Acute effects of sildenafil on exercise hemodynamics in patients with pulmonary vascular disease: The HEXA RCT series

<bold>Introduction:</bold> Patients with precapillary pulmonary hypertension (PH) due to pulmonary vascular disease (PVD) have reduced exercise capacity, which limits daily activity and quality of life. Phospodiesterase-5 inhibitors (PDE5-i) including sildenafil are widely used as therapy for PVD due to their pulmonary vasodilator effect. We studied whether an additional dose of sildenafil would have beneficial effects on invasively measured pulmonary hemodynamics during low-intensity exercise in PVD. <bold>Method:</bold> PVD-patients scheduled for clinically indicated right heart catheterization were investigated in semi-supine position (45°) at and exposed to cycling exercise at 10-20 and 20-30 Watts for two 3min steps once before and 40-70 min after 50mg oral sildenafil. Main hemodynamic parameters assessed at rest and the end of each step were mean pulmonary arterial pressure (mPAP), cardiac output (CO, assessed by direct Fick method and mPAP/CO slope. <bold>Results:</bold> 23 PVD-patients (15 PAH, 8 distal CTEPH, 10 women, 16 prevalent/pretreated) with a mean±SD age 53±15 years, mPAP 40±11 mmHg, pulmonary vascular resistance 6.0±2.7 WU were included. <bold>Conclusions:</bold> Patients with PVD, the majority pretreated, reveal favorable acute hemodynamic changes during exercise after 50mg sildenafil reflected by a reduced mPAP and mPAP/CO slope. The relatively high dose of sildenafil was safe as it was well tolerated despite the mild reduction of systemic blood pressure. Whether an additive dose of sildenafil 50mg in a “pill in the pocket” concept would improve exercise capacity remains to be investigated.