Author + information
- Received April 15, 2013
- Revision received July 8, 2013
- Accepted July 15, 2013
- Published online October 1, 2013.
- W. Y. Wandy Chan, MBChB∗,†∗ (, )
- Christopher M. Frampton, PhD∗,
- Ian G. Crozier, MD†,
- Richard W. Troughton, MD, PhD∗,† and
- A. Mark Richards, MD, PhD∗,‡
- ∗Christchurch Heart Institute, University of Otago, Christchurch, New Zealand
- †Cardiology Department, Christchurch Hospital, Christchurch, New Zealand
- ‡Cardiovascular Research Institute, National University Health System, Singapore
- ↵∗Reprint requests and correspondence:
Dr. W. Y. Wandy Chan, Heart Failure and Transplant Unit, Prince Charles Hospital, Rode Road, Chermside QLD 4032, Australia.
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.
Support for this work was provided through grants from the Health Research Council and the National Heart Foundation of New Zealand. The urocortin-2 peptide was provided by Neurocrine Biosciences Inc. Dr. Crozier is an investigator with Cameron Health and St. Jude Medical; and receives fellowship support from Medtronic. Dr. Troughton has relationships with Roche Diagnostics and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 15, 2013.
- Revision received July 8, 2013.
- Accepted July 15, 2013.
- American College of Cardiology Foundation