Abstract 12887: Role of Bicuspid Aortic Valve Hemodynamics in Valvular Calcification: A Computational and Ex Vivo Study
INTRODUCTION: The bicuspid aortic valve (BAV), a congenital valvular anomaly consisting of two leaflets instead of three, is associated with a high prevalence of calcific aortic valve disease (CAVD). Although CAVD develops in the normal tricuspid aortic valve (TAV), its progression in the BAV is more severe and rapid. While BAV calcification has been linked to genetic and atherogenic origins, hemodynamics has recently emerged as a potential alternate etiology.
OBJECTIVE: Supported by our earlier work that suggested the ability of shear stress alterations to trigger valvular inflammation, we hypothesized that the fluid shear stress abnormalities produced by the BAV anatomy contribute to the onset of CAVD. Therefore, the objectives of this study were to characterize the native hemodynamic stresses experienced by TAV and BAV leaflets and to compare their acute effects on valvular pathogenesis.
METHODS: Idealized fluid-structure interaction (FSI) models coupled with realistic material models were designed to quantify the native side-specific wall-shear stress (WSS) distributions on TAV and BAV leaflets. The FSI models were validated with respect to particle image velocimetry measurements carried out through similar valve anatomies in a left-heart simulator. Porcine leaflets were exposed for 96 hours to the native side-specific TAV and BAV WSS predicted by the FSI models using a novel double-sided shear stress bioreactor. Tissue response was characterized via Western blot and immunohistochemistry in terms of markers of endothelial activation (VCAM-1 and ICAM-1) and inflammation (BMP-4 and TGF-β1).
RESULTS: Consistent with clinical observations, the FSI results confirmed the existence of a skewed systolic jet and an intrinsic degree of stenosis in the BAV. Comparison of the regional WSS onTAV and BAV leaflets suggested differences in both pulsatility and magnitude. Exposure of fresh leaflets to the native BAV leaflet WSS resulted in an overall increase in inflammatory response as compared to tissue exposed to normal (TAV) leaflet WSS.
CONCLUSION: This study demonstrates the key role played by BAV hemodynamics in the onset of CAVD and provides new support to the hemodynamic theory of BAV pathogenesis.
- © 2011 by American Heart Association, Inc.