Mechanisms and Management of

Arrhythmias
Yoga Yuniadi
Division of Arrhythmia, Department of Cardiology and
Vascular Medicine, Faculty of Medicine, University of
Indonesia,
and National Cardiovascular Center Harapan Kita,
Jakarta
Mechanisms
 Myocardial
Depolarisation-Repolarisation

T ECG
Q
20 1 2
0

mV 0 3
tp
-60
-90 rmp 4 MAP

Na,Ca Ca K Na K
Goldschlager et al. 1989
 Normal Heart Conduction

Sinoatrial Node
Isolative fibrous skeleton
 Normal Heart Conduction

Atrioventricular Node
Normal Heart Conduction

Left Bundle Branch (LBB)

Posterior Fascicle of LBB

Anterior Fascicle of LBB

Right Bundle Branch (RBB)

Impulse propagation during SR
Epidemiology of SVT
 MESA (Marshfield Epidemiologic Survey Area)
 2.25/1000 medical record
 35/100,000 persons-year
 Prevalence (Percentage of total discharges)
MESA HCUP 3
AF 44.8 0.78
AFL 5.2 0.1
SVT 3.8 0.11
 Arrhythmia Mechanisms
 Abnormal Impulse Initiation
 Automaticity
 Normal automaticity
 Abnormal automaticity
 Triggered Activity
 Early afterdepolarizations
 Delayed afterdepolarizations

 Abnormal Impulse Conduction

 Conduction block leading to ectopic pacemaker "escape"
 Unidirectional block & reentry
 Ordered reentry: functional anisotropic, anatomical
 Random reentry
 Reflection

 Simultaneous Abnormalities of Impulse Initiation and Conduction

 Parasystole

Janse: Mechanisms of Arrhythmias, 1993

Diagram of the arrhythmias
mechanisms

Atrial fibrillation
SNRT Atrial flutter

AT AVRT
AVNRT

JT

VT

VF
Reentry Mechanism
Triggered Activity
Tachycardia Classification (1)
 Narrow QRS complex
 Reguler
 Atrioventricular Reciprocating Tachycardia (AVRT)
 Atrioventricular Nodal Reentrant Tachycardia (AVNRT)
 Atrial Flutter (AFL)
 Atrial Tachycardia (AT)
 Junctional Tachycardia (JT)
 Narrow complex Ventricle Tachycardia
 Irreguler
 Sinus Arrhythmia
 Atrial Fibrillation
 AFL or AT with varying degree block
Tachycardia Classification (2)
 Wide QRS complex
Ventricle Tachycardia (VT)
Supraventricle Tachycardia (SVT) with bundle
brach block (BBB)
 Abberancy
 Pre-existing BBB
SVT with pre-excitation
 Antidromic AVRT
 AVNRT with pre-excitation
 AFL or AT with pre-excitation
AV Nodal Reentry
Common form of recurrent, paroxysmal SVT,
(60-65% of PSVTs)
ECG – Discrete P waves not visible
– A&V depolarize simultaneously
Symptoms – Palpitations
– Lightheadedness
– Dyspnea
– Chest discomfort
– Anxiety
Difficult to control with AA drugs

Kay GN. Am J Med. 1996.

AV Nodal Reentry Tachycardia

Morady F. N Engl J of Med. 1999.

Illustrations of AVNRT
1. wavefront
2. ecg
 Wolf-Parkinson-White (WPW)
Syndrome
 Definition: Presence of accessory pathway
and tachycardia (AVRT)
 Symptoms: asymptomatic to sudden
cardiac death
 Conduction through the accessory
pathway: Antegrade and/or retrograde
 30% of PSVTs are orthodromic AVRT:
Antegrade conduction over AV node
Retrograde conduction over accessory
pathway
 Sudden death in WPW Syndrome

 0.15-0.39% over 3-10 years follow-up

 50% cardiac arrest in WPW: first
manifestation
 High incidence of SCD in familial WPW
Illustrations of WPW syndrome
1. AP locations
2. Wavefront propagation (SR)
3. ECG-SR
4. Wavefront propagation (AVRT)
5. ECG-AVRT
 Atrial Flutter

