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Abstract & Commentary
Synopsis: Data do not support early implantation of prophylactic ICDs in patients with nonischemic cardiomyopathy.
Source: Strickberger SA, et al. For the AMIOVIRT Investigators. J Am Coll Cardiol. 2003;41:1707-1712.
In this paper, Strickberger and colleagues report the results of the Amiodarone Versus Implantable Cardioverter-Defibrillator: Randomized Trial in Patients With Nonischemic Dilated Cardiomyopathy and Asymptomatic Nonsustained Ventricular Tachycardia (AMIOVIRT). Patients could be included in this study if they had no evidence for, or only minor, coronary artery disease, an ejection fraction < 0.35, asymptomatic nonsustained VT, and were older than 18. Study enrollment began in 1996. Optimal medical therapy according to current guidelines was encouraged in both groups. Patients were randomized to receive either amiodarone or an ICD. The primary end point was total mortality. Secondary end points included sudden cardiac death, nonsudden cardiac death, syncope, arrhythmia-free survival, quality of life, and cost.
One hundred three patients were enrolled in the study, with 52 randomized to receive amiodarone and 51 randomized to receive an ICD. The mean age was 59 years. The mean left ventricular ejection fraction was 0.22. Symptoms related to their cardiomyopathy had been present for approximately 3 years. Although the study had a planned enrollment of 438 patients, the study was stopped after the first interim analysis. The event rates in the study were lower than expected, with no significant difference between the groups.
At the time the study was stopped, the mean follow-up was 2.0 ± 1.3 years and there were 52 patients randomized to amiodarone and 51 randomized to receive an ICD. The 1- and 3-year survival rates among the amiodarone-treated patients were 90% and 80%, respectively, compared with 96% and 88%, respectively, among the 51 patients treated with an ICD. There was no difference in the distribution of sudden vs nonsudden cardiac deaths between the 2 groups.
Arrhythmia-free survival was calculated using symptomatic arrhythmias in the amiodarone group and ICD-treated arrhythmias in the ICD group. The arrhythmia-free survival rates among the amiodarone-treated patients were 82% and 73% at 1 and 3 years vs 78% and 63% among the patients treated with an ICD.
There was no difference in 2 measures of quality of life between the 2 groups. Cost of medical therapy was significantly different in a subset of patients in whom these data were collected. The cost in the first year after entry into the study was $8,879 ± $27,614 in the amiodarone group compared with $22,079 ± $22,039 in the ICD group.
Amiodarone therapy was discontinued in 25 of 52 patients, a mean of 17.8 ± 13 months after initiation of therapy. The reasons that led to amiodarone discontinuation are not specified in the report. In the ICD group, 11 of 51 patients eventually received amiodarone for treatment of either frequent ventricular arrhythmias or atrial arrhythmias.
Strickberger et al conclude that their data do not support early implantation of prophylactic ICDs in patients with nonischemic cardiomyopathy. Amiodarone appears to have a modest effect on arrhythmia frequency. Empiric therapy with amiodarone, therefore, seems a reasonable first step in previously asymptomatic patients.
Comment by John DiMarco, MD, PhD
A number of trials have now shown benefits with ICD therapy in patients with ischemic cardiomyopathy and left ventricular dysfunction. In the original Multicenter Automatic Defibrillator Implantation Trial (MADIT), patients with an ejection fraction < 0.35, nonsustained VT, and inducible VT showed benefit after ICD implant as compared to "conventional medical therapy." In MADIT II, electrophysiologic studies were not included, and a benefit from ICD therapy was shown in patients with ischemic cardiomyopathy and ejection fractions £ 0.30. Although benefit in patients with nonischemic dilated cardiomyopathy with a prior history of cardiac arrest was demonstrated in both the Antiarrhythmics vs Implantable Defibrillators Trial and the Canadian Implantable Defibrillator Study, the only previous trial, the Cardiomyopathy Trial, had reported no benefit in patients with nonischemic dilated cardiomyopathy.
When interpreting this trial, it is important to note the unexpectedly good outcome in both groups. Therapy for nonischemic dilated cardiomyopathy has changed significantly in the last decade. In this study, high proportions of patients received angiotensin converting enzyme inhibitors but relatively modest proportions of patients received beta blockers and spironolactone, 2 agents recently shown to improve survival significantly in patients with heart failure. As therapy has improved and the overall mortality has dropped, it has become more and more difficult to define a "high risk" group that is likely to benefit from an intervention directed at arrhythmias.
It must be recognized that this was a relatively small trial that was discontinued early because of futility. Two much larger studies, the DEFINITE Trial and the SCD-HeFT Trial hopefully allow us to better assess the role of ICD therapy for primary prevention in patients with primary cardiomyopathy. However, until the results of those trials become available, ICD implantation in these patients without prior symptomatic arrhythmias cannot be recommended.
Dr. DiMarco is Professor of Medicine Division of Cardiology University of Virginia, Charlottesville.