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).

Abstract

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) < or = 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.

• Authors: Robert P Frantz, Brian D Lowes, Paul A Grayburn, Michel White, Heidi Krause-Steinrauf, Vaishali Krishnan, Lauren Uyeda, John C Burnett, BEST Neurohumoral Substudy Investigators
• Journal: Journal of cardiac failure (J Card Fail) Vol. 13 Issue 6 Pg. 437-44 (Aug 2007) ISSN: 1532-8414 [Electronic] United States
• PMID: 17675057 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adrenergic beta-Antagonists
• Biomarkers
• Endothelin-1
• Endothelins
• Propanolamines
• big-endothelin (1-22)
• Natriuretic Peptide, Brain
• Atrial Natriuretic Factor
• bucindolol

Topics

• Adrenergic beta-Antagonists (therapeutic use)
• Aged
• Atrial Natriuretic Factor (blood)
• Biomarkers (blood)
• Endothelin-1 (blood)
• Endothelins (blood)
• Female
• Follow-Up Studies
• Heart Failure (blood, drug therapy, mortality)
• Humans
• Male
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• Propanolamines (therapeutic use)
• Radioimmunoassay
• Stroke Volume
• Survival Rate
• Treatment Outcome