 Macro reentry in the atrium

 Clinical significance:
Tachycardiomyopathi
Thrombo-embolic event
Mechanism of Atrial Flutter
 Cavotricuspid Isthmus dependent
 Typical AFL
 Reverse Typical AFL
 Lower Loop Reentry
 CTI Independent
 Upper Loop Reentry
 Scar Reentry
 Double Loop Reentry
 Left Atrial AFL

Wellens. PACE, 2003

Variable ECG Morphologies of Typical
Atrial Flutter

 CCW-AFL ECG morphologies:

Type Inferior V1 n
1 F-/f+ F+ or F+/f- 32
2 F- F+
4
3 f-/F+ F+
2

 CW-AFL ECG morphologies:

Type Inferior V1 n
1 F+ F-
4 Yuniadi Y, et al. Circulation 2003
Different RA Activation of Typical AFL

Type 2 Type 3

Yuniadi Y, et al. AHA Meeting 2003

Illustration of Atrial Flutter
1. Wavefront propagation
2. ECG
Management
 Vaughan-Williams AA Classification

 Class I: bind to sodium channel, decrease

speed of depolarization
 Class II: beta blocking drug, decrease
sympathetic tone. Affect mainly SA and AV node
(indirectly by blocking beta receptors)
 Class III: increase action potential duration
 Class IV: calcium channel blocker, affect SAN
and AVN directly
 Class V: digitalis agents, affect SAN and AVN
indirectly by increasing vagal tone
 Vaughan-Williams AA Classification

 Class I
 IA: quinidine, procainamide, dysopiramide
 IB: lidocaine, phenytoin, tocainide, mexiletine
 IC: flecainide, encainide, propafenon
 Class II: atenolol, labetolol, metoprolol,
propanolol, nadolol, timolol, esmolol
 Class III: amiodarone, bretylium, N-
acetylprocainamide, sotalol
 Class IV: diltiazem, verapamil
 Class V: digitalis
AA influence to MAP
Symptom Oriented SVT Management

Circulation 2003; 107: 1096-99

 The level of evidence

 Level A (highest): derived from multiple

randomized clinical trials;
 Level B (intermediate): Data are based on
a limited number of randomized trials,
nonrandomized studies, or observational
registries;
 Level C (lowest): Primary basis for the
recommendation was expert consensus.
 Classification of Indication
 Class I: Conditions for which there is evidence and/or
general agreement that a given procedure or treatment
is useful and effective.
 Class II: Conditions for which there is conflicting
evidence and/or a divergence of opinion about th
usefulness/efficacy of a procedure or treatment.
 Class IIa: Weight of evidence or opinion is in favor of
usefulness/efficacy.
 Class IIb: Usefulness/efficacy is less well established by
evidence or opinion.
 Class III: Conditions for which there is evidence and/or
general agreement that the procedure or treatment is not
useful/effective and in some cases may be harmful.
 Recommendations for Acute Management of Hemodynamically Stable
and Regular Tachycardia
ECG Recommendation* Classification Level of Evidence

Narrow QRS Vagal maneuvers I B

tachycardia Adenosine I A
(SVT) Verapamil, diltiazem I A
Beta blockers IIb C
Amiodarone IIb C
Digoxin IIb C
Wide QRS
tachycardia
•SVT and BBB See above
•Pre-excited SVT/AF† Flecainide‡ I B
Ibutilide‡ I B
Procainamide‡ I B
DC cardioversion I C
•Wide QRS-complex Procainamide‡ I B
tachycardia of Sotalol‡ I B
unknown origin Amiodarone I B
DC cardioversion I B
Lidocaine IIb B
Adenosine§ IIb C
Beta blockers¶ III C
Verapamil** III B
Wide QRS Amiodarone I B
tachycardia, DC cardioversion, I B
Unknown origin, lidocaine
poor LV function
 Recommendations for Long-Term Treatment of Patients With
Recurrent AVNRT
Clinical Presentation
Poorly tolerated AVNRT
with hemodynamic
intolerance
Recurrent symptomatic
AVNRT
Recurrent AVNRT
unresponsive to BB or CCB,
not desiring RF ablation
AVNRT with infrequent or
single episode, desire
complete control of arrhythmia
Documented PSVT with only
dual AV-nodal pathways or
single echo beats demonstrated
during electrophysiological
study and no other identified
cause of arrhythmia
Infrequent,
well-tolerated AVNRT
Recommendation
Catheter ablation
Verapamil, diltiazem,
beta blockers, sotalol,
amiodarone
Flecainide,* propafenone*
Catheter ablation
Verapamil
Diltiazem, beta blockers
Digoxin†
Flecainide,*
Amiodarone
Catheter ablation
Verapamil, diltiazem,
beta blockers, flecainide,*
propafenone*
Catheter ablation‡
No therapy
Vagal maneuvers
“Pill-in-the-pocket”
Verapamil, diltiazem,BB
Catheter ablation
Class Level of Evidence
I B
IIa C
IIa C
I B
I B
I C
IIb C
IIa B
IIb C
I B
I C
I B
I C
I B
I B
I B
I B
 Recommendations for Treatment of Focal and
Nonparoxysmal Junctional Tachycardia
Syndromes
Clinical Presentation Recommendation Class Level of Evidence

Focal junctional Beta blockers IIa C

tachycardia Flecainide IIa C
Propafenone* IIa C
Sotalol* IIa C
Amiodarone* IIa C
Catheter ablation IIa C
Nonparoxysmal Reverse digitalis toxicity I C
junctional tachycardia Correct hypokalemia I C
Treat myocardial ischemia I C
Beta blockers, CCB IIa C
 Recommendations for Long-Term Therapy of
Accessory Pathway–Mediated Arrhythmias
Arrhythmia Recommendation Class Level of Evidence

WPW syndrome Catheter ablation I B

(pre-excitation and Flecainide, propafenone IIa C
symptomatic Sotalol, amiodarone, BB IIa C
arrhythmias), Verapamil, diltiazem, III C
well tolerated digoxin
WPW syndrome (with Catheter ablation I B
AF and rapid-conduction
or poorly tolerated
AVRT)
AVRT, poorly Catheter ablation I B
tolerated (no Flecainide, propafenone IIa C
pre-excitation) Sotalol, amiodarone IIa C
Beta blockers IIb C
Verapamil, diltiazem, III C
digoxin
Single or infrequent None I C
AVRT episode(s) Vagal maneuvers I B
(no pre-excitation) ’Pill-in-the-pocket”— I B
verapamil, diltiazem, beta blockers
Catheter ablation IIa B
Sotalol, amiodarone IIb B
Flecainide, propafenone IIb C
Digoxin III C
Pre-excitation, asymptomatic None I C
Catheter ablation IIa B
 Recommendations for Treatment of Focal Atrial
Tachycardias*
Clinical Situation Recommendation Class Level of Evidence

Acute treatment†
A. Conversion
Hemodynamically DC cardioversion I B
unstable patient
Hemodynamically Adenosine IIa C
stable patient Beta blockers IIa C
Verapamil, diltiazem IIa C
Procainamide IIa C
Flecainide, propafenone IIa C
Amiodarone, sotalol IIa C
B. Rate regulation (in absence of
digitalis therapy) Beta blockers I C
Verapamil, diltiazem I C
Digoxin IIb C
Prophylactic therapy
Recurrent symptomatic Catheter ablation I B
AT Beta blockers, CCB I C
Disopyramide‡ IIa C
Flecainide, propafenone‡ IIa C
Sotalol, amiodarone IIa C
Asymptomatic or Catheter ablation I B
symptomatic incessant ATs
Nonsustained and No therapy I C
asymptomatic Catheter ablation III C
 Recommendations for Acute Management of
Atrial Flutter
Clinical Status/ Level of
Proposed Therapy Recommendation* Class Evidence
Poorly tolerated
•Conversion DC cardioversion I C
•Rate control Beta blockers IIa C
Verapamil, diltiazem IIa C
Digitalis† IIb C
Amiodarone IIb C
Stable flutter
•Conversion Atrial or transesophageal pacing I A
DC cardioversion I C
Ibutilide‡ IIa A
Flecainide§ IIb A
Propafenone§ IIb A
Sotalol IIb C
Procainamide§ IIb A
Amiodarone IIb C
•Rate control Diltiazem, verapamil I A
Beta blockers I C
Digitalis† IIb C
Amiodarone IIb C
 AF: Rate Control Preferred

