title: Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial.
abstract: OBJECTIVE
  Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression.
  
  
  OBJECTIVE
  To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction.
  
  
  METHODS
  The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction.
  
  
  METHODS
  Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up.
  
  
  METHODS
  The equally ranked co-primary end points were changes in diastolic function (E/e') on echocardiography and maximal exercise capacity (peak VO2) on cardiopulmonary exercise testing, both measured at 12 months.
  
  
  RESULTS
  Diastolic function (E/e') decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, -1.5; 95% CI, -2.0 to -0.9; P < .001). Peak VO2 did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, -0.6 to +0.8 mL/min/kg; P = .81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, -6 g/m2; 95% CI, -10 to-1 g/m2; P = .009) and improved neuroendocrine activation (N-terminal pro-brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P = .03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (-15 m; 95% CI, -27 to -2 m; P = .03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P < .001) and decreased estimated glomerular filtration rate (-5 mL/min/1.73 m2; 95% CI, -8 to -3 mL/min/1.73 m2; P < .001) without affecting hospitalizations.
  
  
  CONCLUSIONS
  In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: ISRCTN94726526; Eudra-CT No: 2006-002605-31.
authors: Department of Cardiology and Pneumology, Heart Center, University of Göttingen, Göttingen, Germany.
authors: Frank
authors: F
authors: Edelmann
authors: Rolf
authors: R
authors: Wachter
authors: Albrecht G
authors: AG
authors: Schmidt
authors: Elisabeth
authors: E
authors: Kraigher-Krainer
authors: Caterina
authors: C
authors: Colantonio
authors: Wolfram
authors: W
authors: Kamke
authors: André
authors: A
authors: Duvinage
authors: Raoul
authors: R
authors: Stahrenberg
authors: Kathleen
authors: K
authors: Durstewitz
authors: Markus
authors: M
authors: Löffler
authors: Hans-Dirk
authors: HD
authors: Düngen
authors: Carsten
authors: C
authors: Tschöpe
authors: Christoph
authors: C
authors: Herrmann-Lingen
authors: Martin
authors: M
authors: Halle
authors: Gerd
authors: G
authors: Hasenfuss
authors: Götz
authors: G
authors: Gelbrich
authors: Burkert
authors: B
authors: Pieske
mesh_terms: D000368:Aged; D003971:Diastole / Q000502:physiology; D004311:Double-Blind Method; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D054144:Heart Failure, Diastolic / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D011446:Prospective Studies; D011788:Quality of Life; D013148:Spironolactone / Q000627:therapeutic use*; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone