
(a)
Dynamicrate Steprate
response(bpm) response(bpm)
STEP_SLOPE
STEP_DURATION
STEP_
RESPONSE’
RADJ1" ~
TAW ¯ i ~ ~ i g g ~’ g Differential
cycle
(c)
Temperature
Calculatedpacing
rate w/osaturation
control&noratelimit
Time
(e)
Figure15.15Curvesthat ~de~ctibethe various rate responseparametersof the Intermedics

Circadiapacemaker
AdaptedfromCalfeeet al. (1989).
[if ((TAVG - REFTMP) 0)

I Natural Rate Response = KNATPCTAVG -;EFTMP);
]else Natural! Rate’ Response = KNATN(TAVG REFTMP) l
Figure 15.16. Pseudocode
that determinesthe CircaddaNatural,Rate
Response.Adaptedfrom
Calfeeet al. 0989).
RATE ADAPTATIONBY TEMPERATURE 357
C~cadia Dynamic Rate Response

Figure. 15.17 describes the pseudocode governing theDynamic Rate Response.
~-f (RTAVG > RBCRIT)

{
if ((TAVG- DYNRFT) < BP1)
Dynamic Rate Response = KP0(TAVG - DYNRFT);
if (BP1 < (TAVG - DYNRFT) < BP2)
Dynamic Rate Response = RADJ1 + KPI (TAVG - DYNRFT);
if ((TAVG - DYNRFT) > BP2)
,Dynamic Rate Response = RADJ2 + KP2 (TAVG - DYNRFT);
l~i~ure 15.17PSeudocode
that determinesthe.Circadia Dynamic
Rate Response.Adaptedfrom
Calfeeet al. (1989).
~here
RTAVG isthe rate ofchangeof the average CVT(’C).
RBCRITis the minimal programmablerate of change threshold value, which
..indicates whether or not the subject is exercising (typically
0.02"C/differential~ cycle), A differential .cycle is given as 8 pacing
cycles.
TAVGis thecurrent averageCVT(’C).
DYNRFris a valuewhichtracksthe TAVGvalueuntilthe momentRTAVG
> RBCRIT at whichit remains constant (se~-Tl on Figure 15.15(a)).
KP0,KP1,andKP2arethefirst, second, thirdexercise coefficients with
typical values of90,66,and48 bpm/°C, respectively.
RADJ1,andRADJ2arethefirstandsecondconstant rateadjustments with
typical values of27 and46.8bpm,respectively
BPI,andBP2arethefirstandsecond temperature breakpoints withvalues
of0.3and0.6"C, respectively.
It should be apparent that the values KP0, KPI, KP2, RADJI, RADJ2,BP1,
and BP2are interrelated such that they will provide a smooth pacing rate..when
the two breakpoints are crossed (see Figure 15.15(c))~ These parameters
rprOgrammableinsuch a way as toretain the smooth transition: In’addition, the
subsequent decreasing slopes of KP0, KP1, and KP2closely follow the natural,
exponential HRas the HR(and CVT)increase.
~ .Onc~: the TAVGrate of ¢h~nge fal!s~ be!ow the value RBCRIT(fo!lowing
cessation bf exelcise; see ~ Orl Figure 15~i5(a)), DYNRFTdoes not ~ediately
tr~ck TANG;instead,~ D~ i~s incremented according to a programmable
~ func~0naccording ~t0 parameters~TSTP ~d.~ DELAYin o~der to
provide a smoothpacingrate decrease such as a normal, liealthy heart Would.
goveraj’ng the Step Rate Response.
Rate
T_CTR is a counter that ensures that the patient has been at rest for a certain
period of time before the Step Rate Responsecan be added to the overall
pacing rate (initially set by the algorithm to MAX_COUNT, which is
typically about 22 diferenfial cycles).
TL is the average CVTfrom the previous differential cycle.
DIPSLOPEis the programmable CVT dip slope criterion (typically
0.006*C/differential cycle).
DIPSIZEis the dip magnitude criterion.
RATE is the present calculated pacing rate.
STPCRTR is a programmable criterion associated with the present pacing
rate, which assures that the Step Rate Response is not added to the
pacing rate when the CVTdip is not due to the onset of exercise
(typically 80 bpm).
STEP_RESPONSE the step rate adjustment contributed to the overall pacing
rate (equal to STEP_SIZE which is typically 15 bpm).
STEP2DURATION is the criterion that determines how lotig the StepRate
Response will contribute to the overall pacing rate (equal to
STEP_DURATION_MAX, which is typically 4 differential’ cycles).
TPEAKis a peak TAVG which is calculated by the following:
if(TAVG>TNL) then TPEAK = TAVG
where TNLis the previous TAVG value.
if ((TAVG- DYNRFT) < STPCRIT) (I)

{
if (T~CTR # 0) (2)
decrement T_CTR ;
else if ( ( (TL - TAVG) > DIPSLOPE) and ((TPEAK- TAVG)
DIPSIZE) and (RATE < STPCRTR)) (3),(4),(5)
{
=
s~E~_R~.sPoNs~.
else T__CTR = MAX_COUNT;
Figure 15.18 Pseudocode that determines the Circadia~tep Rate Response through the use of 5
criteria. Adaptedfrom Calfee et al. (1989).
Overall:, the" pseudocode of Figure ~15.18 (1) ensure~that a Step Rate

Response is not added to the overall pacing rate Whenthe exercise response is
already underway, (2) ensures that the Step Rate Response:is not added to the
overall pacing rate if the patierit was not previously at rest for~a period of about
10 min, (3) ensures that the CVTtemperature drop rate is below ~a threshold
value before the Step Rate Response is added to the overall pacing rate, (4)
ensures that the CVTtemperature drop magnitud~ ig above a thre~i~old value
before the Step Rate Responseis added to the overall pacing rate, and (5) ensures
that the Step Rate Response is not added to the overall pacing rate when the
calculated pacing rate indicates that the dynamicrate response has already taken
hold.
Similar to the .Nova MRalgorithm, the C[rCadi9 algorithm ~ill not let the
overall pacing rat~ e£ceed a ce~ain threshbld, M~_s~’EP,RATE,due to the
additiot~ of ~e StepRate Response. A typi6ar ~al~e of MAk_STEP_RATE is
85 bpm.
Also similar to the previous algorithms is the limited amountof time that the
step: rate response is added to the overall pacing rate. The point-at whichthe Step
Rate Response begins to decay is given by the programmable parameter
STEP_DURATION, which has a typical value of 4 differential cycles after the
Step Rate Response, STEP_RESPONSE, has been added to the overall pacing rate
(see. Figure 15.15(d’)). The Step Rate Response decays during
STEP_DURATION period by the value STEP_SLOPE,Which has a typical value
of 4 bpm, until the Step Rate Responseno longer contributes to the pacing rate. -
Additional features of the Circadia pacemaker algorithm

Another feature of the Circadia pacemaker algorithm is slew rate Control. Each
time that a new pacing rate is calculated_ (every 4 or 8 beats), a difference
between the new calculated pacing rate, RATE,and the current pacing ..rate,
LAST_RATE,is determined. If this difference exceeds the programmable
maximal slew rate value, MAX_SLEW_RATE, then ,the new pacing rate increase
is limited to MAX_SLEW_RATE, which is typically around 2 bpm/rate
calculation cycle. The slew rate control limits ;pacing ~ncreases,: ,of’. all the
parameters whichcontribute to the overall pacing rate~(see Eq, (15.9)).::
Another feature, which is present on all types of pacemakers, is the upper-
rate limit, MAX_RATE_LIMIT, which is typically around 133 bpm. Once the
calculated pacing .rate matchesor exceeds this value (see T1 on Eigure ~[5.15(e)),:
the actual pacing, rate is limited to:MAX..RATE_LIMIT~and DYIb]RFTis
increased by the same amountas TAVG so that the calculated pa~ing_rat¢ remains
constant until TAVG ceases rising and:begins to fall (see T2 on ~Figure :!5.15(e)).
On.re, this happens, DYNRFT will start ramping up as descdb.ed earlier,, and the
DynamicRate Response contribution to the overall pacing rate, RATE,will cause
RATEto decrease. This prevents pacing at the maximal rate even after the
exercise has ceased.
~dvantages and disadvantages of the Circadia pacemaker algorithm ¯

~The improvements of this algorithm over the previously described algorithms
were listed at the beginning of this section. Overall, the Circadia pacemakerhas
performed exceptionally well (Sneed, 1994). It is difficult to determine any
inherent disadvantages of this algorithm due to its complexity. Also; information
’regarding the success or problems of this, as well as the Nova, model is
extremely limited because neither of these advanced beyond clinical trials. The
only disadvantages of this algorithm may be due to an individual’s CVT
icha~racteristics. Someof these potential problemsare described in section 15.6.
15.3.4 Cook Sensor® Model Kelvin® 510 Series Pacemaker
The CookSensor ModelKelvin 510 Series pacemaker (available in both ~ unipolar

and bipolar models), like.the Kelvin 500 Series, bases its algorithm on Eq. (15.7),
but it does go with an algorithm that adjusts the pacing rate in a waythat:better
simulates the rate response of a normal, healthy heart under conditions such as
rest, circadian rhythm, exercise, and fever. This not on!y, indudes a more
accurate response but also a more rapid response than previously mentioned
~algorithms(Fearnot ~and_E~ans~!.99 !),
The Kelvin 510 Series algorithm contains five parameters that contribute to
the overall.pacing.rate as given i n Eq:
e (15.!3). The, se factors ar¢.,simi.~’[~ ~o .~os
used in the Circadia algorithm with 6ne major disfincti6n .being. that the Kelvin
510 Series algorithm uses the absolute magnitudeand derivative of the exercise-
evoked CVTdip as an indication of an amount the pacing rate should be
increased, ratherthan their values relative to thresholds. This results in an earlier
increase in pacingrate following the onset of exercise.
TR = LR + DIU + DT + STX + TXB (15.13)
where
TRis the target pacingrate
LRis the base heart rate as well as the lower pacing limit (typically 70 bpm)
DIUis the desired addition to pacing rate with a CVTchangedue to natural
causes such as fever andcircadian cycles
DT is the desired addition to pacing rate due to the rate of change of the
CVT
STXis the desired addition to the pacing rate due to the magnitudeof the
exercise-evoked temperaturedip
TXBis the desired addition, to the pacing rate’ due to the increase in CVT
above a local minimum during exercise
These values are calculated according to the pseudocodeof Figure 15.19 and
the programmable coefficients for tau which are listed .in Figure 15.20. These
coefficients were developed by studies relating CVTand HRin both normaland
pacemakerpatients having normal sinus node activity. In addition, the above
pacing parameters are determined primarily by comparing a plurality of
temperaturedeviations from three movingbaseline temperature values that are
shownin Figure 15.21.
STX = tau5(RST -- D/6); Dip Magnitude

if STX < 0 then STX = 0;
TR = LR + STX;
DIU = tau4(RST -- DV); Diurnal Variation

if DIU < 0 then DIU = 0;
TR = TR + DIU;
TXB = tau3(M0 -- BLM); Deviation from Local Minimu~

if TXB < 0 then TXB = 0;
if D < E then: Negative dT/dt

DT = taul(E - D);
TR = TR + DT;
if TR > IR then TR = IR;
TR = TR + TXB;
if TR > UR then TR = UR;
if D ~ E then: Positive (or zero) dT/dl

DT = tau2(D - E);
if TR > IR then TR = IR;
TR = TR + DT + TXB;
if TR > UR then TR = UR;
~R = (PR + TR)/2 Rate Smoothing
Figure15.19Pseudeeode
flaat determines
the pacingrote of the CookSensorModelKelvin510
Series pacemaker.
Adapted
fromFeamotandEvans( 1991).
~TE ADAPTATION IBY ~MPE~TURE 361
~ ¯ ’ Coefficients for ~ul throughtauS~gain , ~

. ~Minimal, [ , Nomin~ ,[ ~,~ Maximal
~ Programmabl e KelvM Set number
,,,
Tau 1 2 3 ! 4 5 6 7 8 / 9 10
1 0.011 0.013 0.016 0.020 0.025 0.03 ! 0~039 0.04
T 0.059 0.070
2 0.059 0.070 0.0940.109 0.141 0.172 0.203 0.25~0¯0.313 0.375
3 0.234 0.281 0.375 0.438 0.563 0.688 0.813 1/..00 1.25 1.50
4 0.055 ~
0.055 0.055 0.055 0.055 0.055 0.055 0.055 0.055 0.055
5 0.203 0.234101281 0.375 0.438 0.53 0.688 0.813 1.00 1.25
Figure15.20Taucoefficients usedin calculating the:pacingrate of the CookSensorModel

Kelvin510~Series pacemaker.
ThedesiredKelvinSet number(1-10), whichrepresentsa set of tau
coefficients, is programmed
by the physician.AdaptedfromCookPacemaker Corporation(1992).
¯ The Kelvin 510 Series pacemaker samples the CVTonce every 10 s and
adjusts:fiae pacing rate every 5 s whenthe pacing rate is increasing and every 10 s
whenthe pacing rate is d~creasing. In addition;~ pacing is adjusted in increments
of 1 bpm for pacing rates between 50 and 130 and in increments of 2 bpm for
pacing rates between 130 and 160. The range of possible pacing rates is between
50 and 160 bpm (Cook Pacemaker Corporation, 1992).
It should be evident from Figure 15.19 that the target rate, TR, is adjusted in
steps. ~ first possible addition to the target rate is that due to the magnitudeof
a exereiffe~evoked CVT dip (STX).
Kelvin 510 Series determination of STX

Figures 15.20 and 15.21(a) and (c) illustrate how STXis determined.
average of the six most recent temperature samples is sampled every 1 rain by
taking the sum of these measurements D, dividing by the number of
measurements(6), and storing this value in the resting ¯buffer; which contains
~gisters.~,After ea6finew average caicuiatkm,i~the~lde~t ~alue, Whichis stored in
RT, is discarded and the remaining values are shifted up.:to makeroom for the
new average. At any given time, th~ baseline resting temperature, RST, is given
by the fourth minimumvalue in the R (resting temperature) buffer. STX
determined during every CVTsample ~(every I0 s) and is given by ~ultiplying
gain constant, tau5, by the:differen~e between"the resting temper~turi~,: R~T,a~ad
the average of the six most recent temperature samples, DI6~ Thus when an
ex~rcise-evoked CVTdipoccurs, the average of the 6mo~ti~ecent temperature
s~les~ D I6, will beless’than therestirigtemperatttre, RSTcausing an addition,
STY, iwthe target pacing rate. If STXis n~gative, indicating that’ there is a
~mperature increase, then STXis 0 (see Figure~ 15.19).
! , :
Kelvin 510 Series detertninaaon of DIU

Figures 15~20 and 15.21(a) ~ and (c)’ illustrate howDIUis determined. The value
DILl, whichrepresents the addition to the pacing rate." due ; to diurnal variations, is
given by multiplying a gain Constant, tau4, by the difference between the resdng
temperature baseline, RST, and the daily minimal temperature baseline, DV. At
s ~,a[n~ pie periods of 5 min during each 24-h~period; ~ ~i.ng t~inpemlure, RST,
i~:...~tfipared against the lowest resting tempera~;~!D!~,in the DIB[tuffer. ifthe
Present RSTis less thanthe value DIB,.then thepres~nt ~STb6eomesthe value
DIBin the DIBbuffer. ~r the ~ 24:h period has ~x~ttCd~ ~e:.~talue DIBbecomes
the Value DV,. which is the diurnal te~tature ~61~e~Thus when the CVTis
greater than the previous dally minimal temperature, DIU will be added to the
target pacing rate due to the diurnal variation. If the value calculated for DIUis
negative, then DIUis 0 (see Figure 15.19)~
~DT Local minimum Rest

--N BLM = 1 4th
minimum / minimum
Buier
IDV- changed
2rid min. D value I every 24 h
CVT- sampled
every 10 s
- sampled every
1 min I
D/6
I - sampled
every 5 min. I
Diurnal
(a) (b) (C)

Figure15.21 The data buffers that are ug~din the CookSensor ModelKelvin 510 Series
pacemakeralgorithmto help,determine
the pb.cingrate. (a) ThetemperatureI~uffers(T)’; (b)
minimalvaluebuffer (M);(c) Th6resting temperaturebuffer (R). Alsoindicatedare the
movingbaseline values, BLM, ,RST,andDV,corresponding to the local minimal,.resting, and
diurnal moving
baselines,respectively.AdaptedfromFearnotandEvans(1991).
Kelvin 510 Series determination of TXB

Figures 15.20 and 15.21(a) and (b~).illustrate howTXBis ~determined. The value
TXB,which represents the addition to the pacing rate due to exercise, is given
by multiplying a gain constant, tau3,1 by the difference between the local minimal
temperature baseline, BLM,and ~the latest addition to the minimal value buffer
(M0). Every minute the second minimal CVTvalue in the temper.a .tu~e buffers
T0-T5 is added to the Mbuffer by discarding th6 oldest Mbuffer value and
shifting the remaining values up. The local minimal baseline value, BLM,is the
smallest of the six values in the Mbuffer. Thu’s~-duringexercise ~whenthe value of
M0is greater than BLM,TXBwill. be added to the target pacing rate. If the value
c~c~ulated for TXBis negative, then TXBis 0 (see Figure 15.19).
Kelvin 510 Series determination’ bf. DT

Figures 15.20 and 15.2!(a),jllus .txate bo.w DTis@termined.As stated earlier, the
temperature buffers-T0-T5 represent the six most recent temperature samples.
These values are added together into a sum, D. The temperature buffers T6-T11
represent the six oldesttemperature, samples~Thesevalues are added together into
RATE ADAPTATION BY, TEMP~ERATURE 363
asum, E. The difference between these two values, D- E, represents the

derivative of the CVT.~If D_>E, then the temperature is rising, and tau2 is
multiplied by the aforementioned derivative to obtain~DT. This -value is then
added to the target,rate, TR. :If D<E,~ which would bedue to; an exercise-evoked
CVTdip, then the temperature is falling, and taul is multiplied by the additive
inverse of the aforementioned derivative t0obtain DT. This ,value is then added
to ~the targetrate; TR. Note also that according to the:pseudocode of Figure
~.5~19, if the target rate, TR, is alreadygreafer than a..value, IR(set intermediate
rate; most likely around 85’bpm), then the target rate isset tolR before adding
DTto the .target rate.~.~This has-a similar overall effect to the:intermediate rate
provided in the.Kelvin 500 Series pacemakerin that it .adjusts the overall pacing
rate~do to the initiation 6r cessation of exercise around an intermediate rate. This
algorithm, however, is not li.mited to three pacing rates and ~ responds .much
quicker than the Kelvin 500 Series algorithm.
Additional features of the Kelvin ~$10~ Series pacemaker, algorithm

In addition to the already mentioned parameters, the Kelvin 510 Series algorithm
also provides an upper pacing rate limit (UR, typically 110 bpm). In addition,
programmable~limitations.on~the slew rateis als0 provided. These ,rates, ca~ed
Rate Rampp~eters, are i2, 24, 36, 48, and60 bpirdmi_~’n f0r an increase in the
pacing rate, and 6, 12, 18, 24, and 30 bpm/minfor a decrease in the pacing rate.
(Cook Pacemaker Corporation, 1992).
A plot showi~,g ~e simulated pacing, rate using this algorithm along with the
a~tual paciri~ rate i~ ~hown~inFigure 15.22.
S~MU~m~ ~ ~
Figure15.22~Anindividual’s intrinsic rates compared with simulatedrates producedby the

Kelvin510Ssdespacemakeralgorithmin responseto treadmillexercise.Thes,imulatedandactual
HR~iiow~a s~brlg: e0~elationto each o~eras Well~ ~ to ihe CVT.FromF6amot ~, N: .E~~ hnd
Evans;M:~L.
1~988.HeartratS,correlation~response~timeand. effect of previouspxerciseusingan
advanced.pacing
rate algorithm,for [emperature-basedrate modulation. PACE,~11:1846-1852.
Adv’~a}ages. ~nd:disadvhntage~ Of the Kelvin/510 Series pacemaker

algori h
Like the provides
coe~f’,~ie.nt~:
usf/ig’theKelvin
S~ries 22
patients is reported to be 0.92 with a meanresponse , although the
meaning of chronotropic is questionable since the temperature data were

recorded and then telemetered from patients with implanted Kelvin 500 Series
pacemakers. At least someof these patients most likely were being paced based on
their CVTaccording to the Kelvin 500 Series algorithm, although a VVICmode
is possible for patients whocan benefit from it.
By studying the algorithm and the available information, at least one
disadvantage is apparent: If a patient has a constant fever whichlasts longer than
the period required to determine :tbe minimal temperature baseline, then the
minimal temperature baseline will be adjusted to the value of the CVTduring the
prolonged fever. This would then inhibit the pacing rate increase provided by the
diurnal variation parameter, DV. This problem may be easily solved by
increasing the time period over which a new minimal temperature baseline is
calculated (similar to the length of time the Intermedics Circadia takes to
calculate the REFTMP parameter in the Natural Rate Response).
Presently the Cook Kelvin 510 Series pacemaker is the only CVTrate-
adaptive pacemakerthat is commerciallyavailable in the US.
15.4 ADDITIONAL FEATURES ~OF CVT RATE-ADAPTIVE

PACEMAKERS
In addition to the features already described and to the features that are common
to all pacemakers, there are several additional features that are present in the
Cook Kelvin 510 Series pacem~er; arid presumably similar features in all CVT
rate-adaptive pacemakers. These include the following:
1. Both rate-responsive modes (VVIR, VOOR)and nonrate-responsive modes

(VVIC, VOOC),the latter of which are the default values for the former
modesin case of a low-battery or lo~s-of-temperamre sensing.
2. The ability to telemeter temperature and pacing rate information for
determining the rate-adaptation effectiveness (see section 15.5).
15.5 FOLLOW-UP FUNCTIONS OF CVT RATE-ADAPTIVE

PACEMAKERS
In the event that a CVTrate-adaptive pacemaker is determined to be beneficial

and is subsequently implanted it is important~to determine the patient’s
physiological Condition, keeping in mind things such as age,, exercise capacity,
and overall functionality of the heart whendetermining the initial values of the
programmable parameters. After doing So, close monitoring of the patient is
recommended for the first few months..after implantation (as it is for any type of
pacemaker). In addition to the con~enti0nal parameters which should be checked,
such as refractory period and pulse width, the effectiveness of the, temperature
sensing and rate ~dap~ati0n s~uld be Checked. This ~S determined~in the Cook
Kelvin 510 Series. ~cemak~ not 0nly,by the..patien~"S co~en’ts ~a§ ~otheir
experiences, especially during ieXerci~e, but also ~y ~telemet6ring CVTor pacing
data in one of three ways:
RATE~ ADAPTATION BY TEMPERATURE 365
1. A short term :(up to 4Omin)snap shot histogram, which is initiated using the
programmer, that is most helpful for set activities, such as ,walking or
bicycle ergometry, during office .visits. Mile in this mode, every time the
pacemaker measures temperature, and updates the pacing rate, one of six
counters is incremented, The counters represent the .temperature ranges, of
~ 50-64, 65-79, 80-94, 95-109, 110-124, and 125-160bpm with a limit of
255 for each counter. ~
2.,: A long term histogram (up. tO 5 years), which is also initiated~ by the
programmer,that will ~tell the numberof times the pacing rate was above or
below a programmabledistribution rate.
3. A synchronized telemetry option is also available, which will cause the
pacemakerto telemetgr the.pacing rate and CVTdata.every 10 s. TM’sallows
the l~h~si~ian to test the effectiveness of ~hangingthe vai’ious programmable
values during an office visit.
15,6 OVERALL- ADVANTAGES ANDDISADVANTAGES OF CVT

RATE,ADAPTIVE PACEMAKERS
CVTrate-adaptive pacemakers ha~e an’advantage Over other rate-adaptive

pacemakers-in that they are reliable and stable over time, require minimal
hardwarechanges that are easily implemented, andhave a direct correlation with
metabolic need. ~ ~ " - ~
Although CVTrate-adaptive pacemakers have been criticized for their
relatively slow response to exercise in the past, recent algorithms have reportedly
improvedupon this. Somepatients, however, because of their physical conditions
mayexperience the following problems:
1. Some padents may show a slo~er and prolonged exercise-evoked CVTdip.

This is commonwith patients suffering from chronic .heart .disease andis
caused by constriction of the peripheral blood vessels that service the limbs.
The dip iS prolofiged due to the d~reased blood ~flow to the mUScles, which
are responsible for the heat production during exercise. Depending on the
rate and magnitude of change, the CVTdip may’not be ~de,t~eted possibly
. cahsing’aninitial decrease in the pacing rate followed by a delayed increase.
2. After experiencing .the dntermediate pacing rate incregse after the dip is
detected, somepatients mayexperience a decrease (after the time limit at the
intermediate at an intermediate rate-has expired) due, to the previously
described prolonged dip:~ ~
3. In addition, if such a patient stops exercise, his vessels, maythen dilate
causing a greater volume of blood to pass through ihe ~ (due to
exercise) peripheral muscles. Thus, hisCVTwill suddenly increase even
though he is no longer exercising, This would cause an undesirable increase
in the pacing rate.
In addition,, some types o,f exercising, such as Swimming,may. not provide

sufficienf rate increases; ~though studies reladng normal HI~ and simulated HR
using CVT.rate-adaptive pacemakers during this type of exercise (where CVT
maybe affected by the environment) have not been reported.
366 DESIGN.OF CARDLA(~ PACEMAKERS
Also, some .pacemakers, such as the Intermedics Nova and Circadia, have not
progressed, beyond clinical trials, not due to ineffectiveness, but due to business
decisions. These .business decisions were primarily , based on the fact that
physicians do not like to be forced to.~use.a certain type .of pacing lead (the
number of types of pacing leads with integrated~thermistors is extremely limited)
as well as the fact that rate-adaptive pacemakers using activity sensors, which do
not require changes to the conventional pacing leads, have shown acceptable rate-
adaptation during most types of. exercise. (Sneed, t99~). These .types of rate-
adaptive pacemakers, however, will not provide increased pacing rates due to
fever, anxiety, or inherent circadian type cycles.
15.7 IMPROVEMENTS IN CVT RATE’ADAPTIVE PACEMAKERS
Because CVTrate-adaptive pacemakers are relatively new, it is likely that further

improvements will be made to the algorithm that determines the pacing rate.
However, .some of the potential~problems that~were previously.mentioned may
not be solved this way. A likely improvement: in rate-adaptive~pacemakers is the
addition of an additional sensor. Because CVTsensors (thermistors) have proven
thus far to be the most reliable and accurate metabolic sensors, it is likely that a
rate-adaptive pacemaker having multiple sensors may include CVTmeasurement.
Examples of such systems tha~ h/~ve been Pr0~osed include respiratory and CVT
rate control (Sugiura et al., 1988, 1991), activity and CVTrate control (Heggs
al., 1990), and blood oxygen contenk and CVTrate control (Lekliolm’et al.,
1993). ....... .~ ~. ~, .~..
15.8 REFERENCES
Alt, E. 1987. Temperaturedriven rate responsivecardiac pacemaker.USpatent 4,688,573.

Alt; E.~ 1991. Rate responsive cardiac pacemaker.USpatent5/01’4,700. ¯
Alt, E., Barold, S. S., and Stangl, K.(eds~)1993. Rate adaptive cardiac pacing. Berlin:Springer-
3/edag., ~ . ..... ~, ~ .........
Alt, E., and CJdfee,’R.V. 1988. Exercise-resp0asi~erate-adaptive eardiad pacemaker.USpatent
4,719;920:
Air, E, vHirgstetter, C~, Heir, M., and Biomer,H. 1986. Rate control of physiologic pacemakers
¯ by central ~enousblood.te~,.t,u.re__: Circulation, 73~ 1206~1212, ¯
Behre~be~LDJ W., Fontaine, ~3., and Winter, U, J. i985. C~rdiac Pacemakers. NewYork:
Berggren,G., and Chri~tensen, E~ H.- 1950. Heart r~ite-and body., temperature as itidices of
:metabolic rate during work. Arbeitsphysiologie~. 14: 255-260.: ..... : ~ "
Berne, RcM., and Levy~:M,N. 198 !. Cardiovascular phy~ology. St. ~Louis: M0sby,.. h
Bixler, J. 1994 (Personal conversation with CookPaceinaker~.~.orpo~ationengineer). Marc
1994.
Boal, B., Buckingham,T.~ Fearnot~ N. E., ~elahy/I~, Gent~.ler, R,~ Geiger, J.¢ Grogan, W.,
Platia, E., Politte, L., Rao, G.~’~Redd;’R.,~Sellers,. D., and Shirey, R, 1987. Temperature-
based, variable~rate pacing: a multicenterstud~of the ftrst 31 Kd!vin.’m~plantsioProceedings
of the Vlllth WorldSymposium on CardiacPacingand ,El~ectrophysiology.
Calfee, R. V., Adkins, R. A., Alt~ E. U:, and Baker, R. G. 1989. Temperature responsive
controller for cardiac pacemaker.USpatent 4,803,987.
Cook Pacemaker Corporation. 1992. Sensor Model Kelvin 513 and 514 Pulse Generators:
Physicians Manu~ !. Leechburg, PA.
Cool W.~.’, F6arnot, N~~ E., and Geddeg,L. A~198~ :EXe/:ci~responsive cardiac pacemaker.
US patent 4A36,092~ ..... ¯ ~’:::~’~ ....... ~
Cook,W.A., Fearnot, N. E., and Geddes,L.~A.. 19..85. Exercise:responsivecardiac pacemaker.
USpatent 4,543,954.
Fearnot, N. E., and Evans, M. L. 1988. H~art~ rate collation, response time and effect of
previous exercise using an advancedpacing rate algorithm for temperature-based rate
modulation. PACE,11: 1846-1852.
Fearnot, N. E., and Evans, M. L. 1991. Temperature-basedrate-modulated cardiac therapy
apparatus and method.USpatent 5,005,574.
Fearnot, N. E., and Smith, H. J. 1987. Six possible factors affecting intercardiac temperature
duringrest and exercisetesting (abstract). Circulation,76 (suppl. IV): 1447.
Fearnot, N. E., Osamu,K., Fujita, T:,’Okamura,H.; and Caldefini~ ~VI~1989. Case studies on the
effect of exercise and hot water submersionon intercardiac temperature’andthe performance
of a pacemakerwhichvaries pacingrate basedontemperature. Japanese Heart Journal, 30:
35~-363.
Furman,S..1990. Rate-modulatedpacing. Circulation, 82: 1081-1094."
Gillette, P. 1984. Critical analysis 0f.~en,so~ for physio!ogi~al responsive pacing. PACE,7:
1263-1265.
Griffin, J. C., Alt E.~ Nielsen, A, and Ca!fee, R. 1986, Venousbloodtemperatureto pacing rate:
importanceof the algorithm(abstract). C//~ PrOg.Electr~physiol.Pacing,4 (suppl):
Griffin, J. C:, Jutzy, J:’P., and Knutti, J.W. i983. Central body’temperamrea~ a guide to
optimal heartrate..PACE~6: 498-=501.
Hauser, R. G. 1984. Techniques,for imp[ovingcardiac performance’with.implantable devices.
PACE,7: 1234-1239.
Heggs, K~ S., Johnson, W. L,, and Stevens, D. A. 1990. Temperature-controlled cardiac
" pacemakerresponsive to bodymotion. USpatent 4,905;697:
Houdas,Y;, and Ring, E. F. J. 1982.~~ Human body temperature:Its tn~¢asurementand regulation.
¯ ~ NewY~k: Plenum PreSs.
Jolgren, D. !984. A rate-responsivepacemakercontro~lledby~right ventticular bloodtemperature.
PACE,7: 794-801. ¯ °
Laczkovics, A. 1984. The central venous blood temperature as a guide for rate control in
’ " pacemaker therapy: PACE;7: 822-830: ¯ ~’~ ". .... , ¯~ ’
Lekholm,A. 1993. Apparatus for in v~vo in~ardi ~ of a measuredsignal corresponding to the
physical activity of a subject and a he~ pacemakerhaving a stimulation rate controlled
thereby. USpatent 5,218,961. ’ ’ ’¯ ¯.
Morgane~.P.J., and Panksepp, J~ (eds.)’ 1980. BehaPioralStudies~ the HypothalamusVolurne 3
Part A. NewYork: Marcel Dekker.
M.~unteanu,~ J.;:.Alt, E.~,"Hirgstette~C.,~ ~andHeinz~,M: 1986. Central’venousbloodtemperature
’" represeriting metabolic rattatid~individuals exereise capab~ility (abstract). Clin. Prog.
Electrophysiol.Pacing,4 (suppl): 27.
Nielsen, B. 1966. Regulationof bodytemperatureand heat dissipation at different levels of energy
and heat production in man.Acta. Physiol. Scand, 68: 215.
Rhoades, R., and Pflanzer, R. 1992. HumanPhysiology. NewYork: Saunders.
Saltin, B., and Hermansen,L. 1966. Esophageal,rectal and muscletemperatureduring exercise.
J. Appl. Physiol., 21: 1757-1762.
Schaldach,M.1992. Electrotherapyof the heart. Berlin: Springer-Verlag.
Sellers, T. D., Fearnot, N. E., Johnson,R. E., Shirley, D. A., DiLorenzo,D. M., and Knight, J.
A. 1985. Right ventdcular blood temperature profiles for physiologic pacing (abstract).
Circulation, 72 (suppl. lll): 1730.
Sellers, T. D., Fearnot, N. E., Smith, H. J., DiLorenzo,D. M., Knight, J. A., and Schmaltz,M.
J. 1987. Right ventricular blood temperatureprofiles for rate responsivepacing. PACE,10:
467-479.
Sneed, R. 1994(Personal conversation with Intermedics engineer). March24, 1994.
Sugiura, T., Kimura, M., Mizushina, S., Yoshimura,K., Harada, Y. 1988. Cardiac pacemaker
regulated by respiratory rate and blood temperature. PACE,11: 1077-1084.
Sugiura, T., Mizushina,S., Kimura,M., Fulmi, Y., Harada, Y. 1991. A fuzzy approach to the
rate control in an artificial cardiac pacemakerregulatedby respiratory rate andtemperature:a
preliminary report. J. Med.Eng. Technol., 15: 107-110.
Volosin, K. J., O’Conner, W: H., Fabiszewski, R., and Waxman,H. L. 1989a. Pacemaker-
mediated tachycardia from a single chambertemperature sensitive pacemaker.1989. PACE,
I2: 1596-1599.
Volosin, K. J., Rudderow,1L, and Waxman,H. L. 1989b. VOOR ~ Nondemandrate modulated
pacing necessitated by myopotentialinhibition. PACE,I2: 421-424.
Zegelman,M., Winter, U. J., Alt, E., Treese, N., Kreuzer, ~., Henry,L., Mugica,J., Schroeder,
E., Klein, H., and Vulker, R. t990 Effect of different body-exercise modeson the rate
response of the temperature-controlled pacemakerNovaMR.Thorac. Cardiovasc. Surg.,
38: 181-185.
15,1 Explain whyCVTrate-adaptive pacemakerssample the blood temperature from the right
ventricle.
15.2 Explain howthe body tempera~ regulated.. ¯
15.3 Sketchthe CVT and HRas a person is at rest, then begins to exercise, and finally ceases
exexcise..Statethe r~asonsfor tl~ shapeof ~ ctu, ve.
15.4 Explain whyCVTrate-adaptivdpace~rs have ndgative fcedb_ack.
15.5 Drawa basic block diagramof the CVTrate-adaptive pacemakersystemand explain the
purposeof each of the-blocks.
15,6 ~)escribethe impo~~rt~. c~. of isolating the :the ~rn~tor frompossiblefluid intrusion.Explain
the resulting CVTrate-fidaptive pacemaker responseinthe event of fluid intrusion if it were
not detected.
15,7 Explain why~thecircuitof Figu~15.8 is moreoptimal tha~ that of Flgm¢15..
15,8 DesCribehi~wtbe prc~nt t~n~peratm¢is determinedusi~gthe Circuifof Figure 15.8.
15.9 Describe which factors need to’be considered whendeveloping an alg0rithm for a CVT
rate-adaptive pacemaker.,
15.10 Describe howthe Kelvin 500 series pacemakeralgori~ Changesthe pacing ~ate based on
the CVT.
15,11 Explain the advantages and disadvantages, of the Cook Kelvin 500 series pacemaker
algorithm.
15.i2 Describe howthe IntermedicsNova MRpacemakeralgorithrn~changes the,pacing rate
based on the CVT.
15.13 Explain the advantages anddi~advantages of the~Intermedies Nova MRpacemaker
algorithm. ¯ ~,
15,14 St~td the equation whichtheIntermedicsCircadia algorithmuses to adjust the pacing rate
and describe the proposeof each of the p~ameters,
15,15 Explain howthe Int¢~e~cs Circadia de~ermines whether or not an exercise-invoked
ten~peratur~
dip has ~d.
15,16 Explain~ hoWthe Sensor ModelKelvin 510 pacemakeralgorithm adjusts the pacing rate
following exercise.
15.17, Explain the importanceof the followrupfunctions of CVTrate’adaptive pacemakers..
15.18 Explainhowan additional sensor world increase the ¢ffectivenes~of the CVTrate-adaptive
pacemaker.
Rate Adaptation by Electrogramand Intracardiac
Impedance
Clark Hochgraf
This chapter discusses methods of using electrogram (EGM)and intracardiac

impedance signals to determine the optimal paced heart rate.,:When _the .body
desires to increase cardiac output, it will,signal an increase in the heart rate and
the contractility of the ~heart. In a chronotropically insufficient heart, the natural
heart rate will not increase, but there will be an increase in the contractility of the
heart. ~Changes will: occur in the .EGM-andintracardiac impedance and these
changes can be processed by an:algodthm to produce,a paced,heart rate that
meets physiological demand~forcardiac output.
A pacemaker that takes its cues ~from the body’s cardiac control system
pacemaker acts as part of the closed loop,control system for cardiac output, A
heart rate determined in this, fashion allows increased-tolerance for ,exercise,
better~regulation of blood pressure andreducedstress on the heart; and will best
meet a patient’s changing physiological needs. .
Algorithms for processing the measured EGMand intracardiac impedance
attempt, to detect the sympathetic tone of the heart.: The algorithms must avoid
producing the wrongheart rate as aresult of changes in. the EGM.and.impedance
due to factors other than the sympathetic tone. Circuits for measuringthe signals
are described and the rate adaptation algorithms examinedfor their ability to
detect sympathetic tone and avoid false indications. Information, about Clinical
studies of the performanceof various algorithms is included.
16.1 ~ ,BENEFITS OF, USING INTRACARDIAC SIGNALS FOR RATE

