Long-term effects of bosentan therapy in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical and haemodynamic impact.

Background: Oral bosentan is an established treatment for pulmonary arterial hypertension (PAH). Objective: The aim of the present study was to evaluate safety, tolerability, and clinical and haemodynamic impact of bosentan in patients with PAH related to congenital heart disease (CHD). Patients: Twenty-two patients with PAH CHD-related (8M, 14F, mean age 38±10) were treated with oral bosentan (62.5 mg x 2/die for the first month and then 125 mg x 2/die). Main outcome measures: clinical status, liver enzymes, WHO functional class, resting oxygen saturations and 6-min walk test (6MWT) were assessed at baseline and at 1, 3, 6 and 12 month. Haemodynamic evaluation with cardiac catheterization was performed at baseline and at 12-month follow-up. Results: Twelve patients had ventricular septal defect, 5 atrio-ventricular canal, 4 single ventricle and one atrial septal defect. All patients tolerated bosentan well. No major side effects were observed. After a year of therapy we observed an improvement in WHO functional class (2.5±0.7 vs 3.1±0.7; p<0.05), oxygen saturation at rest (87±6% vs 81±9; p<0.001), heart rate at rest (81±10 vs 87±14 bpm; p<0.05), distance travelled in the 6MWT (394±73 vs 320±108 m; p<0.001), oxygen saturation at the end of 6MWT (71±14 vs 63±17%; p<0.05), Borg’s index (5.3±1.8 vs 6.5±1.3; p<0.001), pulmonary vascular resistances index (PVRi: 14±9 vs 22±12 WU.m 2 ; p<0.001), systemic vascular resistances index (SVRi: 23±11 vs 27±10 WU.m 2 ; p<0.01), PVRi/SVRi (0.6±0.5 vs 0.9±0.6; p<0.05); pulmonary (