Update on Management of Symptomatic Carotid Stenosis.

Carotid artery stenosis (CAS) is one of the leading causes of cerebral ischemia and stroke.7 When plaque builds up in the internal carotid artery, it blocks blood flow to the brain. Oftentimes, this condition only comes to light after a patient experiences a stroke or stroke-like symptoms. When this occurs, cholesterol-lowering medications and blood thinners can help to increase blood flow to the brain. However, if the plaque is so large that it severely narrows the lumen of the artery, surgery may be required to restore blood flow to the brain. Patients with severe stenosis can undergo procedures such as carotid endarterectomies (CEA), stenting, and transcarotid artery revascularization (TCAR) for this purpose. In this review, we discuss these procedures and which patients warrant which type of intervention. We look at the pathophysiology of internal carotid artery stenosis and current treatment options, while highlighting emerging treatment options. This review aims to increase understanding of the management of symptomatic carotid artery stenosis as well as provide a groundwork for more innovative treatments.

A magnetic resonance imaging-based computational analysis of cerebral hemodynamics in patients with carotid artery stenosis.

Management of asymptomatic carotid artery stenosis (CAS) relies on measuring the percentage of stenosis. The aim of this study was to investigate the impact of CAS on cerebral hemodynamics using magnetic resonance imaging (MRI)-informed computational fluid dynamics (CFD) and to provide novel hemodynamic metrics that may improve the understanding of stroke risk. CFD analysis was performed in two patients with similar degrees of asymptomatic high-grade CAS. Three-dimensional anatomical-based computational models of cervical and cerebral blood flow were constructed and calibrated patient-specifically using phase-contrast MRI flow and arterial spin labeling perfusion data. Differences in cerebral hemodynamics were assessed in preoperative and postoperative models. Preoperatively, patient 1 demonstrated large flow and pressure reductions in the stenosed internal carotid artery, while patient 2 demonstrated only minor reductions. Patient 1 exhibited a large amount of flow compensation between hemispheres (80.31%), whereas patient 2 exhibited only a small amount of collateral flow (20.05%). There were significant differences in the mean pressure gradient over the stenosis between patients preoperatively (26.3 vs. 1.8 mmHg). Carotid endarterectomy resulted in only minor hemodynamic changes in patient 2. MRI-informed CFD analysis of two patients with similar clinical classifications of stenosis revealed significant differences in hemodynamics which were not apparent from anatomical assessment alone. Moreover, revascularization of CAS might not always result in hemodynamic improvements. Further studies are needed to investigate the clinical impact of hemodynamic differences and how they pertain to stroke risk and clinical management.

Mediating roles of leukoaraiosis and infarcts in the effects of unilateral carotid artery stenosis on cognition.

Background and objectives: Leukoaraiosis and infarcts are common in patients with carotid artery stenosis (CAS), and CAS severity, leukoaraiosis and infarcts all have been implicated in cognitive impairments. CAS severity was not only hypothesized to directly impede specific cognitive domains, but also transmit its effects indirectly to cognitive function through ipsilateral infarcts as well as periventricular leukoaraiosis (PVL) and deep white matter leukoaraiosis (DWML). We aimed to delineate the contributions of leukoaraiosis, infarcts and CAS to different specific cognitive domains. Materials and methods: One hundred and sixty one participants with unilateral CAS (>50%) on the left (n = 85) or right (n = 76) side and 65 volunteers without significant CAS (<50%) were recruited. The PVL, DWML, and infarct severity were visually rated on MRI. A comprehensive cognitive battery was administered and standardized based on age norms. Correlation and mediation analyses were adopted to examine the direct and indirect influence of CAS, leukoaraiosis, and infarct on specific cognitive domains with adjustment for education, hypertension, diabetes mellitus, and hyperlipidemia. Results: Carotid artery stenosis severity was associated with ipsilateral leukoaraiosis and infarct. Left CAS had direct effects on most cognitive domains, except for visual memory and constructional ability, and transmitted its indirect effects on all cognitive domains through ipsilateral PVL, and on constructional ability and psychomotor through infarcts. Right CAS only had negative direct effects on visual memory, psychomotor, design fluency and color processing speed, and transmitted its indirect effects on visual memory, word and color processing speed through ipsilateral infarcts. The trends of direct and indirect cognitive effects remained similar after covariate adjustment. Conclusion: Left and right CAS would predominantly lead to verbal and non-verbal cognitive impairment respectively, and such effects could be mediated through CAS-related leukoaraiosis and infarct. Given that cognition is subject to heterogeneous pathologies, the exact relationships between markers of large and small vessel diseases and their composite prognostic effects on cognition requires further investigation.

