EFFECTS OF ENALAPRIL ON HEART-RATE-VARIABILITY IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Congestive heart failure (CHF) is characterized by sympathetic activat ion and parasympathetic withdrawal, and the magnitude of sympathoneura l activation is associated with adverse outcome. Angiotensin-convertin g enzyme inhibitor therapy has been shown to reduce mortality and impr ove prognosis in patients with CHF, but whether this therapy improves cardiac autonomic control is not well known. This double-blind, placeb o-controlled, crossover study examines the effects of enalapril on aut onomic control in 12 patients with mild to moderate CHF by heart rate variability analysis. Compared with placebo, enalapril increased the S D 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 f rom 33 +/- 12 to 42 +/- 15 ms (p <0.01), and the mean of the SDs of al l RR intervals fbr all 5-minute segments (SDNN index) from 19 +/- 5 to 23 +/- 6 ms (p <0.01). The root-mean-square successive differences an d the percent differences between adjacent RR intervals >50 ms were al so 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 h igh-frequency power were increased from 560 +/- 349 to 786 +/- 504 ms( 2)/Hz (p <0.01), from 125 +/- 107 to 179 +/- 135 ms(2)/Hz (p <0.01), a nd from 46 +/- 32 to 94 +/- 78 ms(2)/Hz (p <0.01), respectively, The p lasma angiotensin II level was decreased significantly from 131 +/- 66 to 47 +/- 18 pg/ml (p <0.01). Changes in heart rate variability measu res after enalapril therapy were positively related to changes in plas ma angiotensin II level. These results indicate that enalapril therapy attenuates the autonomic imbalance associated with a poor prognosis i n patients with CHF, which is related to the inhibition of the initial ly activated renin-angiotensin system.