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

基本信息

批准号：
10364760
负责人：
James K Min
金额：
$ 56.05万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
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/10364760
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 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 base calcification clinical care coronary computed tomography angiography experience high risk improved innovation insight mortality novel novel diagnostics particle patient population pressure prognostic prognostication residence risk stratification shear stress tool ultrasound virtual

项目摘要

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.

项目概要冠状动脉疾病（CAD）是全世界发病率和死亡率的主要基础，超过一半的人患有急性心肌梗塞 (AMI) 的人没有先兆症状。血管造影是一种非侵入性技术，可以对冠状动脉进行低剂量体积成像。单次心跳与侵入性血管造影相比，CT 更准确，并且可以显示冠状动脉的血管造影严重程度。 CT 诊断疾病 (CAD) 可以预测 ACS 和死亡除了管腔狭窄之外，CT 还可以实现 ACS 和死亡的预后。一系列动脉粥样硬化斑块特征（APC）的评估此外，定量应用。 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)，例如血流储备分数、内皮壁剪切应力、涡度、颗粒驻留时间、轴向斑块迄今为止，在 CPC 中，只有 ESS（在我们小组进行的研究中）具有。评估了其对未来 ACS 风险的影响，并在选定的 ACS 后患者群体中进行了评估然而，其余 CPC 的预后重要性尚未得到评估。 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。使用 APC 来改善未来 ACS 的风险分层实际上仍未被探索。该提案的总体假设是冠状动脉粥样硬化与冠状动脉生理特征将有助于识别稳定的个体，这些个体随后将经历 ACS 超越任何冠状动脉特征，我们提出 3 个目标：目的 1. 描述与未来 ACS 相关的 CPC 的特征：动脉内的 CPC 及其作用。与未来 ACS 相关的斑块上的 CPC 与动脉内的 CPC 不同，并且作用在以下斑块上：不会牵涉到未来的 ACS。目标 2. 将 CPC 与 APC 集成，以增强对将经历的稳定个体的识别未来的 ACS 假设：整合整个冠状动脉粥样硬化的多维框架和病理生理学特征将优于不整合冠状动脉粥样硬化和用于识别未来将经历 ACS 的个体的病理生理学特征。目标 3. 在患有疑似 CAD 的稳定个体中验证目标 2 中开发的临床工具。假设：适用于患有疑似但未知 CAD 的稳定个体的一般人群在随机对照 SCOT-HEART 试验中，这是一种将冠状动脉粥样硬化和冠状动脉病理生理特征对ACS的预测有效。如果成功，该提案中的工作将为新型诊断和预后提供理论依据此外，这项工作还将提供可轻松应用于疑似 CAD 患者临床护理的范例。对 CAD 病理生理学的独特见解。