Developing Biomechanical Predictors of Ascending Thoracic Aortic Aneurysm Growth and Dissection

退伍军人事务部(VA)医疗系统服务&144家医院的900万退伍军人 全国范围内。主动脉瘤是导致35岁以下患者死亡的第16大原因。 美国。主动脉夹层和破裂是灾难性的心血管疾病 紧急情况具有显著的院前(40%)和手术(17-25%)死亡率。外科手术 指南依赖于Ataa最大直径、生长速度和症状来指导可选 修复，手术死亡率低。然而，我们和其他人 显示直径本身不足以预测夹层或破裂--~60%-90% A型夹层事件发生在直径<5.5 cm的ATA中，否则不满足 择期手术修复指征。从生物力学的角度来看，破裂或夹层是一种 当动脉瘤壁应力超过壁强时可能发生的机械故障。指导方针 根据圆柱体的拉普拉斯定律，只需用直径代替壁应力即可。我们的 已发表的研究表明，直径不能很好地预测壁应力，因为 单个Ataa几何图形的复杂性。 我们建议前瞻性地评估Ataa壁应力和膨胀性的变化 确定他们是否有能力改进直径标准，以预测解剖或死亡或需要 对患有不符合手术标准的动脉瘤的退伍军人进行手术。我们建议 前瞻性评估动脉瘤壁切应力、血流速度和涡旋的变化。 非手术大小的退伍军人随着时间的推移确定他们预测动脉瘤的能力 生长和手术需求。该方案为临床实际应用奠定了基础。 应用患者特有的生物力学和流体动力学来改进主动脉风险预测 解剖、猝死、Ataa生长和手术需求，目的如下： 目标1：使用有限元分析(FEA)确定纵向壁应力的变化 与主动脉夹层的临床复合终点、是否需要手术修复或突然发生相关 非手术治疗的退伍军人(n=400)在4年内死亡5.5 cm。 目的2：用体内主动脉替代物测定Ataa壁强度的变化 扩张性与Ataa手术的主动脉夹层的临床复合终点相关 非手术治疗的退伍军人(n=400)的修复或猝死 &lt；5.5厘米，超过4年。 目的3：测定Ataa环向壁应力和壁面剪应力的变化， 流体结构相互作用(FSI)的流速和偏心率，用4D流动进行验证 磁共振成像(MRI)，并与临床主动脉复合终点相关 接受非手术治疗的退伍军人(n=400)的生长发育或需要手术修复 Ataa&lt；超过4年5.5厘米。 目标4：开发一种机器学习(ML)方法来确定生物力学和流体 前瞻性跟踪非手术治疗退伍军人(n=320)AIM 1-3的动力学参数 Ataa&lt；5.5 cm，验证结果(n=80)，简化个性化过程 生物力学预测。 在项目结束时，我们将开发一种新的基于生物力学的临床工具 非手术治疗的Ataa患者的有效临床管理。

Veterans Affairs (VA) Healthcare System services >9 million veterans at 144 hospitals nationwide. Aortic aneurysms are the 16th leading cause of death in patients >35 years old in the United States. Dissection and rupture of aTAAs are catastrophic cardiovascular emergencies carrying significant pre-hospital (40%) and operative (17-25%) mortality. Surgical guidelines rely on aTAA maximum diameter, growth rate, and symptoms to guide elective repair, which can be performed with low operative mortality. However, we and others have demonstrated that diameter alone is not adequate to predict dissection or rupture—~60-90% of type A dissection events occur in aTAAs with diameter <5.5cm and otherwise not meeting elective surgical repair indications. From a biomechanics perspective, rupture or dissection is a mechanical failure that can occur when aneurysm wall stress exceeds wall strength. Guidelines simply use diameter as a surrogate for wall stress based on LaPlace’s Law for cylinders. Our published studies showed that diameter was a poor predictor of wall stress due to the complexity of individual aTAA geometries. We propose to prospectively evaluate changes in aTAA wall stresses and distensibility to determine their ability to improve on diameter criterion to predict dissection or death or need for surgery in veterans with aneurysms that do not meet criteria for surgery. We propose to prospectively evaluate changes in aneurysm wall shear stresses, flow velocities, and vortices in veterans with nonsurgical sized aTAAs over time to determine their ability to predict aneurysm growth and need for surgery. This proposal lays the foundation for practical clinical application of patient-specific biomechanics and fluid dynamics to improve risk prediction of aortic dissection, sudden death, aTAA growth, and need for surgery with the following aims: Aim 1: To determine changes in longitudinal wall stresses using finite element analysis (FEA) to correlate with clinical composite endpoint of aortic dissection, need for surgical repair, or sudden death in prospectively followed veterans (n=400) with nonsurgical aTAA <5.5cm over 4 years. Aim 2: To determine changes in aTAA wall strength using the surrogate of in vivo aortic distensibility to correlate with clinical composite endpoint of aortic dissection, aTAA surgical repair, or sudden death in prospectively followed veterans (n=400) with nonsurgical aTAA <5.5cm over 4 years. Aim 3: To determine changes in aTAA circumferential wall stresses and wall shear stresses, flow velocities, and eccentricity using fluid structure interaction (FSI), validate with 4D flow magnetic resonance imaging (MRI), and correlate with clinical composite endpoint of aortic growth or need for surgical repair in prospectively followed veterans (n=400) with nonsurgical aTAA <5.5cm over 4 years. Aim 4: To develop a machine learning (ML) approach to determine biomechanical and fluid dynamic parameters in Aim 1-3 in prospectively followed veterans (n=320) with nonsurgical aTAA <5.5cm, validate the results (n=80), and simplify the process of personalized biomechanics prediction. At the end of the project, we will have developed a new biomechanics based clinical tool for effective clinical management for non-surgical aTAA patients.