Baseline and Serial Neurohormones in Patients With Congestive Heart Failure Treated With and Without Bucindolol: Results of the Neurohumoral Substudy of the Beta-Blocker Evaluation of Survival Study (BEST)

Robert P. Frantz, Brian D. Lowes, Paul A. Grayburn, Michel White, Heidi Krause-Steinrauf, Vaishali Krishnan, Lauren Uyeda, John C. Burnett

Research output: Contribution to journalArticle

16 Scopus citations


Background: Serial neurohormones may serve as markers of efficacy of congestive heart failure (CHF) therapy. We measured serial plasma big-endothelin (Big-ET), ET-1, N-terminal atrial natriuretic peptide, and brain natriuretic peptide (BNP) in 206 patients randomized to bucindolol or placebo in Beta-Blocker Evaluation of Survival Trial (BEST). Methods and Results: Neurohormones were measured at baseline and 3 and 12 months. At baseline, BNP and Big-ET levels were greater in New York Heart Association (NYHA) Class IV than in Class III patients (median 122 pg/mL versus 447 pg/mL, P = .001; and 20.0 pg/mL versus 9.9 pg/mL, P = .003), and in patients with left ventricular ejection fraction (LVEF) ≤20% compared with LVEF >20% (median 211 pg/mL versus 99.1 pg/mL; and 12.9 pg/mL versus 8.0 pg/mL, both P = .003). Big-ET and BNP were the strongest predictors of the composite end point of CHF hospitalization or death. LVEF at 12 months correlated inversely with 12-month BNP levels (r = -0.41, P = .0001). Bucindolol had no effect on neurohormones except that bucindolol treated patients had lower Big-ET levels at 3 months than patients receiving placebo (median 9.1 pg/mL versus 10.9 pg/mL, P = .05). A decline in ET-1 was associated with increased risk of the composite endpoint. Conclusions: Lack of effect of bucindolol on natriuretic peptide levels appears consistent with its overall lack of efficacy in BEST.

Original languageEnglish (US)
Pages (from-to)437-444
Number of pages8
JournalJournal of Cardiac Failure
Issue number6
Publication statusPublished - Aug 1 2007



  • CHF
  • endothelin
  • natriuretic peptides
  • prognosis
  • β-adrenergic antagonists

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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