Apoptosis in heart failure: a real problem?

Progressive left ventricular (LV) dysfunction is a characteristic feature of the failing heart. The mechanism or mechanisms that drive this progression are not known. In recent years, we advanced a working hypothesis that progressive LV dysfunction in heart failure results, in part, from ongoing loss of cardiomyocytes. More recently evidence emerge based on studies in animals with heart failure and in explanted failed human hearts that ongoing cardiomyocyte death through apoptosis occurs in heart failure, a finding that supports the original hypothesis. While these findings created considerable enthusiasm, some skepticism remains even today as to whether cardiomyocyte apoptosis plays an important role in the progression of heart failure. The evidence garnered over the past few years, when considered in aggregate, does favors apoptosis as a key culprit in the progression of the heart failure. Nonetheless, additional key studies are needed to determine if direct inhibition of apoptosis with specific pharmacologic probes prevents progressive LV dysfunction in heart failure. Only then can one fully appreciate the importance of cardiomyocyte apoptosis in the pathophysiology of heart failure.