Identifying cardiovascular risk factors that impact cerebrovascular reactivity: An ASL MRI study.

BACKGROUND: To maintain cerebral blood flow (CBF), cerebral blood vessels dilate and contract in response to blood supply through cerebrovascular reactivity (CR). PURPOSE: Cardiovascular (CV) disease is associated with increased stroke risk, but which risk factors specifically impact CR is unknown. STUDY TYPE: Prospective longitudinal. SUBJECTS: Fifty-three subjects undergoing carotid endarterectomy or stenting. FIELD STRENGTH/SEQUENCE: 3T, 3D pseudo-continuous arterial spin labeling (PCASL) ASL, and T1 3D fast spoiled gradient echo (FSPGR). ASSESSMENT: We evaluated group differences in CBF changes for multiple cardiovascular risk factors in patients undergoing carotid revascularization surgery. STATISTICAL TESTS: PRE (baseline), POST (48-hour postop), and 6MO (6 months postop) whole-brain CBF measurements, as 129 CBF maps from 53 subjects were modeled as within-subject analysis of variance (ANOVA). To identify CV risk factors associated with CBF change, the CBF change from PRE to POST, POST to 6MO, and PRE to 6MO were modeled as multiple linear regression with each CV risk factor as an independent variable. Statistical models were performed controlling for age on a voxel-by-voxel basis using SPM8. Significant clusters were reported if familywise error (FWE)-corrected cluster-level was P < 0.05, while the voxel-level significance threshold was set for P < 0.001. RESULTS: The entire group showed significant (cluster-level P < 0.001) CBF increase from PRE to POST, decrease from POST to 6MO, and no significant difference (all voxels with P > 0.001) from PRE to 6MO. Of multiple CV risk factors evaluated, only elevated systolic blood pressure (SBP, P = 0.001), chronic renal insufficiency (CRI, P = 0.026), and history of prior stroke (CVA, P < 0.001) predicted lower increases in CBF PRE to POST. Over POST to 6MO, obesity predicted lower (P > 0.001) and cholesterol greater CBF decrease (P > 0.001). DATA CONCLUSION: The CV risk factors of higher SBP, CRI, CVA, BMI, and cholesterol may indicate altered CR, and may warrant different stroke risk mitigation and special consideration for CBF change evaluation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:734-747.

Eotaxin Augments Calcification in Vascular Smooth Muscle Cells.

Calcification of atherosclerotic plaques in elderly patients represents a potent risk marker of cardiovascular events. Plasma analyses of patients with or without calcified plaques reveal significant differences in chemokines, particularly eotaxin, which escalates with increased calcification. We therefore, hypothesize that eotaxin in circulation augments calcification of vascular smooth muscle cells (VSMCs) possibly via oxidative stress in the vasculature. We observe that eotaxin increases the rate of calcification significantly in VSMCs as evidenced by increased alkaline phosphatase activity, calcium deposition, and osteogenic marker expression. In addition, eotaxin promotes proliferation in VSMCs and triggers oxidative stress in a NADPH oxidase dependent manner. These primary novel observations support our proposition that in the vasculature eotaxin augments mineralization. Our findings suggest that eotaxin may represent a potential therapeutic target for prevention of cardiovascular complications in the elderly. J. Cell. Biochem. 118: 647-654, 2017. © 2016 Wiley Periodicals, Inc.

Volume of subclinical embolic infarct correlates to long-term cognitive changes after carotid revascularization.

