The discipline "Modern medical equipment (Medical Devices)"

Practice 5

IMPLANTABLE CARDIAC PACEMAKERS

WILEY ENCYCLOPEDIA OF BIOMEDICAL ENGINEERING Metin Akay,

Editor /Published by John Wiley & Sons, Inc., Hoboken, New Jersey-2006

Electrical stimulators are used in health care for different applications, some for
diagnostic purposes (e.g., the measurement of the propagation velocity of nervous
impulses), but most of them for therapeutic purposes. Typical therapeutic
applications are concerned with the stimulation of muscles or efferent peripheral
nerves that may be achieved either invasively by direct contact or
transcutaneously, of the bladder, the auditory system (i.e., the cochlear implant),
the visual system, the pulmonary system via the phrenic nerve, the brain in order to
suppress epileptic events, and the spinal cord for pain control. The electrical
stimulators, however, that have found the broadest application in clinical routine
are the cardiac pacemakers (PMs), especially the implantable cardiac pacemakers
(IPMs), and shockwave generators or defibrillators. Defibrillators also employ
electrical stimuli for the control of the proper function of the heart and can be
applied either as extracorporeal devices or as implantable cardioverter defibrillator
(ICDs). IPMs as well as ICDs are large device families for the management of
cardiac arrhythmias. Growing evidence exists that these two families become
integrated in one ‘‘universal’’ family for arrhythmia management.
Although twitches of living muscle as a consequence of electric stimuli were
already known from experiments performed by Otto von Guericke and Gottfried
Wilhelm von Leibnitz about one century earlier, Luigi Galvani in the 1770s had
been the first researcher who systematically studied the effect of electrical
stimulation on the frog’s nerves with the subsequent contraction of the muscle as
indication for successful stimulation. Although the employed electrical means had
been rather primitive from the present view, Galvani’s studies had been an
essential step into the era of electrophysiology. In his famous publication, he
described the ‘‘effect of electricity on muscular motion’’ (1) and interpreted the
results of these experiments as caused by ‘‘animal electricity.’’ He claimed that
this form of electricity in living tissue was different from the ‘‘ordinary’’
electricity. This interpretation as special ‘‘animal electricity’’ was already rejected
by AlessandroVolta, a contemporary of Galvani, who emphasized the common
nature of ‘‘animal’’ and ‘‘ordinary’’ electricity. Already in the middle of the
eighteenth century, it was known that beats of the isolated heart can be achieved by
electrical stimulation. In 1855, the French neurologist Guillaume Benjamin
Armand employed an electrical means to affect the heart rate of a patient who
suffered from tachyarrhythmia. In 1882, Hugo von Ziemssen from Germany
showed in a patient during open-chest surgery that cardiac activity in man can be
controlled by electric pulses.

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The first real PM was developed in the United States by Albert Hyman between
1927 and 1932. This device was a magneto-powered impulse generator with a
weight of 7.2 kg, driven by a spring motor that had to be recharged manually every
6 min. It was intended for employment in cases of emergency and for the
resuscitation of the asystolic heart . The first defibrillator was developed in 1952
by the American Paul Maurice Zoll and successfully employed to resuscitate 2
patients from ventricular asystole by the application of external cardiac
stimulation. The most powerful impulse for further technical progress regarding
intelligent and implantable devices came from the side of electronics, especially
from the development of the transistor by W. Shockley, J. Bardeen, and W. H.
Brattain in 1948, who received the Nobel Prize in Physics for their ‘‘researches on
semiconductors and their discovery of the transistor effect’’ in 1956. Already in
1956 a first transistorized PM was developed by W. Greatbatch, one of the
outstanding pioneers in pacemaker technology.
The first really implantable pacemaker was developed by R. Elmquist and
implanted by A. Senning in 1958 in Stockholm in the patient A. Larsson. Larsson
died in 2002 at the age of 86 (i.e., 44 years after he had received his first of 26
IPMs). This first IPM was actually an astable multivibrator, powered by an
externally rechargeable Ni/Cd cell and connected with the heart through epicardial
leads. Fixing the leads to the heart was achieved by suturing and required
thoracotomy (i.e., the opening of the chest in order to enable access to the heart).
The first implantable cardiac defibrillator was developed and implanted in 1980 in
Baltimore by M. Mirowski, who was born in Poland.
Progress in cardiac electrophysiology and surgery was also fundamental for the
advancement of PM technology. W. Einthoven was the first to succeed in
recording the electrocardiogram (ECG) with sufficient resolution of the signal
morphology that enabled pathophysiological interpretation and resulted in better
understanding of the occurrence, conduction, and spreading of excitations in the
heart. Einthoven received the Nobel Price in Physiology and Medicine ‘‘for his
discovery of the mechanism of the electrocardiogram’’ in 1924, about 25 years
after his pioneering development that rendered possible ECG recording.
In 1931, W. Forssmann demonstrated on himself that a catheter could be passed
through the venous vessels to the heart. This technique was evaluated not earlier
than 20 years later by A. F. Cournand and D. W. Richards. These three researchers
received the Nobel Prize in Physiology and Medicine in 1956 ‘‘for their
discoveries concerning heart catheterization and pathological changes in the
circulatory system.’’ Although cardiac catheterization has originally been
investigated with the aim to withdraw blood from the right heart in order to
measure oxygen saturation in the mixed venous blood, it was finally the most
important step toward the transvenous introduction of pacemaker electrodes to the
heart (i.e., to the intracardiac spaces).
The first PM was a single-chamber device without a sensing feature (i.e., it was a
simple fixed-rate pulse generator). As it did not consider any spontaneous cardiac

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activity, it was called an asynchronous device. The electrical circuit of such a
device is shown in Fig. 1.

Figure 1. Electrical circuit of an asynchronous pacemaker. (Russia, 1961)

Today, such a device is classified as type V00 in accordance with the most usual
classification, the NASPE/BPEG coding. The progress in stimulating, sensing, and
controlling capabilities regarding implantable cardiac stimulators is represented in
the following timetable (classification in accordance with the NASPE/BPEG code
(see Table 1):
1958 - First pacemaker implantation asynchronous type by Senning.
1959 - 1 ventricular stimulating channel, 1 atrial sensing channel, triggered:
VAT.
1962 - Controllable pacemaker based on programmability.
1962 - Transvenous endocardial electrode and access
to the right heart.
1967 - 1 ventricular stimulating channel, 1 ventricular sensing channel,
inhibited: VVI.
1970 - 2 stimulating channels (atrial, ventricular), 1 ventricular sensing channel,
inhibited: DVI.
1970 - Lithium-based primary cells (e.g., the lithiumiodine cell). These cells
replaced the primary Zn/HgO cell and the rechargeable Ni/Cd cell.
1971 - Transtelephonic pacemaker monitoring and post-implant surveillance .
1971 - Integrated circuits and first steps towards telemetric programmability.
1975 - 2 stimulating channels (atrial, ventricular), 2 sensing channels (atrial,
ventricular), both triggered and inhibited: DDD.
1979 - Bidirectional telemetry.
1980 - First Automated External Defibrillator (AED).
1980 - First ICD: 1 ventricular channel for shock delivery, 1 ventricular
sensing channel, signal processing for arrhythmia detection: VVICD.
1984 - 1 ventricular stimulating channel, 1 ventricular sensing channel,
inhibited, rate adaptive by using a sensor for matching with hemodynamic
needs: VVIR.

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 1990 - 2 stimulating channels (atrial, ventricular), 2 sensing channels (atrial,
ventricular), both triggered and inhibited, rate adaptive (1 sensor): DDDR.
1990 - Closed-loop approach for rate-adaptive pacing.
1994 - 2 stimulating channels (atrial, ventricular), 2 sensing channels (atrial,
ventricular), both triggered and inhibited, rate adaptive (several sensors for
hemodynamic demands): DDDR.
1996 - First ICD for atrial defibrillation.
1996 - Multisite pacing, e.g. biatrial, biventricular or combinations of both
types with any number of electrodes.
2002 - IPM Internet-based post-implantation follow up home-monitoring.

