Natural history data on clinical coronary artery disease (CAD) indicates that there is a critical need to prospectively identify rapidly progressing and vulnerable coronary lesions that may cause potentially fatal acute coronary events [1]. Recent prospective clinical investigations have evaluated the value of wall shear stress (WSS) as a prognostic marker for identifying rapidly progressing coronary lesions [2,3]. Data indicate that low WSS is associated with significant plaque progression, while regions of high WSS are associated with plaque regression and phenotypic transformation towards a more vulnerable lesion. While these studies provided unprecedented data on the role of hemodynamic-induced mechanical forces in lesion dynamics, they were limited by a lack of focal understanding of the association between WSS and plaque progression. Specifically, despite the understanding that WSS and plaque progression are heterogeneous around the artery’s circumference, in each image slice WSS values were spatially averaged around the circumference and correlated with average values for changes in virtual histology-intravascular ultrasound (VH-IVUS) defined plaque constituent areas.

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