title: Effects of sildenafil on cardiac structure and function, cardiopulmonary exercise testing and health-related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension.
abstract: We recently showed that sildenafil did not improve pulmonary pressures and exercise capacity in a cohort of patients with heart failure and preserved ejection fraction (HFpEF) and predominantly postcapillary pulmonary hypertension. Here, we present the effects of sildenafil on cardiac structure and function, cardiopulmonary exercise testing, laboratory parameters and health-related quality of life measures.
  
  
  
  Fifty-two HFpEF patients with pulmonary hypertension (mean pulmonary artery pressure >25 mmHg; pulmonary artery wedge pressure >15 mmHg) were randomized to sildenafil 60 mg three times a day or placebo and treated for 12 weeks. Sildenafil neither changed cardiac structure nor function on echocardiography compared with placebo. Considering all patients irrespective of maximal effort, sildenafil reduced peak heart rate by 8 b.p.m. [95% confidence interval (CI) -14.97 to -1.03] and peak blood pressure by 13.8 mmHg (95% CI -22.04 to -5.47)/7.3 mmHg (95% CI -13.60 to -1.07) (both P < 0.05 vs. placebo). The minute ventilation/carbon dioxide production (VE/VCO2) slope remained unchanged in the sildenafil group (0.3, 95% CI -1.37-1.98), while it was reduced in the placebo group (-7.6, 95% CI -12.97 to -2.25, P = 0.002). In both groups, renal function improved and N-terminal pro-brain natriuretic peptide concentration reduced equally. Haemoglobin and glycated haemoglobin levels slightly decreased in the sildenafil group (P < 0.05 vs. placebo). All domains of the Kansas City Cardiomyopathy Questionnaire increased during treatment, but no differences between sildenafil and placebo were found.
  
  
  
  Treatment with sildenafil for 12 weeks in patients with HFpEF and predominantly isolated postcapillary pulmonary hypertension did not affect cardiac structure and function, integrative exercise responses, laboratory parameters, and/or quality of life. Clinicaltrials.gov number NCT01726049.
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
authors.forename: Licette C Y
authors.initials: LC
authors.lastname: Liu
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
authors.forename: Yoran M
authors.initials: YM
authors.lastname: Hummel
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van der Meer
authors.affiliation: Department of Pediatric and Congenital Cardiology, University of Groningen, University Medical Centre 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 Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
authors.forename: Kevin
authors.initials: K
authors.lastname: Damman
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Voors
authors.affiliation: Department of Cardiology, University of Groningen, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
authors.forename: Elke S
authors.initials: ES
authors.lastname: Hoendermis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D006328:Cardiac Catheterization; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006304:Health Status; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure; D011788:Quality of Life; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D013318:Stroke Volume; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D006454:Hemoglobins; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate; C517652:hemoglobin A1c protein, human; C109794:pro-brain natriuretic peptide (1-76)
keywords: Heart failure with preserved ejection fraction; Pulmonary hypertension; Sildenafil