To evaluate safety, tolerability, clinical and haemodynamic impact of bosentan, an orally administered endothelin-1 antagonist, in patients with pulmonary hypertension due to congenital heart disease (Eisenmenger syndrome).
Twelve patients with ES (5M, 7F, mean age 33.6±8.7) were treated with oral bosentan (62.5 mg x 2/die for the first month and then 125 mg x 2/die). Patient clinical status, liver enzymes, WHO functional class, resting oxygen saturations, 6 min walk test and transthoracic echocardiography were assessed at baseline and at 1, 3 and 6 month. Haemodynamic evaluation with cardiac catheterization was performed at baseline and at 6 month follow-up.
At baseline 10 patients were in III and 2 in IV WHO functional class. Six had ventricular septal defect, 3 single ventricle, 2 atrio-ventricular canal, 1 truncus arteriosus. All 12 patients well tolerated bosentan, but in 2 patients we reduced the maintenance dose from 125 mg x 2/die to 62.5 mg x 2/die for a transient elevation of liver enzyme (1 patient) and transient leg oedema (1 patient). After six month therapy, oxygen saturation at rest (78.3±9.3% vs 85.8±5.6%; p<0.05) and after 6-min walk test (64.4±8.8% vs 73.5±12%; p<0.05), the distance travelled in the 6-min walk test (321±101 vs 445±45 m; p<0.05) and Borg’s index (5,9±1.4 vs 3±2.3; p<0.05) significantly improved. A significant change of total pulmonary indexed resistances (19.1±9.5 vs 9.3±5.3 WU, p<0.05), arterial pulmonary indexed resistances (15.2±7.2 vs 7.62±4.7 WU, p<0.05) and systemic-to-pulmonary blood flow ratio (0.74±0.34 vs 1.36±1.14, P<0.05) was observed suggesting an improvement of pulmonary haemodynamics. At six month follow-up 5 patients were in II, 6 in III and 1 in IV WHO functional class.
Bosentan treatment was safe and well tolerated in adults with ES after a mid-term follow-up (6 months of oral therapy). Oxygenation, functional status and pulmonary haemodynamics of patients improved with minimal side effects.
Bosentan is useful in the management of the Eisenmenger syndrome in adults but larger clinical investigation are necessary.
Michele D’Alto, None.