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Endoplasmic reticulum (ER) stress is an important process during the progression of atherosclerosis. The aim of this study was to elucidate the association of ER stress and clinical instability of carotid plaque. One hundred ninety-three patients with carotid stenosis undergoing carotid endarterectomies (CEAs) were enrolled. We classified the patients into 3 groups: the asymptomatic, symptomatic, and cTIA (crescendo transient ischemic attack)/SIE (stroke in evolution) groups. Immunohistological staining was performed to assess ER stress and apoptosis. The correlation between ER stress marker expression and clinical instability was analyzed by Tukey–Kramer test and ordinal logistic regression. From the 193 CEAs, 24 asymptomatic plaques and 24 symptomatic plaques were randomly selected, and all 7 plaques in the cTIA/SIE group were selected. Glycophorin A staining demonstrated significant correlation between intraplaque hemorrhage and clinical instability (odds ratio [OR], 1.27; 95%CI, 1.14–1.41). The expression of ER stress markers (glucose-regulated protein 78 [GRP78] and C/EBP homologous protein [CHOP]) exhibited a significant correlation with clinical instability (GRP78: OR, 1.25; 95%CI, 1.14–1.38, CHOP: OR, 1.39; 95%CI, 1.16–1.66). Double-label immunofluorescence demonstrated ER stress markers were detected in CD68-positive cells and smooth muscle actin (SMA)-positive cells. The coexpression of the ER stress markers exhibited a significant correlation with clinical instability (CD68/GRP78: OR, 1.13; 95%CI, 1.05–1.20, CD68/CHOP: OR, 1.092; 95%CI, 1.04–1.14, SMA/CHOP: OR, 1.082; 95%CI, 1.04–1.13). However, the colocalization of CHOP and cleaved caspase-3 (apoptosis marker) did not correlate with clinical instability. These findings indicated that the ER stress pathway may be a potential therapeutic target in the prevention of stroke.

Carotid endarterectomy (CEA) has historically demonstrated a higher rate of perioperative adverse events for female patients. However, recent evidence suggests similar outcomes for CEA between genders. In contrast, fewer studies have examined gender in carotid artery stenting (CAS). Using contemporary data from the American College of Surgeons National Surgical Quality Improvement Program database, we aim to determine if gender impacts differences in postoperative complications in patients who undergo CEA or CAS.The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2017 using Current Procedural Terminology and International Classification of Diseases codes for retrospective review. Patients with carotid intervention (CEA or CAS) were stratified into asymptomatic vs symptomatic cohorts to determine the effect of gender on 30-day postoperative outcomes. Symptomatic patients were defined as those with perioperative transient cerebral ischemic attack or stenosis of carotid artery with cerebral infarction. Descriptive statistics were calculated. Risk-adjusted odds of 30-day postoperative outcomes were calculated using multivariate regression analysis with fixed effects for age, race, and comorbidities.There were 106,568 patients with CEA or CAS (104,412 CEA and 2156 CAS). The average age was 70.9 years, and female patients accounted for 39.9% of the population. For asymptomatic patients that underwent CEA or CAS, female gender was associated with significantly higher rates of cerebrovascular accident (CVA)/stroke (13%; P = .005), readmission (10%; P = .004), bleeding complication (32%; P = .001), and urinary tract infection (54%; P = .001), as well as less infection (26%; P = .001). In the symptomatic cohort, female gender was associated with significantly higher rates of CVA/stroke (32%; P = .034), bleeding complication (203%; P = .001), and urinary tract infection (70%; P = .011), whereas female gender was associated with a lower rate of pneumonia (39%; P = .039). Subset analysis found that, compared with male patients, female patients 75 years old have an increased rate of CVA/stroke (21%; P = .001) and readmission (15%; P .001), whereas female patients ≥75 years old did not. In asymptomatic and symptomatic patients that underwent CEA, female gender was associated with significantly higher rates of CVA/stroke (13%; P = .006 and 31%; P = .044, respectively), but this finding was not present in patients undergoing CAS.In patients undergoing carotid intervention, female gender was associated with significantly increased rates of postoperative CVA/stroke in the asymptomatic and symptomatic cohorts as well as readmission in the asymptomatic cohort. Female gender was associated with higher rates of CVA/stroke following CEA, but not CAS. We recommend that randomized control trials ensure adequate representation of female patients to better understand gender-based disparities in carotid intervention.

An 84-year-old woman with a history of hypertension, diabetes mellitus, dyslipidaemia and aortic stenosis (AS) was referred to our hospital for transcatheter aortic valve implantation (TAVI). She occasionally recognised dyspnoea on exertion for the last 2 years, but she had no symptoms of chest pain

Cerebral hyperperfusion syndrome is a rare but severe complication of carotid artery stenting or carotid endarterectomy. Staged angioplasty is reportedly an effective strategy to avoid cerebral hyperperfusion syndrome. We encountered a case of internal carotid artery stenosis with a rare clinical presentation of limb shaking that was successfully improved by staged angioplasty. To our knowledge, there are no reported cases of limb shaking treated with staged angioplasty. A 76-year-old woman presented with continuous chorea in her left lower limb and shoulder. Medical examination revealed a tiny cerebral infarction in the right corona radiata and severe right internal carotid artery stenosis. Angiography showed near occlusion of the right internal carotid artery. Staged angioplasty was performed to avoid the risk of cerebral hyperperfusion syndrome. The first angioplasty resulted in an expanded diameter of 2.5 mm and was followed by definitive carotid artery stenting using a closed-cell stent 3.5 weeks later. Limb shaking improved in a stepwise manner along with an improvement in internal carotid artery stenosis and distal flow state with no signs of cerebral hyperperfusion syndrome. Patients with internal carotid artery stenosis or occlusion presenting with limb shaking have been suggested to have impaired cerebrovascular reactivity, which is also thought to be a risk factor for cerebral hyperperfusion syndrome. The stepwise improvement in limb shaking observed in this case supports the idea that the pathophysiology of limb shaking is related to cerebral haemodynamic impairment. Measures to prevent cerebral hyperperfusion syndrome, including staged angioplasty, should be actively considered in patients with limb shaking because the symptoms themselves suggest severe hypoperfusion.

Transcarotid arterial revascularization (TCAR) has gained popularity as an alternative to carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS), potentially combining the benefits of a minimally invasive approach with a lower risk of procedural stroke compared with TFCAS. Emerging evidence shows TCAR to have excellent perioperative outcomes. However, the cost-effectiveness of TCAR is not well-understood.Incorporating data from Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), the Vascular Quality Initiative Surveillance Project, and local cost data, we compared the cost-effectiveness of these three treatment modalities (TFCAS, CEA, and TCAR) for both symptomatic and asymptomatic carotid stenosis using a Markov state-transition model to quantify lifetime costs in United States dollars and effectiveness in quality-adjusted life-years (QALYs). We accounted for perioperative stroke and myocardial infarction, as well as long-term risks of stroke and restenosis. Based on CREST, we assumed a start age of 69 years and a cost-effectiveness acceptability threshold of $100,000/QALYs gained. Sensitivity analyses were performed.In the base-case scenario, TCAR cost $160,642/QALY gained compared with CEA, greater than the frequently cited $100,000/QALY gained threshold. TFCAS was more expensive and less effective than other strategies, largely due to a greater periprocedural stroke risk. In one-way sensitivity analysis, if TCAR stroke risk was 0.9% (base-case risk, 1.4%), than it was economically favorable compared with CEA at its current procedural cost. Alternatively, if TCAR procedural costs were reduced by approximately $2000 (base-case cost, $15,182), it would also become economically favorable. In a probabilistic sensitivity analysis, varying all parameters simultaneously over distributions, CEA was favored in 80% of model iterations at $100,000/QALY, with TCAR favored in 19%.At current cost and outcomes, TCAR does not meet a traditional cost-effectiveness threshold to replace CEA as the primary treatment modality for carotid stenosis. TFCAS is the least cost-effective strategy for carotid revascularization. Given these observations, TCAR should be limited to select patients, specifically those at high physiologic and anatomic risk from CEA. However, TCAR can become cost-effective if its cost is reduced. Given the current outcomes and cost, CEA remains the most cost-effective treatment for carotid revascularization.

Introduction Carotid angioplasty and stenting (CAS) of the cervical segment is a safe and effective procedure for the treatment of carotid artery disease. In rare cases, this procedure causes intracranial hemorrhage (ICH), which is described most often as an ipsilateral intra-parenchymal hematoma. This ICH is the result of a cerebral hyperperfusion syndrome (CHS). Isolated subarachnoid hemorrhage may occur exceptionally, with only 9 cases that have been reported in the literature. Observation We reported a case of a 71-year-old man who presented a massive non-aneurysmal subarachnoid hemorrhage one hour after angioplasty and stenting of the cervical segment of the left internal carotid artery. Medical and surgical management included external ventricular drain placement. Rebleeding occurred two days later, worsening the patient's clinical condition. Finally, the patient died 2 weeks later. Comments This rare presentation of ICH following CAS allows us to discuss the risk factors, complications and management of CHS.

