@article{9c0a8b1648594e77a62460dd3c104279,
title = "Prognostic value of baseline and changes in circulating soluble ST2 levels and the effects of nesiritide in acute decompensated heart failure",
abstract = "Objectives: The study sought to investigate the association between soluble growth stimulation expressed gene 2 (sST2) level and adverse outcomes in acute heart failure (HF). Background: Several studies have demonstrated the prognostic utility of sST2 levels in HF. Methods: sST2 levels were measured in sequential baseline and follow-up (48 to 72 h and 30 days) plasma samples from 858 acute HF subjects enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial biomarker substudy and were related to in-hospital and post-discharge clinical outcomes. Results: Higher sST2 levels were associated with increased death risk at 180 days (baseline hazard ratio [HR]: 2.21; follow-up HR: 2.64; both p < 0.001). These results were not independent of covariates and aminoterminal pro-B-type natriuretic peptide for baseline sST2 (HR: 1.29, p = 0.243), but were borderline significant for follow-up sST2 (HR: 1.61, p = 0.051). Subjects with persistently high (>60 ng/ml) sST2 levels at follow-up had higher 180-day death rates than those with lower follow-up sST2 levels (adjusted HR: 2.91, p = 0.004). Neither baseline nor follow-up sST2 levels were associated with dyspnea improvement. Changes in sST2 from baseline were less in the nesiritide versus placebo group at follow-up, but were similar at 30 days. Conclusions: Elevated levels of sST2 were associated with an increased risk of adverse clinical events in acute HF, but prognostic value of baseline sST2 diminished after adjusting for clinical covariates and aminoterminal pro-B-type natriuretic peptide. In those with elevated baseline sST2 levels, persistently elevated sST2 levels at follow-up were associated with increased mortality risk. In addition, nesiritide did not demonstrate an incremental impact on sST2 levels over standard therapy.",
keywords = "Acute decompensated heart failure, Nesiritide, Prognosis, Soluble ST2",
author = "Tang, {W. H.Wilson} and Yuping Wu and Grodin, {Justin L.} and Hsu, {Amy P.} and Hernandez, {Adrian F.} and Javed Butler and Marco Metra and Voors, {Adriaan A.} and Felker, {G. Michael} and Troughton, {Richard W.} and Mills, {Roger M.} and McMurray, {John J.} and Armstrong, {Paul W.} and O'Connor, {Christopher M.} and Starling, {Randall C.}",
note = "Funding Information: The ASCEND-HF study, including the biomarker substudy, was funded by Scios, Inc., Janssen Research & Development, LLC, retains operational responsibility for the ASCEND-HF study. Critical Diagnostics provided soluble ST2 assays to be used and financial support. ST2 measurements, statistical analyses, and manuscript preparation were conducted independent of the sponsors, and the authors have access to all the data in its entirety. Dr. Hernandez has received research grant support from Johnson & Johnson (significant), Novartis, and Amgen. Dr. Butler has served as a consultant for and received advisory board funding from Johnson & Johnson (modest). Dr. Metra has served as a consultant for and received advisory board funding from Corthera, Daiichi, Novartis, and Serrvier (modest). Dr. Voors has served as a consultant for and received advisory board funding from Johnson & Johnson, Alere, Bayer, Boehringer Ingelheim, Cardio3Biosciences, Celladon, Merck/MSD, Novartis, Servier, Trevena, and Vifor Pharma (modest); and has served as a member of the ASCEND-HF trial steering committee. Dr. Felker has received research grant support from Johnson & Johnson, Roche Diagnostics, Critical Diagnostics, and BG Medicine (significant); and has served as a consultant for Roche Diagnostics and Singulex. Dr. Troughton has served as a consultant for and received advisory board funding from St. Jude Medical (modest) and Roche Diagnostics. Dr. Mills is an employee of Janssen Research and Development, LLC (formerly Johnson & Johnson). Dr. McMurray has received research grant support from Johnson & Johnson (significant). Dr. Armstrong has received research grant support from Johnson & Johnson and Ortho Biotech (significant). Dr. O{\textquoteright}Connor has received research grant support from Johnson & Johnson (significant), BG Medicine, Critical Diagnostics, and Roche Diagnostics; and has served as a consultant for Cardiorentis. Dr. Starling has received research support from Johnson & Johnson (modest); consultant/advisory board for Johnson & Johnson (modest). 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 the Guest Editor for this paper. Publisher Copyright: {\textcopyright} 2016 American College of Cardiology Foundation.",
year = "2016",
month = jan,
day = "1",
doi = "10.1016/j.jchf.2015.07.015",
language = "English (US)",
volume = "4",
pages = "68--77",
journal = "JACC: Heart Failure",
issn = "2213-1779",
publisher = "Elsevier BV",
number = "1",
}