LA size > 50 mm Symptoms secondary to

AF > 6 months uncontrolled rapid rates
CHF > NYHA II I, III-induced proarrhythmia
EF < 40% Proarrhythmic risk factors
Sick sinus syndrome No contraindication to
Drug refractory (CV> 3 chronic warfarin
I, III intolerant Old age and sedentary
Asymptomatic
Carlsson et al, PACE 2000; 23: 891-903
 Control of Ventricular Rate in
Atrial Fibrillation
ADVANTAGES DISADVANTAGES
 Reduces symptoms  Requires long-term
 No ventricular anticoagulation
proarrhythmia  Impaired hemodynamics
 Reduces tachycardia-  No long-term prevention of
induced atrial remodeling
cardiomyopathy  AF becomes permanent
 Low cost
Drugs to Control Ventricular Rate
in Atrial Fibrillation

CHF HCM
 Digoxin  Verapamil
 B-blockers  β-blockers
 Amiodarone SSS
No CHF  Pindolol
 Verapamil Pre-excitation
 Diltiazem  Procainamide
 B-blockers Ibutilide
 Maintaining NSR in Atrial Fibrillation
ADVANTAGES
 Avoids electrical and
anatomical remodeling
 Improves hemodynamics
 Enhanced exercise
capacity
 Symptom relief
 Decreases PACs
 Improves QOL
 Restores atrial transport
function
 Reduces thromboembolic
events?
DISADVANTAGES
 Ventricular proarrhythmia
 Enhanced mortality?
 Drug-induced
bradyarrhythmias
 End-organ toxicity
 Subjective toxicity
 Recurrences are likely
 Silent AF
 Drugs for Restoration and
Maintenance of NSR

CLASS IA
 Quinidine,* procainamide, disopyramide
CLASS IC
 Flecainide,* propafenone,*
CLASS III
 Sotalol,* amiodarone, defetilide,* azimilide
(investigational)

* FDA approved
 Antiarrhythmic Drug Algorithm to Prevent AF

Heart Disease Lone AF

HBP CHF CAD

Initial Initial Initial Initial

Propafenone Amiodarone Sotalol* Flecainide

Dofetilide Sotalol*

Secondary Secondary Secondary

Sotalol* Disopyramide CR
Disopyramide CR
Disopyramide CR Dofetilide
Propafenone
Amiodarone Amiodarone
Amiodarone
Quinidine

*BETAPACE ATTM: The only sotalol formulation FAD-approved for treatment of AF/AFL.
CAD= coronary artery disease, CHF= congestive heart failure, HBP= high blood pressure.
Prystowsky EN. Am J Cardiol 2000; 85: 3D-11D.
 Selection of An Individual Agent
CLASS I
 Give AV node-blocking drugs with Class I drugs
 Avoid Class I drugs in patients with structural heart
disease (ie, and old MI or coronary artery disease)
CLASS III
 Use amiodarone or dofetilide in patients with LV
dysfunction or CHF
 Avoid class III drugs (except amiodarone) in patients
with a history of long QT syndrome
 Use sotalol and dofetilide cautiously in women and
patients with renal dysfunction
Rhythm Control for AF: Antiarrhythmic Drugs

Treatment Choices (Oral)

Class IA Class IC Class III

Quinidine Flecainide Sotalol
Procainamide Propafenone Amiodarone
Disopyramide Dofetilide
Azimilide*

* Under investigation
ACC/AHA/ESC Guideline of Catheter
Ablation in SVT Patients (1)
Clinical Presentation Class Level of Evidence

1. AVNRT
 Poorly tolerated
 Recurrent symptomatic
 Willing to complete control
of arrhythmia
 Documented but not inducible
 Infrequent, well tolerated
2. AVRT
 WPW, well tolerated
 WPW with AF, poorly tolerated
 AVRT (no preexcitation), poorly
tolerated I B
 Single/infrequent AVRT
no pre-excitation
 Pre-excitation, asymptomatic
I B
I B
I B
I B
I B
I B
I B
IIa B
IIa B

JACC 2003
ACC/AHA/ESC Guideline of Catheter
Ablation in SVT Patients (2)
Clinical Presentation Class Level of Evidence

