Sudden death in heart failure: underlying electrophysiological mechanisms.

Abstract

Congestive heart failure continues to be a very significant problem in cardiovascular medicine. Up to 8–10 million people in the western world are affected by clinical or subclinical forms of heart failure. Ischemic heart disease and consequent systolic dysfunction is the major cause of heart failure. However, in up to 40% of patients, the cause is not well understood [1]. Whether the original cause is a viral infection, prior myocardial infarctions, or hypertensive heart disease, the end result or phenotype is similar. The annual mortality, even with current therapy, remains between 5 to 20% depending upon the severity of the clinical state. Approximately 50% of deaths are sudden [2], presumed to be due to ventricular arrhythmias or asystole. The importance of sudden death as the mode of death in heart failure has been reemphasized in the last decade. This is the result of information collected from clinical trials, which have provided further insight into the natural history of the disease. The mode of death in heart failure is related in part to the severity of the disease. In patients with mild to moderate heart failure (NYHA class II and III) sudden death represents the major mode of death, accounting for approximately two thirds of the mortality. In more severe heart failure, progressive heart failure is the most frequent mode of death although sudden death still accounts for about a third of the deaths. The arrhythmia associated with sudden death is usually ventricular tachycardia or fibrillation although bradycardia or asystole is also seen in advanced heart failure [3,4]. Despite investigations, the underlying mechanisms responsible for sudden death in these patients remain poorly understood [4]. Heart failure is a heterogeneous problem where multiple mechanisms may contribute to the development of arrhythmias. These include fibrosis, conduction system disease, electrolyte abnormalities such as hypokalemia and hypomagnesemia, increased stretch of the heart chamber, hypertrophy and increased muscle mass, abnormal neurohormonal activation as well as the addition of antiarrhythmic drugs with potentially proarrhythmic effects. In addition to these, it is being increasingly recognized that these hearts may also have abnormalities in ion channels/currents as well as ion transport mechanisms which can lead to electrical dysfunction in both systole and diastole. In this article we will review the electrophysiological mechanisms that are thought to underlie the risk of sudden death in this condition, especially the available evidence on abnormalities of ion currents in patients with heart failure and their potential relevance to arrhythmogenesis.