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 investigate the correlation between LDL and hemodynamic properties, the alternation of
hemodynamics and LDL due to the LVAD, calcification pattern, and calcific aortic valve response.
