Aims: 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.
Methods and results: 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.
Conclusion: 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.
Keywords: Heart failure with preserved ejection fraction; Pulmonary hypertension; Sildenafil.
© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.