title: Circulating biomarkers of collagen type I metabolism mark the right ventricular fibrosis and adverse markers of clinical outcome in adults with repaired tetralogy of Fallot.
abstract: BACKGROUND
  Right ventricular (RV) fibrosis is common in patients with repaired tetralogy of Fallot (rTOF). Although accumulating evidence indicates the role of circulating biomarkers of collagen metabolism in left ventricular fibrosis, rTOF data are lacking. This study examined the expression profile and clinical relevance of circulating biomarkers of collagen type I metabolism in rTOF patients.
  
  
  METHODS
  Serum biomarkers of collagen type I synthesis (carboxy-terminal propeptide of procollagen type I, PICP), degradation (carboxy-terminal telopeptide of collagen type I, CITP), and enzymes regulating collagen degradation (matrix metalloproteinases, and type I tissue inhibitor, TIMP-1) were measured in 70 rTOF and 91 control adults. All patients had complete clinical data and received cardiovascular magnetic resonance scans with late gadolinium enhancement (LGE).
  
  
  RESULTS
  Compared to the controls, rTOF patients had higher PICP levels (p<0.001), PICP:CITP ratios (p<0.001), and TIMP-1 concentrations (p<0.001). Increasing PICP levels correlated with higher RV LGE scores (r=0.427, p<0.001), lower VO2max (r=-0.428, p=0.002), and larger RV volumes. Furthermore, stepwise multivariate linear regression analysis identified RV end-diastolic volume index >150mL/m(2) (β=40.52, p=0.016), RV LGE score (β=3.94, p=0.008), and age (β=-1.77, p=0.011) as independent correlates of circulating PICP levels.
  
  
  CONCLUSIONS
  Patients with rTOF exhibited a profibrotic state with excessive collagen type I synthesis and dysregulated degradation. Elevated circulating PICP levels might reflect RV fibrosis, and link to adverse markers of clinical outcome.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun-An
authors.initials: CA
authors.lastname: Chen
authors.forename: Wen-Yih Isaac
authors.initials: WY
authors.lastname: Tseng
authors.forename: Jou-Kou
authors.initials: JK
authors.lastname: Wang
authors.forename: Ssu-Yuan
authors.initials: SY
authors.lastname: Chen
authors.forename: Yen-Hsuan
authors.initials: YH
authors.lastname: Ni
authors.forename: Kuo-Chin
authors.initials: KC
authors.lastname: Huang
authors.forename: Yi-Lwun
authors.initials: YL
authors.lastname: Ho
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Chang
authors.forename: Ing-Sh
authors.initials: IS
authors.lastname: Chiu
authors.forename: Mao-Yuan Marine
authors.initials: MY
authors.lastname: Su
authors.forename: Hsi-Yu
authors.initials: HY
authors.lastname: Yu
authors.forename: Ming-Tai
authors.initials: MT
authors.lastname: Lin
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Lu
authors.forename: Mei-Hwan
authors.initials: MH
authors.lastname: Wu
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D024042:Collagen Type I / Q000097:blood*; D005260:Female; D005355:Fibrosis / Q000097:blood / Q000175:diagnosis; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D013771:Tetralogy of Fallot / Q000097:blood* / Q000601:surgery*; D018497:Ventricular Dysfunction, Right / Q000097:blood* / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D024042:Collagen Type I