OBJECTIVE To test the hypothesis that intraplaque hemorrhage is a predictor of restenosis after carotid artery stenting (CAS), the association between intraplaque high-intensity signal (HIS) on time-of-flight MR angiography (TOF-MRA), as a marker of intraplaque hemorrhage, and restenosis after CAS was assessed in the present observational study. METHODS Consecutive patients who underwent initial CAS for atherosclerotic stenosis in the cervical internal carotid artery in the authors’ department were enrolled. Of these, patients without preprocedural cervical TOF-MRA were excluded. Outcome measures were ≥ 50% restenosis, defined as a peak systolic velocity of > 1.3 m/sec; or occlusion and ≥ 70% restenosis, defined as a peak systolic velocity of > 2.1 m/sec; or occlusion on carotid duplex ultrasound. RESULTS Of 230 consecutive patients who underwent initial CAS, 22 without preprocedural cervical TOF-MRA were excluded. Of the remaining 208 patients (mean age 73 years; 33 women), 46 had intraplaque HIS. Ultrasound follow-up was not performed in 4 patients. The median follow-up duration was 3.2 years (interquartile range 1.7–5.1 years). During the follow-up period, 102 patients had ≥ 50% restenosis and 36 had ≥ 70% restenosis. Intraplaque HIS was significantly associated with increased risk of ≥ 50% restenosis (adjusted hazard ratio 2.18; 95% CI 1.28–3.68) and ≥ 70% restenosis (adjusted hazard ratio 3.12; 95% CI 1.32–7.52). CONCLUSIONS Intraplaque HIS on TOF-MRA was associated with increased risk of restenosis after CAS. The present results indicate that intraplaque hemorrhage is a predictor of restenosis after CAS.

Objective Recent literature and societal recommendations support early revascularization of symptomatic carotid patients over the traditional six-week period. Nonetheless, the timing of these interventions can vary widely among populations. The goal of this study is to identify any factors influencing carotid revascularization during the index hospitalization for patients with symptomatic disease. Methods The Texas Department of State Health Services database was queried to identify all patients >45 years old admitted to non-federal Texas Hospitals between 2009 to 2013 with an admission diagnosis of carotid artery stenosis and either transient ischemic attack (TIA), cerebrovascular accident (CVA), or amaurosis fugax. Diagnoses codes and demographic data were also used to adjust for clinical, social, and demographic factors (including area of residence and treatment). Descriptive statistics and multivariable logistic regression were used to identify significant factors for index admission revascularization. Results A total of 29,046 symptomatic patients were identified among the 153,484 patients who had an eligible admission diagnosis. This included 16,244 (55.9%) males and 12,802 (44.1%) females. Only 4,594 (15.8%) patients were revascularized during the index hospitalization. The majority of these patients presented with amaurosis (OR 5.58; 95% CI 4.84-6.44) instead of CVAs (OR 0.48; 95% CI 0.45-0.51) or TIAs (Table 2). Adjusting for hospital volume, insurance coverage, residence, and other clinical factors, rates of index admission carotid intervention remained significantly lower for women (OR 0.85; 95% CI 0.79-0.91), persons categorized as black (OR 0.60; 95% CI 0.53-0.69), and persons categorized as Hispanic (OR 0.77; 95% CI 0.70-0.86). Conclusion Gender, race and ethnicity appear to correlate with rates of carotid intervention at index hospitalization despite thorough risk adjustment for clinical, social and demographic factors. Efforts should be directed towards reducing these disparities.

BACKGROUND: Conventional ultrasound and contrast-enhanced ultrasound play an important role in the application of carotid plaque. AIMS: To establish carotid artery vulnerable plaques model by conventional ultrasound combined with contrast-enhanced ultrasound, identify high-risk plaques that may lead to cerebrovascular events, and provide clinical risk warning of high-risk plaques of stroke. METHODS: 205 cases of patients selected in 5053 patients with symptoms from 2018 to 2019 who were verified carotid plaques by conventional ultrasound and contrast-enhanced ultrasound image characteristics, 147 cases as a training set, establishing the carotid artery plaque model, analyzing the characteristic of the plaques and the relationship between cerebrovascular event, with 58 cases as a test set, verify the model. Routine carotid ultrasound and contrast-enhanced carotid ultrasound were performed in all enrolled patients. RESULTS: The gray-level characteristics of conventional ultrasound in the training concentration showed statistical differences in plaque morphology, fibrous cap morphology, uniformity and calcification degree in cerebrovascular events. The contrast enhanced ultrasound characteristics of plaques showed statistical differences in neovascularization and perfusion mode in cerebrovascular events. In the test set, there were statistical differences in the above conventional gray scale features and CEUS features. CONCLUSION: The vulnerable plaque model established by conventional ultrasound combined with contrast-enhanced ultrasound has good diagnostic value for the characteristic plaque of carotid artery with cerebrovascular events.

Contralateral carotid stenosis (cICS) has been described as a perioperative predictor of mortality after carotid endarterectomy (CEA). However, its predictive value on long-term cardiovascular events remains controversial. The study aims to assess the potential role of cICS as a long-term predictor of major adverse cardiovascular events (MACE) in patients who underwent CEA. From January 2012 to July 2020, patients undergoing CEA under regional anesthesia for carotid stenosis in a tertiary care and referral center were eligible from a prospective database, and a post hoc analysis was performed. The primary outcome consisted in the occurrence of long-term MACE. Secondary outcomes included all-cause mortality, stroke, myocardial infarction, acute heart failure, and major adverse limb events. A total of 192 patients were enrolled. With a median 50 months follow-up, chronic kidney disease (CKD) (mean survival time (MST) 51.7 vs. 103.3, P < 0.010) and peripheral artery disease (PAD) (MST 75.1 vs. 90.3, P = 0.001) were associated with decreased survival time. After propensity score matching (PSM), CKD (MST 49.1 vs. 106.0, P = 0.001) and PAD (MST 75.7 vs. 94.0, P = 0.001) maintained this association. On multivariate Cox regression analysis, contralateral stenosis was associated with higher MACE (hazard ratio (HR) = 2.035; 95% CI: 1.113-3.722, P = 0.021 and all-cause mortality (HR = 2.564; 95% CI: 1.276-5,152 P = 0.008). After PSM, only all-cause mortality (HR 2.323; 95% CI: 0.993-5.431, P = 0.052) maintained a significant association with cICS. On multivariable analysis, cICS (aHR 2.367; 95% CI: 1.174-4.771, P = 0.016), age (aHR 1.039, 95% CI: 1.008-1.070), CKD (aHR 2.803; 95% CI: 1.409-5.575, P = 0.003) and PAD (aHR 3.225, 95% CI: 1.695-6.137, P < 0.001) were independently associated with increased all-cause mortality. Contrary to MACE, cICS is a strong predictor of long-term all-cause mortality after CEA. However, MACE risk may compromise CEA benefits by other competitive events. Therefore, further studies are needed to establish the role of cICS on postoperative events and on patients' specific assessments in order to determine the best medical treatment and easy access to surgical intervention. info:eu-repo/semantics/publishedVersion

Management of carotid bifurcation stenosis in stroke prevention has been the subject of extensive investigations, including multiple randomized controlled trials. The proper treatment of patients with carotid bifurcation disease is of major interest to vascular surgeons and other vascular specialists. In 2011, the Society for Vascular Surgery published guidelines for the treatment of carotid artery disease. At the time, several randomized trials, comparing carotid endarterectomy (CEA) and carotid artery stenting (CAS), were reported. Since the 2011 guidelines, several studies and a few systematic reviews comparing CEA and CAS have been reported, and the role of medical management has been reemphasized. In the present publication, we have updated and expanded on the 2011 guidelines with specific emphasis on five areas: (1) is CEA recommended over maximal medical therapy for low-risk patients; (2) is CEA recommended over transfemoral CAS for low surgical risk patients with symptomatic carotid artery stenosis of50%; (3) the timing of carotid intervention for patients presenting with acute stroke; (4) screening for carotid artery stenosis in asymptomatic patients; and (5) the optimal sequence of intervention for patients with combined carotid and coronary artery disease. A separate implementation document will address other important clinical issues in extracranial cerebrovascular disease. Recommendations are made using the GRADE (grades of recommendation assessment, development, and evaluation) approach, as was used for other Society for Vascular Surgery guidelines. The committee recommends CEA as the first-line treatment for symptomatic low-risk surgical patients with stenosis of 50% to 99% and asymptomatic patients with stenosis of 70% to 99%. The perioperative risk of stroke and death in asymptomatic patients must be 3% to ensure benefit for the patient. In patients with recent stable stroke (modified Rankin scale score, 0-2), carotid revascularization is considered appropriate for symptomatic patients with50% stenosis and should be performed as soon as the patient is neurologically stable after 48 hours but definitely 14 days after symptom onset. In the general population, screening for clinically asymptomatic carotid artery stenosis in patients without cerebrovascular symptoms or significant risk factors for carotid artery disease is not recommended. In selected asymptomatic patients with an increased risk of carotid stenosis, we suggest screening for clinically asymptomatic carotid artery stenosis as long as the patients would potentially be fit for and willing to consider carotid intervention if significant stenosis is discovered. For patients with symptomatic carotid stenosis of 50% to 99%, who require both CEA and coronary artery bypass grafting, we suggest CEA before, or concomitant with, coronary artery bypass grafting to potentially reduce the risk of stroke and stroke/death. The sequencing of the intervention depends on the clinical presentation and institutional experience.

