title: 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: OBJECTIVE
  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.
authors.affiliation: Christchurch Heart Institute, University of Otago, Christchurch, New Zealand; Cardiology Department, Christchurch Hospital, Christchurch, New Zealand. Electronic address: wandy_chan@health.qld.gov.au.
authors.forename: W Y Wandy
authors.initials: WY
authors.lastname: Chan
authors.affiliation: Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Frampton
authors.affiliation: Cardiology Department, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Crozier
authors.affiliation: Christchurch Heart Institute, University of Otago, Christchurch, New Zealand; Cardiology Department, Christchurch Hospital, Christchurch, New Zealand.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Troughton
authors.affiliation: Christchurch Heart Institute, University of Otago, Christchurch, New Zealand; Cardiovascular Research Institute, National University Health System, Singapore.
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: D000208:Acute Disease; D000368:Aged; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D054832:Urocortins / Q000008:administration & dosage*
chemical_list: D054832:Urocortins
keywords: acute heart failure; double-blind method; hormone; randomized controlled trial; urocortin-2