Cervical Dissection in Patients With Tandem Lesions Is Associated With Distal Embolism and Lower Recanalization Success.

BACKGROUND: Tandem lesions consist of cervical internal carotid artery (ICA) stenosis or occlusion, most commonly of atherosclerosis or dissection etiology, plus a large vessel occlusion. In this study, we compare outcomes in patients with atherosclerosis versus dissection of the cervical ICA. METHODS: This multicenter retrospective cohort study includes data from tandem lesion patients who underwent endovascular treatment from 2015 to 2020. Atherosclerosis was defined as ICA stenosis/occlusion associated with a calcified lesion and dissection by the presence of a tapered or flame-shaped lesion and intramural hematoma. Primary outcome: 90-day functional independence (modified Rankin Scale score, 0-2); secondary outcomes: 90-day favorable shift in the modified Rankin Scale score, modified Thrombolysis in Cerebral Infarction score 2b-3, modified Thrombolysis in Cerebral Infarction score 2c-3, symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, distal embolization, early neurological improvement, and mortality. Analysis was performed with matching by inverse probability of treatment weighting. RESULTS: We included 526 patients (68 [59-76] years; 31% females); 11.2% presented dissection and 88.8%, atherosclerosis. Patients with dissection were younger, had lower rates of hypertension, hyperlipidemia, diabetes, and smoking history. They also exhibited higher rates of ICA occlusion, multiple stents (>1), and lower rates of carotid self-expanding stents. After matching and adjusting for covariates, there were no differences in 90-day functional independence. The rate of successful recanalization was significantly lower in the dissection group (adjusted odds ratio, 0.38 [95% CI, 0.16-0.91]; P=0.031), which also had significantly higher rates of distal emboli (adjusted odds ratio, 2.53 [95% CI, 1.15-5.55]; P=0.021). There were no differences in other outcomes. Acute ICA stenting seemed to increase the effect of atherosclerosis in successful recanalization. CONCLUSIONS: This study reveals that among patients with acute stroke with tandem lesions, cervical ICA dissection is associated with higher rates of distal embolism and lower rates of successful recanalization than atherosclerotic lesions. Using techniques to minimize the risk of distal embolism may mitigate this contrast. Further prospective randomized trials are warranted to fully understand these associations.

Prediction of Severe Baseline Asymptomatic Carotid Stenosis and Subsequent Risk of Stroke and Cardiovascular Disease.

BACKGROUND: Risk models to identify patients at high risk of asymptomatic carotid artery stenosis (ACAS) can help in selecting patients for screening, but long-term outcomes in these patients are unknown. We assessed the diagnostic and prognostic value of the previously published Prevalence of ACAS (PACAS) risk model to detect ACAS at baseline and to predict subsequent risk of stroke and cardiovascular disease (CVD) during follow-up. METHODS: We validated the discrimination and calibration of the PACAS risk model to detect severe (≥70% narrowing) ACAS with patients from the Reduction of Atherothrombosis for Continued Health registry. We subsequently calculated the incidence rates of stroke and CVD (fatal and nonfatal stroke or myocardial infarction or vascular death) during follow-up in 4 risk groups (low, medium, high, and very high, corresponding to sum scores of ≤9, 10-13, 14-17, and ≥18, respectively). RESULTS: Among 26 384 patients, aged between 45 and 80 years, without prior carotid procedures, 1662 (6.3%) had severe baseline ACAS. During ≈70 000 patient-years of follow-up, 1124 strokes and 2484 CVD events occurred. Discrimination of the PACAS model was 0.67 (95% CI, 0.65-0.68), and calibration showed adequate concordance between predicted and observed risks of severe baseline ACAS after recalibration. Significantly higher incidence rates of stroke (Ptrend<0.011) and CVD (Ptrend<0.0001) during follow-up were found with increasing PACAS risk groups. Among patients with high PACAS sum score of ≥14 (corresponding to 27.7% of all patients), severe baseline ACAS prevalence was 11.4%. In addition, 56.6% of incident strokes and 64.9% of incident CVD events occurred in this group. CONCLUSIONS: The PACAS risk model can reliably identify patients at high risk of severe baseline ACAS. Incidence rates of stroke and CVD during follow-up were significantly higher in patients with high PACAS sum scores. Selective screening of patients with high PACAS sum scores may help to prevent future stroke or CVD.

Association of HIV and HCV Infection With Carotid Artery Plaque Echomorphology in the MACS/WIHS Combined Cohort Study.

BACKGROUND: HIV and hepatitis C virus (HCV) are associated with increased risk of carotid artery atherosclerotic plaque and stroke. We examined associations of HIV- and HCV-related factors with echomorphologic features of carotid artery plaque. METHODS: This cross-sectional study included participants from the MACS (Multicenter AIDS Cohort Study)/WIHS (Women's Interagency HIV Study) Combined Cohort Study who underwent high-resolution B-mode carotid artery ultrasound. Plaques were characterized from 6 areas of the right carotid artery. Poisson regression controlling for demographic and cardiometabolic risk factors determined adjusted prevalence ratios (aPRs) and 95% CIs for associations of HIV- and HCV-related factors with echomorphologic features. RESULTS: Of 2655 participants (65% women, median age 44 [interquartile range, 37-50] years), 1845 (70%) were living with HIV, 600 (23%) were living with HCV, and 425 (16%) had carotid plaque. There were 191 plaques identified in 129 (11%) women with HIV, 51 plaques in 32 (7%) women without HIV, 248 plaques in 171 (28%) men with HIV, and 139 plaques in 93 (29%) men without HIV. Adjusted analyses showed that people with HIV and current CD4+ count <200 cells/µL had a significantly higher prevalence of predominantly echolucent plaque (aPR, 1.86 [95% CI, 1.08-3.21]) than those without HIV. HCV infection alone (aPR, 1.86 [95% CI, 1.08-3.19]) and HIV-HCV coinfection (aPR, 1.75 [95% CI, 1.10-2.78]) were each associated with higher prevalence of predominantly echogenic plaque. HIV-HCV coinfection was also associated with higher prevalence of smooth surface plaque (aPR, 2.75 [95% CI, 1.03-7.32]) compared with people without HIV and HCV. CONCLUSIONS: HIV with poor immunologic control, as well as HCV infection, either alone or in the presence of HIV, were associated with different echomorphologic phenotypes of carotid artery plaque.

SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.

Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.

Evaluating the influence of altered cerebral hemodynamics on cognitive performance in asymptomatic carotid artery stenosis: A systematic review.

OBJECTIVE: Substantial controversy exists regarding asymptomatic carotid stenosis (ACS) and its potential role in the pathophysiology of cognitive impairment. If proven, this hypothesis may suggest an additional definition for symptomatic carotid disease that would alter current management. This study aimed to synthesize the literature evaluating the relationship between impaired cerebral hemodynamics and cognition in patients with ACS. METHODS: A literature search was performed using MEDLINE, Embase, and EBM Reviews through May 2022. We included prospective case-control studies that used validated, objective measure(s) of either global cognition or one or more domains of cognitive function and assessed cerebrovascular reserve (CVR). RESULTS: Five studies were included, comprising a total of 782 patients with moderate (50%-69%) to severe (70%-99%) ACS. Patients with ACS and impaired ipsilateral CVR demonstrated significant cognitive impairment compared with controls. Patients with unilateral or bilateral ACS and normal CVR had cognitive scores similar to controls. Those with bilateral CVR impairment demonstrated the lowest cognitive scores. CONCLUSIONS: This review lends support to the claim that cognitive impairment, likely the result of impaired cerebral hemodynamics, is an under-recognized morbidity in patients with ACS. CVR may serve as an additional tool to determine whether patients are in fact symptomatic from their carotid stenosis and warrant consideration for intervention.

Surveillance duplex ultrasound prompted interventions after carotid endarterectomy.

