title: Differential interaction of clinical characteristics with key functional parameters in heart failure with preserved ejection fraction--results of the Aldo-DHF trial.
abstract: BACKGROUND
  To investigate the interaction of clinical characteristics with disease characterising parameters in heart failure with preserved ejection fraction (HFpEF). Methods and results In the multicenter, randomized, placebo-controlled, double-blinded, Aldo-DHF trial investigating the effects of spironolactone on exercise capacity (peakVO2) and diastolic function (E/e') n=422 patients with HFpEF (age 67 ± 8 years, 52% females, LVEF 67 ± 8%) were included. After multiple adjustment, higher age was significantly related to reduced peakVO2, and to increased E/e', NT-proBNP, LAVI as well as LVMI (all p<0.05). Female gender (p<0.001), CAD (p=0.002), BMI (p<0.001), sleep apnoea (p=0.02), and chronotropic incompetence (CI, p=0.002) were related to lower peakVO2 values. Higher pulse pressure (p=0.04), lower heart rates (p=0.03), CI (p=0.03) and beta-blocker treatment (p=0.001) were associated with higher E/e'. BMI correlated inversely (p=0.03), whereas atrial fibrillation (p<0.001), lower haemoglobin levels (p<0.001), CI (p=0.02), and beta-blocker treatment (p<0.001) were associated with higher NT-proBNP. After multiple adjustment for demographic and clinical variables peakVO2 was not significantly associated with E/e' (r=+0.01, p=0.87), logNT-proBNP (r=0.09, p=0.08), LAVI (r=+0.03, p=0.55), and LVMI (r=+0.05, p=0.37). The associations of E/e' with logNT-proBNP (r=0.21, p<0.001), LAVI (r=+0.29, p<0.001) and LVMI (r=0.09, p=0.06) were detectable also after multiple adjustment.
  
  
  CONCLUSIONS
  Demographic and clinical characteristics differentially interact with exercise capacity, resting left ventricular filling index, neurohumoral activation, and left atrial and ventricular remodelling in HFpEF. Exercise intolerance in HFpEF is multi-factorial and therapeutic approaches addressing exercise capacity should therefore not only aim to improve single pathological mechanisms.
  
  
  BACKGROUND
  ISRCTN94726526 (http://www.controlled-trials.com), Eudra-CT-number 2006-002605-31.
authors.affiliation: Department of Cardiology and Pneumology, University of Göttingen, Robert-Koch-Str. 40, D-37075 Göttingen, Germany; German Center for Cardiovascular Research, Germany. Electronic address: fedelmann@med.uni-goettingen.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
authors.forename: Götz
authors.initials: G
authors.lastname: Gelbrich
authors.forename: André
authors.initials: A
authors.lastname: Duvinage
authors.forename: Raoul
authors.initials: R
authors.lastname: Stahrenberg
authors.forename: Anneke
authors.initials: A
authors.lastname: Behrens
authors.forename: Christiane
authors.initials: C
authors.lastname: Prettin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kraigher-Krainer
authors.forename: Albrecht G
authors.initials: AG
authors.lastname: Schmidt
authors.forename: Hans-Dirk
authors.initials: HD
authors.lastname: Düngen
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kamke
authors.forename: Carsten
authors.initials: C
authors.lastname: Tschöpe
authors.forename: Christoph
authors.initials: C
authors.lastname: Herrmann-Lingen
authors.forename: Martin
authors.initials: M
authors.lastname: Halle
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
mesh_terms: D000368:Aged; D015331:Cohort Studies; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone
keywords: Aldosterone receptor blockade; Diastolic function; Exercise capacity; Heart failure with preserved ejection fraction; Neurohumoral activation