Biblioteca Central EsSalud

Heart failure with reduced ejection fraction remains a progressive and ultimately lethal condition for millions of patients worldwide. Although current therapies prolong survival and reduce symptoms, they do not address the fundamental pathologic substrate: the irreversible loss of cardiomyocytes and their replacement with fibrotic scar. Patients with advanced heart failure — particularly those with ischemic heart failure — may lose as many as a billion cardiomyocytes, and the annual mortality among patients with advanced heart failure is approximately 50%. Among patients with heart failure of any severity, the inability of the heart to regenerate muscle and the physiological stress of a dilated failing heart result in a 5-year mortality of approximately 50%. For decades, the notion of replacing lost cells — of truly remuscularizing the human heart — has been a central aspiration of regenerative medicine. Major approaches currently being advanced for cardiac regeneration (see Key Concepts) include unlocking cell division in resident cardiomyocytes, reprogramming of resident cardiac fibroblasts into induced cardiomyocytes, and transplantation of pluripotent stem-cell–derived cardiomyocytes, each with a goal of creating more contractile units.