ADAPTATION
A rate-adaptive pacemaker that is sensitive to metabolic demandincreases the

~paced heart rate if a rise in sympathetic nerve activity is detected. ~Therate’is
maintained until the demands of the sympathetic nervous system are met. The
rate-responsive algorithm tries to provide a heart rate which corresponds in a
normal ~fashion to the level of’sympathetic activity., By havingthe pacemaker
detect and ratei the pacemakeris usifig the
~’s the physiologically correct heart rate~
owncardiac control signals and their response to metabolic demandfor cardiac

output often is not appropriate.
The sympathetic tone responds to manyfactors that influence the heart rate
such as workload and emotional stress. In comparison, activity-based rate
adaptation schemes can only estimate the workload and cannot adapt for
emotional demands. The ability to respond to emotional and mental stress is a
feature of the methods based on cardiac signals. Impedance-based measurement
of stroke volumeand ejection~fraction mayliave additional utility~in the detection
of tachycardia. The sensors for EGMand impedance signals are~ simple and
robust.
Of the manysignals that maybe used for rate adaptation, intracardiac signals
have certain advantages. The signals are often obtainable using a standard or
slightly modified pacing lead. As such, they do not need additional sensor leads or
complex sensors such as required for detecting blood pressure or blood oxygen
levels. Rate algorithms based on the EGMrequire no additional sensor energy.
Rate algorithms based on impedance do require additional sensor energy. Both
the impedance and the EGMsignals contain information about the state of the
heart’s natural control system--the autonomic nervous system.
Derived parameters such as the Q-T interval,, stroke volume, ejection
fraction andothers give indirect information about the sympathetic .tone of the
heart. In a normal heart, an increase inactivity in the sympathetic,nervoussystem
would cause an increase in the heart rate. In the. damaged, chronotropically
insufficient heart, the normal mechanismsfor.changing the heart rate°are not
fully functional. However,the effect of sympathetic activity can still be observed
in the heart’s operation through other indications such as contractility.
The impedance-sensing scheme can use unipolar, bipolar or multipolar
electrode, configurations. Processing of the EGM and impedancesignals is easily
performed. One disadvantage of using cardiac signals such as-the Q,T interval is
that there is a large patient-to-patient~ variability, iwthe ,relationship of the ideal
rate to the detected signal. Thus to achieve a good, rate response, the pacemaker
must be trained during, an exercise regime, wherein the heart is taken ~throughits
paces, so to speak. For a patient with poor,,cardiovascular health, it may-berisky
or simply not feasible to perform the exercise training required.
16.2 SYMPATHETIC TONE
The goal of a rate-adaptive artificial pacemakeris generate a heart rate which

corresponds well,to the physiological demandfor, cardiac output. This section
will describe the reasoning behind utilizing the sympathetic tone to regulate the
heart rate. Later sections of this chapter will show the different means used in
measuring the sympathetic tone.
16.2.1 The control system of the heart
To understand the relationship between sympathetic tone and the normat sinus
rate, a simplified control system model of the heart is used. Schaldach (1992)
describes a control system mode!:,~of the. cardiovascular system, with particular
focus .on the, heart~s regulatory:role. Figure 16.1 shows the-influence of the
sympathetic and parasympathetic tone on ,theEheart rate, Par~ympathetic nerve
activity decreases the heart rate via the SAnode .andAVnode.Sympathetic nerve
activity increases the hea~ rate via the SAandAVnodes as well as affecting the
heart muscle itself. Sympathetic nerve stimulation affects the heart muscle by
RATE ~ADAPTATION BY EGM AND IMPEDANCE 371
causing an increase in the .contractility of the heart, resulting in an increase ,in the
stroke volume. Stroke volumeis the, volume of blood,ejected from the heart in
each beat.
Highereffects
(stress,fight or flight, etc.)
I Medullan]circulatory
centers
Di =
variables:
(workload,etc.)
Figure16.1 Schematic diagramof the heart s control system.Therole of.the sympatheticand

parasympathetic nervesonthe. heart rate iS shown.Anincrease: in sympathetictone Causesan
increasein the heartrate. Thesympathetic
tonealSOinereaseStheContractility0ftheheart andthus
increasesthe strokevolume. Thevariablewhichis beingregulatedin the healthy:heartis the mean
~artedalbloodpressure.Evenwith a damaged sinus node,the symp~athefic,~tonee~anbe observed
~ughits effect on the con~tility Of the hem.FromSehaldach,M~M.19,92; EIectrotherapy of
the h~art. Berlin: Spdnger-Vedag; " ’ ¯
The heart rate multiplied by the stroke volume determines the’:~cardiac

output--the total volumetric blood flow through the heart in liters per minute.
The blood pumpedby ~the heart passes through the vascular system,, encountering
the: flow resistance of the arteries and veins. Be flow of blood requixesa, certain
blood pressure ,in the vascular system. The Mean ArteriaL,Blood Pressure
(MABP)is the ,central variable controlled bythe regulatory system of the ,hea~.
While heart rate; cardiac output and vascular resistance can vary greatly with
workload, the MABPremains relatively constant., ~
-The regulat0ry~ system gets information from the baroreceptors, ~whieh are
sensors that detect the blood pressure and~relay~ this information to~:the, nervous
system. The nervous system responds , to : the MABP as well,,as influences from
higher effects (stress, emotions, etc,)-in controlling-,the~ cardiac, output=:~
indicated in Figure 16.1, the heart,rate is set by two opposing influences, the
parasympathetic and sympathetic nerves. A normally functioning sinus node

receives both influences and uses both ~to determinethe heart rate.
Whenthe sinus node is damaged, the heart rate must be determined by some
other means. If an ideal artificial rate-adaptive pacemaker could be made, it
would be able to detect the presence of the both parasympathetic and sympathetic
activity and decide on the intended heart rate. Rate-responsive pacemakersbased
on detecting and regulating the meanarterial blood pressure will work well in
that they achieve the desired MABP,however, they will ignore the body’s own
autonomic nervous system (ANS)control signals.
The utility of the sympathetic tone for determining the heart rate is limited
because the effect of the parasympathetic tone is not incorporated. The sensing
methods described in this chapter, such as Q-T interval and stroke volume, only
measure the sympathetic tone and as such have only part of the information which
is availableto the sinus node. This mayexplain the less-than-perfect rate response
profiles obtained with these methods.
16.2.2 Clinical evidence for Mean Arterial Blood Pressure as the

regulated quantity
There is clinical evidence that rate response to the sympathetic tone produces
beneficial regulation of the MABP. Grubbet al. (1993) reported on the successful
application of a rate-responsive pacemaker in regulating the’MABPin a patient.
with severe refractory orthostatic hypotension. The pacing rate was modulated in
response to the changes in sympathetic tone resulting in improved regulation of
MABP.
The patient’s condition was such that standing would cause him to faint due
to a marked decrease in blood pressure. Drug therapy was ineffective in this
patient. Continuous tachycardia pacing would have prevented hypotension except
that upon lying down, the patient would suffer from hypertension. Therefore, a
fixed-rate pacemaker that boosted his standing blood pressure, would
overcompensate whenhe was in a supine position.
A pacemakerwith rate adaptation based on the right ventricular pre-ejection
interval (Precept DRModel 1200 from Cardiac Pacemakers Inc.) was employed
to help moderatehis blood pressure. Whenthe patient stood up, the pacemaker
detected a sudden decrease in the pre-ejection period and correspondingly
increased the heart rate. The MABP was thus controlled quite effectively,
allowing the patient to resumea normal life.
16.2.3 Methods fo.r detecting the sympathetic tone
The activity of the sympathetic nervous system is not’directly measured. Rather it

is inferred from its effect on the heart’s contractility and systolic time intervals.
Effects of sympathetic appear in the Q-T interval, ventricular depolarization
gradient (area under the QRScomplex), pre-ejection period, stroke volume, and
ejection fraction. Various studies have found cause to consider each of these
signals as useful for rate adaptation.
The relationship of a~particular parameter to the heart rate is studied by
correlating the change in the parameter of interest to the normal sinus rate. The
correlation is evaluated for conditions of rest, exercise, upright and supine
position, and emotional stress.-The relations so found are .examined with the goal
of calculating a relationship that will adequately, determine the heart rate for all
RATE ADAPTATION BY EGM AND IMPEDANCE 373
such stress conditions. The ideal would be to have a signal that has a constant
simple relation to the normalheart rate in all cases.
For someof the signals, the relationship betweenthe signal and the sinus rate
is ambiguous ’or conflicting during some of the stressor conditions. The
processing algorithm inside the artificial pacemakermust take this into account.
Positive feedback must be avoided, otherwise the pacing rate will start to respond
to itself and~notto the physiological demand.
One of the more severe examples of a methodprone to this positive feedback
is the use of the Q-Tinterval .signal. The Q-Tinterval shortens during exercise,
indicating the need for the heart rate to increase. However,Q-T interval also
shortens if the resting heart rate is artificially, increased through paced
stimulation. This positive feedback effect can cause pacemaker-mediated
tachycardia~ Careful adaptation of the rate can compensate for this effect and
pernut succdssful use ofthe Q,Tinterval in rate adaptation
The standard pace sensing leads are used to detect the Q-T interval and
sVentricular
ensedfrom thedepolarization
pacing !cad aregradient. Changes inthethepre-ejectlon
used to determine intraeardiacimpedance as
period, stroke
volumeand ejection fraction.
16.3~ BIOPOTENTIAL-BASED MEASUREMENT SYSTEMS (Q-T

~- INTERVAL AND DEPOLARIZATION GRADIENT) .
Tti~ intracardiac .electrogram EGM can be used for altering the paced heart rate
in response to sympathetic activity. The EGMis usually measured from the same
lead (bii3olar or unipolar) as used for pacing which makes these signals
c0i~venient to obtain. Measurement of the Q-T interval, and ventricular
depolarization gradient can be used. for detecting changes in metabolic demands.’
The use of these parameters for rate response is :described in detail in the
following sections.
I!6,3.1,Q-T interval
Figure 16.2 ~defines the Q-T interval, which ~reflects the timing ~of ventricular
activity. The. onset of ventricular activity can be markedby either a~ natural QRS
complex or a pa~ed QRScomplex, thus the Q--Tinterval is sometimes referred to
asthe Stimulus to T interval. The Q-T interval is strongly correlated with the
ievel~ofexereise. Forthese reasons, it has been used in several pacemakermodels
as a signal for rate adaptation. The most challenging aspect of using the Q--T
interval is not its detection but finding an algorithm that safely and correctly
converts the timing information into a suitable heart rate. Problems with the use
of this~Signal for rate response have largely been caused-by ~the algorithm used.
Early algorithms did not account for the coupling of changes in the-paced heart
rate back to changes in the Q-T interval.
Relation ¢oo ~sympathetic activity

The,relationof Q-T’interval to the normal sinus rhythm has been investigated in
numerousstudies. The~Q-T.interval has been established to:shorten in proportion
to increases in workload, mental stress and heart rate. The Q-Tinterval has also
been seen to increase slightly at night.
PeakNegativeSlope
~ ""
%
of the T wave
~!l~T-wave sensing window
Q-T interval - I
Figure16.2 Definitionof Q-Tinterval usedin rate-adaptivepacemakers as measuredfromthe

EGM.Thestart of the Q-Tinterval is frpmeither the onsetof a natural QRScomplexor fromthe
pacingstimulus~Theendof the interval is marked bythe peaknegativederivativeof the T wave.
Sensingof the derivativeof the Twaveoccursduringa limitedtimewindow.
The normal sequence of ventricular contraction begins with the rapid

depolarization of the muscle tissue resulting in the QRScomplex. Bloodis ejected
from the heart, then the tissue relaxe~ and repblarizes resulting in the EGMT
wave. The Q-Tinterval is defined as the time from onset of ventricular electrical
activity to the peak negative slope of the T wave. The fact that the Q-T interval
decreases in response to exercise and stress makesit a candidate for use in rate
adaptation.
Jordaens et al. (1990) established a strong correlation between the Q-T
interval and the level of catecholamine in the blood. The. Q-T interval closely
tracked the level of norepinephrine in the blood during exercise. Since
norepinephrine is released by the sympathetic nervous system, the indication is
that the sympathetic tone can be well detected by the Q-Tinterval.
If the resting heart rate is artificially increased by a pacemaker, the Q-T
interval shortens in proportion to the heart rate. The reduction of the Q-T
interval due to the heart rate is a form of positive feedbackand if the adaptation
gain or slope is set too high, the-pacemaker rate can increase on its ownto the
point of tachycardia. Various modelshave been proposed, for the relation of the
heart rate to the Q-Tinterval. Bazett (1920) corrected the Q-T.interval for heart
rate differences by dividing the Q-Tinterval by the square root of the heart rate.
Recent studies indicate that the relationship of heart rate to Q-T interval
shortening is better approximatedby ~a negative exponential function.
Circuits for sensing Q-T interval

A standard sense amplifier as described in Chapter 8 is used for detecting the
EGM.If the heart beat is paced, the interval starts.when the pacing pulse is
applied, otherwise the start of the QRScomplexis used as the starting point. The
detection of the slope of the T wave can be performed in analog circuitry by a
differentiator circuit followed by a peak detector. The peak detection window
starts 200 ms after the QRScomplexis detected. The peak detector is configured
so as to detect only the negative peak of the slope. If the EGM is converted to a
digital signal by an analog-to-digital.~converter then detection of the negative peak
of the derivative is performed during the same time window.
RATE ADAPTATION BY EGM AND-IMPEDANCE 375
Algorithm for rate adaptation

The first Q-T rate,adaptive pacemaker was implanted in 198I (Vitratron Model
TX; The.Netherlands). The features and operation of the system were discussed
in Connelly.and Rickards (1992). The change in heart rate above the base rate
was calculated using a programmed slope parameter with units~of beats~per
minute per t millisecond .of Q-T shortening. The sensing of the T wave. was
windowed.After ~the pacing, pulse was applied, the EGMsignal was~ignored for
200 ms. A search window was then opened and the negative peak of the first
derivative :of the EGM was watched for.
If the measuredQ-T interval on the last beat was shorter than the previous
value, then the rate was increased by a small increment. If the Q-Tinterval was
longer, the paced heart rate was reduced by a small amount. The pacing rate-was
subject to upper and lower limits and was programmedto drift back downto the
basic rate over a period of time. ~
The appropriate slope for rate response varies greatly :from patient to
patient,-requiting the slope to be set for each individual. Setting of the slope
involves having the-patient~ perform several exercise tests where the changes in
the Q-T interval are reeorded,.~The extensive~ training required is a disadvantage
of this system, However,once trained for a particular patient, the performance of
the algorithm was good and patients showedimproved tolerance for exercise.
The Q-T-based system was also. seen to work well in five year follow-ups of
patients.~ Bloomfield et al. (1989)reported that in a small.study group, the rate
adaptation worked wall in a high percentage of patients and only a smalLpercent
of the group required someadjustment of the slope to achieve optimal response.
Examplesof suboptimal rate response include an overly rapid increase in heart
rate at the start of activity or a peakingof the heart rate several minutesafter the
cessation of activity.
¯
!~p~oved algorithms
~e:motivationfo~ improvements to the linear~ s!0pe.alg0rithm e~e from a
numberof directions and reveal the influential factorsqn the refinement process.
Shortcomings of the algorithm were seen in performance tests of the pacemaker
Where the prOportionality of response was n0t~unifo~m withworkload. The
requirement for individual training to calculate a patient-specific slope was ’time
consumingand involved physically, stressing the patient, Studies revealed that the
relationship of Q:-T interval to h~art rate during exercise is better represented
by a negative exponential rather than a linear function as was used in the original
version of the pacemaker. In addition, it was obserVed that whenthe heart rate
reached its upper limit, the rate tended to oscillate around the limit. Whenthe
slope was .too high; ~ the risk Of inducing tachycardiaby the positive feedback of
heart rate t0’Q-T shortening was also a concern.
The essential problem with the Q-T-interval-based pacemaker is that the
paced h~art’rate has an effect on the Q’Tinterval. This positive’ feedback effect
from the’heart rate to the Q-Tinterval needs to be accounted for.
,In light of this additional information, an improved algorithm was
developed~ Heijer et ali-(1989) presented the new algorithm:anti its resulting
performance. The improved algorithm encompassed severaladditional featu~res~
First, the pacemakercould nowperform self training for the individual patient as
well as adapt its slope to slow changes over the course of days. Second, the Q-T
to heart rate relationship was no longer linear but rather reflected the actual
nonlinear relation that had been observed in other studies. ~Thechange in slope
with heart rate allowed the pacemakerto respond more rapidly to exercise.
To test the algorithm’s performance before actually building it into a new
model of pacemaker, the real-time bi-directional telemetry capabilities of
previously implanted pacemakerunits, was utilized. The new algorithm was tested
in 37 existing pacemakersby using an external computerto continually.update the
programmedslope parameter. The external computer received, in real time, the
heart rate and internally measured Q-T interval and then told the pacemaker
what slope to use. The new algorithm became known as the dynamic slope
algorithm.
Dynamic slope algorithm

Instead of having a constant relating the Q.-T shortening to an increase in paced
heart rate, the slope of the relationship is madeto decrease as the heart rate
increases. Byhaving a high rate adaptation slope at rest, the delay of pacing rate
change at the onset of exercise is.reduced. By having a lower, slope at high heart
rates, the_risk of paced tachycardia and heart-rate oscillations at~e upper limit is
reduced. The pacemaker’s programmed Q-T interval to heart-rate curve then
better reflects the actual observed-relation of Q-Tto heart rate during exercise.
As-an illustrative example, the following-set.of adaptation equations are
presented to show one possible’rate adaptation sehemein whichthe feedback of
paced heart rate to the Q-T interval can be accounted for. The nonlinear slope
characteristic of the dynamicslope algorithm.haS-a physically insightful basis for
its shape. Considerthat in a linear (constant) slope adaptation algorithm, the rate
is given by the formula
Rate = BaseRate + [(Q-T)rest- (Q-~T)sensed] × Slope (16.1)
where (Q-T)rest is the measured Q-T interval during rest. If the coupling
between the resting Q-T interval to heart rate is included, the formula is
modifiedso that the slope is a function of the rate. Theunits o~ thesI0pe are beats
per minute per millisecond of Q’T shortening. In Eq. (I6.2), the slope is now
partially a ~unetion 0f the’heart rate throu~i the ~oupling factor~.M, which
represents the-~nonexercise-related change in the Q-T interval with a change in
heart rate.
Slope = OnsctSlope. MX (Rate -; B~eRate) (16.2)
with the newslope, the formula for the rate becomes¯
Rate = BaseRate + OnsetSlope x ’1 +(Q-T)rest- (Q-T)sensed

Mx [(Q-T)rest, (Q-T)sensed] (16.3)
The adaptation term is the second term. Since the value of Q-Trest minus Q-
Tsensed is always positive, the numerator term is increased during exercise, but
the denominatoris also increased due to the resting Q,T to heart rate relation as
expressed in the factor M. As the Q.T interval gets shortgr, the adaptation, slope
is reduced by a factor of
1
(16.4)
1 + M x ((Q-T)rest ~.(Q-T)sensed)
The dynamic nature of the slope is expressed in this term. The coupling
factor Mis readily derived from observing the Q±Tshortening when the paced
heart rate is temporarily increased in a resting patient. The Q-Tshortening is due
entirely to the artificially induced changein the paced heart rate and not due to a
change in sympathetic tone. Thus the measured parameter M represents the
coupling between the paced heart rate and Q-T shortening. By knowing M, we
can minimize its effect in determining the physiologically appropriate heart rate.
Figure 16.3 shows the value of the rate,adaptation slope, and it showsthat if Mis
not zero, then the rate-adaptation slope should decrease as the heart rate
increases.
A heart rate induced

M = - A (Q-T)sensed (16.5)
2.5
1.5
1
M=O
0.~
0’
60 80 100 120 140
Heart rate (beats / min)~
Figure 16.3 Exampleof change in the rate-adaptation slope when the effec t of the heart rate on
the Q-Tinterval is included. Anincrease in tilt of the line correspondsto a larger effect of the heart
rate on Q--T shortening. The coupling factor Mis measuredwith the patient at rest.
Figure I6.4 shows~t’:ih’ large value of Mcauses the paced Q-Tto heart rate
characteristic to havea significant curvature to it.
At low .heart rates, the slope is l~ge, so that small changes in the Q-T
interval cause a rapid response in the paced heart rate. However,at high heart
rates, the slopeis small so that the sensitivity to Q-Tshortening is reduced.
The higher slope atonset of Q-T shortening reduces the delay in responding
to activity. Withthe dynamicslope algorithm,-the slope at near the upper rate
l~mit rapidly, .~tppr0aclies zero. By having the slope go to zero, the problemwith
upper rate oscillations is avoided.
Clinical Studies
Studies of the linear and,,dynamic slope algorithm have. shown that the
proportionality of the response ~to workload is quite good. Figure 16.5 shows the
dynamicslope algorithm-to have a quicker, onset and better proportionality or
response than the linear slope. Dynamicslopehas also reduced the:tendency for
the pacemaker to oscillate in frequency near the upper limit and assists in
avoiding positive feedback leading totachycardia.
i40
120
100
"~ 8O
6O
330 340 350 360 ~ 3?0 380 390 400
Q-T interval (ms)

Figure16.4 Thedynamicslope algorithm.Therate-adaptationrelationshipof Q-Tinterval to
pacedheart rate is shownfor different couplingfactors M.TheparameterMdescribeshowmuch
the heart rate affects the Q-Tinterval(ms/beat/rain).When
the heat~rate has a largeeffect onthe
Q-Tinterval (large M),the curvatureis greater. Abenefit of compensatingfor the ratecoupling
that the adaptatibnslope at onset canbe madehigher. Theslopeis also reducedat higherheart
rates, preventingrunaway tachycardia.
120
115
¯ o
o
o
7O
Tlme[secl
o U,~. ~.,~o~m ~
~ 16~ Pacing ram d~ng exerci~ for ~e L~e~ ~gofi~m and ~prov~ ~n~c slo~
flgori~m. Notice howtbe improv~flgofi~ has a quicker~ ~s~nse to~ exewise ~d ~tter
pro~onflity to exewi~. ~e l~e~ flgofi~ can~s a rapid inc~e in rate ~. ~e pac~g~te
ge~ ~gber ~d ~e~T~fl ge~ sho~er.FmmHeijer, P. D., Nagelkerke, D., Pe~ns, E. J.,
Horst~, E., V~W~em,R. J., Neiderlag, W., Jord~ns, L., Wilde~P. D., H~el~rS, W.
B., ~d Lie, H. 1989. ~proved ~ ~s~nsive flgofi~ in ~T ~ven pace~e~vflu~on
of ~ififl respon~to exerci~. PACE.,12:805~11.
The proportionality of the Q-T interval m the workload is quite good.

However,the method suffers from the fact.that there isstill considerable delay
from theonset of activity to the shortening- of the, Q-T interval. Horstmannand
Koenn(1989)~reported ,in one study~of patients with Q-T interval rate-adaptive
pacemakers (standard: linear algorithm) that there was a 63,4-s delay from the
onset of exercise to a 4-ms shortening of the Q-T interval. The dynamic slope
algorithm helps to minimize this delay, bm the limitation of the method seems
tied to the fact that. changes in the Q-T waveform seem to lag changes in
noradrenaline levels by about 1 rain. The maximalheart rate was seen to occur
29.2 s to 69.5 s ~after the cessation of exercise, .depending on the programmed
rate
adaptation slope.
Self-training of slope
The slope parameters of the algorithm can be programmedby a physician during
exercise training or~they can.be programmedautomatically by the pat.croaker
through self-training-algorithms. Twoself-training modesof the pacemaker are
the Fast~ Learning ~algodthm and the Automatic Slope Adaptation algorithm. In
the fast learning mode,the lower heart rate slope is set by having the patient sitat
rest while :the pacemaker setsits rate to 70 bpm then 80 bpm then 70 bpm,
holding each for 1 minute, while recording the Q-T interval~ The coupling
parameter Mfor low heart rates is then directly calculated. The patient is then
exercised at high workload until the upper rate limit is reached. If the Q-T
interval continue~tO .get,shorter .once the rate limit is reached, then it is known
that the slope (for high heart rates) is too high. The’ Slop~ fo~high heart rates
then reduced.
The Automatic Slope Adaptation method sets the lower rate slope once every
night (asdetermined by its 24-h Clock). During sleep, the lower et~d slope
calculated in much the same way as for the Fast Learning algorithm. The slope
for upper heart rate is adjusted if theupper rate limit is reached, and the Q-T
interval ~ontlnues to decrease even further. This indicates that the limit w~smet
prematurely and that the upper heart rate slope Should be reduced by one
increment. If, on the other hand, the upper rate limit is not reached once in a
period of 8 days, the~ sl~3pe for the.upptr heart rate is increased by one increment
ti~all0w the full range of heart rates to be used.
LimitatiOns of the method ~

Inadequate sensing of the:Q-T interval can arise in a number0f ways=First, the
T wave may not l~eadequately sensed; The electrode polarization ~ may "be
excessive or the lead contact maydegrade. Second, the change in"theQ=T interval
can-be affected by calcium levels and ischemia ~. ’Class III and Class IA
anti~thmia drugs affect Q~,T length-and Shortening and may affect the
response. Third, the patient may: have Q-TinterVal which for whatever ~ reason,
does not vary sufficiently in response to changes in the catecholamine levels as
~
mentioned in Katritsis and Carom(1992).
Overall, the methodis simple, reliable, and sufficient to provide a good rate
pefft~ance. The hardw/tre~e~uired to iniplement the methodconsists hiostly of
the s~nse"amplifier~and standardEGMfilter: A~micrtproceSsor makes ~e stir
tramm~and nonhnear aspects Of the algorithm relatwely easy to ~mplement. T-
waye sensing may also be helpful ~n determ~mngwhen to apply burst puls st
iht~t tachyc~dia.
16.3.2 Ventricular depolarization,gradient
Zhe ventrieular depolarization gradient (VDG)is the area ’under the QRS
complex.. It ~has been observed that. in normal heart operation, ~ the ventricul~
depolarization gradient stays fairly constant: During, exercise, the ventricular
depolarization gradient decreases. Whenthe pacing rate is ~increased, the VDG
38O DESIGN OF CARDIAC PACEMAKERS
increases. The rate-adaptive pacing algorithm uses the ventricular depolarization

gradient as a negative feedback signal and changes the pacing rate in an effort to
keep it constant, The VDGrespondS quickly to the onset of exercise (Lau, 1992).
One problem with the method is that passive tilting of the body produces a
paradoxical change in the VDGleading to an inappropriate rate response. The
proportionality of the VDGto exercise tends also to be lost in just a few minutes
after the onset of exercise (Lau, 1992).
After the pacing pulse is applied, the pacing tip of the electrode is shorted to
the case for 10 ms so that the polarization of the electrode ;is minimized: The
sensing is then enabled,, It seemsthat a rate-adaptive algorithm using~ this signal
Wouldbe susceptible tO noise and to degradation of the electrode-myocardium
interface over time, Since the area under the QRS-is the detected signal,
degradation of the detected EGMamplitude affects the paced rate and thus the
performance of the system.
16.4 IMPEDANCE-BASEDI MEASUREMENT SYSTEMS
The contractility of the heart can be inferred, from a number Of measurable

parameters including the stroke volume, ejection fraction,~,and pre-ejection
period. A convenient meansfor the pacemakerto sense these signals is to use th6
standard pacing lead and to sense the intra~ardiac impedance. Changes in the
impedancecan be seen to correlate to the volumeof blood in the heart as well as
changes in theheart’s geometry. , ~:~
Theimpedance is measured by applying a controlled current to ,a setof
electrodes andsensing theresulting voltage. Theelectrodesize_and position arc
chosen to maximize thespecificity of theimpedance signal to changes in blood
volume. Motionandventilation effectsalsoneedto.beminimized as wellas
electricaleffects from,theQ.RS:complcx,
.thepacingsignal,andpoI~~ariza~on atthe
electrode-myocardium interface.Thecurrcm forsensing is usually chosen to bc
an ac ~signal,of moderatefrequency (i-100kHz)so as to minimize thee!ectrodc
polarization. Thecurrent injectionfrequencyshouldalsobc distinct in,frequency
content fromtheEGMsignal..This :simplifiesfiltering,andprevents thecurrent
frominterfering withthe~ensing oftheEGM.signa!,.~
16.4.1 Electrodes f0i" curr~nt iiijection ~.
The electrode design issues ~ complex and there ,have~ been numerous
arrangements proposal for achi~ving~ good leveI of sensing. Unipola~,i~ip01ar,
trtpol~r, quadr~polar~ and multiple ~onopolar leads have been mentioned in the
~t~frits.
literature and it ~ee~s that With ~ppropria~e SignalP~essing, ~chhas its
The standard leadg are unipolar or bipolar. If the pacemaker is used as a
replacement then it is undesirable to removean already implanted lead. The feel
of the lead also affects the probability that the lead will be used. Somephysicians
maynot want to use a lead that has morewires init becaus~itis less’flexible than
they are accustomedto.
-~ As an example of two arrangements, Figure 16.6 shows two conftgurations.
¯ he first~arrangemerntUseS-tworing electrodes for current injection ~and a third
electrode at the tip of the lead for pacing. The second lead uses two electrodes in
a split ring arrangementfor current injection and a third tip electrode for pacing.
RATE ~ADAPTATION BY EGM AND IMPEDANCE 381
The separate use of current injection electrodes avoids the effect of electrode
polarization at the pacing electrode.
¸26
Figu~16.6. Twolead,arr.angements for impedance sensing.Theti~st arrangement uses tworing

~ctrodesfor c,u,~,entinjectionand,a,third elec~gde~at the ~ip of the leadfor pacing.Thesecond
l~i~l usestwbel~etr0de~in a split ring" anangenithtfqi~cur~ntinjectionandvoltagesensinganda
~ktl tip electrodefor !pacing.The~useof separat~~lectrades:for~bacingandturrent injection
r~uCesthe effect of electrode polarization on the impedancemeasurement. From’Sale and
Pederson (1993).
Whenthe current flow paths are considered, the split ring arrangement turns
out to have a lower sensitivity. Its sensitivity to impedancechanges drops off as
the ..cosine of the angle from the ,split between ~tlae electrodes. The electrode
position thenplays a large role ~in the quality of the impedancesignal, If,the split
line is , close to the heart,wall, then motionartifacts may.playan excessively large
role ~in the detected sigual.
, ;A monoP0!ararrangement uses the pacemaker case as a~remrrt point,,Geddes
et a~.~,:O991) found ~that bipolar !eads~d not produce a go~ current ~stribution.
~,. ~ ~urrent tended to,hug, to the ca~eter and not intercept the heart wall,
Increasing the spacing between the rings didnot improve, the-signal greatly. With
the bipolar!arrangement, if one of the,e!ec~odes .came, in contact with the heart
wall, ~e relationship of impedance change tostroke volume was altered. Geddes
et aLproposed ~that the monopolar arrangement ~produeed a radial flow. of
ct!~eut~ with a correspondingly large path through the blood ,of the ,heart and a
goodsignal. Figure 16.7 showsthe,situation.
In. general it would seem desirable to have the electrode far from the heart
wall~ ~sqm~what centered in the ventricIe chamber, however, due .to the irregular
~ati~ Of a damagedheart, the ideal electrode position-varies from-patie~it to
p~en~,¯ Geddes proposed to have multiple monopolar electrodes on the catheter
and use~.the remote programmer~andan internal.: multiple~Xer~.to ~choose the
electrode which best reflected the stroke volume, for the p~eular-patient. The
numberof wires needed wouldseem~tocause the lead to be: excessively stiff..
¯ "i il .
Figure16.7 Comparison ofthe current flow path for bipolar, eleetrode~:(l~ft) andmonopolar
electrode(right)eonfigurafions.Thecurrentin the bipolar arrangement hug~~e :.caOeter. The
monopolar lead causescurrenttoflowradially throughthe bloodof the:~art ~6~.rem0felylocated
sink (the paeemakdrcase). FromGeddes et al. (1991) ~~’
................
:’~
Even with the monopolar dectrode configuration, Geddeset al. (1991) noted
that the ’relationship between stroke volume and changes in itripedance is not
hnearover a very wide range of stroke volumes. However, this does not seem to
be a problem for rate adaptation since the goal of most schemes is to .hold the
stroke volume unchangedby changing the hedrt rate.
16.4.2 Geometric modeling of the stroke-volume-to’impedance

relation
Attempts have been made tO come up with models for the observed changes in
impedance with the beating of the hem., The .heart Chamberhas been modeled as
a cylinder, a stackof different diameter disks and~ a crescent shaped volumeall
with little success in accurately predicting the time variations in impedance
observed: There are a number of reasoris why model attempts have been
unsuccessful. First,, the current"flow ~p~hs canbe. affected by the chambers
adjacent to the right ventricle. S~ond,title’heart tissue and blood~aredifferent in
bulk resistivity but-only by a~relativ~ly smallfact0r, with blood being
approximately three times more Conductive than heart wall~tissue. This means
that although we wish~;to detectonly blood Volumec~ges in the heart, changes
in the heart, wall position relative to the electrode can~havea significant affect on
the impedance. Third, and most troublesome’ for-modeling; is th/at the
conductivity of blood is highly anisotropic during flow due to the shape of blood
cells, It has been observed that the blood resistivity decreases with flowdueto the
alignment of blood cells (Ovsyshcher and Furman, 1993). ~This would appear
be asignificant complication in any.detailed modeling attempt.
The creation of an accurate geometric model for~the relation of impedance
to stroke volume-is not critical to,the uge ~f intracardiac impedance’ for rate~
adaptive pacemakers~, Numerousalgorithms have beeh~ foundthat: p,errnif the
available impedanceinformation to be successfully Osedfor rate adaptation:
Impedancevariation caused by ventricle geometry
100 ms after 300 ms after

stimulus stimulus
smallerfraction of myocardium larger fraction of myocardium

low impedance high impedance
Figure16.8 Illustration of the impedancevariation Causedby changesin"ventricle geometry..
Theimpedancesignal froma unipolarpacingtip electrodeisprimarilyinfluencedbychangesin the
wallgeometryof the ventriclein the regionverynearthe pacingtip.(Courtesy
of M.Schaldach).
16.4.30 Algorithms for rate adaptatign.

~e ~mpedanc~signal can .be used to e~/~mate stroke vblfime~ ejection fraction,
peak to peak impedance Variation and pre-ejection period. The rate adaptation
algorithm determines how the paced rate should respond to changes in each of
these parameters. The rate response of a pacemaker should be:~uick:at onset~
p~portional to workload, quick to recover whenexercise ends and se.nsitive to
d~i~ex6rcise demandssuch as 6m~)tional stress. If thd r~te response-is :~xce~sive,
thepatient .may "suffer angina. If the rate response is inadequate, e~rclge
~
6fidt~rancewill be, diminish6& ’ "
i6.4,4 Relation of stroke volume to the sympathetic tone
~e stroke Volume(SV) is the’volhm~ Of blood ejected"fr0m the left ~,~ntri~le

each beat. Stroke volume is the difference between tlie left ventricle blood’
q6ium~ befor~ contraction (End Diastolic Volume(EDV)) and after contraStion
(~d!’Sysiolic :Volume (ESV))." St/oke Vol~,~e is increas6d by two. fa~tOrs:
ihcr6ase~l ’~ontra~tility andthe Frank-Starlil~g mechitni~m. The ’increase in
C,b~tra&iiityi~cteas~sthe SVand provides ~0od indication Of sympathetic tone
d~ng e~6r6i~:. Th~Frank-Starling mechatltsm Causes the SV to increase.~When
the preload (EDV) increases and complicates th~ relationship of SV
sympathetic tone.
During exercise, a healthy heart will keep its stroke-~Olumenearly constant
by varying the heart rate to achieve the correct cardiac output. If the heart rate is
l~ld eonstam’during exercise, the~SV can inereaseby, a, factor of two.in an
a~tempt ~toincrease car~ac output: Thas:~ SV man mdlCauonof workload an can
be used,td adapt the paced heart rate,by increasing the heart rate in response to an
increase in~the SV. "lrhere is an inverse finear relationship between.stroke volume
and the paced heart rate in a resting individual over a moderate range of heart
rates. Fortunately, the effect provides negative feedback rather than positive
feedback as was the case for the Q-T interval.
Rate determination
The rate-adaptive algorithm has to determine, how to respond to the stroke
volumesignal. In response to exercise, an increase in SVindicates the heart rate
should increase so that the SVis returned .to its nominalvalue. The nominalvalue
can be a fixed value or just a long term average of the past measured values of
SV. The rate can be proportional to the error or it can integrate the error
between the SVsetpoint and the measured SVas shownin Saloet al. (1993). Salo
proposed that the rate be determined in response to the derivative of the SV. If
the SV decreased, the paced heart rate should be decreased. The proposed time
constant for the differentiator was 10 rain so that after 30 rain, the rate would
have settled back downto its resting rate.
The stroke volume paradox

The SV responds paradoxically to posture changes due to the Frank-Starling
mechanism. If a person stands up, the venous return of blood to the heart
decreases causing the SV to decrease. A decrease in stroke volume signals the
pacemaker to drop its rate which is opposite to what should occur. This is the
stroke volume paradox. The problem has been overcome by combining SV with
other parameters extracted from the impedance waveform. One such solution is
to computethe ejection fraction as described in the next section.
Figure 16.9 shows the change in stroke volume with exercise and its
relatively quick recovery after the cessation of exercise. The SVreturns to its
nominal level approximately 30 s after exercise has ceased.
16.4.5 Ejection fraction
Chirife (1992) proposed using the ejection fraction (EF) as the rate-controlling
parameter for the pacemaker. Ejection fraction is the SV divided by the End
Diastolic Volume.Figure 16.9 showsthat the ejection fraction tracks the SVquite
closely. The ejection fraction has an advantage in that preload effects are taken in
account in its calculation. Stroke volumeis somewhatlacking in specificity for
metabolic demandin part due to preload effe~tS~ Ventilation, posture~ and heart
rate can affect SV. At high heart rates, the EndDiastolic Volumefalls due to the
reducedtime available for filling and SVcorrespo~n"dmglyfalls.
Figure 16.10 shows the effect of reduced filling at high heart rates on the
stroke volume whena resting heart has its paced rate increased. The drop in SV
closely tracks the dropi n EDV.The ejection fraction howeverremainsrelatively
constant and thus is not coupled to the paced rate. This decoupling makes the
design of the control algorithm simpler, as feedback between the pacing rate and
the sensed parameter is minimal.
16.4.6 Peak derivative ,of impedance
The stroke volume paradox has also been solved by using additional information
from the intracardiac impedance signal. Olive et al. (1988) used the peak of the
first derivative of the impedance(dZIdt)p as .a rate-correcting factor. The signal
(dZIdt)p was found to be proportional to contractility and~ independent of the
RATE-ADAPTATION BY EGM AND~IMPEDANCE 385
heart rate. The deviations in (dZ/dt)p are directly proportional to the level of
exercise. Therate response algorithm sets the pacing rate so that it is increased in
direct proportion to the difference between (dZIdt)p at rest and the current
measuredvalue of (dZtdt)p.
10
o. -10
lot 120 140 160 180

.... "riMe
(s)
Figure16.9 Relative RightVentricularVoltimesduringexerciseas measured by changesin the
intracardiacimpedance
usinga bipolarpacinglead. Theresponseof differentheart volumes during
exerciseare shown.TheSVrespondsquicklywithexerciseandit is relatively quickin returningto
:l~pronOrmal
~im~telylevel after
30 S. Thethe eess.ation of exercise.
ejec~i~nfracti0n TheSVSV
(EF) traekSt~e returns
quite to its nominal
closely. Fromlevel after
Chirif~,R,
0~g~D. F~and Sal~ar; A~(1993. Feasibility of me~iJi-ingrelative right. Ventrictii~ volumes
~ ejection fraction with implantablerhythmcontrol d~vices,eACe,16i 1673,1683.
Posmral cli~ges can be compensated for by using SV information, with

(dZIdt)p information. The S_V responds to both posture and metabolic demands
where (dZ/dt)p responds only to metabolic demand. Thus if SVdecreases without
a corresponding change in (dZIdt)p,"thenwe:ican assume the persoa has stood up
and thus the heart rate is temporarily raised for about a minute to prevent any
~
li~eadedneSs:
16.;4.7 Pre,ejectio’n period
The pre~ejection period (PEP) is yet another pararlieter used in rate-adaptive

pacemakerS. The pre-ejection, period is the time from the onkef of el6etrical
activity in the ventricle-(R wave)’ ~,the time~ whenthe-valves open and blood is
ejected into the arteries, "l-laePEP;Changesin response to the contractility of~the
hea~!,and ~o an increase~ in end diast~lie,-volttme: ~ The derivativeof intracardiac
good indication of:volUmechange, so that~the Start of theejeetion
pe~of the~first d6rivative of the impedances
: ~PEP~i~~ affexeelle~at indicati6n’:0fworldoad ,as it shortens ,in,~t ~pmporfion
to :workload. ,However, the relationship vadi~s from patient to patient and’
requires exercise training to establiSh~the appropriate rate response. The PEPis
independent of pacing rate. Lau (1992) reported that the PEPhas been shown
behave paradoxically upon assuming a standing posture. While the pre-ejection
interval has been shownto be. a good indication of heart contractility, Grubbet
al. (1993) proposed that pre-ejection period might also shorten due to reduced
filling arising from a drop in venous pressure.
WI PACING
.11 .... .
~4 , i I I 1 ~170
0 10 20 30 40 50 60 70
-"- TIME(sec)
Figure16.10Theeffect of forcedchangegin the pacingrate on a re~ting individual’s blood

voiume parameters.At30 secondsint0,’the test,:the pacingrate iS"forcedto increase,.thereduced
fiili~g~(en~ldiastolic volume El)V)can ~ observedat ~ghheart, rates=The dropin stroke volume
SVcloselytracks-thedropin EDV.Theejectionfraction however remainsrelatively Constantand
thus is not coupledto the pacedrate. FromChirife, R., Ortega,D. F., andSalazar, A. 1993.
Feasibilityof measuring relative right ventricularvolumesand~jectionfraction withimplantable
~
rhythmcontrol devices; PACE,16: 1673-:1683., :~, ~, -
16.4.8 Ventricular lnotropie parame .er
Sehaldach (1992) defined a useful rate-adaptation parameter derived from the

intracardiac impedance waveformuthe ventricular inotropic parameter (VIP).
The VIP indicates either rest or exercise in smoothly v~i~g, fa~ ~hign and is
derived by examining the slope of the impedance w~vefo~n~ ’ ~rbuhd the time
whenboth the aortic and pulmonaryv, alves ~are opening. The VIP indicates the
ino~opi¢state~ of the heart~,].e, the strength of contraction, ,~and thus provides an
indication of the sympathetic tone. The use of the V!Pprovides a rate-adaptation
signal that has less patient to patient variance than the PEPalgorithm.
The intracardiac impedance is meas~,ed over, a 24,ms ,window. The slope of
the ,impedanceover,,thi~,, .time ,is ~observed,~. This time windowor -Region ~ Of
Interest (ROI)~Spgsjtioned 100~msto~ 300~ras~Mterlthepacing S "~timulusis~pplied.,
Th~ placement ~0f~ the ROIvaries ,from patie~ntto patientand is chosewso~asto
coincide with the time inte~al where there is a large difference in the,impedance
slope between periods of rest and peri~ods of exercise..- .
The slope of the impedance over the region of in’terest is denoted as the
Regional effective slope Quantity (RQ). The RQis the regional slope of the
impedance over the ROI. The RQis different during exercise than it is during
rest. The RQchanges in response to mental stress the same way it changes with
physical stress. The change in RQis used to smoothlyadapt the pacing rate.
Impedance
(rel. counts)
150
. resting
t.=d .......... ,of interest,
"°" "~ ""i + ....

~40 _ ~.’.’;~ ...
120
110
~’ ~ Qexercis~’ "’
leO
104 120 136 152 168 184 216 232 248 264 280
Time frompace (ms) ....
Figure,16,1l~:’intracardiac illustratingth6 how

impedancelwaveforms~’~ the regionalslope’quantity
(RQ)~ ~i* ~¢ inotropie state ~.~,~h~impedanceneed only be m.,easured i~ a g~Ml24-ms
region’6f intbres~JNotethat in tile regi6n6f interest, the slope0~f’theintraca~dia~impedance
eh~ng~jn proprtiontodie Contractilityof the,hem.(Courtesyof M~Schaldach).
:3chaldh~l{’, ft al. (1992) give a simple formula used to calculate the paced
heart ~ate using ;th~ changein slope of the intracardiac impedancein a particular
region of interest. Thestimulated heart rate is
¯
..... ¯ , -RQacmal - RQrest
HeartRate = BaseRate + R(~max - RQrest X~MaxRate L BaseRate) (16.,6)
WhereRQacmalis the measured regional effective slope; RQrest° ig the regional

and
16.5 CIRCUIT IMPLEMENTATIONS
16.5.1 Measurement of impedance
Figure 16.12 shows a typical impedance measuring circuit which consists of an

oscillator supplying a 1-100-kHzsignal to a controlled current source with high
output impedance. The current source pushes a current of 1-100/zA through the
heart and th~ heart’s time-varying imiJe~c~ produces a V.0,1tage. ~ The ~01tage is
then amplified by a high-gain tuned amplifier~ rl’he amplifier s output is iiigh-pass
or bandpass
filteredsothat the carrierfrequency,
elf the currentsource,is passed
on. The carrier signal is then removed.in, a process of demodulation. The
demodulation may be a synchronous demodulator which acts as a narrowband
filter, or as simple as a rectifier and a low-pass filter. After demodulation, the
signal that remains is the intracai?diac impedance. The impedancesignal is then
processed to produce the desired paramet¢(::iSV, EF, PEP, VIP, or (dZIdt)
p.
Figure 16.12 Measuringcircuit for intrac~diae impedance.Anac ~onstantcurrent source

appliesa measuring
currentto the heartvia the intraeardiaecatheter.Atunedamplifier,filter, and
demodulatorfollow. Theresulting signal is the time-varyingintracardiac impedance whichis
processedto providea rate-adaptivesignal to the~pacemaker’s pulsegenerator.FromSaloet al.
(1993).
16.5.2 System design criteria
Design specifications ~for include energy

with the
1 benefit of
myocardiuminterface.
To illustrate the signal levels involved, assumethe electrode and cardiac

impedancetotals 500 fL Thenthe total intracardiac voltage is only 5 mV,for a
10-/~Acurrent. Thevoltage variations due to changesin stroke volumeare only a
portion of this voltage. Thelow .level of this signal in comparisonto the pacing
and EGM voltages makesdesigning the impedancemeasuringsystem a challenge.
To improvethe sensitivity and noise immunity,the current amplitudecould
be raised. The voltage signal wouldthen be larger, but the extra current drawn
wouldreduce the battery life. The energy~ budget for the pacemakeris very
limited, the total battery current is usually.held to under 20/~Afor the entire
system. To conserve power, manyimpedance-basedalgorithms have the current
source turned off most of ithe time and be impedanceis only sampled. The
samplingmayoccur in short predeterminedinte~al s of interest such as used by
Schaldach (1992), r t he i mpedance amy be s ~pled i n r egular, e qually s paced
time intervals.
16.5.3 Demodulationand filtering
Noise immunityand sensitivity can be improved %yusing narrowbandsignal

techniques. In this mannerthe effect of amplifier thermal noise as well as
external noise cab be minimized.Typically, a narrowb~/nd~high-frequehc~’carrier
signal is usedfor.the current sourceto alloweasy filtering ~and.distinguishing.of
SVinformation from EGM and interference signals~ Theresulting.voltage, which
~
contains the impedance"information, is also narrowband.,.A synchronous
demodulatoris then used tO bandpassfilter the sensed vo!tag~~andreifi0~e most
undesiredinterference. If a stan~lard bandpas~tilteris ~us~don the a~nplified
voltage, the demodulationcan also be performedby envelopedetection consisting
of a rectifier anda low-passfilter.
Figure 16.13 illustrates howthe demodulationof the sensed ac voltage
becomesthe waveformfor detecting stroke volumerand ejectibn fradion changes.
The voltage is amplitude modulated by the changing heart impeda~nce. The
envelope Of the VoltageContainsthe, inf-ormatign about the s~oke Volume~ The
impedance
vO!.u .me.~signal
Toseparate
contains
out the
information
signalofabout
interest,
ventilation,
~th~frequency
~ motion;
bandOf
and " Can
~nterest.
evenstroke
be filtered out and passedon to the signal-processingcircuits. Motionartifacts;

WhiCh couldlead to rapid changesin:pacing ra.te,~can be: .mini.~’.mizedby aver~g
over several beats (Pickett and. Buell, 1993). ~Thestroktvo!hmec~ also suff~
from beat-torbeat variability during VVIpacingas a result oft~e variable
preioad effect’comingfrom the atria (Dritsas et aL, 1993).
¯ A filter.which separates venfilati0h sigiialg from stroke volum~signals’is
moreof a challenge. At rest, the heart rate’can be 60 beats/rain, while at high
rates of exercise the ventilation rate can be inthe sam~frequencyrange, but the
he~ rate’will be two to three times as high; Hauck(1991), p~tpofi~d ysing
filter with a comerfrequencythat changeswi~ the heart ~ate. Afilter with this
time variation can easily be implemented with a SWitched capacitor falter b~ using
a ~ignals derived from the heart rate to c~tige~’the Clockingfrequency of the
SwitChed capacitors. ~ ’ ~ ~~ ...... ,~ "
’ The~ ~ne~~ amplifier’s c0mmon2mode~rejeetion ratio should be~high to
attenuate coupling of the EGMsignal tO &e impedance~ me~u~,emenL Using
separate pacing ~d impedance-sen~ing electrodes will helpto eliminat~~ electrod~
polarizationeffects dueto the pacingpulse.
ONSETOF I R.V.
SYSTOLE
(ENO-DI~..~
!IASTOLE
! CARRIER
DIASTOLIC
LEVEL(DL) ""~
IEFffi (OL-SL)
~~ SYSTOUC
LE~U(SL)
Figure16.13Illustration of demodulationfor detecting stroke volumeandejection fractioh

changes.Theappliedconstantcurrentproducesa
voltage~tcrossthe heart. Thevoltageis amplitude
mqdu!ated by-thechangingheart impedance.
Theenvelopeof the voltagecontainsthe information
aboutthe strokevolume.
~Ahigh-frcqaeacy.carrier
is usedto allow.¢~yfiltering anddistinguishing
Ot s VinformationfromEGM andifit~ffe/~ncesignals, FromChid~e.(1992). " _
16.5.4 ,Design of the current Sourcf . ~ ~ _
The design parameters of the.cu~nt ~ource are its output impedance and voltage
compliance range~ Volt,age ComplianCeis the range of vOltages over which the
cu~r~nt sourc~ is able’to "p~0Vi~e’ a’~onstant current. The ~,~lta~e compliance
range is Usual!y !ess than ~ supply Voltage and Can be .muchless than the supply
voltage dep~t~ding on the~cifcuit"topo~ogy agd C0mpohent .valUes used to
im~l~nerlt ~e current source. ~n &e voi~age’ comliahce range.is exceeded,
the 6~rreilt ini~o the ibad become~dncontrolled and U~own.
The otltput impedance’ refleet~ the q~Jality of~’~he current s~urce. If the
current so~ce’s output current doffhot Change wi~i the vol,tage ~cross its
terminals, then the current sourc~ is said" to have infinit~ output impedance. A
finite output imp,ed ,~,cf provides an undesired coupling between ~the electrode
voltage and the cu~bnt ~lelivered :to the heart. Since ~e current is no .longer
preciseI3 ..... re~ent accuracy is reduced. ’
..... currdn(is06rce s accuracy can be
of the
affects
ofthe
output
RATE ADAPTATION BY EGM~ AND IMPEDANCE 391
Amplifier
source Zo Vo ~
Output Lumped
impedance impedance of
of current lead, electrode,
source and heart
Figure 16.14 Schematicdiagramof the impedance-measuring system showingthe current

sourceoutput impedance,the lumpedload impedance, andthe senseamplifier. Theload seen by
the currentsourceincludesthe impedanceof the lead, electrodeinterface, andheart tissue. The
voltagecompliance
rangemustbe sufficientlylargeto allowfor all voltagesseenonthe electrode.
Similarly,the outputimpedance of the current sourcemustbe large in comparison to the total
lumped
loadimpedance.
? , IL = Is - ~o (16.7)
The expression can be simplified by eliminating Vo from ~tbe equation. The

a~CcuracyOf the current s0hrce is dependent on howclose t L is to Is. BYtaking
the ratio of IL to Isourc¢ ~d compmngit tounity, w~c~ get a fed for ~¢
accuracy and what p~am~ters effect it. ~ resulting ratio of cu~ents is a
function of bo~ ~e ou~ut impe~ce ~d ~e load im~d~ce.
Io Zo
-~ (16.8)
~ =ZL + Zo
To show more ctearly the effect of the relativesize of the output impedance to
the load impedance, we use the ratio Of Zo to ZL~Toaehievea;eertain number Of
bitsof aceuracy, the ratio of Zo to ZLmust be
Z°
i 2Nbit~ ~ .~ (16.9)
ZL I=-1 ÷
For example, in a 8-bit precise system, :the ratio-of :output to ~ load.imPe~ce

MuSt begreaferthaa 256, th~ui~if ZL isS00 f~;Zo must be gi!eater, th~ 128
Tl~e Wo~hed~efo~ fhis rafi~ ~ is’when the load i~ce is it~fii~hds~X~ted
~alu~~ Th6t~,piCal reqtfired prdcision of the imti~ce signal’ d6~eeted’i~ 0iiiy
digital bits, but this: figure is for all sources of ~6rror, not just the Current hburee
otitput impedance.
16.5.5 Circuits for the current source
The circuits used for current sources are commonlybased on voltage-to-current

converters since the oscillator signal is~typically a voltage. Figure 16.15 showsa
Current source which works for floating (nongrounded) loads. The voltage signal
for the ac current is input to capacitor Cac which removes any dc bias from the
voltage. The inverting input of the op ampis a virtual grounddue to the action of
negative feedback. The current that flows through the resistor Rg also flows
through the load impedance(the heart).
Cac Rg Cdcblock
I
Rbias
Vin
Figure 16.15 Acontrolled current sourcewith a floating (nongrounded)load. Thecurrent

sourceis formedfroma voltage-to-currentconverterusingthe invertingnodeof an op amp.The
voltagesignal for the ac current is input to capacitorCacwhichremovesanydc bias fromthe
voltage. Theinverting input of the op ampis a virtual grounddueto the action of negative
feedback.Thecurrent that flowsthroughthe resistor R~also flowsthroughthe load impedance
(the’ heart). Capacitor
Cdcblock iS putin series withthe lieart to p~ve.ntde currentsfromflowing
throughthe heartandelectrodeinterface.Theloadfloats ~lative~t0 ground,so this circuit will not
workfor a imipolarlead"arrangement. Here,the current "gourc~~i~ctrodes are distinct fromthe
pacingelectrodes.Adapted fromSaloet al. (1993).
A relatively large capacitor, Cdc. bloek,~is put in series with the heart to
prevent de currents from flowing through the heart and electrode interface. A
high valued resistance, Rbias, is used to provide a path for the small de input bias
current of the amplifier and helps retain negative feedback at de.
The current source load floats relative to ground, so this circuit will not
work for a unipolar lead arrangement. In this application, the current source
electrodes are distinct fromthe pa,cing electrodes,
The output impedance of this current source is quite highand the voltage
compliance is also good. However, the full load current must flow through the
resistor Rg and thus there are losses in this resistor. This resistor also sets the
voltage-to-current gain ratio of the current source, so we can not make it
arbitrarily small as the voltage commandsignal would also have to be scaled
down.and resolution would becomea proble~m.
Another current source cire~t which can be~JSed for groundedioads uses
two instrumentationampliflers a n~ d a current sens~g resistor as shownin Figure
16.16., The arnpi~fier with gain A1 provides the ioad’~ .~. e~nt; all of whichp~ses
through resistorR. The amplifier with gain A2 senses and’amplifies the.voltage
drop across R and thus measures the load current that is being produced. By
having a large gain, A2, on the feedback amplifier, .,the voltage drop across R is
magnified.
The transfer function for the voltage-tO-current converter is
Io = (16.10)
E2
E1
Figure16.16A controlled Currentsourcewith a groundedload. Thecurrent.sourceis fomied

f~ma voltageto Currentconvet~erusingir~tmmentation amplifiers. All’theload,.~urrentflows
throughresistor R. ,This arrangement is suitable, fora un~pdlarlead current souse. Here,the
currentsourceele~trbdesare distinct fromthe pacingelectrodes.Adapted fromKiesh(1992).
The advantage of the circuit is that R can be made very small so that the
losses in it are minimal~The voltage-to-current conversion ratiois controlled by
the an~lifier gains instead of just the resistance value.
The output impedanceof this circuit is very~ high and the compliance range
can be controlled by~be second amplifier. The Circuit requires that the common
moderejection ratio of the amplifier A2 be good and that the sense and return
sense input on amplifier A 1 are of high input impedance and have good common
moderejection, since the electrode voltage is seen as a commonmodesignal to
these inputs.
16.6 PERFORMANCE~ EVALUATION
Rate response ,curves for impedance-based~(PEP and VIP) and Q-T interval-
based pacemak~ are compared. Figure 16.17shows the rate.~s~nse of the Q-
T interval-based pacethaker has a long iag (120 s) in its ra~decay after the
cessation of exercise, The ideal sin~ xate is not shownin Figure 16A7, so. Be
~0fiallty of rate response can t~ be compared to .that of the PEP-based
pacemaker~ In ~FigurelO.18, the rate response of a PEP-based-pacemaker is
comparedtO sinus-~rate~For the PEP-based.SYstem,rat e :i~rease s rapidly ~ith
moderate onset delay, of approximately 10 s. The" rate doceleration is less,
occurring approximately~45 s after the cessation of exercise. .
Figure 16.19 Showsthat a pacemakerwhich detects tlae symp~tth6tic tone
respond to emotional demandsfor an increase in heart rate. The patient wasgiven
a~psyeho!0gLcMly~stressful color word test. During the test, differem cards
containing ~e name~ofa color (e.g. green) written in the letters of another color
(e,g.~ blue) are shown.to the patient whomust respond quickly with the color:of
the letters.
394 DESIGN OF CARDIAC PACEMAKERS~
Figure 16.17Pacingrate responseduringexercise testing (modifiedBruceprotocol) for

number of patients usinga Q-Tinterval basedrate-adaptivepacemaker (VitratronModelTX).The
rate returnsto ,restinglevels in 2-3 min.Notethat after the peakrate ! ,,msafter the cessationof
exercisein .,ohe patient dueto a poorslopesettigg. Thedashedlinere_lJ ~en~tl~ rate responsefor
the Sarlle patient after the slope was retuned.~m Bloo~eld, P.;M~..uea~ey,D.., Keer,F., and
Fananapazir,’L.1989.Long-term follOw-up~f patientswiththeQ:-Trate,:adaptix~e pacemaker,
PACE, 12: 111-114. .... ~"
PEP
HR-
min-1
3- Exercise .’6 -. Recovery (~ ~- ~to ~ ~
Figure16.18COmparison of the measured PEPSodthe normalsinus rate for ~ variety of

~onditions.
TI~~ i-ate (~0mmand derivedfromthe PEP ~lo~¢ly;ttacldsthe desima siaus’r~te.The
delayin theratechange iss~lduringtheonsetof exercise, bt~t thedelayin the~fallo£.heart
rate
duringrecoveryis relatively.long.Theproportionality
of respo.ase,isq ,m,’te good,.iFrom
Schaldach,
M.M.1992:ElectrotheraP~ Of the heart. Berlin:’Spfihger-V~da~.
’
16.7 FUTURE OF. CARDIAC SiIGNAL-SE~SING METHODS,
The future of~rate-adaptive pacemakers:’h’¢s in,:extei~siVe~studie~s ~if,~ehuman

body and-heartcontrol System:Much m6re needs to bemtderstoo~! :ab’but,the
relations and’responses ofthe heart rate to the .Condition. ’of the patient.
Improvements in the near term may include using combinations of sensors to
improve the appropriateness of response. Cowell et al. (1993) report that

combining the signals ’from an activity sensor and with a detected Q-T interval
helped reduce the incidence of angin~ in a patient with ischemic h~art disease.
Their study did not achieve a significantly improvedrate response by using dual
sensors versus using just the activity sensor. This maybe due to the algorithm
they used for determining the rate from the sensor signals.
~ It would appear that there is room for improvement in the algorithms used
to determine the heart rate from the multiple sensor signals~ Algorithm
refinements will likely provide the greatest improvementin performance for the
patient’ s quality oflife:. The, use of advanced telemetry features commonin
modern pacemakers will help make the refinement development time shorter and
sh0rter~
130
120
Recovery Recovery Recovery---’~
110
00:00 00~05 .. 90!15 . , 00:20

,+ Time(hours:minutes). - ....
.. ANSControlled DDD:/ FPa¢ing
Psychological
affect on heartrate; Pt:170~,
Figure16.19Illustration of howemotional demandsfor cardiacoutt)u~canbedetectedby
ANScontrolled pacemaker.Thepacemakerused changes in, intr~cardiac imped+~+ ce (VIP
algorithm)
to determine OfM.~ Schaldach~,
the pacingrate. Courtesy ~ ~" : ~ ¯ :~+:..... +.’,
~
16.8 REFERENCES
Bazett,H. ~. 1920.Ananalysisof the time-relationsof electrocardiograms.HEART,7: 353~-370.

BlOomfield,Pi; Maeareavey, D.; ~Keer,F., and Fananapazir,L: 1989.L0ng-termf011ow-up Of
+ patients with the Q-Tr~te-adaptivepacemaker, PACE,12: 111~114.
Cowell,R., Morfis-Thurgood, J., Paul, V., Ilsley, C., and Carom,A. J. 1993;~ Arewebeing
driv6n-by two,sens6rs?:clinical benefits of sbnsotcrosscheeking.
PACE, 16.’-144121~14.
~e,R., Ortegai.D:F.,andSalazar, A,1993. Feasibility of’rrieasuring:~elati#e
rightventficular
volumes andejection fraction withimplantable rhythmcontroldevices.PACE, I6:1673-
Dritsas, A., Joshi, J., Webb,S. B., Athatassopoulos, G.,. Oakley, C. M, and Nihoyannopoulos,
P., 1993. Beat to beat variability in stroke Volumeduring VV!/pacingas predictor of
bemodynamicbenefit from DDDpacing. PACE,16: 1713-1718.
Grubb,B. P.~, Wolfe,D. A., Samoil,D. A. Hahn,H.~, and Elliott, L. 1993. Adaptiverate pacing
controlled by right ventricular pre-ejection interval for severe refractory orthostatic
hypotension. PACE,16: 801-805.
Geddes, L. A. , Fearnot, N. E., and Wessale, J. L.. 1991. Multiple monopolar methodof
measuringstroke volumeof the heart. USpatent 5,058,583.
Hanck,J. A. 1991. Rate adaptivecardiac~pacerincorporatingswitchedcapacitor filter-with cutoff
frequencydeterminedby heart rate. USpatent 5,074,303. -~
Heijer, P. D., Nagelkerk~;D., Pert’ins, E. J., Horstman,E., VanWoersem,R. J., Neiderlag,
W., Jordaens, L., Wilde, P. D., Hameleers, W. B., and Lie,= H,I 1989. Improvediat~
responsive algorithm in Q-Tdriven Pacemakers--evaluati0nof initial;response to exercise.
PACE., 12: 805-811. "’~
Horstmann,E, and Koenn,B, 1990. Temporalrelationship betweenexercise and Q-Tshortening
in patients with Q-T pacemakers. PACE,12: 1080-1084.
Jordaens, L., Bakcers, J., Moerman,E., and Clement, D. ~L. 1990. Catecholarnine levels and
pacing behavior of Q-T~venpacemakers during exe~i~.PACE,13: 603--607.
KatritsiS, D. and Camm,A. J., 1992.~ Adaptive-rate pacemakers. Cardiologyclinics: Cardiac
Pacing, 10:671-688. .
Lau, C. 1992..:’I’he range of sensors ~andalgorithmsused in rate-adaptive cardiac pacing PACE,
15:1177-1211.
Maloney,J. D., Helguera, M. E., and Woscoboinik,L R. 1992. Physiology of rate responsive
pacing Cardiologyclinics: CardiacPacing,10: 619-629,
Klesch, L J. 1992. Precision voltage controlled current source with variable ~ compliance. US
patent 5,153,499.
Olive, A. L., Pederson,B. D., and Salo, R. W.1988. Closedloop control of stimulator utilizing
rate of changeof impedance.USpatent 4,733,667.
Ovsyshcher,I. and Furman,S. 1993. Impedancecardiography for cardiac output estimation in
pacemaker patients: reviewof the literature. PACE,16i i~t13--1422.
Ohte, N., Hashimoto,T.,Narita, H. Takase, R.,Kobayashi,K., Haynao,J., ~and~Fi~jinami,T.
1990. Noninvasive evaluation of left ventricular performancewith a newsystolic time interval:
.the QVpeak, and comparisonwith established systolic time intervals Am.J. Cardiol., 66:
1018-1020.
Pickett~ B. R. and Buell, J. C. 1993. Usefulness of,the impedancecardiogramtO’reflect left
ventricular diastolic function. Am..J.Cardiol., 71: 1099.-~1103
Salo, R: and Pederson, B. D. 1993. Biomedicalmethodfor controlling the ~administration of
therapyto a patient in responseto physio!6gicaldemand.US1~ t, ent 5,190,035
Schaldach,M. M. 1992:Electrotherapyof the heart. Berlin: Spfifi~r-Verlag.
Schaldach,M. and Hutten, H. 1992. i~tr:acardiac :impedanceto determinesympatheticactivity in
rate responsive pacing, PACE,.lS: 1~78-1786 .... ~ .... .~
Schaldach, M. M. 1990~(~ardiac ~e,~r’withphysiologidal c0ti~l, USpatent 4,919,137.
Steinhaus, B. M., Napph61z,T. A:,’ Nol/m,J. A. and Morris; R. A~:, 1993. Minutevolumerate
responsive pacemakeremployingimpedancesensing on a unipolar lead. USpatent 5,201,808
16.9 INSTRUCTIONAL OBJECTIVES~
16.1 Describe three disadvantages of using an impedance-measuringsystem over an activity

sensor.
16.2 Describe one condition under which the Q-Tinterval changes in ~ponseto a factor Other
than sympathetictone and describe the significance of this effect in determiningthe rate-
adaptation slope.
16.3 Describehowthe Q-Tinterval-based pacemakercan self-train its own~lope parameter. If the
Fast Learning Algorithm produced aQ-Tinterval change of 2 ms, what is the value of
coupling factor M7
16.4 Give three reasons whyan impedance-sensingSystemusing asinglepacing :tip electrode for
current inje¢~tion might not.workas well for sensing stroke volumeas a set of monopolar
electrodes.
16.5 Describe howthe Frank--Starling mechanismaffects therate response of a pacemakerusing
Strok~ Volumefor rate adaptatiom.Describehowthis response c0mparesthe response of a
pacemaker using Ejection Fraction for rate,adaptation: . -.~ :-:, ,
16.6 List three factors.that infl~nce the choice,of frequencyused for the ~u,~entsource and list
twofactors that influencethe amplitudeusedfor tlie current source.
Rate Adaptation by Minute Ventilation
John. G. Webster
Rate-adaptive pacemakers measure minute ventilation to adjust the heart rate.

Examples are the METAMV TM Model 1202, ~ METAII Model 1204 TM, META
DDDRModel 1250 TM, andkMETA DDDRModel 125~4 TM (metabolic minute

ventilation) from Teletronics Pacing. Systems and the ’Chorus RMfrom ELA
Medical; Montrouge, France.~Th6 Legend Plus TM SSIR pacemaker from
Medtronic, Inc. measures both minute ventilation and body motion to gain more
information..
17.1 ADVANTAGES AND~DISADVANTAGES OF MINUTE

VENTILATION
Of all,the. S~nsors considered for rate-adaptive pacemakers, minute ventilation

(MV:)provides one,of the best physiologic sensors of hem’rate, Minuteventilation
is the product of ventilatory rate and tidal volume.It is the physiologic variable that
most~closely reflects.the, metabolic demandsof exercise: Resting’ MVis ab’out 6
L/rain. With moderately severe exercise MVincreases to 60 L/min. These changes
in MVaccurately reflect oxygen uptake, which is the,most accurate :measure of
haman:energy expenditure (M0nd,~ 1993). Minute ventilation corresponds almost
linearly with the aerobic oxygen consumption~dudngexercise up to the anaerobic
threshold (approximately 60 to70% of VO2ma~,changes in cardiac output, and
heart rate. Thus by measuring minute ventilation, we are able to use this
information to set the correct heart rate. Thestand.ard bipo!~ lead that is used for
pacing can also be used for measuring electrical impedance~ f/:om which we can
obtain minute ventilation.
yield an output that is most sensitive to changes in the immediatevicinity of the

electrodes wherethe current density is high, rather than in the desired larger area of
the lung between the two electrodes where the current density is low. Twolarge
electrodes can be used to minimizethis problem of sensitivity to changes near the
electrodes because the current density is low everywhere.
Pacemakerscompromiseby using the three (tripolar) electrodes as shown
Figure 17.1. The pacemaker can serves ~as alarge electrode for both injecting
current and measuring voltage. Injecting current through the ring electrode and
measuring voltage at the tip electrode avoids the sensitivity to changes in
impedancethat wouldoccur by using a single small electrode.
Lead
can
Heaff
Inject
current
Measure
~ectrode
voltage
electrode
Figure17.1 Thepacemaker can is large and serves to both inject current andmeasurevoltage
withoutemphasizinglocal sensitivity: The:ringelectrode~itrjdcts currentandthe tip electrode
measuresvoltage, whichalso avoidsemphasizing local sensitivity. .
In order to avoid undesirable stimulation of cardiac cells, we choose current

having very narrow pulse widths of 7-30 #s and 1 mA,at 20:Hz. ,This permits
measurementofimpedance,at an average current drain of 1-3 ~ ~/zA, whichdoes not
decrease battery life substantially .......
These electrodes are also used for sensing and, s "timulatingthe heart. Figure
17.2 shows, Switches that connect to the impedance-measu~fingcircuit only when
the sense amplifier and pulse, generator are, not,connected (Nappholz,1990).
The measured impedance is ablout 10OfL Change.in impedance caused by
ventilation is about 1 ~. Todetect~ small:changesin.minute ventilation, the circuit
mustdistinguishchangesof 0.06 I2 (Nappholz)etal,, ~1995).,.......
. . ,’~." :. ~ ,’~
17~ SIGNAL PROCESSING
For Teletronics pacemakers, after determining the impedancefrom the samples, the
signal is filtered for information,~ro~ 0,!-1 ~z*, This~ miniroizgs undesirable
in~pedance changes caused by ~strtke~;olume’ch~ges. A zer0]6r6~S~g detector
measuresthe ventilatory rate. If 7 of 10 samples are of one polarity, the signal is
consideredof that pol, ~arity, Eachtime th~ po!a4"itYch ~anges,,it is rec~rde~!and used
to compute the ~’~ntilatory rate VR, assh(~wninFigureAT~3~ ~ i ’~, .
Tile impedlahee~ signal is also rectified a~d filtered to ~yie!d"a Signal
propoMOnal io tidal ~olu~ne: ~s i~ multipliedbY Ve~til!ttory~iiate ~i ~eld m~nute
Ventilation (MV). The resting MVdtfin~ ~e lo~er ~ pacing rate. B~cause the
impedance may dd’ft with~, the rtS~gMVis dttem~ned b~/a long-’term (1 h~
averager. The MVis determined by a short-term. (36’ s) averager. The long-term
RATE A;~DAPTATION BY MINUTE VENTILATION 399
resting MVis subtracted from the short-term measured MVto yield thechange in
MV,AMV.This algorithm works.correctly if the patient has been resting for 1 h,
then begins exercise. However,if the patient continues exercising for 1 h, the long-
term average creeps up to the short-term average and AMV goes to zero, whereas it
should stay high. To prevent this problem, any time that impedance change
exceeds 50%of its maximalvalue within 35 s, it locks the long-term average so it
doesn’t creep up.
TO SWITCHES
Figure17.2 When the lowerpair of switchesis closed, the pacemaker can sense electrograms
andstimulate the heart. Whenthe upperpair of switchesis closed, the pacemakercan measure
impedance
betweenthe tip andthe case (Nappholz,1990).
,~rI I ..
l i ’: -l’ ~ Target
~ ~,. : hei~t
r rate
¯ --
l-termI ~
Head
rate
~i~re17.3 Fromimpedanceweobtain ventilation rate (VR)arid tidal volume(’rv),

~i~l~plyto yield short-termminuteventilation (MY).After subtracting10ng-temiresting MV,
~e,multiplyby a rate-responsefactor to yield the target heart rate, whichheart rate approaches
With,~ slowtimeconstant.
TheAMVisconvertedto heartrateby therate-response

factor
(RRF),which
differs
foreachpatient.
~Tbe~ physician
selectsa lower.,pacing
:rate.
Tbepatient
exercises
~tohisor hersymptomatic
limit
,(usuallypastthe,anaerobic
thrcsh0!d).
~aeprogrammer,uses
themeasured maximalvalueof upperbeartrateandMV and
chooses
~oncoff6relationships(slopes) betweenbeartrateandAMV(usually
l’mear).
For Medtronic pacemakers, so that heart rate changes are not sudden, the
physician also programs in acceleration and deceleration time constants of 0.25,
0.5, 1, 2.5, 5 or-lOrain.
17.4 INTERFERENCE
Because the voltage-sensing electrodes that measure impedance are widely

separated, external electrical interference can cause measuredimpedancechanges
that can incorrectly changethe heart rate. Electrosurgical units (ESUs)and radio-
frequency (RF) ablation equipment used during surgery emit large broadband
electromagnetic fields. Thus the rate,adaptive function of minute ventilation
pacemakersshould be turned off prior to. sur"gery.
The rate-adaptive function of minute ventilation pacemakersshould be turned
off prior to placing the patient on a Ventilator. In this case, the :nonphysiologic
changesin lung volumecan incorrectly ch ~angethe heart rate;
Armswinging on the side of the pacemakerat~30to 40 ann swings per minute
can result in an artifactual increase in" pacing rate. ~ Ctughingand hyperventilation
can also increase the heart rate. Talking during exercise can decrease the expected
pacing rate (Lau et al., 1989).
To prevent pacemaker sense ~mplifiers from sensing the impedance pulses,
the sense amplifier can be blanked by the switches shownin Figure 17.2 whenever
an impedance pulse appears.
To prevent impedance pulses from appearing on the surface electrocardiogram
(ECG),the 7-/~s positive pulse can be followed by a 60-/.ts lower amplitude balance
pulse in the reverse direction. This yields a zero net pulse whenfiltered by the
ECGamplifier.
17.5 AUTOMATIC MODE SWITCHING
If the atrial rhythmis sinus tachycardia, it is physiologically appropriate and we

wouldlike to sense the atrial rate to pace the ventricle. If the atrial rhythmis
pathological (e,g., atrial fibrillation, atrial flutter, atrial tachycardia), it would
best to switch off the AVsynchronization. Teletronics models 1250 and 1254
DDDRpacemakers use automatic mode switching (AMSTM) to achieve this
control. Figure 17.4 showsthat whenatrial rh.ythm occurs at long enoughintervals,
the pacemaker operates in the dual chamber DDDR modeW~thAVsynchronization
(region. III). Whenthree atrial beats occur at intervals shorter than the
postventricular atrial refractory period (PVARP);this rhythm is inappropriately
rapid and causes the pacemaker to switch to single chamber VVIRmode (region
II). If only a single atrial beat occurs prematurely, no atrial pacing pulse is
delivered in order to prevent atrial pacing in the vulnerable period of
repolarization, whichcould cause induction of an atrial tachyarrhythmia.
If the pacemakersenses a P waveduringthe-atrial absolute refractory interval,
it ignores it for all purposes (region I)~ If the pacemakersenses P wavesduring the
atrialmonitor interval, the AMS switches to VVII~, mode(region II). If the pacer
senses~P waves~during the DDDR atrial inhibit interval, it paces AVsynchronous
with sensing of the ventricle inhibiting pacing in the ventricle (region III). If the
intrinsic atrial rate is too low, causing time-out of the atrial alert timer and entering
RATE ADAPTATION BY ~MINUTE VENTILATION
the DDDR atrial pace region~ the ~pacer stimulates the atrium at the metabolic
indicator rate (region IV) (Nappholzet al.,. 1992).
Figure 17.5 shows timing diagram of acardiac cycle and its associated time
intervals indicating howthe pacemakerresponds to a cardiac event whensensed in
different time intervals (Nappholzet al., 1992).
900 ms
Ird~’val
600rn~
WIR atrial monitor ~

400 m6
180 ms
Resting AMV Maximal exercise
Hgure17.4 Whenthe atrial rhythmis at long intervals, the AMS pacemakeroperates in the
DDDRmode(regions tIT and IV). When
the interval is shorter than PVARP,
it operates in the
VVIRmode(regions I and ID. ThePVARP limit and AVdelay shorten with increasing AMV.
t I I Ti~
VBITRiCLEi/llx"
vvt ~ AU[RT
~I
TARP j I
ATRIkL "VVIR W,: r i |
SENSING
Ki~VlOIt I AD.,~X,UT~
NONITORI INHIBIT I , .....
ltEFIIACTO~Y
I Tr t ~Tr I
I
Figure 17.5 If a P wave is sensed, after the,AV delay the, ventricle is paced, During file atrial
alert time, a sensed P wavewill trigger a synchronized pacing of the ventricle (Nappholz et al.,
]992).
If ,after the, pacemaker generates a ventricular pacing pulse, re¢ograde

conductioncauses~ sensing of a P: .w,a~e in tl~e atrium with~, da~, pvAR~,the.
pacemakerextends the timer for the atrial alert period sufficiently to allow the
~tOum,to r~p01arize following, the retrograde depolarization~k This prevents
pacemaker-nibxliated VVIRmOde.
The AMSfeature allows automatic switching from an atrialTtracked DDDR
modeto a nonatrial-tracked VVIRmodein the setting of unphysiologic atrial beats.
402 DESIGN OF-CARDIAC PACEMAKERS
This-has allowed implementation and programming of DDDRpacemakers and

DDDRpacing modes in patients who have intermittent episodes of atrial
tachyarrhythmias(atrial flutter and atrial fibrillation). Thus, these patients enjoy
full AVsynchrony during periods of normal atrial activity without a physician
constantly reprogrammingtheir pacemakers.
17.6 MINUTE VENTILATION AND BODY ACTIVITY SENSORS
Figure 17.6 shows that the Legend Plus pacemaker from Medtronic, Inc. extracts
information from two sensors. A piezoelectric ceramic bondedto the inside of the
flexible pacemaker can provides a signal caused by the mechanical muscle
movementunder the can. Thus body movementprovides information that yields a
rapid increase in pacing rate at the onset of activity. An impedance-based
measurement of minute ventilation provides a more accurate pacing rate for
sustained exercise.
IO
I00 8~ 83
26
65 24 I
Figure17.6Dualsensorrate-responsivepacemaker.
Piezoelectricsensor20 yields fast response
to motions"Impedancecircuit 82 ,measuresminuteventilation to yield long-termaccuracy
(Wahlstrand
et al., 1993).
Cooper (1994) has designed an algorithm that combines inputs from activity
and minute ventilation inputs. The algorithm isbased on a hierarchical fuzzy logic
expert system. A group of expert etectrophysiologists recommended that: ~
1. Except as otheiaviSe recommended,the dual-sensorrate output should follow

the minute ventilation indicated rate. ’
2. At theonset ofex~rcise, the dual-sensor rate output should follow the activity-
indicated rate, but only up to 50%of the maximalrate elevation.
RATE ADAPTATION BY MINUTE VENTILATION 403
If the activity responseis very low, andthe minuteventilation response’is very

high, limit the dual-sensorrate responseto 25%of the maximalrate elevation.
This cross-check prevents long-term pacing at high rates due to
~hyperventilationin a~restingpatient:
Figure 17.7(a) showsthe response to a simulated step function of exercise.

