This Article Full Text Full Text (PDF) CME: Take the course for this article: Circulation: July 28, 2009, Volume 120, Number 4 Data Supplement All Versions of this Article: 120/4/310    most recent CIRCULATIONAHA.109.856310v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Ky, B. Articles by Cappola, T. P. PubMed PubMed Citation Articles by Ky, B. Articles by Cappola, T. P. Related Collections Congestive Related Article

(Circulation. 2009;120:310-317.)
© 2009 American Heart Association, Inc.

Heart Failure

Neuregulin-1β Is Associated With Disease Severity and Adverse Outcomes in Chronic Heart Failure

Bonnie Ky, MD, MSCE; Stephen E. Kimmel, MD, MSCE; Radwan N. Safa, BS; Mary E. Putt, PhD, ScD; Nancy K. Sweitzer, MD, PhD; James C. Fang, MD; Douglas B. Sawyer, MD, PhD; Thomas P. Cappola, MD, ScM

From the Penn Cardiovascular Institute (B.K., S.E.K., T.P.C.) and Center for Clinical Epidemiology and Biostatistics (S.E.K., M.E.P.), University of Pennsylvania School of Medicine, Philadelphia, Pa; Department of Molecular Medicine, Boston University, Boston, Mass (R.N.S.); Cardiovascular Medicine, University of Wisconsin, Madison, Wis (N.K.S.); Cardiovascular Medicine, Case Western Reserve University, Cleveland, Ohio (J.C.F.); and Cardiovascular Division, Vanderbilt University Medical Center, Nashville, Tenn (D.B.S.).

Correspondence to Dr Thomas P. Cappola, 6 Penn Tower, 3400 Spruce St, Philadelphia, PA 19104. E-mail thomas.cappola{at}uphs.upenn.edu

Received February 4, 2009; accepted June 2, 2009.

Background— Neuregulin-1 (NRG-1) is a paracrine factor released by microvascular endothelial cells that has cardioprotective effects in animal models of heart failure. However, circulating NRG-1 has not been studied in human heart disease. We used a novel immunoassay to test whether circulating NRG-1β is associated with disease severity and clinical outcomes in chronic heart failure.

Methods and Results— Serum NRG-1β was quantified in 899 outpatients in the Penn Heart Failure Study, a referral cohort representing a broad spectrum of systolic heart failure. Circulating NRG-1β was significantly elevated in patients with worse disease severity (median, 6.2 ng/mL for New York Heart Association class IV versus 4.4 ng/mL for class I; P=0.002). In adjusted models, NRG-1β was independently associated with an increased risk of death or cardiac transplantation over a median follow-up of 2.4 years (adjusted hazard ratio, 1.58; 95% confidence interval, 1.04 to 2.39; P=0.03 comparing fourth versus first NRG-1β quartile). Associations with outcome differed by heart failure cause and symptom severity, with the strongest associations observed in patients with ischemic cardiomyopathy (interaction P=0.008) and New York Heart Association class III/IV symptoms (interaction P=0.01). These findings were all independent of brain natriuretic peptide, and assessment of NRG-1β and brain natriuretic peptide jointly provided better risk stratification than each biomarker individually in patients with ischemic or New York Heart Association class III/IV heart failure.

Conclusions— Circulating NRG-1β is independently associated with heart failure severity and risk of death or cardiac transplantation. These findings support a role for NRG-1/ErbB signaling in human heart failure and identify serum NRG-1β as a novel biomarker that may have clinical applications.

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Clinical Summaries
Circulation 2009 120: 267-268. [Extract] [Full Text]