Background and Purpose: The net benefit of carotid endarterectomy (CEA) is determined partly by the risk of procedural stroke or death. Current guidelines recommend CEA if 30-day risks are Methods: We conducted a systematic search in MEDLINE and EMBASE for prediction models of procedural outcomes after CEA. We validated these models with data from patients who underwent CEA in the American College of Surgeons National Surgical Quality Improvement Program (2011–2017). We assessed discrimination using C statistics and calibration graphically. We determined the number of patients with predicted risks that exceeded recommended thresholds of procedural risks to perform CEA. Results: After screening 788 reports, 15 studies describing 17 prediction models were included. Nine were developed in populations including both asymptomatic and symptomatic patients, 2 in symptomatic and 5 in asymptomatic populations. In the external validation cohort of 26 293 patients who underwent CEA, 702 (2.7%) developed a stroke or died within 30-days. C statistics varied between 0.52 and 0.64 using all patients, between 0.51 and 0.59 using symptomatic patients, and between 0.49 to 0.58 using asymptomatic patients. The Ontario Carotid Endarterectomy Registry model that included symptomatic status, diabetes, heart failure, and contralateral occlusion as predictors, had C statistic of 0.64 and the best concordance between predicted and observed risks. This model identified 4.5% of symptomatic and 2.1% of asymptomatic patients with procedural risks that exceeded recommended thresholds. Conclusions: Of the 17 externally validated prediction models, the Ontario Carotid Endarterectomy Registry risk model had most reliable predictions of procedural stroke or death after CEA and can inform patients about procedural hazards and help focus CEA toward patients who would benefit most from it.

Vascular contributions to cognitive impairment and dementia (VCID) is a spectrum of cognitive deficits caused by cerebrovascular disease, for which insulin resistance is a major risk factor. A major cause of VCID is chronic cerebral hypoperfusion (CCH). Under stress, sustained hypothalamic-pituitary-adrenal axis (HPA) activation can result in insulin resistance. Little is known about the effects of CCH on the HPA axis. We hypothesized that CCH causes sustained HPA activation and insulin resistance. Male rats were subjected to bilateral carotid artery stenosis (BCAS) for 12 wk to induce CCH and VCID. BCAS reduced cerebral blood flow and caused memory impairment. Plasma adrenocorticotropic hormone was increased in the BCAS rats (117.2 ± 9.6 vs. 88.29 ± 9.1 pg/mL, BCAS vs. sham, P = 0.0236), as was corticosterone (220 ± 21 vs. 146 ± 18 ng/g feces, BCAS vs. sham, P = 0.0083). BCAS rats were hypoglycemic (68.1 ± 6.1 vs. 76.5 ± 5.9 mg/dL, BCAS vs. sham, P = 0.0072), with increased fasting insulin (481.6 ± 242.6 vs. 97.94 ± 40.02 pmol/L, BCAS vs. sham, P = 0.0003) indicating that BCAS rats were insulin resistant [homeostasis model assessment of β-cell function-insulin resistance (HOMA-IR): 11.71 ± 6.47 vs. 2.62 ± 0.93; BCAS vs. control, P = 0.0008]. Glucose tolerance tests revealed that BCAS rats had lower blood glucose areas under the curve (AUCs) than controls (250 ± 12 vs. 326 ± 20 mg/dL/h, BCAS vs. sham, P = 0.0075). These studies indicate that CCH causes sustained activation of the HPA and results in insulin resistance, a condition that is expected to worsen VCID. NEW & NOTEWORTHY Cerebrovascular disease and insulin resistance are two major risk factors for the development of dementia. Here, we demonstrate that chronic cerebral hypoperfusion results in glucocorticoid excess and hyperinsulinemia. This study indicates that chronic cerebral hypoperfusion, glucocorticoid excess, and insulin resistance participate in a detrimental cycle that could exacerbate cerebral vascular disease and dementia.

Introduction Peri-procedural embolic events are the Achilles’ heel of carotid stenting. To overcome this complication, transcervical access to the carotid artery was introduced. In this study we describe our “our life” experience with the transcervical approach in a community hospital. Material and Methods All carotid stent procedures between January 2010 and December 2020 were included in this retrospective analysis. The transcervical approach was compared to the transfemoral approach. In both procedures open-cell, closed-cell design and hybrid stents were used. In-hospital stroke was the primary outcome measure. Results A total of 340 procedures were performed, in 184 patients the transfemoral approach was used and in 156 patients the transcervical approach was used. In 12 patients (3.5%) an in-hospital stroke was diagnosed, 4 in the transfemoral group (2.2%) and 8 in the transcervical group (5.1%) (P = 0.14). In the multivariate analyses a symptomatic lesion was associated with in-hospital stroke. Neither type of access nor cell design was associated with increased risk of in-hospital stroke. Conclusions In contrast to previous studies, we could not confirm the advantages of the transcervical approach. However, conclusions should be carefully drawn, since this study is retrospective and was performed with multiple surgeon and different kind of stents.

Carotid plaque vulnerability features beyond the degree of stenosis may play a key role in the pathogenesis and recurrence of ischemic cerebrovascular events. This study sought to compare intraplaque hemorrhage (IPH) as a marker of plaque vulnerability in symptomatic patients with mild ( We included patients who experienced ischemic cerebrovascular events with no other identifiable sources and underwent carotid endarterectomy for mild (n=32), moderate (n=47), and severe (n=58) carotid artery stenosis. The degree of stenosis and imaging hallmarks were assessed by computed tomography angiography or magnetic resonance angiography. Plaque specimens were stained with hematoxylin and eosin and Movat pentachrome staining. Carotid plaques of patients with mild stenosis had a higher extent of IPH (%) on tissue analysis compared with patients with moderate (mild, 15.7% [interquartile range, 7.8%–26.7%]; moderate, 3.9% [0.0%–9.2%]; P P P Our major finding is the association of IPH with mild carotid artery stenosis based on histological analysis. The current study may suggest that IPH potentially plays a role in the mechanism of stroke in patients with nonobstructive carotid stenosis.

Objective Blood pressure (BP) management is a vital aspect of stroke prevention and post-stroke care. Different surgical carotid endarterectomy (CEA) techniques may impact on BP control post-operatively. Specifically, the carotid sinus nerve, which innervates the carotid baroreceptors and carotid body, is commonly left intact during conventional CEA but is routinely transected as part of eversion CEA. The aim of this study was to assess long term BP control after eversion and conventional CEA. Methods Patients from the International Carotid Stenting Study (ICSS cohort) and a personal series of patients from the Stroke Clinical Trials Unit at University College London (UCL cohort) were separately analysed and divided into eversion and conventional CEA groups. Mixed effect linear models were fitted and adjusted for baseline demographic data and antihypertensive treatment to test for changes in BP from baseline over a three year follow up period after the respective procedures. Results There were no differences in changes in baseline BP readings and follow up readings between eversion and conventional CEA in the ICSS or UCL cohorts. In the ICSS cohort a mild but significant systolic (–8.6 mmHg; 95% confidence interval [CI] –10.6 – –6.6) and diastolic (–4.9 mmHg; 95% CI –6.0 – –3.8) BP lowering effect was evident at discharge in the conventional group but not in the eversion CEA group. BP monitoring during follow up did not reveal any consistent BP changes with either conventional or eversion CEA vs. baseline levels. Conclusion Neither conventional nor eversion CEA seem to result in clinically significant long term BP changes. Potential concerns related to either short or long term alterations in BP levels with transection of the carotid sinus nerve during eversion CEA could not be substantiated.

