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Background Wall shear stress (WSS) plays an important role in coronary atherosclerosis. Low WSS is associated with inflammation, endothelial dysfunction, and progression of atherosclerosis; while high WSS leads to vulnerable plaque transformation and future myocardial infarction. Defining the relationship between WSS and the currently available coronary physiology indices would provide valuable insights into potential mechanisms for predicting future adverse cardiac events. Purpose To investigate the relationship between WSS and the coronary epicardial/microvascular physiology indices. Methods Patients undergoing coronary angiography and physiology testing were prospectively recruited. Physiology measurements were performed under resting and hyperaemic conditions using a pressure/temperature sensor guidewire. Fractional flow reserve (FFR), non-hyperaemic pressure ratios (NHPRs), coronary flow reserve (CFR), and corrected index of microcirculatory resistance (IMR) were measured. The NHPRs including resting full-cycle ratio (RFR), resting distal/aortic pressure (Pd/Pa), instantaneous wave-free ratio (iFR), diastolic pressure ratio (dPR) and diastolic hyperaemia-free ratio (DFR) were derived offline by a blinded expert reader. Values of FFR ≤0.80, NHPR ≤0.89, CFR &amp;lt;2, or IMR &amp;gt;25 were considered ischaemic/abnormal. Computational fluid dynamics analysis was performed and fluid motion equations were solved using finite-volume based software. The inlet and outlet boundary conditions were set to the patient-specific Pa and Pd respectively. The lesion WSS, mean WSS in five segments (WSSupstream = 5mm proximal to lesion, WSSprox = proximal third of lesion, WSSmid = middle third of lesion, WSSdistal = distal third of lesion, WSSdownstream = 5mm distal to lesion), and the total area of low WSS (defined as &amp;lt;1 Pa) along the entire vessel were calculated (Figure A). Results A total of 112 vessels from 93 patients were included in the study. The total area of low WSS was significantly larger in lesions with ischaemic FFR, NHPRs, and CFR values (Figure B), and not significantly different in lesions with abnormal IMR values. There was no significant difference in lesion WSS between groups stratified by all physiology indices. Within the lesion WSS sub-segments, WSSprox was significant higher in ischaemic lesions stratified by normal/abnormal FFR, iFR, and dPR (4.2 vs 3.3 Pa, 4.2 vs 3.3 Pa, 4.3 vs 3.3 Pa respectively, all p=0.04), and not significantly different when stratified by RFR, DFR, Pd/Pa, CFR, and IMR. Conclusion Functionally significant coronary lesions classified by the epicardial physiology indices have significantly larger total area of low WSS and higher WSSprox which may explain the higher cardiovascular event rates in patients with ischaemic lesions. There was no significant relationship between WSS and coronary microcirculatory resistance. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation of Australia Health Professional Scholarship

Size of low wall shear stress areas in coronary arteries is related to epicardial physiology and not to microcirculatory resistance