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 缺血性冠心病是全球死亡率和发病率的主要原因。 疾病实体，许多患者患有心肌缺血，但未发现冠状动脉阻塞 动脉（INOCA）。这些患者发生心血管事件的风险很高。 基于导管的方法的诊断和评估 INOCA 的生理效应是有限的。 侵入性，增加了风险、手术时间和成本。 共振 (CMR) 是两种用于临床评估 INOCA 的无创技术，但都有局限性，例如 幽闭恐惧症 (CMR)、成本和辐射剂量 (PET) 以及当地的专业知识和可用性（两者都不是）。 无创测试可以准确地得出冠状动脉粥样硬化程度及其相关的解剖学信息。 我们开发了一种无创、低剂量动态 CT 灌注。 可以精确测量心肌灌注（mL/min/g）的技术。该过程结合了病理学。 使用 CT 钙和 CT 血管造影进行解剖学评估，以及使用 CT 得出的应力流量（以 mL/min/g 为单位）和冠状动脉血流储备 (CFR)，将其组合起来计算冠状动脉 当前的研究旨在测试这种用于评估 INOCA 患者的新型心脏 CT 方法。 我们的技术测量应力流和 CFR 的准确性已在临床前模型中得到验证，其 我们建议前瞻性地研究其准确性。 用于评估 INOCA。该研究旨在 (1) 检验测量静息流量、应力流量和 CFR 的假设。 INOCA 患者的无创动态 CT 灌注与有创测量高度相关； (2)建立由无创动态CT灌注确定的应力流和CFR参考范围，可以 用于设置应力流和 CFR 的最小正常阈值；以及 (3) 检验以下假设： 综合心脏CT可用于区分有或无生理症状的患者 疑似患有严重冠状动脉疾病 (CAD) 的患者 INOCA 目标 1 将招募 150 名患者。 阳性压力测试和 INOCA 患者将接受我们的全面心脏 CT 检查，然后进行侵入性压力检查。 目标 2 将招募 50 名进行阴性压力测试并测量侵入性压力灌注的患者。 大于 1.21 mL/min/g 且 CFR > 2.0，以确定基于 CT 的应力流和 CFR 的规范范围。 目标 3 将通过动态 CT 区分患有和不患有生理学显着 CAD 的患者 灌注，以侵入性应激灌注和CFR作为参考标准，该研究顺利完成。 允许对冠状动脉解剖和生理学进行全面同步评估的侵入性工具 有 INOCA 症状的患者。