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

摘要 缺血性冠状动脉心脏病是世界上主要的死亡和发病原因。在这个复杂的 疾病实体，许多患者患有心肌缺血，但发现没有阻塞的冠状动脉 动脉（INOCA）。这些患者发生心血管事件的风险很高。然而，目前的方法， 诊断和评估INOCA的生理效应是有限的。基于导管的方法是 侵入性，增加了风险、手术时间和成本。正电子发射断层扫描（PET）和心脏磁共振成像（MRI） 共振（CMR），这两种用于临床评估INOCA的非侵入性技术，具有局限性， 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）。没有这些 非侵入性测试准确地产生关于冠状动脉粥样硬化程度的解剖学信息， 病理生理后果。我们开发了一种无创、低剂量的动态CT灌注成像技术 可以准确测量心肌灌注（mL/min/g）的技术。这一过程结合了病理- 使用CT钙和CT血管造影进行解剖学评估，以及使用 CT衍生的应力流量（mL/min/g）和冠状动脉血流储备（CFR），将其结合起来计算冠状动脉 流量目前的研究旨在测试这种新的心脏CT方法来评估INOCA患者。 我们的技术在测量应力流和CFR方面的准确性已经在临床前模型中得到了验证， 初步验证，安全性和可行性在患者中显示。我们建议前瞻性地研究其准确性 评估INOCA。本研究的目的是（1）测试假设，休息流，应力流，和CFR测量 INOCA患者无创动态CT灌注与有创测量结果高度相关; (2)通过无创动态CT灌注确定应力流和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可用于区分患有和不患有生理性心脏病的患者。 疑似INOCA患者中的显著冠状动脉疾病（CAD）。目标1将招募150名患者， 积极的压力测试和INOCA。患者将接受我们的全面心脏CT检查， 流量和CFR测试。目的2将入组50例负荷试验阴性并测量有创负荷灌注的患者 大于1.21 mL/min/g和CFR > 2.0，以建立基于CT的应力流和CFR的标准范围。 目的3将通过动态CT区分患有和不患有生理学显著CAD的患者 灌注，使用有创应力灌注和CFR作为参考标准。研究的顺利完成 有创性工具，允许全面的冠状动脉解剖学和生理学同步评价， INOCA的症状患者。

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.