Effects of enalapril on heart rate variability in patients with congestive heart failure

Congestive heart failure (CHF) is characterized by sympathetic activation and parasympathetic withdrawal, and the magnitude of sympathoneural activation is associated with adverse outcome. Angiotensin-converring enzyme inhibitor therapy has been shown to reduce mortality and improve prognosis in patients with CHF, but whether this therapy improves cardiac autonomic control is not well known. This double-blind, placebo-controlled, crossover study examines the effects of enalapril on autonomic control in 12 patients with mild to moderate CHF by heart rate variability analysis. Compared with placebo, enalapril increased the SD of all normal RR intervals (SDNN) from 39 ± 13 to 48 ± 15 ms (p < 0.01), the SD of the average RR intervals for all 5-minute segments from 33 ± 12 to 42 ± 15 ms (p < 0.01), and the mean of the SDs of all RR intervals for all 5-minute segments (SDNN index) from 19 ± 5 to 23 ± 6 ms (p < 0.01). The root-mean-square successive differences and the percent differences between adjacent RR intervals >50 ms were also increased from 17 ± 8 to 21 ± 8 ms (p < 0.01) and from 1.1 ± 2.1 to 2.8 ± 2.9% (p < 0.05). In addition, total, low-frequency, and high-frequency power were increased from 560 ± 349 to 786 ± 504 ms2/Hz (p < 0.01), from 125 ± 107 to 179 ± 135 ms2/Hz (p < 0.01), and from 46 ± 32 to 94 ± 78 ms2/Hz (p < 0.01), respectively. The plasma angiotensin II level was decreased significantly from 131 ± 66 to 47 ± 18 pg/ml (p < 0.01). Changes in heart rate variability measures after enalapril therapy were positively related to changes in plasma angiotensin II level. These results indicate that enalapril therapy attenuates the autonomic imbalance associated with a poor prognosis in patients with CHF, which is related to the inhibition of the initially activated renin-angiotensin system.