C h a p t e r 2... ICD : Indian Experience TS Kler , Vanita Arora

C h a p t e r
2 2
ICD : Indian Experience
TS Kler1, Vanita Arora2
Senior Consultant & Interventional Cardiologist,
Head of the Department of Cardiac Pacing and Electrophysiology,
Escorts Heart Institute and Research Centre, New Delhi
2
Junior Consultant, Escorts Heart Institute and Research Centre, New Delhi
1
Introduction
In 1970, Mirowski et al1 published their first experience with the standby automatic defibrillator in
animals. Ten years later, the first implantable cardioverter–defibrillator (ICD) was used in 3 patients.2 In
the past 10 years, there has been an exponential growth in our knowledge, and technological evolution
of the device has been striking.
In the United States, the incidence of sudden cardiac death is between 300 000 and 400 000 a year.3
Only 2%–15% of the patients suffering from sudden cardiac death reach the hospital, and half of
these early survivors die before discharge. The understanding that sudden cardiac death (SCD) from
fatal ventricular arrhythmias is one of the most common causes of death in Indian population, which
is facing the epidemic of coronary artery disease (CAD), has increased the awareness as to the use of
ICD in our country. Clinicians need to carefully consider and analyze the various studies done in the
last decade proving the efficacy of ICD over and above the drug therapy in the management of patients
with CAD and severe LV dysfunction.
This poses a major therapeutic challenge. It is however difficult to predict with certainty which
particular patients will have fatal arrhythmias and which others will remain clinically stable and free of
serious ventricular arrhythmias. If such patients could be identified, then therapy could be targeted to
only that selective population which would constitute about 40-60% of all patients with moderate to
severe LV dysfunction.4
“High Risk Predictors” of SCD are
1.
2.
3.
4.
5.
6.
Documentation of nonsustained ventricular tachycardia (NSVT) on holter
The presence of ECG abnormalities of depolarization and repolarization using the signalaveraged ECG
The presence of microvolt T-wave alternans
The presence of abnormal autonomic modulation of cardiac function i.e. abnormally low heart
rate variability (HRV)
Depressed baroreceptor sensitivity
Left ventricular ejection fraction (LVEF)
ICD : Indian Experience
177
7.
The inducibility of VT or VF on invasive electrophysiological study (EPS)
Although each of these tests is of some prognostic value, they are individually insufficiently accurate for
practical clinical purposes, to direct therapy. Hence patients with poor ejection fraction, past history of
myocardial infarction & presence of ventricular scar are actually believed to be at high risk of SCD.
However there is no available diagnostic modality by which one can identify the exact population of
patient liable to have SCD amongst thousands with these characteristics. This is a serious limitation
in our capability to identify patients requiring protection from SCD, as the incidence of sudden death
amongst all patients with prior myocardial infarction is relatively low.
Another practical problem is the inability to identify the timing of sudden death from VT/VF. Such
events occur suddenly with no clearly identifiable factors which precede SCD in most individuals.
However, in known cases of CAD the most important etiologic factors leading to life threatening
ventricular arrhythmias are angina, sudden worsening of heart failure and behavioral factors such as
stress or exercise are observed to immediately precede sudden death. Improved acute and long term
therapies have increased survival for patients with myocardial infarction, hence leading to a relative
increase in the number of the patients with chronic coronary disease and LV dysfunction.
Beyond the universal requirement for beta blockers unless absolutely contraindicated, there is however
not much room for optimism that antiarrhythmic therapy (AAT’s), at least for the time being, will be
even a partial solution to the problem of SCD in susceptible coronary populations like ours. ICD’s
are being increasingly used in such patients with previous MI, depressed ventricular function and
nonsustained VT inducible by EPS. In addition, ICD has been commonly used as primary prevention
in conditions that predispose to SCD, such as long QT syndrome, Brugada syndrome, idiopathic VF,
arrhythmogenic right ventricular dysplasia and hypertrophic cardiomyopathy
ICD
The implanted defibrillator represents an effective, intellectual therapy to prevent death from ventricular
arrhythmias. The device does not prevent such arrhythmias but only treats them after they occur. The
device is expensive and the follow-up of patients is technically challenging.
