W Y Wandy Chan1, Christopher M Frampton2, Ian G Crozier3, Richard W Troughton4, A Mark Richards5. 1. Christchurch Heart Institute, University of Otago, Christchurch, New Zealand; Cardiology Department, Christchurch Hospital, Christchurch, New Zealand. Electronic address: wandy_chan@health.qld.gov.au. 2. Christchurch Heart Institute, University of Otago, Christchurch, New Zealand. 3. Cardiology Department, Christchurch Hospital, Christchurch, New Zealand. 4. Christchurch Heart Institute, University of Otago, Christchurch, New Zealand; Cardiology Department, Christchurch Hospital, Christchurch, New Zealand. 5. Christchurch Heart Institute, University of Otago, Christchurch, New Zealand; Cardiovascular Research Institute, National University Health System, Singapore.
Abstract
OBJECTIVES: The purpose of this study is to investigate the effects of urocortin-2 as adjunct therapy in acute decompensated heart failure (ADHF). BACKGROUND:Urocortin-2 produced favorable integrated effects in experimental heart failure but there are no equivalent human data. We describe the first therapeutic study of urocortin-2 infusion in ADHF. METHODS:Fifty-three patients with ADHF were randomly assigned to 5 ng/kg/min of urocortin-2 or placebo infusion for 4 h as an adjunct therapy. Changes in vital signs, plasma neurohormonal and renal indices during treatment were compared using repeated-measures analysis of covariance. Ten patients in each arm underwent more detailed invasive hemodynamic evaluation. RESULTS:Urocortin-2 produced greater falls in systolic blood pressure compared to placebo (16 ± 5.8 mm Hg, p < 0.001) with nonsignificant increases in heart rate (5.7 ± 3.8 beats/min, p = 0.07) and increased cardiac output (2.1 ± 0.4 l/min vs. -0.1 ± 0.4 l/min, p < 0.001) associated with a 47% reduction in calculated total peripheral resistance (p = 0.015). Falls in pulmonary artery and pulmonary capillary wedge pressures did not differ significantly between groups. Urocortin-2reduced urine volume and creatinine clearance during infusion but these returned to above baseline level in the 8 h after infusion. Plasma renin activity rose briefly with urocortin-2 coinciding with reductions in blood pressure (p < 0.001). B-type natriuretic peptide levels fell significantly over 24 h with urocortin-2 (p < 0.01) but not with placebo. CONCLUSIONS:Urocortin-2 infusion in ADHF markedly augmented cardiac output without significant reflex tachycardia. Renal indices fell transiently concurrent with urocortin-2-induced reductions in blood pressure. Further investigations are required to uncover the full potential of urocortin-2 in treating ADHF.
RCT Entities:
OBJECTIVES: The purpose of this study is to investigate the effects of urocortin-2 as adjunct therapy in acute decompensated heart failure (ADHF). BACKGROUND:Urocortin-2 produced favorable integrated effects in experimental heart failure but there are no equivalent human data. We describe the first therapeutic study of urocortin-2 infusion in ADHF. METHODS: Fifty-three patients with ADHF were randomly assigned to 5 ng/kg/min of urocortin-2 or placebo infusion for 4 h as an adjunct therapy. Changes in vital signs, plasma neurohormonal and renal indices during treatment were compared using repeated-measures analysis of covariance. Ten patients in each arm underwent more detailed invasive hemodynamic evaluation. RESULTS:Urocortin-2 produced greater falls in systolic blood pressure compared to placebo (16 ± 5.8 mm Hg, p < 0.001) with nonsignificant increases in heart rate (5.7 ± 3.8 beats/min, p = 0.07) and increased cardiac output (2.1 ± 0.4 l/min vs. -0.1 ± 0.4 l/min, p < 0.001) associated with a 47% reduction in calculated total peripheral resistance (p = 0.015). Falls in pulmonary artery and pulmonary capillary wedge pressures did not differ significantly between groups. Urocortin-2 reduced urine volume and creatinine clearance during infusion but these returned to above baseline level in the 8 h after infusion. Plasma renin activity rose briefly with urocortin-2 coinciding with reductions in blood pressure (p < 0.001). B-type natriuretic peptide levels fell significantly over 24 h with urocortin-2 (p < 0.01) but not with placebo. CONCLUSIONS:Urocortin-2 infusion in ADHF markedly augmented cardiac output without significant reflex tachycardia. Renal indices fell transiently concurrent with urocortin-2-induced reductions in blood pressure. Further investigations are required to uncover the full potential of urocortin-2 in treating ADHF.
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