Intraleaflet haemorrhage as a mechanism of rapid progression of stenosis in bicuspid aortic valve

BackgroundThe 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.MethodsWe 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: cm2/year) which was evaluated by serial echocardiography with the continuity equation.ResultsNeoangiogenesis, 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.ConclusionsNeoangiogenesis, 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.