BackgroundPlaques associated with abnormally low physiological flow reserve indices are appropriate for percutaneous coronary intervention (PCI). However, recent trials demonstrate that PCI of ischemia-producing lesions does not reduce major adverse cardiac events (MACE). Low endothelial shear stress (ESS) or high ESS gradient (ESSG) are associated with MACE wherever they occur along the plaque. This study aims to determine the presence of high-risk ESS metrics in obstructive coronary plaques with high-risk (<0.80) vs. borderline-risk (0.80–0.89) vs. normal Instantaneous Wave-free Ratio (iFR) (>0.89). MethodsWe included 50 coronary arteries (50 patients) with variable iFR values who underwent coronary angiography and optical coherence tomography (OCT), followed by 3D reconstruction and computational fluid dynamics calculations of ESS/ESSG. The cohort was divided into 3 groups: iFR < 0.80, iFR 0.80–0.89, and iFR > 0.89. Spatial distribution of ESS metrics was reported along the course of each plaque, and high-risk ESS metrics and their location were compared among the 3 iFR subgroups. ResultsHigh-risk ESS features (Minimal ESS, Maximum ESSG) were similarly distributed along the course of the atherosclerotic plaque in the three iFR subgroups, both in absolute value and in location: Min ESS: 0.5 ± 0.3 vs. 0.4 ± 0.2 vs. 0.4 ± 0.2 Pa respectively (p = 0.60); Max ESSG any direction: 13.7 ± 9.4 vs. 10.4 ± 10.6 vs. 10.0 ± 7.8 Pa/mm respectively (p = 0.30). ESS metrics were spatially located up to ≥18 mm from the plaque minimal luminal area (MLA) in both directions. ConclusionHigh-risk ESS metrics are similarly observed in plaques with normal or abnormal iFR, both in absolute value and spatial location in reference to the MLA. Utilizing iFR to identify plaques likely to cause MACE would miss the majority of plaques mechanistically at high-risk to destabilize and cause future adverse cardiac events.