The premise, promise, and perils of the prevention of lethal ventricular tachyarrhythmias.

Sudden cardiac death caused by ventricular tachyarrhythmias claims about 360,000 lives a year in the United States. The premature ventricular complex (PVC) hypothesis has been the cornerstone for understanding this problem, but it is now recognized as an incomplete explanation for this catastrophy. The recognition of the importance of structural heart disease in this process has led to the development of the Substrate Hypothesis as an alternative explanation. In this construct, PVCs may trigger lethal arrhythmias but only if an abnormal electrophysiologic substrate is present. This hypothesis more completely describes the pathophysiology of the process, provides the basis for understanding the value and limitations of the techniques used for risk assessment and management, and helps clarify the potential endpoints and potential adverse effects of therapy to prevent arrhythmias. Since no single diagnostic technique is ideal and no therapeutic modality is universally effective, an approach to the management of this problem must be multidimensional and based on a firm understanding of the actual risk of a life threatening arrhythmia, the potential but unproven benefits and uncertain endpoints of drug therapy, the cost, and the potential for arrhythmia exacerbation or significant side effect.