The Influence of Aortic Valve Hemodynamics and LVAD on bio-transport processes in Calcific Aortic Valve Disease

项目摘要 钙化性主动脉瓣（CAV）是最常见的主动脉瓣缺损类型之一，影响2 - 4%的 65岁以上人口。高弹性主动脉瓣（AV）附近的生物运输过程 小叶在CAV的形成中起重要作用。尽管有大量关于主动脉的研究 瓣膜血流动力学，AV周围的生物运输和钙化过程尚未完全探索。此外，本发明还提供了一种方法， 在美国，晚期心力衰竭的持续流行已经看到左心室的使用急剧上升， 心室辅助装置（LVAD）在过去十年中。尽管技术进步， 当前一代LVAD，LVAD支持的患者仍然容易发生AV并发症， 极大地改变了左心室辅助装置以外的血流动力学尽管有大量的研究， LVAD改变了血液动力学，血液动力学改变对生物转运的级联效应 进程和CAV未知。在这个项目中，我们将开发第一个计算工具， 模型低密度脂蛋白（LDL）运输，被称为CAV发展的关键组成部分，接近 高度变形的主动脉瓣我们的目标是了解主动脉瓣叶的运动 影响LDL转运和钙化过程以及LVAD如何与LDL转运相互作用。我们 我假设小叶附近LDL浓度的局部热点并不总是与壁相关 瓣叶上的剪应力以及空间和时间的壁面剪应力梯度。我们 我还假设跨瓣压差升高会增加LDL的局部热点， 在瓣叶的主动脉侧，加速CAV的发展。为了验证这两个假设， 拟议的研究将包括三个具体目标。本研究的目的1是开发一种创新的 浸入边界法称为最高浸入边界法（SIB）。SIB绕过了限制 以及现有浸入边界法在精确求解速度和LDL方面的不足 高度变形的主动脉瓣叶上的运输边界层。在目标2中，我们将检验第一个假设 通过模拟血流动力学、LDL转运和机械响应的值来检查 血流动力学切应力与运动瓣叶上LDL浓度分布之间的相关性。在 此外，我们将使用瓣叶上的LDL浓度水平局部改变瓣叶的硬度 并代表钙化区域。然后将预测钙化瓣膜的生物力学响应， 与健康的瓣膜相比。在目标3中，我们将通过将HeartMate III包括在 目标2中使用的模型。瓣膜和LDL转运的血流动力学性能将 研究了两种泵方案（低和高rpm）和两种模式（脉冲和非脉冲）。在这一目标下， 我们还将研究LDL和血流动力学特性之间的相关性， 血流动力学和LDL由于LVAD，钙化模式，和钙化主动脉瓣反应。

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.