Deep learning-based hemodynamic prediction of carotid artery stenosis before and after surgical treatments.

Hemodynamic prediction of carotid artery stenosis (CAS) is of great clinical significance in the diagnosis, prevention, and treatment prognosis of ischemic strokes. While computational fluid dynamics (CFD) is recognized as a useful tool, it shows a crucial issue that the high computational costs are usually required for real-time simulations of complex blood flows. Given the powerful feature-extraction capabilities, the deep learning (DL) methodology has a high potential to implement the mapping of anatomic geometries and CFD-driven flow fields, which enables accomplishing fast and accurate hemodynamic prediction for clinical applications. Based on a brain/neck CT angiography database of 280 subjects, image based three-dimensional CFD models of CAS were constructed through blood vessel extraction, computational domain meshing and setting of the pulsatile flow boundary conditions; a series of CFD simulations were undertaken. A DL strategy was proposed and accomplished in terms of point cloud datasets and a DL network with dual sampling-analysis channels. This enables multimode mapping to construct the image-based geometries of CAS while predicting CFD-based hemodynamics based on training and testing datasets. The CFD simulation was validated with the mass flow rates at two outlets reasonably agreed with the published results. Comprehensive analysis and error evaluation revealed that the DL strategy enables uncovering the association between transient blood flow characteristics and artery cavity geometric information before and after surgical treatments of CAS. Compared with other methods, our DL-based model trained with more clinical data can reduce the computational cost by 7,200 times, while still demonstrating good accuracy (error<12.5%) and flow visualization in predicting the two hemodynamic parameters. In addition, the DL-based predictions were in good agreement with CFD simulations in terms of mean velocity in the stenotic region for both the preoperative and postoperative datasets. This study points to the capability and significance of the DL-based fast and accurate hemodynamic prediction of preoperative and postoperative CAS. For accomplishing real-time monitoring of surgical treatments, further improvements in the prediction accuracy and flexibility may be conducted by utilizing larger datasets with specific real surgical events such as stent intervention, adopting personalized boundary conditions, and optimizing the DL network.

Quantitative Optical Coherence Tomography Angiography Detects Retinal Perfusion Changes in Carotid Artery Stenosis.

BACKGROUND: Carotid artery stenosis (CAS) is a multifaceted disease characterized by possible ocular involvement. Treatment with carotid endarterectomy helps to restore cerebral perfusion, which may prevent ocular and cerebral complications. The main aim was to assess retinal and choroidal vascular perfusion changes before and after endarterectomy in patients affected by CAS. METHODS: The design of the study was prospective and observational, including patients affected by CAS and healthy controls. The follow-up was 3 months. We performed quantitative optical coherence tomography (OCT) angiography (OCTA) analyses of retinal perfusion changes, before and after endarterectomy. The main outcome measures were the quantitative changes of choroidal thickness (CT), retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL); vessel density (VD); and vessel tortuosity (VT) OCTA metrics were also measured. RESULTS: Sixty eyes of 30 patients affected by CAS and 30 eyes of 30 controls were included. We separately considered the ipsilateral eyes to CAS, the contralateral eyes to CAS, and the healthy eyes. Visual symptoms were absent in all the patients. RNFL and GCL resulted similar between patients and controls (p > 0.05). CT was significantly thinner in ipsilateral eyes than controls (p < 0.01), and it resulted unchanged after surgery (p > 0.05). VD resulted significantly altered only in some plexa of the ipsilateral eyes (p < 0.01), whereas VT disclosed decreased values of the entire retinal vascular network, both in ipsilateral and contralateral eyes (p < 0.05). Endarterectomy was followed by statistically significant improvement of retinal perfusion (p < 0.05). CONCLUSION: Optical coherence tomography angiography can noninvasively detect postendarterectomy retinal perfusion improvements in CAS patients with baseline diabetes and hypertension as a systemic risk factor.

