A long term follow-up study of patients with mild to moderate group 2 pulmonary hypertension treated with Pde5-inhibition: a comparison between heart failure with reduced and preserved ejection fraction

Background: Single center studies suggest a remarkable effect of PDE5-inhibition on pulmonary hemodynamic and clinical status of heart failure patients with group 2 PH and both reduced (HFrEF) and preserved ejection fraction (HFpEF). We tested whether PDE5-inhibition treatment with sildenafil may have durable effects at long term observation (2 years) and whether LVEF makes a difference. Methods: According to a double-blind, placebo-controlled design, 84 stable and optimally treated HF patients with systolic (n= 54; NYHA Class II-III; average LVEF: 32±4%) and diastolic (n=30; NYHA Class II-III; average LVEF: 54±5%) were randomly assigned to receive placebo (50% in each group) or sildenafil (40 mg, 3 times/day) and were followed for up to 2 years. LVEF and pulmonary systolic pressure (PASP), peak oxygen consumption (VO2) and the minute ventilation-carbon dioxide production (VE/VCO2) slope were assessed at 6, 12, 18 and 24 months. Results: During the follow-up, 6 HFrEF patients needed hospitalization (4 in the placebo and 2 in the sildenafil group) for acute decompensated HF while 3 HFrEF patients (all in the placebo group) were hospitalized for atrial arrhythmias (2) and decompensated HF (1). Baseline LVEF and peak VO2 differed in both sildenafil and placebo arms of each group. In the sildenafil arm, PASP and VE/VCO2 slope reduced and peak VO2 increased significantly in both HFrEF and HFpEF at each follow-up period. LVEF increased significantly just in HFrEF. Percent changes in PASP and VE/VCO2 slope in HFpEF group exceeded those in HFrEF (table). Conclusions: In optimally treated HFrEF and HFpEF patients with mild to moderate group 2 PH, PDE5 inhibition is persistently effective in improving PASP, exercise performance and ventilatory efficiency. Benefits seem to be greater in HFpEF, and PASP rather than LVEF seems to be involved in these effects. These findings warrant a morbidity/mortality trial for assessment of PDE5 inhibition in larger HF populations.