Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated with Lower Mortality and Heart Failure Hospitalization Rates in Patients with Heart Failure with Mid-Range and Preserved Ejection Fraction

Gianluigi Savarese, Camilla Hage, Nicola Orsini, Ulf Dahlström, Pasquale Perrone-Filardi, Giuseppe M C Rosano, Lars H. Lund

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background-In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients. Methods and Results-In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF≥50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median follow-up of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36-0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29-0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately. Conclusions-In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.

Original languageEnglish
Article numbere003105
JournalCirculation: Heart Failure
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

Fingerprint

Brain Natriuretic Peptide
Hospitalization
Heart Failure
Mortality
Confidence Intervals
Morbidity
Registries
Outpatients
Biomarkers
Drug Therapy

Keywords

  • Heart failure with mid-range ejection fraction
  • heart failure with preserved ejection fraction
  • N-terminal pro-B-type natriuretic peptide
  • prognosis
  • registry

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated with Lower Mortality and Heart Failure Hospitalization Rates in Patients with Heart Failure with Mid-Range and Preserved Ejection Fraction. / Savarese, Gianluigi; Hage, Camilla; Orsini, Nicola; Dahlström, Ulf; Perrone-Filardi, Pasquale; Rosano, Giuseppe M C; Lund, Lars H.

In: Circulation: Heart Failure, Vol. 9, No. 11, e003105, 01.11.2016.

Research output: Contribution to journalArticle

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abstract = "Background-In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients. Methods and Results-In the Swedish Heart Failure Registry, HFmrEF (EF=40{\%}-49{\%}) and HFpEF (EF≥50{\%}) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median follow-up of 1.65 years, 361 patients (55{\%}) showed a reduction and 289 patients (45{\%}) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16{\%}) who decreased their NT-proBNP versus 78 patients (27{\%}) who increased it died from any cause (adjusted hazard ratio=0.53; 95{\%} confidence interval=0.36-0.77), 61 (17{\%}) versus 86 (30{\%}) were hospitalized for HF (hazard ratio=0.41; 95{\%} confidence interval=0.29-0.60), and 96 (27{\%}) versus 125 (43{\%}) reported the composite outcome (hazard ratio=0.46; 95{\%} confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately. Conclusions-In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.",
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AU - Savarese, Gianluigi

AU - Hage, Camilla

AU - Orsini, Nicola

AU - Dahlström, Ulf

AU - Perrone-Filardi, Pasquale

AU - Rosano, Giuseppe M C

AU - Lund, Lars H.

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N2 - Background-In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients. Methods and Results-In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF≥50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median follow-up of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36-0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29-0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately. Conclusions-In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.

AB - Background-In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients. Methods and Results-In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF≥50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median follow-up of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36-0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29-0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately. Conclusions-In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.

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KW - heart failure with preserved ejection fraction

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KW - prognosis

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