title: Safety and tolerability of bosentan in adults with Eisenmenger physiology.
abstract: BACKGROUND
  Bosentan, a dual-endothelin receptor antagonist, is an established treatment for pulmonary arterial hypertension. We hypothesized that bosentan is safe and well tolerated in patients with Eisenmenger physiology.
  
  
  METHODS
  In this pilot open-label study, we primarily examined safety and tolerability of oral bosentan. Patients were recruited from our adult congenital heart clinic following informed consent. Baseline and 3-month assessment included WHO functional class, resting oxygen saturations, 6-min walk test, transthoracic echocardiography and respiratory mass spectrometry. Patient clinical status and liver enzymes were closely monitored throughout.
  
  
  RESULTS
  All 10 study patients (42+/-4 years; eight female) tolerated bosentan well. No major adverse events or significant liver enzyme elevations were observed. All but one patient felt better; none felt worse. Four patients experienced transient leg oedema. Resting oxygen saturations (83+/-5 versus 80+/-5%; P=0.011) and the distance travelled in the 6-min walk test (348+/-112 versus 249+/-117 m; P=0.004) increased relative to baseline. Changes in echocardiographic parameters (maximum aortic forward flow velocity 1.3+/-0.1 versus 1.1+/-0.2 ms, P=0.013; pulmonary arterial acceleration time 66+/-10 versus 58+/-12 m/s, P=0.02) and pulmonary blood flow (3.45+/-1.2 versus 2.58+/-1.0 L/min, P=0.008) suggested improved pulmonary haemodynamics by study end. Other echocardiographic changes suggested improved right ventricular systolic function (septal amplitude 1.0 versus 1.1 cm, P=0.048; systolic tissue Doppler velocity 4.8 versus 2.3 cm s(-1), P=0.002) by study end.
  
  
  CONCLUSIONS
  Bosentan was safe and well tolerated in adults with Eisenmenger physiology both at initiation and after 3 months of oral therapy. Clinical status of patients and pulmonary haemodynamics appeared to improve, and this warrants further investigation.
authors.affiliation: Adult Congenital Heart Program, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. m.gatzoulis@rbh.nthames.nhs.uk
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gatzoulis
authors.forename: Paula
authors.initials: P
authors.lastname: Rogers
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Carl
authors.initials: C
authors.lastname: Harries
authors.forename: Derek
authors.initials: D
authors.lastname: Cramer
authors.forename: Simon
authors.initials: S
authors.lastname: Ward
authors.forename: Ghada W
authors.initials: GW
authors.lastname: Mikhail
authors.forename: J Simon R
authors.initials: JS
authors.lastname: Gibbs
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D004541:Eisenmenger Complex / Q000188:drug therapy* / Q000503:physiopathology*; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008131:London; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D010865:Pilot Projects; D011652:Pulmonary Circulation / Q000187:drug effects; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome; D016278:Ventricular Function, Right / Q000187:drug effects; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan