Identification of the haemodynamic environment permissive for plaque erosion

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.

Figure 1

CFD analysis of artery wall underlying adherent thrombi. CFD was used to calculate the spatially averaged TAWSS within a non-diseased area and under the thrombus (n = 17) identifying a significant elevation of TAWSS, the median value is displayed on the graph (*p < 0.05, **p < 0.01, ***p < 0.001 paired T-test). No significant difference in OSI was observed between groups.

Figure 2

The log2 fold change displayed as a heatmap between the non-diseased reference segment and thrombus-covered areas, with red representing an increase and blue indicating a decrease.

Figure 3

Reconstructed lumen geometries of the LAD, LCX and RCA arteries. Haemodynamic metrics were extracted from CFD simulations. Spatially averaged Time-Averaged Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), Relative Residence Time (RRT) and Time-Averaged Wall Shear Stress Gradient (TAWSSG). Both ‘rest’ and ‘exercise’ flow rate conditions were simulated. The thrombus is the opaque portion of the metrics, whilst the remainder of the lumen is semi-transparent. Flow is from top to bottom for all images. Minimum and maximum values for the legends are the lower and upper quartiles of the respective metrics averaged across the rest and exercise cases separately, as shown in Table S4 & Table S5. RRT ranges are normalised with respect to the averaged median RRT at the ‘non-diseased’ location, with the median values being 1.11 and 0.43 for rest and exercise respectively (see “Supplementary data S1” for full results). Ensight 10.2.3, was used to post-process and visualise the results. *The median value for the respective metric.

Figure 4

Probing the haemodynamic conditions permissive for plaque erosion. OCT and bi-plane angiography of coronary arteries were collected and used to reconstruct lumen geometries (n = 17). Red sections are high accuracy reconstructions from hybrid OCT/bi-plane angiography, blue sections use bi-plane angiography and OCT to determine the diameter and branch of angle for the flow extensions, with adherent thrombus in green. At ‘rest’ and ‘exercise’ pulsatile flow conditions were simulated for 4 cardiac cycles. Haemodynamic flow results were post-processed to quantify additional wall shear-based haemodynamic metrics of interest. Ensight 10.2.3, was used to post-process and visualise the results.