Long QT Syndrome as a Cause of Cardiac Sudden Death

Abstract

Recent molecular biological approaches to the familial long QT syndrome (LQTS) have increased our understanding of diseases associated with a prolonged QT interval. Accumulated findings have highlighted the importance of the modulation of cardiac ion channel function to generate the long QT: (1) gain of function in the channels carrying inward currents such as Na⁺ and Ca²⁺ channels, and (2) loss of function of K⁺ channels that carry outward currents. In contrast, in patients with acquired myocardial dysfunction such as heart failure (postmyocardial infarction), abnormality in repolarization has been shown to cause fatal dysrhythmias. Regardless of the etiology (i.e., congenital or secondary), the presence of QT prolongation implies a failure of cellular repolarization, which facilitates the occurrence of early afterdepolarization, degenerating to torsades de pointes (TdP) type ventricular tachyarrhythmias (VT) and cardiac sudden death. Here, the clinical aspects of delayed repolarization are discussed based on an analysis of a typical TdP-type VT case, with particular reference to diverse mechanisms underlying LQTS, and these aspects are then compared with the findings in familial LQTS, for which a genetic basis has already been elucidated. It is of clinical importance to learn the pathophysiology underlying myocardial repolarization failure so as to avoid excess QT prolongation and therefore cardiac sudden death.