Integrating Coronary Atherosclerosis with Physiologic Features for Optimized Risk Stratification

项目摘要 冠状动脉疾病（CAD）是全球发病率和死亡率的主要基础， 经历急性心肌梗塞（AMI）的个体没有先兆症状。冠状动脉CT 血管造影术是一种非侵入性技术，其允许对冠状动脉进行低剂量体积成像， 一次心跳CT与有创血管造影、冠状动脉造影严重程度比较准确 通过CT诊断冠心病（CAD）能够明确ACS和死亡。除了管腔狭窄，CT还可以 动脉粥样硬化斑块特征（APC）阵列的定量评价。此外，应用 CT的计算流体动力学使得能够确定冠状动脉生理特征的阵列 这些参数包括血流储备分数、内皮壁剪切应力、涡度、颗粒驻留时间、轴向斑块 应力和斑块结构应力。到目前为止，在CPC中，只有ESS-在我们小组进行的研究中- 评估其对未来ACS风险的影响，并在选择的ACS后患者人群中进行评估 进行侵入性成像然而，其余的CPC还没有被评估其预后的重要性 ACS风险，并且没有在没有已知CAD的稳定人群中进行评估。此外，结合CPC APC用于改善未来ACS的风险分层实际上尚未探索。 这项提议的总体假设是，冠状动脉粥样硬化与 冠状动脉生理学特征将改善对随后将经历 ACS超出任何冠状动脉特征。我们提出三个目标： AIM 1.表征与未来ACS相关的CPC。假设：动脉内的CPC和施加 与未来ACS有关的斑块上的CPC将不同于动脉内的CPC， 不会被牵连进未来的ACS AIM 2.将CPC与APC相结合，以增强对将经历 未来的ACS假设：整合冠状动脉粥样硬化整体的多维框架 和病理生理特征将上级不整合冠状动脉粥样硬化的框架， 病理生理学特征，用于识别未来将经历ACS的个体。 AIM 3.在疑似CAD的稳定个体中验证Aim 2中开发的临床工具。 假设：适用于入组的疑似但无已知CAD的稳定个体的一般人群 在随机对照的SCOT-HEART试验中，一种整合冠状动脉粥样硬化和 冠状动脉病理生理特征对ACS的预测是有效的。 如果成功的话，这项建议的工作将为一种新的诊断和预后方法提供理论基础。 这一范例可以很容易地应用于疑似CAD患者的临床护理。此外，这项工作将提供 对CAD病理生理学的独特见解。

PROJECT SUMMARY Coronary artery disease (CAD) is the principal basis of morbidity and mortality worldwide, and more than half of individuals experiencing acute myocardial infarction (AMI) have no premonitory symptoms. Coronary CT angiography is a non-invasive technique that permits low-dose volumetric imaging of the coronary arteries in a single heartbeat. CT is accurate compared to invasive angiography, and angiographic severity of coronary artery disease (CAD) by CT enables prognostication of ACS and death. Beyond luminal narrowing, CT enables quantitative evaluation of an array of atherosclerotic plaque characteristics (APCs). Further, application of computational fluid dynamics to CT enables determination of an array of coronary physiologic characteristics (CPCs), such as fractional flow reserve, endothelial wall shear stress, vorticity, particle resident time, axial plaque stress and plaque structural stress. To date, among CPCs, only ESS—in studies performed by our group—has been evaluated for its influence on future ACS risk, and was done so in select post-ACS populations of patients undergoing invasive imaging. Yet, the remainder of CPCs has not been evaluated for their prognostic importance to ACS risk, and none has been assessed in a stable population without known CAD. Further, combining CPCs with APCs for improved risk stratification of future ACS remains virtually unexplored. The OVERALL HYPOTHESIS of this proposal is that integration of coronary atherosclerosis with coronary physiologic features will improve identification of stable individuals who will subsequently experience ACS beyond any coronary feature alone. We propose 3 aims: AIM 1. To characterize CPCs associated with future ACS. Hypothesis: CPCs within arteries and exerted on plaques that will be implicated in future ACS will differ from CPCs within arteries and exerted on plaques that will not be implicated in future ACS. AIM 2. To integrate CPCs with APCs for enhanced identification of stable individuals who will experience future ACS. Hypothesis: A multi-dimensional framework that integrates the entirety of coronary atherosclerosis and pathophysiologic features will be superior to frameworks that do not integrate coronary atherosclerosis and pathophysiologic features for identification of individuals who will experience future ACS. AIM 3. To validate the clinical tool developed in Aim 2 in stable individuals with suspected CAD. Hypothesis: Applied to a general population of stable individuals with suspected but without known CAD enrolled in the randomized controlled SCOT-HEART trial, a clinical tool that integrates coronary atherosclerosis and coronary pathophysiologic features will be effective for prediction of ACS. If successful, the work in this proposal will provide the rationale for a novel diagnostic and prognostic paradigm that can be readily applied in clinical care of patients with suspected CAD. Further, this work will offer unique insights into the pathophysiology of CAD.