Mechanisms of Diastolic Dysfunction in Heart Failure

Abnormalities of diastole are common to most forms of congestive heart failure (HF). Diastolic function is broadly defined as the ability of the heart to fill adequately and at normal pressure to charge the ventricular pump for each subsequent contraction. It is determined by both active and passive processes occurring at the level of the myocyte, extracellular matrix, and left ventricular chamber. Forces extrinsic to the myocardium—such as the influence of right heart filling, pericardial and extracardiac constraints, and cardiac preload and afterload also contribute. Nearly half of patients with HF have apparently preserved systolic function, and this has focused attention on diastolic dysfunction as a dominant contributor to symptoms, sparking interest for understanding and treating diastolic abnormalities. This review focuses on the mechanisms determining normal and pathologic cardiac relaxation and distensibility and highlights how these abnormalities may be therapeutically targeted to improve diastolic function in human HF.