Thedual-sensor responseat onset of exercise is morerapidthanminuteventilation
alone, but the activity contribution is containedat 50%of maximalrate elevation
untii minuteventilation catches up. Figure 17.7(b) showsthe reg~nse to a Stepped
ramp:function of. exercise. The difference between dual-sensor response and
minute ventilation response mainly occurred at the onset of the first step of
exercise.
, ,. .... ,-7""5 ol.. V": , ,,

0 1 2 $ 4 5’ ’6’ 7 8 9 10 0 1 2 3 :it "5 ~.6 7, 8 9 10
Time,
.... minutes ,: Time,minutes~
(a) (b)
Figure 17.7 (a) Dual-sensor response to a simulated step function of exercise. (b) Dual-sensor
response to a simulated stepped ramp function of exercise. From Cooper, D. 1994. A dual-sensor
rate-responsive pacemaker algorithm incorporating a fuzzy logic expert system. Computers in
cardiology 1994. Piscataway, NJ: IEEE.
17.7 REFERENCES
Cooper, D. 1994. A dual-sensor rate-responsive pacemaker algorithm incorporating a fuzzy logic

expert system. Computers in cardiology 1994. Piscataway, NJ: IEEE.
Lan, C. P. 1993. Rate adaptive cardiac pacing: single and dual chamber pacing. Mt. Kisco, NY:
Futura.
Lau, C. P., Antoniou, A., Ward, D. E. et al. 1989. Reliability of minute ventilation as a parameter
for rate responsive pacing. PACE,12: 321-330.
Mond,H. G. 1993. Respiration. In Alt, E., Barrold, S. S., and Stangl, K. (Eds.), Rate adaptive
cardiac pacing, Berlin: Spdnger-Vedag.
Nappholz, T. A. 1990. Minute volume rate-responsive pacemaker. US patent 4,901,725.
Nappholz, T. A., Lubin, M., and Valenta, H. L. Jr. 1987. Metabolic-demand pacemaker and
method of using the same to determine minute volume. US patent 4,702,253.
Nappholz, T., Maloney, J. D., and Kay, G. N. 1995. Rate-adaptive pacing based ot~ impedance-
derived minute ventilation. In K. A. Ellenbogen, G. N. Kay, and B. L. Wilkoff (eds.) Clinical
cardiac pacing. Philadelphia: Saunders.
Nappholz, T. A., Swift, S., Hamilton, J. R., and Gani, M. J. 1992. Metabolic demanddriven rate-
responsive pacemaker. US patent 5,085,215.
Katritsis, D., and Camm, A. J. 1994. Unwanted rate modulations in respiration-guided,
impedance measuring rate responsive pacemakers. In U. J. Winter, R. K. Klocke, W. G.
Kubicek, and W. Niededag (eds.) Thoracic impedance measurement in clinical cardiology.
~ Stuttgart: Georg Thieme Verlag.
Wahlstrand, J. D., Borgerding, G. B., Greeninger, D. R., and Baxter, D. J. 1993. Method and
~ apparatus for rate-responsive pacing. US patent 5,271,395.
17~8 INSTRUCTIONAL OBJECTIVES
17.1 Explain the advantages and disadvantages of the use of minute ventilation as compared
with the use of bodymotionfor rate-adaptive pacemakers.
17.2 Whenmeasuringelectrical impedancein the body, explain the problemwith using small
electrodes~ instead oftarge electrodes.
17.3 Whenmeasuring electrical impedancein the body, explain the advantage of using four
electrodes instead of twoelectrodes.
17.4 Whenmeas~ngelectrical impedance in the body, explain how to avoid undesirable
tissue stimulation.
17~5 Whenmeasuring electrical impedance in the body~ explain how to avoid pickup by
pacemaker~ sensing amplifiers.
17.6 Whenmeasuring electrical impedance in the body, explain how to avoid pickup by
surface ECGs.
17.7 Explain howto calculate minuteventilation from impedance.
17.8 Whenmeasuring minute ventilation, explain howto avoid errors due to the long-term
drift of impedance.
17.9 Whenmeasufiagminuteventilation by impedance, explain howto avoid errors due to
long-termsustained e~ercise.
¯ 17.10 Whenmeasuring’initiate ventilation by impedance,explain howto avoid sudden changes
of packingrate.
17.11 Explain the situations where external interference maycause malfunction in minute
ventilation r~te-adaptivep~acemakers.
17.12 Explain-theresu~ of sensing P wavesduringthe atrial monitorinterval.
17.13 E~plainthe resdl~ of sensin~P wavesduringthe atfialinhibit~interval.
17.14 Explainthe result of the atrial alert timertimingout.
17.15 Explain the- advantagesof using dual minuteventilation andbodymotionsensors in rate-
adaptive pacemakers.
18
Antitachycardia Pacing
Rex S. Piper
Antitachycardia pacemakers (ATPs) are specialized pacemakers designed

specifically for the electrotherapeutic treatment of tachycardia. Tachycardia
occurs whena process other than the sinus node usurps control of the heartbeat
for one or more cycles. The result is normally a faster, irregular heart rhythm.
All previously described pacemakers have dealt with the treatment of
bradycardia, a slow heart rate caused by a process which acts to block normal
sinus node control of the heart.
This chapter deals with the use, design, and results concerning
antitachycardia pacemakers.It starts with a brief historical introduction, followed
by an overview of alternative tachycardia treatments. Then, it presents the
theoretical,aspects of antitachycardia pacing. The heart of the chapter includes a
comprehensive .review of current and proposed pacemaker detection, termination,
and prevention algorithms. The chapter concludes with a survey of reported
results and an overview of commerciallyavailable devices before discussing third
generation antitachycardia pacemakertechnology.
18.1 THE FIRST ANTITACHYCARDIA PACEMAKER
In May1968, the first permanent antitachycardia pacemaker was implanted at

Rochester General .Hospital, Rochester, NewYork (Barold, 1989). The recipient
was a 52 year old female whohad suffered frequent attacks of tachycardia for
years. As the patient.was nor responding to pharmacologi.cal therapy, during one
tachycardia episode it was decided to insert a temporarypacing lead into the right
ventricle with hopes of terminating tachyc~ardia via mechanical induction of an
extra beat. Remarkably, a single mechanically induced beat immediately restored
sinus rhythm: A pacemakerwas actually never connected to,, the pac~g lead. Since
the tacl~ycardia ~vas So easily terminated by ventricular pacing,’ .a permanent
VVIpacemaker was implanted. A simple patient activation system using a magnet
enabled temporary slow ventricular pacing until termination(see Figure 18.1).
Her first attack outside the hospital occurred.~,at the:hairdresser. She was sitting
with a dryer over her head w~henshe became light headed .and thought she was
going to faint, but she was able to reach the magnet and activate the pacer,
thereby terminating the tachycardia in a few seconds. Over the next several years
(during which the pacemaker was replaced a number of times), the patient
terminated an average of 2-3 attacks of tachycardia per day.
Figure18.1 Typicalelectrocardiogramshowingterminationof a tachycardiaepisodeby pulse

train, initiated by the patient usinga magnet.Themagnetis withdrawn
immediately
after normal
rhythmreturns. Eacharrowhead representsonepacemaker
pulse.
18;2 ANTITACHYCARDIA TREATMENT ALTERNATIVES
Even though the first use of pacemakersfor termination of recurrent tachycardia

was more than 20 years .ago, and even though there-have been tremendous
advances in the field of pacemaking, antitachycardia pacing has not gained
widespread use. This is due to the inherent risk of fatality associated with
tachycardia. As is pointed outin section 4.3.2, the very techniques commonly
used to terminate tachycardias are employedin the clinical laboratory to induce
arrhythmias; Because of the inherent risk of inducing or accelerating a
tachycardia with an antitachycardia pacemaker, all other treatment methods are
considered first, and only .certain stable tachycardias are considered for
pacemaker treatment. A clinically stable tachycardia is characterized by a
monomorphicwave form, an intermediate to high rate, and an ability to maintain
consciousnessin the patient.
Alternative treatments for tachycardia other than pacing include drugs,
ablation, surgery and implantable cardioverter/defib.rillators (ICDs).
Pharmacological treatments attempt to effect the underlying abnormal conduction
mechanismsdirectly. Cardioversion and defibrillation are discussed in Chapter
19. Surgery and ablation techniques physically destroy the knownreentrant
substrate or ectopic center. For example, laser or radio frequency ablation would
be appropriate methodsfor treating a reentrant tach~,cardia emanatingfrom a His
bundle branch circuit as Shownin Figure 18.2~Ata’~strategic location, the cardiac
tissue is rendered nonconductiveby ablation;, the circuit is broken and tachycardia
can no longer occur.-
The decision making process for antitachycardia treatment has been analyzed
by Fisheret al((1987) to include thefactors shown in’Figure 18;3.In general,
ablation and. surgery render the highest ratings. This is due primarily to their
excellent long term efficacy and cure rate. - Pacing is Viewedas a rescue system
not a cure, as is reflected by the data. Development of intolerance or
noncompliance make the long term risk of drugs higher than pacing. Even the
successof pharmacological therapy is rated slightly higher than pacing, making
antitachycardia pacing a last resort. However,notice that whenantitachycardia
pacing is augmentedWith implantable cardioversion/defibdllation e~pability, its
success score is the highest of all the therapies. As is discussed in the patient
selection section later on, treatment of tachycardia with antitachycardia
pacemakersis ideal for well selected patients.
ANTITACHYCARDIA PACING 407
His
RBB
Ablation
LBB
Figure 18.2 Showsa reentrant circuit of His bundle branches. The right.bundle branch with its
slowconduction(shaded)is the critical part Of the self propagatingcircuit. A cut u~ing~urgery
~blafion"]h’ the slowconductionpath Canterminatethe tach~,c~rdia. His = His bundl&RBB = right
bundlebranch; LBB= left bundle"branch..
Factor / Drugs Ablation ATP ’ Pacer With

maximal score
Long-term
efficacy /20 ~ 1’5~ :20 ~ ,~ 20 ’~15 .~~’~, ~ 1,5
Comfort/5 :
Sideeffects/5
Convenience/5 1 4 5 3 2
Cost/lO 6 6 10 . 5 2
Pmscfibin~Eas~e/5 5 I I, ’ " I’ " ’ I
CUre/15 ~ ~
Rescue/t5 , = .... 0 - 0, ,’=-
0 11: - 15
Risk/IS . , 13 4 ..... 12:: ,’::.7.’5" 12
Compliance/1O= ,3 ..... ,10 :10 i ~ ’8 " ¯ .... 8
Success/l~0 ,. 7 .8 6 , z,.~5 -10
Figure ,18.3 ¯ Graded:advantages of various antitachyc~dia therapy options.. The relati,v,e

importanceb~ e~ich factor iS reflected by its maximalscJre/Compliance pertains tO the patient s
willingneSStb :folloW ~ the-prescribed th6rapy.- ATP=
antitaehy6ardia pacemaker.ICD= implantable
cardioverter/defibrillator. From’Fisher,J.. D., Kim,S, G.,and Mercando¢ A: D., t987, Arguments
~r antitachycardia th~erapies usinga gradedpoint score model.Ini’G. Breit~,dt, M.Borggrefeand
Dr~’Zipes(eds) NonpharmbColbgical therapy bf tachyarrhythmias.Futura Publishing. ,
18~3 ANTITACHYCA~IA THEORY
This discussion of tachycardia theory pertains to the underlying mechanisms of

those arrhythmias deemed treatable by antitachycardia pacemakers and the
interaction between their electrically paCedevents and the:¢representative
tachycardia cause. A good understanding of the fundamental causes of abnormal
eonduetio~n~is ~assumed (see ,Chapter 3).~,.To further .comprehend the
electrophysiologic mechanisms for~ anfitachycardia pacemaker therapy,
researchers use advanced models to analyze ,the interaction between ,a paced
electrical wave front and the tachycardia generating circuit. Here we present
these higher level models to enable study of pacemaker effectiveness and
interactions.
18.3.1 Underlying mechanisms
Almost all clinically important tachycardias are due to the phenomenonof

reentry (Fisher, 1990). The electrical characteristics of reentrant circuits have
been studied in animals and even some humanpatients for years. During this
time, three models of reentraht-tachycardias have been developed: the ring
model, the figure-of-eight modeland the leading-circle model. The mechanisms
of other causes of tachycardias including reflection, reexcitation, and
autoactivation are presented in Chapter 3. These causes are normally treated with
drug therapy, but in some cases antitachycardia pacemaker prevention or
inhibition can be utilized as is discussed in subsequentsections.
Ring model of reentry

The most wellknownmodel of a reentrant circuit consists of a conducting ring
around an inexcitable center. Typically there is a fixed anatomic obstacle ~around
which the encircling wavefront propagates (see Figure 3.11); The model includes
these required elements: a nonconductingcenter, a locus of unidirectional block,
and a S~gment of sl0w conduction. ’T[a’e first element alone cannot cause a
reentrant~circuit. This may explain why ablation and surgery do not induce
reentrant tachycardia. The second element is needed to initiate the reentrant wave
front and the third element ensures that the encircling wavedoes not collide with
its, ownrefractory tail and thus extinguishitself.
Figure-of~eight model of reentry

Studies of reentry in the thin layer of ischemically injured myocardiumoverlying
infarcted tissue in canines have discgvered the features of the figure-of-eight
model. Ischemically injured~myocardium is the most 60mmon source of
ventricular arrhythmias in the .clinical setting (Rosen, 1990). As shownin. Figure
3.10, the model consists of two circulating wave fronts advancing around two
zones of functional conduction block. Ischemia provides for both the functional
arcs of block and the slowed conduction in the circuit. It should be notedthat this
phenomenonis dynamically unstable~, the arcs can shift, disappear and reappear.
During monomorphictachycardia, the two arcs are relatively stable, but during
polymorphic tachycardia; both the .arcs and ~e encircling wave fronts change
their geometry.
Leading Circle model of reentry

In this model, the center of the circuit is functionally inexcitable. It is rendered
refractory by wavelets initiated by the encircling wavefront (s~e Figure 3.12).
For the purpose of antitachycardia pacemaker analysis, this model represents a
special case of the more general figure-of-eight model.
18.3.2 ~, Resetting, entrainment and acceleration ~
Using the models of reentrant tachycardia~ modesof antitachycardia pacemaker

termination can be analyzed. All methods Of tachycardia capture or termination
seek to reset or entrain the reentrant wavefront to destroy the circuit. Becauseof
their dynamicnature, some figure-of-eight circuits can present dire consequences

whenattempts to capture them result in acceleration of the tachycardia.
Resetting a tachycardia cycle

Resetting a ring model reentrant circuit consists of using a properly timed
stimulus generated wave front to terminate the encircling wave: As can be seen
by Figure 18.4, there is an excitable gap between the. front of the circling wave
and its tail; the tissue in this gap is not refractory. The objective of tachycardia
resetting is to insert a properly timed second wave front into this gap. The new
entering excitation front fails to conductwhenit reaches the tail of the encircling
wave, and in the other direction, it collides with the head of the encircling wave.
Thus ~the encircling wav9is captured by refracto~ tissue and dissipates; at this
point the circuit is terminated.
(a) (b) (c)

Figure18.4 Resettinga ring modelof reentry. In (a), the refractorytissue (shaded)is narrow
allowinga larger entry window for a secondarywavefront to enterthe circuit andreset it. In (b),
the entry window is verynarrowanddifficult to reset. In (c), an extrastimuluswavefront has
enteredthe reentrantcircuitproperlyandwill resetthe circuit.
Tachycardia circuit entrainment

Entrainment is a procedure which uses a multiple pulse train to terminate those
taehycardias which are represented by-figure-of-eight and leading circle models.
It is amethOdof identifying the slowest possible=rapid burst pacing ~rate that will
both terminate a reentrant circuit and minimize :the risk Of ac~deratibn. By
definition, entrainment results in a monomorphicstable wave form from the
interaction of two wave fronts. To start, bursts of pulses are sent into the
reentrant circuit at a rate just above the normal tachycardia rate (see Figure 18.5
(c)). Then,the burst pacing ~rate is slowly increased until, at somecritical, e the
morphologyof the electrically summedwave fronts breaks to a smooth regular
form. At this rate, if a particular numberof burst pulses entrains the circuit, the
same numberof pulses at a-critically shorter cycle length would terminate: the
ta~chycardi:a (EI-Sherif, 1990; Fisher, 1990). Figure 18.5(b) demonstrates~this
phenomenon.It should be noted that some authors define entrainment to include
the actual determination of the critical frequency, however,, this is one step
b~yOndactual entrainment:
TachyCardia acceleration
Just as the dynamicnature of some reentrant tachycardia circuits is utilized to
terminate their encircling waves, this same principle can result in the formation
of newpotentially fatal circuits. At the completionof a burst train, a newcircuit

can terminate, dissipate to its original morphology, or degenerate into an even
faster form, one resulting in fibrillation. As shown in Figure 18.5(c),
prematurely ending the pulse train or inappropriate pulse cycle lengths can
induce tachycardia acceleration if a newcircuit with a shorter revolution time is
formed. This is whyantitachycardia pacemakers are tested numeroustimes (often
in the hundreds) in the clinical setting before being released in automatic mode.It
is the samereason, third generation devices include defibrillation capabilities.
(a) Entrainment (b) Termination (c) Acceleration
Figure18.5Entrainment,termination,andaccelerationof tachycardiausingthe figure-of-eight

model.Functionallynonconducting arcs (thick lines) are shownto changeshapeas the burst
pulses(1 through4) mergewiththe encirclingwave.Thetime sequenceof eventsis left to right
andthen top to bottom.In (a), entrainment is achievedwhenthe shapesof the nonconducting
arcs
stabilize. At this burst pulse frequency, the resultant waveform becomesregular and
monomorphic. Thesamenumberof pulses at a critically higher frequencywill terminate the
reentrantcircuit as shown
in.(b). In (c), incorrectpulsetiminghas modifiedthe arcsandshortened
the encirclingwave’scycletime, resulting in accelerationof the tachycardia.FromEI-Sherif,N.
1990.Electrophysiologicmechanisms .in electrical therapyof ventricular tachycardia.In S.
saksenaandN.~oldsclilager(eds) EleCtricaltherapyof cardiacarrhythmias. Saunders.
18.3.3 Factors influencing termination success
Factors affecting termination of tachycardia by antitachycardia pacemakers

include (Saksena, 1990): refractory period and conduction velocity of the
stimulation site, reentrant circuit, and intervening myocardium;numberof entry
routes into the reentrant circuit; the relative locations of the stimulation site and
the circuit; the rate of the tachycardia; stimulus pulse timing and number;
pharmacological factors; and the disease process or substrate. If any or all of
these relationships prevent termination by single extrastimulus pulses, multiple
burst pulse trains maybe e~fecdve.
The two antitachycardia pacemaker parameters that corr~ate .very highly to

successful termination are number of stimulation pulses and stimulation pulse
timing. Determiningthe optimal numberof pulse stimuli is the first step towards
termination success. In unresponsive tachycardias, two or more stimuli are often
moreeffective than a single stimulus. The first pulse compressesthe length of the
refractory tissue in the reentrant circuit whenit collides with and slows the
encircling wave momentarily. The resultant wider excitable gap allows the second
pulsed wave to reach the reentrant circuit early enough to fully interrupt the
circulating wave. Determining optimal pacing pulse timing is very critical to
tachycardia termination. Protocols for timing single, double, and burst pulse
stimuli are discussed later.
The most important clinical parameter for determining tachycardia
termination success is the site of stimulation. Studies have shown (E1-Shedf,
1990) that reentrant circuits can be terminated by fewer pulses when the
stimulation site is located in the normal myocardial tissue proximal to the slow
conduction zone (were the arcs tend to come together). The optimal site for
success is in the ischemic zone itself, close to the proximalside of the slow zone.
A balloon.shaped sensor~ with 64 separate electrodes has been used during, open
heart surgery to map and localize ventricular reentrant circuits within four
minutes (de Bakker et al., 1987). However, noninvasive techniques
determining the precise location of a reentrant circuit, particularly its slow zone
of reentry and the direction of the wavefront in this zone, are topics of future
research. Practical clinical restrictions on mapping reentrant circuits and
electrode placement currently limit implementationof precise site of stimulation
manipulation.
18.4 TACHYARRHYTHMIA DETECTION
Programmabletachycardia detection schemes:for antitachycardia pacemakers fall

into two general categories: patient Oriented detection, and automatic pacemaker
detection. Automatic detection can be very complex, involving a variety of
algorithms and parameters, while manual patient detection is simple and straight
forward.
18.,4,1 Manualactivation
Manually activated antitachycardia pacemakers have been used since the first
antitachycardia pacemaker was installed in 1968. They are ~i~eally, suited for
patients whoremain conscious during their periods of tachyc~dia. The patieht,
by sensing, characteristic symptomso~ ia rapid pulse rate, can be as accurate asthe
piaysician s reading of an electrocardiogram. ~s tends to limit false triggfring,
although some patients can become overconfident in their ’abilities and may
initiate pacemaker therapy inappropriately. Older externally activated
antitachycardia pacemakers employ a sihaple n~agnet while, ,some newer models
are activated i b3~ radiofrequency transmitters. Because mantmi intervention is
requtred, their overall usefulne.ss and convemenceIs hmlted. Since patlen
cooperation is mandatory, disabling symptomsC~ be fatal. The~advantages of
manualdetection include simplicity and the ability to restrict patient activation to
a hospital setting wherea physician and defibrillation can~ be p~esent.
18.4.2 Automatic detection
Automatic tachycardia detection by the pacemaker itself presents a considerable

convenience and responds more quickly without intervention by the patient or
physician. One or more sensed parameters may be used to determine if
tachycardia exists. These include heart rate related criteria and in some newer
models electrogram characteristics. Proposed future parameters include the use
of biosensors to detect concurrent activity levels and hemodynamic
stability in the
patient.
Baseline heart rate

The most useful parameter for detection of tachycardia is baseline heart rate.
When the sensed rate exceeds a preprogrammed threshold, tachycardia is
considered valid and the termination protocol is commenced.The rate threshold
is programmedindividually to accommodate different tachycardias and peak
normal beats per minute. For an average patient with a normal sinus rhythm of
70 bpm, a rate of 190 bpmis considered tachycardia and a rate above 210 bpm,
fibrillation. The major disadvantage of rate only detection is its lack of
specificity; it can be difficult to distinguish between an exercise induced rapid
rate anda tachycardia rate. Additionally, it cannot be used to detect tachycar~dias
whichfall belowthe threshold cutoff.
Rate-related parameters
More sophisticated detection algorithms now use additional rate-related
parameters to further classify the baseline heart rate. The rate of onset, the
stability of the heart rate and the duration of the rapid rate are commonly used to
enhance baseline heart rate data. Rapid onset of a high rate is associated with
tachycardia, whereas gradual onset usually characterizes exercise. A study
examining rate of onset in patient subjected to 30 s of maximal bicycling
(Mercandoet al., 1988) demonstrated excellent tachycardia detection results using
this scheme. A .number of’commercial devices already incorporate, rate of onset
parameters. Measurementof a regular R--R interval is .also used to distinguish
exercise related high rates, with its respiratory related variation, from more
stable tachycardia intervals. However,such stability parameters must be chosen
very carefully, since some tachycardias will include a limited amount of R-R
interval variation. Finally, the duration of the tachycardia in terms of the number
of consecutive cycles measured can be used to prevent responses to temporal
arrhythmias and to allow spontaneous termination of transient tachycardias.
Oversensing and biosensors

There exists a need for more reliable and exacting detection of tachycardia.
Because oversensing is a critical problem(see Figure 18.6), rate related detection
parameters are currently set to conservative levels, leaving some tachycardias
undetectable. With the advent of rate-adaptive bradycardia pacemakers in recent
years (see Chapters 13,through 17), useful biosensor technology is becoming
available that mightbe used to augmentand fine tune tachycardia detection: Using
these sensors, patient activity level could theoretically be used to enhance
detection of tachycardias outside the realm of exercise. Measurementsof blood
pressure and stroke volumecould be used to differentiate hemodynamicallystable
tachycardias from, unstable ones and further delay or abort the termination
algorithm. Hiles" et al. (1993) demonstrated in laboratory tests with dogs that
aortic blood temperature was responsive to induced tachycardia; :the blood

temperature showed a transient decrease during induced arrhythmia. Saksena
(1990) recommendsusing cardiac impedance to detect stroke volume, which has
been shownto drop significantly during tachycardia.
Figure 18.6 Antitachycardia pacemakerinduced tachycardia occurred whenoversensing

resultedin a pulsetrain (see arrowheads)
duringa normalheart rhythm.Thispropagated
an actua~
tachycardia
episode,as seenfollowingthe pulsetrain.
To be useful in tachycardia detection, the sensed parameter, must be

relatively stable at baseline, respond rapidly and ~ significantly during unstable
tachyca/dias, and return to baseline promptly after termination. Someof the
biosensors that have been investigated for tachycardia discrimination include
pressure, oxygen saturation, impedance, pH, temperature; a~tivity/motibn,
respiration, cardiac output hnd various combinations. Details regarding
biosensors are covered in Chapter 13.
Rate BC TC fibrillation
Activity low high high q0w
Hemo- stable [ unstable stable [ unstable

dynamics
Pacer BC monitor
mode pacing. pacin~
Figure18.7 Abiosensoraugmented antitachycardiapacemaker algorithra could utilize activity

level andhemodynamic stability to optimizetaehycardiadetection. For example,if a high rate
indicatesa tachycardia,activitylevel andhemodynamic
stability canbe checked.
If the activitylevel
is highandbloodpressureis stable (indicatingexercise),unnecessary pacingcanbe avoided.TC
tachyeardia;BC= bradycardia;CV/DF = cardioversion/defibrillation.
Additional physiological and activity related biosensor information may

enhance the specificity of tachycardia detection. This would help prevent
oversensing and allow rate based detection n~es to be broadened. As shown in
Figure 18.7, stable tachycardias could be discriminated and treated accordingly,
while unstable tachycardias could be .aggressively treated by pacing or
cardioversion/defibrillation. Hemodynamic data could be used to select optimal
termination algorithms, At this stage~, research regarding biosensor integration
into antitachy~ardia pacemakers is pro~sing; however, the cli~ca[usei~of these
systems remains to be validated. Practical disadvantages of bitsensors include
slow response time, higher costs, increased complexity, andchronic performance.
Electrogram
Some experimental third generation antitachyeardia pacemakers with
cardioversion/defibrillation capabilities perform advanced analysis of the
tachycardia wave form to differentiate between simple tachycardia and
fibrillation. Fast Fourier analysis, template matching, gradient pattern detection
and probability density function are someof these sophisticated calculations. As
these algorithms becomemore available and more efficient, they could be used to
distinguish tachycardia itself from normal rapid heart rate.
18.5 TERMINATION ALGORITHMS
The theory and mechanismsof reentrant tachycardia demonstrate that resetting,

entrainment and termination of tachycardia is highly correlated to the stimulus
pulse delivery algorithm, specifically, variations in pulse number and timing.
Today’s multiprogrammable, .second generation antitachycardia pacemaker
devices offer a numberof pulse delivery protocols, All of these protocols can be
categorized into tWO groups; those based on the delivery of one or two
extrastimuli andthose based on the delivery of a:puise train.
18.5.1 Single/double extrastimulus
ProgrammedeXtrastimulus pulse delivery or PESis used by devices tha t deliver a

few cfitiCaliy timed stimuli. If the numberof p~ulses can be limited to one or two
there i~ a p~tential reduction in the risk oftadhycardia a~celerati0n (Echt et al.,
1990). Earlier models delivered one or two pulses at a preprogrammed delay
time following a tachycardia beat. Newermodels can adaptively change both the
number of pulses and the delivery timing of the pulse/s (see Figure 18.8). Some
devices can remember the timing of successful pulses and adaptively tune
themselves. Others respond to changing tachycardia rate adaptively by adjusting
their timing parameters proportional-ly.
Adaptive PES Rampdown
Double PES Rampup-down
Burst Underdrive
Fta~gUre.18.8
hyca/dia Tachycardia:terrnination
wave algorithms-are
fdrm.PacedpU!s~s~are representedby~’ demonstrated
arr~vheads. PES~against a background
paciiaginclude~pulse
number"andtimingvariability: Burst; ramp;and ~indetdriveprotocols include pulse timing,
number~andfrequ~ncyvariation. Since’ a!tachycardia’s response to a pulse train is very
unpredietable,.for
clarity, the waveformis not~shownafter pulsetrains start.
18.5.2 Pulse train stimulus
Since rapid tachycardias rarely respond to the single capture techniques used by
PESstimulation, pulse train delivery is used. Within the two classes of pulse train
algorithms, burst and underdrive pacing, there are a large numberof protocols.
As can be seen in Figure 18.8, a number of delivery parameters are adjusted by
these different algorithms, including burst delivery initiation and termination
timing, pulse to pulse interval, and the numberof pulses.
Burst pacing utilizes a .short train of pulses,~ ,usually between 5 to 15,
delivered at a rate faster than the tachycardia to effect termination. Since the risk
of acceleration is greater for multiple pulses, even for slow well tolerated
tachycardias (Fisher, 1990),~a key operational objective is to keep the numberand
rate of pulses as low as possible. Earlier burst delivery algorithms used a short
burst of traditionally fixed cycle length pulses. Moresophisticated algorithms can
adaptively adjust the cycle timing as a percentage of the tachycardia cycle timing,
and/or shift the burst train forward or backward. Another type of burst pacing
uses ramping to .modify the pulse train. Ramping-the pulse frequency down is
designed to help minimize the risk of accderation. Somedevices will ramp the
frequency up and then down,which has less Side effects than a very fast burst but
still reaches a peak target frequency.
~-Underdrive is a technique used to treat some patients with slow, well
tolerated, hemodynamicallystable tachycardias (Echt et al., 1990). Unlike burst
pacing whichdelivers short trains of pulses, underdriving can continue for a long
period of time. It delivers a slow constant train of pulses, which randomly
interact with the tachycardia until an appropriately timed pulse terminates it:
Care must be taken to ensure that the frequency of the pulse train is not a
harmonic of the tachycardia wave form or the .tachycardia maybe reinforced or
accelerated. Burst pacing and PES are substantially more effective for the
treatment of frequent, reentrant tachycardias.
18.6 PREVENTION PACING
Someantitachycardia pacemaker algorithms are designed to detect the onset of

tachycardia and immediately prevent further pr0p~at~on. Prevention pacing
deals primarily with triggered tachycardia and pacemaker mediated tachyC~dia.
18.6.1 Triggered tachycardia
Initiation oftachycardia requires, a trigger event (see section ~3.4.~3) and

associated substrate .to propagate reentry. To prevent tachycardias, one or both of
these influences must be altered. Antitachycardia pacemakers can be used as.a
preventative measure to suppress-or inhibit either the trigger mechanismor the
tachycardia causing substrate.
Overdrive suppression
The occurrence of triggers, for example early or late afterpotentials, .have a
strong, relationship toheart rate. There appears to be an optimalintermediate rate
in the range of 10 to15 beats .per minute above :the normaLheart rate where
trigger frequency is suppressed, Manystudies confirm thatov.er.driving the heart
rate can significantly reduce the number of tachycardias (Mehra, 1990).
preventing torsades de pointes tachycardias caused by early afterdepolarization

triggers, temporary overdrive pacing was the only consistently effective therapy.
However, chronic pacing at rates in excess of 90 to 100 beats per minute is
usually not well tolerated. In some patients, pacing at evenmoderately elevated
rates worsens the tachycardia by producing hemodynamicdeficits and inducing
ischemia. Nevertheless, in the treatment of patients with frequent triggers leading
to sustained tachycardia, overdrive suppression can be invaluable.
Someantitachycardia pacemakers use. the concept of dynamic overdrive to
increase the pacing rate whenevertriggers are observed. If an irregular trigger
pulse is detected, the overdrive pacing frequency is increased by a
preprogrammedvalue. The pulse cycle time is then gradually reduced until the
baseline heart rate is reached. This algorithm has demonstrated a reduction in
trigger events of 80%(Mehra, 1990). However, concerns about frequent high
rate pacingstill exist.
Inhibition
Inhibition is used to prevent tachycardias by prolonging the refractory period of
the causative substrate. Preexcitation is administered to the site by a pulse during
the refractory period, thereby extending the refractory period of the tissue. If
applied to strategic points, the resultant prolonged refractoriness can choke the
substrate and prevent tachycardia from occurring. However, due to electrode
implantation restrictions, inhibition remains primarily a laboratory phenomenon.
Vagus nerve stimulation

Strong evidence that the sympathetic :nervous system can play a significant role in
the initiation of tachycardia suggests using, the vagus nerve, of the
parasympathetic nervous system, to induce the relaxation response and decrease
susceptibility to tachycardia (Schaldach, 1992). The: role of vagal activity
antitachycardia effects is controversial, the associatedheart rate reduction might
play a more significant role (Mehra, 1990). If vagal stimulation does have
antitachycardia effects, electrical stimulation of the vagus nerve could be used to
prevent tachycardias. Schaldach proposes an autonomic nervous system controlled
antitachycardia pacemaker. His system would monitor sympathetic tone using a
contractility sensor and heart rate. Whenhigh sympathetic tone and heart rate are
detected, indicating susceptibility to tachycardia, the afferent fibers of the vagus
nerve are stimulated to effectively relax the heart.
18.6.2 Pacemaker-mediated tachycardia
With the advent of dual chamber pacing, pacemaker-mediated tachycardia has

becomean increasingly important issue. For patients with a variety of conditions
like sick sinus node or AVblock who require DDDmode, any sensed atrial
activity is relayedto the ventricles. Unfortunately, if atrial tachyarrhythmias
occur they are perpetuated in the ventricle by the pacemaker;this has been named
pacemaker mediated tachycardia. It includes two phenomena. Irregular atrial
events can be from direct atrial tachycardia or from retrograde (back
propagating) ventricle signals. Otherwise knownas, endless loop tachycardia
(ELT), thislater phenomenon is supported by a ,reentrant circuit whose
anterograde conduction is provided by the pacemaker (seeFigure 18:9). Three
conditions are necessary-for endless loop tachycardia to occur: ventricular atrial
conduction mustbe present, a trigger event is normally required; and retrograde
ANTITACHYCARDIA PACING. 417
ventricular signals must be sensed by the atrial sensor. In patients using DDD
mode, 41%have shownretrograde conduction from the ventricle (Nitzsche et al.,
1992). The incidence of ventricular atrial conduction varies from 66%to 100%
(note that VAconduction can appear and disappear) when AVconduction
normal to 0% to 25%with third degree AVblock (Bertholet et al., 1985). The
order of events starts whenthe pacemaker senses a premature atrial event. This
trigger can comefrom numerous sources: a premature atrial contraction (PAC),
a retrograde premature ventricular contraction (PVC), electromagnetic
interference with the pacemaker, and myopotentials from skeletal muscle. In
response, the pacemaker then paces the ventricle at a time whenthe retrograde
conduction pathway is not refractory, allowing the ventricular pulse to back
propagate. Whenthis is sensed as an atrial event, a racing endless loop
tachycardia cycle begins.
Pacemaker
~mode ! ( [7~r~go~tion
%
~anterograde_~ ~ VA c~nduction}
AV conductio n ~
Figure18,9 Pacemaker-mediated tachycardiaoccursin DDD modewhenirregular atrial events

are relayed to the ventricle throughthe pacemaker’s anterogradepathway.For endless loop
tachycardia,retrogradeP wavesare sensedas atrialeventscompleting
a reentrantcircuit.
Traditional prevention methods