Increased carotid intima-media thickness (C-IMT), a marker of atherosclerosis, is known to be associated with cerebrovascular and cortical abnormalities and cognitive impairment. This prospective observational study investigated the association between increased C-IMT and postoperative cognitive dysfunction (POCD) in older adult patients undergoing off-pump coronary artery bypass surgery. A total of 201 patients (57 females, 144 males; >60 years) were classified into increased (n = 105) or normal (n = 96) C-IMT groups by a cut-off value of 0.9 mm (bilateral C-IMT mean). Cognitive function was serially assessed with the Korean Mini-Mental State Examination, and Korean Montreal Cognitive Assessment scores preoperatively and at 7 days and 3 months postoperatively. POCD was defined as the deterioration of 1 standard deviation in at least one of the postoperative tests compared with their corresponding baseline scores. Independent risk factors for POCD were evaluated using multivariable analysis. Overall, POCD occurred in 46 patients (23%) over the 3 months. The incidences of POCD at 7 days and 3 months after surgery were similar, and there was no difference in both Korean Mini-Mental State Examination and Korean Montreal Cognitive Assessment test scores before and after surgery between groups. Chronic obstructive lung disease and intraoperative hyperglycemia episodes (>180 mg/dL), but not increased C-IMT, were independent risk factors for POCD. Unlike in nonsurgical cohorts, increased C-IMT was not significantly associated with the occurrence of POCD in older adult patients undergoing off-pump coronary artery bypass surgery.

Objective To investigate whether staged angioplasty (SAP) is a safe and effective treatment to prevent hyperperfusion syndrome after carotid artery stenting (CAS). Methods A systematic literature search was performed according to established criteria to identify eligible articles published before October 2020. Pooled dichotomous data were presented as odds ratios (OR) and corresponding 95% confidence intervals (CI) using random-effect models. The efficacy endpoints were hyperperfusion syndrome (HPS), hyperperfusion phenomenon (HPP), and intracerebral hemorrhage (ICH). The safety endpoint was post-procedural thromboembolic events. The feasibility of the procedure was assessed by device-related adverse events (vessel dissection and failed angioplasty) in SAP. Results Ten studies (1030 participants) were eligible. SAP was superior to regular CAS in preventing HPS (OR = 0.35, 95% CI 0.14–0.86, P = 0.02). There was no significant difference in the rate of thromboembolic events between the SAP group and the regular CAS group. The rates of vessel dissection and failed angioplasty with the use of a 3.0-mm-diameter balloon were 5.4% and 0.4%, respectively. Conclusion SAP may reduce the incidence of post-CAS HPS without increasing procedure-related complications. A 3.0-mm-diameter balloon used in SAP may be appropriate for Asian populations. However, the confounded study design and confused definitions of reporting items hinder the current recommendation of SAP in clinical use.

It is well known that post-stroke depression might be a negative factor for stroke recovery, however there is limited evidence to establish the link between pre-stroke depression and stroke outcome such motor recovery. The objective is to determine clinical risk factors in ischemic stroke patients with pre-stroke depression that are associated functional ambulatory outcome.Data from acute ischemic patients from a regional stroke registry were collected for consecutive recombinant tissue plasminogen activator(rtPA)-treated acute ischemic stroke patients between January 2010 and June 2016. Logistic regression model was used to predict risk factors that served as predictive variables, while the increase or reduce odds of improvement in ambulatory outcome was considered as the primary outcome. Multicollinearity and possible interactions among the independent variables were analyzed using the variance inflation factor.A total of 1446 patients were eligible for recombinant tissue plasminogen activator (rtPA) and 596 of these patients received rtPA. Of the 596 ischemic stroke patients, 286 patients presented with recent pre-stroke depression, 310 had no pre-stroke depression. Carotid artery stenosis (OR = 11.577, 95% CI, 1.281-104.636, P = 0.029) and peripheral vascular disease (OR = 18.040, 95% CI, 2.956-110.086, P = 0.002) were more likely to be associated with increase odds of improvement in ambulation in patients with no pre-stroke depression treated with rtPA, while antihypertensive medications (OR = 0.192, 95% CI, 0.035-1.067, P = 0.050),previous TIA (OR = 0.177, 95% CI, 0.038-0.818, P = 0.027), and congestive heart failure (OR = 0. 0.160, 95% CI, 0.030-0.846, P = 0.031) were associated with reduced odds of improvement in ambulation. In addition, carotid artery stenosis (OR = 0.078, 95% CI, 0.10-0.614, P = 0.015, congestive heart failure (OR = 0.217, 95% CI, 0.318-0.402, P = 0.030), previous TIA (OR = 0.444, 95% CI, 0.517-0.971, P = 0.012), higher NIHSS scores ((OR = 0.887, 95% CI, 0.830-0.948, P 0.001), and antihypertensive medications (OR = 0.810, 95% CI, 0.401-0.529, P = 0.019) were associated with the reduced odd of improvement in ambulation in an ischemic stroke population with pre-stroke depression treated with rtPA.Our findings indicate that more risk factors were associated with the decreased odds of an improvement in ambulation following thrombolytic therapy in an ischemic stroke population with pre-stroke depression when compared with those without pre-stroke depression. This finding maybe helpful in the development of management strategies to increase the use of thrombolytic therapy for pre-stroke depressed ischemic stroke to increased their eligibility for rtPA.

The purpose of this study was to explore the relationship between plaque characteristics and re-occlusion after surgical treatment of internal carotid artery occlusion (ICAO). From January 2015 to January 2021, 177 patients with ICAO underwent surgery. Eighty-five cases were included in the study, and in 13 of them, re-occlusion occurred within 6 mo after surgery treatment (13/85, 15.85%). The calcification at the base of the plaque was longer in the re-occlusion group than in the non-occlusion group (10.70 ± 4.22 mm vs. 7.15 ± 1.41 mm, p = 0.001). Multivariate regression analysis revealed that the length of calcification at the base of the plaque was an independent risk factor for postoperative re-occlusion (odds ratio [OR]: 1.414, 95% confidence interval [CI]: 1.078–1.855, p = 0.012). The cutoff value for the length of calcification at the base of the plaque predicting re-occlusion after ICAO was 8.5 mm (95% CI: 0.700–0.962, p = 0.001). The area under the receiver operating characteristic curve was 0.831. Sensitivity and specificity were 70% and 80.9%, respectively. These results indicate that pre-operative ultrasound examination of the length of calcification at the base of the plaque could predict re-occlusion after surgical treatment of ICAO.

Background and Purpose: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. Methods: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. Results: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles ( P P =0.015). Lower performance was attributed largely to Word List Recall ( P P ≤0.01). The scores for left versus right carotid disease were similar. Conclusions: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02089217.

Cerebral hyperperfusion syndrome (CHS) is a critical complication after carotid artery stenting (CAS). However, few CAS studies have evaluated immediate and temporary changes in ipsilateral cerebral blood flow (CBF) quantitatively. The study was performed to evaluate immediate changes in CBF after CAS and subsequent CBF changes in patients with cerebral hyperperfusion (HP) using 123I-IMP SPECT. The subjects were 223 patients with chronic extracranial carotid artery stenosis who underwent CAS in our department between March 2010 and March 2020. Quantitative CBF and cerebrovascular reactivity to acetazolamide in the middle cerebral artery were assessed before CAS by 123I-IMP SPECT. CBF was also measured immediately after CAS by 123I-IMP SPECT. When HP was detected, CBF was measured again 3 and 7 days after CAS. The median (interquartile range) ipsilateral quantitative CBF change after CAS was − 0.1% (− 9.5–8.2%), and the upper value of the 95% CI of the quantitative CBF change was 48.2%. Thus, we defined HP after CAS as an increase in quantitative CBF of > 48.2% compared with the preoperative value. Of 223 patients, 5 (2.2%) had HP, and 4 of these patients (80%) developed CHS. In the CHS patients, HP was maintained for about 3 days and improved after about 7 days. An immediate CBF increase of > 48.2% after CAS may lead to development of CHS. In CHS after CAS, HP persisted for about 1 week and postoperative management may be required for at least 1 week.

Carotid artery stenting (CAS) is an attractive option in order to treat carotid artery stenosis. However, its safety in elderly patients is questioned. Aim of this single-center retrospective study was to assess data of elderly patients undergoing CAS, and to compare them with those of the younger (75 years).We collected data of 580 consecutive patients undergoing CAS between December 2007 and June 2020 and compared clinical and procedural characteristics as well as in-hospital major adverse events (MACCE) and long-term mortality between patients75 years and patients ≥ 75 years old.There were 272 patients (46.9%) with age ≥ 75 years and 308 patients (53.1%) with age75 years. The median follow-up was 48 months (range 2-144). There was no significant difference about in-hospital MACCE between the two groups (4.7% in the older vs. 3.5% in the younger group, p = 0.9), but a higher rate of cerebral hemorrhage occurred in the older group (1.8% vs. = 0.3%, p = 0.07), even if not significant. Long-term mortality was significantly higher in the older group (27.9 vs. 20.1%, p = 0.027). Multivariate predictors of 12-months mortality were neurologic symptoms within 6 months (OR: 4.83; 95% CI: 2.04-11.42; p ≤ 0.001), smoking status (OR: 2.84; 95% CI: 1.17-6.86; p = 0.02) and age ≥ 75 years (OR: 2.78; 95% CI: 1.14-6.76; p = 0.024).In elderly patients, CAS can be carried out efficaciously with acceptable procedural risks, if performed by expert operators and after a correct selection by a multidisciplinary team.

