Evolution and Pathophysiology of Chronic Systolic Heart Failure

Understanding of the pathophysiology of chronic systolic heart failure evolved from a purely mechanical model to one in which a cascade of neurohormones and biologically active molecules are thought to be critical in the development, maintenance, and progression of the disease. Two important neurohormonal systems are the sympathetic nervous and renin‐angiotensin‐aldosterone systems. Initially, increases in norepinephrine concentrations from the sympathetic nervous system and in angiotensin II and aldosterone are beneficial in the short term to maintain cardiac output after an insult to the myocardium. However, long‐term exposure to these neurohormones causes alterations of myocytes and interstitial make‐up of the heart. These alterations in myocardium lead to progression of heart failure and, eventually, death.