Effects of spironolactone on heart rate variability and left ventricular systolic function in severe ischemic heart failure

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Abstract

Recent data show that blockade of aldosterone receptors by spironolactone reduces the risk of morbidity and death among patients with severe heart failure. Heart failure secondary to ischemia is characterized by an imbalance of the autonomic nervous system, which can be assessed by analysis of the heart rate variability (HRV). Spironolactone’s effects on HRV are not well defined. If spironolactone has beneficial effects on HRV, this would contribute to favorable results. We therefore measured Holter-derived HRV indexes in a group of 126 patients with heart failure, aged 36 to 83 years, with angiographically proved coronary artery disease, on 3 separate occasions. Patients’ sodium intake was restricted; therapy with enalapril, furosemide, and digoxin was begun, and 2 weeks after this standard therapy, spironolactone 50 mg/day was added. Evaluations were done at baseline, and the first and 12th months. After spironolactone, the triangular interpolation of the NN histogram (from 233.0 ± 98 to 291.7 ± 74 ms and 340.5 ± 130 ms, p <0.001) and the percentage of differences between successive normal RR intervals differing >50 ms over a 24-hour electrocardiography (from 2.9 ± 2.4% to 4.3 ± 5.2% and 3.9 ± 2.6%, p <0.002) increased significantly. Ejection fraction and functional classes were also improved. These data imply that in patients with heart failure who are taking conventional drugs, the addition of spironolactone induces a favorable sympathovagal balance. These changes, as assessed by the triangular interpolation of the NN histogram and the percentage of differences between successive normal RR intervals differing >50 ms over a 24-hour electrocardiography, and observed at 1 month after therapy, persisted in the long term.

Section snippets

Patients

Patients were eligible for enrollment if they had had New York Heart Association class II to IV heart failure at the time of enrollment, and if they had undergone coronary angiography and had been found unsuitable for coronary revascularization because of poor anatomy, and if their left ventricular ejection fraction was ≤35%. Patients who fulfilled these criteria and who had given written informed consent were included. Treatment with digitalis and vasodilators was allowed, but

Patients

In all, 126 patients (111 men and 15 women, mean age 60 ± 9 years [range 36 to 83]) were admitted to the study between May 1997 and December 1998. Twenty-nine patients (23%) had diabetes, 51 (40%) had hypertension, 76 (60%) had dyslipidemia, and 88 (70%) were smokers. The clinical condition of the patients was evaluated by detailed history and complete physical examination. Before the commencement of standard therapy, 70 patients (55%) were taking digoxin, 68 (54%) were taking diuretics, 35

Discussion

Our data clearly showed that, when added to standard therapy, spironolactone causes both a dramatic clinical improvement and favorable changes in TINN and pNN50. These changes were evident after the first month of therapy and continued in the long term, until the end of the follow-up period. However, we have not seen a significant change in the spectral components of HRV. We have no ready explanation for this. Maybe spectral components are much more complicated and controlled by various

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