Impact of cerebral ischemic lesions on the outcome of carotid endarterectomy.

Patients with carotid artery stenosis (CAS) are commonly defined as asymptomatic or symptomatic according with their neurological conditions, however, emerging evidences suggest stratifying patients according also with the presence of cerebral ischemic lesions (CIL). In asymptomatic patients, the presence of CIL increases the risk of future neurologic event from 1% to 4% per year, leading to a stronger indication to carotid revascularization. In symptomatic patients, the presence of CIL does not seem to influence the outcome of the carotid revascularization if the volume of the lesion is small (<4,000 mm3); the benefit of the revascularization is also more significant if performed within 2 weeks from the index event. However, high volume (>4,000 mm3) CIL are associated in some experiences with a higher risk of carotid revascularization suggesting to delay the carotid revascularization for at least 4 weeks. As a matter of fact, the evaluation of CIL dimensions and characteristics in patients with CAS gives to the physician involved in the treatment a valuable adjunctive tool in the choice of the ideal treatment.

In-hospital clinical outcomes of transcatheter aortic valve replacement in patients with concomitant carotid artery stenosis: Insights from the national inpatient sample.

BACKGROUND: Carotid artery stenosis (CAS) is a common occurrence in elderly patients undergoing transcatheter aortic valve replacement (TAVR). We conducted a retrospective study to identify the impact of CAS on in-hospital outcomes following TAVR. METHODS: We queried the National Inpatient Sample (NIS) for 2016-2017 and identified patients who underwent TAVR with concomitant CAS using the ICD-10 codes. The primary endpoint of our study was in-hospital mortality and acute ischemic stroke. RESULTS: We identified 80,740 TAVR-related hospitalizations. Of these, 6.9% (N = 5555) patients had concomitant CAS. The mean age for CAS patients was 80 ± 7.4 years. Females were represented equally in both groups. Traditional comorbidities like dyslipidemia [78.3% (N = 4350) vs. 68.2% (N = 51261); P < 0.001] and peripheral arterial disease [27.4% (N = 1525) vs. 12.7% (N = 9526); P < 0.001] were more frequently observed among CAS patients. Patients with CAS had higher rates of previous stroke [17.5% (N = 970) vs. 11.8% (N = 8902); P < 0.001] and CABG 23.8% (N = 1320) vs. 18.6% (N = 14022); P < 0.001]. Other cardiovascular risk factors were similar between the two groups. Moreover, no differences in in-hospital outcomes including mortality [odds ratio (OR): 1.35, CI: 0.48-3.83; P = 0.57] were observed in the propensity matched cohort. CONCLUSIONS: Our study did not find any major differences in outcomes in the CAS group following TAVR; however, a more detailed randomized controlled study with long-term follow-up of these patients is needed.

Pentraxin 3, TNF-α, and LDL-C Are Associated With Carotid Artery Stenosis in Patients With Ischemic Stroke.