3. Atrial Tachycardia
 Recurrent, symptomatic I B
 Incessant I B
 Non-sustain, asymptomatic III C
4. Atrial Flutter
 1st episode, well tolerated IIa B
 Recurrent, well tolerated I B
 Poorly tolerated I B
 After Class 1C or 3 AA of AF I B
 Symptomatic Non CTI dependent
after failed AA therapy IIa B

JACC, 2003
 Conclusion
 Arrhythmia is the important and significant
health problem but frequently under-
treatment
 Knowledge of mechanisms and
classification of arrhythmias help to
diagnose arrhythmias accurately
 Radio frequency catheter ablation is the
procedure of choice for long term
treatment of most arrhythmias
Case Report
 Autopsied of 85 yo man with ARVC
 Treated with Amiodarone 100 mg/day for 4
years
 High concentration in lipophylic tissue
In the epicardial fat (570.4 microg/g)
In the right atrium (165.3 microg/g)
The ratios of amiodarone/ desethylamiodarone
concentrations in both tissues were >1
 Low dose is enough ?
Hosaka et al. Heart Vessels. 2002;16:154-6
 CAMIAT
Canadian Amiodarone Myocardial Infarction
Arrhythmia Trial
 Disease: AMI with ventricular premature depolarisations
 Purpose: To investigate the effect of amiodarone on the risk of resuscitated
ventricular fibrillation or arrhythmic death in survivors of MI with frequent or
repetitive ventricular premature depolarisations (VPDs)(≥ 10 VPDs per h or
≥ 1 run of ventricular tachycardia)
 Randomised, double-blind, placebo-controlled
 Treatment regimenAmiodarone, loading dose 10 mg/kg daily for 2 weeks,
maintenance dose 300-400 mg daily for 3-5 months, 200-300 mg daily for 4
months, and 200 mg for 5-7 days per week for 16 months, or placebo
 ResultsAmiodarone therapy results in a relative risk reduction of 48.5% in
the occurrence of resuscitated ventricular fibrillation or arrhythmic death
among survivors of MI with frequent or repetitive VPDs on ambulatory ECG
monitoring. Death occurred in 31 patients (6.0%) in the placebo group and
in 15 (3.3%) in the amiodarone group. Intention-to-treat analysis showed a
corresponding reduction of 38.2% - primary outcome events occurred in 24
(6.9%) patients in the placebo group and in 15 (4.5%) in the amiodarone
group

Lancet 1997;349:675-82
 EMIAT
European Myocardial Infarct Amiodarone Trial
 PurposeTo evaluate the effect of amiodarone on mortality post-MI in
patients with left ventricular ejection fraction ≤ 40%
 Randomised, double-blind, placebo-controlled, Median 21 months
 Patients:1486 patients (743 amiodarone, 743 placebo)
 Treatment regimen: Amiodarone, 800 mg/day for 2 weeks,
followed by 400 mg/day for 3.5 months, and then 200 mg/day, or
placebo
 Results: At mean of 16 months’ follow-up, total mortality was
13.4%. 37% of the first 72 deaths occurred in patients without
frequent or complex ventricular arrhythmias. At a median of 25
months of follow-up, all-cause mortality and cardiac mortality did not
differ between the groups. In the amiodarone group there was a
35% risk reduction (95% CI 0-58; p = 0.05) in arrhythmic deaths

Lancet 1997;349:667-74
Proarrhythmia

Before

After
Potassium Channel Blocker
CAST: Cardiac Arrhythmia Suppression Trial
- RESULTS continued-

Mortality and cardiac arrest

Placebo Encainide/flecainide
Relative risk
(n=725) (n=730)
(95% CI)
No. (%) No. (%)

Non-fatal cardiac arrest 9 (1.2) 33 (4.5) 3.6 (1.7 –8.5)

or death from arrhythmia
Other cardiac death 6 (0.8) 14 (1.9) –
Non-cardiac or unclassified death 7 (1.0) 9 (1.2) –
or cardiac arrest

Total death or cardiac arrest 22 (3.0) 56 (7.7) 2.5 (1.6 –4.5)

Average days of exposure 300 293

CAST Investigators. N Engl J Med 1989;321:406 –12.