Antiarrhythmic therapy, ventricular premature depolarizations and sudden cardiac death: the tip of the iceberg.

IN ACUTE MYOCARDIAL INFARCTION it is generally accepted that ventricular premature depolarizations (VPDs) lead to ventricular tachycardia and ventricular fibrillation (VF). Therefore, suppression of VPDs should result in a lower incidence of fatal ventricular dysrhythmias. Randomized controlled trials in patients with acute myocardial infarction have demonstrated fewer episodes of VF and ventricular tachycardia with the routine prophylactic administration of lidocaine or procainamide.1 2 However, it is not clear whether this salutary response is effected by suppression of VPDs per se, modification of underlying myocardial vulnerability to VF, or perhaps by affecting a critical interaction between the two. Several workers have demonstrated that frequent, complex VPDs are associated with sudden cardiac death, presumably resulting from VF. This association has been observed in post-myocardial infarction patients3-5 and in patients who have survived previous episodes of out-of-hospital VF.6 While high-density ventricular ectopic activity is a predictor for future sudden death in patients with underlying cardiac disease, it has not been shown to be definitely independent of associated manifestations of heart disease, such as depressed ventricular function or the extent of coronary artery obstruction.7 An additional confounding factor in assessing the prognostic significance of ventricular ectopic activity is the spontaneous variability of VPD frequency in a patient.8' In this issue of Circulation, Myerburg and coworkers report the results of a long-term follow-up of 16 survivors of out-of-hospital VF treated with procainamide or quinidine. The authors observed that patients whose plasma levels of these drugs were in the therapeutic range had fewer episodes of recurrent sudden death than patients in whom lower plasma levels were obtained. This apparent effect on recurrent sudden death was not consistently related to suppression of VPDs. In addition, the presence of therapeutic levels of antidysrhythmic agents was not correlated with control of ventricular ectopic activity. However, these findings should be interpreted cautiously, particularly as they relate to the large groups of patients who are at risk for sudden cardiac death. The group studied by Myerburg was small, and