Intraleaflet haemorrhage is associated with rapid progression of degenerative aortic valve stenosis

Eur Heart J. 2011 Apr;32(7):888-96. doi: 10.1093/eurheartj/ehq479. Epub 2010 Dec 29.


Aims: The haemorrhage in the plaque (intraplaque haemorrhage) plays a critical role in the progression of atherosclerosis. The purpose of this study is to clarify whether the haemorrhage in the aortic valve leaflet (intraleaflet haemorrhage) accelerates the progression of aortic valve stenosis (AS).

Methods and results: We examined specimens of aortic valve leaflets obtained from 36 patients who had undergone aortic valve replacement for degenerative AS and in whom echocardiographic data were available just before the operation and at least 180 days before the last study. The stenotic valves were examined by immunohistochemistry to detect intraleaflet haemorrhage with antibody against glycophorin A, an erythrocyte-specific protein. The progression of AS was assessed by annualized change in the aortic valve area (ΔAVA: cm(2)/year). The patients were divided into two groups, namely the rapid progression group (ΔAVA ≥ 0.1 cm(2)/year) and the slow progression group (ΔAVA < 0.1 cm(2)/year), according to the reported average progression rate of AS. Intraleaflet haemorrhage was observed in 78 % of the specimens. Intraleaflet haemorrhage was associated with neovascularization and macrophage infiltration. The areas of intraleaflet haemorrhage and macrophage infiltration were greater in the rapid progression group than in the slow progression group. Multivariate analysis has shown that the area of intraleaflet haemorrhage was the sole independent factor that positively correlated with ΔAVA.

Conclusions: Intraleaflet haemorrhage was frequently observed in the valve leaflets of degenerative AS and associated with a rapid progression of AS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aortic Valve / pathology*
  • Aortic Valve Stenosis / complications*
  • Aortic Valve Stenosis / pathology
  • Biomarkers / metabolism
  • Case-Control Studies
  • Disease Progression*
  • Female
  • Glycophorins / metabolism
  • Hemorrhage / complications*
  • Hemorrhage / pathology
  • Humans
  • Macrophages / pathology
  • Male
  • Oxidative Stress


  • Biomarkers
  • Glycophorins