W H Wilson Tang1, Matthias Dupont2, Adrian F Hernandez3, Adriaan A Voors4, Amy P Hsu5, G Michael Felker3, Javed Butler6, Marco Metra7, Stefan D Anker8, Richard W Troughton9, Stephen S Gottlieb10, John J McMurray11, Paul W Armstrong12, Barry M Massie13, Robert M Califf3, Christopher M O'Connor3, Randall C Starling5. 1. Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: tangw@ccf.org. 2. Department of Cardiology, Ziekenhuis Oost Limburg, Genk, Belgium. 3. Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina. 4. University Medical Center Groningen, Groningen, the Netherlands. 5. Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. 6. Cardiovascular Division, Stony Brook University, Stony Brook, New York. 7. Department of Cardiology, University of Brescia, Brescia, Italy. 8. Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany. 9. Department of Cardiology, University of Otago, Christchurch, New Zealand. 10. Department of Cardiology, University of Maryland, Baltimore, Maryland. 11. Department of Cardiology, University of Glasgow, Glasgow, United Kingdom. 12. Department of Cardiology, University of Alberta, Edmonton, Canada. 13. San Francisco Veterans Affairs Medical Center, University of California-San Francisco, San Francisco, California.
Abstract
OBJECTIVES: The purpose of this study was to investigate the predictive values of baseline and changes in cystatin C (CysC) and its derived equations for short-term adverse outcomes and the effect of nesiritide therapy on CysC in acute decompensated heart failure (ADHF). BACKGROUND: Newer renal biomarkers or their derived estimates of renal function have demonstrated long-term prognostic value in chronic heart failure. METHODS:CysC levels were measured in sequential plasma samples from 811 subjects with ADHF who were enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) biomarker sub-study (randomized to nesiritide therapy vs. placebo), and followed for all-cause death (180 days) and recurrent hospital stay (30 days). RESULTS:Median CysC levels were 1.49 (interquartile range [IQR]: 1.20 to 1.96) mg/l at baseline, 1.56 (IQR: 1.28 to 2.13) mg/l at 48 to 72 h, and 1.58 (IQR: 1.24 to 2.11) mg/l at 30 days. Higher baseline (but not follow-up) CysC levels were associated with increased risk of 30-day adverse events and less improvement in dyspnea after 24 h as well as 180-day mortality, although not incremental to blood urea nitrogen. Worsening renal function (defined as a 0.3 mg/l increase in CysC) occurred in 161 of 701 (23%) patients, but it was not predictive of adverse events. Changes in CysC levels were similar between the nesiritide and placebo groups. CONCLUSIONS: Our findings confirmed the prognostic value of baseline CysC levels in the setting of ADHF. However, worsening renal function based on CysC rise was not predictive of adverse events. Nesiritide did not worsen renal function compared with placebo.
RCT Entities:
OBJECTIVES: The purpose of this study was to investigate the predictive values of baseline and changes in cystatin C (CysC) and its derived equations for short-term adverse outcomes and the effect of nesiritide therapy on CysC in acute decompensated heart failure (ADHF). BACKGROUND: Newer renal biomarkers or their derived estimates of renal function have demonstrated long-term prognostic value in chronic heart failure. METHODS:CysC levels were measured in sequential plasma samples from 811 subjects with ADHF who were enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) biomarker sub-study (randomized to nesiritide therapy vs. placebo), and followed for all-cause death (180 days) and recurrent hospital stay (30 days). RESULTS: Median CysC levels were 1.49 (interquartile range [IQR]: 1.20 to 1.96) mg/l at baseline, 1.56 (IQR: 1.28 to 2.13) mg/l at 48 to 72 h, and 1.58 (IQR: 1.24 to 2.11) mg/l at 30 days. Higher baseline (but not follow-up) CysC levels were associated with increased risk of 30-day adverse events and less improvement in dyspnea after 24 h as well as 180-day mortality, although not incremental to blood ureanitrogen. Worsening renal function (defined as a 0.3 mg/l increase in CysC) occurred in 161 of 701 (23%) patients, but it was not predictive of adverse events. Changes in CysC levels were similar between the nesiritide and placebo groups. CONCLUSIONS: Our findings confirmed the prognostic value of baseline CysC levels in the setting of ADHF. However, worsening renal function based on CysC rise was not predictive of adverse events. Nesiritide did not worsen renal function compared with placebo.
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