Elsevier

JACC: Heart Failure

Volume 3, Issue 1, January 2015, Pages 40-49
JACC: Heart Failure

Clinical Research
Comparative Assessment of Short-Term Adverse Events in Acute Heart Failure With Cystatin C and Other Estimates of Renal Function: Results From the ASCEND-HF Trial

https://doi.org/10.1016/j.jchf.2014.06.014Get rights and content
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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.

Key Words

acute heart failure
cystatin C
nesiritide
renal insufficiency

Abbreviations and Acronyms

ADHF
acute decompensated heart failure
BUN
blood urea nitrogen
CKD-EPI
Chronic Kidney Disease Epidemiology Collaboration
CysC
cystatin C
GFR
glomerular filtration rate
WRF
worsening renal function

Cited by (0)

The ASCEND-HF biomarker substudy is funded by Johnson & Johnson (now Janssen Pharmaceuticals, Inc.). Dr. Felker has received research grants from Johnson & Johnson, Roche Diagnostics, Critical Diagnostics, and BG Medicine. Dr. Hernandez has received a research grant from Johnson & Johnson. Drs. Gottlieb, Voors, Butler, and Massie are consultants to and on the advisory board of Johnson & Johnson. Dr. Metra is a consultant to and on the advisory board of Corthera, Daiichi, Novartis, and Servier. Dr. Anker has received honoraria from, is a consultant to, and is on the advisory board of Alere Inc., Europe, ThermoFisher Scientific, and Vifor Pharma. Dr. Troughton is a consultant to and on the advisory board of St. Jude Medical. Drs. McMurray, Califf, and O’Connor have received research grants from Johnson & Johnson. Dr. Armstrong has received research grants from Johnson & Johnson and Ortho Biotech. Dr. Starling has received other research support, is a consultant to, and on the advisory board of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

John R. Teerlink, MD, served as Guest Editor for this paper.