The ICD has two components, the pulse generator and the leads. Most of the newer generation of
pulse generators weigh less than 100 g and are the size of <60 cc. They are implanted pectorally by
electrophysiologists in the electrophysiology laboratory under local anesthesia. The leads are inserted
via the subclavian vein into the right ventricle (single-chamber ICD). Additional lead is required in right
atrium for dual chamber ICD. Most patients are hospitalized for only 1–2days.
The device detects ventricular arrhythmia by analyzing the heart rate and duration of the arrhythmia.
The rate criterion differentiates a tachycardia from normal rhythm and the duration criterion prevents
the detection and treatment of nonsustained tachycardias. All these criterias are programmable. An
ICD terminates VT or VF in three ways:
1.
Anti tachycardia pacing (overdrive) (Fig. 1)
2.
Synchronized shock (cardioversion) (Fig. 2)
3.
Nonsynchronized shock (defibrillation).
All these treatments are programmable. While VF is treated by defibrillation, VT is often treated by anti
tachycardia pacing or low-energy cardioversion when anti tachycardia pacing fails. ICD’s can deliver
4–8 successive shocks with maximum shock energies ranging from 25 to 42J.
Up to 30% of ICD recipients may experience sinus bradycardia or high-degree atrioventricular
block which requires physiologic pacing. The presence of atrial fibrillation or flutter may also trigger
inappropriate ICD intervention because the device may read this supraventricular tachycardia as VT.
Hence, dual-chamber ICD has been developed for physiologic pacing and also for better differentiation
178
CME 2004
Fig. 1
Fig. 2
of supraventricular and ventricular tachycardias to avoid spurious shocks.5-7 Another recent advance
has been the incorporation of ICD and biventricular pacing into a single device to prevent SCD and to
improve LV function by resynchronizing left and right ventricular contraction.
Appropriately tested devices have a 99% or greater probability of successfully restoring a normal
sinus rhythm in patients with VT or VF. Current devices can be implanted with a less than 1%
major morbidity or mortality. Studies in patients with a prior history of cardiac arrest, or sustained
ventricular tachycardia i.e. the “secondary prevention” have demonstrated convincingly that the
implanted defibrillator is both effective and superior to antiarrhythmic drug therapy in preventing all
cause mortality in such patients. Since the majority of SCD occur in patients without a prior history
of documented sustained VT or VF, studies have assessed the usefulness of defibrillators as “primary
prophylaxis” of SCD.
Analysis of Various Clinical Trials
The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, which was a secondary
prevention trial, enrolled 1016 patients. It compared ICD implantation and drug therapy with
amiodarone in the prevention of SCD.5 All the patients presented with resuscitated VF or
symptomatic VT (chest pain, pre syncope or hypotension) and had LV dysfunction(EF<40%).
At 3-year follow-up, mortality was reduced by 29% in patients treated with ICD implantation. AVID
data also indicate that patients with a relatively good ejection fraction (>0.35) do not have better
survival when treated with an ICD as compared with amiodarone therapy.6 However, ICD implantation
was associated with improved survival in patients with lower ejection fraction (0.20–0.34) when
compared with AAT’s.
The Canadian Implantable Defibrillator Study (CIDS) was another large, randomized, multicenter
secondary prevention trial, comparing ICD therapy with amiodarone.7 In this trial, 659 patients with
unmonitored syncope were randomized into ICD therapy (328 patients) and amiodarone and followed up
for a mean period of 3 years. The risk of death in the ICD arm was reduced from 10.2% per year to 8.3% per
year, a 19.7% relative risk reduction. However, this relative risk reduction was statistically nonsignificant7.
