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 Citations (Scopus)

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) ≤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
Volume13
Issue number6
DOIs
StatePublished - Aug 1 2007

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Brain Natriuretic Peptide
Neurotransmitter Agents
Endothelin-1
Heart Failure
Survival
Stroke Volume
Placebos
Natriuretic Peptides
Atrial Natriuretic Factor
Hospitalization
bucindolol
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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

In: Journal of Cardiac Failure, Vol. 13, No. 6, 01.08.2007, p. 437-444.

Research output: Contribution to journalArticle

Frantz, Robert P. ; Lowes, Brian D. ; Grayburn, Paul A. ; White, Michel ; Krause-Steinrauf, Heidi ; Krishnan, Vaishali ; Uyeda, Lauren ; Burnett, John C. / 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). In: Journal of Cardiac Failure. 2007 ; Vol. 13, No. 6. pp. 437-444.
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T2 - Results of the Neurohumoral Substudy of the Beta-Blocker Evaluation of Survival Study (BEST)

AU - Frantz, Robert P.

AU - Lowes, Brian D.

AU - Grayburn, Paul A.

AU - White, Michel

AU - Krause-Steinrauf, Heidi

AU - Krishnan, Vaishali

AU - Uyeda, Lauren

AU - Burnett, John C.

PY - 2007/8/1

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N2 - 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.

AB - 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.

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KW - endothelin

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KW - prognosis

KW - β-adrenergic antagonists

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