OBJECTIVE: Carotid intervention is safe and effective in stroke prevention in appropriately selected patients. Despite minimal neurologic complications, procedure-related subclinical microemboli are common and their cognitive effects are largely unknown. In this prospective longitudinal study, we sought to determine long-term cognitive effects of embolic infarcts. METHODS: The study recruited 119 patients including 46% symptomatic patients who underwent carotid revascularization. Neuropsychological testing was administered preoperatively and at 1 month, 6 months, and 12 months postoperatively. Rey Auditory Verbal Learning Test (RAVLT) was the primary cognitive measure with parallel forms to avoid practice effect. All patients also received 3T brain magnetic resonance imaging with a diffusion-weighted imaging (DWI) sequence preoperatively and within 48 hours postoperatively to identify procedure-related new embolic lesions. Each DWI lesion was manually traced and input into a neuroimaging program to define volume. Embolic infarct volumes were correlated with cognitive measures. Regression models were used to identify relationships between infarct volumes and cognitive measures. RESULTS: A total of 587 DWI lesions were identified on 3T magnetic resonance imaging in 81.7% of carotid artery stenting (CAS) and 36.4% of carotid endarterectomy patients with a total volume of 29,327 mm3. Among them, 54 DWI lesions were found in carotid endarterectomy patients and 533 in the CAS patients. Four patients had transient postoperative neurologic symptoms and one had a stroke. CAS was an independent predictor of embolic infarction (odds ratio, 6.6 [2.1-20.4]; P < .01) and infarct volume (P = .004). Diabetes and contralateral carotid severe stenosis or occlusion had a trend of positive association with infarct volume, whereas systolic blood pressure ≥140 mm Hg had a negative association (P = .1, .09, and .1, respectively). There was a trend of improved RAVLT scores overall after carotid revascularization. Significantly higher infarct volumes were observed among those with RAVLT decline. Within the CAS cohort, infarct volume was negatively correlated with short- and long-term RAVLT changes (P < .05). CONCLUSIONS: Cognitive assessment of procedure-related subclinical microemboli is challenging. Volumes of embolic infarct correlate with long-term cognitive changes, suggesting that microembolization should be considered a surrogate measure for carotid disease management.

A Prospective Evaluation of Systemic Biomarkers and Cognitive Function Associated with Carotid Revascularization.

OBJECTIVE: To determine factors affecting cognition and identify predictors of long-term cognitive impairment following carotid revascularization procedures. BACKGROUND: Cognitive impairment is common in older patients with carotid occlusive diseases. METHODS: Patients undergoing carotid intervention for severe occlusive diseases were prospectively recruited. Patients received neurocognitive testing before, 1, and 6 months after carotid interventions. Plasma samples were also collected within 24 hours after carotid intervention and inflammatory cytokines were analyzed. Univariate and multivariate logistic regressions were performed to identify risk factors associated with significant cognitive deterioration (>10% decline). RESULTS: A total of 98 patients (48% symptomatic) were recruited, including 55 patients receiving carotid stenting and 43 receiving endarterectomy. Mean age was 69 (range 54-91 years). Patients had overall improvement in cognitive measures 1 month after revascularization. When compared with carotid stenting, endarterectomy patients demonstrated postoperative improvement in cognition at 1 and 6 months compared with baseline. Carotid stenting (odds ratio 6.49, P = 0.020) and age greater than 80 years (odds ratio 12.6, P = 0.023) were associated with a significant long-term cognitive impairment. Multiple inflammatory cytokines also showed significant changes after revascularization. On multivariate analysis, after controlling for procedure and age, IL-12p40 (P = 0.041) was associated with a higher risk of significant cognitive impairment at 1 month; SDF1-α (P = 0.004) and tumor necrosis factor alpha (P = 0.006) were independent predictors of cognitive impairment, whereas interleukin-6 (P = 0.019) demonstrated cognitive protective effects at 6 months after revascularization. CONCLUSIONS: Carotid interventions affect cognitive function. Systemic biomarkers can be used to identify patients at risk of significant cognitive decline postprocedures that benefit from targeted cognitive training.

Brain structural connectivity distinguishes patients at risk for cognitive decline after carotid interventions.

While brain connectivity analyses have been demonstrated to identify ill patients for a number of diseases, their ability to predict cognitive impairment after brain injury is not well established. Traditional post brain injury models, such as stroke, are limited for this evaluation because pre-injury brain connectivity patterns are infrequently available. Patients with severe carotid stenosis, in contrast, often undergo non-emergent revascularization surgery, allowing the collection of pre and post-operative imaging, may experience brain insult due to perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post-operative cognitive decline. We hypothesized that a distributed function such as memory would be more resilient in patients with brains demonstrating higher degrees of modularity. To test this hypothesis, we analyzed preoperative structural connectivity graphs (using T1 and DWI MRI) for 34 patients that underwent carotid intervention, and evaluated differences in graph metrics using the Brain Connectivity Toolbox. We found that patients with lower binary component number, binary community number and weighted community number prior to surgery were at greater risk for developing cognitive decline. These findings highlight the promise of brain connectivity analyses to predict cognitive decline following brain injury and serve as a clinical decision support tool. Hum Brain Mapp 37:2185-2194, 2016. © 2016 Wiley Periodicals, Inc.

