title: Drug therapy in the prevention of failure of the Fontan circulation: a systematic review.
abstract: BACKGROUND
  The Fontan circulation is the optimal treatment for patients with univentricular hearts. These patients are at high risk of circulatory failure. There is no consensus on the optimal drug treatment for the prevention of failure of the Fontan circulation. The aim of this systematic review was to provide an overview of evidence for drug therapy used in the prevention of Fontan circulatory failure.
  
  
  METHODS
  We searched the Embase database for articles that reported drug therapy in Fontan patients. Studies published between 1997 and 2014 were included if efficacy or safety of medication was assessed, drug therapy aimed to prevent or treat failure of the Fontan circulation, and if the full text was available. Case reports were excluded.
  
  
  RESULTS
  A total of nine studies were included with a total of 267 Fontan patients; four studies evaluated the medication sildenafil, one iloprost, three bosentan, and one enalapril. Among all, two sildenafil studies reported improvement in exercise capacity, one in exercise haemodynamics, and one in ventricular performance. In the largest study of bosentan, an increase in exercise capacity was found. Enalapril did not result in improvements.
  
  
  CONCLUSIONS
  The studies analysed in this review suggest that bosentan, sildenafil, and iloprost may improve exercise capacity at the short term. Given the limitations of the studies, more, larger, placebo-controlled studies with longer follow-up periods are needed to better understand which drug therapies are effective in the prevention of failure of the Fontan circulation.
authors.affiliation: 1Department of Pediatrics,Division of Pediatric Cardiology,Erasmus University Medical Center,Sophia Children's Hospital,Rotterdam,The Netherlands.
authors.forename: Nathalie J
authors.initials: NJ
authors.lastname: Oldenburger
authors.affiliation: 1Department of Pediatrics,Division of Pediatric Cardiology,Erasmus University Medical Center,Sophia Children's Hospital,Rotterdam,The Netherlands.
authors.forename: Arenda
authors.initials: A
authors.lastname: Mank
authors.affiliation: 2Department of Cardiothoracic Surgery,Erasmus University Medical Center,Rotterdam,The Netherlands.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Etnel
authors.affiliation: 2Department of Cardiothoracic Surgery,Erasmus University Medical Center,Rotterdam,The Netherlands.
authors.forename: Johanna J M
authors.initials: JJ
authors.lastname: Takkenberg
authors.affiliation: 1Department of Pediatrics,Division of Pediatric Cardiology,Erasmus University Medical Center,Sophia Children's Hospital,Rotterdam,The Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Helbing
mesh_terms: D000077300:Bosentan; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D018729:Fontan Procedure / Q000009:adverse effects*; D006330:Heart Defects, Congenital / Q000601:surgery; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000068677:Sildenafil Citrate / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D016285:Iloprost; D000077300:Bosentan
keywords: Fontan circulation; bosentan; drug therapy; enalapril; sildenafil