Background Carotid artery stenting is an alternative to carotid endarterectomy, especially in patients deemed to have significant anatomic or medical risk for the latter. There is scant literature, however, on indications for and outcomes of carotid stent (CAS) explant. We sought to determine indications and outcomes of CAS explant at our institution. Methods We queried a prospectively maintained institutional vascular surgery database as well as hospital records to identify patients undergoing carotid stent explant from 2010–2020. Ten patients were identified. Their charts were reviewed to obtain demographic, comorbidity, procedural, and outcomes data. Data of particular interest were preoperative atherosclerotic factors, indications for CAS explant, carotid repair strategy, and 30-day post-procedural complications. Data were analyzed for ranges and means. Results Ten patients were identified. Comorbidity was common: all patients had at least 1 atherosclerotic risk factor, with hypertension and hypercholesterolemia being the most common. Seven (70.0%) patients had recurrent stenosis as the indication for explant. Seven (70.0%) presented symptomatically. Five (50.0%) cases of restenosis had been refractory to angioplasty. There were 3 (30.0%) instances of CAS explant due to infection. Only 1 (12.5%) index CAS was performed at our institution. There was a mean hospital length of stay of 4.5 days. One patient had vocal cord paralysis requiring no intervention. There was no (0%) 30-day mortality, stroke, or postoperative wound infections. Conclusions Our series had 0% 30-day mortality, stroke, and postoperative wound infection suggesting that CAS explant may be performed safely. Our series is small but represents the largest single institution series to date. This procedure may become increasingly common in the coming years with the more frequent use of CAS; additional data is needed to rigorously understand outcomes.

Carotid artery stenosis (CAS) is one of the leading causes of ischemic stroke. However, knowledge of the changes in the plaque itself is lacking. Information about the ultrasound and clinical features of CAS will help elucidate the changes in prognostic and risk factors.We evaluated 736 patients with carotid stenosis for an average 18-month follow-up. According to their degree of CAS stenosis, patients were allocated to one of three groups: regression (n=125), stable (n=443), or progression (n=168). An ordinal regression analysis was used to determine the risk factors for atherosclerosis progression. A logistic regression was subsequently applied to investigate the effects of CAS stenosis on cerebrovascular events after adjusting for various factors.The progression group had more male patients (P=0.02), hypoechoic plaque (P0.01), high-risk high sensitivity C-reactive protein (hs-CRP) (P=0.02), ulcerative plaque (P=0.05), and hyperlipidemia (P=0.05) than the other two groups. There were no significant differences in residual ultrasound and clinical features among the three groups, including age, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), intima-media thickness (IMT), body mass index (BMI), diabetes mellitus (DM), hypertension (HTN), coronary heart disease (CHD), statin use, ulcerative plaque. The ordinal regression analysis identified hypoechoic plaque (OR, 1.53; 95% CI: 1.14-2.05; P0.01) and high-risk hs-CRP (OR, 1.75; 95% CI: 1.17-2.61; P0.01) as independent risk factors for CAS progression. Logistic regression analysis revealed that the stroke/transient ischemic attack adjusted odds ratio was 1.80 (95% CI: 1.03-3.13) in the progression group.High-risk hs-CRP and hypoechoic plaque are independently associated with CAS progression. The progression of carotid stenosis is associated with a high risk of cerebrovascular events.

Objective Ischaemic strokes can be caused by unstable carotid atherosclerosis, but methods for identification of high risk lesions are lacking. Carotid plaque morphology imaging using software for visualisation of plaque components in computed tomography angiography (CTA) may improve assessment of plaque phenotype and stroke risk, but it is unknown if such analyses also reflect the biological processes related to lesion stability. Here, we investigated how carotid plaque morphology by image analysis of CTA is associated with biological processes assessed by transcriptomic analyses of corresponding carotid endarterectomies (CEAs). Methods Carotid plaque morphology was assessed in patients undergoing CEA for symptomatic or asymptomatic carotid stenosis consecutively enrolled between 2006 and 2015. Computer based analyses of pre-operative CTA was performed to define calcification, lipid rich necrotic core (LRNC), intraplaque haemorrhage (IPH), matrix (MATX), and plaque burden. Plaque morphology was correlated with molecular profiles obtained from microarrays of corresponding CEAs and models were built to assess the ability of plaque morphology to predict symptomatology. Results Carotid plaques (n = 93) from symptomatic patients (n = 61) had significantly higher plaque burden and LRNC compared with plaques from asymptomatic patients (n = 32). Lesions selected from the transcriptomic cohort (n = 40) with high LRNC, IPH, MATX, or plaque burden were characterised by molecular signatures coupled with inflammation and extracellular matrix degradation, typically linked with instability. In contrast, highly calcified plaques had a molecular signature signifying stability with enrichment of profibrotic pathways and repressed inflammation. In a cross validated prediction model for symptoms, plaque morphology by CTA alone was superior to the degree of stenosis. Conclusion The study demonstrates that CTA image analysis for evaluation of carotid plaque morphology, also reflects prevalent biological processes relevant for assessment of plaque phenotype. The results support the use of CTA image analysis of plaque morphology for risk stratification and management of patients with carotid stenosis.

To investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single‐center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP

BACKGROUND Intraplaque neovascularization (IPN) in advanced lesions of the carotid artery has been linked to plaque progression and risk of rupture. Quantitative measurement of IPN may provide a more powerful tool for the detection of such "vulnerable" plaque than the current visual scoring method. The aim of this study was to develop a phantom platform of a neovascularized atherosclerotic plaque within a carotid artery to assess new methods of quantifying IPN. METHODS Ninety-two synthetic plaque models with various IPN architectures representing different ranges of IPN scoring were created and assessed using contrast-enhanced ultrasound. Intraplaque neovascularization volume was calculated from contrast infiltration in B mode. The plaque models were used to develop a testing platform for IPN quantification. A neovascularized enhancement ratio (NER) was calculated using commercially available software. The plaque model NERs were then compared to human plaque NERs (n = 42) to assess score relationship. Parametric mapping of dynamic intensity over time was used to differentiate IPN from calcified plaque regions. RESULTS A positive correlation between NER and IPN volume (rho = 0.45; P

Stroke is the fifth leading cause of death in the United States and is a leading cause of disability.(1) Extracranial internal carotid artery stenosis is a major cause of ischemic stroke, as it is estimated to cause 8–15% of ischemic strokes.(2,3) It is critical to improve our strategies for stroke prevention and treatment in order to reduce the burden of this disease. Here, we review approaches for the diagnosis and risk-stratification of carotid artery disease as well as interventional strategies for the prevention and treatment of strokes caused by carotid artery disease. Several critical questions in the field remain and are active areas of research. First, medical therapy has evolved significantly since early trials comparing medical therapy with interventional therapies, and patient outcomes while on contemporary medical therapy are unknown. Therefore, the benefit of revascularizing severe carotid artery disease in the current era of medical therapy is also unknown. Second, optimal management of patients with asymptomatic carotid stenosis continues to be a topic of debate. Third, the role of imaging for further risk-stratification of patients using characteristics of carotid plaques continues to be explored. Fourth, an understanding of how the presence of silent infarcts on brain imaging impacts risk-stratification and selection of treatment strategies is needed. Finally, the optimal use of endovascular management strategies for carotid artery disease, including carotid artery stenting and transcarotid artery revascularization, is an active area of investigation.

Objective Carotid endarterectomy is recommended for the prevention of ischaemic stroke due to carotid stenosis. However, the risk of stroke after carotid endarterectomy has been estimated at 2% - 5%. Monitoring intra-operative cerebral oxygenation with near infrared spectroscopy (NIRS) has been assessed as a strategy to reduce intra- and post-operative complications. The aim was to summarise the diagnostic accuracy of NIRS to detect intra-operative ischaemic events, the values associated with ischaemic events, and the relative contribution of external carotid contamination to the NIRS signal in adults undergoing carotid endarterectomy. Data sources EMBASE, MEDLINE, Cochrane Centre Register of Controlled Trials, and reference lists through May 2019 were searched. Review methods Non-randomised and randomised studies assessing NIRS as an intra-operative monitoring tool in carotid endarterectomy were included. Studies using NIRS as the reference were excluded. Risk of bias was assessed using the Newcastle Ottawa Scale, RoB-2, and QUADAS-2. Results Seventy-six studies were included (n = 8 480), under local (n = 1 864) or general (n = 6 582) anaesthesia. Seven studies were eligible for meta-analysis (n = 524). As a tool for identifying intra-operative ischaemia, specificity increased with more stringent NIRS thresholds, while there was unpredictable variation in sensitivity across studies. A Δ20% threshold under local anaesthesia resulted in pooled estimates for sensitivity and specificity of 70.5% (95% confidence interval, CI, 54.1 - 82.9) and 92.4% (95% CI 85.5 - 96.1) compared with awake neurological monitoring. These studies had low or unclear risk of bias. NIRS signal consistently dropped across clamping and recovered to pre-clamp values upon de-clamp in most studies, and larger decreases were observed in patients with ischaemic events. The contribution of extracranial signal to change in signal across clamp varied from 3% to 50%. Conclusion NIRS has low sensitivity and high specificity to identify intra-operative ischaemia compared with awake monitoring. Extracranial signal contribution was highly variable. Ultimately, data from high quality studies are desperately needed to determine the utility of NIRS.