OBJECTIVE: Current societal guidelines recommend duplex ultrasound (DUS) surveillance beyond 30 days after carotid endarterectomy (CEA) for patients with risk factors for restenosis or who underwent primary closure. However, the appropriate duration of this surveillance has not yet been identified, and the rate at which DUS surveillance prompts intervention is unknown. Multiple calls for decreasing health care spending that does not provide value, including unnecessary testing, have been made. The purpose of this study was to examine the rate of intervention prompted by surveillance DUS on the ipsilateral or contralateral carotid artery after CEA and determine the value of continued surveillance by determining the rate of DUS-prompted intervention. METHODS: A single-center, retrospective chart review of all patients older than 18 years who had undergone CEA from August 2009 to July 2022 was performed. Patients with at least one postoperative duplex in our Intersocietal Accreditation Council-accredited ultrasound lab were included. Exclusion criteria were patients with incomplete medical charts or patients who underwent a concomitant procedure. The primary end point was return to the operating room for subsequent intervention based on abnormal surveillance DUS findings. Secondary end points were the number of postoperative surveillance duplexes, duration of surveillance, and incidence of perioperative stroke. The study participant data were queried for patients who had a diagnosis of stroke that occurred following their procedure. RESULTS: A total 767 patients, accounting for 771 procedures, were included in this study, which resulted in 2145 ultrasound scans. A total of 40 (5.2%) patients required 44 subsequent interventions that were prompted by DUS surveillance scans. The average number of ultrasound scans per patient was 2.8 (range: 0-14), and the average duration of surveillance was 26.4 months (range: 0-155 months). Of the 767 patients, 669 (87.2%) had a unilateral CEA. A total of 62 of 767 (8.1%) patients had planned endarterectomies on the contralateral side based on initial imaging, not prompted by interval DUS surveillance scans. Of 767 patients, 28 (3.7%) patients who underwent CEA had a subsequent procedure for progression of contralateral disease, which was prompted by duplex surveillance scans. The average duration between index CEA and intervention on contralateral carotid was 29.57 months (range: 3-81 months). A total of 11 patients, accounting for 12 procedures, underwent a subsequent procedure for restenosis of their ipsilateral carotid, prompted by duplex surveillance scans. The average duration between index CEA and reintervention on the ipsilateral carotid was 17.9 months (range: 4-70 months). Three of 767 (0.4%) patients in total were identified as having a perioperative stroke. CONCLUSIONS: The overall rate of ipsilateral reintervention after CEA is low. A small percentage of patients will progress their contralateral disease, ultimately requiring surgical intervention. These data suggest that regular duplex surveillance after CEA is warranted for patients with at least moderate contralateral disease; however, the yield is low for ipsilateral restenosis after 36 months based on this single institution study. Further study is needed to better delineate which patients need follow-up to decrease unnecessary testing while still targeting patients most at risk of restenosis or contralateral progression of disease.

Long-term outcomes of carotid endarterectomy vs transfemoral carotid stenting in a Medicare-matched database.

