Usefulness of temporal changes in neurohormones as markers of ventricular remodeling and prognosis in patients with left ventricular systolic dysfunction and heart failure receiving either Candesartan or Enalapril or both

Raymond T. Yan, Michel White, Andrew T. Yan, Salim Yusuf, Jean L. Rouleau, Aldo P. Maggioni, Christian Hall, Roberto Latini, Rizwan Afzal, John Floras, Serge Masson, Robert S. McKelvie

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Abstract

Although various neurohormones at initial measurement confer prognostic value in heart failure and correlate with the left ventricular ejection fraction (EF) and cardiac volumes, the significance of their temporal changes (Δ) remains undetermined. This study examined temporal changes in neurohormones related to cardiac remodeling and prognosis in patients with systolic dysfunction and heart failure receiving therapeutic inhibition of the renin-angiotensin-aldosterone system. Temporal changes in plasma renin, angiotensin-II, aldosterone, epinephrine, norepinephrine, B-type natriuretic peptide (BNP), and N-terminal atrial natriuretic peptide (NT-ANP) in 768 treated patients with heart failure measured at baseline and 17 and 43 weeks after randomization were examined for their relations with concurrent changes in the EF, cardiac volumes, and risk for subsequent adverse clinical outcomes. Increasing BNP (p <0.0001) and NT-ANP (p = 0.01) over time were associated with a concurrent decreasing EF, increasing end-diastolic volume (EDV), and increasing end-systolic volume (ESV; all p <0.0001). In multivariable analysis, ΔBNP and ΔNT-ANP were independent predictors of ΔESV and ΔEDV, whereas ΔBNP also predicted ΔEF (all p <0.0001). Patients who died or experienced heart failure hospitalization had larger antecedent increases in NT-ANP (+293.7 vs -21.5 pmol/ml, p = 0.006) and lesser decreases in norepinephrine (-22.3 vs -48.5 pg/ml, p = 0.04). Increasing NT-ANP (hazard ratio [HR] 3.45, p = 0.009) and norepinephrine (HR 2.04, p = 0.02) over time independently predicted increased risk for subsequent death or heart failure hospitalization. In conclusion, in treated patients with heart failure, increasing NT-ANP and BNP over time predict a decreasing EF and ventricular dilatation, while increasing NT-ANP and norepinephrine independently predict greater mortality and morbidity. Serial measurements of these neurohormones may serve as useful surrogate markers of ventricular remodeling and prognosticators for clinical risk stratification.

Original languageEnglish
Pages (from-to)698-704
Number of pages7
JournalThe American Journal of Cardiology
Volume96
Issue number5
DOIs
Publication statusPublished - Sep 1 2005

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Systolic Heart Failure
Ventricular Remodeling
Enalapril
Left Ventricular Dysfunction
Atrial Natriuretic Factor
Neurotransmitter Agents
Brain Natriuretic Peptide
Heart Failure
Norepinephrine
Cardiac Volume
Stroke Volume
Hospitalization
Renin-Angiotensin System
Random Allocation
candesartan
Aldosterone
Renin
Angiotensin II
Epinephrine
Dilatation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Usefulness of temporal changes in neurohormones as markers of ventricular remodeling and prognosis in patients with left ventricular systolic dysfunction and heart failure receiving either Candesartan or Enalapril or both. / Yan, Raymond T.; White, Michel; Yan, Andrew T.; Yusuf, Salim; Rouleau, Jean L.; Maggioni, Aldo P.; Hall, Christian; Latini, Roberto; Afzal, Rizwan; Floras, John; Masson, Serge; McKelvie, Robert S.

In: The American Journal of Cardiology, Vol. 96, No. 5, 01.09.2005, p. 698-704.