A number of traditional methods have been used to prevent pacemaker mediated
tachycardia. The primary method is to lengthen the post .ventricular atrial
refractory period, PVARP (see section 9.2.1),: thus delaying atrial sensing so that
trigger events are not sensed as atrial activity. This is precisely whyendless loop
tachycardia was not an issue with older pacemakers. They had long atrial
refractory periods used to limit the maximumbeat rate for. hemodynamic
reasons..However, this limits the ability of pacemakers to track during high
demandactivity because the upper rate interval (URI) is usually set equal to the
sum of the PVARP and the atrial ventricular interval (AVI). Whenthe heart rate
exceeds the URI, either the fixed ratio block method or the Wenckebach
algorithm are triggered to prevent high rate tracking (see section 9,2.4).
VACT prevention
As modern pacemakers have sought to track higher rates by lowering the
PVARP,ELT has become much more prevalent. Some have :added an anti-ELT
algorithm which utilizes the ventricular atrial conduction time (VACT)
differentiate true atrial events from retrograde P waves (Fisher et al., 1986;
Limousin et aL, 1990). This procedure starts with monitoring ~the VACTfor
normal timing, If the VACTdrops below 450 ms, ELT is suspected and tested
for by shortening the ~AVIa~preprogrammedvalue (see Figure 18.10)~ If the
VACTremains constant within, a range limit,, back propagating P waves are
confirmed. A normal atrial pulse signal would be unaffected by an early
ventricular pace. To terminate the ELT, the PVARP is then lengthened to 450 ms
for one cycle, rendering the next P wave unsensable. Additional proposed
sophistication includes adjusting the length of the PVARP to a value longer than
the longest VACT as measured during the last ELT. This would prevent future P
wavesensing but also tends to limit high rate tracking.
(b)
I lAW- VACT
+ I
Figure18.10Usingthe ventdcularatrial conductiontime (VACT) to preventELT.Timingbar

(a) showsa baselinebeat to beat sequence.In (b), ELTis suspectedandtested for by decreasing
the AVIby a smallamount,Del. Thisresults in early ventricle activation, shown as the dashed
triangle. If the followingVACT time has increased by Del, ELTdoes not exist. If the VACT
remainsconstant(the atrial pulsemoved forwardto the dashedposition)as shownin (c), ELT
confirmed;
the atrial pulseis trackingthe ventriclebeatvia retrograde
ventriclesignals.
WARAD prevention
Since endless loop tachycardia trigger events are well known, it would be
advantageousto prevent the initiation of this tachycardia. To do this, Nitzsche et
al. (1992) introduced a new parameter called the window of atrial rhythm
acceleration detection (WARAD), which is equal to 75%of the preceding P-P
interval. As shown in Figure 18All if an atrial event is sensed during the
WARAD, it is considered to be a trigger (a ~ premature ventricular or atrial
contraction). Instead of resetting the AVI delay on this event, only the AEI
(Atrial escape interval, also knownas ventriculoatrial, interval, VAI)is reset and
atrial activity is monitored.If no atrial event occurs within the AEI, the trigger is
considered to be isolated and after the atrium is paced, the AVI.is temporarily set
to 31 ms to maximize the next atrial sensing: Endless loop tachycardias are
prevented if the trigger event falls within the W~ARAD. If a newatrial event is
detected during the AEI, the pacemaker suspects atrial tachycardia and
temporarily limits the pacing rate to 120 bpm. As a final fallback, the pacemaker
defaults to VDImode.
Enhanced sensing and prevention

As is discussed in section 18.4.2, biosensor data can be utilized to augment
tachycardia algorithms. An implanted activity sensor could be used to judge the
appropriateness of the P waverate. If the .rate is considered beyondthe patients
activity level a pacemaker mediated tachycardia is detected. .In this case,
tachycardia termination or fallback procedures could then be pursued. Lau et al.
(1992) successfully used respirationrate and~body acceleration sensing
distinguish correctly pacemaker mediated tachycardia from normal high activity
heart rate. Another method’ suggests using activity related biosensors to set the
PVARPto two different levels (Lau, 1991). The resting PVARP can be kept long
Figure 18.11 Usingthe windowof atrial rhythmacceleration detection (WARAD) to prevent

ELT.Asshown in timingbar (a), the WARAD starts at an atrial eventandis equalto 75%of the
previousP-Pinterval. If a prematureatrial eventoccursduringthe WARAD the ventricle is not
paced,rather the AEIis reset as shownin (b). If noatrial eventoccursduringtheAEI,the atrium
is.paced with the AVIset to 31 ms. If anotheratrial event occursduringthe AEI,an atrial
tachycardiais contrmned.
to exclude retrograde P waves from atrial sensing and during exercise the
PVARPcan be ,shortened to allow high rate tracking in DDDRmode. The main
disadvantage of using activity sensors for ELTprevention is if the sensor does
not have a fast response time, high heart rates from quick physical exertions
might be mistaken for tachycardia. However, the future prospect s of using
biosensors for pacemaker mediated tachycardia discrimination remain promising.
A very different approach to ELTprevention using atrial sensor sensitivity
adjustment has been successfully demonstrated by Rognoniet al, (1991).-Atrial
sensing in advanced DDDpacemakers with programmable sensing parameters
were optimized. ~The LEM/CCS Twinal 20/30 pacemaker allows a wide rangeof
atrial sensing options, and its telemetry options include transmissions of sensed
electrograms used ~for optimization. After recording and analyzing the sensed
characteristics of both atrial and retrograde P wave signals, optimal threshold
levels were used to filter P waves from true atrial beats. Reprogrammingthe
atrial sensing parameters resulted in immediate ELTinterruption in 14 out of 15
patients. The obvious risk in atrial sensing optimization is undersensing due to
small safety margins.
18.7 REPORTED RESULTS
Documented results regarding antitachycardia pacemakers with and without

cardioversion are generally very good. This can be attribtited, in large part, to
the strong patient screening, careful testing and conservative operational
modalities employed in prescription. The limited use of antitacliycardia
pacemakerswill remain so as long as they continue to pose a risk of acceleration
and as long as they remain unable to distinguish reliably slower tachycardias
from high rate physiologic rhythms. Fortunately~ the use ’of augmented
biosensory input data and combined cardioversion/defibrillation promise wider
future acceptance and.application.
18.7.1 Patient selection
It is important ;to note that allthe patients selected for: antitachycardia pacing
therapy have been very carefully screened. This tends to bias the results. ~ The
typical patient is resistant to drug treatment and must have a characteristically

stable mediumto high rate, monomorphictachycardia, which is reproducible.
The hemodynamicstability of the patient must be strong enough during the
tachycardia to maintain patient consciousness. In all cases the termination
algorithm of antitachycardia pacemakers used in automatic modeare thoroughly
tested and confirmed by inducing and terminating at least 100 consecutive
tachycardia episodes.
18.7.2 Surveys
In order to present both sides of the results, the negative results of

antitachycardia pacemakers are presented first. As has been stated previously,
pacemaker treatment of tachycardia can have detrimental and potentially
hazardous side effects. Figure 18.12, some cases have induced acceleration or
proarrhythmiceffects. Becauseof available data, this is a very limited survey, but
it does reflect whyan antitachycardia pacemakeris prescribed cautiously.
First author, I No. of

~,ear I patients
12
I
Pacing ] Proarrhythmic
mode I effect .
Manual ~- Atrialfibrillation,2 Atrialflutter,2
Kalan,1976
Peters, 1978 10 Manual Atrialfibrillation,3
Nathan, 1983 15 Auto Atrialfibrillation,.
3
Peters, 1978 6 Manual VTacceleration,2
Falkoff, 1986 2 Auto VTacceleration,1
Figure18.12Tachycardia accelerationeffects of antitachycardia.pacemakers. Flutter is a fast

tachycardia
Usuallytreatedwithcardioversion.Fibdllatiianis an extremely
fast tachycardia treated
with cardioversionand/ordefibrillation. VT= ventriculartachyeardia.FromRosenthal,M.E.,
Marchlinski,F. E., and Josephson,M. E. 1990.Complications of implantableantitachycardia
devices:diagnosisandmanagement. In S. SaksenaandN. Goldschlager (eds) Electricaltherapyof
cardiacarrhythmias.Saunders:
Figure 18.13 summarizesthe reported results of antitachycardia pacemakers

in the absence of backup defibrillation. In the absence of effective backup
defibrillation, most detection schemes have been patient activated. As is shown,
patients have been very effectively managedwith the majority reporting good to
excellent results.
Figure 18.14 summarizesthe reported results of antitachycardia pacemakers
when combined with backup defibrillation. An important obserwation is the
relatively small numberof episodes requiring shocks for termination. Bearing in
mind patient selection, this can be interpreted as evidence that when used in
automatic modeantitachycardia pacing techniques have a high degree of efficacy.
18.8 COMMERCIAL DEVICES
Current antitachycardia pacemakers offer a number of treatment options

including a variety of programmabledetection and termination, criteria. Some
have additional cardioversiort/defibdllation backup c~pabiliiy u~das the final
step if pacing fails to terminate the tachycardia. A brief desc~ription of a few
commercial devices follows.
First author, I No. of I Pacer, Pacing

year , ~r..]:patients ] model mode ~
Ruskinl 1980 3 Medtronic 5998
Luderitz, 1982 3 2 Magnet Manual, NS 2 1
1 Cordis underdrive
Orthocor 234 A Manual,burst
den Dulk, 1984 6 Medtronic SPO500 Manual,variable 4 2
modes
Griffin, 1984 52 Intermedics Cybert Auto,,burst 30
(multicenter)
Rothih~n, 1984 53 Cordis Orthocor Maii~alburst 45
(multicen.ter)
Fail, off, 1986 2 lntermed C~¢bertach Burst~ ’ 2
Fisher, 1987 20 Miscellaneous Miscellaneous 16 2 3
Fr0me~, i987 1 lntermedIntertach PESscan
Palakurthy, 1 Telec PASAR Autoscan PES
1988
Moll~r~1989 2 Telec PASAR Burst’ 2
Oechetta, 1989 1 Cordis Orthocor Burst 1
Bertholet. 1985 13 PASAR4151 Auto, scan PES 7 3 3
Medtronic SPO500 mailual PES
bu~st~
Spurrel!, 1984 21 PASAR4151, 4171 Auto, shiftscan 16
bursts
Sowton, 1984 ~ 16 Siemens-Elma Auto, scan, PES 14
,~-~ Tachylol~,, bursts
Zipes~,,1984 21 : Medtronic SymbiosAuto,scan,PES 21
7008 bursts
Portillo, 1982 8 Medtronic DVI-Mn Auto 5
IL
Fahraeus, 1984
uderitz; 1982
] Kahn, 1976
8
9
12
PASAR4151
Intermedics
C-~bettach
Medtronic 5998
Auto, scan
Auto, manual
underdrive, burst
Manualburst-
4
5
10
I (multieenter)
Figure 18.13 Survey of antitachycardia pacemakerresults demonstratinga majority of good to

excellent results. EX= excellent results; GD= good results; PR = poor.results; PES=
programmed.extrastimulus; NS = not stated. From Roth, J. A. and Fisher, J. D, 1993.
Antitachyeardiapacing-ICDinteraction: In G. V. Nacearelli and E. P. Veltri (eds) lmpIantable
cardioverters-defibrillators.BlackwellScientific.
Ventak ~ PRX (Cardiac" Pacemakers, Inc.)

This device is.designed to detect-and treat multiple ventricular tachyeardias while
providing a variety of electrical therapeutic alternatives, bradycardia support,
and extensive diagnostic data. The device has several additional sensing .features
that improve detection of ventricular tachycardia. These include a sudden onset
criterion and a stability criterion that evaluates the degree of variation in cycle
length during an arrhythmia. This criterion is designed to help differentiate
taehycardia~from fibrillation.’ The Ventak PRX also has bradycardia pacing
capabilities in VVImode only.
PCD (Medtronic Inv.) "

The PCDis capable of detecting and treating bradycardia, ventficular :tachycardia
and fibrillation. Therapies include VVI pacing, adaptive ramp or burst
First author, No. of

~ear patients
11
Pacer ,
model
Intermed-
I Pacing] No. of Percent ~
mode i pacin~s termination
NS 87
No. of
shocks
approx. 50% 43. ,
Greve, 1988
Intertaeh, ICD
Newman, 1989 11 Intermed. PES, >1998 2
Int~rvach ICD burst,
Bonnet, 1991 14 4 Cordis Orthocor Burst 6029 ~ 103

¯
284A, 6 Intermed
Intertach ICD
Fromer, 1991 4 Medtmnic PCD Ramp 16 70% ¯ 19
7216A, 7217B
Leitch, 1991 46 Medtronie PCD Burst, 909 92.4% : 44
7216, 7217 Ramp .... ¯ ,
Ludertiz, 1991 6 Siemens-Elma ’ Burst 1631 227
¯ Tachylog ICD
Saksena, 1991 16 Medtronic PCD Burst, 96 81% 27
7216A Ramp . 71
Singer, 1991 .5 Telectronics Burst 226 " 127
Guardia9 4210
Block, 1991 21 Medtro~c PCD NS 439 99% 16
Ellenbogen, 100 Teleetr~nics NS 128 59% 9
1991 Guardiar14210 .
Figure 18.14 Survey of reported results for antitach3/eardia pacemakers ~ with

cardioverter/defibrillation capability. A relatively high rate of success for pacing terminationof
taehyeardia is shown.NS= not stated. FromRoth, J. A. and .Fisher, J. D. 1993. Antitaehycardia
pacing-ICDinteraction. In G. V. Naccarelli and E. P. Veltri (eds) Implantablecardioverters-
defibrillators. BlackwellScientific.
antitachycardia pacing, or cardioversion :or defibrillation from-0.2 to 34 J.

Detection of tachycardia using this device is predominantly via rate
(100-214 beats/min) with optional stability and onset criteria. Fibrillation
detected by rate only.
RES,Q (Intermedics Inc.)

This device features VVI pacing, antitachycatdia pacing, synchronized low
energy shocks and defibrillation shocks up to 40 L Ten different tachycardia
detection schemes are available, four therapies are selectable for each patient.
Cadence V-lOO(Ventritex Corp.)

The Ventritex Cadence has unique features capable of delivering a biphasic shock
wave form and storing electrograms. In~.211 patients~ .~7541 episodes of
tachycardia received therapy with the device; 337 tachycardia episodes terminated
with a shock as first therapy (92% efficacy), and 6763 were terminated with
pacing as first therapy (94% efficacy). Ninety six (1%) episodes were accelerated
with pacing.
Siecure P59 (Siemens)

The Siecure is a multitiered antitachycardia device with VVI pacing. The
detection scheme includes three rate zones (tachycardia low zone, tachycardia
high zone, and tachycardia zone). Detection is primarily by rate, but rate of
onset, stability and number of beats are also programmable, Amitaehycardia
pacing can be either aburst or a ramp.
18.9 THIRD GENERATION ATP DEVICES
Often third generation antitachycardia pacing devices utilize built in

cardioversion and defibrillation - capabilities. Most second generation
antitachycardia pacemaker devices are applied conservatively because~ they lack
sufficient backupin’the form of defibrillation. As more third, generation devices
becomeavailable manymore tachyeardias will be treated with elbctr6therapy.
18,9.1 Automatic drug infusion
Off~ radichl proposal for an advanced antitachycardia pacemaker device involves

a~ltomatie dispensing ~d injection of antitaehycardia drugs. Arzbaecher et. al.
(1989) .has investigated.the possibility of developing such ~a device for the
dispensing of procainamide ~ and disopyrami.de~ both normal-antitachycardia
pharmacological treatments, Preliminary studies showed quicker conversion of
tachyca~dia, using disopyramide and more accurate, control of concentrations
whenreleased exi)onentially. Results showedtermination of tachycardia in three
patients and significant increase in tachycardia cycle length in three others,
prompting easy pace termination. However, thedevice is bulky, difficult to
implant, and limited in its flexibility. Euture, objectives, include miniaturization
and interconnection between tachycardia detection and drug delivery capabilities
in one implantable system.
18.9;2 Tiered therapy and the ideal device
The ideal antitachycardia device would include treatment options for bradycardia,
tachycardia; and fibrillation. The features of such a device are listed in Figure
1,8.!5. Third generatign antitachycardia devices including cardioversion and
defibrillation capability are the subject of Chapter 19..
Sensing’
Distinguishp~thologic from physiologietachycardias
Differentiatetwo(ormore) pathologic tachycardias
Recognize nonsustaincd tachycardias
.,Autorf!aticsensitivitygainfor differentrhythms
Pacing ~.. .
¯ Bradycardia pacing(single anddualchamber,physiologicsensor)
Antitaehye,ardiapacing(extmstimulus, burstor adaptive)
Differentantitachycardiatherapiesfor,differenttaehycardias
Noninvasiveelectrophysiologic studycapabilities
Taehyeardia prevention
Cardloversion/defibrillation
Lowenergysynchronizedcardioversion
Highenergycardioversion of defibrillation
Bidirectional,biphasic,or sequentialshocks
Figure18.15The"ideal" antitachycardiadevice. Onedeviceincludes .sensing, pacing, and

preventionfor bothbradyeardiaandtaehycardia.It also has cardioverter/defibrillation
optionsfor
backup.FromKlein, L. S., Hackett,F. IC, Miles,W,M., Mohamed, Y., andZipes, D. P. 1993.
Clinical experiencewith newimplantableantitachycardiacardioverter-defibrillators.In G. V.
NacearelliandE. P. Veltri(eds)lmplantable
cardioverters-defibrillators.
BlaekwellScientific.
18.10 REFERENCES
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Implantable microprocessor based devices for the management of arrhythmia. Computersin
Cardiology, 9: 29-34.
Barold, S., Ryan, G. F., and Goldstein, S. I989. The first implanted tachycardia-terminating
pacemaker. PACE,12: 870-874~
Bertholet, M.~Materne,P., Dubois, C., Mareelle, P., Beckers, L, Demo~ulin,J. C., Fourny,
and Kulbertus,~H. E. 1985. Artificial circus movement tachyeardias: incidence, mechanisms,
and prevention. PACE,8: 415"423.
Bertholet, M., Demoulin, J. C., Waleffe, A., and Kulbertus, H. 1985. Programmable
extrastimulus pacing for long-term managementof~supraventricular and:~ ventricular
tachycardias:clinical experiencein 16 patients. Am.HeartJ., 110: 582-589.
Block, M., Borggrefe, M., and Hammel,D., et al. 1991. Pacer-cardioverter-defibfillator (PDC),
utilization, efficacy and complicationsof antitachycardia pacing (abstract). J. Am.Coll.
Cardiol., 17: 54A "- ~ ¯
Bonnet, C. A., Fogoros,R. N~; Elson; J. J., Fiedler, S: B., and Burkholder,J. ’A. 1991. Long-
term efficacy of an antitachycardia pacemakerand implantable defibrillator combination.
PACE,14: 814-822.
de Bakker, J. M.T., Vancapelle, F. J. L., and Janse, M~.L 1987~..L0calizationof the site of
origin of Ve~tficulartachycardiain the ChrOnicptiase’of my0eardi~l:infarction. In G: B~ithardt,
M. Borggrefe and D. Zipe$ (eds)Nonpharmocological therapy of tachyarrhythmias. Mt.
Kisco, NY: ¯ Futura Publishing.
den Dulk, K., Bertholet, M.,. Bi’ugada, P., et~fl. 1984. Clinical experience with implantable
devices for control of tachyarrhythmia.PACE,7: 548-556. ¯
Echt, D. S., Lee, J. T. and Hammon, J.: W:1990. !mplantableand intra0perative .assessment of
antitaehycardia devices. In S. SaksenaandN:Goldschlager(eds) Electrical therapy Of cardiac
arrhythmias.Philadelphia: Saunders.
EI-Sherif, N. 1990. Electrophysiologicmechanisms in electrical therapyof ventricular tachycardia.
In S. Saksena and N. Goldschlager (eds) El, ectri,cal therapy of cardiac arrhythmias.
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Ellenbogen,K., Welch,W., and Luceri, R., et al. 1991. Clinical evaluation of the GuardianATP
4210ir/aplaatable pacemaker/defibrillator:worldwideexperience(abstract). PACE,14: 623.
Fahraeus, T.,-.Lassvik, C., and Sonnhag, C. 1984. Tachycardias initiated by automatic
~ antitachycardia pacemakers. PACE,7: 1049.
Falkoff, M. D., Barold, S. S., Goodfriend, M. A~Otig, L. S., andHeinle, R. A. 1986. Long-
term managementof ventricular tachycard~a by implantable automatic burst tachycardia-
terminating pacemakers.PACE,9: 885--895.
Fisher, J. D. 1990. Clinical results with antitachycardia pacemakers. In S. Saksenaand N.
Goldschlager(eds) Electrical therapyof cardiacarrhythmias.Philadelphia:Saunders.
Fisher, J. D. 1990. Antitachycardia pacing in the acute care setting. In S. Saksena~ndN.
Goldschlager(eds) Electrical therapyof cardiacarrhythmias.Philadelphia:Sannders.
Fisher, J. D., Kim,S. G., and Mercando,A. D. 1987. Argumentsfor antitachyeardia therapies
using a graded point score model. In G. Breithardt~:M. Borggrefe ~a~a~dD. Zipes (eds)
Nonpharmocologicaltherapy oftachyarrhythmias. Mt: Kisco, N¥:Futura Publishing~
Fisher~ J. D., Johnston, S. K., Furman,S., and Mercando,A. M. 1986. Implantable phcers for
tachycardia termination: Stimulation techniquesand long:termefficacy. PACE,9:!325-~1333.
Fromer, M., Shensa, M., Kus, T.~ and Page, P. 198~ Managemen~t,of ~ a~patient with recurrent
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ElectrophysioL, 1:133-139
Fromer, M., Schlapfer, J., Fischer, A., and Kappenberger, L. 1991. Experience witha new
implantablepacer-cardioverter-defibrillator for the therapy of recurrent sustained~ventricular
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tachycardiaby use of an automaticdefibrillator (AICD)in combinationwith an antitachycardia
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feasibility study. PACE,16: 2266-2278.
Kahn,A., Morals, J. J., and Citron, P. 1976. Patient,initiated rapid atrial pacing to manage
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implantable sensors for ~the: control of pacemakermediated tachycardias: a comparative
evaluation betweenminute ventilation sensing and acceleration sensing dual chamberrate
adaptive pacemakers. PACE,15: 34-44.
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18: 145-151.
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DDD Pacing: a multi center study of 91 patients. PACE,13: 867-874.
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Mehra,R. 1990. Electrical stimulation techniquesfor preventionof ventricular tachyarrhythmi~s.
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scanning tschycardia. PACE,7:1296
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18.1Whyand why not prescribe A~treatment?

18.2 Whyis the leading circlem~lel morelike the figure-of-eight modelthan the ring model?
18.3 How does refractoriness effect resetting? ~
18.4 Explain entrainment
18.5 Whyprescribe manual modeover automatic mode?
18.6 Diagramand give a shortlsummaryfor PES,Bur~t and underdrive antita~hycardia pacing.
18.7 List 3 reasons whyearly ATPsdid not enter ELT.~
18.8 Whatis the disadvantageto traditional ELTprevention? Pick one of the new’methods and
explainit.
18.9 Explainthe sequencebf e,~ents for a typical ELT~-
18.10- Whyare~the reported result generaily goodfor ATPs?
18.11 Since P~Cs are so commonin,the general population, c~m you explain ,under what
conditiOnsthey are not safe?
18.12 Canyouthink of a partic~ul~ situation wheretachycardiais not faster than what"wouldbe"
(hint) the "normal"sinus nodeheart rate7
18.13 List the pros and cons of prescribing ATPtreatment.
Implantable Cardioverter-Defibrillators
Adrianus Djohan
One~. disadvantage of antitachycardia pacemakersis the possibility of a sustained

tachy.arrhy~mia that is L not terminated or even accelerated to ventricular
tachy, cardia by ~.,antimchycardiapacing. Thetreatments that ~the physician has found
to ,~evert the tachycardia or fibrillation.back to normal pacing are using
cardioversion (which requires synchronizati0n 9 an i ntrinsic d epolariz’, a tion)and
d~fibrillation. Both cardioversion and defibrillatirh use a single energy pulse
(muchlarger than the pacing pulse). It is applied directly to the heart, whichcauses
synchronousstimulation of the heast(in ~e case of cardioversion) or asynchronous
stimulation of the heart (in the case of defibrillation) so that the myocardium
becomes refractor. This method is already known to be effective, and the
challenge isto build the implantable device to sense the tachyarrhythmia accurately
and deliver the pul~.eappropriately.
19.1 IMPLANTABLE CARDIOVERTER-DEFIBRILLAT( DRHISTORY
~.~eid 1960:Israeli 6ardiol,

fibriiiator.
ogigt Michel Mirowski conCeives of implantable
~ .... :~ :
, ’ 1969: Mirowskibecomeshead 6f coronary care at Sinai’Hospi.tal, Bal.tiI~n~ .ore.
He and associate Morton M0wer,:MD,personally fund research On defibrillatbr
pmt, oty~e.Prototype designed with William Staewen, ’CCE,and sucr~ss .fu!l~
i n idb0rat0r~.animals.
1970-!972 i Mirowski and Mower.enter patent agreement with Medtr0nie,
Inc. on c0mmer~ialdevelopm~nCMedtr0nic Subsequently.decides n:ot ’ tQ pursue
the project and re~ all patents.
!972-1980: Mirowski ~d. M0wer.~nter agreement with Medrad, Inc., of
Pittsburgh to de#e!op(the i~pl~tabl¢ defibrillator.. Engineers wprk t6 resolve
fundfirn~ntal devel~oGrnti~des g~ieh~ Wfi~,eform, tissue6onductivi~, fibriliation
detecla0n, electrolytic capacitors, batteries, and packagingof the device. Precl~mc
0,
1979"1980: Intec Systems, a subsidiary of Medrad, is granted an
Investigational Device Exemption(IDE) by the FDAto continue clinical studies.
1980: First experimental defibrillator humanimplant takes place on 4

February at John Hopkins Hospital, Baltimore. The operation was a success, and
the patient, a 57 year-old woman,is subsequently discharged with the implant ih
place ....
1982: Cardioversion capability added to Intec’s experimental device, now
called the automatic implantable cardioverter-defibdllator (AICD). ¯
1983: Medtronic introduces an implantable tachycardia device with
cardioversion capability. Intec files suit-against Medtronic, alleging ¯patent
infringement.
1985: Intec is acquired by Eli Lilly & Co., which assigns the defibrillator
business to its subsidiary, Cardiac Pacemakers,Inc. (CPI) of St. Paul, Minnesota.
In October, FDAclears the f’u’st AICD(manufactured by CPI) for marketing.
Medtronic, new chief executive officer expedites research on "tiered therapy"
pacer-cardioverter-defibfillator (PCD).
1988: Medtronic is enjoined’ from making, using, or selling implantable
devices with defibrillation capabilities in th~ U.S. Research and manufacturing of
PCDmovedto the Netherlands; U:S. clinical trials postpone&Initial PCDmodel is
implanted experimentally in Europe~ CPI Ventak 1550 second-generation
programmable ICDis FDAapproved~
1989: Courtof Appealsrules that patent statutes permit testing ofd~vices for
the purpose of satisfying FDArequirements even if the product iscovered l~y~a
competit0r’s patent. In’ November,Medtronicauthorized to begin clinical implants
of the PCDin the U.S.
1990: SupremeCourt upholds appeals court ruling in patent infringement suit.
MichelMirowsld,in,~entof of the Implantable defibfillafioncdies.
1991: Commercialmarketing of Medtronic PCDbegins in-Europe: Medtronic,
Lilly, and CPI announce settlement of all litigation and an agreement to cross-
license all relevant patents. CPI VentakP, with low-energyeardioversion and first
shock delay programmability, is approved by FDA.
1993: On February 11, Medtronic PCD7217B first tiered therapy with
epicardial’ lead was cleared for marketing~by FDA.OnApril 30, the-Cadence V-
100, manufactured by Ventritex, Inc. of Sunnyvale, California, is cleared for
marketing by FDA.On December9, Medtronic Transvene transvenous lead system
is cleared for marketing by FDA.
From the time line of the development of implantable cardioverter-
defibrillators, the first device FDAapproyed was, the CPI Automatic Implantable
Cardioverter Defibrillation (AICD), and ii was considered asa Second-generation
of the implantable d~fihrillator as opposed to the CPI experimental AID, Which
didn, g, have cardiov6rsion capability~ "~lae next two devices;’ whichwere approved
by th~ FDAin 1993; theMedtronic PCD,CPIPRxand the Ventritex ~ Cadence, are
considered as the third-generation of ICDsince they have added antitachy~ardia
pacing, bradycardia pacing,, biphasic waveform(only in Cadence),¯ and’tiered
therapy, iherapy that uses antitachycardia pacing to terminate ventricular
tachy~ardia or ~tentricular fibrillation ~fore resortin~ to a higher level of shock
energy.
In spite of the relatively recent developmentof the ICDcomparedto those of
pacemal~r, ~e market ’of I~D sales alone~eady to~ $300 ~ilion/yr, and it is
pr0j6cted to i~a6h $1 billion/yr r by the end of~e decade (~uclos, ~ 1993)..: ’Life-
threatening arrhythmias thh~ clai~n over 400~o00")km6dca~lives from sudden
cardiac death (SCD) each year provide the impetus for development o( these
devices.
IMPLANTABLE CARDIO~RTER-DEFIBRILLATORS 429
19.2 SUDDEN CARDIAC DEATH
Sudden cardiac death (SCD), a major problem in Europe and in North America,
accounts for 1200 deaths in the U.S. every day. In the Framinghamstudy, for
deaths between the age of 35 to 64, nearly one out of three is caused by heart
disease. Suddendeath itself is defined as death occurring within 24 h of onset .of
symptoms. :-
Depending on the underlying mechanism of SCD, the duration .of illness
beforethe-death vades~ For k example, most SCD caused by ventdcular
tachycardia/ventricular fibrillation occurs in a few minutes. ~Onthe.other hand,
SCD caused by pump failure could take considerably longer ........
SCDis a multifactodal problem that is usually associated with various forms
of structural cardiac abnormalities that interact with acute triggers. Someof the
more apparent triggers include myocardial ischemia, neurohumoral changes,
electrolyte abnormalities, pharmacological agents, and electrophysiologic events
(Naccarelli, et al., 1993).~ ~
19.2.11 Role of ICDin preventing suddencardiac death’
Since the first automatic implantable cardioverter-defibrillator (ICD)developed

Michdi~iirowski was implanted on February 4,.. 1980, more than 25,000 devices
have been implanted worldwide. Manystudies have demonstrated the efficacy of
the ICDin preventing SCDin patients with life-threatening tachyarrhythmias.
Figure 19~1 shows the survival curves constructed from a ~’~tudy,~n 52patients
wherein deaths are classifiedas sudden unless they were clearly @erwise. The
one-year mortality rate from all causes was 22.9%¢ whilethe sudden death was
8.5%. The other curve called "expected mortality" refers to a successful out-of-
hospital discharge of the defibrillator as a prevention of death. Thins was a figure
used to estimate what might have been expected if the,,defibrillato~ had not been
present and discharged appropriately. So this figure, suggested approximately a
52%decre~ein total mortality during the first yearfogowingICDi ,mplantation.
sudden death
total
expected
TIMEFRONIMPLANTATION
IN Y~EARS
Figure:19.1 Kaplan-Meiersurvival, cu~eshowing;changesin survi,,val, duertosuddendeathand

total (any causeof death). "Expected"
refers.to, ~ appropriat~out~gf-hgspit,~.defibri!lation,
whichwasassumed to havebeenfatal (mortality)if (he defibritlati0n h~dhot ~presefft. Frora
Naeearelli;G.V., andVeltri,:E: P. (eds) 1993;im~ldntable cardio~efte~lefibril~tors~Boston:
Blaekwell Scientific. ~
43O DESIGN OF CARDIAC PACEMA~RS
19.3 THE ICD DEVICE
Figure 19.2 shows an example of a paper design of an ICD system based on a

microprocessor. This system uses four integrated circuits and a set of discrete:
components. IC1 is the microprocessor, which communicates through data, and
address bus to IC4. IC4 has the band-gapvoltage,reference circuit, whichgenerates
1.235 V. It is used by the regulator to produce a 3-V power supply for the digital
circuits, by the~ 12-bit general purpos~ analog,to-digital converter (ADC)
measure, battery voltage and other diagnostic voltages, and bythe pacing generator
(pace atrium and pace ventricle). These both have a digital~to-analog converter
(DAC)to provide a programmablepacing pulse.
HV DISCRETES
CONTROL& DATABUS
POWERSUPPLY & PULSE DEL~ERY
Figure19.2 Microprocessor-based
third generationICDFromCarroll andPless (1991).
Each pacing circuit communicateswith the atrium (for pacing the atrium)
the ventricle (for pacing the ventricl~e) thn ~ugh two lines, Oneof the lines is
switchableground,and the other is ff~’p,a,~it i8 electr0de~ whichis also the input to
the sense amphfier in IC2. Both the atn~ an, t v~n~ial~ pacing lines pass through
IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS 431
through a set of switches in the HVdeliveryblock, the microprocessor delivers the

cardioversion or defibrillation pulse tothe heart.
IC2 is a microprocessor that runs the whole device. It provides timing,
interrupt, telemetry, and sensing function. The sensed electrogram acquired by the
sensing amplifier is amplified and digitized. The amplifier has multiple gain
settings, whichare under automatic gain control of the microprocessor to maintain
constant peak voltage. IC3 provides ECGstorage.
The crystal and monitor block has a 100-kHzcrystal oscillator that provides
clocks to the entire system. The monitor is a conventional R C oscillator that
providesa backup clock if the crystal should fail.
This chapter will not explain every element in the system, but it will go
through some elements that are different from the design of cardiac pacemaker,
such as the battery, voltage downconverter, and pulse generator circuit.
19.4 BATTERY
Oneof the major obstacles to th~ developmentof implantable defibrillators comes

from the inadequacy of the power supply. The pacemakerpulses are in the range of
25//J, and they are about a milliohth’ 6f the’energy neededto defibrillate, whichis
in the range of 15-40 J. Conventional bradycardia or antitachycardia pacing
produces peak current drains in themilliampere range, whereas defibrillation takes
peak current in the range of 1-2 A for approximately I0 s during high-voltage
capacitor charging operations. Lithium iOd~lie batteries, which are used in the
pacemaker, can not provide these high current requirements because the internal
impedanceis too high.
There was a consideration of using nickel cadmiumrechargeable cells for the
implantable defibrillator, but it had limited initial appeal because of the need for
fre~luent recharging, lZechakgeablelithium powersoul-bes were also considered, but
no ~,anufacturer has developeda device that used them.,
’.~ Lithiumvanadi~m~pent0xidebattery chemistry was~developedfor a National
Aeronautics and Space Administration application ’in ..1968. These battery ceils
have high charge density and output impedance low enough to efficiently charge
the capacitor but still high enoughto provide current,limiting an~ prevent venting
in Cas6 of a short circuit. The Cells ~sb’tendt0 m~iitain their vblta~e6venhnde~
loading with only a slight decline in vdtage a~t the end 0f.40--50%of Us~iblebhttery
life? Thepropei’ty oi~ maintaining th6 openci~:buit ~/~!tage is an undesirable
char~6~terisfic b~ause it has becam6ha~deito det~ the cad of life.~Apoasi~le way
f6~ ~/,e.Cfing the end 6~ lii~e 0fthese battery Cdls~i~-to me~uretli6 " b~i~ery voltag6
~6athe l~tt6ry ~is ehargilig da~ capacitor, because’ ur/ddr 10~ding the batte~ ¯
6~b~sa Vol~get.hat~ i~ rei~t~d to its l~e time (seeFigulm19.3).. ~’’
:i LikUta ~.anadium pehtoxide.cells have:bee~nab.an’dbiiectas ~th~ p6w6rs0iirce
for defibiillatorsby most manufactiirers in fa(~f of lithium ~ilvel vanadium
pentoxide cells. Lithium silver vanadiumpentoxide cells have two particularly
desirable features: they have much ~gher energy density and lower internal
resistance than lithium Vafladiu~pbn~bfidee~lls ~6,~the!batfe~ ,vOltage. gradub, lly
declines over lime as the cells discharge. The last characteristic makesit very easy
to detect the e~d of bat.tery !~fe as the open ,circuit vol~geand,khe loaded, battery
voltag~ correlat~e with~t.h~ ~6mainihg,~s~abteeli~rgyi ~)~ure .~9~3(a),shows ~the
t~pical Opencircuit voltage for the lithium ’vanadi~a pe~oxide ~eilk, and Figure
DISCHARGE CURVE FOR ALITHIUM/

VANADIUM PENTOXlDE CELL
(Honeywell G306 IB)
A
~ _ _ ./~- ~,.,..~ .~.v,.¢o vet,.
DISCHARGE CURV~ FOR A LITHIUM/

