Mechanisms Underlying Arrhythmogenesis in Long QT Syndrome

Abstract

Prolongation of the QT interval is caused by an increase in the duration of action potential (APD) of ventricular myocytes. It can result from several causes, including congenital defects, or can occur in response to an increasing number and diversity of drugs that prolong APD. Accentuation of spatial dispersion of refractoriness within the ventricular myocardium, secondary to exaggerated transmural or transseptal dispersion of repolarization, is the principal arrhythmogenic substrate in acquired and congenital long QT syndrome (LQTS). This article discusses the molecular, genetic, cellular, and ionic mechanisms underlying the development of arrhythmogenesis associated with LQTS.