Direct Stimulation of Cardiogenesis: A New Paradigm for Treating Heart Disease.

Abstract

Heart failure (HF) is highly prevalent and is associated with substantial mortality and morbidity, despite the many treatment options currently available. We propose a potential new approach to treating heart disease: promoting cardiogenesis from existing cardiac myocytes by inhibiting the Hippo pathway, a stop growth pathway in the heart. HF is the third leading cause of cardiovascular death in the United States. It is a syndrome associated with high mortality, considerable morbidity, and an economic burden that is often relentlessly progressive. The American Heart Association and American College of Cardiology classify HF into 4 stages: stage A, presence of risk factors, but with normal cardiac function and structure; stage B, subclinical changes in left ventricular (LV) structure and function; stage C, clinical HF; and stage D, advanced HF. Coronary artery disease is present in approximately half of patients with new-onset clinical HF and is especially prevalent in patients with a reduced LV ejection fraction. Data from Framingham show a rise in post–myocardial infarction (MI) clinical HF rates between 1971 and 2000, which is primarily due to an increase in HF incidence in the early post-MI period. It has been speculated that because intervention and thrombolytic therapy have improved survival in patients with MI, the population of patients at risk of post-MI HF has grown. Major clinical risk factors for HF include age, male sex, hypertension, electrocardiographic evidence of LV hypertrophy, MI, diabetes mellitus, valvular heart disease, and obesity. …