Apoptosis in the genesis of cardiac rhythm disorders.

Programmed cell death has provided a potential pathogenetic mechanism that could play a role in several diseases of the cardiac conduction system and the myocardium that are clinically expressed as disorders of the cardiac rhythm (Fig. 4). Most of these studies have been descriptive. The exact nature of the triggers for apoptotic cell death is not well understood and is a subject of current investigation. Alterations in the architecture of the myocardium play an important role in the pathogenesis of ventricular arrhythmias that are responsible for a large proportion of sudden cardiac deaths. Although apoptosis is essential for normal development, excessive apoptosis resulting from pathological triggers may result in destruction of tissues and in the development of heart disease in which a fatal arrhythmic event may be a final common pathway. At present, the triggers for programmed cell death in disorders of the cardiac rhythm are not understood completely. Because diverse conditions trigger apoptosis, treatment strategies may have to be directed toward attenuating such triggers and, in some instances, toward modifying the process itself. If future therapies that can favorably modulate the apoptotic process in conditions such as dilated cardiomyopathy and postmyocardial infarction are developed, they will have the potential to prevent the pathologic alteration of myocardial architecture that is conducive to arrhythmogenesis.