BACKGROUND: Carotid endarterectomy (CEA) is associated with lower risk of perioperative stroke compared with transfemoral carotid artery stenting (TFCAS) in the treatment of carotid artery stenosis. However, there is discrepancy in data regarding long-term outcomes. We aimed to compare long-term outcomes of CEA vs TFCAS using the Medicare-matched Vascular Quality Initiative Vascular Implant Surveillance and Interventional Outcomes Network database. METHODS: We assessed patients undergoing first-time CEA or TFCAS in Vascular Quality Initiative Vascular-Vascular Implant Surveillance and Interventional Outcomes Network from January 2003 to December 2018. Patients with prior history of carotid revascularization, nontransfemoral stenting, stenting performed without distal embolic protection, multiple or nonatherosclerotic lesions, or concomitant procedures were excluded. The primary outcome of interest was all-cause mortality, any stroke, and a combined end point of death or stroke. We additionally performed propensity score matching and stratification based on symptomatic status. RESULTS: A total of 80,146 carotid revascularizations were performed, of which 72,615 were CEA and 7531 were TFCAS. CEA was associated with significantly lower risk of death (57.8% vs 70.4%, adjusted hazard ratio [aHR], 0.46; 95% confidence interval [CI], 0.41-0.52; P < .001), stroke (21.3% vs 26.6%; aHR, 0.63; 95% CI, 0.57-0.69; P < .001) and combined end point of death and stroke (65.3% vs 76.5%; HR, 0.49; 95% CI, 0.44-0.55; P < .001) at 10 years. These findings were reflected in the propensity-matched cohort (combined end point: 34.6% vs 46.8%; HR, 0.53; 95% CI, 0.46-0.62) at 4 years, as well as stratified analyses of combined end point by symptomatic status (asymptomatic: 63.2% vs 74.9%; HR, 0.49; 95% CI, 0.43-0.58; P < .001; symptomatic: 69.9% vs 78.3%; HR, 0.51; 95% CI, 0.45-0.59; P < .001) at 10 years. CONCLUSIONS: In this analysis of North American real-world data, CEA was associated with greater long-term survival and fewer strokes compared with TFCAS. These findings support the continued use of CEA as the first-line revascularization procedure.

Locoregional anesthesia is associated with decreased cardiac complications in symptomatic heart failure patients undergoing carotid endarterectomy.

OBJECTIVE: Although the current literature reports no advantage for locoregional anesthesia (LRA) over general anesthesia (GA) in patients undergoing carotid endarterectomy (CEA), there remains a gap in understanding the impact of LRA on individuals with congestive heart failure (CHF). This study aims to assess whether the choice of anesthesia influences the rates of perioperative complications within this patient population. METHODS: Using the Vascular Quality Initiative CEA module, all patients undergoing CEA between 2013 and 2023 were identified. The subset of patients with CHF was included, and patients were divided based on the type of anesthesia received. Patient characteristics and outcomes were compared using the χ2 or Fischer's exact test as appropriate for categorical variables and the independent t test or Mann-Whitney U test as appropriate for continuous variables. A sensitivity analysis was performed based on the symptomatic status of CHF, and the association between anesthesia modality and postoperative outcomes was studied using multivariable logistic regression analysis. The primary outcomes of this study included perioperative stroke, myocardial infarction (MI), acute HF, and the combination of MI and acute HF defined as major cardiac complications. RESULTS: A total of 21,292 patients (19,730 receiving GA, 1562 receiving LRA) with a diagnosis of CHF undergoing CEA were identified. On multivariable logistic regression analysis, LRA was independently associated with lower MI (odds ratio [OR]; 0.35; 95% confidence interval [CI], 0.13-0.96), acute HF (OR, 0.27; 95% CI, 0.09-0.87), major cardiac complications (OR, 0.30; 95% CI, 0.13-0.67), hemodynamic instability (OR, 0.64; 95% CI, 0.53-0.78), cranial nerve injury (OR, 0.40; 95% CI, 0.19-0.81), shunt use (OR, 0.25; 95% CI, 0.20-0.31), and neuromonitoring device use (OR, 0.20; 95% CI, 0.17-0.24) compared with GA in patients with symptomatic CHF. No difference in MI, acute HF, and major cardiac complications was seen in patients with asymptomatic CHF. CONCLUSIONS: CEA can be performed safely in patients with CHF. Using LRA is associated with a decreased incidence of perioperative cardiac complications in patients with symptomatic HF undergoing CEA.

Predicting vulnerable carotid plaques by detecting wall shear stress based on ultrasonic vector flow imaging.

