Integrating Coronary Atherosclerosis with Physiologic Features for Optimized Risk Stratification

将冠状动脉粥样硬化与生理特征相结合以优化风险分层

• 批准号: 10590718
• 负责人: James K Min
• 金额: $ 63.91万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-04 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590718
• 关键词: Acute myocardial infarction; Anatomy; Angiography; Arterial Fatty Streak; Arteries; Behavior; Biomechanics; Blood; Blood flow; Categories; Cessation of life; Characteristics; Clinical; Clinical Data; Coronary; Coronary Arteriosclerosis; Coronary artery; Diagnosis; Dimensions; Dose; Endothelium; Enrollment; Evaluation; Functional disorder; Future; General Population; Goals; Grant; Image; Individual; Ischemia; Liquid substance; Measurement; Methods; Modeling; Morbidity - disease rate; Multicenter Trials; Myocardial Infarction; Necrosis; Nested Case-Control Study; Patient Care; Patient risk; Patients; Pattern; Physiological; Physiology; Property; Quantitative Evaluations; Randomized; Risk; Rotation; Severities; Stable Populations; Stenosis; Stress; Symptoms; Techniques; Thrombus; Time; United States National Institutes of Health; Validation; Work; X-Ray Computed Tomography; acute coronary syndrome; arterial remodeling; attenuation; calcification; clinical care; coronary computed tomography angiography; experience; high risk; improved; innovative technologies; insight; mortality; novel; novel diagnostics; particle; patient population; pressure; prognostic; prognostication; residence; risk stratification; shear stress; tool; ultrasound; virtual

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.

项目总结 冠心病(CAD)是全世界发病率和死亡率的主要基础，超过一半的 经历过急性心肌梗死(AMI)的人没有先兆症状。冠状动脉CT 冠状动脉造影术是一种非侵入性技术，可以对冠状动脉进行低剂量的容积成像 一次心跳。与有创血管造影术和冠状动脉造影术相比，CT更准确。 通过CT诊断疾病(CAD)可以预测急性冠脉综合征和死亡。除了管腔狭窄，CT还可以 一系列动脉粥样硬化斑块特征(APC)的定量评估。此外，还将应用 CT的计算流体动力学能够确定一系列冠状动脉生理特征 (CPC)，如流动储备分数、内皮细胞壁切应力、涡度、颗粒停留时间、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-有 评估了其对未来急性冠脉综合征风险的影响，并在选定的急性冠脉综合征后患者群体中进行了评估 正在接受侵入性成像。然而，其余的CPC尚未被评估其预后重要性。 对急性冠脉综合征的风险，在没有已知冠心病的稳定人群中没有进行过评估。此外，合并CP 使用APC改善未来急性冠脉综合征的风险分层实际上仍未被探索。 这一提议的总体假设是冠状动脉粥样硬化与 冠脉生理特征将改善对随后将经历 超越任何冠脉特征的冠脉综合征。我们提出三个目标： 目的1.鉴定与未来急性冠脉综合征相关的CPC。假设：CPC在动脉内并发挥作用 在未来将牵涉到的斑块上，ACS将不同于动脉内的CP，并作用于 不会牵涉到未来的ACS。 目标2.将CPC与APC相结合，以增强对将经历 未来的ACS。假设：一个整合了冠状动脉动脉粥样硬化整体的多维框架 而病理生理特征将优于不整合冠状动脉粥样硬化和 用于识别将经历未来急性冠脉综合征的个体的病理生理学特征。 目的3.验证在AIM 2中开发的临床工具在疑似冠心病的稳定个体中的有效性。 假设：适用于有疑似但未登记已知冠心病的稳定个体的一般人群 在随机对照的SCOT心脏试验中，一种结合了冠状动脉粥样硬化和心脏疾病的临床工具 冠脉病理生理特征将是预测急性冠脉综合征的有效方法。 如果成功，这项建议中的工作将为新的诊断和预后提供理论基础 可以很容易地应用于疑似冠心病患者的临床护理。此外，这项工作将提供 对CAD的病理生理学有独特的见解。