ALDOSTERONE BLOCKADE REDUCES VASCULAR COLLAGEN TURNOVER, IMPROVES HEART-RATE-VARIABILITY AND REDUCES EARLY-MORNING RISE IN HEART-RATE IN HEART-FAILURE PATIENTS

Background: Experimental data suggest that aldosterone has harmful eff ects promoting myocardial fibrosis and disturbing autonomic balance. T here has been no evidence of these potential effects in intact man. Me thods and Results: We report the findings in 31 patients with stable c hronic heart failure (CHF) who were treated with spironolactone (50-10 0 mg/day) or placebo in addition to diuretics and angiotensin converti ng enzyme (ACE) inhibition. In a controlled randomised double-blind st udy, we found that spironolactone treatment reduced circulating levels of procollagen type III N-terminal amino peptide, a marker of vascula r collagen turnover, and in addition increased time-domain parameters of heart rate variability (n = 24). These latter parameters suggest a parasympathomimetic effect for additional spironolactone. Spironolacto ne significantly reduced heart rate (prolonged RR interval) particular ly during the dawn hours (06.00-09.00 h). In this unbalanced study it was not possible to provide a detailed diurnal assessment of the impac t of spironolactone on heart rate variability, but the preliminary dat a suggest that there may be an interaction with the autonomic nervous system which varies in time. Conclusions: These are the first human da ta to show that use of the aldosterone antagonist, spironolactone, can positively improve time-domain heart rate variability and reduce myoc ardial collagen turnover, as reflected by further reductions in serum procollagen peptide, despite concurrent ACE inhibitor treatment. Resid ual aldosterone after ACE inhibitor treatment may therefore have a rol e promoting arrhythmia and cardiac death by two mechanisms. Effects of additional spironolactone on slowing heart rate (and potentially the detrimental effect of aldosterone) were most prominent between 6 a.m. and 10 a.m. when cardiac death is also known to be most prominent.