Patient-Informed Fluid-Structure Interaction Simulations of Bicuspid Aortic Valve in Young Adults Reveal Regionalized...

Bicuspid aortic valve (BAV) is a common congenital cardiovascular defect characterized by two, rather than three, cusps. Many BAV patients prematurely develop calcification and aortic stenosis by age 35, which is more severe with fusion of the right and noncoronary (RC/NC) cusps. The mechanisms underlying calcification observed within the coaptation, attachment, and fusion regions of BAV patients are unknown. While abnormal mechanical stimuli induced by the bicuspid anatomy likely plays a role, little is known about regionalized mechanical stimuli in these susceptible cusp regions of young patients prior to calcification. Strongly coupled fluid-structure interaction simulations were conducted using physiologic boundary conditions derived from data of a 23-year-old patient with RC/NC BAV and an age-matched tricuspid aortic valve control. Cusp material properties were implemented for the first time from biaxial testing of non-calcific BAV tissue. Additional simulations elucidated the independent and collective contributions of cusp fusion, material properties and boundary conditions. Results show BAV cusps experience higher time-averaged wall shear stress (TAWSS) over the coaptation region (2.92-fold increase), decreased oscillatory shear index (OSI) within the free edge (1.6-fold) and coaptation (1.4-fold) regions, and an increase in von Mises stress in the coaptation (5.72-fold), belly (6.79-fold), and attachment (5.18-fold) regions of the fused and nonfused cusps. These results reveal putative regions susceptible to calcification in BAV patients experience differences in mechanical stimuli that may contribute to the onset of calcification and provide insight for future in vitro and ex vivo studies focusing on mechanosensitive pathways involved in BAV-induced calcification.