The molecular and cellular pathophysiology of heart failure

In the United States, it is estimated that heart failure develops in 465,000 people each year. Heart failure occurs in both men and women and is associated with a high morbidity and mortality rate in both sexes and in all races. Our knowledge of the pathophysiology of heart failure has advanced beyond the cardiorenal-neurohumoral model and now includes changes in myocyte structure and function. Cellular changes in heart failure include myocyte hypertrophy, abnormalities in calcium homeostasis, excitation-contraction coupling, cross-bridge cycling, and changes in the cytoskeletal architecture. Data also indicate that some of these changes are found during the compensated stage of heart failure; whereas other changes are found during overt decompensation and are associated with changes in systolic and diastolic function. The transition from compensated to decompensated heart failure is more than likely related to the overexpression of neurohormones and peptides such as norepinephrine, angiotensin II, and proinflammatory cytokines. The purpose of this article is to review the epidemiology and cellular pathophysiology of heart failure.