The role of endothelial shear stress, shear stress gradient, and plaque topography in plaque erosion

Abstract

Background and aims: Plaque erosion is a common underlying cause of acute coronary syndromes. The role of endothelial shear stress (ESS) and endothelial shear stress gradient (ESSG) in plaque erosion remains unknown. We aimed to determine the role of ESS metrics and maximum plaque slope steepness in plaques with erosion versus stable plaques.

Methods: This analysis included 46 patients/plaques from TOTAL and COMPLETE trials and Brigham and Women's Hospital's database who underwent angiography and OCT. Plaques were divided into those with erosion (n = 24) and matched stable coronary plaques (n = 22). Angiographic views were used to generate a 3-D arterial reconstruction, with centerlines merged from angiography and OCT pullback. Local ESS metrics were assessed by computational fluid dynamics. Among plaque erosions, the up- and down-slope (Δ lumen area/frame) was calculated for each culprit plaque.

Results: Compared with stable plaque controls, plaques with an erosion were associated with higher max ESS (8.3 ± 4.8 vs. 5.0 ± 1.9 Pa, p = 0.02) and max ESSG any direction (9.2 ± 7.5 vs. 4.3 ± 3.11 Pa/mm, p = 0.005). Proximal erosion was associated with a steeper plaque upslope while distal erosion with a steeper plaque downslope. Max ESS and Max ESSG any direction were independent factors in the development of plaque erosion (OR 1.32, 95%CI 1.06-1.65, p = 0.014; OR 1.22, 95% CI 1.03-1.45, p = 0.009, respectively).

Conclusions: In plaques with similar luminal stenosis, plaque erosion was strongly associated with higher ESS, ESS gradients, and plaque slope as compared with stable plaques. These data support that ESS and slope metrics play a key role in the development of plaque erosion and may help prognosticate individual plaques at risk for future erosion.

Keywords: Acute coronary syndrome; Endothelial shear stress; Plaque erosion.

Fig. 1.

Representative images of 3D reconstruction and color-coded lumen radius (A), endothelial shear stress (ESS) (B), and endothelial shear stress gradient (ESSG) (C) values from a patient with plaque erosion; and a patient with a control plaque (D), (E), and (F), respectively. Location of thrombus noted in the patient with plaque erosion. Arrows identify the location of severe lumen obstruction (MLA), high ESS (throat of obstruction), low ESS (up-, down-stream from the MLA), and high ESSG (differences in the magnitude of ESS in immediately adjacent endothelial cells, located at the site of abrupt change in lumen area and ESS).

Fig. 2.

Differences in endothelial shear stress metrics between the erosion group (n = 24) and the control group (n = 22). The Wilcoxon Rank test was used for statistical comparisons. Plaques with an erosion were associated with higher max ESS (8.3 ± 4.8 vs. 5.0 ± 1.9 Pa, p = 0.027), Max ESSG any direction (9.2 ± 7.5 vs. 4.3 ± 3.11 Pa/mm, p = 0.005), Max ESSG circumferential direction (4.0 ± 3.3 vs. 1.9 ± 1.4 Pa/mm, p = 0.003) and Max ESSG along the plaque upslope (5.0 ± 6.1 vs 2.1 ± 2.3 Pa/mm, p = 0.009) compared to the control plaques. There was no difference in min ESS between erosion and control plaques (0.8 ± 0.5 vs 0.6 ± 0.4, p = 0.40).

Fig. 3.

(A) Representative image of erosion site as it appears in a longitudinal OCT pullback, which enables assessment of erosion location and plaque topography (quantitative shape); (B) three-dimensional OCT view of plaque erosion showing the relationship between plaque slope steepness and ESS metrics: (C) three-dimensional OCT flythrough view of the plaque erosion.

Fig. 4.

The geometry of plaque lumen obstruction (slope) influences local blood flow surrounding plaque and may biomechanically contribute to the nature and severity of plaque destabilization and thrombus formation (red arrow).

Fig. 5.

Schematic presentation of the study’s main points showing the effect of plaque slope steepness on erosion development (left part of the panel), the process of 3-D vessel reconstruction and CFD, and the 3-D color map of the ESS (middle part of the panel), and a table summarizing the main study results concerning the differences in ESS metrics (ESS and ESSG) between the plaque erosion group and the control group (right side of the panel).