ICD : Indian Experience
179
A nonsignificant reduction in the risk of arrhythmic death was also observed, from 4.5% to 3.0%, which
is equivalent to a 32.8% relative risk reduction. However, in a presentation at the American Heart
Association annual scientific meeting in 2002, long-term follow-up of a subgroup of CIDS patients
11 years after the ICD implantation found that the ICD was associated with a significant decrease in
cardiac death compared with amiodarone-treated patients.
Patients with the highest risk of SCD benefit most from ICD therapy. CIDS investigators retrospectively
stratified the 659 patients into 4 risk quartiles on the basis of reduced ejection fraction, advanced age,
and poor NYHA functional class.8 In the highest risk quartile, a 50% relative risk reduction in death
occurred with ICD therapy when compared with amiodarone, with no benefit from ICD treatment over
amiodarone in the 3 lower risk quartiles.8 The patients who are most likely to benefit from an ICD are
those who are 70 years of age and above, those with a left ventricular ejection fraction <0.35, and
those in NYHA class III or IV.
In the Cardiac Arrest Study Hamburg (CASH) trial, 228 cardiac arrest survivors were randomized
to ICD, amiodarone, metoprolol or propafenone groups.9 ICD therapy was associated with a 23%
reduction (p<0.08) in all-cause mortality as compared with drug therapy, after a mean follow-up
period of 57 months.
The above data show that ICD therapy is more effective than AAT’s in cardiac arrest survivors and in
patients with hemodynamically unstable ventricular arrhythmias.The meta-analysis of AVID,6 CIDS,8
and CASH9 studies10 have shown an approximately 20-30% reduction in all cause mortality
The CABG PATCH study randomized patients undergoing coronary bypass surgery to either an
implanted defibrillator or control therapy without the ICD.11 The inclusion criteria were ejection
fraction <35% and a positive signal-averaged ECG. This study failed to show any benefit whatsoever
from the implanted defibrillator, but both defibrillator and no defibrillator patients had a low cardiac
mortality (5.9% per year), suggesting that surgical revascularization has a very important protective
effect against sudden death
The MADIT I study assessed patients with CAD, poor LV function and asymptomatic nonsustained
ventricular tachycardia (NSVT), with inducible VT or VF at electrophysiological study (EPS), not
suppressible by AAT’s.12 This study showed a 54% reduction in mortality in patients implanted with
a defibrillator as opposed to those receiving “conventional medical therapy” and hence was the first
to document a potential benefit from prophylactic ICD. In the MADIT study, the reduction in sudden
cardiac death following ICD therapy occurred mainly in patients with an ejection fraction <0.26.13
However, the clinically impractical sequence of EP study and need for VT induction, followed by
attempted VT/VF suppression with procainamide, that was required for risk stratification, a relatively
small total patient number, inadequate therapy with beta blockers and ACE inhibitors were a few
drawbacks of this trial. Nevertheless, the results from this study led to FDA approval of implanted
defibrillators for the particular subset of patients meeting the inclusion criteria for this study.
The MUSTT study, like the MADIT study, selected patients with coronary artery disease and ejection
fraction <40% having either asymptomatic nonsustained VT on holter or inducible VT in EP study14.
They were randomized to either EPS guided therapy or no AAT’s. The EPS guided arm included
either AAT’s to suppress the inducibility of VT or implantation of ICD. The choice between defibrillator
versus drug therapy was not randomized. SCD at the end of 5 years was significantly lower in the EPS
guided arm (25 vs. 32%, p<0.04) but all cause mortality was not (48 vs. 42%, p=0.06). However, a
secondary analysis showed some striking trends. The relative risk of death from all causes in the ICD
group compared to the no AAT’s group was 0.45 (95%, CI 0.32-0.63) and compared to EPS guided
AAT’s was 0.40 (0.27-0.59). Although this was not strictly a randomized therapy outcome, the study
was widely and reasonably interpreted as showing superiority of the ICD to no AAT’s or AAT’s. As
a consequence of the MUSTT study most expert bodies stipulating guidelines for the treatment of
180
CME 2004
���
���
���
��
���
���
���
�
��
����
���
���������������������������
�����
�����
������
�����
����
����
�
����
��
�����
���
������������������������������
��
�������������������������
Fig. 3
ventricular arrhythmias concluded that patients with CAD, ejection fraction <40%, and nonsustained
VT if they had inducible ventricular tachycardia at EP study, should preferably be treated with an
implanted defibrillator.14
Fig. 3 shows the meta-analysis of various primary and secondary prevention trials resulting in significant
reduction in mortality.
