Sildenafil reduces pulmonary vascular resistance in single ventricular physiology

Int J Cardiol. 2016 Oct 15;221:122-7. doi: 10.1016/j.ijcard.2016.06.322. Epub 2016 Jul 2.

Abstract

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 (6MWT) 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±1.5WU to 2.1±0.6WU (p<0.01) in patients before a Glenn shunt, from 3.2±0.5WU to 1.6±0.6WU (p<0.001) in patients after a Glenn shunt, and from 3.9±1.7WU to 2.3±0.8WU (p<0.001) in patients after Fontan. In patients after Fontan, the 6MWT increased from 416±74m to 485±72m (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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Child, Preschool
  • Female
  • Fontan Procedure / adverse effects*
  • Fontan Procedure / methods
  • Heart Defects, Congenital* / diagnosis
  • Heart Defects, Congenital* / physiopathology
  • Heart Defects, Congenital* / surgery
  • Heart Ventricles* / abnormalities
  • Heart Ventricles* / physiopathology
  • Heart Ventricles* / surgery
  • Hemodynamics / drug effects*
  • Hemodynamics / physiology
  • Humans
  • Hypertension, Pulmonary* / etiology
  • Hypertension, Pulmonary* / physiopathology
  • Hypertension, Pulmonary* / prevention & control
  • Infant, Newborn
  • Japan
  • Male
  • Outcome and Process Assessment, Health Care
  • Phosphodiesterase 5 Inhibitors / administration & dosage
  • Phosphodiesterase 5 Inhibitors / adverse effects
  • Postoperative Complications* / physiopathology
  • Postoperative Complications* / prevention & control
  • Sildenafil Citrate* / administration & dosage
  • Sildenafil Citrate* / adverse effects
  • Vascular Resistance* / drug effects
  • Vascular Resistance* / physiology
  • Vasodilator Agents / administration & dosage
  • Vasodilator Agents / adverse effects

Substances

  • Phosphodiesterase 5 Inhibitors
  • Vasodilator Agents
  • Sildenafil Citrate