Acute effects of 50 mg additive oral sildenafil on invasive exercise haemodynamics in pulmonary vascular disease

Background and aims Patients with precapillary pulmonary hypertension (PH) due to pulmonary vascular disease (PVD) have reduced exercise capacity, limiting daily activity and quality of life. Phospodiesterase-5 inhibitors, including sildenafil, are used to treat PVD. This study examined effects of sildenafil on pulmonary haemodynamics during exercise in PVD. Method PVD patients diagnosed with pulmonary arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH) underwent right heart catheterisation assessed at rest and during mild exercise. Main outcomes were mean pulmonary artery pressure (mPAP), cardiac output (CO) and the mPAP/CO slope before and ∼60 min after additive sildenafil (50 mg oral). Results 22 PVD patients (14 PAH, 8 CTEPH, 9 women and 15 pretreated (9 combination therapy)) with a mean±sd age of 54±14 years, mPAP 39±10 mmHg, CO 4.7±1.5 L·min$^{−1}$ and pulmonary vascular resistance 6.9±3.8 WU were included. After sildenafil, mPAP and CO at rest were unchanged, but at end-exercise, mPAP and the mPAP/CO slope significantly decreased (mPAP 61±16 versus 54±16 mmHg; mean difference −7, 95% confidence interval (CI) −11 to −4; p<0.001 and mPAP/CO slope 9.8±4.9 versus 6.6±3.3; −3, 95% CI −4.9 to −1.2; p=0.002). The mean systemic arterial pressure was significantly lower after additive sildenafil at rest (−9 mmHg, −13 to −5; p<0.001) and at end-exercise (−9 mmHg, −13 to −5; p<0.001). One patient experienced dizziness. Conclusions Patients with PVD, showed favourable acute pulmonary haemodynamic changes during exercise after additive sildenafil, indicated by a reduced mPAP and mPAP/CO slope. Sildenafil was generally well tolerated despite lower blood pressure. Further investigation is needed to determine if sildenafil as a “pill-in-the-pocket” strategy improves exercise capacity in PVD patients.