SILVER VANADIUM PENTOXIDE CELL
(WG 8615 or 8612)
3.S
Figure19.3 (a) Discharge

curvefor li~iumvariadiuthpentoxide,(b) dischargecu~efor lithium
silver vanadiumpentoxide.FromTroup,P. J. 1989.Implantable
Cardiovertersanddefibrillators.
Curr.Probl. Cardiol.,XIV:679-815.
19.3(b) shows the typical open circuit voltage for the’ lithium silver vanadium
pentoxide Cells.
Figure 19.3 shows that the vanadium~iiver pento~de pro~,ides approximately
3.2 V per cell ~nd’typicaliy two cellsare cbnne~tedins~ri~s in thedefibrillator so
that the battery voltage at ’the beginningof life is i~n ~the rang6of 6.4 V. Becausethe
digital circuits take 3.3 V, there is a ’n~ed for an ~ffi~ient~/oitage downconverter
and regulation. SomeICDdevices use two batteries~ ~~e lithium Silver vanadium
pentoxide for the high~v~ttage ~harging circuit and li~ium m~ganesedioxide or
lithium iodine for the 10w-voltagecircfiit. This arrangementeliminates the need of
a voltage downConverter.
The most impo~ant feature of any battery-powered system is longevity. The

limiting componentin: the life~ ofthos~systems ate almost invariably the battery
ampere hour or charge capacity. It is also knownthat the power consumptionof a

digital system is approximately proportional to the square of the power supply
voltage. Therefore reducing the voltage from 5 V to 3.3 V would yield twice the
battery life.
In a system that uses a microprocessor, two operating voltages are required: a
battery terminal voltage that is going to vary, dependingon battery condition, from
6.4 V to 4.5 V at the end of the battery life and a regulated 3.3-V supply from
whichmost of the device’s digital logic operates. It is also obvious that the 3.3 V
supply has to be maintained, even though large current is being drained from the
battery to charge the shock capacitor, because a voltage dip could cause a hardware
reset to the either digital logic or the microprocessorand erase all the setups that
are programmedby the .physician.
As the need for a lower voltage becomes dear, the system could just use a
linear vokage regulator without voltage downconversion, but substantial power
wouldbe dissipated in the regulator. Thepowerloss in the regulator is given by
Ploss= lload(Vbattery- Vregulator) (19.1)
and it is a function of the voltage drop in the regulator. Thus, an efficient voltage
downconverter to an intermediate voltage in between the battery voltage and the
regulated voltage would improve the efficiency of the systems. Efficiency without
a voltage down converter could be derived by dividing the power used in the
digital circuit by the powersupplied by the battery, and it could be Simplified as
efficiency = Vregulator (19.2)

Vbattery
Withregulated voltage at 3.3 Vand battery voltage at 6.4 V,~ the efficiency is
52%, and it would improve as the battery voltage goes downto 4.5 V, which gives
efficiency only up to 73%.
Using the downconverter, the efficiency is defined as
efficiency = Vregulator x y (19.3)

Vintermediate
where y is efficiency of the downconverter. Assuminga lossless downconverter,

the intermediate voltage is equal to two~thirds of the battery voltage whichis 6.4
V, the efficiency is 77%right from the beginning of the battery life. Figure 19.4
displays a possible circuit to reduce the battery voltage to an intermediate voltage.
It uses capacitors as a switched capacitor voltage divider to divide the battery
voltage into s~ve~ral intermediat e voltages.. ~ ¯ -
¯ -~ Switch S1 through S18 il driven by th/ee different clo~k pulses that are out of
phase and not overlapped. These clock pulses can be generated by the system dock
using circuit shown in Figure 19.5. Switches SMI, SM2, and SM3choose the
intermediate~vOltageSuch that the intermediate voltage is always higher than. the
regulated voltage. For example, if five capacitors are used to implementthe down
converter, 315 of the batteiTy voltage would be chosen at’the beginning of the
battery ~ fife to-give an intermediate voltage at 3:84 V, Asthe battery voltage drops
VBATTERY
i ~ SM2
aC2 7 I
S 10~,
!
!
I I I
P! P2 P3 ~
(a)
VBATTERY VBATTERY
CI~"
C2 ~"
C3 ~"
X7
~
.p1
Figure19.4 (a) Avoltage downconver~erconsis~g

limited by the numberof cap~a¢itoras more{i~m6dla~te
arrangement
of ~e ~C~acitb~
d~ngcf~k~
c~cte~P~1,~ P2’~~ :P3. Fmm~
Pless ~d~Ry~,~(..
1989~).
to 5.5 V, 4/5 of~e ba~e~ vol~ge would~be ehoseq ~give ~ ~~ate vol~ge
feedback voltage and a reference voltage, as shown in Figure 19.6. OP1 and
COMP1 work as a backup voltage regulator in case the intermediate voltage drops
below the regulated voltage which will be detected by COMP1 and ~ mrri disable
OP2. As the current is not being supplied by OP2, the voltage at the inverting
terminal of OP1will drop to slightly belowreference voltage, and OP1will turn on
and regulate the voltage, taking the supply directly from the battery terminals.
PI P2 P3
MASTER ~
CLOCK
(a)
MASTER
CLOCK
Figure19.5 (a) Adigital circuit to generatethree clockpulses. (b) Timingdiagramshowing

clockgeneratedbycircuit (a). FromPless andRyan,(1989).
19.6 PULSE GENERATOR CIRCUIT
19.6.1 Pulse waveforms
Fi~ure~ 19~7~§hows output"Waveforms used in implantabl~ cardi0verter

de~brillators. To conserve voitime’ and w~ight, the capaditJr ~]S~ ~alie? than that
V BATTERY
~ R BATTERY
BAbY
DETECTOR
....
CS~’b.EDI ~cos~v~ I
VOLTAGE
DOWN
CONVERTER
RGAP~
1
MASTER
CLOCK
Figure 19.6 Regulated power supply system for the digital circuit using a voltage down
converter, voltage regulator, and baeleap regulator. From Pless and Ryan, (1989).
used for external defibrillators. Thus, the exponential decay (til0 is morerapid.
solid-sate switch closes at 4-8 msto dumpthe.. charge. This truncates the waveform
to yield a higher success rate than is the exponential is allowed to continue. The
leads maybe interchanged half way through to yield the single pathway biphasic
truncated exponential waveform, which results in lower energy-requirements. The
leads maybe switched to a different pair of electrodes half waythrough to yield the
sequential biphasic truncated exponential waveform.
Monophasic ’~ Biphasic
truncated truncated
exponential exponential
Figure 19.7 Defibrillation wave forms. The monophasic

¯ truncated exponential waveform is
~5~ ms.,The biphasic truncated
IM LAN’I~ABLE CARDIOVERTER-DEFIBRILLATORS 437
The defibrillation threshold (DFT) is the shock magnitude at a given pulse

duration just high enough to defibrillate. This causes a required change in
transmembranepotential in a critical mass of the ventricles. The strength-duration
relationship for pacing level energies does not seem to apply to defibrillation.
Duringpatient testing, a small shock puts the patient into defibrillation and then the
patient shocked to determine the DFT. The ICD output is set higher to ensure
success. It should not be set higher than needed or it might damage the
myocardium.The ICDrequires a large safety factor, which is usually expressed as
shock energy minus the DFT.
19.6.2 Capacitorcircuits
While manyICDs use a single capacitor, some use two ~apacitors. An. efficient
capacitor-charging technique was developed based on flyback pritleiple~, where
energy was stored in an inductor and transferred to the capacitors .duriog a short
flyback pulse. Figure 19.8 showsthe circuit to charge the capacitors and generate
the shock pulse. The inductor was .formed by the primary of Tl.and the Sefondary
is split into two coils having advantage of charging each of the series-cormefted
energy storage capacitors to the same voltage, while providing a vol~ge doubler
action requiring fewer turns on each secondary. Reducing the~turns on:~each
secondary also has the advantage of reducing the energy lost ~ repeated~l~ycharging
and discharging the stray capacitance of each secondary.
Battery
Voltage
DI Q4:
R2 D2
T1
Patient
Terminals
Figure19.8 Asimplifiedschematicfor the capacitorchargingandpulse generatorcircuit inthe

implantabledevice.
The capacitors are discharged into the patient or the test load by silicon-
controlled rectifiers (SCRs) Q2,:Q3, and Q4 while D2 was added to~proteetthe
circuit from external defibrillation pulses. Oneinteresting feature about theeireuit
is the use of R1 and D1, whichconstantly supply battery voltage to the electrolytic
capacitors, as opposed to no voltage in the idle state, to reduce the effect of
deforming overlong periods of time when the c~pacitorsare not~i~ar~ed. Most
ICDsautomatically fully charge and discharge the~ap~cit0rs everyfew n~onths, i~
438 DESIGN OF CARDIAC PA( ~EMAKERS
19.6.3 The capacitors
Capacitors used in the implantable defibrillators have to be chosen for high energy
density. Generally, a capacitor consists of two electrically conductive layers with
dielectric or insdator in between. Manydifferent constructions and materials are
used for makingcapacitors, but, for an energy storage capacitor, there were two
technologies to choose from: the electrostatic type, which Uses film technology,
and the electrolytic style. Becausethe capacitance values are proportional to the
surface area, film capacitors optimized for high capacitance per volumeare often
the metalized type wherea very thin f’dm of metal is directly applied to a very thin
film of dielectric. The layers are then wrappedaround into a cylindrical structure
containing as muchsurface interface as possible. These film capacitors can be built
to accurate tolerance and are very reliable. Unfortunately, it is-difficult to achieve
high capacitance values at around 300 V as they have high-energy density only at
high voltage above 2500 V (Kolenik 1993).
In an~aluminumelectrolytic capacitor, a very thin layer of aluminumoxide.is
formed on the surface of an aluminumanode by an electrolyticprocess, where it
acts as a dielectric. This dielectric can be madevery ’thin and has high dielectric
strength. By etching or roughing the surface of the anode, the contact surface area
of the anode:can be multiplied’ manytimes: The film is formed by oxidation and
the thickness of the film is proportional to the oxidation voltage.
The forming process is important as it determines the maximal operating
voltage that can be applied to the capacitors. If a higher operating voltage than the
forming voltage is applied, high leakage current will flow. Deforming is one
problem associated with this oxide layer. With the absence of voltage across the
terminals of the capacitor, the thickness of the aluminumoxide layer is slowly
reduced due to normal chemical reactions within the capacitors. If the capacitors
were formed using a lower forming voltage, wheh higher voltage is applied,
leakage current increases and performancedifferences can he noticeable as it takes
longer to charge up the capacitors to ~he same voltage level. To solve these
deformation problems, the e~ly AICDfr~om~CPIused battery voltage to constantly
charge the capacitors and stop the deformation process. Another technique, as in
the Cadence VT-100 from:Ventritex uses automatic capacitor maintenance in
whichthe microprocessorwill charge the capacitors to a factory preset voltage and
discharge it through an internal 19ad. Figure 19~9 displays someICDdevices from
CPI and Medtronic with their d~ensions and volume, which are primarily due to
the size of the capacitors and battery, capacitance value, and energy output.
AID AID-B/BR Ventak Vental( Ventak-P PCD Jewel

1300 1400-I430 1500-1530 1550 1600 7217 7219
Height, cm 7.1 11.2 10.8 10.1 " 10.I 10.1 8.8
Width, em 4.6 7.1 7.6 7.6 7.6 7.0 6.3
Depth, cm 2.6 2.5 2.0 2.0 2.0 2.0 1.8
Weight,g 250 292 250 235 235 197 132
Volume,cc 145 162 148 145 145 113 83
Capacitance,./iF: 120 125 128 128~ 128 120 120
Ou~ut,.J ¯ 25-35, 23~37 23,37. ¯ ~: 26-30 ~ 0.1-30 0.2-34 0,2-34
Figure 19.~ Thedimensionsof someiCDde~ices, capacitancex~alues, ~ndrange of energy

output. FromTtoup,
P. J. 1989;Implantable
~ cardloverters and defibrillators. Curr. ProbI.
, :~
Cardiol~,.XIV:679~15. ~
19.7 LEAD SYSTEM AND IMPLANTATION TECHNIQUES
19.7.1 Electrodes and leads
Figure 19.10 shows that, after a thoracotomy, patch electrodes maybe sutured to
the parietal pericardium or directly to the epicardial surface. These are madeof
titanium screen and maybe backed with silicone rubber or polyurethane. Patch-to-
patch defibrillation requires about:~800V. Patch:to-patch pacing could be achieved
with about 5 V, but the large area~elec~odes require larger pacing currents.
Therefore, separate small-area electrodes are Used for pacing for reliable sensing
and to reduce power consumption.~
~ A~oraebtomy
Figure"lg.~0 throughthe upper~ dashedline permitsi~iaeemeh~t
’ of twi5 pa{~h
el~ctrbde;sfor pulses~andtw0screw-inelectrodes for sensinga~d~p~in~elowerdashe~lline
incision pen~its 91aeementof
Wepulse generator, in ~ abd~en.
To avoid the trauma of a thoracotomy, plattnum indium transvenous leads
in the
Figure 1~.11 The Endotak d~fibfillator consists 0~ a single w~1~ ~ sh~ng.el~s.~

~ su~fior vena cava ~d ven~cle (a, b) ~d a, ~in~nsing el~e ~ (c) ~n ~e ne~
a~x. ~e l~d is a~ac~ ~ugh a ~u~u~us ~nel to a pulse genera~r (~ impl~wo
¯ e a~o~n.
19.8 ~~ DETECTION
19.8.1 Automaticgain control
ICDelectrodes sense the 10-15-mVelectrograms and easily detect the individual

beats to determine the rate. The Cadence V-100 Series uses an automatic gain
control circuit because the electrogram amplittde often chang~s~ sig~canflY
be~een sinus rhy~and- tachycar~lia~ I~ there is a rapid.~ythm, the aut%~a~c
gain control will respond more quickly to a change in ¢lec~ogram ampnmae
(Ventritex, 1993a).
19.8.2 Fibrillation detection
D&~cti0n0f fibrillation is based on a

~ detected
minimumof 12 intervals is required. Detection of

fibrillation detection as long as normal sinus rhythm is not detected. If sinus

rhythmis detected prior to.therapy delivery, charging is terminated and no therapy
is delivered.
The fibrillation detection rate in the Defib Only configuration may be
programmedfrom 140-207 bpm (430-290) ms). In the Tach and 2 Tach Systems,
the range is 150-222 bpm(400-270 ms).
A bigeminal rhythm mayhave intervals short enough to meet the fibrillation
detection interval criterion and an aver.age rate that meets the tachycardia detection
criterion. Thus the pulse generator must detect more tachyarrhythmiaintervals than
sinus intervals before a shock is delivered. After capacitor charging is complete,
presence of an arrhythmia is confirmed before therapy is delivered (Ventritex,
1993a).
19.8.3 Tachycardia detection
Detection of tachycardia is based on both a programmedrate criterion and number

of intervals. The pulse generator classifies detected events~ based on both the
individual interval and a running interval average. The tachycardia detection rate in
a 1 Tach System may be programmed from 102-200 bpm (590-300 ms). In a
Tach System, Tach A may be programmed between 102-182 bpm (590-330 ms).
Tach B, which must be faster than Tach A, may be programmedbetween 109-200
bpm (550-330 ms). The number of intervals required for detection
programmablefrom 6 to 25, with an extended range of 30 to 100. After tachycardia
has been detected and a therapy is delivered, a minimum of six intervals is required
to detect taehyeardia and initiate the next therapy (Ventritex, 1993a).
A tiered response is used:: Morphologyanalysis is usedto differentiate
ventricular from supraventricular tachycardias. If sustained ventricular tachycardia
is detected, antitachyc~a pacing is implementedto prevent it from degenerating
info ven~eul~fibrillatioh. Failing that, a larger Shock is administered toperfo~
synch(~n~ed~ardioversibn. If v~ntricular fibrillation occurs’, a full shock is
fidmini~tefed. "
19.9 PARAMETERS OF PROGRAMMABLEDEFIBRILLATOR

(CADENCE CT-100 FROM VENTRITEX)
Fig~lre~lg~12 shtw~s th~ ventritex Cadence model V~100 Tiered Therapy

defibriilator i~ade by.Ve/~tritex, Inc., Sunnyvale,CA,USA.It is a thirdkgener~fion
antita~h~ythmia de¢ice. The implan~ble pulse’generator is multiprO~r~able
~d is capable of defil~rili~tion~ low er~e~gyeardiove~ion,and antitaehycardia and
bradycardia pacing. The device was designed to be a~defibrillator ,with other
capabilities, not an antitachycardia pacemakerwi~ backup defibrillation. During
sequential tiered therapies, a therapy less aggressi~,e than ~e pre~iou~~ therapy is
never delivered. In addition if less aggressive therapies, for example
fail to terrainate~ an episode of ventricular
these therapies are ~ibandoned!
for use with theVentritex
tuency
,gramming programming wand can be
442 DESIGN OF CARDIA~C PACEMAKERS
ethylene oxide gas sterilized for use in the operating room, The programmeris
menu driven with parameter values selected from overlays that display the
available range of selections.
tqoclel V-100
Pulm ~eneratof
Figure 19.1,2 Ventritex CadenceModelV-100Pulse Generatorand,ModelsDP~5019 ;and DP-

5038DefibrillationLeads.FromVentritex,1993a:Cadence;.
Tieredtherapydefib/r~llatorsystem;
V-tO0Se~r~ !e:s~puls¢~gener~ator
andprogrammer,Sunt~v~e,
iC~.~ .~o . ¯
¯ Th~.,Model VrlO0 pulse~generator ~an~/be ~progfammed’to fi~ei~d[f,ferent

configur~itions: All functions Off, Brd~yca’i~diapaCingon!y; de~fibdll~,tor ~fth no
tachyc~dia response (Defib offl~), defibriUaiorwahtachyca~dia re~po~e/smgle
tachycard~a discriminataon (1 tach system), or defibrillator w~th ~ta~hycardia
response/tach A and tach B discrimination (2 tachsystem).
19.9.1 All functions, off . ~ ¯ ~. ~ ~ ,~ :: ~ ~ ~

In the all functions off mode, the pulse ~ generator wdl not ~l~liver ta~h~,~~a
therapy or bradycardia pacing pulses. No tachyarrhythmia diagnostic information
or electrocardiograms are stored. This m0de, c~be us ~e4[,~?n,y time ~e patient is
n_mder~,continuoussurveillance, in ,the~h6spital. In addition, the pulse ge~rator
shoUld ~e p~ogrammed function off’~luring~surge~.,utilizi~i/~i~gieal
urhtS that ~gh~ trigger hlgh,voltage0u~utsl.fr0~,thdA, e~:~gi:. ’~ ge/a itor
~
1~9’.9.2 Bradyc~dia pacing o~y ~ ~ ~, ~..,,
’niode
be
IMPLANTABLE CARDIOVERTER-DEFIBRH~LATORS 443
19.9.3 Defibrillator with no tachycardia ~r~ponse (Defib only)
This configuration allows programming of the detection rate of one

tachyarrhythmia. A maximumof six synchronous defibrillation shocks can be
delivered during a tachyarrhythmia episode. Two of these shocks may ~be
programmedin the range of 100-750 V; the remainder must be at the maximum of
750 V, The waveform can be programmed to be either biphasic or monophasic
truncated exponential. Ventricular-inhibited bradycardia~pacing may be
programmedto a rate between 25-90 ppm, or turned off.
19.9.4 Defibrillator with tachycardia response/single tachycardia

discrimination ( I tach system)
Tw~tachyarrh~a, d~tection rates’ Can~be programmedin this configuration:

tachycardia(the 8!owerr~te) and fibrillation (the faster rate). Available tachycardia
ther,apies ,include antitachycardia l~acing and upto four synchronouscardioyersion
Sho~i~’at thre~e progr~ed levels or~p to five synchronous c ~ digverslon shocks
at,four prggra~ed !evel~ .(with0ut ~titachycardi~ pacing). Antitachycardia
pacing ~r one cardioversion shock between 50-750 Vm~ybe: ~lected for the first
tachycardia therapy. The second and ~ird therapies (which can be ~rned ¢~f0 are
cardioversion shocks programmable between 50-750 ,V with th~ condition that
successive therapy voltages must be greater than 6~’qual to p~evioUs therapy
voltages. On~ or two cardiover~ion sh~cks programmablebetween 550-750 V may
~ selected ~f0r the fourth ther~Y (whiChCa~~ als0 be turned Off):
19,9.5 Defibrdiator with tachycardta respons~(T~ach K and Tach~ ~

~rinflr~O~/ti~n (2 tach system) .... ~ ~~ r ~
Three tachyarrhythmia detection rates can be programmedinthis configuration:

TachA (the slowest rate), TachB (a faster rate), and fibrillation (the fastest rate).
Tach A can be treated by delivering antitachycardia pacin~g and up to two
synchronous cardioversion shocks at one programmed level or up to three
synchronous c~irdici~erSitn shocks at two programmed levels’ (withoat
antitachycardiapa~ing). -" ¯ ¯ ¯
:Tach B therapies consist of synchronous eardioversion shocks only. The first
therapy can be programmed: between 50-750 V. One or twocardiover~ion shocks
programmable between 550-750 V can be selected for the second therapy (which
~anbe’tumed off) ~ :
"An additional ~ parameter, Extended High Rate~ (EHR), is,used tO: detect
sustained tachycardia inthe eventthat the tachyeardia therapies delivered within a
programmable length of time have not been successful. After detection of
fibrillation or Extended High Rate, a maximum of six synchronous defibrillation
shocks can be delivered and they can be configured just as in’ the defibrillation
mode only.
19.9,6Fibrillationidetection ¯ ~ ~
Detection of fibrillation is ~based On a programmed:rate criterion~r The pulse

generator classifies detected events based~on both the individualinterval and a
running, inte~al average~:Thearrhythnfia cycle length must be shorter than or equal
to the fibrillation detection interval~:to.,~satisfy !the detection criterion, and a
minimumof 12 intervals is required~Detection ,of long intervals will not reset
fibrillation detection as long as normal sinus rhythmis not detected..ff .sinus

rhythmis detected prior to therapy delivery, ’ charging is terminated and no therapy
is delivered.
The fibrillation, detection rate in the Defib Only ~configuration may be
programmed from 140-207 bpm (430-290 ms).In the 1 Tach and2 Tach Systems,
the range is 150-222 bpm(400-270 ms).
19.9.7 Tachycardia detection
Detection of tachycardia is based on both a programmedrate criterion and number

of interVals. The’ pulse generator classifies ~ detected events based On both the
individual interval and a running interval average. The taehycardia detectiOn rate in
a 1 Tach System may be programmed from 102-200 bpm (590-300 ms). In
2 Tach System, T/~ch Amaybe programmedbetween 102~182 tipm (590-330 ms).
Tach B; which must he’faster than Tach A; may be progr~/mniedbetween 109-
200 bpm (55&300 ms). The number’0f intervals required for detedtion
pro~a,ble’from 6 to 25, withan extend~ ~ge of 30 tO i~:After t~chycai~dia
has been:dete~tedand a therapy is delivered, ~i minimum: Of ’six"~terval~ is required
to redetect tachycardia and initiate the next~ ~apy.
19.9.8 High-voltage waveform
Tachycardia and fibrillation therapy ni~ay beperf0rmed with either a biphasic or

monophasic truncated exponentiaJ Wax~e~orm:Theselec~edWavefoftn i~ u~ed for
~1 high-~vo!t~ge theropy;~ (t~ is not independently programmablefor c~ov~rsion
and defibnilat~on. The bip)iasic wavefbrmis generated by the concaten~on of
positive polarity truncated exponential waveformand a negative pol~t~ ~ncated
exponential waveform.
19.9.9 Pulse width
The waveformpulse width is selected on the High Vol~ge Wavef0rmScree~n~ If a

biphasic waveformis selected, the duration of both the positive and negative
phases areprogrammable. The selected pulse width is used for all high:v~ltage
therapies and is not independently ~programmable ~.fo~:~gardioversion~ and
defibrillation.
The pulse width of a monophasic truncated ~, exponential wavef9~ is
programmable from 3.0-12~ ms, ~The biphasic ~waveformhas. a positive: phase
programmable from, 3.0,10.0 ~ms and a negative phaso progtammab]e~from
1.0-10.0 ms.
19.9.10 High,voltage lead impedance .....
The high-voltage lead impedance, along with the programmedwaveform, therapy

voltage, and pulse width, is used for calculation of estimated d~li~ere~~ne~gy.
Before the pulse generator has delivered any shocks to the patient’s implanted
leads, nO impedance data~ ate stored inthe device and
estimated impedanceblock on the Fibrillafitn~ ~Therapy
screens. After the pulse generator~’has ,deliVered shocks to irdplanted.l~ads,
interrogation of,the device.will retrieve,~the nieasured im~dan¢~~ftomthe last
shock and display it in the estimatedimpedance~block.
19.10 THIRD-GENERATION ICD
The third generation of implantable eardioverter-defibdllators are marked by

devices that can give tiered therapy, antitachycardia pacing, bradycardia pacing,
extensive diagnostic information, more complicated ventricular tachyarrhythmia
andventriculat fibrillation detecti0nalgodthms, biphasic waveform,noncommitted
shotk; :andcapability to store electrocardiograms. Figure 19,13 shows a cutaway
viewOf:fi_n ICD.
Figure 19.13 This cutawayview of a JewelmPCD® Model7219Dimplantable cardioverter-

defibrillator fromMedtmnic,Inc., Minnepolis,MN
showsthat the battery andcapacitorconsume
a ~arg¢portionof the volum.e.
19.10.1 Biphasic waveform
Comparedto epicardial lead systtnis, nonthoracotomydefibrillation lead systems

require higher shock energies for effective defibrillation. Whenimplanting a
cardioverter-defibrillator with a nonthoracotomylead system, getting sufficient
dwefibrillation
aveform pulses efficacy is a major issue. Several efficacy
yield increased:defibrillation studies show
whenthat biphasic
compared to
defibrillation with monophasicwaveforms.At present, there has not been sufficient
study of the influence of .biphasic defibrillation waveform pulses on the
defibrillation efficacy of different nonthoracotomydefibrillationlead systems.
Neuzner~et al. _(1994) showfor 30 p~tients that the meandefibrilla,tion threshold
(DFT)’~r mon0phasicshocks, was 22.2+_5.6 J, whereas the meanDFTfor biphasic
waveformswas 12:5+__4.6J.
¯ ¯
446 DESIGN OF CARDIAC PACEMAKERS~:
19.10.2 Stored electrograms

A major limitation of first and second generation implantable cardioverter-
defibrillators has been the inability to determine the rhythm preceding shock
therapy. The presence and severity of symptoms preceding ICD shock are
unreliable indicators of the presence of sustained ventricular arrhythmias, Even
rapid ventricular tachyarrhythmias maynot produce significant symptomsprior :to
ICDshock. Physicians evaluating patients whohave received ashock from the first
or second generation ICD can not easily determine whether the detection was
appropriate or inappropriate.
Several of the latest generation of ICDdevices provide stored electrograms of
electrical events leadin to device therapy. Eleetrograms are recorded from either
the local pacing or from the
wider
or
can
be
is
foundin surface ECG
; cardioverter-
of
during
detection ~the
If a rate less
immediately
and no therapy is only when the device has
chargedto deliver a shock, not whenantitachycardia pacing therapy is initiated.
19.11 REFERENCES
PAt,E, Klein, H., andGriffin, J. C. (eds.) 1992.TheimplantableCardioverter/defibrillatOr:

BedimSpringer.
Beckman,D. J., Crevey, B. J., Foster, P. R., Bandy,M., and Evans, M. 1992. Subxiphoid
approachfor implantablecardioverterdefibrillator in patients withpreviouscoronarybypass
surgery, PACE,15: 1637-1638.
Brachmann, J., Stems,L. D., Hilbel, T., Schoels,W.,Beyer,T., Mehmanesh, H., Lange,R., Ruf-
Richter,J., Kra~,t,P., Hagl,S., andKubler,W.1994.Acuteefficacyandchronicfollow-upof
patients with non-thoracotomy third generationimplantabledefibrillators, PACE,17: 499-
505.
Carroll, K, J., ~ndHess, B. D. 1991.Implantable~eardiacdefibrillator employinga.switched
capacitor filter stage havinga low charge-injectioninducedoffset voltage.. USpatent
4,989,603.
Duclos,’D. L. 1993.TheICDmarket(!mplan~bl¢ cardioverter-defibrillators). Wessels,Arnold
., & Henderson,Telephone’612-~73-6234:’ ~ ’ "~
Estes, N: A. M. IIL ManoliS,’A. S.~ and .Wang,P:. J. 1994. ImplantableCardiove:ter-
defibrillators: a comprehensive textbook:NewYork:Dekker.
Fain, E. S., .andiWinkleiR. A~1993,Implantablec~dioverterdefibrillator::VentfitexCadence:
iTardiovasc, ’E!ectrophysiol., 4: ~ 1 i-~23~ ....
~ R., Brodman,
Frame, R., 0r0ss, J~; Hollinger,L Fisher, J. D., Kim,S. G., Ferriek, K:~
and FUrman,S. 1-993. Initiar~e~perience with transvenousimplantable~ eardioverter
defibrillator lead systems:Operativemorbidityandmortality.PACE,: 16: 149-152.
Frame,R., Brodman,R., Furman,S., Gross, J., Kim,S. G., Ferdck, K., Roth, J., Hollinger, I.,
and Fisher, L D. 1993. Long-termstability of defibrillation thresholds with intrapericardial
defibrillator patches. PACE,16: 208-212.
Frumin, H., Goodman,G. R., and Pleatman, M. 1993. ICD implantation via thoracoscopy
without the need for stemotomyor thoracotomy. PACE,16: 257-260.
Gordon, T. and Kannel, W. B. 1971. Premature mortality from coronary heart disease: The
Framingham study. J. Am.Med. Assoc. 215: 1617-1625.
Haaser, R. G., Kurschinski, D. T., McVeiglLK., Thomas~A., anffMower,M. M. 1993. Clinical
result with nonthoracotomyICD. PACE,16:141-148.
Kelly, P. A., Mann,D. E., Dande,R. S., and Reiter, M. J. 1994. Oversensingduring ventrieular
pacingin patients with a third-generation implantablecardioverter-defibrillator. J. Am.Coll.
Cardiol., 23: 1531-1534.
Kolenik, S. A., Langer, A. A., Heilman, M. S., and Staewen, W. S. 1993. Engineering
considerations in the developmentof the automatic implantable cardioverter defibrillator.
Prog. Cardim, asc. Dis., XXXVI: 115-136.
Marchlinski, F. E., Gottlieb, C. D., Sarter, B., Finkle, J., Hook, B., Callans, D., and
Schwartzman,D. 1993. ICDdata storage: Value in arrhythmia management,PACE,16: 527-
53~4.
- Nacearelli, G.V., and VeltH~E. P. (eds) 1993. implantabIecardioverter-defibrillators. Boston:
Blackwell ScientifiC. ¯
Neuzner, J:, Pitschner, H.F., Huth, C:-; and SChlepper,M, 1994. Effect of biphasic waveform
pulse on endoeardial defibrillation effic~y ~in humans,PACE,~ 17: 207-212.
Pless, B. and Ryan, J. G. 198~. powersupply down-conv,~rsion, regulation and low battery
" dete~fion S~teii~.US patentS,g68,908.
Pless, B. arid Ryan, J. G. 1989. Power supply:down-conversion,regulati6n ~and low battery
~.
-itetecfion systerr~ USpatent 4,952,864
Hess, B, Sweeney,M., and Winkle,R.: 1989. Apparatusfor protecting the heart with protected
pacer. USpatent 4,827,936.
Ple~s~ B., Swe.~ey~M.~W~e, R. i989. Apparatfig for protecting the heart with protected pacer.
us patent 5;115,807.:
Saksena, S, .~t ~al. 1993,~¯D~fibrillation thresholds and pefiop~rative meatyassociated with
endoeardialan~¢pieardialdefibrillation lea~ ,syste ~ms
¯ ,, Singe#,i. ~ed~)1994~ImplahtableCardioverter-defibrillator.Arm~onk, NY:Futura Publishing.
Troup,P. J. 1989. Implantablecardioverters and defibrillators. Curr. Probl. Cardiol., XlV:679"
815.
Ventritex. 1993a. Cadence;Tiered therapy defibrillator system; V-IO0Series pulse generator
and programmer,Sunnyvale, CA.
Ventritex. 1993b. Using the Cadenceprogrammer,Sunnyv/de, CA.
Walleott, G. P,, Waleott, K. T., Knisley, S. B., Zhou, X., and Ideker, R. E. 1994. Mechanisms of
defibrillation for monophasicand biphasie waveforms.PACE,17: 478-498.
Winkle, R. A., Mead,R. H., Rudder,M. A., Gaudiani, V., Pless, B., Sweeney,M., and Schmidt,
P. 1989. Improvedlow energy defibrillation efficacy in .man with th~ use of a bipbasic
truncated exponential waveform.Am.Heart J.-, 117: 122-127.
Winter,J., Vester, E. G., Kuhls,S.,, Kantartzis, M., Perings, C., Pausehinger,.M., Straner, B. E.,
and Bir~ks, W. 1993. Defibrillation e~nergyr~quii~ments’withsingle endocardial (End0tak)
lead.PACE,16: 540-546.
19.12-INSTRUCTIONAL OBJECTIVES
19.1 Explainthe conceptof tiered therapy.

19.2 Explain howauto~c gab!,, control works.
19.3 E~plain howtachye~a is detected.
I9.4 Explainhowfibri~ationisdet~ected.
19.5 Explain the problemofusinga lithium vanadiumpentoxide cell ~as a battery for the ICD
and a techniqueto sol~¢the problem.¯
19.6 Explain whyvoltage downconversion is needed and howto efiminate downconversion
but withoutsacrificing the device longevity.
19.7 Explain whya secondvoltage regulator is needed
19.8 Givethe advantageof havingtwosecondarycoils in the pulse generator.
19.9 Explain the problemof deforming.
19.10 Explain the advantageof the stored electrogramin ICDs.
2O
UWPacemaker Tester
Mark D. Werkheiser
A computer simulation that allows observation of a pacemaker’s behavior was

developed at the University of~Wi~consin on a Digital Equipment’C0rp. (DEC)
VAXstation¯ 3200. The pacemaker, tester.:~ was ,developed i in a semester-long
undergraduate comptiter control class and allows the user to designand save test
signals and Use them as a soui’ce for a c~di~ac pacerhak~er~A pacemaker,e!e~trode
Senses these test signals and the signal andthe pacemaker’s behavior can be
examined graphically. The first section of this chapter~briefly discusses some
commercially available pacemaker’ testers~Thenext section of th6 chapter
describes the UWpace~aker tester. The!ast section of th~ chap[er shows some of
the testing algorithms used to observe the behavior of a Medtronie Legend®
single,
the pacemaker’s pacemaker, sueh ~,
chamber tefraetorypefiod as and
the th~
pacemaker
’ pace~aker’.~
in inhibitreactign
and,trigger
to a missed
mode,
heartbeat.
20.1 PACEMAKER TESTING
20.1.1 Pacemaker testers
A pace~?~aker
tester is a device that !s used t6teSt the operating characteristics of a
pacemaker. Someof these characteristics arepuls~ Width, pulse ampli~de, rate,
and demandsensitivity. Pacemaker testers are used in hospitals to verify the
performance of external pacemakers and to test implantable pacemakers before
they are implanted. Twocommercially available pacemaker :testers aredescfibed
below.
Netech®PMT 100 ¯
The Netech PMT100 is a portable, miO~oprocessor.basedpacemaker tester. It is
capable of testing invasive and transthoraoc pacemakers. The PMT100 measures
and displays amplitude, rate, energy, and pulse width of ~the pacing pulse as well
as demandsensitivity tests, refractory period, ~and susceptibifity to 50/60-Hz
intefferen6e~ " ¯ ¯
Environics Adaptively. Technology _ ~,

PaceAlyzer is an PC-based pacemaker tester that~uses software i~n~0njunction
with a plug-in interface card: The PaceAlyzer system iS :capable of testing
" UW PACE~KER TESTER 449
invasive and noninvasive pacemakers. The PaceAlyzer measures pulse duration,

pulse height, pulse energy, pulse rate, AVdelay, sensitivity, refractory periods,
and interference immunity. After the measurements are performed, the results
can be stored in the Device History. There is also adatabase"eontaining Model
Personalities, which are ideal characteristics of different pacemaker models.
These personalities are compared to measured values when~ testing so the
technician performing the test can verify the performance of the pacemaker. A
technician can perform an Auto-Test, which cycles through all the measurements,
and determines the status of the pacemaker by comparing the measurementsto the
ModelPersonality for the specific pacemaker.
20.1.2 UWpacemaker tester
The UWpacemaker tester is different from the two pacemaker testers described
above in that the user can develop test signals and observe howthe pacemaker
behaves while sensing the signal. There are two aspects of the pacemaker tester
that allow for the observation-of a pacemaker’s behavior. The first is the
production of the pacemakertest signal, and the second is the detection of the
pacemaker pulses. Figure 20.1 shows a block diagram of the UWpacemaker
tester.
Pacemaker
DAC
Figure 20.1 Blockdiagramof ~e UWpacemakertester. Thf VA~X is a DECVAXstation3200,

the ADC is a DECADQ-32anal0g-to-digital converter, andthe DACis a DEC AAV 11-Ddigital-
to-analogconverter.Thepacemaker is a MedtronieLegend.TheVAX developsthe test signal and
sends it to the DAC,whichsends it to the pacemaker electrode. TheADC samplesthe pacing
pulsesandsendsthe data to the VAXto be processed.
A DECVAXstation 3200 produces a test signal and sends the signal to a

digital-to-analog converter (DAC, DECAAV1l-D). The pacemaker senses
test signal:and responds by pulsing. The.pulses are sampled by an analog-to-
digital converter (ADC,DECADQ-32)and processed. Next, the test signal and
pacing pulses are displayed graphically on the VAX’smonitor.
Test signal requirements

