Quantitative coronary flow capacity with low-dose CT for ischemia but no obstructive coronary artery disease

低剂量 CT 定量冠状动脉血流容量，用于缺血但无阻塞性冠状动脉疾病

• 批准号: 10719807
• 负责人: SABEE MOLLOI
• 金额: $ 73.31万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10719807
• 关键词: Anatomy; Angiography; Arrhythmia; Blood Vessels; Blood flow; Calcium; Cardiac; Cardiac Catheterization Procedures; Catheterization; Catheters; Cause of Death; Claustrophobias; Clinical; Clinical assessments; Complex; Coronary; Coronary Angiography; Coronary Arteriosclerosis; Coronary Circulation; Coronary artery; Coronary heart disease; Diagnosis; Diffuse; Disease; Dose; Enrollment; Evaluation; Event; Goals; Health Care Costs; Healthcare Systems; Heart failure; Ischemia; Laboratories; Lesion; Low Dose Radiation; Magnetic Resonance; Measurement; Measures; Methods; Morbidity - disease rate; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardial perfusion; Normal Range; Outcome; Patients; Perfusion; Physiological; Physiology; Positron-Emission Tomography; Pre-Clinical Model; Procedures; Prospective Studies; Radiation Dose Unit; Reference Standards; Reference Values; Reporting; Resolution; Rest; Risk; Safety; Severities; Stress; Stress Tests; Symptoms; Techniques; Testing; Time; Validation; X-Ray Computed Tomography; accurate diagnosis; cardiovascular risk factor; clinical implementation; coronary artery calcification; coronary calcium scoring; coronary computed tomography angiography; coronary plaque; cost; high risk; low dose computed tomography; mortality; mortality risk; non-invasive imaging; novel; patient safety; public health relevance; recruit; successful intervention; sudden cardiac death; tool

Abstract Ischemic coronary heart disease is the world’s leading cause of mortality and morbidity. Within this complex disease entity, many patients suffer from myocardial ischemia but are found to have no obstructed coronary arteries (INOCA). These patients have a high risk of cardiovascular events. Yet current methods for accurately diagnosing and assessing the physiological effects of INOCA are limited. Catheter-based approaches are invasive, with added risk, procedural time, and cost. Positron-emission tomography (PET) and cardiac magnetic resonance (CMR), both noninvasive techniques for clinically assessing INOCA, have limitations such as claustrophobia (CMR), cost and radiation dose (PET), and local expertise and availability (both). None of these noninvasive tests accurately yields both anatomical information on the extent of coronary atherosclerosis and its pathophysiological consequences. We have developed a noninvasive, low-dose dynamic CT perfusion technique that can accurately measure myocardial perfusion in mL/min/g. This procedure combines patho- anatomical assessment using CT calcium and CT angiography, as well as pathophysiologic assessment using CT-derived stress flow (in mL/min/g) and coronary flow reserve (CFR), which are combined to calculate coronary flow capacity. The current study seeks to test this novel cardiac CT method for assessing patients with INOCA. Our technique’s accuracy in measuring stress flow and CFR has been validated in preclinical models, and its preliminary validation, safety, and feasibility shown in patients. We propose to study prospectively its accuracy for assessing INOCA. The study aims to (1) test the hypothesis that rest flow, stress flow, and CFR measured by noninvasive dynamic CT perfusion highly correlate with that by invasive measurement in patients with INOCA; (2) establish a stress flow and CFR reference range determined by noninvasive dynamic CT perfusion that could be used to set the minimum normal thresholds for stress flow and CFR; and (3) test the hypothesis that comprehensive cardiac CT can be used to differentiate between patients with and without physiologically significant coronary artery disease (CAD) in patients with suspected INOCA. Aim 1 will enroll 150 patients with positive stress test and INOCA. Patients will undergo our comprehensive cardiac CT followed by invasive stress flow and CFR tests. Aim 2 will enroll 50 patients with negative stress test and measured invasive stress perfusion greater than 1.21 mL/min/g and CFR > 2.0 to establish the normative range of CT-based stress flow and CFR. Aim 3 will discriminate between patients with and without physiologically significant CAD with dynamic CT perfusion, using invasive stress perfusion and CFR as the reference standard. The study’s successful completion invasive tool that allows comprehensive concurrent evaluation of coronary anatomyand physiology in symptomatic patients with INOCA.

抽象的 缺血性冠心病是世界死亡率和发病率的主要原因。在这个综合体中 疾病实体，许多患者患有心肌缺血，但发现没有阻塞冠状动脉 动脉（inoca）。这些患者患心血管事件的风险很高。但是当前的方法准确 诊断和评估INOCA的物理作用是有限的。基于导管的方法是 侵入性，带有增加的风险，程序性时间和成本。正电子发射断层扫描（PET）和心脏磁 共振（CMR）是临床评估INOCA的两种无创技术，都有局限性 幽闭恐惧症（CMR），成本和辐射剂量（PET）以及本地专业知识和可用性（两者）。这些都不是 非侵入性测试准确地得出有关冠状动脉粥样硬化程度及其其程度的解剖信息 病理生理后果。我们已经开发了一种无创，低剂量的动态CT灌注 可以准确测量ML/min/g中心肌灌注的技术。此过程结合了病原 使用CT钙和CT血管造影以及使用病理生理评估的解剖学评估 CT衍生的应力流（以mL/min/g）和冠状动脉流量储备（CFR），它们合并以计算冠状动脉 流量。当前的研究旨在测试这种新颖的心脏CT方法，用于评估INOCA患者。 我们的技术在临床前模型中已经验证了我们的技术在测量应力流和CFR方面的准确性，其 患者显示的初步验证，安全性和可行性。我们建议研究其准确性 用于评估Inoca。该研究的目的是（1）测试静止流，应力流和CFR的假设 通过非侵入性动态CT灌注与Inoca患者的侵入性测量高度相关。 （2）建立通过非侵入性动态CT灌注确定的应力流和CFR参考范围 用于设置应力流和CFR的最小正常阈值； （3）检验以下假设 全面的心脏CT可用于区分和没有身体的患者 可疑inoca的患者中，明显的冠状动脉疾病（CAD）。 AIM 1将注册150名患者 阳性应力测试和INOCA。患者将经历我们的全面心脏CT，然后进行侵入性压力 流量和CFR测试。 AIM 2将招募50名患有负压力测试和测量侵入性应力灌注的患者 大于1.21 mL/min/g和CFR> 2.0，以建立基于CT的应力流和CFR的正常范围。 AIM 3将区分具有动态CT和动态CT的物理显着CAD的患者 灌注，使用侵入性应力灌注和CFR作为参考标准。该研究成功完成 侵入性工具允许全面评估冠状动脉解剖学和生理学 有症状的INOCA患者。