Background: Carotid artery stenosis (CAS), typically resulting from atherosclerotic progression, is more common than intracranial atherosclerotic disease in patients with cerebrovascular disease. Prior literature has incompletely established the relationship of Pentraxin 3 (PTX3) and CAS complexity and severity. This study aims to more thoroughly evaluate the association of plasma PTX3 levels and the prevalence and severity of CAS in patients with cerebrovascular disease. Methods: Two hundred and six patients with ischemic stroke underwent multiphase computerized tomography angiography (CTA) of the head and neck to assess the presence and severity of carotid artery stenosis. Patients were divided into groups with either no carotid artery stenosis (CAS-free) or carotid artery stenosis (CAS). The CAS group was further divided into groups based on the degree of stenosis and the number of involved vessels. The PTX3 and Tumor Necrosis Factor-alpha (TNF-α) concentration were measured by ELISA. Results: Plasma levels of PTX3, TNF-α, and low-density lipoprotein cholesterol (LDL-C) were increased significantly in the CAS group patients vs. the CAS-free group (p = 0.000, 0.002, 0.002, respectively). Within the CAS group, PTX3, TNF-α, and LDL-C were significantly elevated in stenosis of ≥50% group compared to <50% group (p = 0.001, 0.002, 0.049, respectively). The multivariate logistic binary regression analysis revealed that increased age, elevated levels of PTX3, LDL-C, and TNF-α were all independent risk factors for occurrence of carotid stenosis. PTX3 level correlated with the severity of carotid stenosis. Conclusions: High plasma PTX3 levels, TNF-α, and LDL-C are significantly correlated with the prevalence and severity of carotid artery stenosis. PTX3 may be a more powerful predictor for the severity of carotid artery stenosis.

Progression of asymptomatic mild carotid artery stenosis: Implications for frequency of surveillance.

We looked retrospectively at the 3- to 5-year progression of mild, asymptomatic carotid artery stenosis (CAS). A random sample of 600 patients who had undergone at least two carotid artery duplex ultrasounds between 31 October 2006 and 1 November 2016 with a second duplex ⩾3 and ⩽5 years following the initial one were screened for inclusion. Internal carotid arteries (ICAs) were included if they had 20-49% stenosis on the initial duplex, with 440 carotid arteries meeting this criteria. Analyses were performed utilizing chi-squared and two-tailed t-tests. Twenty-four (5.45%) of the initial 440 carotid arteries progressed to moderate CAS. There was a statistically significant increase in the prevalence of hypertension (68% vs 47%, p=0.022) and diabetes mellitus (44% vs 22%, p=0.008) in patients with carotids that progressed to moderate CAS. There was a decrease in moderate-intensity statin use (32% vs 58%, p=0.005) and an increase in patients not on statins (36% vs 11%, p=0.001) in the group of carotids that progressed to moderate CAS. One carotid artery (0.2%) progressed from mild CAS to severe CAS. If supported by others, our data may lead to a change in the recommendations regarding appropriate follow-up of asymptomatic CAS.

Prevalence of carotid artery stenosis in Chinese patients with angina pectoris.

BACKGROUND: The prevalence of carotid artery stenosis (CAS) in Chinese patients with angina pectoris is unknown. METHODS: The study population consisted of 989 consecutive patients who were scheduled to undergo nonemergent coronary angiography for suspicion of coronary artery disease (CAD) because of angina pectoris between January 2013 and December 2014. All patients underwent carotid ultrasonography to screen for CAS within one month before or after coronary angiography. We defined cases with 0-50%, 50%-70%, and >70% stenosis as mild, moderate, and severe stenosis, respectively. RESULTS: CAD was presented in 853 patients (86.2%) of whom 191 patients (19.3%) had 1-vessel disease, 246 patients (24.9%) had 2-vessel disease and 416 patients (42.1%) had 3-vessel disease; left main trunk stenosis present in 137 patients (13.9%). In carotid ultrasonography, the prevalence of mild, moderate, and severe stenosis as well as that of total occlusion of the carotid artery was 54.5%, 13%, 4.7% and 0.8%, respectively. Significant CAS (>50% stenosis and total occlusion) was present in 10.3%, 13.9%, 19.9% and 22.8% of patients with 0-vessel, 1-vessel, 2-vessel and 3-vessel CAD. The severity of CAS was directly correlated (r=0.194, P<0.001) with the extent of CAD. The independent predictors of severe CAS and total carotid artery occlusion were increased age, male sex, hypertension, diabetes mellitus, hyperhomocysteinemia, a previous history of stroke and 3-vessel CAD. CONCLUSIONS: The prevalence of CAS was not rare in China when compared with that in western countries, and the presence of CAS was weakly correlated with the extent of CAD. Screening for CAS should be recommended in Chinese patients with CAD, especially in those with one or more CAS-associated risk factors.