title: [The effect of an endothelin receptor antagonist in Eisenmenger syndrome: a single-center experience of 11 patients].
abstract: The Eisenmenger syndrome is a complication of congenital heart disease with significant left-to-right shunts, such as large ventricular septal defects, and corresponds to fixed pulmonary hypertension with shunt reversal. Bosentan, an inhibitor of endothelin A and B receptors, is a new molecule previously validated in the treatment of primary pulmonary hypertension. The authors report their monocentric experience of bosentan in 11 consecutive patients with the Eisenmenger syndrome treated for at least one year. This retrospective study comprised 7 females and 4 males with an average age of 34 years (range 17 to 51 years). The underlying lesion was ventricular septal defect (n = 4), atrial septal defect (n = 3), pulmonary atresia with septal defect (n = 4 of which 2 were treated palliatively). Before treatment, the patients were classified according to the NHYA functional class (I, II, IIIa and IIIb, IV or, respectively from 1 to 5) with a distribution in this series between Classes IIIa and IV (average 3.81 +/- 0.75) and from 3 to 10 on Borg's dyspnoea scale (average 6.54 +/- 2.29). The ambient oxygen saturation (SaO2) at rest was, on average 77 +/- 9%, the haemoglobin concentration 16.6 +/- 2.4 g/dl; hepatic transaminase levels were normal. The 6 minute walk test before treatment was 216 +/- 111 m with marked desaturation on exercise (49 +/- 18%). With Bosentan, patients were globally much better clinically with a decrease in dyspnoea, improvement in NHYA class and increased 6 minute walking perimeter. Improvement in NYHA class was observed from 3 months' treatment (3.0 +/- 0.8, p = 0.0002) and was sustained to one year (2.54 +/- 0.7, p< 0.001). An improvement of dyspnoea on Borg's scale was observed from the second month's treatment (5.56 +/- 1.65, p = 0.0201) and persisted throughout follow up to one year (3.81 +/- 1.32, p < 0.0001). Similarly, the 6 minute walking perimeter increased from the first control at 6 months (323 +/- 82 m, p < 0.0001) and at one year (322 +/- 62 m, p <0.0004). Finally, although a significant increase in SaO2 was observed at 6 months (p = 0.0032), this was hardly significant at one year (82 +/- 10 %, p = 0.0512). Transaminase levels did not rise significantly at the follow up visits (p = ns) and the haemoglobin concentration was unchanged. No patient died during the study period. This study showed a clear functional improvement in patients with Eisenmenger's syndrome treated with bosentan. The drug was well tolerated clinically with few adverse effects and a good safety margin of usage.
authors.affiliation: Service des malades cardiovasculaires infantiles et congénitales, Hôpital cardiologique, Université de Lille 2, CHRU Lille.
authors.forename: D
authors.initials: D
authors.lastname: Poindron
authors.forename: F
authors.initials: F
authors.lastname: Godart
authors.forename: A
authors.initials: A
authors.lastname: Duhamel
authors.forename: A
authors.initials: A
authors.lastname: Richard
authors.forename: C
authors.initials: C
authors.lastname: Francart
authors.forename: G M
authors.initials: GM
authors.lastname: Brevière
authors.forename: C
authors.initials: C
authors.lastname: Rey
mesh_terms: D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D004541:Eisenmenger Complex / Q000188:drug therapy* / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D016138:Walking
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan