Effect of nesiritide (human b-type natriuretic peptide) and dobutamine on heart rate variability in decompensated heart failure

Abstract

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 μg/kg/min, n = 56) or high (0.03 μg/kg/min, n = 58) dose, or to dobutamine (≥ 5 μg/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.