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The Multicenter Unsustained Tachycardia Trial (MUSTT) enrolled a study population similar to that in the first MADIT. Patients with a history of myocardial infarction, an ejection fraction of 40 per-cent or less, and spontaneous, nonsustained ventricular tachycardia underwent an electrophysio-logical study. Patients who did not have inducible ventricuar tachycardia were followed in a registry. Patients with inducible ventricular tachycardia were randomly assigned to either no therapy or antiarrhythmic therapy, which was guided by serial electrophysiological studies, and could receive a defibrillator if one or more of the trial drugs were not beneficial. Although MUSTT has often been described as a defibrillator trial, it may be better described as a test of an electrophysiologically guided treatment strategy in which implantable cardioverter–defibrillators were prescribed at an investigator’s discretion. The frequency of the prescription of an implantable defibrillator varied among centers and over time. However, at five years the mortality from all causes among the 161 subjects who received defibrillators during the initial hospi-talization (24 percent) was much lower than among the 171 subjects who were treated with drugs (55 percent) and the 353 subjects who received no therapy (48 percent).
All the clinical trials cited above included patients who had had myocardial infarctions. The role of defibrillator therapy for the primary prevention of death from cardiac causes in patients with non-ischemic cardiomyopathy has not yet been established. The Cardiomyopathy Trial enrolled 104 subjects with nonischemic cardiomyopathy and an ejection fraction of 30 percent or less who were randomly assigned either to implantation of a defibrillator or to no therapy. No significant difference in survival was observed. As cited by Raj and Sheldon, preliminary data from the Amiodarone versus Implantable Cardioverter–Defibrillator Trial (AMIOVIRT) showed no improvement in survival with implantation of a defibrillator as compared with amiodarone therapy in 103 patients with non-ischemic dilated cardiomyopathy. Two large, ongoing trials, the Defibrillators in Nonischemic Cardio-myopathy Treatment Evaluation (DEFINITE) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HEFT), may help to clarify the comparative benefits of these therapies in patients at high risk for sudden death from cardiac causes.
Ventricular arrhythmias that lead to sudden death can result from a number of congenital syndromes and acquired diseases that have been treated with implantable defibrillators. Some examples are hypertrophic cardiomyopathy, the long-QT syndrome, the Brugada syndrome, sarcoidosis, arrhythmogenic right ventricular dysplasia, and certain congenital heart diseases. Since these conditions are relatively uncommon, it is unlikely that randomized trials of defibrillator therapy for them will be conducted. On the basis of large completed trials, ongoing trials, and other clinical evidence, revised guidelines for therapy with implantable cardioverter–defibrillators have recently been published in the United States and Europe. The list of indications includes both primary prevention of sudden death in persons at high risk and secondary prevention, after an initial episode of sustained ventricular tachyarrhythmia, in most forms of cardiac diseases.