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

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.

SUBMITTER: Morbiducci U

PROVIDER: S-EPMC7723943 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Morbiducci Umberto U Mazzi Valentina V Domanin Maurizio M De Nisco Giuseppe G Vergara Christian C Steinman David A DA Gallo Diego D

Annals of biomedical engineering 20200914 12

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 endartere ...[more]

PMID: 32929560

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Project description:This study aimed to describe the duplex ultrasound (DUS) findings associated with carotid restenosis after carotid endarterectomy (CEA) and to determine whether carotid restenosis is associated with the clinical outcomes of CEA. Between January 2007 and December 2016, a total of 660 consecutive patients who underwent 717 CEAs were followed up at our hospital with DUS surveillance for at least 3 years after CEA. These patients were analyzed retrospectively for this study. Following CEA, restenosis was defined as the development of ≥50% stenosis, diagnosed on the basis of DUS findings of the luminal narrowing and velocity criteria. The study outcomes were defined as restenosis of the ipsilateral carotid artery after CEA and late (>30days) fatal or nonfatal stroke ipsilateral to the carotid restenosis. During the median follow-up period of 74 months, the restenosis incidence was 2.8% (20/717), and there were 2 strokes (2/20, 10%) ipsilateral to the restenosis after CEA; reintervention was performed for 11 patients with carotid restenosis (55%). Within 2 years after CEA, restenosis was identified in 9 cases (45%, 9/20), and 8 reinterventions (72.7%, 8/11) were performed. According to DUS findings, the morphologic characteristics of carotid restenosis were different from the preoperative plaque morphology. Among the 20 carotid restenosis cases, we observed the following DUS patterns: homogenous isoechoic restenosis (n = 14, 70%), homogenous hypoechoic (n = 2, 10%), isoechoic with hypoechoic surface (n = 3, 15%), and hypoechoic with isoechoic surface (n = 1, 5%). Although 9 carotid restenosis patients received prophylactic reintervention to mitigate the progression of restenosis, the 2 symptomatic restenosis patients had isoechoic lesions with hypoechoic surfaces on DUS. On Kaplan-Meier survival analyses, in terms of stroke-free survival rates, there was a higher risk of stroke among patients with carotid restenosis compared with patients without restenosis, with a non-significant trend (P = 0.051). In conclusion, most carotid restenoses were identified within 2 years after CEA, and there was a non-significant trend toward a higher risk of stroke among patients with carotid restenosis.

Project description:PurposeWe aimed to evaluate the long-term outcome of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in patients who underwent both procedures on different sides.MethodsIn this single-center retrospective study (2001-2019), 117 patients (men, N = 78; median age at CEA, 64.4 [interquartile range {IQR}, 57.8-72.2] years; median age at CAS, 68.8 [IQR, 61.0-76.0] years) with ≥50% internal carotid artery stenosis who had CEA on one side and CAS on the other side were included. The risk of restenosis was estimated by treatment adjusted for patient and lesion characteristics.ResultsNeurological symptoms were significantly more common (41.9% vs 16.2%, P<0.001) and patients had a significantly shorter mean duration of smoking (30.2 [standard deviation {SD}, 22.2] years vs 31.8 [SD, 23.4] years, P<0.001), hypertension (10.1 [SD, 9.8] years vs 13.4 [SD, 9.1] years, P<0.001), hyperlipidemia (3.6 [SD, 6.6] years vs 5.0 [SD, 7.3] years, P = 0.001), and diabetes mellitus (3.9 [SD, 6.9] years vs 5.7 [SD, 8.9] years, P<0.001) before CEA compared to those before CAS. While the prevalence of heavily calcified stenoses on the operated side (25.6% vs 6.8%, P<0.001), the incidence of predominantly echogenic/echogenic plaques (53.0% vs 70.1%, P = 0.011) and suprabulbar lesions (1.7% vs 22.2%, P<0.001) on the stented side was significantly higher. Restenosis rates were 10.4% at 1 year, 22.3% at 5 years, and 33.7% at the end of the follow-up (at 11 years) for CEA, while these were 11.4%, 14.7%, and 17.2%, respectively, for CAS. Cox regression analysis revealed a significantly higher risk of restenosis (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.05-3.10; P = 0.030) for CEA compared to that for CAS. After adjusting for relevant confounding factors (smoking, hypertension, diabetes mellitus, calcification severity, plaque echogenicity, and lesion location), the estimate effect size materially did not change, although it did not remain statistically significant (HR, 1.85; 95% CI, 0.95-3.60; P = 0.070).ConclusionIntra-patient comparison of CEA and CAS in terms of restenosis tilts the balance toward CAS.

Project description:Introduction: Carotid geometry and wall shear stress (WSS) have been proposed as independent risk factors for the progression of carotid atherosclerosis, but this has not yet been demonstrated in larger longitudinal studies. Therefore, we investigated the impact of these biomarkers on carotid wall thickness in patients with high cardiovascular risk. Methods: Ninety-seven consecutive patients with hypertension, at least one additional cardiovascular risk factor and internal carotid artery (ICA) plaques (wall thickness ≥ 1.5 mm and degree of stenosis ≤ 50%) were prospectively included. They underwent high-resolution 3D multi-contrast and 4D flow MRI at 3 Tesla both at baseline and follow-up. Geometry (ICA/common carotid artery (CCA)-diameter ratio, bifurcation angle, tortuosity and wall thickness) and hemodynamics [WSS, oscillatory shear index (OSI)] of both carotid bifurcations were measured at baseline. Their predictive value for changes of wall thickness 12 months later was calculated using linear regression analysis for the entire study cohort (group 1, 97 patients) and after excluding patients with ICA stenosis ≥10% to rule out relevant inward remodeling (group 2, 61 patients). Results: In group 1, only tortuosity at baseline was independently associated with carotid wall thickness at follow-up (regression coefficient = -0.52, p < 0.001). However, after excluding patients with ICA stenosis ≥10% in group 2, both ICA/CCA-ratio (0.49, p < 0.001), bifurcation angle (0.04, p = 0.001), tortuosity (-0.30, p = 0.040), and WSS (-0.03, p = 0.010) at baseline were independently associated with changes of carotid wall thickness at follow-up. Conclusions: A large ICA bulb and bifurcation angle and low WSS seem to be independent risk factors for the progression of carotid atherosclerosis in the absence of ICA stenosis. By contrast, a high carotid tortuosity seems to be protective both in patients without and with ICA stenosis. These biomarkers may be helpful for the identification of patients who are at particular risk of wall thickness progression and who may benefit from intensified monitoring and treatment.

Project description:BackgroundIn the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion.MethodsPatients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732.Findings2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42).InterpretationRestenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation.FundingNational Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

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

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

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