endothelin-1 and Eisenmenger-Complex

Differences in clinical effects between selective and dual endothelin (ET) receptor antagonists (ERA) in patients with pulmonary arterial hypertension (PAH) are currently unknown. We aimed to assess prospectively how transition from selective (sitaxsentan) to dual (bosentan) ERA affected exercise capacity and cardiocirculatory performance in patients with Eisenmenger's syndrome.. A series of seven stable patients with Eisenmenger's syndrome aged 40.0 (30.0-56.0) years old treated with sitaxsentan were assessed before and three months after transition to bosentan. Six minute walk test and magnetic resonance to assess LV and RV mass, volume and ejection fraction, and pulmonary flow, and laboratory tests were performed.. We observed an increase in LV mass [96.5 (66.0-116.0) vs. 123.0 (93.0-146.0)g; p=0.03], LV ejection fraction [55.0 (44.0-63.0) vs. 65.0 (58.0-70.0)%; p=0.02)], and pulmonary flow [64 (53.0-71.0) vs. 69.0 (55.0-84.0)ml/beat; p=0.046]. This was accompanied by an increase of oxygen saturation, elongation of 6MWD [435.0 (378.0-482.3) vs. 474 (405.0-534.7); p=0.02], decrease of NTproBNP level and increase of ET-1 level.. Three month follow-up of stable patients with Eisenmenger's syndrome transitioned from sitaxsentan to bosentan revealed improvement of exercise capacity despite significant elevation of ET-1 level. Concurrent increase of LV ejection fraction and pulmonary flow might have contributed to these favourable effects.

Topics: Adult; Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin Receptor Antagonists; Endothelin-1; Exercise; Female; Follow-Up Studies; Humans; Isoxazoles; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Sulfonamides; Thiophenes

Topics: Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin-1; Humans; Sulfonamides; Tetralogy of Fallot

Bosentan, an endothelin-1 antagonist that can be administered orally, has been shown to be effective in the treatment of idiopathic pulmonary arterial hypertension and may be of benefit to patients with the Eisenmenger syndrome. Nine patients with Eisenmenger's syndrome were treated with bosentan at a dose of 125 mg twice a day. After treatment with bosentan, 6 of 9 patients (67%) had an improvement in New York Heart Assocation classification of >/=1 grades (p = 0.03). Oxygen saturation levels increased from 79 +/- 5% to 88 +/- 6%, (p = 0.03). The side effects of bosentan therapy were minor; no significant changes in liver function tests were noted. These preliminary data suggest that oral administration of bosentan therapy for Eisenmenger's syndrome results in improved oxygenation and functional status with minimal side effects.

Topics: Adult; Aged; Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin-1; Female; Humans; Male; Middle Aged; Retrospective Studies; Sulfonamides