Microembolization is associated with transient cognitive decline in patients undergoing carotid interventions.

OBJECTIVE: Carotid interventions are important in helping to reduce the risk of stroke for patients with high-grade carotid artery stenosis; however, subclinical cerebral microemboli can occur during these procedures. Associations have been found between the incidence of microemboli and postoperative decline in memory. We therefore sought to determine whether this decline persisted long-term and to assess changes in other cognitive domains. METHODS: Patients were prospectively recruited under an Institutional Review Board-approved protocol at a single academic center. Neuropsychological testing was administered preoperatively and at 1-month and 6-month intervals postoperatively. Cognitive domains that were evaluated included verbal memory, visual memory, psychomotor speed, dexterity, and executive function. Diffusion-weighted magnetic resonance imaging sequencing was performed preoperatively and ≤48 hours postoperatively to identify procedure-related microemboli. Univariate and multivariate regression models were used to identify relationships among microembolization, demographics, and cognition. RESULTS: Included were 80 male patients with an average age of 69 years. Forty patients underwent carotid artery stenting and 40 underwent carotid endarterectomy. Comorbidities included diabetes in 45%, coronary artery disease in 50%, and prior neurologic symptoms in 41%. New postoperative microemboli were found in 45 patients (56%). Microembolization was significantly more common in the carotid artery stenting cohort (P < .005). Univariate analysis demonstrated that patients with procedurally related embolization showed decline 1 month postoperatively in verbal memory and Trail Making A measures. Multivariate analysis demonstrated that procedurally related embolization (odds ratio [OR], 2.8; P = .04) and preoperative symptomatic stenosis (OR, 3.2; P = .026) were independent predictors of decline for the Rey Auditory Verbal Learning Test Short Delay measure at 1 month. At 6 months, no significant relationship was found between emboli and decline on Rey Auditory Verbal Learning Test Short Delay, but age (OR, 1.1, P = .005) and chronic obstructive pulmonary disease (OR, 7.1, P = .018) were significantly associated with decline at 6 months after the intervention. CONCLUSIONS: Microembolization that is associated with carotid artery intervention predicts short-term cognitive decline. However, some of these cognitive deficits persist at 6 months after the intervention, and further investigation is warranted to determine individual patient risk factors that may affect recovery.

SPY technology as an adjunctive measure for lower extremity perfusion.

OBJECTIVE: Lack of a reliable outcome measure often leads to excessive or insufficient interventions for critical limb ischemia (CLI). SPY technology (Novadaq Technologies Inc, Bonita Springs, Fla), widely adapted by plastic and general surgeons, uses laser-assisted fluorescence angiography (LAFA) to assess tissue perfusion. We sought to determine the role of SPY as an alternative, perhaps more reliable outcome measure for vascular interventions. METHODS: All patients undergoing elective or urgent revascularization for claudication and CLI were prospectively recruited from June 2012 to August 2014. LAFA using SPY technology was performed before and after revascularization procedures under a standard Institutional Review Board-approved protocol. Quantitative measures of perfusion at plantar surfaces were analyzed and compared with ankle-brachial index. RESULTS: A total of 93 patients with claudication or CLI underwent LAFA before and after a revascularization procedure in the study period. The mean preoperative ankle-brachial index increased from 0.60 to 0.84 (P < .001) after a revascularization procedure. Plantar perfusion as measured by LAFA also improved significantly after intervention. Ingress, defined as the rate at which fluorescence intensity increases on the plantar surface during LAFA, increased from 7.1 to 12.4 units/s (P < .001). Peak perfusion, defined as the difference between the baseline and the peak of fluorescence intensity, increased from 97.1 and 143.9 units (P < .001). Egress, defined as the rate at which intensity diminishes after reaching peak perfusion, increased from 1.0 to 1.9 units/s (P = .035). Procedure-related digital embolization was also observed in several patients despite lack of an angiographic finding. CONCLUSIONS: This is the largest prospective study evaluating SPY technology in peripheral vascular interventions. Our study shows that SPY is a valuable tool in visualizing real-time procedural outcomes and providing additionally useful information on regional tissue perfusion. Further investigation is warranted to standardize outpatient use and to determine threshold values that predict wound healing.

