Dispersions of repolarization and ventricular arrhythmogenesis: Lessons from animal models

Sudden cardiac death resulting from ventricular arrhythmogenesis is a leading cause of mortality in the developed world, accounting for up to 400,000 deaths per year in the US alone. Within the past forty years we have taken considerable leaps forward in our understanding of the causes and mechanisms underlying cardiac arrhythmias, particularly in the setting of inherited and acquired dysfunctions in ionic currents which constitute human long QT syndrome (LQTS). Impaired repolarization seen in LQTS commonly gives rise to an altered dispersion of repolarization, which is considered to provide the functional substrate necessary for the perpetuation of lethal arrhythmias. This review examines the bases for arrhythmias arising from repolarization heterogeneities and explores the applicability of the genetically amenable mouse for the study of arrhythmias arising from such mechanisms.