F. Zannad et al., Treatment of congestive heart failure - Interfering the aldosterone-cardiac extracellular matrix relationship, HYPERTENSIO, 38(5), 2001, pp. 1227-1232
Citations number
49
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Cardiac extracellular matrix undergoes extensive and continuous turnover in
volved in the lesion-reparation process, such as in cardiac remodeling, in
hypertensive cardiac hypertrophy, in dilated cardiomyopathy, after myocardi
al infarction in the transition to heart failure, and during the progressio
n of left ventricular dysfunction. Cardiac fibrosis is a major determinant
of diastolic dysfunction and pumping capacity, and it may provide the struc
tural substrate for arrhythmogenicity, thus potentially contributing the to
progression of heart failure and sudden death. Aldosterone was shown to pr
omote cardiac fibrosis in various experimental models. It was demonstrated
that spironolactone may oppose the effect of aldosterone in promoting cardi
ac fibrosis. Measurement of cardiac collagen turnover by use of serological
markers is a useful tool for monitoring cardiac tissue repair and fibrosis
in experimental models or clinical conditions. We found that high serum le
vels of a marker of collagen turnover (procollagen type III N-terminal pept
ide) in patients with chronic heart failure receiving conventional therapy,
including ACE inhibitors, was associated with high mortality and hospitali
zation rates. In RALES (Randomized Aldactone Evaluation Study), in patients
randomized to placebo, markers continued to increase or remained unchanged
after 6-month follow-up. On the contrary, adding spironolactone 25 mg dail
y significantly decreased the levels of these serum markers during the same
period. Most importantly, the spironolactone-related morbidity and mortali
ty benefit was most predominant in subgroups with highest baseline levels o
f serum markers. These results suggest that limitation of the aldosterone-r
elated excessive extracellular matrix turnover may be one of the various ex
trarenal mechanisms contributing to the beneficial effect of spironolactone
in patients with chronic heart failure.