Long-term effect of bosentan in pulmonary hypertension associated with complex congenital heart disease.
BACKGROUND
Bosentan is recommended for symptomatic patients with Eisenmenger syndrome due to simple congenital lesions such as atrial and ventricular septal defects (VSD). However, its long-term efficacy and safety in patients with pulmonary arterial hypertension (PAH) associated with complex congenital heart disease (CHD) is unknown.


OBJECTIVE
We examined the short- and long-term effects and safety profile of bosentan in patients with PAH and complex CHD.


METHODS
We followed 14 patients with PAH and complex CHD for a mean of four years. Demographic parameters, exercise capacity assessed by the six-minute walking test (6MWT) and oxygen saturation were assessed at baseline, six months and at follow-up.


RESULTS
Mean age was 37.1 ± 11.7 years; 90% were in WHO class III or IV. The most common diagnosis was pulmonary atresia with VSD (35.7%), followed by truncus arteriosus (28.6%), patent ductus arteriosus (21.4%) and transposition of the great arteries (14.3%). After six months of treatment, six-minute walking distance (6MWD) increased from 371.9 to 428.4 m (p=0.005) and functional class was improved (p=0.005). After four years, one patient discontinued bosentan due to side effects and four patients were started on sildenafil, after a mean 38 months of bosentan treatment. Mean 6MWD for patients on bosentan monotherapy (n=8) was 440.1 ± 103.8 m, whereas for patients on bosentan-sildenafil combination therapy (n=4) it was 428.8 ± 96.9 m, after four years of therapy. Two patients died during follow-up.


CONCLUSIONS
Bosentan was safe and was associated with improved exercise capacity in patients with PAH and complex CHD. This improvement was sustained for up to four years and the safety profile was similar to simple CHD patients.
Unidade de Hipertensão Pulmonar, Serviço de Cardiologia, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. ruibaptista@gmail.com
Rui
R
Baptista
Graça
G
Castro
António Marinho
AM
da Silva
Pedro
P
Monteiro
Luís Augusto
LA
Providência
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000150:complications; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D008297:Male; D011446:Prospective Studies; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan