BACKGROUND: The syndrome of congestive heart failure (CHF) entails complex autonomic and hormonal responses. Profound abnormalities in autonomic function, characterized by sympathetic overactivity and parasympathetic withdrawal, exert direct deleterious effects on the heart and contribute to progressive circulatory failure. We investigated the relationship of heart rate variability (HRV) with levels of neurohormones in plasma. METHODS AND RESULTS: We studied 64 patients admitted to the hospital for treatment of decompensated CHF (mean age, 59 +/- 2 years; New York Heart Association class III [72%] and IV [28%]). Time- and frequency-domain HRV indices were obtained from 24-hour Holter recordings. Neurohormonal activation was assessed by measuring plasma renin activity and aldosterone and norepinephrine levels. In the time domain, norepinephrine correlated negatively with average NN interval (r = -.34; P =.007), SDNN (r = -.35; P =.005), and SDANN (r = -.36; P =.004). In the frequency domain, norepinephrine was negatively associated with the total power (r = -.39; P =.001) and ultralow power (r = -.43; P =.0005). No correlation was found between indices indicative of parasympathetic modulation, except for a borderline correlation with the high-frequency power (r = -.25; P =.048). CONCLUSIONS: Reduced HRV may be associated with increased norepinephrine levels in patients with severe CHF. The ability of long-term HRV parameters to reflect in part the activation of diverse hormonal systems may explain their greater prognostic power for risk stratification in patients with CHF.