title: Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial.
abstract: BACKGROUND
  Heart failure with preserved ejection fraction (HFpEF), with associated pulmonary hypertension is an increasingly large medical problem. Phosphodiesterase (PDE)-5 inhibition may be of value in this population, but data are scarce and inconclusive.
  
  
  RESULTS
  In this single centre, randomized double-blind, placebo-controlled trial, we included 52 patients with pulmonary hypertension [mean pulmonary artery pressure (PAP) >25 mmHg; pulmonary artery wedge pressure (PAWP) >15 mmHg] due to HFpEF [left ventricular ejection fraction (LVEF) ≥45%]. Patients were randomized to the PDE-5 inhibitor sildenafil, titrated to 60 mg three times a day, or placebo for 12 weeks. The primary endpoint was change in mean PAP after 12 weeks. Secondary endpoints were change in mean PAWP, cardiac output, and peak oxygen consumption (peak VO2). Mean age was 74 ± 10 years, 71% was female, LVEF was 58%, median NT-proBNP level was 1087 (535-1945) ng/L. After 12 weeks, change in mean PAP was -2.4 (95% CI -4.5 to -0.3) mmHg in patients who received sildenafil, vs. -4.7 (95% CI -7.1 to -2.3) mmHg in placebo patients (P = 0.14). Sildenafil did not have a favourable effect on PAWP, cardiac output, and peak VO2. Adverse events were overall comparable between groups.
  
  
  CONCLUSIONS
  Treatment with sildenafil did not reduce pulmonary artery pressures and did not improve other invasive haemodynamic or clinical parameters in our study population, characterized by HFpEF patients with predominantly isolated post-capillary pulmonary hypertension. (ClinicalTrials.gov, number NCT01726049).
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands e.s.hoendermis@umcg.nl.
authors.forename: Elke S
authors.initials: ES
authors.lastname: Hoendermis
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Licette C Y
authors.initials: LC
authors.lastname: Liu
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Yoran M
authors.initials: YM
authors.lastname: Hummel
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: Center for Congenital Heart Diseases, Department of Pediatric Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rolf M F
authors.initials: RM
authors.lastname: Berger
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
mesh_terms: D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate
keywords: Heart failure with preserved ejection fraction; Mean pulmonary artery pressure; Phosphodiesterase type 5 inhibition; Pulmonary hypertension; Sildenafil