Objective Carotid web (CaW) is reported as one of the causes of cryptogenic strokes. However, its pathophysiology is not known, which makes clinicians debate CaW treatment. The current study presents the mechanism of ischemic stroke in CaW and finds a potential indicator for ischemic stroke in CaW. Methods Computational fluid dynamics (CFD) was applied to computer-aided artificial human CaW models to investigate the correlation between stenosis rate and CaW angle. The CFD results were compared with stroke or symptomatic CaW including adequate reported images for anatomic analysis of the stenosis rate and CaW angle. Results The CFD result of the CaW models shows that the velocity decreases and the turbulence generation of blood flow increases in the area under CaW (AuCaW). In AuCaW, turbulence intensity (TI) is high in the high stenosis rate and small angle conditions. Moreover, TI remained high in the AuCaW throughout the cardiac cycles. The analysis of 67 anatomic figures appeared in 36 articles merged with CFD results, and a CaW scoring system was introduced for clinicians to determine patients with CaW with a high risk of ischemic stroke. Conclusions This study is believed to be the first to apply TI to CaW. Because most ischemic strokes in CaW occurred at a high stenosis rate and small angle, TI may be used as a potential indicator of ischemic stroke in CaW. Furthermore, TI is easily used in the daily clinical field by applying CaW scores.

Objective Closure of the artery during carotid endarterectomy (CEA) can be done with or without a patch, or performed with the eversion technique, while the use of intra-operative shunts is optional. The influence of these techniques on subsequent restenosis is uncertain. Long term carotid restenosis rates and risk of future ipsilateral stroke with these techniques were compared. Methods Patients who underwent CEA in the International Carotid Stenting Study were divided into patch angioplasty, primary closure, or eversion endarterectomy. Intra-operative shunt use was reported. Carotid duplex ultrasound was performed at each follow up. Primary outcomes were restenosis of ≥ 50% and ≥ 70%, and ipsilateral stroke after the procedure to the end of follow up. Results In total, 790 CEA patients had restenosis data at one and five years. Altogether, 511 (64.7%) had patch angioplasty, 232 (29.4%) primary closure, and 47 (5.9%) eversion endarterectomy. The cumulative incidence of ≥ 50% restenosis at one year was 18.9%, 26.1%, and 17.7%, respectively, and at five years it was 25.9%, 37.2%, and 30.0%, respectively. There was no difference in risk between the eversion and patch angioplasty group (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.45 – 1.81; p = .77). Primary closure had a higher risk of restenosis than patch angioplasty (HR 1.45, 95% CI 1.06 – 1.98; p = .019). The cumulative incidence of ≥ 70% restenosis did not differ between primary closure and patch angioplasty (12.1% vs. 7.1%, HR 1.59, 95% CI 0.88 – 2.89; p = .12) or between patch angioplasty and eversion endarterectomy (4.7%, HR 0.45, 95% CI 0.06 – 3.35; p = .44). There was no effect of shunt use on the cumulative incidence of restenosis. Post-procedural ipsilateral stroke was not more common in either of the surgical techniques or shunt use. Conclusion Restenosis was more common after primary closure than conventionally with a patch closure. Shunt use had no effect on restenosis. Patch closure is the treatment of choice to avoid restenosis.

Objective Intra-operative near infrared spectroscopy (NIRS) is a non-invasive tool used to monitor regional cerebral oxygen saturation during carotid endarterectomy (CEA), for which accuracy remains unclear. Therefore, this systematic review and meta-analysis aimed to determine the diagnostic accuracy of NIRS in patients undergoing CEA under regional anaesthesia (RA). Data sources MEDLINE, Scopus, and Web of Science were searched for studies that compared NIRS with the “awake test” in patients undergoing CEA under RA. Review methods Bivariable random effects meta-analysis was performed to determine the diagnostic accuracy of NIRS to detect cerebral ischaemia. Meta-regression was performed to explore causes of heterogeneity. Meta-analysis of proportions was also performed to determine the accuracy of NIRS in predicting 30 day stroke. Study quality was evaluated using the QUADAS-2 criteria. Results Eleven primary studies were included, assessing 1 237 participants. The meta-analysis obtained a partial area under the summary receiver operating characteristic curve for diagnosing brain ischaemia of 0.646, with a summary sensitivity of 72.0% (95% confidence interval [CI] 58.1 – 82.7; I2 = 48.6%) and a specificity of 84.1% (95% CI 78.5–88.4; I2 = 48.6%). In meta-regression analysis, the frequency of hypertension (p = .011) and patients with symptomatic carotid stenosis (p = .031) were significant effect modifiers. Higher frequency of arterial hypertension (z score = –2.15; p = .032) and diabetes (z score = –2.12; p = .034) were associated with lower summary sensitivity, while a higher frequency of symptomatic carotid stenosis (z score = 2.11; p = .035) was associated with higher summary sensitivity. Point estimate sensitivity and specificity for predicting 30 day stroke occurrence were 41% (95% CI 19.5 – 66.6; I2 = 0%) and 81.4% (95% CI 74.4 – 86.9, I2 = 65.6%), respectively. Conclusion The results of this study suggest that NIRS as a cerebral monitoring technique does not have sufficiently high sensitivity or specificity to be used alone in the neurological monitoring of patients undergoing CEA under RA.

Carotid atherosclerosis is a pathological process that leads to narrowing of the vessel lumen and a consequent risk of stroke. Revascularization procedures such as carotid endarterectomy (CEA) and carotid stenting aim to reduce occurrence of stroke in selected patients. Due to the proven benefit and low intraoperative risk, CEA is currently the preferred choice in candidates for carotid revascularization. However, the risk of cognitive impairment subsequent to CEA has not been fully elucidated and is unclear whether certain conditions, such as frailty, may increase this risk. There is consistent evidence that shows that frail patients have higher risk of cognitive impairment after surgical procedure. Moreover, brain pre-existing conditions may play a role in cognitive impairment after CEA. Cerebral small vessel disease (SVD) is a pathology that involves microcirculation and is detectable with computed tomography or magnetic resonance. SVD shares common vascular risk factors with carotid atherosclerosis, is a major contributor to vascular cognitive impairment and vascular dementia, and has been proposed as a marker of brain frailty. In this review, we discuss the current evidence about the link between carotid revascularization and cognitive impairment and advance the hypothesis that SVD may play a relevant role in development of cognitive impairment after carotid revascularization.

The present research aims to explore the relationship between circulating microRNA and carotid artery stenosis (CAS). To evaluate the diagnostic significance of miR-637 in CAS patients and its potential predictive value for cerebral ischemia events through clinical studies. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the differences in serum miR-637 between enrolled 97 CAS patients and 90 healthy individuals. Logistic regression analysis of the correlation between the level of miR-637 and the degree of carotid artery stenosis. The receiver operating characteristic (ROC) curve evaluated the diagnostic significance of miR-637 in identifying CAS patients from healthy individuals. Kaplan-Meier survival and Cox regression were used to evaluate the potential predictive ability of serum miR-637 levels during follow-up for cerebral ischemia events. Serum miR-637 of CAS patients was significantly reduced which was a good indicator of severe carotid stenosis (P

To evaluate and compare efficacy of intraoperative neurophysiological monitoring (IONM) and intraoperative transcranial Doppler (TCD) techniques for identification of hypoperfusion during carotid artery clamp and hyperperfusion after release of occlusion during carotid endarterectomy.This was a retrospective, consecutive case series of 152 patients undergoing carotid endarterectomy between June 2018 and March 2020. Somatosensory evoked potentials, motor evoked potentials, electroencephalogram, and TCD were obtained.Three patient cohorts were observed after clamping the carotid artery: A, in 132 of 152 patients (87%), TCD blood flow velocity decreased by50% and there were no changes in IONM; B, in 5 of 152 (3%) patients, TCD blood flow rate was reduced 50%-100% with no changes in IONM; C, in 15 patients (10%), blood flow velocity was reduced by 50%-100% and all IONM modalities met warning criteria. With increased blood pressure, IONM and blood flow velocities improved to less than warning criteria in 8 of 15 patients. In 6 of the 7 remaining patients, IONM modalities recovered to baseline immediately after clamps were removed from the carotid artery. The 1 patient with persistent motor evoked potential deterioration experienced postoperative proximal muscle weakness, which recovered 48 hours later. In 22 patients, TCD detected hyperperfusion at the moment of clamp release.TCD blood flow velocity is correlated with motor evoked potential and somatosensory evoked potential amplitude changes after clamping. After declamping, TCD can detect hyperperfusion and help regulate blood pressure to prevent hyperperfusion.

Background Large artery atherosclerotic disease is an important cause of stroke, accounting for 15–46% of ischaemic strokes in population-based studies. Therefore, current guidelines from west recommend urgent carotid imaging in all ischaemic strokes or transient ischaemic attacks and referral for carotid endarterectomy. However, the clinical features and epidemiology of stroke in Asians are different from those in Caucasians and therefore the applicability of these recommendations to Asians is controversial. Data on the prevalence of carotid artery stenosis (CAS) among South Asian stroke patients is limited. Therefore, we sought to determine the prevalence and associated factors of significant CAS in a cohort of Sri Lankan patients with ischaemic stroke. Methods We prospectively studied all ischaemic stroke patients who underwent carotid doppler ultrasonography admitted to the stroke unit of a Sri Lankan tertiary care hospital over 5 years. We defined carotid stenosis as low ( Results A total of 550 ischaemic stroke patients (326 (59.3%) male, mean age was 58.9 ± 10.2 years) had carotid doppler ultrasonography. Of them, 528 (96.0%) had low-grade, 12 (2.2%) moderate and 7 (1.3%) severe stenosis and 3 (0.5%) had total occlusion. On multivariate logistic regression, age was associated with CAS ≥ 50% (OR 1.12, p = 0.001) and CAS ≥ 70% (OR 1.14, p = 0.016), but none of the other vascular risk factors studied (sex, hypertension, diabetes mellitus, smoking, past history of TIA, stroke or ischemic heart disease) showed significant associations. Conclusions Carotid stenosis is a minor cause of ischemic stroke in Sri Lankans compared to western populations with only 4.0% having CAS ≥ 50 and 3.5% eligible for carotid endarterectomy. Our findings have implications for the management of acute strokes in Sri Lanka.

Background Little is known about the impact that cardiovascular (CV) risk factors have on the formation of various carotid atherosclerotic plaque features. This study set out to assess the association between CV risk factors and plaque characteristics on computed tomography (CT) angiography (CTA). Materials and methods A retrospective review was completed of consecutive patients that underwent a carotid endarterectomy and had CTA imaging of the head and neck vasculature. Atherosclerotic plaques of both carotid arteries were evaluated for calcification(s), low-density plaque (LDP) components, ulceration(s), and degree of stenosis. Various clinical CV risk factors were assessed using medical records. Last recorded laboratory levels were dichotomized into categories: total cholesterol Results Of 97 included patients, 62 were male (63.9%); the average age was 72.7 (standard deviation = 9.5). Calcifications were in 95/97 (97.9%) of patients (one or both carotid plaques); LDP components were in 73/97 (75.3%), and ulcerations were in 21/97 (21.6%). Elevated total cholesterol and elevated LDL levels were both associated with a higher likelihood of LDP components ( p = 0.004 and p = 0.02, respectively). There were no other statistically significant associations between individual plaque features or severity of arterial stenosis and CV risk factors. Conclusion In carotid atherosclerotic plaques, LDP components are more frequently present in one or both carotid arteries in patients with elevated total cholesterol and/or LDL levels. Such findings raise the possibility that cholesterol levels may be directly related to the formation of specific high-risk plaque features.

Background and Purpose: The circle of Willis (CoW) and leptomeningeal anastomoses play an important role in transforming infarct topography following middle cerebral artery occlusion. Their role in infarct topography following anterior cerebral artery occlusion is not well understood. The aim of this study was to evaluate the role of the CoW and leptomeningeal anastomoses in modifying regional variation in infarct topography following occlusion of the anterior cerebral artery and its branches. Methods: Perfusion and magnetic resonance imaging of patients with anterior cerebral artery stroke and evidence of vessel occlusion were segmented and manually registered to standard brain template for voxel-wise comparison. Next, a computer model of the cerebral arteries was formulated as network of nodes connected by cylindrical pipes. The experiments included occlusion of successive branches of the anterior cerebral artery while the configurations of the CoW were varied. Results: Forty-seven patients with a median age of 77.5 years (interquartile range, 68.0–84.5 years) were studied. The regions with the highest probabilities of infarction were the superior frontal gyrus (probability =0.26) and anterior cingulate gyrus (probability =0.24). The regions around the posterior cingulate gyrus (probability =0.08), paracentral lobule (probability =0.05), precuneus and superior parietal lobule (probability =0.03) had a low probability of infarction. Following occlusions distal to the anterior communicating artery, the computer model demonstrated an increase in flow (>30%) in neighboring cortical arteries with leptomeningeal anastomoses. Conclusions: Traditionally the CoW has been regarded as the primary collateral system. However, our computer model shows that the CoW is only helpful in redirecting flow following proximal vessel occlusions (pre-anterior communicating artery). More important are leptomeningeal anastomoses, which play an essential role in distal vessel occlusions, influencing motor outcome by modifying the posterolateral extent of infarct topography.

The purpose of this study was to evaluate the level of agreement between flow/velocity data obtained from 2D-phase-contrast (PC) and 4D-flow in patients scheduled for treatment of carotid artery stenosis. Image acquisition was performed using a 1.5 T scanner. We compared mean flow rates, vessel areas, and peak velocities obtained during the acquisition with both techniques in 20 consecutive patients, 15 males and 5 females aged 69 ± 5 years (mean ± standard deviation). There was a good correlation between both techniques for the CCA flow (r = 0.65, p &lt, 0.001), whereas for the ICA flow and ECA flow the correlation was only moderate (r = 0.4, p = 0.011 and r = 0.45, p = 0.003, respectively). Correlations of peak velocities between methods were good for CCA (r = 0.56, p &lt, 0.001) and moderate for ECA (r = 0.41, p = 0.008). There was no correlation for ICA (r = 0.04, p = 0.805). Cross-sectional area values between methods showed no significant correlations for CCA (r = 0.18, p = 0.269), ICA (r = 0.1, p = 0.543), and ECA (r = 0.05, p = 0.767). Conclusion: the 4D-flow imaging provided a good correlation of CCA and a moderate correlation of ICA flow rates against 2D-PC, underestimating peak velocities and overestimating cross-sectional areas in all carotid segments.

Background and Purpose: XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors. Methods: Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured. Results: Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median [interquartile range]: 1.24 [2.09] versus 0.16 [0.34]; P P P =0.010, r =−0.30) and directly with circulating uric acid levels ( P r =0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median [interquartile range]: 93.37% [25] versus 46.15% [21], respectively; P Conclusions: XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.

Background Tandem occlusion (TO) describes not only occlusion of the middle cerebral artery but a contemporaneous occlusion of the cervical internal carotid artery. There is a paucity of data over whether mechanical thrombectomy (MT) alone, MT with angioplasty, or MT with carotid artery stent placement is superior. We aim to address a gap in the literature comparing carotid stenting with mechanical thrombectomy (CSMT) and carotid angioplasty with mechanical thrombectomy (CAMT) in patients presenting with acute anterior circulation TOs. Methods This is a multicenter, retrospective study from 2012 to 2020 comparing CSMT and CAMT presenting with acute anterior circulation TOs. Primary outcomes of interest were functional status, perioperative stroke, mortality, and symptomatic intracranial hemorrhage (sICH). A total of 92 patients (66 vs. 26 in CSMT and CAMT, respectively) met inclusion criteria for analysis. Results There was no statistically significant difference in functional outcomes at 90-day follow-up (adjusted odds ratio [aOR] 0.82; 95% confidence interval [CI] 0.20–3.5; P = 0.46). In addition, there was no statistically significant difference in 90-day mortality (aOR 0.361; 95% CI 0.016–2.92; P = 0.532) and perioperative stroke rate (aOR 1.76; 95% CI 0.160–15.6; P = 0.613). However, sICH risk was significantly greater in the stent-treated cohort (aOR 3.94; 95% CI 0.529–37.4; P = 0.003). Conclusions Functional outcomes, mortality, and perioperative stroke rates do not significantly differ in CSMT and CAMT procedures in the acute setting. However, CSMT-treated patients do appear to have an increased risk of sICH, potentially due to the use of additional antiplatelet agents following stent placement.