OBJECTIVE: Carotid plaque vulnerability is a significant factor in the risk of cardiocerebrovascular events, with intraplaque neovascularization (IPN) being a crucial characteristic of plaque vulnerability. This study investigates the value of ultrasound vector flow imaging (V-flow) for measuring carotid plaque wall shear stress (WSS) in predicting the extent of IPN. METHODS: We enrolled 140 patients into three groups: 53 in the plaque group (72 plaques), 23 in the stenosis group (27 plaques), and 64 in the control group. V-flow was used to measure WSS parameters, including the average WSS (WSS mean) and the maximum WSS (WSS max), across three plaque locations: mid-upstream, maximum thickness, and mid-downstream. Contrast-enhanced ultrasound examination was used in 76 patients to analyze IPN and its correlation with WSS parameters. RESULTS: WSS max in the stenosis group was significantly higher than that in the control and plaque groups at the maximum thickness part (P < .05) and WSS mean in the stenosis group was significantly lower than that in the control group at the mid-upstream and mid-downstream segments (P < .05). WSS mean in the plaque group was significantly lower than that of the control group at all three locations (P < .05). Contrast-enhanced ultrasound examination revealed that plaques with neovascularization enhancement exhibited significantly higher WSS values (P < .05), with a positive correlation between WSS parameters and IPN enhancement grades, particularly WSS max at the thickest part (r = 0.508). Receiver operating characteristic curve analysis of WSS parameters for evaluating IPN showed that the efficacy of WSS max in evaluating IPN was better than that of WSS mean (P < .05), with an area under the curve of 0.7762 and 0.6973 (95% confidence intervals, 0.725-0.822 and 0.642-0.749, respectively). The cut-offs were 4.57 Pa and 1.12 Pa, sensitivities were 74.03% and 63.64%, and specificities were 75.00% and 68.18%. CONCLUSIONS: V-flow effectively measures WSS in carotid plaques. WSS max provides a promising metric for assessing IPN, offering potential insights into plaque characteristics and showing some potential in predicting plaque vulnerability.

Modality-specific outcomes of patients undergoing carotid revascularization in the setting of recent myocardial infarction.

OBJECTIVE: Recent myocardial infarction (MI) represents a real challenge in patients requiring any vascular procedure. There is currently a lack of data on the effect of preoperative MI on the outcomes of carotid revascularization methodology (carotid enterectomy [CEA], transfemoral carotid artery stenting [TFCAS], or transcarotid artery revascularization [TCAR]). This study looks to identify modality-specific outcomes for patients with recent MI undergoing carotid revascularization. METHODS: Data was collected from the Vascular Quality Initiative (2016-2022) for patients with carotid stenosis in the United States and Canada with recent MI (<6 months) undergoing CEA, TFCAS, or TCAR. In-hospital outcomes after TFCAS vs CEA and TCAR vs CEA were compared. TCAR vs TFCAS were compared in a secondary analysis. We used logistic regression models to compare the outcomes of these three procedures in patients with recent MI, adjusting for potential confounders. Primary outcomes included 30-day in-hospital rates of stroke, death, and MI. Secondary outcomes included stroke/death, stroke/death/MI, postoperative hypertension, postoperative hypotension, prolonged length of stay (>2 days), and 30-day mortality. RESULTS: The final cohort included 1217 CEA (54.2%), 445 TFCAS (19.8%), and 584 TCAR (26.0%) cases. Patients undergoing CEA were more likely to have prior coronary artery bypass graft/percutaneous coronary intervention and to use anticoagulant. Patients undergoing TFCAS were more likely to be symptomatic, have prior congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and undergo urgent operations. Patients undergoing TCAR were more likely to have higher rates of American Society of Anesthesiologists class IV to V, P2Y12 inhibitor, and protamine use. In the univariate analysis, CEA was associated with a lower rate of ipsilateral stroke (P = .079), death (P = .002), and 30-day mortality (P = .007). After adjusting for confounders, TFCAS was associated with increased risk of stroke/death (adjusted odds ratio [aOR], 2.69; 95% confidence interval [CI], 1.36-5.35; P = .005) and stroke/death/MI (aOR, 1.67; 95% CI, 1.07-2.60; P = .025) compared with CEA. However, TCAR had similar outcomes compared with CEA. Both TFCAS and TCAR were associated with increased risk of postoperative hypotension (aOR, 1.62; 95% CI, 1.18-2.23; P = .003 and aOR, 1.74; 95% CI, 1.31-2.32; P ≤ .001, respectively) and decreased risk of postoperative hypertension (aOR, 0.59; 95% CI, 0.36-0.95; P = .029 and aOR, 0.50; 95% CI, 0.36-0.71; P ≤ .001, respectively) compared with CEA. CONCLUSIONS: Although recent MI has been established as a high-risk criterion for CEA and an approved indication for TFCAS, this study showed that CEA is safer in this population with lower risk of stroke/death and stroke/death/MI compared with TFCAS. TCAR had similar stroke/death/MI outcomes in comparison to CEA in patients with recent MI. Further prospective studies are needed to confirm our findings.

Association of stroke or death with severity of carotid lesion calcification in patients undergoing carotid artery stenting.

OBJECTIVE: Carotid artery stenting (CAS) for heavily calcified lesions is controversial due to concern for stent failure and increased perioperative stroke risk. However, the degree to which calcification affects outcomes is poorly understood, particularly in transcarotid artery revascularization (TCAR). With the precipitous increase in TCAR use and its expansion to standard surgical-risk patients, we aimed to determine the impact of lesion calcification on CAS outcomes to ensure its safe and appropriate use. METHODS: We identified patients in the Vascular Quality Initiative who underwent first-time transfemoral CAS (tfCAS) and TCAR between 2016 and 2021. Patients were stratified into groups based on degree of lesion calcification: no calcification, 1% to 50% calcification, 51% to 99% calcification, and 100% circumferential calcification or intraluminal protrusion. Outcomes included in-hospital and 1-year composite stroke/death, as well as individual stroke, death, and myocardial infarction outcomes. Logistic regression was used to evaluate associations between degree of calcification and these outcomes. RESULTS: Among 21,860 patients undergoing CAS, 28% patients had no calcification, 34% had 1% to 50% calcification, 35% had 51% to 99% calcification, and 3% had 100% circumferential calcification/protrusion. Patients with 51% to 99% and circumferential calcification/protrusion had higher odds of in-hospital stroke/death (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.02-1.6; P = .034; OR, 1.9; 95% CI, 1.1-2.9; P = .004, respectively) compared with those with no calcification. Circumferential calcification was also associated with increased risk for in-hospital myocardial infarction (OR, 3.5; 95% CI, 1.5-8.0; P = .003). In tfCAS patients, only circumferential calcification/protrusion was associated with higher in-hospital stroke/death odds (OR, 2.0; 95% CI, 1.2-3.4; P = .013), whereas for TCAR patients, 51% to 99% calcification was associated with increased odds of in-hospital stroke/death (OR, 1.5; 95% CI, 1.1-2.2; P = .025). At 1 year, circumferential calcification/protrusion was associated with higher odds of ipsilateral stroke/death (12.4% vs 6.6%; hazard ratio, 1.64; P = .002). CONCLUSIONS: Among patients undergoing CAS, there is an increased risk of in-hospital stroke/death for lesions with >50% calcification or circumferential/protruding plaques. Increasing severity of carotid lesion calcification is a significant risk factor for stroke/death in patients undergoing CAS, regardless of approach.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.

Carotid stenosis and cryptogenic stroke.

