Urocortin-2 infusion in acute decompensated heart failure: Findings from the UNICORN study (urocortin-2 in the treatment of acute heart failure as an adjunct over conventional therapy)

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-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. © 2013 American College of Cardiology Foundation.