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

摘要 缺血性冠心病是世界上导致死亡和发病的主要原因。在这个建筑群里 疾病实体，许多患者患有心肌缺血，但被发现没有冠状动脉阻塞 动脉(INOCA)。这些患者发生心血管事件的风险很高。然而，目前的方法可以准确地 诊断和评估INOCA的生理效应是有限的。基于导管的方法有 侵入性，增加了风险、程序时间和成本。正电子发射断层扫描(PET)与心脏磁学 磁共振(CMR)是临床上评估INOCA的两种非侵入性技术，但存在以下局限性 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获得性(两者)。这些都不是 无创检查准确地提供了关于冠状动脉粥样硬化程度的解剖信息和它的 病理生理学后果。我们已经开发了一种无创、低剂量的动态CT灌注 这项技术可以准确地测量心肌血流灌注(以毫升/分钟/克为单位)。 使用CT钙化和CT血管造影术进行解剖评估，以及使用 CT导出的应力流量(单位：毫升/分钟/克)和冠状动脉血流储备(CFR)，结合计算冠状动脉 流量。目前的研究试图测试这种新的心脏CT方法来评估INOCA患者。 我们的技术在测量应力流动和CFR方面的准确性已在临床前模型中得到验证，其 初步的有效性、安全性和在患者身上显示的可行性。我们建议前瞻性地研究它的准确性。 用于评估INOCA。本研究的目的是(1)检验静止流、应力流和CFR测量的假设 INOCA患者无创动态CT血流灌注值与有创值高度相关； (2)建立由无创性动态CT灌注确定的应力流量和CFR参考范围。 用于设置应力流动和CFR的最小正常阈值；以及(3)检验假设 全面的心脏CT可用于区分生理性和非生理性的患者 疑似INOCA患者存在严重的冠状动脉疾病(CAD)。AIM 1将招募150名患有 压力测试和INOCA呈阳性。患者将接受我们的全面心脏CT检查，然后进行侵入性应激 流量和CFR测试。Aim 2将招募50名接受阴性负荷试验和有创负荷灌流的患者。 大于1.21毫升/分/克和CFR&GT；2.0，以建立基于CT的应力流动和CFR的标准范围。 AIM 3将通过动态CT区分有无明显生理性冠心病的患者 灌注，以有创应激灌注和CFR为参考标准。这项研究圆满完成 一种侵入性工具，允许对冠状动脉解剖和生理进行全面同时评估 有症状的INOCA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.