Effect of sildenafil on resting and exercise hemodynamics in hypoxia in patients with pulmonary vascular diseases: data from a randomized controlled trial

Background and aims Exercise capacity is limited in patients with pulmonary vascular disease (PVD) exposed to high altitude. The PVD-drug sildenafil, a phospodiesterase-5 inhibitor, has improved exercise capacity and hemodynamics in healthy exposed to hypoxia. This study examined effects of additive sildenafil on pulmonary hemodynamics during rest and exercise in PVD exposed to normobaric hypoxia. Method PVD-patients diagnosed as pulmonary arterial or chronic thromboembolic pulmonary hypertension underwent right heart catheterization assessed at rest and during mild exercise while breathing hypoxic air (FiO2 15%) in a sequence-randomized crossover design. Main outcomes were mean pulmonary artery pressure (mPAP), cardiac output (CO) and mPAP/CO-slope before and ∼60 min after additive sildenafil (50 mg oral). Results 22 patients were included, 64% had PAH and 36% CTEPH; 41% were female with mean± sd age 54±14 y, and a BMI of 26.3±4.0 kg·m −2 . 73% received PH targeted therapy and 56% were on double or triple combination therapy. MPAP remained unchanged at rest, while it was significantly lower at end-exercise compared to the values without sildenafil. The mPAP/CO slope during exercise in hypoxia was reduced with additive sildenafil from 9.9±5.1 to 8.2±4.1 mmHg (mean difference (95% CI) of −1.9 (−3.8 to −0.1) mmHg, p=0.043). Conclusions In PVD patients exposed to normobaric hypoxia, additional 50 mg of oral sildenafil improves exercise pulmonary hemodynamics. Whether the improved hemodynamics would translate into better tolerance or an enhancement in exercise capacity during hypoxia exposure needs to be studied further.