THE MOLECULAR AND CELLULAR PATHOPHYSIOLOGY OF HEART-FAILURE

In the United States, it is estimated that heart failure develops in 4 65,000 people each year. Heart failure occurs in both men and women an d is associated with a high morbidity and mortality rate in both sexes and in all races. Our knowledge of the pathophysiology of heart failu re has advanced beyond the cardiorenal-neurohumoral model and now incl udes changes in myocyte structure and function. Cellular changes in he art failure include myocyte hypertrophy, abnormalities in calcium home ostasis, excitation-contraction coupling, cross-bridge cycling, and ch anges in the cytoskeletal architecture. Data also indicate that some o f these changes are found during the compensated stage of heart failur e; whereas other changes are found during overt decompensation and are associated with changes in systolic and diastolic function. The trans ition from compensated to decompensated heart failure is more than lik ely related to the overexpression of neurohormones and peptides such a s norepinephrine, angiotensin II, and proinflammatory cytokines. The p urpose of this article is to review the epidemiology and cellular path ophysiology of heart failure.