Elsevier

American Heart Journal

Volume 154, Issue 4, October 2007, Pages 776-782
American Heart Journal

Clinical Investigations
Pediatrics
Long-term effect of bosentan in adults versus children with pulmonary arterial hypertension associated with systemic-to-pulmonary shunt: Does the beneficial effect persist?

https://doi.org/10.1016/j.ahj.2007.06.003Get rights and content

Background

Data on long-term response to bosentan in adults and especially children with pulmonary arterial hypertension (PAH) associated with systemic-to-pulmonary shunt are scarce.

Methods

We studied bosentan efficacy in 30 patients (20 adults, 10 children) with the disease at short- (4 months), and long-term follow-up (through 2.7 years). World Health Organization functional class (WHO class), transcutaneous oxygen saturation, and 6-minute walk distance were assessed at baseline, 4 months, 1 year, 1.5 years, and at latest follow-up (median 2.7 years).

Results

At baseline, children tended to have more severe disease compared with adults with regard to WHO class and congenital heart defects. At 4 months' follow-up, WHO class and 6-minute walk distance significantly improved in both adults and children. During long-term follow-up, this improvement persisted through 1 year but declined thereafter in the total group. In the children, a progressive decline in exercise capacity was observed from 1-year follow-up, whereas in the adults, improvement lasted longer. No change from baseline was seen in transcutaneous oxygen saturation. Three (10%) patients died, 2 (7%) discontinued bosentan, and 5 (17%) required additional PAH therapy (of whom 1 eventually died). One- and 2-year persistence of beneficial bosentan effect was 68% and 43% (total group), 78% and 57% (adults), and 50% and 20% (children), respectively.

Conclusions

Our experience with bosentan suggests short-term improvement in both adults and children with PAH associated with systemic-to-pulmonary shunt. At long-term follow-up, a progressive decline in beneficial bosentan effect was observed. The decline appeared most pronounced in the pediatric patients, who, in this study, tended to have more severe disease at baseline.

Section snippets

Patients

Between November 2002 and February 2007, a cohort of 30 patients (20 adults, 10 children) with PAH associated with congenital or surgically created systemic-to-pulmonary shunt and treated with bosentan (Tracleer, Actelion Pharmaceuticals, Allschwill, Switzerland) had standardized follow-up at 2 Dutch tertiary medical referral centers for pulmonary hypertension. Eight patients included in the series initially received bosentan as part of a clinical trial.11 All patients or patients'

Patients

Baseline characteristics are summarized in Table 1. Ventricular septal defect (VSD) was the most common heart defect (53%) and was frequently associated with additional shunt defects, such as atrial septal defect (ASD) and persistent ductus arteriosus. An isolated ASD was seen in 19% of all patients, all of whom were adults. Twenty-six (87%) patients had classic Eisenmenger syndrome, 6 of these with a shunt before and 20 after the level of the tricuspid valve. The remaining 4 patients had

Discussion

This study, to our knowledge, is the first to report long-term response to bosentan through 2.7 years of follow-up in both adults and children with PAH associated with systemic-to-pulmonary shunt. Our results demonstrate short-term improvement in functional class and exercise capacity in both patient groups, which is in congruence with previous reports.11, 20 During longer follow-up, improvement in 6MWD, the major outcome parameter in PAH studies, persisted up to 1 year but declined thereafter.

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    A. Vonk-Noordegraaf, B.J.M. Mulder, and R.M.F. Berger have received lecture fees and/or grant support from Actelion Pharmaceuticals Ltd, Allschwill, Switzerland. R.L.E. van Loon, E.S. Hoendermis, M.G.J. Duffels, and H.L. Hillege have no conflicts of interest to disclose.

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