Table 1. The Revised NASPE/BPEG Generic Code for Antibradiycardia Pacing

The fundamentals of electrical stimulation with special regard to the heart muscle.
Excitable cells (e.g., cardiacmuscle cells, skeletalmuscle cells, or nerve cells) have
the property to respond to a stimulus of sufficient strength (or power) with a short
change in the membrane potential from about -80mV to about +20mV. This
change in the membrane potential is called the action potential. It is caused by
transmembraneous ion fluxes, mainly sodium ions and chloride ions that flow into
the cell and potassium ions that flow out of the cell. The stimulus can have a
mechanical, a thermal, a chemical, or an electrical quality. The most adequate
quality is the electrical stimulus. Mechanical stimulation has long been considered
and is now again in discussion for an external PM that uses ultrasound for
stimulation. In order to generate an action potential, the membrane of the cell must
be depolarized from its resting potential of -80mV to the threshold potential of
about -40mV. If the membrane potential surpasses this threshold, the further
process leading to the action potential becomes autonomous and independent of
the actual strength of the stimulus. The strength of such an electrical stimulus
depends on the following parameters:
– the amplitude of the current density;
– the duration of the current flow;
– the slope or time derivative of the current pulse; and
– the polarity (i.e., whether the membrane is considered beneath the cathode or
anode).
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With regard to the ‘‘amplitude,’’ some discussion still occurs about whether the
exchanged charge, the electrical field gradient, the voltage, the current, or the
current density determines the strength of the electrical stimulus.
For instrumentation aspects, mainly the current and the current density are of
interest. If the active area of the two electrodes is significantly different, the
excitation always originates from the smaller electrode (i.e., from the electrode
with the higher current density), although the current that flows through both
electrodes is the same. For cardiac stimulation, this effect is intentionally used in
the unipolar mode when one electrode (‘‘active’’ electrode) is significantly smaller
than the other electrode, which is usually formed by the metallic case of the
pacemaker or its nonisolated parts.
If the stimulus is a pulse with rectangular shape, the slope as a third parameter can
be neglected. The relation between the amplitude and the duration for a pulse with
sufficient strength is described by the strength–duration relationship (sometimes
also called the WEISS-LAPICQUEE curve), which is actually a rectangular
hyperbola with the rheobase and the chronaxie as characteristic values.
This relation states that the two variables, amplitude and duration, are equivalent
with regard to the depolarizing efficiency. Neither the strength of the stimulus nor
the shape of the stimulated action potential will be changed by the diminution of
one parameter if it is compensated by a corresponding augmentation of the other
parameter. However, the amplitude must always be greater than the rheobase.
Thus, the rheobase is a critical threshold. It is one of the two asymptotes to the
hyperbola. The chronaxie is the duration of a pulse with twice the rheobase as
amplitude that reaches the threshold for stimulation.
For technical reasons (i.e., for simplicity of the employed circuitry), stimulation
with the pacemaker is based on voltage instead of current density. The relation
between feeding voltage and current is constant if the total resistance between the
feeding electrodes remains constant. The relation between feeding voltage and
current density is also constant if the spatial resistivity condition between the
feeding electrodes remains constant. Typical values for direct heart stimulation via
contacting electrodes are 0.5V to 4.5V and 0.15 ms to 1.50 ms. Usually, the
stimulus is realized by discharging a capacitor during a set time interval (i.e., using
truncated discharge). Although the shape of that stimulus is not exactly
rectangular, the depolarizing effect can approximately be described by the above-
mentioned strength–duration relation as long as the resistance between the two
electrodes is rather high. The frequency content of electrical stimuli for cardiac
pacemakers is in such a low range that the impedance can sufficiently be taken into
account by its resistive part only. The following effects, however, have to be
considered:
1. The resistance between the electrode surface and the tissue and, hence, the total
resistance between the two electrodes changes with time; an approximate figure is
500 Ω.
2. The resistance between the electrode surface and the tissue changes during
stimulation as a consequence of current flow.

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3. A fibrotic capsule is growing around the electrode after it has been brought in
contact with the tissue because of mechanical-chemical interactions, and the
conductivity of fibrotic tissue is different from the conductivity of the original
cardiac tissue.
This fibrotic capsule consists of nonexcitable tissue. The growing of this capsule
causes not only an increase in the resistance between the electrodes, but also an
enlargement of the boundary area between the fibrotic and the regular cardiac
tissue and, as a consequence, a diminution of the current density across that area.
Actually, the interface between the fibrotic capsule and the surrounding cardiac
myocardium can be considered to be a “virtual electrode”. Therefore, the voltage
of the stimulus must be great enough to provide the required current
density in the first layer of excitable tissue beyond that fibrotic capsule. Usually,
and for safety reasons, the power of the applied stimulus is set at least twice the
value of the critical threshold. That stimulus strength above the threshold increases
the volume of capture (i.e., that volume that is directly stimulated).
Stimulation of an excitation requires the depolarization of the membrane to the
threshold potential. With the onset of the stimulus, depolarization is achieved
beneath the cathode, whereas the anode causes hyperpolarization. For this reason,
the cathode is usually the ‘‘active’’ electrode, from which the excitation is
originating and spreading. The anode can also be used as an active electrode either
because ‘‘virtual’’ cathodes result in the deeper tissue beneath the anode or as a
consequence of the depolarizing effect when the stimulus is switched off. For the
anode as an active electrode, however, the strength of the stimulus must be
increased significantly. In the unipolar mode, the tip of the electrode is used as
active electrode, and the case of the pacemaker as “passive” electrode. In the
bipolar mode, the active electrode is formed by the tip of the electrode, whereas the
passive electrode is formed by a ring in the distance of some millimeters (10–
20mm) behind the tip with an area that is larger than the area of the cathode (Fig.
2). Typical values for pacemaker electrodes are 1–6 mm 2 for the tip and about 40
mm2 for the ring. Both modes of stimulation yield different current fields in the
tissue. Although the bipolar mode requires higher power for stimulation (i.e.,
causes more battery discharge), its risk is less to stimulate other muscles
additionally (e.g., thoracic muscles, or the phrenic nerve and thereby the
diaphragm).
As the heart muscle is a ‘‘functional’’ syncytium, it is sufficient to stimulate an
excitation elsewhere in that tissue. As a result, the excitation will spread over the
whole heart. It will even propagate from the atria to the ventricles (and inverse or
retrograde) if the AV conduction system is functioning properly. It must be taken
into account, however, that the wave of contraction follows the wave of excitation
(i.e., a nonphysiological temporal pattern for excitation spreading will result in a
nonphysiological temporal pattern for contraction). A nonphysiological temporal
pattern for the contraction may cause a diminution in the hemodynamic efficiency.
Another property of excitable tissue is refractoriness. During the action potential
and a short interval after it, the membrane is not at all excitable (absolutely

