Indications for Implantable Cardioverter-Defibrillators Based on Ejection Fraction and Arrhythmia Morphology

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Left ventricular (LV) systolic dysfunction, defined by depressed LV ejection fraction (LVEF), has been recognised over the last two decades as the most robust parameter for identifying risk of sudden cardiac death (SCD). Specifically, LVEF has been a major determinant for entry into numerous randomised trials that aimed to investigate the efficacy of implantable cardioverter–defibrillators (ICDs) compared with antiarrhythmic or best medical therapy in the primary prevention of SCD. The goal of this article is to review the clinical utility of ICD implantation in patients with structural heart disease. Several trials have attempted to use additional risk parameters beyond low LVEF in order to magnify the benefit of ICD compared with antiarrhythmic therapy. All of these trials were conducted in patients with ischaemic LV dysfunction.


The Multicenter Automatic Defibrillator Implantation Trial (MADIT)1 was the first randomised clinical trial that compared ICD therapy with conventional care in primary prevention, i.e. in patients with no prior history of life-threatening arrhythmias. Patients with ischaemic LV dysfunction (LVEF ?0.35), non-sustained ventricular tachycardias (VTs) and inducible but nonsuppressible sustained ventricular arrhythmias during programmed electrical stimulation were enrolled. MADIT demonstrated a 54% relative mortality reduction (p=0.009) in the ICD arm. The Coronary Artery Bypass Graft Path Trial (CABG Patch)2 compared ICD therapy with usual care in patients undergoing coronary artery bypass grafting and having LV dysfunction (LVEF <0.36) and the presence of late potentials assessed by signal-averaged electrocardiogram (ECG) recording. Although ICD significantly reduced the risk of SCD, no significant reduction in mortality was observed with ICD therapy, probably due to the strong beneficial effect of revascularisation. The Multicentre Unsustained Tachycardia Trial (MUSTT)3 compared antiarrhythmic therapy with best medical therapy in patients with ischaemic LV dysfunction (LVEF ?0.40), non-sustained VT and inducible sustained ventricular arrhythmias during programmed ventricular stimulation. ICD therapy could be used only in a non-randomised fashion after the failure of serial electrophysiologically guided testing of antiarrhythmic drugs. The survival benefit in the electrophysiologically guided therapy group (significant 27% relative reduction in cardiac arrests/arrhythmic deaths compared with conventional care) was limited to those patients who received an ICD. Drug therapy alone was not associated with the reduction in mortality compared with best medical therapy.

In order to simplify the risk stratification procedure, MADIT II4 was conducted. This was the first trial that included patients primarily based on advanced LV dysfunction (LVEF ?0.30) late after myocardial infarction (MI) without the need for invasive testing. Prophylactic ICD implantation was associated with a significant reduction (31%; p=0.016) of all-cause mortality compared with the conventional-therapy group. The survival benefit was similar in strata according to age, sex, LVEF, New York Heart Association (NYHA) class and the QRS width. The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)5 was designed to test whether prophylactic implantation of an ICD would reduce mortality in survivors of a recent MI (six to 40 days after MI) with LV dysfunction (LVEF ?0.35) and impaired cardiac autonomic function manifested as depressed heart-rate variability or an elevated average 24-hour heart rate on Holter monitoring. No difference was found in overall mortality between the ICD and conventional-therapy arms. ICD therapy was associated with a reduction in the rate of death due to arrhythmia, but this was offset by an increase in the rate of death from non-arrhythmic causes. In contrast to the previous two trials in patients with ischaemic heart disease, the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)6 was designed to evaluate the hypothesis that amiodarone or an ICD would decrease the risk of death from any cause in a broad population of patients with mild to moderate ischaemic or non-ischaemic congestive heart failure (LVEF ?0.35) with NYHA class II–III. Patients receiving ICD had a significantly lower risk of death (relative reduction of 23%; p=0.007) compared with those in the placebo arm. Surprisingly, there was no difference in mortality between patients treated with amiodarone and those treated with placebo. The results did not vary according to either ischaemic or non-ischaemic causes of congestive heart failure, but they varied according to NYHA class. ICD therapy had a significant benefit in patients in NYHA class II, but not in those in NYHA class III. However, this unanticipated subgroup effect – which was in conflict with the results of other ICD trials – was not assumed to be a sufficient basis for withholding ICD therapy from patients in NYHA class III. Two other trials focused primarily on subjects with non-ischaemic cardiomyopathy. The Amiodarone versus Implantable Defibrillator (AMIOVIRT) trial7 compared amiodarone with ICD in a randomised fashion in patients with idiopathic dilated cardiomyopathy (LVEF ?0.35), NYHA class I–III and asymptomatic non-sustained VT. Mortality in patients treated with amiodarone or an ICD was not statistically different, probably due to the low number of patients enrolled and the short duration of follow-up. The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE)8 trial randomly assigned patients to ICD or standard medical therapy. Inclusion criteria were non-ischaemic LV systolic dysfunction (LVEF <0.36), history of symptomatic heart failure, NYHA class I–III and non-sustained VT and/or frequent ventricular premature beats (>10 per hour). ICD therapy significantly reduced the risk of SCD and was associated with a statistically borderline reduction in the risk of all-cause death (relative risk reduction of 35%; p=0.08). The lower than expected rate of SCD may have resulted in the non-significant reduction in total mortality.


