title: Ventricular fibrogenesis activity assessed by serum levels of procollagen type III N-terminal amino peptide during the staged Fontan procedure.
abstract: OBJECTIVE
  We tested the hypotheses that volume overload and cyanosis observed in the pre-Fontan single ventricular circulation are associated with increased ventricular fibrogenesis, that the Fontan procedure helps to reduce fibrogenesis, and that persistently increased fibrogenesis in the Fontan ventricle is associated with ventricular diastolic dysfunction.
  
  
  METHODS
  Levels of serum amino-terminal procollagen type III, a marker of tissue fibrogenesis, were measured in 172 patients with single ventricle circulation and 149 controls. Patients were divided into 3 groups according to surgical stage: 59 patients after Blalock-Taussig shunt or pulmonary banding, 60 patients after Glenn surgery (Glenn group), and 53 patients after Fontan surgery (Fontan group).
  
  
  RESULTS
  Serum amino-terminal procollagen type III levels were significantly higher among the 3 single ventricle groups than among control patients, but decreased with each surgical stage (0.604, 0.176, 0.143, and 0.073 U/mL, for Blalock-Taussig shunt or pulmonary banding, Glenn, Fontan, and controls, respectively). Severity of volume load and cyanosis were independent determinants of increased amino-terminal procollagen type III levels in patients before Fontan surgery, and persistently increased amino-terminal procollagen type III after Fontan surgery was associated with ventricular diastolic stiffening (r = 0.494, P = .009). Data also indicated close associations between amino-terminal procollagen type III levels and activation of the renin-angiotensin-aldosterone system, suggesting potential involvement of this hormonal system in the increased fibrogenesis after Fontan surgery.
  
  
  CONCLUSIONS
  These results suggest that serum amino-terminal procollagen type III may provide important diagnostic information on myocardial fibrosis in patients with single ventricle circulation and raise the possibility that ventricular fibrogenesis may be a potential therapeutic target in this population.
authors.affiliation: Department of Pediatric Cardiology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan; Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Department of Pediatric Cardiology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Saiki
authors.affiliation: Department of Pediatric Cardiology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tamai
authors.affiliation: Department of Pediatric Cardiology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seki
authors.affiliation: Department of Pediatrics, University of Tokyo, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Inuzuka
authors.affiliation: Department of Pediatric Cardiology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Masutani
authors.affiliation: Department of Pediatric Cardiology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan. Electronic address: hsenzaki@saitama-med.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Senzaki
mesh_terms: D015415:Biomarkers / Q000097:blood; D058366:Blalock-Taussig Procedure; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D024061:Collagen Type III / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D018729:Fontan Procedure / Q000379:methods*; D006330:Heart Defects, Congenital / Q000097:blood / Q000473:pathology / Q000601:surgery; D006352:Heart Ventricles / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000097:blood / Q000473:pathology / Q000601:surgery; D007223:Infant; D016014:Linear Models; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000097:blood*; D011183:Postoperative Complications / Q000097:blood / Q000209:etiology*; D011347:Procollagen / Q000097:blood*; D018633:Pulmonary Atresia / Q000097:blood / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D018785:Tricuspid Atresia / Q000097:blood / Q000473:pathology / Q000601:surgery; D018754:Ventricular Dysfunction / Q000097:blood / Q000209:etiology*
chemical_list: D015415:Biomarkers; D024061:Collagen Type III; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide
keywords: congenital heart disease; fibrosis; remodeling