title: The safety and effects of bosentan in patients with a Fontan circulation.
abstract: OBJECTIVE
  Adult patients with a Fontan circulation tend to have diminished exercise capacity. The principal objective of this study was to investigate the safety of the endothelin receptor antagonist bosentan in Fontan patients, and, secondarily, to assess effects on cardiovascular performance, New York Heart Association functional classification (NYHA FC), and ventricular function.
  
  
  METHODS
  A 6-month prospective, single-center, pilot, safety study of bosentan in Fontan patients. Setting.  Adult Congenital Heart Disease referral center.
  
  
  METHODS
  All patients ≥18 years old with a Fontan circulation and in NYHA FC ≥II were invited to enroll. Interventions.  Patients started on 62.5 mg bid of bosentan, uptitrating to 125 mg bid after 2 weeks.
  
  
  METHODS
  Safety was assessed by the incidence of anticipated and unanticipated adverse events during the 6-month study period; specifically those relating to hepatic, renal, or hematological dysfunction as measured by monthly blood tests. Other outcome measures included cardiopulmonary exercise test, 6-minute walk distance test, Borg dyspnea index, NYHA FC, and ventricular function parameters using transthoracic echocardiography.
  
  
  RESULTS
  Of the eight patients enrolled, six completed the study. Two patients withdrew from the study (one for non-trial related reasons, one due to adverse events). No clinically significant adverse events relating to bosentan therapy occurred during this study and, in particular, no significant abnormalities in hepatic function tests were observed. Three patients reported transient adverse events. Improvements in NYHA FC and systolic ventricular function were observed after 6 months of bosentan treatment.
  
  
  CONCLUSIONS
  The small number of patients with a Fontan circulation in our study was able to tolerate bosentan for 6 months. The safety and tolerability of bosentan in a larger patient population remains unknown. The results presented here justify further investigation in larger studies.
authors.affiliation: University Hospital Birmingham Foundation NHS Trust, Birmingham, United Kingdom.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Bowater
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Weaver
authors.forename: Sara A
authors.initials: SA
authors.lastname: Thorne
authors.forename: Paul F
authors.initials: PF
authors.lastname: Clift
mesh_terms: D000328:Adult; D000077300:Bosentan; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015150:Echocardiography, Doppler; D065128:Endothelin Receptor Antagonists; D004739:England; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D018729:Fontan Procedure / Q000009:adverse effects*; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011183:Postoperative Complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017466:Receptors, Endothelin / Q000378:metabolism; D020127:Recovery of Function; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D065128:Endothelin Receptor Antagonists; D017466:Receptors, Endothelin; D013449:Sulfonamides; D000077300:Bosentan