title: Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect.
abstract: BACKGROUND
  Oral bosentan is an established treatment for pulmonary arterial hypertension (PAH).
  
  
  OBJECTIVE
  To evaluate safety, tolerability, and clinical and haemodynamic effects of bosentan in patients with PAH related to congenital heart disease (CHD).
  
  
  METHODS
  22 patients with CHD related PAH (8 men, 14 women, mean (SD) age 38 (10) years) were treated with oral bosentan (62.5 mg x 2/day for the first 4 weeks and then 125 mg x 2/day).
  
  
  METHODS
  Clinical status, liver enzymes, World Health Organisation (WHO) functional class, resting oxygen saturations and 6-min walk test (6MWT) were assessed at baseline and at 1, 3, 6, and 12 months. Haemodynamic evaluation with cardiac catheterisation was performed at baseline and at 12 month follow-up.
  
  
  RESULTS
  12 patients had ventricular septal defect, 5 atrioventricular canal, 4 single ventricle, and 1 atrial septal defect. All patients tolerated bosentan well. No major side effects were seen. After a year of treatment, an improvement was seen in WHO functional class (2.5 (0.7) v 3.1 (0.7); p<0.05), oxygen saturation at rest (87 (6%) v 81 (9); p<0.001), heart rate at rest (81 (10) v 87 (14) bpm; p<0.05), distance travelled in the 6MWT (394 (73) v 320 (108) m; p<0.001), oxygen saturation at the end of the 6MWT (71 (14) v 63 (17%); p<0.05), Borg index (5.3 (1.8) v 6.5 (1.3); p<0.001), pulmonary vascular resistances index (14 (9) v 22 (12) WU m(2); p<0.001), systemic vascular resistances index (23 (11) v 27 (10) WU.m(2); p<0.01), pulmonary vascular resistances index/systemic vascular resistances index (0.6 (0.5) v 0.9 (0.6); p<0.05); pulmonary (4.0 (1.3) v 2.8 (0.9) l/min/m2; p<0.001) and systemic cardiac output (4.2 (1.4) v 3.4 (1.1) l/min/m2; p<0.05).
  
  
  CONCLUSIONS
  Bosentan was safe and well tolerated in adults with CHD related PAH during 12 months of treatment. Clinical status, exercise tolerance, and pulmonary haemodynamics improved considerably.
authors.affiliation: Second University of Naples, A O Monaldi, Naples, Italy. mic.dalto@tin.it
authors.forename: M
authors.initials: M
authors.lastname: D'Alto
authors.forename: C D
authors.initials: CD
authors.lastname: Vizza
authors.forename: E
authors.initials: E
authors.lastname: Romeo
authors.forename: R
authors.initials: R
authors.lastname: Badagliacca
authors.forename: G
authors.initials: G
authors.lastname: Santoro
authors.forename: R
authors.initials: R
authors.lastname: Poscia
authors.forename: B
authors.initials: B
authors.lastname: Sarubbi
authors.forename: M
authors.initials: M
authors.lastname: Mancone
authors.forename: P
authors.initials: P
authors.lastname: Argiento
authors.forename: F
authors.initials: F
authors.lastname: Ferrante
authors.forename: M G
authors.initials: MG
authors.lastname: Russo
authors.forename: F
authors.initials: F
authors.lastname: Fedele
authors.forename: R
authors.initials: R
authors.lastname: Calabrò
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077300:Bosentan; D004305:Dose-Response Relationship, Drug; D004541:Eisenmenger Complex / Q000150:complications*; D017079:Exercise Tolerance; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008134:Long-Term Care; D008297:Male; D010101:Oxygen Consumption; D011446:Prospective Studies; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan