Wall Shear Stress Topological Skeleton Independently Predicts Long-Term Restenosis After Carotid Bifurcation Endarterectomy

Umberto Morbiducci,David A Steinman,Maurizio Domanin,Giuseppe De Nisco,Valentina Mazzi,Diego Gallo,Christian Vergara

doi:10.1007/s10439-020-02607-9

Abstract

Wall Shear Stress (WSS) topological skeleton, composed by fixed points and the manifolds linking them, reflects the presence of blood flow features associated to adverse vascular response. However, the influence of WSS topological skeleton on vascular pathophysiology is still underexplored. This study aimed to identify direct associations between the WSS topological skeleton and markers of vascular disease from real-world clinical longitudinal data of long-term restenosis after carotid endarterectomy (CEA). Personalized computational hemodynamic simulations were performed on a cohort of 13 carotid models pre-CEA and at 1 month after CEA. At 60 months after CEA, intima-media thickness (IMT) was measured to detect long-term restenosis. The analysis of the WSS topological skeleton was carried out by applying a Eulerian method based on the WSS vector field divergence. To provide objective thresholds for WSS topological skeleton quantitative analysis, a computational hemodynamic dataset of 46 ostensibly healthy carotid bifurcation models was considered. CEA interventions did not completely restore physiological WSS topological skeleton features. Significant associations emerged between IMT at 60 months follow-up and the exposure to (1) high temporal variation of WSS contraction/expansion (R2 = 0.51, p < 0.05), and (2) high fixed point residence times, weighted by WSS contraction/expansion strength (R2 = 0.53, p < 0.05). These WSS topological skeleton features were statistically independent from the exposure to low WSS, a previously reported predictor of long-term restenosis, therefore representing different hemodynamic stimuli and potentially impacting differently the vascular response. This study confirms the direct association between WSS topological skeleton and markers of vascular disease, contributing to elucidate the mechanistic link between flow disturbances and clinical observations of vascular lesions.

Highlights

Extensive research has investigated the mechanisms through which the hemodynamic environment at the carotid artery bifurcation influences the origin and progression of cardiovascular diseases.[27]
In pre-carotid endarterectomy (CEA) models, a Wall Shear Stress (WSS) contraction region was located in correspondence of the cross-sectional area reduction at the stenosis, while for the post-CEA and healthy cohorts contraction and expansion regions were mainly located at the carotid bulb (Fig. 2), consistently with previous observations.[25]
As for the cycle-average WSS fixed points, saddle points, stable foci and unstable nodes were present on the carotid luminal surface of most of the carotid models, independent of the cohort, but at different locations: (1) in the preCEA cohort, cycle-average WSS fixed points were mostly located in proximity to the stenosis; (2) on postCEA models, cycle-average WSS fixed points were located at the carotid bulb, in general with similarities to the cycle-average WSS topological skeleton of healthy carotid bifurcations (Fig. 2)

Summary

Introduction

Extensive research has investigated the mechanisms through which the hemodynamic environment at the carotid artery bifurcation influences the origin and progression of cardiovascular diseases.[27]. The exposure to low WSS appears promising in terms of predicting the risk of longterm restenosis after carotid endarterectomy (CEA), a surgical intervention consisting in the removal of the plaque on both symptomatic and asymptomatic patients with moderate to severe carotid stenosis.[28]. 0090-6964/20/1200-2936/0 Ó 2020 The Author(s) affecting CEA outcome leading to development of cerebral symptoms or even carotid occlusion and stroke, presents similarities with native carotid artery stenosis[19,28] when the absence of post-CEA residual atherosclerosis and short-term restenosis (i.e., > 6 months and < 24 months14,19) are accounted for. The mechanisms underlying both atherosclerosis and long-term restenosis are mechanistically influenced by the hemodynamic environment. The specificity of the currently considered hemodynamic features based on low and oscillatory WSS, which are significant but only moderate predictors of disease localization,[15,29] and their clinical added value, hampered by the practical challenges of including hemodynamic information from computational modelling in large prospective clinical studies,[31] have been questioned.[15,29]

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Conclusion