Bosentan-sildenafil association in patients with congenital heart disease-related pulmonary arterial hypertension and Eisenmenger physiology

Objectives: The aim of the present study was to evaluate the safety, tolerability, clinical and haemodynamic impact of add-on sildenafil in patients with congenital heart disease (CHD)-related pulmonary arterial hypertension (PAH) and Eisenmenger physiology after failure of oral bosentan therapy. Methods: Thirty-two patients with CHD-related PAH (14 male, mean age 37.1 +/- 13.7 years) treated with oral bosentan underwent right heart catheterization (RHC) for clinical worsening. After RHC, all patients received oral sildenafil 20 mg thrice daily in addition to bosentan. Clinical status, resting transcutaneous oxygen saturation (SpO(2)), 6-minute walk test (6MWT), serology and RHC were assessed at baseline (before add-on sildenafil) and after 6 months of combination therapy. Results: Twelve patients had ventricular septal defect, 8 atrio-ventricular canal, 6 single ventricle, and 6 atrial septal defect. Twenty-eight/32 had Eisenmenger physiology and 4 (all with atrial septal defect) did not. All patients well tolerated combination therapy. After 6 months of therapy, an improvement in clinical status (WHO functional class 2.1 +/- 0.4 vs 2.9 +/- 0.3; P=0.042), 6-minute walk distance (360 +/- 51 vs 293 +/- 68 m; P=0.005), SpO(2) at the end of the 6MWT (72 +/- 10 vs 63 +/- 15%; P=0.047), Borg score (2.9 +/- 1.5 vs 4.4 +/- 2.3; P=0.036), serology (pro-brain natriuretic peptide 303 +/- 366 vs 760 +/- 943 pg/ml; P=0.008) and haemodynamics (pulmonary blood flow 3.4 +/- 1.0 vs 3.1 +/- 1.2 l/min/m(2), P=0.002; pulmonary vascular resistances index 19 +/- 9 vs 24 +/- 16 WU/m(2), P=0.003) was observed. Conclusions: Addition of sildenafil in adult patients with CHD-related PAH and Eisenmenger syndrome after oral bosentan therapy failure is safe and well tolerated at 6-month follow-up, resulting in a significant improvement in clinical status, effort SpO(2), exercise tolerance and haemodynamics. (C) 2010 Elsevier Ireland Ltd. All rights reserved.