Volume 12, Number 3, May-June 2005

Aldosterone: an important mediator of cardiac remodelling in heart failure
Allan D Struthers

Aldosterone is intimately linked to the pathophysiology of heart failure, and high levels of aldosterone are associated with worse prognosis. Many non-renal effects of aldosterone contribute to the congestive heart failure syndrome, including endothelial dysfunction, reactive myocardial fibrosis and cardiac remodelling. The precise mechanism by which aldosterone stimulates myocardial collagen accumulation and fibrosis is not yet fully understood. It may largely occur secondary to aldosterone-related endothelial dysfunction and inflammation, since endothelial dysfunction can lead to micro-thrombus formation and tissue micro-infarction, which repairs itself by fibrosis. Other contributory effects may include a direct impact of aldosterone on the collagen synthesis pathway.
In the RALES study, spironolactone in conjunction with an angiotensin-converting enzyme (ACE) inhibitor was found to reduce mortality in chronic moderate-to-severe heart failure; the EPHESUS study more recently reported significant reductions in death and hospitalisation when eplerenone was added to ACE inhibitor and beta blocker therapy in patients with clinical evidence of heart failure following acute myocardial infarction. Clinicians should now consider routinely adding an aldosterone receptor antagonist to standard therapy of patients with left ventricular dysfunction and heart failure in order to reduce cardiac morbidity and mortality.

Br J Cardiol 2005;12:211-218.

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