title: Adverse pulmonary vascular remodeling in the Fontan circulation.
abstract: BACKGROUND
  The Fontan circulation is a palliation for patients with a functionally univentricular heart. It is characterized by gradual attrition over time. An increase in pulmonary vascular resistance could be a key factor in the long-term failure of the Fontan circulation. In this study we aimed to identify pulmonary vascular remodeling in patients with a Fontan circulation.
  
  
  METHODS
  Pulmonary vascular histomorphometric analysis and immunohistochemistry were performed in lung tissue obtained at autopsy from 12 Fontan patients. These patients had died either peri-operatively (Group A: death during or <15 days after Fontan completion; n = 5) or in mid to long-term follow-up (Group B: death >5 years after Fontan completion; n = 7). Two age-matched control groups (n = 10 and n = 14, respectively) were included.
  
  
  RESULTS
  Intra-acinar pulmonary vessels in the Fontan Group B patients showed decreased medial thickness (p = 0.028) compared with age-matched controls, whereas intimal thickness was increased (p = 0.002). Intimal thickness in the Fontan Group B patients correlated with age at death (r = 0.964, p < 0.001) and with the length of time that the Fontan circulation had been in place (r = 0.714, p = 0.036). Immunohistochemistry revealed a reduction of vascular smooth muscles cells in the medial layer of the intra-acinar pulmonary vessels. The eccentric intimal thickening was composed of mainly acellular fibrosis with collagen deposition.
  
  
  CONCLUSIONS
  We observed a unique pattern of adverse pulmonary vascular remodeling in patients with a long-standing Fontan circulation who had died during follow-up. This remodeling pattern may play a major role in long-term attrition of the Fontan circulation.
authors: Department of Pediatric Cardiology, Beatrix Children's Hospital.
authors: Floris-Jan S
authors: FJ
authors: Ridderbos
authors: Department of Pediatric Cardiology, Beatrix Children's Hospital.
authors: Djoeke
authors: D
authors: Wolff
authors: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Albertus
authors: A
authors: Timmer
authors: Department of Cardiology.
authors: Joost P
authors: JP
authors: van Melle
authors: Department of Cardiothoracic Surgery, Center for Congenital Heart Diseases, University Medical Center Groningen.
authors: Tjark
authors: T
authors: Ebels
authors: Department of Pediatric Cardiology, Beatrix Children's Hospital.
authors: Michael G
authors: MG
authors: Dickinson
authors: Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Wim
authors: W
authors: Timens
authors: Department of Pediatric Cardiology, Beatrix Children's Hospital. Electronic address: r.m.f.berger@umcg.nl.
authors: Rolf M F
authors: RM
authors: Berger
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D018729:Fontan Procedure; D006330:Heart Defects, Congenital / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D066253:Vascular Remodeling; D014655:Vascular Resistance / Q000502:physiology*; D055815:Young Adult
keywords: Fontan operation; congenital heart disease; failing Fontan; pulmonary vascular remodeling; pulmonary vascular resistance; shear stress