To produce a test signal compatible with a pacemaker, the signal devei~oped must
be similar to the signal sensed by the pacemaker electrode whenimplanted in a
humanheart. The signal sensed in the left ventricle (ventricular electrogram)is
different froma surfaceECG, as shown in Figure 20.2. The QRScomplex is the
dominant wave"form in a. ven~cular eleCt~ogram since it is produced by a
ventricular contraction. The T wave is present, but the P waveis not because of
the distance to the atrium from the sensing electrode. The P wavei s not always
absent dependingon wherethe sensing electrode is positioned in the left ventricle.
A ventricular sensing pacemaker uses the QRScomplex to determine when to

pace.
QRS IS QRS QRS
Ventricular
Electrogram ECG
Figure20.2 Acuteventricular electr0gramandatypical ECG.Theventfieular electrOgram is the

signal recordedwhena sensingelectrodeis locatedin the left ventricle. Noticethat the QRS
complex is the dominant
waveshapeinthe signal andthe absenceof the P wave.Theamplitude of
the electrogramQRScomplexis 5 mVand the width of the complexis about 100 ms. These
c~haractefisties
varywithsensoryelectrodeplacement
andpatient.
The sensing circuitry in a pacemaker does not look for an actual QRS
complex, it si~mply senses whenthe signal crosses a voltage threshold that can be
specified by external programming. The QRScomplex is the only part of the
ele6trophysiological signal that eXceedsthis threshold, so the other parts of the
signal, such as the P or T wave, do not have to be incorporated into the test
signal. The UWpacemaker tester uses triangle pulse waveformsto simulate the
QRSsignal and thus the ventricular electrogram. Figure 20.3 showsthe triangles
used in the model. The parameters of the triangles (width of 100 ms and
amplitude of 5 mV)are taken from the ventricular electrogram in Figure 20.2.
Figure20;3 Th~modelusedto simulatethe ventricular eleetrogramal’ea sequenceof triangle

pulse waveforms 100 mswideand5 mVhigh. Thetime intervals betweenthe triangles (T) canbe
specifiedto allowdevelopment
of differenttest signals.
20.2 PROVIDING THE TEST SIGNAL
As described above, triangle pulse waveforms are used in the UWpacemaker

tester to model the QRScomplexand thus the signal seen by anactual pacemaker
electrode located in the left ventricle. The pacemaker tester allows a30s test
signal to be developed in software and then sent to the pacemakerelectrodes via a
hardware interface. The user designs the test signal by specifying where the
triangles are placed and the time betweeneach triangle.
~ UW PACEMAKER TESTER 451
20.2.1 Software
The software aspect of the UWpacemaker tester is written in C code. VAXLAB
software is also used to communicate with the hardware (ADCand DAC), and
MOTIFgraphics environment is used to display the test signal and observe the
pacemaker’s behavior.
The user develops a 30-8 signal by specifying the location of all the triangles
and the ,time beiween each of the triangles. This is done by typing a "Q" for
triangle and typing the time interval (in seconds) between each of the triangles.
This is repeated until a 30-s signal has been developed. Figure 20.4 shows an
example of howthe signal is developed. The triangle data points were developed
using Matlab and are stored on the VAX’shard drive. The 100-ms width of the
triangles has to be accounted for by the user whendeveloping the 30-s test signal.
After the signal is developed, the user has the option of saving the signal. The
user also has the option of loading a predeveloped signal that.is saved, on disk
instead of designing a new signal. Future improvements made to the UW
pacemakertester will incorporate a graphical user interface to develop, load, and
save test signals.
5 2s
Figure20.4 Asampletest signal producedwhenthe user types Q, 1.0, Q,, 1.5, Q, 2, Q.
After the test signal is developed or loaded from disk, it is placed in a

32,768-element array consisting of short, integers (2 bytes). A 32,768-element
array is used be~gause the VAXLAB soft,are ~lo~s. a co~fi~uous"0utput~sign,al
(Continuous, Direct MemoryAccess) when~the buffei:s contain 64 kilobytes
(32,768 elements × 2 by~t~s/element). The.triangle data has~,i!~!4 samples wi~ich
represents 0.104 s in the 32,768-elementarray.
20.2.1 Hardware
After the signal is:put i~n ~e array, i~ is loaded into, four 16-kilobyte data buffers.
The,signal is,sent~ou t through a Digital AAVli-D DAC~,a~ a rate of 1092
samples/s.ThiSrate corresponds,.to, 30 s 0~, Signal for the 32,,7687elementbuffer,
The output signal has a magnitudeof aboilt ~ 5 V,, peak,~ a~ndth~ pacemakerneeds a
Signal of about 5 mVto sense, so the:signal cqming ~t ~oftile DACi s oltage
divided~-down from 5 V to 5 inV, The 5~mVsignal is then s~nsed by the
pacemakerelectrodes, Figure 20.5 is a .block diagram of the Si~iai deveiopment
aspect of the UWpacemakertester.
20.3 MEASURING THE PACING SIGNAL
Whilethe DACis sending out the test signal, the pacemaker responds:by putsing
dependingon the signal it receives. These pulses must be detected so the user can
observe whenthe pulses occur with respect to the test signal. This is done by
sampling the pacemaker electrode voltage using a DECADQ-32ADC.
5V 5 mV
VAX
Figure20.5 Blockdiagramof the signal development aspect of the UWpacemakertester. The

VAX e0mputerproducesthe test signal andthe DACsendsthe signal to the pacemaker.
Avoltage
¢fivideris usedto step the outputof the DAC
from5 Vdownto 5 mV,
20.3.1 Software
The sol, are sa~_ples the pacemaker electrode voltage and uses the samples to
determine whenthe pacing pulses occur with respect to the test signal. First, the
pacing electrode voltage is sampledat the samerate as the test signal is being sent
out by the DAC.This is accomplished by using the ADQ-32internal clock as a
source for both the ADQ-32and the AAVll~D.Since the ’clock rates are the
same for the ADCand the DAC,the DACbegins sending out the test signal as
soon as the ADCbegins to sample the pacing electrode voltage, and each sample
from the ADCcorresponds to ~the same’ point in time a~ the .test signal being’sent
out by the DAC.So after the 39-s test signal is sent out, there is a 32,768-element
array coqtaining ~e test signal as well as a 32,7687element array containing the
sampled pulse dat~.Next, e~ch element of ~the sainpled pulse .data array is
compare~, to a threshold th~it iS detgrmined by the pacing puls~ amplit6de.
Finally; if the eleraent has’an amplitude thai’is greater than’ the threshold, the
corresponding element inthe test,signal arrgy~ is replaced by a flag denoting a
pulse.
20.3.2 Hardware
A pacemaker’s paeitlg pulse-widths are externally programmable and can be as

small as 0:2 ms. In order to’ ef~f,e.c~vely sample~ese pulses, a Samplingrate of at
least 10t~z must be used. If this Sampling rate were used for.30 s, a 300;000-
element .sample array would be produ6ed, which is too big to store in memory
and would take too long to process. To allow a sampling rate of 1092.samples/s,
the UWpacemaker tester uses the pacing pulses to trigger a 555 timer
implemented as a one2shot. The oneshOt prostrates a pulse ~hose width can be
specified by external resistor and capacitor values. Choosing a pulse width of
3 ms allows the data to be sampled at the same rate the electrogram signal is sent
out by the DAC.The maximal timing error involved is only about 1 ms. Figure
~,
20.6 shows the circuit used to sample~e pacingpulseS.
Figure 20.7 is a block diagram of the software used in the pacemakertester.
It shows the output of the test signal and the measurementof the pacing pulses.
Figure 20.Sshows some of.the C eoderused to produce the test signal and process
the pacingpulses.
UW PACEMAKER TESTER 453
0.2-mspulsewidth
_ ~,/’5-V amplitude
Pacemaker ~ 555 timer I

3-mspulse width
amplitude
ADC VAX
Figure20.6 Hardwareblock diagramfor sensingthe pacingpulses. Thepacemaker sends out a

pulse whosewidthcan be specifiedby external programming.
For everypacemakerpulse, the 555
timer producesa 3-mspulse. Thesepulses are sampledby the ADC and processedby the VAX
computersoftware.
20.4 TESTING ALGORITHMS
This section showsthe results of several tests that were developed and run on the
Medtronic Legend pacemaker. These results come directly from the test signal
array with pacing flags as described in section 20.3A, The pacemakerwas put in
ventricular sensing modeand programmedfor a rate of 70 bpm and a refractory
period of 425 ms.
The UWpacemaker tester sends a test signal to the pacemaker and records
whenthe pacemaker pulses. In an actual heart, a ventricular contraction would
result from the pacemaker pulses and a QRScomplex would result. The 30-s test
signal cannot be changed while being sensed by the pacemaker, so any changes in
the test signal, such as a QRSstimulated by a pacing pulse, Cannot be accounted
for. This open-loop characteristic of the UWpacemaker tester brings up three
timing cases that must be observed:
1) pulse-triangle interval > pacemaker refractory, heart
refractory: This case is accounted for by the UWpacemaker tester. If the time
interval between the pacing pulse and the next triangle producedby the tester is
greater than the pacemakerand heart refractory period, no alteration of the test
signal is needed.Figure 20.9 illustrates this timing case.
2) heart refractory < pulse-triangle interval < pacemaker
refractory: This case is also accounted for by the UWpacemaker tester. The
pacemaker pulse would produce a natural QRS, andthe next triangle wave
producedby the tester can occur because it is not in the QRS’srefractory period.
If the time interval between .the pacing pulse and the next triangle produced by
the tester is less than the pacemakerrefractory period, the triangle will not be
sensed by the pacemaker. Figure 20.10 illustrates this ~ng ,case.
¯ 3) pacemaker refractory < pulse-QRS interval ~ heart refractory:
This cage is .not ~/ccounted fOr by the ~UW pacemakertester. A pacing pulse could
occur that~ would produce .a QRS~and the next ffi~ngle .prod-u~ed by the tester
could Occur within the QR~s~efractory period. None~f ~e tests de’~eloped and
run on ’th~ pacemaker allow ~the third timing Case to occur. Figure 20.il
illustrates this timingcase.
Makeor load test

signal fromdisk
and put into DAC
buffers
I Start ADCclock I
Sendout test
signal data point
and sample
pacemakerlead
"~YES
I i=0
I i=i÷ I
~YES
[i] =flag
Saveoutput to disk
andplot to screen
Figure 20.7 A block diagramof the software used in the UWpacemakertester. First, the user
makesor loads a test signal. Next, the signal is loaded into the DAC data buffers. Next, the ADC
clock is started, whichstarts the electrode voltage Samplingand output of the test signal fromthe
DAC.After the ADC buffer is full, every elementof the buffer is checkedagainst a threshold. If
the elementis abovethe threshold, the correspondingelement~inthe.test signal array is flagged.
Finally, the test signal array containingthe pulse flags is savedto disk and plotted onthe screen,
The following diagrams (Figures 20.12 through 20.15) show the results
the tests run on the pacemaker. The top curve in all of the diagrams shows the
triangles produced by the’tester. The middle curve in all of the diagrams shows
the pacemaker pulses sensed by the tester. The bottom curves show the what the
final :results would look like: the triangles produced by the tester (solid lines) and
the QRSs that would be pr6duced by the pacing pulses (dashed lines)~ Remember
that ~theQRSs that would be stimulated by the pacing pulses are not produced by
the UWpacemaker tester.
UW PACEMAKERTESTER ~ :~:~ 455
This code makes the test signal. The user has already entered
the specifications (Qs and time interval s Between the Qs) into
an array called signal_spec. The triangle data has been loaded
into a ll4-element array called triangle. The test signal is
put into a 32,768-element array called test_signal. */
count = 0;
for(i=0; i<300; i++)
{
if (signal_spec[i] == ’done’) break;
if (signal_spec[i] == ’Q’)
/* put triangle data into next 114 elements of test_signal */
current_count = count;
for (j=0; j<l14; j++)
{
count++;
test_signal[current_count + j] = triangle[j];
/* put zeros into test_signal corresponding to the time interval

the user specified. */
else
for (j=0; j<((int) (signal_spec[i]*1092));
{
test_signal[coUnt] = 0.0;
count++;
}
/* This section of code takes the teSt_signal array and puts it

into the four DAC buffers. The DAC buffer is a 4 ×8192-element
array called DA_buffer. */
count = 0;
for (i=0; i<4; i++)
for (j=0; j<8192; j++)
{
/* convert test_signal to short integers and scale for DACo */
DA_buffer[i][j] = (short) (204.8 * test_signal[count]);
count++;
}
/* This section of code checks each pacing pulse sample against
threshold (pulse_threshdld) ~,. -I~flthe ~ples is greater than the
threshold, the corresponding element in the test_signal array
is set equal to a flag (pulse_flag)~
for (i=0; i<32768; i++)

if (samples[i] > pulse_threshold)
test_signal[i] = pulse_flag;
Figure20.8C code~rmakingthetestsignMandsensing
~epacingpulses.
Inhibit and ,trigger modes

The first test ran on the pacemaker
was~ to observethedifference betweeninhibit
and trigger modes.
QRSproduced Triangle produced

by pacing pulse by simulator
Pacing /
puse,,,
Heart
Pacemaker refractory
refractory ~
pulse-triangle
interval
Figure 20,9 Timingcase 1. The time interval betweenthe pacing pulse and the next triangle
producedby the tester is greater than the pacemaker
(lighter shadedrectangle) and heart refractory
period (darker shadedrectangle).

by pac!ng pulse by simulator
Pacing
Pacemaker 1~__..___, ~,-~ refractory

refract°ry ~ . I~k,-N~~ =’- [t
Pulse-~r~angle
in~ewal
Figure20.10 Timingcase 2. The time interval betweenthe pacing pulse and the next triangle
producedby the tester is less the pacemaker
refractory period (lighter shadedrectangle).

Pacing by pac!ng pulse, by simulator
pulse~ J 1
~’~11¥ ~l f Heart
Pacemaker ];i ref
]/ ract°ry
i
refractory ~
Pulse-triangle
interval
Figure 20.11 Timingcase 3. The time interval betweenthe pacing pulse and the next triangle
producedby the tester is less than the heart’s natural refractory period (darkershadedrectangle).
Figure 20.12 shows the results of the test while in inhibit mode. Two triangles
are produced by the tester 0.85 s apart (70 bpm). The pacemaker senses these
triangles and is inhibited from pulsing. After a third triangle is not sensed for
0~85 S, the pacemaker pulses. The bottomcurve shows that the pacemaker would
cause a steady heart rate of 70 bpm.
Patient
simulator
waveform
I
I
I
I
I
Sensed I
pacing I
I
pulses
0.85 s ~
Results
Figure.20,12 This test showsthe pacemaker’sbehaviorin inhibit mode.Thetwo triangles

occurat a rate of 70 bpm(0.85 s apart). Thepacemaker sensesthe twotrianglesandis inhibited
frompulsing.Aftera third triangle is not sensedfor 0.85s, the pacemaker
respondsbypulsing.
Figure 20.13 shows the results of the test while in trigger mode. A
pacemakerpulse is triggered by the first two triangles in the test signal. After a
third triangle is not sensed for 0.85 s (70 bpm), the pacemaker pulses. The
bottom eurve shows that the pacemakerwill cause a steady heart rate of 70 bpm.
Patient
A
simulator
waveform I
I
I
I
I
Sensed l~,
-pacing
pulses
0.85s 0.85s I
I
I
I
Results
Figure 20.13 This test showsthe pacemaker’sbehavior in trigger mode.Thetwo triangles

occurat a rate of 70bpm(0.85s apart). Thepacemaker
is triggeredbythe first twotriangles.After
a third triangleis notsensedfor 0.85s, the pacemaker
respondsbypulsing.
Missed beat
The next t~st on the pacemakerwas to observe its behavior whenthe input signal
missed a beat. Figure 20.14 shows the resilltS of the miss6d beat test whi!e in
triggered mode. The pacemaker is triggered off the first two triangles. Afier a
third is. not sensed for 0.85 s, the pacemakerpulses. Next, the third triangle is
sensed.witl!in 0.85 s dter the pulse and the pacemaker is triggered. The bottom
curve :shows t.hat the pacemakerproduceda steady heart rate of 70 bpm.
Patient
simulator
waveform
Sensed
pacing
pulses
"--’-
0.85 ’~-
s
It
!
Results t
Figure 20.14 Representation of a missed beat. The top curve shows that two triangles are
produced by the simulator 0.85 s apart. The next triangle produced by the simulator does not occur
until 1.7 s later, representing amissed heat, The pacemakertriggers off the first two triangles and
produces a pulse after a third triangle is not sensed for 0.85 s. The pacemakertriggers off the third
triangle producedby the simulator.
Refractory period
The last test performed on the pacemaker was to observe its refractory period.
Figure 20.15 shows the results of the refractory period test while the pacemaker
is in trigger mode. The first triangle produced by the simulator is triggered on
by the pacemaker. The next triangle occurs 0.85 s later and is also triggered on
by the pacemaker. This pacing pulse starts the pacemaker 425-ms refractory
period. The next triangle produced by the simulator occurs within the refractory
period, so it is not sensed. The next pacing pulse occurs 0.85 s after the second
pacing pulse because no triangle wavehad been sensed.
Patient
simulator
waveform
425-mspacemaker
refractorypedod
Sensed
pacing
pulses ~\\\\",,\N1
0.85 s 0.85 s
I
!
lit
Results
Figure 20.15 Testing the refractory period of the pacemaker. The third triangle is not sensed by
the pacemakerbecause it occurs within the pacemaker425-msrefractory period. So the next pacing
pulse occurs 0.85 S after the Secondtriangle producedby the simulator.
The four tests shownabove are just a few that can be performed using the
patient simulator. The flexibility of the simulator allows manydifferent heart
signals to be developed and sensed by a pacemaker. Further study of different
pacemaker programmingcharacteristics such as rate adaptation, hysteresis, and

sensitivity can also be done using the patient simulator.
A future improvement to the UWpacemaker tester would incorporate a
conduction model of the heart to produce the signals instead of having the user
develop them. This would allow real time observation of pacemaker behavior to
realistic patient heart rhythms. It wouldallow analysis of dual chamberas well as
single chamberpacemakers because both atrial and ventricular signals would be
produced by the conduction model. The conduction model .could also proEide
abnormal heart rhythm signals so the pacemaker’s pacing algorithms could be
examined. In order to accomplish this, a computer capable of developing a test
signal and sampling the pacemaker pulses in real time as well as and displaying
them would be needed. The speed of the VAXstation 3200 would not allow real
time development of a test signal that would adapt for changes, such as a QRS
produced by a pacing pulse.
Patient simulators have been developed by pacemaker manufacturers that use
conductiofi models of the heart to produce test signals. These patient simulators
are used to demonstrate real time pacemaker behavior. Pacemaker manufacturers
also use the simulators to analyze and design pacing algorithms. For example, a
conduction model that includes heart blocks, tachycardia, or premature beats can
be used to analyze or develop pacing algorithms to control these abnormalities.
Pacemaker manufacturer patient simulators also include provisions to simulate
rate adaptation signals that control the rate response of rate adaptive pacemakers,
such as respiration signals, temperature signals, and motionsignals.
20.5 REFERENCES
EnvironicsAdaptiveTechnology PaceAlyzer~
Malik,M., andCamm, A. J. 1988.Computermodelingof cardiac rhythmdisturbancesand heart-
pacemaker interaction. Pace,11: 2101-2108.
Malik, M., Cochrane,T.; Davies,D. W., andCamm, A. J. 1987.Clinically relevant computer
modelof cardiac rhythmandpacemaker/hem interaction. Med.Biol. Eng. Comput.,25: 504-
512.
Malik,M., Nathan,A., and Carom,A. J. 1985Computer simulationof dual chamberpacemaker
algorithms usinga realistic heart model:PacingClin. Electrophysiol.,
8: 579-588.
® PMT
Netech 100, 60 BethpageDrive, Hicksville, NY11801.
20.1 Explain the difference betweena the two commerciallyavailable pacemaker testers
describedin section20.1.1 andthe UW pacemaker tester.
20.2 Explainwhytriangle pulsewaveformsare adequatein modeling the electrogram
signal.
20.3 Calculatethe minimal pulsewidthof the one-shotoutputthat allowsat least twopointsin
the pulseto be sampled at a rate of 1092samples/s.
20.4 Explain howthe UWpacemakertester determineswhenthe pacing pulses occur with
respectto thetest signal.
20.5 Sketchthe test signalthat wouldbe developed if the usertypedQ,1.0, Q,2.0, Q,1.5, Q:
20~6 Explainthe "open-loop" characteristicof the UW pacemaker tester.
20~7 Explainwhythe UW pacemaker tester can accountfor the situationin Figure20.9.
20.8 Explainwhythe UW pacemakertester canaccountfor the situation in Figure20.10.
20.9 Explainwhythe UW pacemakertester cannotaccountfor the situation in Figure20.11.
20.10 Describeinhibit modeusingFigure20.12.
20.11 Describe trigger mode ~,s.ingFigure20.13.
20.12 Describethe pacemaker s behaviorwhenthe test signal missesa beat usingFigure20.14.
20:11 Explainwhythe pacemaker (whilein trigger mode)doesnot trigger onthe third triangle
Figure20.15.
Appendix
Microprocessor-based pacemakerdesign
Surekha Palreddy
The purposeof this appendixis: to present the design of a simplemicroprocessor-b~asedpacemaker

giventhe algorithmto be implemented’.Therate-adaptive pacemaker responsiveto variations in the
cardiac AVinterval (Baker,1988)is selected as an exampleto illustrate the methodofdesign.
A,1 RATE-ADAPTIVE PACEMAKERS
Cardiacpacemakers that provide pacing stimuli to the heart at a predetermined~te ~ Sufficient to

sustain life but are incapableof respondingto the changingcardiac demandsthat accompany daily
life including physical exertion. Rate-adaptivepacemaker s overcomethis limitation. Rate-adaptive
pacemakershave been developed.that respond to various physiological parameters such asthe
oxygenContentOf the blood, blood~ressure,respiratory volume,and bloodpH.
The AVrate-responsive pacemakeris considered here as an exampleto explaifi the design
process of a microprocessor-basedpacemakerprovides rate-adaptive pacing responsive to the
physiologyof the heart in patients withintact AVconduction.
TheAV~rate-resP0nsive algorithmis used to adjust the pacing rate of the heart accordingto
the patients AVcOnddctiontime. Implementation of this algofithrn dependson the detection of the
P waveand the Q wave. Twotimers are used to track’the patient’s AVinterval (time interval
betweenthe P waveand Q wave)and paeingeseapeinterval. Basedon the intervals measured,the
algorithm calculates and updates the pacing escape interval regularly. The algorithm requires
detailed study before the microprocessorinstruction set, i~s ¢!esigned~.Therate adaptiv9pacemaker
algorithmexplainedin Baker’spatent wasehtsen to illUSth~te the dtsign process. The instruction
set architecture and the codewere used for the purposeof a course project (VLSIsystemsdesign)
at the University of Wiseonsin-Madisom Membersof the project team were David Burger, Kirk
Dunsavage,and SurekhaPalreddy. The pr0ject was not completed. Therefore, no claims are made
for accuracyof the design, The discussion is intended.to give, the’reader an understandingof the
design process.
The AVinterval, as described here~ is the time intervai~etweenthe depoiari~ation of the
atriumandthe ventricle. It varies, with physicalexertiondue to increasedcatecholamine circulation
indicative of increased cardiac demand(Baker, 1988). The AV-responsivealgorithm must detect
the P waveand Q waveof the electrocardiogramwhichcan be accurately detected. The AVinterval
is directly related to the conduction.timethrough the AVnode, The AVnode whenfatigued, is
characterizedby increasedconductiontim~in responseto increasedheart rate. This occurssinceit
is unaccompanied by increased catecho[~aminecirculatiom This property eliminates the risk ~f
pacemaker-induced tachycardia. A pacemake~r,utilizing~reduction inAVinterval as the pacing
control parameter naturally tends to oppose increases in pacing rate unless accompaniedby
increasedphysical exertion
:, This pacemakerincludes: (1) separate functions for tracking spontaneouslyoccurring atrial
cardiacactivity and for atrial pacingwhenappr0pdate,(2) gradualrate responsesimilar to that of
normallyfunctioning humanheart, and (3) a built-in bias towardspontaneousrather than paced
cardiacactivity.
APPENDIX 461
A.2 MICROPROCESSOR DESIGN
This pacemakerdetects the onset of atrial depolarizations by detecting the P waveand the
subsequentventricular depolarization by identifying the Q wave.The microprocessorprovides the
pacemakercomputationalabilities and control. Otherforms of analog or digital circuitry can be
used in place of the microprocessor.Amicroprocessoris preferred for itsminiature size and its
flexibility, both of whichare of critical importancein the implantablesystem(Figure A. 1).
microprocessoris designed with input--output ports connecte~iin a conventional manner~;ia a
bidirectional bus to memory,an AVtimer, and a pacing timer. The timers are external to the
microprocessorand are conventionalup or downcountersof the type that are initially loadedwith a
count value and count up or downfrom the value and output a roll-over bit uponcompletingthe
programmed count. The initial count values are loaded into the timers and the roll-over bits are
output to the microprocessor.
i I generator
AV Atria[
[ interval I~ Microprocessor ~ .L~I "J
i~DatI
sense
I timer I I
I / Ventricular Part
sense
I Pacing. a bus
J interva~ ~ Ventricular
I timer / stimulus
|
.~ generator
Figure A.1 Block diagram of a microprocessor-based pacemaker, which contains the

fundamentalcomponentsrequired to implementthe AVrate-responsive alg0dthm(Baker, 1988).
The microprocessor is designed with memory, both ROMand RAM.The pacemaker

operating routine is stored in ROM, while RAM stores the various programmable parameters and
variables that are used in conjunctionwith the pacemaker operation and the preferred rate-control
algorithm..An input/output port to the telemetry interface is also provided. The implanted
pacemakeris thus enabled to receive pacing and rate-control parameters from an ~ external
programmer and send data to an external receiver.
Theoutput ports of the microprocessorare connectedto inputs of an atrial stimulus pulse
generator and a ventricular stimulus pulse generator. The pulse parameterdata, such as amplitude
and width, as well as enable/disable and pulse initiation codesare transmitted to the genbrators
fromthe microprocessor.Theinput ports of the microprocessorare cormectedto the outputs of the
atrial and ventricular sense amplifiers to detect the occurrencesof P wavesand Qwaves.The.s~nse
amplifiers. Output a signal to .the. microprocessorWhena P waveor a Q waveis detected on
res~tive li~!es of information.Thesignal..is latchtd to the microprocessorinput by a ctnVentional
la~h~, ~e p~cemakeris operated by a dual Clockmechanism.The timers are operated witha low7
frequency clo6k in the sleep phase Whenthe microprocessor is at rest. The occurrence of an
interesting event alerts the. microprocessorby enabling its high-frequency’d.i~ck tO performthe
required calculation quickly (Ch~tpter 10). The dual dock design o~ the pacemakerhelps save
battery powerin im-plantable devices. _P.,a_cemakerdesigns are impieiiaented using CMOS
technologytO take advantageof the circuitry s lowpowerrequirements.
A.3 SOFTWARE ALGORITHM: AV-RESPONSIVE RATE-

ADAPTIVE ALGORITHM
Figure A.2 and Figure A.3 showthe flowcharts of the AVrate-responsive algorithm (adapted from
Baker, 1988). Whenthe microprocessor is alerted from a sleep state to execute the control
algorithm, it tests to determineif a P wavehas beendetected. If a P wavehas beendetected, the
AVinterval timer is loaded with a maxAV intervall (programmed)value and enabled to start
counting. The pacing interval timer is also loaded with the current pacing interval value (from
RAM) and is enabled to start counting. A paced/sensedflag is cleared (’0’) to indicate that
spontaneousatrial activity wassensed. The algorithmthen puts the microprocessorto sleep until
another wakeupevent is encountered.
Wakeup
Load and start [ _ IClear pace~

interval t~mer :~acinginterval timer I-’] sensedflag
No
Readand reset Calculate new ~ Store new L-~

AV pacing interval ~ Ipacing intervall I
/
pacing pulse Initiate ventricular
interval time
Loadatrial pacing
pacing pulse
Loadand start AV
interval timer
and start pacingi~] Set paced/
interval timer I~l sensed flag
I
|
Figure A.2 The AVrate-responsive algorithm. The detection of P-wave, Q-waveand time=out
si.gnals from the AVinterval timer and pacer interval timer serve as wakeupevents to the
rmcroprocessor(Baker, 1988).
If a P waveis not detected, the microprocessortests-~o determineif a Q wavehas been

detected. If a Q wavehas been detected, the current count value of the AVtimeris read by the
microprocessorand reset. The difference betweenthe initial AVtimer count and the value read
indicates the elapsed time betweenthe detected P waveand Q wave.The control is then passed to
the pacing interval calculation algorithrmA newpacingintervalis calculated by the pacingroutine
based on the measuredAVinterval. The value of the pacing interval sets the time after the
occurrence of a P wavein which another P wavemust occur to"inhibit atrial pacing. Upon
returning from the pacing routine, the new pacing intervalis stored in memorybefore ~ the
microprocessor enters the sleep state.
Ifno P waveor Q wavehas been detected, the microprocessor tests to determine if the
maximalAVinterval has expired. If the AVinterval timer has timedout withoutthe detection of a
Qwave,the ventricular pulse parametersare loadedinto the ventricular pulse generatorand a pulse
is initiated. TheAVtimeris reset beforegoinginto the sleep state.
APPENDIX 463
~~j pi~ount++ ~PAcount = 0
1 ’, V. N,w ac~ ,nte i
NoVe. I_ Current urrent

interval 2
interval+ Increment
~ I ..
I Currentinterval = ~1oi~_urr_em ~
lCurrentinterval - Increment
b
~Curmnt padng interval
"~.t~r~aS, . Mln ’nlerval

~,/’~
= Current
pacingintervalI
I ÷oo, I
Figure A.3 The pace routine to calculate the new pacing interval, based on the recorded AV
interval and the programmedparameters. TAVrefers to the measured AVinterval (Baker, 1988).
If no P wave or Q wave has been detected and the AVinterval has not timed out, the
microprocessor tests to determine if the pacing interval timer has expired. If the pacing interval
timer has timed out, without a P wavebeing detected, the control initiates pacing of the atrium by
loading atrial pulse,parameters into the atrial pulse generator. The controt algorithm then loads the
AVinterval,timer with max AVinterval2 and the pacing interval timerwith the current pacing
interval. The paced/sensed flag is set (,1") to indicate that the atrium has been paced before
entedngthe sleep state.
Figure A.5 shows the various programmableparameters used inthe algorithm for calculating
a newpacing interval based on the, AVinterval.
The microprocessor entersthe wakeup state only when one of the above four conditions are
detected to perform the appropriate functions before going to the sleep state again.
MaxAVintervall MaxAVinterval2
Maxinterval
(1 s)
Pacing
interval
Mininterval
(0.5s)
MeasuredAVinterval
Figure A.4 The rate response function of the AVrate-responsive pacemaker.Pacing rate is
calculated as a function of the patient’s measuredAVinterval. Twodifferent linear functions axe
indicated for rate calculation basedon whetherthe atriumis pacedor sensedin the previouscardiac
cycle. This compensates for the differences in conductiondelay whenthe atrium is pacedand When
it is sensed.Linearfunctionsare preferredfor ease of calculation. Mininterval (0.5 s) corresponds
to 120bpmand Maxinterval (1 s) correspondsto 60 bpm(Baker, 1988).
Parameter Normal Value Identifier

MAX AVinterval 1 200 ms MxAV1
MAX AVinterval 2 160 ms MxAV2
Mininterval 500 ms Mnint
Slope P 15 ms/ms SloP
Slope S 15 ms/ms SloS
Offset P 2000 ms OffP
Offset S 1400 ms OffS
Maxcount 20 ms MxCnt
Increment 10 ms , Inc
Delta 100 ms ’ Delta
Ventricle pulse width Prosrammable~’ VentPW
; i.
Ventricle pulse amplitude P~ble VentPA
Atrial pulse width Programmable AlrialPW
Atrial pulse amplitude Programmable AtdalPA"
Fig.ure A.5 The parameters used in the AVrate-responsive algorithm for calculating a new
pacing interval based on AVinterval and programmed
parameters.
Someof the special features of the pacinginterval calculation algorithmare discussedbriefly

to indicate the robustnessof the algorithmin consideringthe effdcts of prematureventricular heats
whichmayaffect the calculated pacing interval and also to maintain the heart rate betweenthe
desired maximaland minimalrate intervals.
The pacing interval calculation algorithmcalculates the newpacing interval only whenthe
atrium is paced(" 1") or sensed ("0") in the previouscardiac cycle. If the atrium is not paced
sensedin the previous cardiac cycle and the sensed/pacedflag is set to"2" indicating a premature
ventricularcontraction,the routine returns control to the mainfunction returning to the previously
calculatedpacinginterval:
If the atrium is pacedin the previouscardiac cycle, the algorithmincrementsthe pacedcount
(to keeptrack of successivepacedbeats), and thenewpacinginterval is calculated as a function
the pacedlinear function as shownin Figure A.4. If the atri~m~was~,sensedJn the previous cardiac
cycle, the pacedcountis reset to zero and the newpacinginterval is calculated as a functionof the
sensed linear function as shownin Figure A.4.
APPENDIX 465
The difference betweenthe sensed and paced linear functions (slopes and offsets), which
mapthe measuredAVinterval to a new pacing interval is to compensatefor the effects of
spontaneousand inducedcardiac activity on the newpacinginterval. Whenthe atrium is paced, the
exact onset of the P waveis known,whereasthere is a delay associated with P-wavedetection
whenthe atrium is sensed. To avoid these dine delays whichinfluence the calculation of the new
pacinginterval, the offset andslope of the functionsare adjustedaccordingly.
If the newcalculatedpacinginterval is less than the current pacinginterval, the current pacing
interval is incrementedby a prefuted amount"increment".If the incrementedcurrent pacinginterval
is greater than the newpacinginterval, the current pacing,interval is set to the newpacinginterval.
If the current pacinginterval is greater than the newpac,nginterval, the current pacinginterval is
decremented by a prefixed amount.If the decremented value is less than the newpacing interval, it
is set equal to the newpacing interval. Thishelps to avoidthe rapid increasein pacingrate due to
increased catecholaminewith the onset of exercise. This algorithm provides a smoothgradual
responseas is obtainedin a natural heart.
The algorithm also tests to determineif the paced count exceededa predeterminedmaximal
count. If the pacedcount is greater than or equal to the maximalcount (i.e. the atrium has been
pacedfor the past maximalcount cardiac cycles), the paced count is reset and the current pacing
interval is incrementedby a prefixed amount"delta". This adjustmentenables the emergenceof
spontaneous activity in the atrium, if present.
Finally, before control is returned to the mainprogram,the sensed/pacedflag is set to "2" to
avoid the sensing of a prematureventricular contraction from incorrectly influencing the pacing
rate.
A.4 DESIGN PROCESS
To facilitate the design of a microprocessor-basedpacemaker,the algorithm that needs to be

implementedis thoroughlystudied to understandits special requirements.The flow chart of the
algorithm is then converted into pseudo code. Based on the pseudo code, the instruction set
architecture of the microprocessor
is decided.
A.4.1 Pseudo code
Theflowchartof the AVrate-res, ponsivealgorithmis transformedinto pseudo-codein Figure A.6.
if( Asense == i)
Load MaxAVI -> R7
Loadtimer R7 -> AVtimer
Load Paceint -> R6
Loadtimer R6 -> Pacetimer
LoadImm R1 #0 # (Paceflag = 0)
SLEEP
if( Vsense == i)
Storetimer R7 <- AVtimer
Load MaxAvl -> R6
Load Paceaddr -> R5
Jump&Link R5(to) R4(return)
Store R3(Acc) -> newpaceint
SLEEP
if( AVtimerout == i)
Load Vepulwid -> R7
Load Vepulamp -> R6
Enable # (R7 & R6)
Load MaxAVI -> R5
SLEEP
if(Pacetimerout == i)
Load Atpulwid -> R7
Load Atpulamp -> R6
Enable # (R7 & R61
Load MaxAV2 -> R5

Load Paceint -> R4
Loadtimer R4 -> Pacetimer
LoadImm R1 #i # (Paceflag = Pace "i’)
SLEEP
Paceaddr:
if(paceflag = "2"]
Load curpaceint -> R3
JAL R4(to) R5(from)
BNE(paceflag,R0) Elsel
Store R0 -> PAcount
Load Slopes -> R3
Mult R3 R7 # R3 <- R3 * R7
Load OffsetS -> R6
Add R3 R6 # R3 <- R3 + R6
Store R3 -> Newpaceint
JMP Loopl
Elsel:
Load PAcount -> R3
Increment R3 # R3 <- R3 ÷ 1
Store R3 -> PAcount
Load SlopeP -> R3
Mult R3 R7 # R3 <- R3 * R7
Load OffsetP -> R6
Add R3 R6 # R3 <- R3 + R6
Store R3 -> Newpaceint
Loopl:
Load Newpaceint -> R6
,Load Incre -> R5
BGE(R3 >= R5) Else2
Add R3 R5 # R3 <- R3 + R5
Store R3 -> curpaceint
BLE(R3 =< R6) Else2
Else3:
JMP loop2
~Else2:
Sub R3 R5 # R3 <- R3 - R5
Store R3 -> curpaceint ~
BLT(R3 < R6) Else3
Loop2:
Load Minint -> R6
BGE(R3 > R6) Else4
Else4:
Load Maxcount -> R6
Load PAcount -> R3
BGE ( R3 >= R6) Loop3
Load curpaceint -> R3 # R3 <- Curpaceinterval
JAL R4(to) R5(from) # R4 <-~(return);
# R5 <- (present)
Loop3:
Load R0 -> PAcount # R0 <- PAcount
Load Delta -> R6 # R6 <- Delta
Add R3 R6 # R3 <- R3 + R6
LoadImm R1 #2 # (Paceflag = ’2’)
JAL
I .R4(to) R5(from
Figure A.6 The flowchart of the AVrate responsive algorithmsdiscussed by Baker, 1988 is
converted
into a Pseudocodeto decideuponthe instructionset architecture.
APPENDIX 467
A.4.2 Instruction set design
Thecommands that a microprocessorexecutesare instructions. Theyarea collection of binary bits

that a processor understands. The wordsof such a machinelanguage are instructions and its
vocabularythe instruction set. Simpleinstructions are selectedto constitute the instruction set so as
to implementthe proposedalgorithmefficiently. Theselection of an instruction set plays a role in
deciding the hardware(datapath elements)and hence the complexityof datapath and control. For
applications such as a pacemaker,in which Several algorithms can be loaded and modified via
telemetry, reducedinstruction set architecture (RISC)is useful. Thesimpleand basic instructions
of this architecture can be used to code any complexalgorithm without muchdifficulty. Each
instruction takes a few clock cycles for execution. However,to accommodate the power-saving
features of a pacemakersuch as the dual clock mechanism,somespecial instructions need to be
addedto the instructionset.
Instructions are broadly classified into Load/store, Arithmetic and logic unit (ALU)~
control, and special purpose instructions. Dueto a lack of information on the instruction set
architecture of commerciallyavailable pacemakers,we designed our owninstruction set based on
the need for proper programming of the selected algorithm. This instruction set architecture is
presentedhere to illustrate the design processof a microprocessor-based pacemaker.
Theinstruction format (bit patterns) for each instruction werechosenbYgroupingtheminto
functional classes. Theinstructions fetched frommemory are 8 bits long. Eachinstruction has an
opcodefidd and a register specifier or offset field. Theopcodefield indicates the type of the
instruction that wasfetched. The register specifier indicates the address of the register in the
register file on which the operations are performed. The offset field in branch and jump
instructions is used to calculate the address of the memorylocation, the control needs to be
transferredto.
Generalregister operations:
Opcode
field (7 - 3) I Re~ister 9r offset field (2- 0)
Wechosean accumulator-based architecture in whichall the arithmetic and logic operations
are performedbetweenthe register specified and the accumulator.This architecture is preferred by
the designersas the accumulatoris implicitly specified obviatingthe needfor moreinstructional
bits. This wouldallow more"bits" to be used by the opcodeand henceroomfor moreinstructions
in the instructionset.
Theinstruction set is shownin Figure A.7
A.4 3 Datapath
After the instruction set is designed,the hardwarecomponents required to execute the instructions
are identified whichconstitute the datapath. Basedon the complexityof the algorithms.that needto
be implemented,the sizeof storage elements suchas the register file, ROM and RAM is decided.
A register file is a collectionof registers in whichanyregister can be read fromor written to
by specifyingthenumberof the registe~ in the file. Thep~oposeddesign has eight registers, with
three special purposeregisters(0-2) and five ,general pu~s,e registers (3-7), as shown~inFigure
A.8. Register "0" alwaysholds the value "zero. Register ’1 is dedicated to the sensed/pacedflag.
Register "3" is an accumulatoron whichall the arithmetic and logic operations are performed.The
read/write addressport providesa 3-bit addressto identify the register beingread or written into.
The write data port provides 8-bit data to be written into the registers either fromRAM or timers.
Readenablecontrol, whenasserted ~nablesthe register f’de to provide’dataat the read data port.
Writeenable control enables writing of data being providedat the write data port into a register
specified by the read/write address.
The instructions and programmable parametersare stored in 256 bytes of ROM (Readonly
memory).The load/storeinstructions can read data from and write data into the locations of this
memory.The parametersUsedin the AVrate-responsive pacemakerare listed in Figure A.5. The
intermediate parameters are stored in RAM (Randomaccess memory).
Twotimers are required to implementan AVrate-responsive pacemaker.One is used to
measurethe AVinterval (~1"1) and the other for the pacing interval (T2). The timers are read’and
written into just as any other memory location. These timers are provided with read and write
enablecontrols.
468 DESIGN OF CARDIAC,PACEMAKERS
Instruction Function
LDI ### LoadAccumulatorwith 3-bit immediatevalue
LD (rx) LoadAccumulatorwith ROM location (rx)
LDR3I ##### LoadR3 with 5-bit immediatevalue
LDFLG Loadwakeupcondition inputs into R2
LDACC(rx) LoadAccumulatorwith RAM location (rx)
LDT1 rx LoadTimer#1 with value in rx
LDT2 rx LoadTimer#2 with value in rx:
ST (~) Store Accumulatorwith ROMlocation specified in rx
STT1 rx Store Timer#1 in rx
STT2 rx Store Timer#2 in rx
ALU
CP rx CopyAccumulatorto rx
Addrx to accumulator
Subtract (rx) from accumulator
Incrementrx
DEC rx Decrementrx
SHR rx Shift accumulatorrisht by amountin rx
SHL Shift accumulatorleft by amountin rx
NOP Nooperation
Control ’
BGE rx Branchif (ace) > (rx)
BLT rx Branchif (ace) < (rx)
BEQ rx Branchif (acc) ==(rx)
JMP rx Jumpto memory location in rx
Special
SLEEP Put the microprocessorto sleep
Figure A.7. Theinstruction set. designedto implementthe AVrate-responsive algorithm,
Read/write= Register
file
RAM
Intermediate
register
parameters
ROM
Instructions
Curpaceinterval Acc
Newpaceinterval
MaxAvl
MaxAv2
Paceinterval =~Write ,
PaceAddress
VPulWidth Read
VpulAmp
Apul Amp
Apul Width
Delta
Increment
Minlnt AVtimer
SlopeP
OffsetP Pacetimer
Slopes
Offsets Read Wnte
PACount Clock enable enable
Figure A.8. A schematicdiagramof the register file; timers and ROM/RAM. Three registers of
the register file’are dedicatedfor special purp0se s and the rest are general purposeregisters. An
instruction register is usedto load the instruction fetchedfrommemory.
APPENDIX 469
Eachof these datapathelementshavecontrol signals that needto be set appropriatelyduring

different clock cycles of the instruction executioa.Dataflows fromone elementto the other along
the datapathwhenappropriatesignals are set by the control.
The datapath of the pacemakerdesigned by the group based on the discussed considerations
is as shownin Figure A.9.
A.4.4 Control and finite state machine
Control tells the datapath and Input/Output devices what to do according to the wishes of the
instructions of the program.The methodused to specify the multicycle control is afinite state
machine.A finite state machineconsists of a set of states and directions on howto changestates.
Eachstate specifies a set of controls that needto be asserted whenthe machineis in that state. An
exampleof a state machinefor RISCinstructions is shownin Chapter10. The control is designed
to be implementedusing a programmable logic array (PLA);whichenables the forcing of any set
of output conditions in responseto any set of defined input conditions. The PLAis programmed to
set the required controls of the datapath elementsshownin Figure A.9basedon the opcodeof the
instruction being executed. Since each instruction is executed in several clock cycles, a state
register is used as part of the control to indicate the next state to be executed.Thestate machine
changesstates basedon the inputs from the opcodeof the instruction and the state register. For
more information on the design of control, the book Computerorganization & design: The
hardware/software interface serves as anexcellent reference.
A.5 PROGRAM EXECUTION
Oncethe datapath and control are designed, the required algorithm that needs tobe executed is
loaded into the memoryof the microprocessor.Eachinstruction fromthe memory is fetched one at
a tame and executedby setting the appropriate controls. Theloaded programscould be modifiedor
updated with newerversions by the use of telemetry, The simple instruction architecture chosen
makesit easy to implementcomplexalgorithmswith relatively simple hardware.
A.6 REFERENCES
Baker, R. G. 1988..A-Vresponsive rate adaptative pacemaker,USPatent 4,856,524.