The MADIT II study, published in March 200215, took a simplified approach to the testing of the
hypothesis that implanted defibrillators would reduce all cause mortality in high risk populations. The
only criteria to identify patients at risk from SCD were the presence of CAD, a prior MI and an ejection
fraction of <30%. This study randomized a total of 1232 patients to either the ICD (742 patients) or
conventional medical therapy (490 patients). Neither nonsustained VT nor an EPS was required for
entry into this study. The patient population in this study was reasonably representative of a potentially
very large group of patients with chronic CAD and prior MI. Patients were followed to a common
primary endpoint of death from any cause. The defibrillator therapy resulted in an increasing mortality
benefit over conventional therapy with a 31% reduction in the risk of death. In absolute terms, this
meant a 1%, 6%, and 9% reduction in mortality at 1, 2, and 3 years.
Conclusion
The latest data from the MADIT II trial will have a major impact on future ICD therapy. First, it has
further clarified the indications for ICD therapy and provided more insight in guiding routine therapy for
patients with impaired LV function as defined by a reduced left ventricular ejection fraction. Currently,
approximately 300 000 patients each year in the United States are estimated to be eligible for receiving
an ICD. Results from MADIT II have indicated that ICD implantation is an effective primary prevention
for SCD in post MI patients with poor LV function. These findings will substantially increase the
population of patients eligible for implanted devices in the USA and worldwide.
The main barrier to more widespread use of prophylactic implanted defibrillators, at least in the Indian
context seems to be the cost of device and resource limitations i.e. the non availability of medical
personnel to perform the procedures and follow the patients. For the time being, in all patients with
a history of prior MI and ejection fraction of <30%, optimal pharmacological therapy including betablockers, ACE inhibitors, aspirin, statins should be given. If revascularization is indicated and feasible,
it should be performed. The presence of nonsustained VT on Holter monitoring probably adds to
ICD : Indian Experience
181
Fig. 4
Fig. 5
prognostic significance, although the amount of information contained in this finding is not clear.
Performing an EPS for risk stratification is probably required for most such patients. If VT is inducible
on EPS then these patients should be given the benefit of implantation of ICD.
The first ICD implantation in India was implanted on April 1995 at Escorts Heart Institute and Research
Centre (Fig. 4) and All India Institute of Medical Sciences, New Delhi.16 The annual ICD implantations
in India are increasing every year (Fig 5). Single-chamber ICD is still the most popular choice for
cardiologists and patients. Dual-chamber ICDs have been increasingly used in patients with a standard
indication for permanent pacing and ICD implantation. The cost of one ICD device, depending upon
the model or complexity of function, ranges from Rs 4.5 to 9 lakh18 in our country. Incorporation of an
ICD with biventricular pacing may provide a better clinical outcome than the ICD alone in patients with
interventricular conduction delay and congestive heart failure.
182
CME 2004
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
Mirowski M, Mower MM, Staewen WS, Tabatznik B, Mendoloff AI. Standby automatic defibrillator: an approach
to prevention of sudden coronary death. Arch Intern Med 1970; 126: 158–161
Mirowski M, Reid PR, Mower MM, Watkins L, Gott VL, Schauble JF, et al. Termination of malignant ventricular
arrhythmias with an implanted automatic defibrillator in human beings. N Engl J Med 1980; 303: 322–324
Myerburg RJ, Kessler KM, Castellanos A. Sudden cardiac death: epidemiology, transient risk and intervention
assessment. Ann Intern Med 1993; 119: 1187–1197
Hauer RN, Aliot E, Block M, Capucci A, Luderitz B, Santini M, Vardas PE. Indications for implantable cardioverter
defibrillator (ICD) therapy. Study Group on Guidelines on ICDs of the Working Group on Arrhythmias and the
Working Group on Cardiac Pacing of the European Society of Cardiology. Eur Heart J 2001 Jul;22(13):107481.
