BACKGROUND: Previous studies have suggested that natriuretic peptides may have direct sympathoinhibitory effects. Nesiritide (recombinant human B-type natriuretic peptide) has been recently approved for treatment of decompensated congestive heart failure (CHF). We sought to assess the effects of nesiritide compared with dobutamine on time-domain indices of heart rate variability (HRV) in patients with decompensated CHF. METHODS: The study population consisted of 185 patients, who were randomized to intravenous nesiritide at a low (0.015 microg/kg/min, n = 56) or high (0.03 microg/kg/min, n = 58) dose, or to dobutamine (> or = 5 microg/kg/min, n = 58). Time-domain HRV indices were obtained from 24-hour Holter recordings immediately before and during study drug therapy. RESULTS: Dobutamine therapy resulted in a decrease in standard deviation of the R-R intervals over a 24-hour period (SDNN), standard deviation of all 5-minute mean R-R intervals (SDANN), and the percentage of R-R intervals with >50 ms variation (pNN50) (all P < .05). Low-dose nesiritide induced an increase in SDNN (P < .05), and high-dose nesiritide resulted in a nonsignificant decrease in all measures of HRV. A significant interaction was noted between baseline HRV and the effect of vasoactive therapy on HRV (P = .028). Therefore, the effect of nesiritide and dobutamine was analyzed in relation to baseline HRV. In the dobutamine group, patients with moderately depressed HRV at baseline displayed a reduction in SDNN (P = .01), SDANN (P = .01), pNN50 (P = .04), and the square root of mean squared differences of successive R-R intervals (RMSSD) (P = .05), whereas no significant changes occurred in patients with severely depressed HRV. In the low-dose nesiritide group, patients with severely depressed HRV displayed an increase in SDNN (P = .001), SDANN (P = .02), and RMSSD (P = .01), with no significant changes in patients with moderately depressed HRV. HRV response to high-dose nesiritide was similar to that of dobutamine. CONCLUSIONS: Low-dose nesiritide therapy in patients with decompensated CHF improves indices of overall HRV and parasympathetic modulation, particularly if HRV is severely depressed at baseline. Dobutamine and possibly high-dose nesiritide can potentially lead to further deterioration of autonomic dysregulation.