Recent data show that blockade of aldosterone receptors by spironoloctone 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.