A prospective evaluation of using IVUS during percutaneous superficial femoral artery interventions.

BACKGROUND: The outcomes of endovascular interventions of the superficial femoral artery (SFA) are variable. Completion angiography is typically performed to confirm satisfactory outcomes after SFA angioplasty and/or stenting. However, two-dimensional angiography may not accurately reflect the extent of residual stenosis. We sought to determine whether intravascular ultrasound (IVUS) can help with residual disease assessment and procedure outcome. METHODS: Patients with anticipated SFA disease were prospectively recruited to the study. Patients with primary SFA disease on diagnostic angiography were included. After SFA endovascular intervention with angioplasty and/or stenting, a completion angiogram was performed to confirm satisfactory results before IVUS evaluation. IVUS-detected maximal residual stenosis, maximal residual lesion volume, and number of nonconsecutive posttreatment SFA segments with >50% residual stenosis were evaluated. Periprocedural ankle-brachial indexes (ABIs), Short Form 36 (SF-36) surveys, and Walking Impairment Questionnaires were also collected. RESULTS: Fifty-nine patients were prospectively enrolled. Thirty-three received angioplasty only, and 26 received angioplasty and stenting. All patients were men, mean age was 67 years, and major comorbidities included coronary artery disease (53%), active smoking (56%), hypertension (88%), and diabetes (68%). The angioplasty-only cohort had more nonconsecutive areas of >50% residual stenosis (P = 0.004), greater residual stenosis (P = 0.03), and smaller minimal lumen diameters after treatment (P = 0.01) than the angioplasty and stenting cohort. However, there was no significant difference in ABI between the 2 groups and no difference in ABI improvement after intervention. Sixty-four percent of all patients demonstrated a >0.2 increase in postintervention ABI. Improvement in ABI at 1 month after procedure significantly correlated with postintervention SF-36 survey physical scores (r = 0.435, P = 0.007). CONCLUSIONS: IVUS evaluation provides more-accurate intraprocedural insight on the extent of residual stenosis after SFA interventions. Future studies are warranted to determine whether IVUS-guided postangioplasty and/or stenting can impact long-term interventional outcome.

Intravascular ultrasound as a clinical adjunct for carotid plaque characterization.

OBJECTIVE: Virtual histology intravascular ultrasound (VH IVUS) is valuable for estimating minimal lumen diameter and plaque characterization. The clinical use of IVUS in carotid intervention is not well characterized. We aim to evaluate the role of IVUS in carotid plaque characterization and determine whether it could be predictive of procedure-related microemboli. METHODS: From July 2010, patients with severe carotid stenosis who underwent elective carotid stenting procedures were prospectively enrolled. IVUS evaluation was performed before stent placement. Patient demographics, comorbidities, and preoperative images were recorded. Comparison of pre- and postoperative diffusion-weighted magnetic resonance images was used to identify the number of procedure-related microemboli. IVUS-derived minimal lumen diameter and vessel wall plaque characteristics were collected. Univariate and multivariate logistic regressions were used to search for associations between IVUS-derived VH data and incidence of microemboli. RESULTS: A total of 38 high-risk patients receiving carotid stenting were enrolled. Among them, 25 patients had type I aortic arches and 17 of the patients were symptomatic (preoperative stroke or transient ischemic attack). VH IVUS data did not show strong associations with microemboli, however, a trend was found between the area of fibrous tissue and median or more incidence of microemboli (P = .099). IVUS-defined vessel diameter maximum was associated with median or more incidence of microemboli (P = .042). In addition, median or more incidence of microemboli showed trends with proximal common carotid artery calcification (P = .056) and with being over the age of 80 (P = .06). Contralateral carotid occlusion or high-grade stenosis was associated with postoperative contralateral microemboli (P = .036). CONCLUSIONS: We demonstrate that periprocedural carotid IVUS is clinically feasible. VH IVUS may be helpful in better understanding plaque morphology and determining optimal stent placement. However, its use in predicting microembolization remains limited.

Contralateral microemboli following carotid artery stenting in patients with a contralateral internal carotid artery occlusion.

Subclinical microembolization identified on diffusion-weighted magnetic resonance imaging is recognized as an important outcome measure for carotid revascularization procedures. It is generally believed that arch manipulation is the primary reason for developing microemboli in the contralateral hemisphere during carotid artery stenting. However, we identified three patients who developed postprocedure microemboli of the contralateral hemisphere despite a known chronic contralateral internal carotid artery occlusion. Our cases highlight that ipsilateral microemboli may be an underappreciated but an important source of contralateral lesions through patent intracranial collateral pathways.

Prospective neurocognitive evaluation of patients undergoing carotid interventions.

OBJECTIVE: Distal cerebral embolization is a known complication of carotid interventions. We prospectively investigated whether subclinical microembolization seen on postoperative magnetic resonance imaging (MRI) leads to cognitive deficits in patients undergoing carotid revascularization procedures. METHODS: Patients undergoing carotid interventions and eligible for MRI scanning were recruited. Among 247 patients who received preoperative and postoperative MRI evaluations, 51 also completed neuropsychologic testing before and at 1 month after their procedure. Cognitive evaluation included the Rey Auditory Verbal Learning Test (RAVLT) for memory evaluation and the Mini-Mental State Examination (MMSE) for general cognitive impairment screening. RESULTS: The 51 patients (all men), comprising 16 with carotid artery stenting (CAS) and 35 with carotid endarterectomy (CEA), were a mean age of 71 years (range, 54-89 years). Among them, 27 patients (53%) were symptomatic preoperatively, including 11 who had prior stroke and 16 who had prior preoperative transient ischemic attack symptoms. Most patients had significant medical comorbidities, including hypertension (96%), diabetes (31.3%), coronary artery disease (47%), and chronic obstructive pulmonary disease (15.7%). Two patients (4%) had prior ipsilateral CEA and eight had contralateral carotid occlusion (15.7%). Memory decline evident on RAVLT was identified in eight CAS patients and 13 CEA patients. Eleven patients had evidence of procedure-related microemboli. Although there was no significant difference in baseline cognitive function or memory change between the CEA and CAS cohorts, the CAS cohort had a significantly higher incidence of microembolic lesions. Multivariate regression analysis showed that procedure-related microembolization was associated with memory decline (P = .016) as evident by change in RAVLT. A history of neurologic symptoms was significantly associated with poor baseline cognitive function (MMSE; P = .03) and overall cognitive deterioration (change in MMSE; P = .026), as determined by Wilcoxon rank sum test and linear regression analysis, respectively. CONCLUSIONS: Although CEA and CAS are effective in stroke prevention, with minimal neurologic complication, neurocognitive effects remain uncertain. Procedure-associated microembolization and pre-existing neurologic symptoms are associated with poor baseline cognitive function and memory decline after the procedures. Further comprehensive cognitive evaluation to determine the benefit of carotid interventions is warranted.

Convergence Analysis of Micro-Lesions (CAML): An approach to mapping of diffuse lesions from carotid revascularization.

Carotid revascularization (endarterectomy, stenting) prevents stroke; however, procedure-related embolization is common and results in small brain lesions easily identified by diffusion weighted magnetic resonance imaging (DWI). A crucial barrier to understanding the clinical significance of these lesions has been the lack of a statistical approach to identify vulnerable brain areas. The problem is that the lesions are small, numerous, and non-overlapping. Here we address this problem with a new method, the Convergence Analysis of Micro-Lesions (CAML) technique, an extension of the Anatomic Likelihood Analysis (ALE). The method combines manual lesion tracing, constraints based on known lesion patterns, and convergence analysis to represent regions vulnerable to lesions as probabilistic brain atlases. Two studies were conducted over the course of 12 years in an active, vascular surgery clinic. An analysis in an initial group of 126 patients at 1.5 T MRI was cross-validated in a second group of 80 patients at 3T MRI. In CAML, lesions were manually defined and center points identified. Brains were aligned according to side of surgery since this factor powerfully determines lesion distribution. A convergence based analysis, was performed on each of these groups. Results indicated the most consistent region of vulnerability was in motor and premotor cortex regions. Smaller regions common to both groups included the dorsolateral prefrontal cortex and medial parietal regions. Vulnerability of motor cortex is consistent with previous work showing changes in hand dexterity associated with these procedures. The consistency of CAML also demonstrates the feasibility of this new approach to characterize small, diffuse, non-overlapping lesions in patients with multifocal pathologies.

PKC-epsilon and TLR4 synergistically regulate resistin-mediated inflammation in human macrophages.

BACKGROUND AND AIMS: Resistin has been associated with atherosclerotic inflammation and cardiovascular complications. We and others have previously shown that PKC-epsilon (PKCε) is involved in resistin-induced smooth muscle cell (VSMC) dysfunction at a high pathological concentration. This study aimed to evaluate the role and potential pathways of resistin at a physiological concentration, in atherosclerosis-related inflammation. METHODS: Plasma from patients with atherosclerosis was analyzed for resistin concentration. Patients were divided into tertiles based on resistin levels and cytokines were compared between tertiles. Macrophages were then treated with resistin in the presence or absence of PKCε inhibitor and/or TLR4 blocking-antibody, and their inflammatory state was evaluated with ELISA, RT-PCR, immunocytochemistry, and Western blot. RESULTS: We observed significant associations between plasma resistin levels and TNF-α, IL-6, IL-12, MIP-1α, MIP-1ß, and CD40L. Our in vitro analyses revealed that resistin activated PKCε via TLR4. This was followed by NF-kB activation and induction of a pro-inflammatory phenotype in macrophages, significantly upregulating CD40, downregulating CD206 and stimulating gene expression and secretion of the inflammatory cytokines, for which we found association in our plasma analysis. Resistin also induced persistent TRAM and CD40L upregulation up to 36 h after resistin treatment. PKCε and TLR4 inhibitors suppressed gene expression to levels similar to control, especially when used in combination. CONCLUSIONS: Resistin, at a physiological concentration, exacerbates the inflammatory response of macrophages. PKCε is a key upstream mediator in resistin-induced inflammation that may interact synergistically with TLR4 to promote NF-kB activation, while TRAM is an important signal. PKCε and TRAM may represent novel molecular targets for resistin-associated chronic atherosclerotic inflammation.

Genetic Polymorphisms Influence Cognition in Patients Undergoing Carotid Interventions.

While carotid interventions help decrease the risk of stroke, nearly 40% of patients experience cognitive deterioration. Genetic polymorphism in apolipoprotein E (ApoE) and brain-derived neurotrophic factor (BDNF) have been implicated in cognitive impairment; however, it is unclear whether they may influence cognitive changes in patients undergoing carotid intervention. In this study, we seek to assess the role of genetic polymorphisms in carotid intervention-related cognitive change. Polymorphisms related to cognitive function were chosen for this preliminary analysis. Over 2 years, patients undergoing carotid interventions were prospectively recruited. Patients underwent neuropsychological testing 2 weeks prior to and at 1 month following their procedure. Saliva samples were collected for genetic analysis. Logistic regressions were used to identify associations between polymorphisms and cognitive measures. A total of 91 patients were included; all were male with an average age of 70 years. The majority of patients exhibited hypertension (95%) and a history of smoking (81%). Presence of ApoE 4 allele was associated with depression (p= 0.047). After correcting for age and genetic polymorphisms in BDNF and serotonin transporter (5-HTT), ApoE 4 allele was associated with depression (p= 0.044) and showed a trend with baseline cognitive impairment (p= 0.10). Age ≥ 70 years was associated with baseline cognitive impairment after adjusting for the three genetic polymorphisms (p= 0.03). Patients with ApoE 4 and BDNF A polymorphisms performed less well on the visual and verbal memory measures, respectively. Polymorphisms in ApoE and BDNF may provide insight on cognition in patients undergoing carotid interventions; however, the mechanism of this relationship remains unclear.

Utilization of Intravascular Ultrasound during Carotid Artery Stenting.

For patients at high risk for surgery, carotid artery stenting (CAS) is a viable alternative to help reduce risk of stroke for patients with high-grade carotid artery stenosis; however, a higher incidence of perioperative stroke has been observed in patients undergoing stenting compared to those undergoing open surgery. Intravascular ultrasound (IVUS) is commonly used during coronary artery procedures to help evaluate lesions and to guide stent placement. Multiple groups have sought to determine whether IVUS could also be used during CAS. While IVUS has been shown to be both feasible and safe during CAS, there is limited evidence that demonstrates direct improvement in procedural outcomes. Further studies focusing on clinical outcomes should be conducted in order to justify routine use of this technology during CAS.