Identification of the haemodynamic environment permissive for plaque erosion

Michael Mcelroy,Frank Gijsen,Giampaolo Niccoli,Thomas Johnson,Amir Keshmiri,Filippo Crea,Yongcheol Kim,Stephen J White,Rocco Vergallo,Alexander Langford-Smith

doi:10.1038/s41598-021-86501-x

Abstract

Endothelial erosion of atherosclerotic plaques is the underlying cause of approximately 30% of acute coronary syndromes (ACS). As the vascular endothelium is profoundly affected by the haemodynamic environment to which it is exposed, we employed computational fluid dynamic (CFD) analysis of the luminal geometry from 17 patients with optical coherence tomography (OCT)-defined plaque erosion, to determine the flow environment permissive for plaque erosion. Our results demonstrate that 15 of the 17 cases analysed occurred on stenotic plaques with median 31% diameter stenosis (interquartile range 28–52%), where all but one of the adherent thrombi located proximal to, or within the region of maximum stenosis. Consequently, all flow metrics related to elevated flow were significantly increased (time averaged wall shear stress, maximum wall shear stress, time averaged wall shear stress gradient) with a reduction in relative residence time, compared to a non-diseased reference segment. We also identified two cases that did not exhibit an elevation of flow, but occurred in a region exposed to elevated oscillatory flow. Our study demonstrates that the majority of OCT-defined erosions occur where the endothelium is exposed to elevated flow, a haemodynamic environment known to evoke a distinctive phenotypic response in endothelial cells.

Highlights

The majority of culprit plaques imposed a stenosis on the artery with 16 of the 17 cases having thrombi adhering proximal to, or overlying the point of maximum stenosis
In line with the observed location of the thrombi on stenotic plaques, all metrics related to an elevation of flow were observed. These included an increase in spatially averaged time averaged wall shear stress (TAWSS ~ fivefold for both normal and exercise simulation), maximum wall shear stress (WSSmax, 22 or 20-fold normal/exercise simulation respectively), spatially averaged time averaged wall shear stress gradient (TAWSSG, 6.5 or 5-fold normal/exercise simulation respectively) and reduced relative residence time (RRT, 4 or 2-fold normal/exercise simulation respectively) (Fig. 1)
The profound influence imparted by the haemodynamic environment on regulation of endothelial function[17,18,19,20,21], and the response to noxious stimuli that induce endothelial d ysfunction[26,27,28] suggest that the haemodynamic environment is likely to influence the pathophysiology of plaque erosion

Summary

Introduction

Endothelial erosion of atherosclerotic plaques is the underlying cause of approximately 30% of acute coronary syndromes (ACS). Abbreviations OCT Optical coherence tomography CFD Computational fluid dynamic ACS Acute coronary syndromes LAD Left anterior descending artery LCX Left circumflex artery RCA Right coronary artery TAWSS Time averaged wall shear stress WSSmax Maximum wall shear stress TAWSSG Time averaged wall shear stress gradient RRT Relative residence time OSI Oscillatory shear index. Other traditional risk factors for ACS, including diabetes, hyperlipidaemia and hypertension, identify with plaque rupture, highlighting that the mechanisms of endothelial erosion differ from those of plaque rupture and require better understanding. These considerations mandate further mechanistic investigation of endothelial erosion

Methods

Results

Conclusion