Neuregulin-1β is associated with disease severity and adverse outcomes in chronic heart failure

Bonnie Ky, Stephen E. Kimmel, Radwan N. Safa, Mary E. Putt, Nancy K. Sweitzer, James C. Fang, Douglas B. Sawyer, Thomas P. Cappola

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)310-317
Number of pages8
JournalCirculation
Volume120
Issue number4
DOIs
StatePublished - Jul 2009

Keywords

  • Cardiomyopathy
  • Heart failure
  • Neuregulin-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Ky, B., Kimmel, S. E., Safa, R. N., Putt, M. E., Sweitzer, N. K., Fang, J. C., Sawyer, D. B., & Cappola, T. P. (2009). Neuregulin-1β is associated with disease severity and adverse outcomes in chronic heart failure. Circulation, 120(4), 310-317. https://doi.org/10.1161/CIRCULATIONAHA.109.856310