title: FBN1 gene mutation characteristics and clinical features for the prediction of mitral valve disease progression.
abstract: BACKGROUND
  Until today, FBN1 gene mutation characteristics were not compared with clinical features for the prediction of mitral valve disease progression.
  
  
  METHODS
  Therefore, we conducted a study of 116 patients (53 men, 63 women aged 33 ± 15 years) with a causative FBN1 gene mutation and ≤ moderate mitral valve regurgitation at baseline.
  
  
  RESULTS
  During 7.4 ± 6.8 years 30 patients developed progression of mitral valve regurgitation ≥ 1 grade (primary endpoint), and 26 patients required mitral valve surgery (secondary endpoint). Cox regression analysis identified an association of atrial fibrillation (hazard ratio (HR)=2.703; 95% confidence interval (CI) 1.013-7.211; P=.047), left ventricular ejection fraction (HR=.970; 95%CI .944-.997; P=.032), indexed end-diastolic left ventricular diameter (HR=15.165; 95%CI 4.498-51.128; P<.001), indexed left atrial diameter (HR=1.107; 95%CI 1.045-1.173; P=.001), tricuspid valve prolapse (HR=2.599; 95%CI 1.243-5.437; P=.011), posterior leaflet prolapse (HR=1.075; 95%CI 1.023-1.130; P=.009), and posterior leaflet thickening (HR=3.368; 95%CI 1.265-8.968; P=.015) with progression of mitral valve disease, whereas none of the FBN1 gene mutation characteristics were associated with progression of mitral valve disease. However, Cox regression analysis identified a marginal relationship of FBN1 gene mutations located both in a transforming-growth-factor beta-binding protein-like (TGFb-BP) domain (HR=3.453; 95%CI .982-12.143; P=.053), and in the calcium-binding epidermal growth factor-like (cbEGF) domain (HR=2.909; 95%CI .957-8.848; P=.060) with mitral valve surgery, a finding that was corroborated by Kaplan-Meier analysis (P=.014; and P=.041, respectively).
  
  
  CONCLUSIONS
  Clinical features were better predictors of mitral valve disease progression than FBN1 gene mutation characteristics.
authors.affiliation: Centre of Cardiology and Cardiovascular Surgery, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Kühne
authors.forename: Britta
authors.initials: B
authors.lastname: Keyser
authors.forename: Eike F
authors.initials: EF
authors.lastname: Groene
authors.forename: Sara
authors.initials: S
authors.lastname: Sheikhzadeh
authors.forename: Christian
authors.initials: C
authors.lastname: Detter
authors.forename: Viktoria
authors.initials: V
authors.lastname: Lorenzen
authors.forename: Mathias
authors.initials: M
authors.lastname: Hillebrand
authors.forename: Alexander M J
authors.initials: AM
authors.lastname: Bernhardt
authors.forename: Boris
authors.initials: B
authors.lastname: Hoffmann
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Mir
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berger
authors.forename: Hermann
authors.initials: H
authors.lastname: Reichenspurner
authors.forename: Yskert
authors.initials: Y
authors.lastname: von Kodolitsch
authors.forename: Meike
authors.initials: M
authors.lastname: Rybczynski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D055815:Young Adult; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines