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

主动脉瓣血流动力学和 LVAD 对钙化性主动脉瓣疾病生物转运过程的影响

• 批准号: 10292320
• 负责人: Hamid Sadat
• 金额: $ 35.51万
• 依托单位: UNIVERSITY OF NORTH TEXAS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10292320
• 关键词: Affect; Age-Years; Aging; Aortic Valve Stenosis; Biological Transport; Biomechanics; Cells; Clinical; Computer Models; Coupled; Development; Devices; Disease; Elderly; Epidemic; Generations; Goals; Heart Transplantation; Heart Valve Diseases; Heart failure; Low-Density Lipoproteins; Mechanics; Medical; Methods; Modeling; Movement; Names; Organ; Patients; Pattern; Performance; Physiologic pulse; Play; Population; Prevalence; Process; Property; Pump; Refractory; Reporting; Research; Research Personnel; Role; Sclerosis; Serious Adverse Event; Side; Techniques; Testing; Transport Process; aortic valve; aortic valve disorder; biochemical model; calcification; computerized tools; hemodynamics; implantation; innovation; left ventricular assist device; novel; pressure; response; shear stress; virtual

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.

项目摘要 钙化主动脉瓣（CAV）是主动脉瓣缺陷的最常见类型之一，影响了2-4％ 65岁以上的人口。高度弹性主动脉瓣（AV）附近的生物传输过程 传单在CAV的形成中起着必要的作用。尽管主动脉研究大量研究 瓣膜血流动力学，AV周围的生物传输和计算过程未充分探索。此外， 美国晚期心力衰竭持续的流行病的左派利用率急剧上升 在过去的十年中，心室辅助设备（LVADS）。不管技术的技术进步如何 当前一代LVAD，LVAD支持的患者仍然容易发生AV并发症。 LVADS的血液动力学外部巨大改变。尽管有大量的研究 LVADS改变血液动力学，血液动力学改变对生物传播的级联作用 过程和CAV是未知的。在这个拟议的项目中，我们将开发第一个计算工具 模型低密度脂蛋白（LDL）转运，称为CAV发育的关键成分，附近 高度变形的主动脉瓣。我们的目标是了解主动脉瓣膜的运动如何 影响LDL传输和钙化过程以及LVAD如何与LDL传输相互作用。我们 假设小叶附近的LDL浓度的局部热点不会与墙壁相关 剪切应力在小叶上，应考虑空间和临时壁剪应力梯度。我们 还假设升高的转侧压力梯度将增加LDL的局部热点 在阀门的主动脉侧，加速CAV发育。为了检验这两个假设， 拟议的研究将包括三个具体目标。拟议研究的目标1是开发创新的 沉浸式边界方法名为Supreme浸入边界（SIB）。 SIB绕过限制 和现有的浸入边界方法的缺陷，以准确解决速度和LDL 在高度变形的主动脉瓣膜上传输边界层。在AIM 2中，我们将检验第一个假设 通过对血液动力学，LDL转运和值的机械响应进行建模以检查 血液动力学剪切应力与移动叶子上的LDL浓度分布之间的相关性。在 此外，我们将使用叶子上的LDL浓度水平来局部改变叶子的刚度 并代表钙化区域。然后将预测钙化阀的生物力学响应，并 与健康阀相比。在AIM 3中，我们将通过将心伴侣III包括在 AIM 2中带有的模型。阀门和LDL传输的血液动力学性能将为 研究了两种泵场景（低和高RPM）和两种模式（脉冲和非脉冲）。在这个目标中 我们还将研究LDL与血液动力学特性之间的相关性，这是 由于LVAD，钙化模式和钙化主动脉瓣反应引起的血液动力学和LDL。