Project Summary Calcific Aortic Valve (CAV) is one of the most common types of aortic valve defects, affecting 2–4% of the population above 65 years of age. The biological transport processes near the highly elastic aortic valve (AV) leaflets play an imperative role in the formation of CAV. Despite the significant number of studies on aortic valve hemodynamics, the bio-transport around AV and calcification process is not fully explored. In addition, the ongoing epidemic of advanced heart failure in the U.S. has seen a sharp rise in the utilization of left ventricular assist devices (LVADs) over the last decade. Regardless of technological improvements in the current generation of LVADs, LVAD-supported patients remain prone to AV complications resulting from enormously altered hemodynamics extrinsic to the LVADs. Despite the significant number of studies on altered hemodynamics by LVADs, the cascading effect of hemodynamics alternations on bio-transport processes and CAV is unknown. In this proposed project, we will develop the first computational tool to model Low-Density Lipoprotein (LDL) transport, known as the key component for CAV development, near the highly deforming aortic valve. Our goal is to understand how the movement of the aortic valve leaflets affects the LDL transport and calcification process and how LVADs interact with the LDL transport. We postulate that localized hotspots of LDL concentration near leaflets will not always correlate with the wall shear stress on leaflets and that the spatial and temporal wall shear stress gradient should be considered. We also hypothesize that the elevated transvalvular pressure gradient will increase the localized hotspots of LDL on the aortic side of the valve leaflets and accelerate the CAV development. To test these two hypotheses, the proposed research will include three specific aims. Aim 1 of the proposed research is to develop an innovative immersed boundary method named supreme immersed boundary (SIB). SIB circumnavigates the limitations and deficiencies of existing immersed boundary methods in accurately resolving the velocity and LDL transport boundary layers on highly deforming aortic valve leaflets. In Aim 2, we will test the first hypothesis by modeling the hemodynamics, LDL transport, and mechanical response of the value to examine the correlation between hemodynamic shear stresses and LDL concentration distribution on the moving leaflets. In addition, we will use the LDL concentration level on the leaflets to locally change the stiffness of the leaflets and represent the calcific regions. The biomechanical response of the calcific valve will then be predicted and compared to the healthy valve. In Aim 3, we will test the second hypothesis by including HeartMate III in the model employed in Aim 2. The hemodynamic performance of the valve and LDL transport will be investigated for two pump scenarios (low and high rpm) and two modes (pulse and non-pulse). In this aim, we will also in...