title: Intraleaflet haemorrhage as a mechanism of rapid progression of stenosis in bicuspid aortic valve.
abstract: BACKGROUND
  The mechanisms are unknown why aortic stenosis (AS) progresses faster in patients with bicuspid aortic valve (BAV) than those with tricuspid aortic valve (TAV). The objective of this study is to examine whether neoangiogenesis, haemorrhage in the aortic valve leaflet (intraleaflet haemorrhage) and macrophage infiltration are involved in the mechanisms of rapid progression of AS with BAV.
  
  
  METHODS
  We retrospectively examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve replacement for AS (AS with BAV: n=22, AS with TAV: n=86). The stenotic valve leaflets were examined by immunohistochemistry to detect vascular endothelial cells, red blood cell remnant and macrophage. We assessed the progression of AS by annualized changes in the aortic valve area (ΔAVA: cm(2)/year) which was evaluated by serial echocardiography with the continuity equation.
  
  
  RESULTS
  Neoangiogenesis, intraleaflet haemorrhage and macrophage infiltration were frequently observed in leaflets obtained from AS patients with BAV (neoangiogenesis: 82%, intraleaflet haemorrhage: 91%, macrophage infiltration 91%). These pathological changes were more severe in AS with BAV than TAV, and they were positively correlated with progression of AS in patients with BAV. Multivariated analysis revealed that bicuspid anatomy was the only factor that predicted neoangiogenesis, intraleaflet haemorrhage and macrophage infiltration when patients with BAV and those with TAV were combined.
  
  
  CONCLUSIONS
  Neoangiogenesis, intraleaflet haemorrhage and macrophage infiltration are more severe in leaflets from AS with BAV than TAV and associated with rapid progression of AS with BAV. This pathological process may account for rapid progression of AS with BAV.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Akahori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsujino
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Naito
authors.forename: Chikako
authors.initials: C
authors.lastname: Yoshida
authors.forename: Masaaki
authors.initials: M
authors.lastname: Lee-Kawabata
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Ohyanagi
authors.forename: Masataka
authors.initials: M
authors.lastname: Mitsuno
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.forename: Tohru
authors.initials: T
authors.lastname: Masuyama
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000002:abnormalities* / Q000473:pathology / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000453:epidemiology / Q000473:pathology* / Q000601:surgery; D000082882:Bicuspid Aortic Valve Disease; D018450:Disease Progression; D005260:Female; D006349:Heart Valve Diseases / Q000473:pathology* / Q000601:surgery; D019918:Heart Valve Prosthesis Implantation / Q000639:trends; D006470:Hemorrhage / Q000453:epidemiology / Q000473:pathology*; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000453:epidemiology / Q000473:pathology; D012189:Retrospective Studies; D013997:Time Factors; D014261:Tricuspid Valve / Q000473:pathology* / Q000601:surgery