Chest
Volume 129, Issue 4, April 2006, Pages 1009-1015
Journal home page for Chest

Original Research
Efficacy of Bosentan in a Small Cohort of Adult Patients With Pulmonary Arterial Hypertension Related to Congenital Heart Disease

https://doi.org/10.1378/chest.129.4.1009Get rights and content

Objectives

This study was designed to assess the tolerability and efficacy of the oral endothelin receptor antagonist bosentan in adult patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD).

Background

Severe PAH in the setting of CHD is a debilitating syndrome for which there are limited treatment options. This is the first long-term study experience in adults reporting on the tolerability and efficacy of therapy with bosentan for this patient population.

Methods

A 12-month single-center experience with 19 women and 5 men with PAH associated with CHD (79% in New York Heart Association [NYHA] class III) was analyzed. Hemodynamic responses, exercise capacity, and Borg dyspnea index were assessed prior to the administration of bosentan, and again at 3, 6, and 12 months after the study began. Clinical assessments were performed monthly for up to 12 months. The change from baseline was tested using the Wilcoxon pairs test.

Results

There was significant improvement in hemodynamics from baseline to 12 months (mean [± SD] systolic pulmonary arterial pressure, 99 ± 30 to 87 ± 28 mm Hg [p ≤ 0.001]; mean pulmonary arterial pressure, 60 ± 18 to 52 ± 17 mm Hg [p ≤ 0.001]; mean right atrial pressure, 12 ± 6 to 8 ± 5 mm Hg [p ≤ 0.001]; mean pulmonary vascular resistance, 663 ± 386 to 504 ± 307 dyne · s · cm−5 [p < 0.01]; pulmonary capillary wedge pressure, 15 ± 5 to 11 ± 3 mm Hg [p < 0.001]). NYHA functional class also improved from baseline to 12 months (NYHA class I/II range, 17 to 71%; p < 0.001). There was a marginally significant trend toward improvement in the mean 6-min walk test distance at 12 months (299 ± 85 to 330 ± 95 m; p = 0.05). Three patients needed to discontinue bosentan therapy because of elevated liver function test results. There were no deaths or hospitalizations, and no significant change in arterial oxygen saturation had occurred at 12 months.

Conclusions

Bosentan therapy improved hemodynamics and NYHA class in patients with PAH that was associated with CHD. These effects were seen after 3 to 6 months. Bosentan therapy may provide an effective alternative to current therapies in this patient population.

Section snippets

Materials and Methods

All patients described in this study were followed up in the Pulmonary Vascular Disease Clinic at the University of Alabama at Birmingham and have received a diagnosis of PAH associated with CHD. This diagnosis was made utilizing World Health Organization criteria after an extensive search for other secondary causes for pulmonary hypertension. Adult patients currently receiving either epoprostenol or treprostinil were considered to be eligible for treatment if they were persistently classified

Patient Disposition

Twenty-four adults (19 female, 5 male; mean age, 50 ± 13 years) with primary pulmonary hypertension and other forms of PAH were started on therapy with bosentan. At the start of the study, all participants were in NYHA functional classes II through IV, with a majority (79%) in class III. Eight patients (33%) were being treated with a prostacyclin analog, treprostinil (mean dose, 28.4 ng/kg/min) for a mean duration of 864 ± 317 days. No patients were treated with epoprostenol during the course

Discussion

The functional morbidity associated with severe PAH in patients with CHD, particularly those with Eisenmenger syndrome is considerable. Although the associated mortality is not as high as in other forms of PAH, it is noteworthy. Until recently, lung or heart-lung transplantation was the only hope for improved functional capacity and longer survival time in those patients with end-stage disease. Unfortunately, these forms of transplantation are associated with considerable morbidity and

Acknowledgment

The authors would like to acknowledge the useful and invaluable insights, comments, and suggestions along with the other contributions made by Mark Law, MD, and Krys L. Thomas, RN, BSN.

References (38)

Cited by (0)

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

This work was not supported by any external funding.

View full text