title: 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.
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 (Delta) 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, DeltaBNP and DeltaNT-ANP were independent predictors of DeltaESV and DeltaEDV, whereas DeltaBNP also predicted DeltaEF (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.
authors.affiliation: The University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Yan
authors.forename: Michel
authors.initials: M
authors.lastname: White
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Yan
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.forename: Christian
authors.initials: C
authors.lastname: Hall
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Rizwan
authors.initials: R
authors.lastname: Afzal
authors.forename: John
authors.initials: J
authors.lastname: Floras
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.forename: Robert S
authors.initials: RS
authors.lastname: McKelvie
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001713:Biphenyl Compounds; D002302:Cardiac Output; D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood*; D011379:Prognosis; D013599:Systole; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D015415:Biomarkers; D001713:Biphenyl Compounds; D018377:Neurotransmitter Agents; D013777:Tetrazoles; D004656:Enalapril; C081643:candesartan