Physiological Basis for Angina and ST-Segment Change: PET-Verified Thresholds of Quantitative Stress Myocardial Perfusion and Coronary Flow Reserve

Abstract

This study aimed to determine the quantitative low-flow threshold for stress-induced perfusion defects with severe angina and/or significant ST-segment depression during dipyridamole hyperemia. Vasodilator stress reveals differences in regional perfusion without ischemia in most patients. However, in patients with a perfusion defect, angina, and/or significant ST-segment depression during dipyridamole stress, quantitative absolute myocardial perfusion and coronary flow reserve (CFR) at the exact moment of definite ischemia have not been established. Defining these low-flow thresholds of angina or ST-segment changes may offer insight into physiological disease severity in patients with atherosclerosis. Patients underwent rest-dipyridamole stress positron emission tomography (PET) with absolute flow quantification in ml/min/g. Definite ischemia was defined as a new or worse perfusion defect during dipyridamole stress with significant ST-segment depression and/or severe angina requiring pharmacological treatment. Indeterminate clinical features required only 1 of these 3 abnormalities. The comparison group included patients without prior myocardial infarction, or angina or electrocardiographic changes after dipyridamole. In 1,674 sequential PET studies, we identified 194 (12%) with definite ischemia, 840 (50%) studies with no ischemia, and 301 (18%) that were clinically indeterminate. A vasodilator stress perfusion cutoff of 0.91 ml/min/g optimally separated definite from no ischemia with an area under the receiver-operator characteristic curve (AUC) of 0.98 and a CFR cutoff of 1.74 with an AUC = 0.91, reflecting excellent discrimination at the exact moment of definite ischemia. Thresholds of low myocardial vasodilator stress perfusion in ml/min/g and CFR sharply separate patients with angina or ST-segment change from those without these manifestations of ischemia during dipyridamole stress with excellent discrimination. Stress flow below 0.91 ml/min/g in dipyridamole-induced PET perfusion defects causes significant ST-segment depression and/or severe angina. However, when the worst vasodilator stress flow exceeds 1.12 ml/min/g, these manifestations of ischemia occur rarely.