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refractory) or only with increased strength (relatively refractory) by another
stimulus. For cardiac cells, the refractory period is only slightly longer than the
action potential, which in total is about 250 ms, however, depending on the heart
rate. Refractoriness is the main reason why two excitations will extinguish each
other if and where they meet (i.e., they are not able to continue their propagation
by “overrunning” each other). This meeting of two excitation wavefronts is called
‘‘fusion.’’ Fusion beats can have significant hemodynamic consequences.
Basic concepts of implantable cardiac Pacemakers.
The requirements and challenges with regard to technology, functionality, safety,
and quality are higher for implantable pacemakers than for nonimplantable or
external pacemakers. Although most of the following explanations are valid for
both types of pacemakers, they are primarily concerned with the implantable
devices. In contrast, the principles, concepts, and features of defibrillators are
significantly different, especially with regard to signal processing (i.e., arrhythmia
detection) and stimulation (i.e., high-voltage shocking).
Principle of Sensing and Controlled Stimulation.
The failure of excitation generating and spreading may be permanent or temporary.
In case of temporary failure, the pacemaker must be able not only to stimulate, but
also to recognize whether a spontaneous action takes place or not. This task of
recognition is called ‘‘sensing.’’ The signal that is recorded by sensing is actually
the electrocardiogram (i.e., the summing potential composed of the action
potentials of many individual myocardial cells at the site of the sensing electrode).
If this potential is recorded directly from the heart (e.g., with the electrode in
epimyocardial or intraventricular position), the signal is called an intramyocardial
electrogram (IEGM). Terms that are more specifying with regard to the site of
recording may be, for example, ventricular electrogram (acquired from one of the
ventricles), atrial electrogram (acquired from one of the atria), endocardial or
intracardiac electrogram (acquired from the endocardial layer), and epicardial
electrogram (acquired from the epicardial layer). Sensing is achieved by electrodes
comparable with those that are used for stimulation, and frequently the same
electrode is employed for sensing and stimulating. If the failure is permanent,
sensing is not required at the site where stimulation is applied. Atrial sensing is not
required for permanent SA node failure, but for temporal failure that must be
detected in order to apply atrial stimulation.
Ventricular sensing is not required for permanent
AV conduction failure, but for temporary failure that must be detected in order to
apply ventricular stimulation.
However, for temporary as well as for permanent failure of AV conduction atrial,
sensing is useful. In case of temporary and permanent failure, the atrial signal is
used to achieve synchronization of the ventricular with the atrial contraction. For
such IPMs, the term ‘‘synchronous’’ or even ‘‘rate responsive’’ devices has been
introduced because the ventricular heart rate is synchronized with and also
determined by the spontaneous SA node rate under the influence of the ANS. In
case of temporary failure, the atrial signal can additionally be employed to start the

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interval during which the arrival of the excitation in the ventricles inhibits the
ventricular stimulation. In both cases, atrial sensing renders possible matching of
the AV delay with the actual sinus rate because the AV delay becomes
shorter with higher heart rate.
The most essential units of a PM are (Fig. 3):
– one or more sensing channels (i.e., signal amplifiers with appropriate
transmission characteristics);
– one or more stimulating channels (i.e., pulse shapers with output amplifiers);
– a microprocessor for signal processing and timing control together with a clock,
usually quartz-controlled, and memories (RAM, ROM);
– a power unit (i.e., a battery with voltage converter, together with an ‘‘end-of-
life’’ indicator); a bidirectional telemetry unit for the communication with an
external (i.e., extracorporeal) transmitter-receiver unit in order to check the actual
operational parameters and to use the flexible programming capability (Fig. 4); and
– one or more electrodes [i.e., leads that connect the PM directly or, in case of
external PM, indirectly (e.g., transcutaneously, (or transthoracically), or
transesophageally)] with the heart for sensing and stimulation.

