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 钙化性主动脉瓣(CAV)是最常见的主动脉瓣缺陷类型之一，影响2-4%的 65岁以上的人口。高弹性主动脉瓣附近的生物转运过程 传单在CAV的形成中起着至关重要的作用。尽管有大量关于主动脉的研究 瓣膜的血流动力学、房室周围的生物转运和钙化过程还没有得到充分的研究。此外, 在美国持续流行的晚期心力衰竭中，左心衰的使用率急剧上升 在过去的十年中，心脏辅助装置(LVAD)得到了广泛应用。无论在技术上的改进如何 当前一代的LVAD，LVAD支持的患者仍然容易发生由以下原因引起的房室并发症 极大地改变了左心室外的血流动力学。尽管有大量关于 LVADs改变血流动力学，血流动力学改变对生物转运的级联效应 进程和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来 模型低密度脂蛋白(LDL)转运，被称为CAV发展的关键组件，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 影响低密度脂蛋白的转运和钙化过程，以及左冠状动脉内皮细胞如何与低密度脂蛋白的转运相互作用。我们 假设小叶附近的局部低密度脂蛋白浓度热点并不总是与壁上的相关 小叶上的剪应力，以及空间和时间壁面剪应力梯度应被考虑。我们 也假设跨瓣膜压力梯度升高将增加局部的低密度脂蛋白热点 在瓣叶的主动脉侧，并加速CAV的发展。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是开发一种创新的 一种称为最高浸没边界的浸没边界方法。SIB绕过了这些限制 以及现有浸没边界方法在精确求解速度和低密度脂蛋白方面的不足 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、低密度脂蛋白的转运和机械反应的值来考察 血流动力学切应力与运动叶上低密度脂蛋白浓度分布的相关性。在……里面 此外，我们将利用传单上的低密度脂蛋白浓度水平来局部改变传单的硬度 代表钙化区域。然后将预测钙化瓣膜的生物力学反应，并 与健康的瓣膜相比。在目标3中，我们将测试第二个假设，方法是在 AIM 2中采用的模型。瓣膜的血流动力学性能和低密度脂蛋白的传输将是 研究了两种泵浦方案(低转速和高转速)和两种模式(脉冲和非脉冲)。在这个目标中， 我们还将研究低密度脂蛋白与血流动力学特性的相关性，以及 血流动力学和低密度脂蛋白与左冠状动脉前降支、钙化模式和钙化的主动脉瓣反应有关。