Cell Death of Cardiomyocytes in Heart Failure

Heart failure, a leading cause of death worldwide, is generally defined as a pathophysiological condition in which the heart is unable to eject the arterial blood required by all tissues in the body. Heart failure is broadly classified into acute heart failure and chronic heart failure. In clinical practice, acute heart failure is often considered synonymous with acute myocardial infarction. In acute heart failure, cardiac contractile dysfunction is induced due to necrosis of cardiomyocytes during ischemia/reperfusion. In contrast, in chronic (congestive) heart failure, cardiac contractile dysfunction is enhanced during the development of cardiac remodeling, which is histologically characterized by cardiac hypertrophy and fibrosis. During the development of chronic heart failure, cardiomyocyte death is also induced. The loss of cardiomyocytes is considered to promote hypertrophy of viable cardiomyocytes and collagen production by cardiac fibroblasts, leading to pathophysiological cardiac remodeling. In chronic heart failure, cardiomyocyte death is caused by programmed cell death rather than necrotic cell death. Cardiomyocyte death during the development of chronic heart failure leads to the induction and enhancement of cardiac fibrosis in pathological cardiac remodeling. Therefore, understanding programmed cell death of cardiomyocytes in chronic heart failure may contribute to the development of new treatments for heart failure.