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Aims The association of low endothelial shear stress (ESS) with high-risk plaque (HRP) has not been thoroughly investigated in humans. We investigated the local ESS and lumen remodelling patterns in HRPs using optical coherence tomography (OCT), developed the shear stress score , and explored its association with the prevalence of HRPs and clinical outcomes. Methods and results A total of 35 coronary arteries from 30 patients with stable angina or acute coronary syndrome (ACS) were reconstructed with three dimensional (3D) OCT. ESS was calculated using computational fluid dynamics and classified into low, moderate, and high in 3-mm-long subsegments. In each subsegment, (i) fibroatheromas (FAs) were classified into HRPs and non-HRPs based on fibrous cap (FC) thickness and lipid pool size, and (ii) lumen remodelling was classified into constrictive, compensatory, and expansive. In each artery the shear stress score was calculated as metric of the extent and severity of low ESS. FAs in low ESS subsegments had thinner FC compared with high ESS (89 ± 84 vs.138 ± 83 µm, P < 0.05). Low ESS subsegments predominantly co-localized with HRPs vs. non-HRPs (29 vs. 9%, P < 0.05) and high ESS subsegments predominantly with non-HRPs (9 vs. 24%, P < 0.05). Compensatory and expansive lumen remodelling were the predominant responses within subsegments with low ESS and HRPs. In non-stenotic FAs, low ESS was associated with HRPs vs. non-HRPs (29 vs. 3%, P < 0.05). Arteries with increased shear stress score had increased frequency of HRPs and were associated with ACS vs. stable angina. Conclusion Local low ESS and expansive lumen remodelling are associated with HRP. Arteries with increased shear stress score have increased frequency of HRPs and propensity to present with ACS.

Background: High risk plaque accounts for the majority of acute coronary events. Low endothelial shear stress (ESS) is a key factor of the natural history of atherosclerosis. The role of ESS in high risk plaque formation is not well studied in man. Hypothesis: To explore the association of low ESS with high risk plaque and to identify the ESS milieu and vascular remodeling response in high risk vs. non high risk plaque. Methods: 35 coronary arteries from 30 patients were 3D reconstructed with fusion of coronary angiography and optical coherence tomography (Fig A-D) . ESS was calculated in the 3D reconstructed arteries using computational fluid dynamics (Fig E) and classified into low, moderate and high in 3 mm long segments. In each segment: i) fibroatheromas were classified into high risk and non high risk based on fibrous cap thickness and lipid pool size ii) vascular remodeling was classified into constrictive, compensatory and expansive. Results: Fibroatheromas in low ESS segments had significantly thinner fibrous cap compared to high ESS segments (89±84 vs.138±83 μm, pFig F ). Compensatory and expansive remodeling was the predominant remodeling response in low ESS segments containing high risk plaques. In non-stenotic fibroatheromas (expansive or compensatory remodeling) low ESS was predominantly associated with high risk plaques (29 vs. 3%, p(Fig F) . Conclusions: Novel combined anatomic and functional imaging with 3D OCT showed that low ESS and non-constrictive remodeling are associated with high risk plaque in man. Further studies are needed to assess the role of ESS and vascular remodeling in high risk plaque rupture and precipitation of clinical outcomes.

Low endothelial shear stress (ESS) is associated with high-risk plaques (HRPs) in coronary arteries. We developed the arterial shear stress score, a global metric of the extent and severity of low ESS and investigated its association with the prevalence of HRPs and clinical events. 35 coronary