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

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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.