  1. Moss AJ, Hall WJ, et al., 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;335:1933├óÔé¼ÔÇ£40.
  2. Bigger JT Jr, Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronaryartery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators, N Engl J Med, 1997;337:1569├óÔé¼ÔÇ£75.
  3. Buxton AE, Lee KL, Fisher JD, 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;341:1882├óÔé¼ÔÇ£90.
  4. Moss AJ, Zareba W, Hall WJ, et al., Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction, N Engl J Med, 2002;346:877├óÔé¼ÔÇ£83.
  5. Hohnloser SH, Kuck KH, Dorian P, et al., Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction, N Engl J Med, 2004;351:2481├óÔé¼ÔÇ£8.
  6. Bardy GH, Lee KL, Mark DB, et al., Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure, N Engl J Med, 2005;352:225├óÔé¼ÔÇ£37.
  7. Strickberger SA, et al., Amiodarone versus implantable cardioverterdefibrillator: randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia ├óÔé¼ÔÇ£ AMIOVIRT, J Am Coll Cardiol, 2003;41:1707├óÔé¼ÔÇ£12.
  8. Kadish A, Dyer A, Daubert JP, et al., Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy,N Engl J Med, 2004;350:2151├óÔé¼ÔÇ£8.
  9. Nanthakumar K, Epstein AE, Kay GN, et al., Prophylactic implantable cardioverter-defibrillator therapy in patients with left ventricular systolic dysfunction: a pooled analysis of 10 primary prevention trials, J Am Coll Cardiol, 2004;44:2166├óÔé¼ÔÇ£72.
  10. Desai AS, et al., Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a metaanalysis of randomized controlled trials, JAMA, 2004;292:2874├óÔé¼ÔÇ£9.
  11. Ezekowitz JA, Armstrong PW, McAlister FA, Implantable cardioverter defibrillators in primary and secondary prevention: a systematic review of randomized, controlled trials, Ann Intern Med, 2003;138:445├óÔé¼ÔÇ£52.
  12. Zipes DP, et al., ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death, J Am Coll Cardiol, 2006;48:e247├óÔé¼ÔÇ£346.
  13. Wilber DJ, Zareba W, Hall WJ, et al., Time dependence of mortality risk and defibrillator benefit after myocardial infarction, Circulation, 2004;109:1082├óÔé¼ÔÇ£4.
  14. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators, A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from nearfatal ventricular arrhythmias, N Engl J Med, 1997;337:1576├óÔé¼ÔÇ£83.
  15. Connolly SJ, et al., Canadian Implantable Defibrillator Study (CIDS): a randomized trial of the implantable cardioverter defibrillator against amiodarone, Circulation, 2000;101:1297├óÔé¼ÔÇ£1302.
  16. Kuck KH, Cappato R, Siebels J, et al., Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH), Circulation, 2000;102:748├óÔé¼ÔÇ£54.
  17. Connolly SJ, Hallstrom AP, et al., 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;21:2071├óÔé¼ÔÇ£8.
  18. Oseroff O, Retyk E, Bochoeyer A, Subanalyses of secondary prevention implantable cardioverter-defibrillator trials: antiarrhythmics versus implantable defibrillators (AVID), Canadian Implantable Defibrillator Study (CIDS), and Cardiac Arrest Study Hamburg (CASH), Curr Opin Cardiol, 2004;19:26├óÔé¼ÔÇ£30.
  19. Domanski MJ, Sakseena S, Epstein AE, 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├óÔé¼ÔÇ£95.