Sticherling C, Schaumann A, Klingenheben T, Hohnloser SH. First worldwide clinical experience with a new
dual chamber implantable cardioverter defibrillator. Advantages and complications. The Ventak AV II DR
investigators. Europace 1999; 1: 96–102
Higgins SL, Pak JP, Barone J, Williams SK, Bollinger FM, Whiting SL, et al. The first year experience with the dual
chamber ICD. Pacing Clin Electrophysiol 2000; 23: 18–25
Proclemer A, Della Bella P, Facchin D, Fattore L, Carbucicchio C, Tondo C, et al. Indications for dual-chamber
cardioverter defibrillators at implant and at 1 year follow-up: a retrospective analysis in the singlechamber
defibrillator era. Europace 2001; 3: 132–135
The AVID Investigators. A comparison of antiarrhythmic drug therapy with implantable cardioverter–defibrillators
in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med 1997; 337: 1576–1583
Domanski MJ, Sakseena S, Epstein AE, Hallstrom AP, Brodsky MA, Kim S, et al. Relative effectiveness of the
implantable cardioverter– defibrillator and antiarrhythmic drugs in patients with varying degrees of left ventricular
dysfunction who have survived malignant ventricular arrhythmias. AVID Investigators. Antiarrhythmics Versus
Implantable Defibrillators. J Am Coll Cardiol 1999; 34: 1090–1095
Connolly SJ, Gent M, Roberts RS, Dorian P, Roy D, Sheldon RS, et al. Canadian implantable defibrillator study
(CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone. Circulation 2000;
101: 1297–1302
Sheldon R, Connolly S, Krahn A, Roberts R, Gent M, Gardner M. Identification of patients most likely to benefit
from implantable cardioverter–defibrillator therapy: the Canadian Implantable Defibrillator Study. Circulation
2000; 101: 1660–1664
Kuck KH, Cappato R, Siebels J, Rüppel. Randomized comparison of antiarrhythmic drug therapy with implantable
defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH). Circulation
2000;102(7):748-54.
`Connolly SJ, Hallstrom AP, Cappato R, Schron EB, Kuck KH, Zipes DP, Greene HL, Boczor S, Domanski M,
Follman D, Gent M, Roberts RS. Meta-analysis of the implantable cardioverter defibrillator secondary prevention
trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study
Hamburg . Canadian Implantable Defibrillator Study. Eur Heart J. 2000;21(24):2071-8.
Bigger JT. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias
after coronary-artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl
J Med. 1997;337(22):1569-75.
Moss AJ, Hall WJ, Cannom DS, Daubert JP, Higgins SL, Klein H, Levine JH, Saksena S, Waldo AL, Wilber D,
Brown MW, Heo M. Improved survival with an implanted defibrillator in patients with coronary disease at high
risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med.
1996;335(26):1933-40.
Moss AJ. Implantable cardioverter defibrillator therapy: the sickest patients benefit the most. Circulation 2000;
10: 1638–1640
Buxton, A.E., et al., A randomized study of the prevention of sudden death in patients with coronary artery
disease. Multicenter UnSustained Tachycardia Trial Investigators. N Engl J Med 1999;341(25):1882-90.
Gregoratos,G et al ACC/AHA/NASPE 2002 Guideline for Implantation of Cardiac Pacemakers and Antiarrhythmia
Devices. Available at http://www.acc.org/clinical/guidelines/pacemaker/pacemaker.pdf.
Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, Daubert JP, Higgins SL, Brown MW, Andrews ML.
Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N
Engl J Med 2002;346(12):877-83.
Nair M, Frances J, Venugopal K. Development of pacing, electrophysiology and defibrillation in India. India
Pacing Electrophysiol J 2002; 2: 57–61.
ICD : Indian Experience
183