Mineralocorticoid receptor antagonism and cardiac remodeling in ischemic heart failure.
Aldosterone production in the heart as well as aldosterone plasma levels are increased after myocardial infarction and in congestive heart failure, correlating with the severity of disease. Aldosterone promotes sodium and water retention, sympathoadrenergic activation, endothelial dysfunction, and cardiovascular fibrosis and hypertrophy. Even maximally recommended doses of ACE inhibitors do not completely prevent formation of aldosterone. The Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Post acute myocardial infarction Heart failure Efficacy and SUrvival Study (EPHESUS) demonstrated that aldosterone receptor blockade markedly reduces mortality among patients with heart failure. This review summarizes recent clinical and experimental data on the effect of aldosterone antagonists on left ventricular remodeling and function in ischemic heart failure with special emphasis on potential underlying mechanisms. While reduction of excessive extracellular matrix turnover leading to decreased fibrosis appears to be the most important effect of mineralocorticoid receptor antagonism in heart failure, other mechanisms such as regression of hypertrophy, improvement of endothelial function, reduction of superoxide formation, and enhanced renal sodium excretion may contribute. Recent data showed that in rats with left ventricular dysfunction after extensive myocardial infarction, eplerenone on top of ACE inhibition more effectively improved cardiac remodeling and molecular alterations than ACE inhibition alone.
Medizinische Klinik der Julius-Maximilians-Universität, Würzburg, Germany.
D
D
Fraccarollo
P
P
Galuppo
J
J
Bauersachs
D000450:Aldosterone / Q000502:physiology; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone