Source:Apostolopoulou SC, Manginas A, Cokkinos DV, et al. Effect of the oral endothelin antagonist bosentan on the clinical, exercise, and haemodynamic status of patients with pulmonary arterial hypertension related to congenital heart disease.

Investigators from the Onassis Cardiac Surgery Centre in Athens, Greece report on 21 patients, aged 6 to 43 years (mean 22 years), with pulmonary arterial hypertension secondary to congenital heart disease who received investigational treatment with bosentan, an oral, nonselective endothelin receptor antagonist. Eighteen of the patients had unrepaired congenital cardiac lesions with unrestrictive communications between the systemic and pulmonary circulations. The other 3 had prior surgical repair of congenital cardiac disease but had chronic persistent pulmonary hypertension. This was a significantly symptomatic group before treatment: 76% were in WHO functional class III or IV, 100% had dyspnea on exertion, 71% were cyanotic at rest. In an open label, non-controlled study, patients received bosentan for 16 weeks. Results of cardiac catheterization, exercise testing, 6-minute walk test, resting pulse oximetry, and the Borg dyspnea index were determined at baseline and again after 16 weeks of therapy. Bosentan therapy was associated with a fall in pulmonary pressures and pulmonary vascular resistance, and an increase in pulmonary flow index. Along with these favorable hemodynamic changes, exercise tolerance increased and dyspnea decreased. There were 2 deaths during treatment, ultimately of unknown cause, but attributed by the investigators to possible arrhythmia. The authors conclude that there are favorable effects of endothelin receptor antagonism with bosentan in patients with Eisenmenger’s syndrome (a weakening of the right heart muscle due to pulmonary hypertension), and call for larger-scale studies capable of assessing the safety and efficacy of bosentan in this population.

Dr. Danford has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of a commercial product/device. This commentary does contain a discussion of an unapproved/investigative use of a commercial product/device.

Pulmonary vascular obstructive disease (PVOD) is a cause of serious morbidity and mortality for patients with unrepaired, nonrestrictive communications between systemic and pulmonary circulation.1 Efforts to prevent PVOD have focused intensely on early diagnosis and repair of the cardiac defects, but even today a small proportion of such patients either escape early detection, or fail to respond to timely repair with a fall in pulmonary vascular resistance. These patients tend to be severely and progressively symptomatic2 and have, until recently, responded poorly to medical measures offered to alleviate their symptoms and extend their lives. The authors present encouraging results suggesting that endothelin antagonism with bosentan may be effective in improving both the hemodynamics and the symptoms for patients with PVOD and congenital heart disease. For chronic use, oral administration of bosentan is a major advantage over one of the currently available alternatives, the intravenous infusion of prostacyclin. This small series included 2 deaths on therapy, but it was not primarily designed to assess the safety of bosentan management in this target population with Eisenmenger’s syndome. PVOD is...

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