This study aimed to find out cellular and electrophysiological effects of the edaravone (EDR) administration following induction of vascular dementia (VaD) via bilateral-carotid vessel occlusion (2VO). The rats were randomly divided into control, sham, 2VO + V (vehicle), and 2VO + EDR groups. EDR was administered once a day from day 0-28 after surgery. The passive-avoidance, Morris water-maze, and open-field tests were used for evaluation of memory, locomotor, and anxiety. The field-potential recording was used for assessment of electrophysiological properties of the hippocampus; and after sacrificing, the cerebral hemispheres were removed for stereological study and evaluation of MDA levels. The long-term potentiation (LTP), paired-pulse ratio (PPR), and input-output (I/O) curves were evaluated as indexes for long-term and short-term synaptic plasticity, and basal-synaptic transmission (BST), respectively. The 2VO led to increases in MDA level with considerable neuronal loss and decreases in the volume of the hippocampus, along with a reduction in the BST and LTP induction which was associated with a decrement in PPR and ultimate loss in memory with higher anxiety behavior. However, administration of EDR caused a decline in MDA and prevented the neural loss and volume of the hippocampus, rescued BST and LTP depression, improved memory and anxiety without any effects on PPR. Therefore, most likely through the improvement of MDA level, and the hippocampal cell number and volume, EDR leads to recovery of synaptic plasticity and behavioral performance. Because of the LTP rescue, without recovery of PPR, it is likely that the EDR improved LTP through the post-synaptic neurons.

OBJECTIVE/BACKGROUND: Carotid artery stenting (CAS) is a valuable solution for the treatment of carotid artery stenosis in a high-risk patient population for carotid endarterectomy (CEA). In literature however, there are concerns about the death and stroke rates of CAS in the 'real world' practice. Since Belgium is a small country with a broad offer of medical care, and there is no reimbursement for CAS, only small numbers of patients can be treated per vascular department. METHODS: In our department 45 CAS were performed from January 2006 until May 2018. Patient characteristics, indication for treatment and choice of treatment, minor stroke, major stroke and death rates were analyzed retrospectively. RESULTS: Of these patients 8/45 (18%) had a symptomatic carotid artery stenosis and 37/45 (82%) had an asymptomatic stenosis. A total minor stroke rate of 3/45 (6.6%) was recorded, but no major stroke (0%) or death (0%). Of the 37 patients who were asymptomatic at the start, 1 suffered a minor stroke (1/37, 2.7%) peri-operatively. CONCLUSION: Real world data from a low volume center show that CAS performed in patients with high risk for CEA yields acceptable outcome that is comparable to the literature. Since CAS is a delicate procedure we advice to centralize the procedure to an dedicated experienced interventionalist and to perform rigorous quality control of your 'real world' data.

Serebral silent ischemia is a complication of carotid stenting. If silent ischemia occurs 24 h later of carotid stenting, it called early serebral silent ischemia. The aim of this study was to evaluate the effect of heparin infusion on the prevention of early silent ischemia in patients who underwent carotid stenting.We included 26 patients who underwent carotid stenting. Patients who had carotid stenting, we randomized into two groups. The first group of patients were given continuously heparin infusion a maximum of 20,000 units for 24 h, and screened the aPTT value each 6 h. The aPTT value aimed a range of 2-3 times to up baseline. The second group didn't take heparin infusion. Diffusion weighted magnetic resonance imaging (DWI-MRI) and gradient echo (GRE) sequences performed in all patients at the 24 h of carotid stenting.Early serebral silent ischemia was detected by DWI-MRI in 13 (50%) of 26 patients who underwent carotid stenting. Seven (53.80%) of 13 patients whit early serebral silent ischemia did not receive heparin treatment, while 6 (46.20%) received heparin treatment. There was no symptomatic or asymptomatic acute hemorrhage in patients who treated with heparin.In our study, the continuation of anticoagulant therapy for 24 h to prevent early silent ischemia was not statistically significant. Also there is no reduction for count of serebral silent ischemia between two groups. However, due to the small number of patients in the study, future studies are required with more patients.

Objective: The aim of this study was to contribute to the issue of “Who should we perform Doppler ultrasonography on?” and determine the contribution of comorbid diseases to the development of carotid artery stenosis (CAS) and pre-operative CAS by examining comorbid diseases in patients undergoing coronary artery bypass graft operation (CABG) and also discussing the effect of carotid stenosis levels on postoperative stroke.Method: Between 2011-2015, a total of 921 patients who underwent cardiac surgery retrospectively were examined. Of these, 594 CABG patients aged 60 and over who underwent preoperative carotid Doppler examination were analyzed.Results: Sixty-five percent of patients were male, and 35% were female. The mean age was 69.3 years. Sixty-nine percent of patients were in the 0-29% stenosis group, 12.9% in the 30-49% group, 14.6% in the 50-69% group, 3% in the 70-99% group, and 0.3% in the 100% occlusion group. Peripheral artery disease (PAD), age, gender, and diabe-tes mellitus (DM) were found to have significant (P < 0.05) effects on the occurrence of CAS. CAS increased by 0.9% with an increase of one year in age, 10.8% with the presence of PAD, 3% with male sex, 3.8% with presence of chronic obstructive pulmonery disease (COPD), 1.9% with presence of left main coronary disease (LMCAD), and 0.9% with pres-ence of hypertension. In the decision tree analysis, the rate of 50% and above CAS in the presence of PAH + DM and age older than 65 years was 62.5%. Cerebrovascular accident (CVA) distribution was 2.1% in the 0-29% group, 2.5% in the 30-49% group, 4.5% in the 50-69% group, and 11.1% in the 70-99% group. Postoperative CVA was not observed in 10 patients who underwent carotid endarterectomy (CE). Postoperative CVA developed in six patients with 50% or more stenosis who did not undergo CE. Conclusion: For the preoperative detection of CAS in patients undergoing CABG, the association of advanced age, PAD, DM, male gender, COPD, LMCAD, and hyperten-sion risk factors should be considered. We suggest that carotid screening should be performed in those over 65 years of age and with PAD+DM. Studies with large populations are needed to observe the effects of aortic atherosclerosis load, surgical proce-dure, and unilateral/bilateral CAS presence on the development of stroke in patients with severe CAS and postoperative CVA.

Background Using computed tomography angiography to differentiate between components of carotid atherosclerotic lesions remains largely elusive. This study sought to validate a semi-automated software for computed tomography angiography plaque analysis using histologic comparisons. Materials and Methods A retrospective review was performed of consecutive patients that underwent a carotid endarterectomy, with pre-procedural computed tomography angiography imaging of the cervical arterial vasculature available for review. Images were evaluated using a commercially-available software package, which produced segmented analyses of intraplaque components (e.g. intraplaque hemorrhage, lipid-rich necrotic core, and calcifications). On imaging, each component was assessed in terms of its (1) presence or absence, and (2) both volume and proportion of the total plaque volume (if present). On histological evaluation of carotid endarterectomy specimens, each component was evaluated as an estimated proportion of total plaque volume. Results Of 80 included patients, 30 (37.5%) were female. The average age was 69.7 years (SD = 9.1). Based on imaging, intraplaque hemorrhage was the smallest contributor to plaque composition (1.2% of volumes on average). Statistically significant linear associations were noted between the proportion of intraplaque hemorrhage, lipid-rich necrotic core, and calcifications on histology and the volume of each component on imaging ( p values ranged from 0.0008 to 0.01). Area under curve were poor for intraplaque hemorrhage and lipid-rich necrotic core (0.59 and 0.61, respectively) and acceptable for calcifications (0.73). Conclusion Semi-automated analyses of computed tomography angiography have limited diagnostic accuracy in the detection of intraplaque hemorrhage and lipid-rich necrotic core in carotid artery plaques. However, volumetric imaging measurements of different components corresponded with histologic analysis.

Background The multicenter prospective CREST-2 Registry (C2R) provides recent experience in performing carotid artery stenting (CAS) for interventionists to ensure safe performance of CAS. Objective To determine the periprocedural safety of CAS performed using a transradial approach relative to CAS performed using a transfemoral approach. Methods Patients with ≥70% asymptomatic and ≥50% symptomatic carotid stenosis, ≤80 years of age and at standard or high risk for carotid endarterectomy (CEA) are eligible for the C2R. The primary endpoint was a composite of severe access-related complications. Comparisons were made using propensity-score matched logistic regression. Results The mean age of the cohort was 67.6 ± 8.2 years and 1906 (35.1%) were female. Indications for CAS included 4063 (74.9%) for primary atherosclerosis. A total of 2868 (52.8%) cases underwent CAS for asymptomatic disease. Transradial access was used in 213 (3.9%) patients. The transradial cohort had lower use of general anesthesia (1.5% vs. 6.3%, p = 0.007) and higher use of distal embolic protection (96.7% vs. 89.4%, p = 0.0004). There were no significant differences between radial and femoral access groups in terms of a composite of major access-related complications (0% vs. 1.1%) or a composite of periprocedural stroke or death (3.3% vs. 2.4%; OR = 1.4 [confidence intervals 0.6, 3.1]; p = 0.42). Conclusion We found no significant differences in rates of major access-related complications or periprocedural stroke or death with CAS performed using transradial compared to transfemoral access. Our results support incorporation of the transradial approach to clinical trials comparing CAS to other revascularization techniques.