Patterson, D. A., and Hennessy, J. L. 1994. Computer organization & design: The
hardware~softwareinterface. San Mateo, CA:MorganKaufmarm Pub.
Glossary
John G. Webster
aberration: deviation from a normalcourse

ablation: removalof a part, as by cutting or radio-frequencycatheter
aecelerometer:detects accelerations perpendicularto sensor
acetylcholine: a neurotransmitter at the myoneuraljunctions of striated muscles, at autonomic
effector cells innervatedby parasympatheticnerves, and at the preganglionicsynapsesof the
sympatheticand parasympatheticnerves
action potential: all or nothing response whenthreshold is reached that travels at a constant
-velocity and unattenuatedalong the membrane of an excitable cell
activity estimate (level): proportional to the activity level and is usually generated after
filtering, amplifying,andusing threshold,levels on the rawsensorsignal
adrenergie:activated by or secreting epinephrineor substanceswith similar activity; those .nerve
fibers (sympathetic)that liberate norepinephrineat a synapsewhena nerve impulsepasses
afferent neuroma neuron whosecell body lies outside the ANSand carries information from
the receptors at its peripheralendingsto the ANS
afferent: bringingto; nerves carrying sensationto brain
ALU(Arithmetic and Logic Unit): a functional unit in: the microprocessor that does
arithmeticand logic calculations
angina:brief attacks of chest pain due to insufficient oxygenationof the ,heart muscletissue
anisotropy=a property of cardiac musclein whichthe tissue properties vary dependingon the
direction of measurement
anterograde: forward propagating, in a direction whichis considerednormal
arrhythmia:disorder of the rate and rhythmof the heartbeat; linguistic purists advocatethe use of
dysrhythmia
arteriolar constriction: constriction of the arteries
asynchronous pacing: pacing at a,constant, preset rate, also knownas fixed rate pacing
asystole:a cardiacarrhythmiacharacterizedby. a lack of electrical or mechanical activity~.~,
atrial escape interval (AEI): the time betweena paced or sensed ventdcular event to the next
atrial event; also known as ventriculoatrialinterval
atriomegaly:an abnormaldilation or enlargementof an atrium of the heart
atrioventricular interval (AVI): the electronic analog to the P-R interval: it is the
programmed interval froma paced or sensed atrial activity to the following paced or sensed
ventricularactivity
atrioventdcular: pertaining to an atriumof the heart and to a ventricle
automaticity:the ability to generatean action potential spontaneously
AVsynehrony:for every atrial beat, there is a correspondingventricular beat
baroreeeptor: a sensory nerve ending that is stimulated by changesinpressure
bathmotropic:.influencing the responseof tissue to stimuli
bradyarrhytlunia: resultant dysrhythmiacaused by bradycardia
bradycardia: whereprocesses act to interfere with the control of the heart by the sinus node,
resulting in normallyslowerheart rates
bradykinin:a peptide producedby activation of the kinin system, in a variety of inflammatory
conditions; it is a: potent vas0dilator; it ’also increases vascular permeability, and causes
contractionof a variety of extravascularsmoothmuscles
cardiac output: blood volumepumpedby each ventricle per minute
cholinergie: activated by or stimulated by acetylcholine; those nervefibers (parasympathetic)that
liberate acetylcholineat a synapsewhena nerve impulsepasses
ehronotropic~ affecting the timeor rate, as the rate of contractionof the heart
circadian: a rhythmof biological activity of about24 h

concomitant:accessory, taking place at the sametime
contractility: the state of the muscletissue whichdescribes the speedof contraction
CVT:central venoustemperature;the temperatureof the bloodin the right ventricle
datapath: the hardwarecomponents that performarithmetic calculations and execute instructions
underthe direction of control unit
debounce: to f’dter the electrical signal froma switchso as to eliminateintermittent pulses caused
by mechanical bounce
decode:the reverse processof encoding;to converta formattedsignal into its original values
defibrillator: an electronic apparatusused to counteract atrial or ventricular fibrillation by the
application of a brief electroshockto the heart, either directly or throughelectrodes placedon
the chest wall
depolarization: neutralization of polarity; a changein membrane potential from-90to -70 mV
since it is a decreaseof the potentialdifference,or polarization
diastolic depolarization: the spontaneousrise frommaximaldiastolic potential to threshold in a
pacemakercell
distal: farthest fromthe center
diurna..h see circadian
dromotropic: affecting the conductivityof a nerve fiber
dysrhythmia:disorder of the rate and rhythmof the heartbeat
ectopi¢ rhythm: a cardiac rhythmgenerated by any nonsinus pacemaker
efferent neuron:a neuronthat carries information awayfrom the ANS
efferent: bearing outward, awayfrom brain
efficacy: producingor sure to prOducethe desired result
ejection fraction: a ratio of the bloodvolumeejected froma ventricle in one beat dividedby .the
blood volumepresent in the ventricle before contraction (i.e. the SVdivided by the End
Diastolic Volume); used an indication of sympatheticactivity in rate-adaptation
ELT:Endless Loop Tachycardia, a pacemaker-mediatedtachycardia commonin AVblock and
sick sinus nOdepatients using DDD modepacing
embolism: the suddenMocking 0f an artery by a clot or foreign material that has beenbrought to
its site of lOdgment by the bloodcurrent
encode:to represent a signal in a particular format; in pacemakerprogramming, the numbers
whichspecify parametersare encOdedinto a stream of pulses
end-diastolic volume:the amountof bloOdin the ventricle just prior to systole
endocardium:inside of the heart
entrainment:anystable condition with definable monomorphic periOdicity resulting from the
interaction of tworhythms
epieardium:outside of the heart
epinephrine:a hormonesecreted by the adrenal medullaand involved in regulation of organic
metabolism;it is a catecholamineneurotransmitter
escape rhythm: a cardiac rhythmgenerated from any of.the latent pacemakersof the cardiac
. conductivetissue; escaperhythmsare a subset of ectopic rhythms
esophageal: pertaining to the esophagus, which is the passage between the throat and the
stomach
fixed-ratio block: as the atrial rate continues~to increase abovethe URI,P wavesoccurring
within the TARP are ignored, or blocked
FSM(Finite State Machine):a control unit which mapsthe current state and the inputs to
new state
ganglion:cluster of neuroncell bOdiesoutside the central nervoussystem
hemodynamic: forces involved in circulating blood through the body
l/R: heart rate
humorahpertaining to elementsdissolved in the bodyor bodyfluids
hyperpoiarization: a change in membrane potential from-90to -100 mVsince it is an increase
of the potential difference
hypothalamus:brain region below the thalamus responsible for correlation of neural and
endocrinefunctions
hypoxia: a state of low oxygenation
hysteresis: oceurs whenthe hearts spontaneous rhythm drops below, the LRI; the pacemaker
respondsby pacing the heart at a fast rate, until the heart’s spontaneousrhythmexceedsthe
LRI
ICD:implantablecardioverter/defibrillator
idioventricular: intrinsic to the ventricle
infarction: a cardiac disease in whicha eorona~bloodvessel becomesblocked; it often leads to
ischemia
GLOSSARY 473
infarction: an infarct; area of tissue whichundergoesnecrosis death followingloss ofblood~flow

inhibition: the effect of an impulseunable to conduct thougha depressedarea, leaving the area
refractory so that a subsequem impulseis also blocked
inotropic: affecting the force or energyof muscularcontraction
intercalated disk: dense structure that separates neighboringmyocardialfibers; gap junction
presentto facilitate conduction
interrogation:reading back the value of a pacemakerparameter;used to verify that programming
wassuccessful or to determinethe currently set parametersif they are unknown
interventricular septum:the partition that separates the left ventricle ,from the fight ventricle,
consisting of a muscularand a membranous part
intracavitary: pertaining to the cavity within the heart muscle
ischemia:local and temporarydeficiency of blood supply due to obstruction of circulation to a
part; cardiac disease in whichthe blood supply can no longer meet the oxygenor metabolite
demandsof the tissue
lowerrate interval (LRI):. also knownas the automatic interval, is the longest period between
consecutivepaced or sensed events occumngin the relevant chamber
mapping:converting an activity estimate to target pacing rate using a programmable curve or
lookuptable
maximal diastolic potential: the most negative membranepotential achieved during
repolafization
meanarterial blood pressure (MABP):average blood pressure during cardiac cycle; it
approximately equal to diastolic pressure plus one-third pulse pressure.
monolithic:a formof integrated-circuit construction in whichall circuit elementsare fabricated
on one common semiconductorsubstrate; from Greekmono(one) and lithos (stone)
monomorphic:unchangeable in form
morphology:science of structure and formwithout regard to function
muitiprogranuner: a type of pacemakerprogrammerthat can communicatewith manytypes of
pacemakersusing different formats
myoeardiolysis: local necrosis of the myocardialfibers due to arterial obstruction, in whichthe
fibers are replacedby scar tissue
myocardium: cardiac muscle(generally refers to atrial and ventricular musculature)
myogenicresponse: this is a response originating in muscle(cardiac) to somestimuli
necrosis: death of areas of tissue or bonesurroundedby healthy parts
noise samplinginterval: an interval incorporated into the ventricular refractory period (VRP)
of modernpacemakers; during the noise sampling interval, if a significant amountof
electromagneticinterferenceis sensed, the pacemaker will pace the ventricle regardless
nonactivities: activities not correlated with heart rate increases ~.
nonmaskable interrupt:a signal that interrupts the normalexecutionOf instructions in a -
microprocessorand causes special subroutinesto be executed; the signal Cannotbe blockedor
disabled; used by programming hardwarein pacemakersto put the device in programming
mode
norepinephrine: one of the naturally occurring catecholamines;it is a neurohormone released by
the postganglionicadrenergic nerves, havingsomealpha-adrenergie and somebeta-adrenergic
activity
orthostattc hypotension: excessively low blood pressure while standing:
overdrive:to pace the heart at arate higher than its normal, sinus rhythm0ftenusedto suppress
trigger events ¯ ¯
oversensing:interpretation of false signals as cardiac: events; Usedin reference to detection
accuracyofpacemakersoperating in automatic mode
PAC:prematureatrial contraction; sometimesreferred to as PAB(prematureatrial beat), a trigger
mechanismfor tachycardia
papillary muscle:conical muscularprojections fromthe walls of the cardiac ventricles, attached
to the cuspsof the atrioventdcularvalves by the chordaetendineae
parasympathetic: causes fall in blood pressure and slowing of heart andother organs
patch:a changeto an existing portion of softwarewithout replacing the entire program
pathological: due to a disease
phase4 depolarization:the spontaneousrise from maximaldiastolic potential to threshold in a
pacemakercell
physiological: concerning body function
piezocapacitive:capacitive sensor whichdetects accelerations
piezoelectric: sensor whichproduces a voltage whencompressedorbent
piezoresistive: resistive-based sensor whichdetects strains or accelerations
PLA(ProgrammableLogic Array): a device to generate any set of outputconditions for any
set of definedinputs
pleomorphic:having many:shapes, changing in form

polymorphic: occurring in more than one form
postventricular atrial refractory period (PVARP):an atrial refractory period following a
pacedor sensedventrlcularactivity
postganglionie nerve cells: lie in ganglion and have axon terminals forming neuroeffector
junctions
pre-ejectionperiod (PEP): the time interval betweenthe onset of ventricular excitation and the
openingof the semilunarvalves
preganglionicnerve cells: cells that :have axonsthat lie in ganglions
proarrhythmic:resulting in the creation of arrhythmiaor dysrhythmia
programmer:the external device used to eommtmicatewitha pacemakerfor programmingand
telemetry
progranuning:the process of putting information into a pacemaker,usually parameterswhich
changeits operationor behavior
proximal:nearest the point of attachment,center, or point of reference
pulse-positioncoding: a methodof encodinga series of bits into a pulse stream by using the
interval betweensuccessivepulses to represent one and zeros; for example,a short interval
mayrepresent a zero whereasa long interval mayrepresent a one
Purkinje fibers: complexnetworkof conductingfibers in the subendocardial surfaces of both
ventricles
PVC:premature ventrieular contraction; sometimesreferred to as PVB(premature ventricular
beat), a trigger mechanism~for tachycardia.. .....
Q-Tinterval: the time from the onset of electrical activity in the ventricles to the maximum
negative derivative ofthe ECGT wave
radiopaque:visible on x-ray imagesas an opaqueobject
rate of increase/decrease: howfast/slow the pacing rate can changes~ a function oftime
reed switch: magnetically.sensitive switch used in pacemakersto control whenprogrammir~g or
telemetryis enabled
reentry: reactivation of a tissue for the second or subsequent time by the same impu!~e; a
mechanism of tachycardiacharacterizedby a cyclic excitation of the heart tissue
reflection: a linear formof reentry ,
refractoriness: the inability of:a fiber to respondto a secondstimulus after it has respondedtoa
prior stimulus
refractory period: period duringwhichexcitability is depressed;if stimulated it will respondbut
a strongerstimulusis requiredand the responseis less
refractory: resistant tO stimulation
retrograde: backwardpropagating,in a, direction opposite to that whichis considerednormal
rhythmicity: regdafity of pacemakingactivity
sarcoplasmic reticuinm: a specialized conductingtubule in the cardiac muscle responsible for
2+
storing Ca
seismic mass: mass used to sense accelerations
semilunar valve: valves,having semilunar cusps such as the aortic,and pulmonaryvalves
sensitivity: pacemaker’sability detect appropriateexextionlevels for variousactivities
sinoatrial node: a microscopiccollection of atypical cardiac musclefibers at~the superior end of
the sulcus terminalis, at the junction, of, the superior venacava and right atrium; the cardiac
rhythmnormally takes~it~ origin inthis node¢,whichis, for that reason, also knownas the
pacemakerof the heart.
specificity: pacingrate shouldbe specific to activities whichincrease beart rate so pacing should
not change due to activities not correlated with heart rate increases (nonactivities),
environmentalfactors such as travel, or other noise components
stroke volume:the volumeof bloodejected from a ventricle during one beat of the heart
supraventricular: abovethe ventricle
supine:reclining in a horizontal position on your back
sympathetic:causes general excitation under emergenciessuch as fright/fight, mediatedthrough
release of transmitter agent norepinephine
tachyarrhythmia: resultant dysrhythmiacaused by tachycardia
tachycardia:excessiverapidity in the action of the beart; the termis usuallyappliedto a heart rate
above 100 bpmand maybe qualified as atrial (160-190 bpm), junctional, and ventricular
(>150bpm);whereprocesses act to usurp the control of the heartbeat for one or, morecycles
fromthe normalpacemaker locus the sinus node~resultingin normallyfaster heart rates
target pacing rate: the pacing rate whichshould be obtained for the present.activity estimate
(level)
telemetry: the processof getting informationout of a pacemaker,usually data about the patient or
pacemaker
GLOSSARY 475
temporary progranuner: a type of pacemakerprogrammerwhich can place any pacemakerinto

a basic asynchronousmode(in case of an emergency);a strong magnetis usually sufficient
threshold:point of sufficient cell depolarizationto f~e an action potential, typically between-60
and -70 mVfor fast responsetissue
thrombosis:clotting of blood in the vessels
thrombus:a bloodclot that obstructs a bloodvessel or cavity of the heart
torsade de points: a type of polymorphictachycardia that occurs against a backgroundof long
Q--Tintervals and extra beats precededby long couplingintervals; usually treated withdrags
total atrial refractory period (TARP):represents the total amountof time that the atrial
channelis refractory; it consists of twose~paratetimingintervals; the TARP beginswith a paced
or sensed atrial event and extends through the AVI;the atrial sensing .amplifier is always
refractory for the duration of the AVI;finally, the TARP ends with the completionofthe
PVARP
total peripheral resistance (TPR):the total resistance to flow in systemic blood vessels from
the beginningof the aorta to the end of the venaecavae
transconductance: the ratio of the changein output current of an electronic amplifier to the
change in input voltage whichcaused that changein output current; themost common symbol
for transconductance is gin, whichderives fromthe alternative’ term mutualconductance
trigger: an impulsethat results whenan afterdepolarization reachesthreshold potential; see also
PVC and PAC
triggered rhythm:repetitive action potentials derivedfromearly or delayed.afterdepolarization.s
underdrive: an antitachycardia pacing protocol using a steady pulse rate well below the
taehycardiarate, it is successfulwhenone of the pulsesinteracts appropriatelyto terminatethe
reentranttachycardiacircuit
unidirectional block: phenomenonin which cardiac impulses can pass through the cardiac
tissue in one direction only; it is a majorcomponent in reentry
universal programmer: a type of pacemaker programmerwhich can communicatewith many
types of pacemakers,all using the sameformat
upperrate interval (URI): the shortest period allowable betweenpaced or sensed events in the
relevant chamber,while still maintainingone-to-one( 1:1) atdoventricular (AV)synchrony
VACT: ventricular to atrial conductiontime used to detect ELT
vagus nerve: 10th cranial nerve with motorand sensory functions and a wider distribution than
any of the other cranial nerves, a parasympathetic nervevia the medulla
vasoconstriction:constriction of the blood vessels
vasodilation:dilation of the bloodvessels
ventrieular blanking period (VBP):a brief 10-60-msinterval, incorporated into the first half
of the AVI;,it beginswiththe releaseof the atrial stimulus,andcontinuesfor a brief periodafter
the atrial output pulse; the ventricular blanking period can be thought of as an absolute
ventdcularrefractory period
ventricular depolarization gradient: the area under the QRScomplexin the ECG,measured
by integrating the ECGvoltage during the QRScomplex
ventricular elasticity: the expansioncharacteristics of the ventricles~ of the heart
ventricular refractory period (VRP):in a ventricular-based single chamberpacemaker,the
VRPis defined as the period followinga pacedor sensed ventricular activity during whichno
sensing occurs
ventricular safety pacing (VSP): a period incorporated into the second half of the AVI; any
signal (crosstalk, QRScomplex,etc.) sensed by the ventricular channelduringthis period will
not inhibit the pacemaker; instead, the sensedsignal will initiate a pulse to be deliveredby the
pacemaker
ventriculoatriai interval (VAI): is the time betweena paced or sensed ventricular event to the
next atrial event; also known as atrial escapeinterval (AEI)
visceralorgan: musclesthat line the walls of the internal org.ans
VLSI:technique of laying out millions of transistors on a single chip to producehigh density
circuits
WARAD: windowof atrial rhythmacceleration detection used to prevent ELT;it is an atrial event
observation windowdefined as 75%of the previous P-P interval
wavelength:in reentry, the product of conductionvelocity and the effective refractory period of
the tissue; for reentry to exist, the wavelength of the circuit mustbe shorte~than the length of
the circuit
Wenekebach pacemakerresponse: as the atrial rate increases above the URI, the AVIis
lengthenedso as not to yield a ventricuiar pacingpulse prior to the endof the upperrate limit
Index Carbonelectrode 144
Cardiaccontrol factors 15
Cardiacoutput 37 l
Cardiacvector 65
Acceleration sensing 330 Cathodalstimulation 256
Accelerationtime 319 Ceramics 157
Accelerometer299,308, 31 I, 314, 325 Chargeamplifier 312
Acetylcholine22 Charge dumping 267
Actin filament 10 Chordaetendineae 10
Actionpotential 6, 35 Chronaxie 253
Activityestimate 321 Chronotropic incompetence291
Activity sensor 299 Circadianvariation 337
Adrenergicreceptors 22 Circus reentry 52
Afterdepolarizations41 Closedloop controllers 301
Afterpotential 266 Common-mode rejection ratio 65, 195
Algorithmsfor rate adaptation 383 Conductionbtock 51
Ambulatorymonitoring 71 Conductiondelay 48
Analog-to-digitalconverter241 Conductionsystem 1
Conductionvelocity 9, 13 ¯~
Anisotropy 50
Anodalstimulation 255 Control 236
Antitachycardia pacemaker405 Current reference 206
Anxiety 339 Current source 392
Architecture231 Datapath 235,467
Arithmeticlogic unit 235, 467 DDDpacemaker 221
An~aythmia detection 440 Debouneing278
Arrhythmias 34 Decelerationtime 319
Asynchronouspacing 108, 217 Decodingcircuitry 283 ~
Atrial alert timer400 Deerementalconduction5 I
Atrial escapeinterval 220 Defibrillation threshold437
Atrial fibrillation 98 Defibrillatorcode1~21
Atrial flutter 98 Delayedafterdepolarizations 44
Atrial inhibit interval 400 Depolarization8, 48
Atrial monitorinterval 400 Detectionsensitivity 142
Atrial sensing 293 Dielectric constant 267
Atrial tachyeardia97 Differential amplifier65
Atrioventricul~ (AV)node Digitalis 46
Atrioventdcularblock 83 Dual chamberpacemakers219:
Atdoventficularinterval 219 Dual clock 238, 461
Automaticdrug infusion 423 Dual sensor 402
Automaticgain control 440 Dynamicslope algorithm 376
Automaticmodeswitching 400 Early afterdepolarizations42
Automaticslope, adaptation algorithm379 EctO~icpacemakers39
Automatieity!2, 35 Einthoventriangle 68 ~
Autonomicnervous system 19, 20, 23 Ejectionfraction 384
Autoregulatoryloop 19 Electrical impedance397 ¯
AVnode 28 Electrocardiogram13; 64
Bachman’sbundle 27 Electrochemicalequilibrium2
Baroreceptors 30 Electrochemicalphase boundary134
Battery 106 Electrodefixation 147
Batterylife estimation246 Electrodeimplantation,147
Bifascicular block 91 Electrodepolarization 265
Biocompatibility144, 153 Electrode_recoverytime 265
Biologicalbatteries 161 Electrodes 132
Biomaterials 154 Electrodes for ICDs439
Biphasicstimulation 264 Electrode-myocardium interface 134
Bipolar sensing 171 Electrogram75, 172, 369~ 373, 414, 450
Bipolar stimulation 255, 262 Electromagneticinterference 207
Blankingcircuits 202 Electronic technology229
Blood flow 11 Elgiloy 144 :~
Blood pressure 30 Encapsulation140~~41 ~’~~- ~
Bundlebranch block 87 Encoding 279 ....
Cable properties 49 Endof life 164, 165
Capacitive sensor 315 Endlessloop tachycardia 416
Capacitors for ICDs438 Enhancedsensing 418
INDEX 477
Epinephrine 16 Membrane capacitance 61

Escape pacemakers35 Membranechannels 4
Exercisestress testing 72 Membrane permeability 3
Expert system 402 Membrane potentials 37
Faradayresistance 265 Membrane resistance 49
Faradic current 136 Metabolicsensors 293
Fever 339 Metals 155
Fibrillation detection 440, 443 Microprocessor-basedpacemaker228, 460
Figure-of-eight modelof reentry 408 Minuteventilation 296, 397, 398
Filters 186 Missedbeat 457
Finite state machine237, 469 Modes 217
Fixed-ratio block 225 Multiple sensors 300
Flicker noise 184 Multipleslope control function 302
Fourier transform 177 Musclecontraction 9
Frank-Starling law 16 Myosinheads 10
Frontal plane 66 NASPE specific code 116, 118
Fuzzylogic 402 NASPE/BPEG defibrillator code 121
Gapjunctions 5, 51 NASPE/BPEG generic pacemaker code 117
Glasses 157 Nernst equation 2
Goldman-Hodgkin-Katzequation 3 Nickel--cadmium b .a~tery 161
Helicalactive fixation electrodes147 Noise immunity389
Helrnholtzcapacitance266 Noise samplingiaterval 217
Helmholtz~double layer 135 Noncommittedshock 446
Hemiblock 90 Norepinephrine16, 374
Hexaxialreference system67 Nuclearbatteries 162
His bundle electrogram75 Office visits 286
Holter recording 71 Operationalamplifiers 184, 200
Hormonalcontrol 31 Operationaltranscor~ductance amplifiers 181
Hypothalamus32, 335 Orderedreentry 53
Hysteresis 225, 346 Outputcircuit 251
Impedancemeasurements292 Output waveform257
Implantablecardioverter-defibdllators 427 Overdrive suppression’38, 415
Inflammation 139, 157 Oversensing 412
Inhibit mode456 Oxygensaturation 294
Inhibition 416 Pacemakerrequirements 229
Inotropic effects 23, 26, 29 Pacemakersuppression 38
Instruction set 233, 234, 467, 468 Pacemakertester 448, 453
Intercalated disks 5 Pacemaker-mediated taChycardia 349, 416
Interference 400 Pacing designation 115
Interrogation 285 Pacingindication 111
Interrupt handler245 Pacing mode122
Intracardiac electrogram173 Pacingselection 127
Intracardiac impedance369, 380, 386 Parasitic capacitances194
Ion channels 4 Parasympatheticcontrol 27
Ion concentrations2 Parasystole 62
Isoprotereno123 Passivefixation electrode 148
Kaplan-Meiersurvival curve 429 Patch electrodes 439
Kent bundle 93 Peak derivative of impedance384
Lead system 65, 105, 149 Pericardium10
Lead impedance271 pH sensor 293
Leadinsulation 153 Piezoelectric sensor 309, 310, 317
Leadstiffness 152 Polarization 141
Leadingcircle modelof reentry 408 Polymers 156
Length constant 49 Porosity 143
Lithiumbatteries 162 Porouselectrode 133
Lithium vanadiumpentoxide battery 431 Postventricularatrial refractory period 220
Logic flow diagrams 215 Powerpriority 169
Logic implementation228 Power supply down-conversion432
Lowerrate interval 215 Pre-ejectioninterva} 372
Lown-Ganong-Levinesyndrome 95 Pre-ejection period 385
Mahaim-typepreexcitation 96 Preexcitation arrhythmias93
Marking pulseq67 Preload mechanism16
Maximalheart rate 290 Prematureatrial contractions96
Meanarterial bloodpressure 18, 298, 371 Prematureventricular contractions 100
478 INDEX
Pressure sensor 316 Stellate ganglion26

Programmed electrical stimulation 77 Steroid elution 145
Programmedextrastimulus pulse delivery Stimulationthreshold voltage 138
414 Stimulus duration 254
Programmerhead 280 Stokes-Adams syndrome 81
Programming277 Stored electrograms 446
Propagationof an action potential 9 Strain gage313
Protectioricircuitry 273 Strength--durationcurve 251
Pseudo code 465 Stroke volume382, 383, 384
Pulse generator 107 Suddencardiac death 429
Pulse output 251 Supraventdcularaffhythmias 96
Pulse train stimulus415 Switched-capacitoramplifier 201
Purkinjefibers 12, 39 Switched-capacitor filter 188
QRScomplex I3 Sympatheticcontrol 24
QRSdetection 73 Sympathetic mapping25
Q-Tinterval 298, 373 Sympathetictone 370
Radio-frequency communication279 Synchronouspacemaker 108
Radio-frequencyinterference 209 Syncope 81
Randomaccess memory231 Systolic indices 298
Randomreentry 54 S-T segmentanalysis 74
Rate response function 323, 464 Tachycardiaacceleration 409
Rate-adaptive algorithm 348, 351,355, 362 Tachycardiacircuit entrainment409 "
Rate-adaptive pacemaker108, 290, 305 Tachyeardiadetection 411, 441,444
Rate-responsefactor 399 Target pacing rate 318
Rate-responsivealgorithm 462 Telemetry 285
Read-only memory231 Telephonic monitoring 286 -
Reducedinstruction set computer233 Temperaturechangevs. heart rate 340
Redundant pacemaker245 Temperatureof the blood 297, 335
Reed switch 277 Temporarypacemaker 108
Reentrantcircuit 52, 55, 56, 407 Terminationalgorithms 414
Reflection 61 Terminationof tachycardia 410
Refractoryperiod 8, 59, 216, 400, 458 Thermistor 341
Register fde 234 Thermoregulati0n335, 336
Relaxation response 416 Third-generation ICD445
Resettinga tachycardiacycle 409 Thoracotomy439
Restingpotential 1 Tidal volume399
Retrograde conduction 401 Tiered therapy 423
Reversiblecharge transfer 136 Timeconstants 399
Rheobase 253 Timers 235, 468
Ring modelof reentry 408 Timing diagrams 215
SAblock 80 Torsadede pointes 43
SAnode 27 Tot#l atrial refractory period221
Safety features 244 Transcutaneouspacing 109
Scherlag technique 75 Transesophagealpacing 111
Sense amplifier 180 Transthoracicpacing 111
Sensing/pacingcircuit 204 Transvenouspacing 110
Sensitivity 70 Trifascicular block92
Sick sinus syndrome82 Trigger mode457
Signal averaging 73 Triggered rhythms41, 44
Single chamberpacemakers215 Triggeredtachycardia 415
Sinoatrial (SA)node Truncated exponential waveform436
Sintering 144 Unidirectionalblock 52, 57
Sinus arrest 81 Unipolarleads 66
Sinus bradycardia 78 Unipolar sensing 171
Sinus inhibition 40 Unipolarstimulation 255, 261
Sinus tachycardia 79 Upperrate interval 216
Sleep state 462 Vagalinteractions 30
Slewrate 48 Vagusnerve 21
Slowedconduction 47 Vagusnerve stimulation 416
Sodiumconductance 8 Ventilationrate. 295,399
Specificity 70 Ventricular blankingperiod 222
SPICEanalysis 180 Ventricular depolarizationgradient 298, 379
Stair ascent/descent328 Ventricular escape heats 102
State machine231 Ventficularfibrillation 102
INDEX 479
Ventricularflutter 101 Voltage-controlledoscillator 317

Ventricular inotropic parameter386 Voltage-to-currentconverter392
Ventricularsafety pacing 222 Wakeupevent 462
Ventricular tachycardia100 WARAD prevention 418
Ventriculoatrialinterval 220 Watchdogtimer 244
Vibration sensor 299, 331 Wenckebachpacemaker response 226
Vitreous 144 Wilsoncentral terminal 66
Voltage comparator203 Wolff-Parkinson-White syndrome 93
Voltage doubler 260 Zero-crossingdetector 398
Voltagemultipliers 259 Zinc-mercurybattery 161
Voltagereference 204

Cardiac Pacemakers

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Cardiac Pacemakers

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This book maybe purchased at a discount from the publisher whenordered

in bulk quantities. For moreinformation contact:

©1995by the Institute of Electrical and ElectronicsEngineers,Inc.

Coverphoto © 1993 Medtronic, Inc., from 1993AnnualShareholder’sReport.

Printed in the UnitedStates of America

Designof cardiac pacemakers/ edited by John Webster.

A Volumein the TAB-IEEE

IEEEEngineering in Medicine and Biology Society, Sponsor

R. S. Blicq S. V. Kartalopoulos I. Peden

IEEEEngineering in Medicine and Biology Society, Sponsor

TAB-IEEEPress Book Series Statement

Normal Conduction System of the Heart 1

1.1 Ionic bdsis of the resting potential 1

2 Control Systems of the Heart 15

2.1 Cardiac control factors 15

3 Mechanisms of Cardiac Arrhythmias 34

4.1 Principles of electrocardiography 64

5 Artificial Pacing 105

5.1 Artificial pacemakerunit 105

6 Electrodes, Leads, and Biocompatibility 132

6.1 Pacemaker electrodes 132

7.1 Materials 161

8 Pacemaker Sense Amplifiers 171

8.1 Requirements 171

Logic Flow and Timing Diagrams 215

9.1 Single chamber pacemakers 215

10 Logic Implementation 228

10.1 Microprocessor-based pacemaker unit 228

11 Pulse Output 251

....... 11.1 Considerations for output design 251

12 External Programming 277

12.1 Hardware interface 277

13 Rate-Adaptive Pacemakers 290

13.1 Introduction 290

14.1 Humanactivity and heart rate 306

14.5 Studies on motion-based rate-adaptive pacemakers 328

15 Rate Adaptation by Temperature 335

15.1 Bodytemperature production and regulation 335

16.1 Benefits of using intracardiac signals for rate adaptation 369

17 Rate Adaptation by Minute Ventilation 397

17.1 Advantagesand disadvantages of minute ventilation 397

18 Antitachycardia Pacing 405

18.1 The first antitachycardia pacemaker 405

18.4 Tachyarrhythrnia detection 411

19 lmplantable Cardioverter-Defibrillators 427

19.1 Implantable cardioverter-defibfillator history 427

UWPacemaker Tester 448

20.1 Pacemakertesting 448

Appendix: Microprocessor-based pacemaker design 460

A.1 Rate-adaptive pacemakers 460

This book provides information on the design of cardiac pacemakers. As a

~p~p a0i~s and~received invaluable suggestions .for improvement. I am most

i.i( ’ Ch~ipter. l provides the backgrouiid ~matedalnecessary to unders)and normal

Knowledge of the excitability characteristics of cardiac cells is essential in

1.1 IONIC BASIS OF THE RF~TINGPOTENTIAL

Theelectrical potential difference betweenthe inside and outside of a cardiac cell

EK-- !n . --0.027 [~-~]-- (v)

Ion Extracellular Intracellular Equilibrium

In a real cell~ it is necessary to consider the contributions of other permanent

contribuiJontoward the membranepotential. In cardiac cells, Changesin membrane

Figure1.3 Electrical equivalentof a cardiaccell membrane~. Theequ~bdum voltages predicted

If the transmembraneconductance to a particular ion is increased~.the ~al

molecule of ATP(adenosine triphosphate) hydrolyzed. The active transport

1,2 MEMBRANE CHANNELS AND CARDIAC~CELLS