Research output: Contribution to journalArticle

Yan, Raymond T. ; White, Michel ; Yan, Andrew T. ; Yusuf, Salim ; Rouleau, Jean L. ; Maggioni, Aldo P. ; Hall, Christian ; Latini, Roberto ; Afzal, Rizwan ; Floras, John ; Masson, Serge ; McKelvie, Robert S. / Usefulness of temporal changes in neurohormones as markers of ventricular remodeling and prognosis in patients with left ventricular systolic dysfunction and heart failure receiving either Candesartan or Enalapril or both. In: The American Journal of Cardiology. 2005 ; Vol. 96, No. 5. pp. 698-704.
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abstract = "Although various neurohormones at initial measurement confer prognostic value in heart failure and correlate with the left ventricular ejection fraction (EF) and cardiac volumes, the significance of their temporal changes (Δ) remains undetermined. This study examined temporal changes in neurohormones related to cardiac remodeling and prognosis in patients with systolic dysfunction and heart failure receiving therapeutic inhibition of the renin-angiotensin-aldosterone system. Temporal changes in plasma renin, angiotensin-II, aldosterone, epinephrine, norepinephrine, B-type natriuretic peptide (BNP), and N-terminal atrial natriuretic peptide (NT-ANP) in 768 treated patients with heart failure measured at baseline and 17 and 43 weeks after randomization were examined for their relations with concurrent changes in the EF, cardiac volumes, and risk for subsequent adverse clinical outcomes. Increasing BNP (p <0.0001) and NT-ANP (p = 0.01) over time were associated with a concurrent decreasing EF, increasing end-diastolic volume (EDV), and increasing end-systolic volume (ESV; all p <0.0001). In multivariable analysis, ΔBNP and ΔNT-ANP were independent predictors of ΔESV and ΔEDV, whereas ΔBNP also predicted ΔEF (all p <0.0001). Patients who died or experienced heart failure hospitalization had larger antecedent increases in NT-ANP (+293.7 vs -21.5 pmol/ml, p = 0.006) and lesser decreases in norepinephrine (-22.3 vs -48.5 pg/ml, p = 0.04). Increasing NT-ANP (hazard ratio [HR] 3.45, p = 0.009) and norepinephrine (HR 2.04, p = 0.02) over time independently predicted increased risk for subsequent death or heart failure hospitalization. In conclusion, in treated patients with heart failure, increasing NT-ANP and BNP over time predict a decreasing EF and ventricular dilatation, while increasing NT-ANP and norepinephrine independently predict greater mortality and morbidity. Serial measurements of these neurohormones may serve as useful surrogate markers of ventricular remodeling and prognosticators for clinical risk stratification.",
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AU - Yusuf, Salim

AU - Rouleau, Jean L.

AU - Maggioni, Aldo P.

AU - Hall, Christian

AU - Latini, Roberto

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N2 - Although various neurohormones at initial measurement confer prognostic value in heart failure and correlate with the left ventricular ejection fraction (EF) and cardiac volumes, the significance of their temporal changes (Δ) remains undetermined. This study examined temporal changes in neurohormones related to cardiac remodeling and prognosis in patients with systolic dysfunction and heart failure receiving therapeutic inhibition of the renin-angiotensin-aldosterone system. Temporal changes in plasma renin, angiotensin-II, aldosterone, epinephrine, norepinephrine, B-type natriuretic peptide (BNP), and N-terminal atrial natriuretic peptide (NT-ANP) in 768 treated patients with heart failure measured at baseline and 17 and 43 weeks after randomization were examined for their relations with concurrent changes in the EF, cardiac volumes, and risk for subsequent adverse clinical outcomes. Increasing BNP (p <0.0001) and NT-ANP (p = 0.01) over time were associated with a concurrent decreasing EF, increasing end-diastolic volume (EDV), and increasing end-systolic volume (ESV; all p <0.0001). In multivariable analysis, ΔBNP and ΔNT-ANP were independent predictors of ΔESV and ΔEDV, whereas ΔBNP also predicted ΔEF (all p <0.0001). Patients who died or experienced heart failure hospitalization had larger antecedent increases in NT-ANP (+293.7 vs -21.5 pmol/ml, p = 0.006) and lesser decreases in norepinephrine (-22.3 vs -48.5 pg/ml, p = 0.04). Increasing NT-ANP (hazard ratio [HR] 3.45, p = 0.009) and norepinephrine (HR 2.04, p = 0.02) over time independently predicted increased risk for subsequent death or heart failure hospitalization. In conclusion, in treated patients with heart failure, increasing NT-ANP and BNP over time predict a decreasing EF and ventricular dilatation, while increasing NT-ANP and norepinephrine independently predict greater mortality and morbidity. Serial measurements of these neurohormones may serve as useful surrogate markers of ventricular remodeling and prognosticators for clinical risk stratification.

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