Role of endothelin in modulation of heart rate variability in patients with decompensated heart failure

Endothelin-1 (ET-1) can modulate central and peripheral sympathetic outflow . However, if increased ET-1 levels contribute to autonomic perturbations i n the setting of congestive heart failure (CHF) is not known. The purpose o f this study was to determine if increased ET-1 levels contribute to the de pressed HRV in patients with CHF. Sixty-four patients were admitted to the hospital for treatment of decompensated CHF (mean age 59 +/- 12 years, NYHA Classes III [72%] and IV[28%]). Time and frequency-domain HRV measures wer e obtained from 24-hour Holter recordings. Neurohormonal activation was ass essed by measuring plasma renin activity (PRA), aldosterone, norepinephrine , and ET-1 levels. Among the time-domain HRV indices, ET-1 correlated negat ively with the standard deviation of RR intervals (SDNN) (r = -0.38, P = 0. 002) and standard deviation of all 5-minute mean RR intervals (SDANN5) (r = -0.48, P < 0.0001), but not with time-domain indices indicative of parasym pathetic modulation. Among the frequency-domain HRV indices, ET-1 correlate d negatively with the total power (r = -0.32, P = 0.01) and ultralow freque ncy power (ULF) (r = -0.43, P = 0.0004), but not with indices of parasympat hetic (high frequency) or sympathovagal (low frequency) modulation. Using m ultiple linear regression, adjusting for clinical parameters, drug therapie s, and other neurohormones, the strong negative relationship between ET-1 a nd SDNN (P = 0.027), SDANN5 (P = 0.002), and ULF power (P = 0.017) persiste d. In conclusion, ET-1 may play an important role in the autonomic dysfunct ion characteristic of CHF. The correlation between ET-1 levels and prognost ically important indices of overall HRV suggests that these HRV measures ar e better markers of neurohormonal activation in CHF which may partially acc ount for their greater discriminatory power for risk stratification.