Electrophysiological changes in heart failure: focus on pacemaker channels

Heart failure is a common clinical syndrome occurring as a result of cardiac overload, injury, and a complex interplay among genetic, neurohormonal, inflammatory, and biochemical factors. Occurrence of arrhythmias in heart failure is largely a consequence of disease-induced electrical remodeling of cardiac myocytes, a phenomenon consisting of alterations of ion channels and the ion-transport function that predispose patients to develop lethal arrhythmias. In most cases, the mechanism is the rapid onset of a ventricular tachyarrhythmia progressing to ventricular fibrillation and hemodynamic compromise. This paper highlights some of the important changes in ion channel expression and function that underlie electrical remodeling of the failing heart. Particular attention will be focused on the presence, features, and pharmacologic modulation of f channels expressed in ventricular cardiac myocytes.