Sildenafil reduces pulmonary vascular resistance in single ventricular physiology

Background High pulmonary vascular resistance (PVR) may be a risk factor for early and late mortality in both Glen shunt and Fontan operation patients. Furthermore, PVR may increase long after the Fontan operation. Whether pulmonary vasodilators such as phosphodiesterase 5 inhibitors can decrease PVR in patients with single ventricular physiology remains undetermined. Methods and results This was a prospective, multicenter study. Patients with single ventricular physiology who have a PVR index higher than 2.5 Wood units·㎡ (WU) were enrolled. Cardiac catheterization was performed before and after administration of sildenafil in all patients. After the Fontan operation, a six minute walk test (6 MWT) was also performed. A total of 42 patients were enrolled. PVR was significantly decreased in each stage of single ventricular physiology after sildenafil administration: from 4.3 ± 1.5 WU to 2.1 ± 0.6 WU (p < 0.01) in patients before a Glenn shunt, from 3.2 ± 0.5 WU to 1.6 ± 0.6 WU (p < 0.001) in patients after a Glenn shunt, and from 3.9 ± 1.7 WU to 2.3 ± 0.8 WU (p < 0.001) in patients after Fontan. In patients after Fontan, the 6 MWT increased from 416 ± 74 m to 485 ± 72 m (p < 0.01), and NYHA functional class improved significantly (p < 0.05) after sildenafil administration. No major side effects were observed in any patients. Conclusions Sildenafil reduced PVR in patients with single ventricle physiology. Sildenafil increased exercise capacity and improved NYHA functional class in patients after a Fontan operation. This implies that pulmonary vasodilation is a potential therapeutic target in selected patients with elevated PVR with single ventricle physiology. Long-term clinical significance warrants further study.