Figure 2. Schematic illustration of the different modes for stimulation. (a) Unipolar
mode, (b) bipolar mode.

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Figure 3. Simplified schematic diagram with the basic functional units of a
remotely programmable PM.

Figure 4. Programmer and read head (communication coil).

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 Figure 5. Implantable cardioverter defibrillator

Sensing of intracardiac electrograms can be performed in the unipolar as well as in

the bipolar mode. The voltage amplitude of sensed signals is about 5mV to 20mV
(i.e., much smaller than the voltage amplitude that is applied for stimulation with
about 0.5V to 4.5 V). The amplitude of the sensed signal usually declines during
the first days to weeks following lead implantation before it increases again to a
value that is slightly lower than the initial value recorded immediately after
implantation. The monitored frequency range of sensed signals is about 10–50 Hz.
The morphology of sensed signals from the atria is slightly different from those
sensed from the ventricles.
The morphology of the sensed signals additionally depends on such factors like the
material, the frequencydependent transfer characteristics and the position of the
sensing electrode, the geometric shape of the heart muscle, and the sensing mode.
Usually, the unipolar mode
is less sensitive against disturbances or interferences like action potentials from the
skeletal muscle (e.g., thoracic muscles) and external electro-magnetic fields that
may be caused by safety controls on airports, antitheft controls in shopping centers,
and similar devices.
Controlled stimulation means primarily synchronous stimulation (i.e., that the
sequence of atrial and ventricular excitation and contraction is in accordance with
the physiological sequence). This requirement is not met in the asynchronous
mode. In that mode, the stimulation of the ventricles does not depend on the atrial
excitation and is not synchronized with it. The asynchronous mode has formerly
been used in case of AV conduction failure, both temporarily and permanently, in
older devices that stillmay be working in patients, but now it is no longer used.
In the asynchronous mode, the ventricular contraction can precede the atrial
contraction (i.e., the atrial contraction does not contribute to the ventricular stroke
volume), and the AV valves are stressed by the high ventricular pressure versus the
low atrial pressure. Newer devices use
only the synchronous mode (i.e., the ventricular stimulation follows the atrial
excitation with adequate AV delay). This mode requires a two-chamber IPM with a
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sensing (and possibly stimulating) electrode in the atria and a sensing and
stimulating electrode in the ventricle.
Controlled stimulation means additionally that the stimulation rate is in accordance
with the physiological rate that respective individual would have under the given
conditions. If the SA node generates excitations and only the AV conduction fails
temporarily or permanently,
the SA signals are used to stimulate the ventricles synchronously. In this case, the
synchronous ventricular stimulation is nearly physiological because it is via the SA
node controlled by the ANS activity with its quasi-periodical oscillations (e.g.,
dependent on ventilation and fluctuations of the peripheral vascular resistance). If
the SA node fails to generate spontaneously excitations, atrial stimulation can be
executed either in the fixed rate or in the rate-adaptive mode. Fixed-rate
stimulation is nonphysiological because it does neither consider the quasi-
periodical oscillations or the dependence of the heart rate on both physical exercise
and psychological-emotional stress. The fixed rate must at least meet the
hemodynamic and metabolic needs for the resting condition. An increase in cardiac
output is possible only by the enhancement of stroke volume. In the rate-adaptive
mode, different approaches can be employed to monitor variable quantities that
represent either the physical exercise alone or also other impacts like emotion and
orthostasis and are used to match the heart rate. However, because of the long time
constants for the signal processing (e.g., caused by procedures like averaging
rewired for poor signal quality), it was not possible until now to consider properly
the quasi-periodical oscillations, especially those of the peripheral resistance that
reflect the ANS activity on the vasomotoric state.

Modern pacemakers and implantable cardioverter defibrillators (Fig. 5) are no

longer simple generators, but complex technical systems with high functionality,
flexiblility, and remote programmability, and quality-of-life providing features.
Their most essential properties are sophisticated signal processing, intelligent
information processing, electronic circuitry based on integrated micro and
nanotechnology, outstanding reliability of all employed components, excellent
biocompatibility, and device longevity of nearly a decade.

The task.

Learn the basics of implantable cardiac pacemakers.

Search the Internet for 1-2 examples of implantable cardiac pacemakers and a
video explaining how such devices work.

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