OBJECTIVES: Cryptogenic stroke represents a type of ischemic stroke with an unknown origin, presenting a significant challenge in both stroke management and prevention. According to the Trial of Org 10,172 in Acute Stroke Treatment criteria, a stroke is categorized as being caused by large artery atherosclerosis only when there is >50% luminal narrowing of the ipsilateral internal carotid artery. However, nonstenosing carotid artery plaques can be an underlying cause of ischemic stroke. Indeed, emerging evidence documents that some features of plaque vulnerability may act as an independent risk factor, regardless of the degree of stenosis, in precipitating cerebrovascular events. This review, drawing from an array of imaging-based studies, explores the predictive values of carotid imaging modalities in the detection of nonstenosing carotid plaque (<50%), that could be the cause of a cerebrovascular event when some features of vulnerability are present. METHODS: Google Scholar, Scopus, and PubMed were searched for articles on cryptogenic stroke and those reporting the association between cryptogenic stroke and imaging features of carotid plaque vulnerability. RESULTS: Despite extensive diagnostic evaluations, the etiology of a considerable proportion of strokes remains undetermined, contributing to the recurrence rate and persistent morbidity in affected individuals. Advances in imaging modalities, such as magnetic resonance imaging, computed tomography scans, and ultrasound examination, facilitate more accurate detection of nonstenosing carotid artery plaque and allow better stratification of stroke risk, leading to a more tailored treatment strategy. CONCLUSIONS: Early detection of nonstenosing carotid plaque with features of vulnerability through carotid imaging techniques impacts the clinical management of cryptogenic stroke, resulting in refined stroke subtype classification and improved patient management. Additional research is required to validate these findings and recommend the integration of these state-of-the-art imaging methodologies into standard diagnostic protocols to improve stroke management and prevention.

Ulceration location is associated with clinical course in carotid stenosis.

OBJECTIVE: Plaque ulceration in carotid artery stenosis is a risk factor for cerebral ischemic events; however, the characteristics that determine plaque vulnerability are not fully understood. We thus assessed the association between plaque ulceration sites and cerebrovascular ischemic attack. METHODS: We retrospectively collected the clinical data of 72 consecutive patients diagnosed with carotid artery stenosis with plaque ulcers. After excluding patients with pseudo-occlusion, a history of previous carotid endarterectomy or carotid artery stenting before the ulcer was first discovered, follow-up data of less than 1 month, or carotid endarterectomy or carotid artery stenting performed within 1 month after the ulcer was first discovered, 60 patients were ultimately included. Patients were divided into proximal and distal groups based on the ulcer location relative to the most stenotic point. The primary endpoints were ipsilateral cerebrovascular ischemic events ("ischemic events"), such as amaurosis fugax, transient ischemic attack, or ischemic stroke due to carotid artery stenosis with plaque ulceration. The association between ulcer location and ischemic events was also assessed. RESULTS: In the patients with plaque ulcer, more patients had proximal than distal plaque ulcers (39 vs 21; P = .028). The median follow-up duration was 3.8 years (interquartile range, 1.5-6.2 years). Nineteen patients (32%) experienced ischemic event. Ischemic events occurred more frequently in the distal than in the proximal group (18% vs 59%; P = .005). Kaplan-Meier curves demonstrated a significantly shorter event-free time in the distal group (log-rank P = .021). In univariate analysis, distal ulcer location was associated with ischemic events (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.13-7.65; P = .03). Multivariate analysis using two different models also showed that distal ulcer location was independently associated with ischemic events (Model 1: OR, 3.85; 95% CI, 1.26-11.78; P = .03; Model 2: OR, 4.31; 95% CI, 1.49-12.49; P = .009). CONCLUSIONS: Patients with carotid artery stenosis and plaque ulcers located distal to the most stenotic point are more likely to experience cerebrovascular ischemic attacks. Therefore, carotid plaques with ulcers located distal to the most stenotic point may be a potential indication for surgical treatment.

Outcomes following carotid revascularization for stroke stratified by Modified Rankin Scale and time of intervention.

OBJECTIVES: The relationship between baseline Modified Rankin Scale (mRS) in patients with prior stroke and optimal timing of carotid revascularization is unclear. Therefore, we evaluated the timing of transfemoral carotid artery stenting (tfCAS), transcarotid artery revascularization (TCAR), and carotid endarterectomy (CEA) after prior stroke, stratified by preoperative mRS. METHODS: We identified patients with recent stroke who underwent tfCAS, TCAR, or CEA between 2012 and 2021. Patients were stratified by preoperative mRS (0-1, 2, 3-4, or 5) and days from symptom onset to intervention (time to intervention; ≤2 days, 3-14 days, 15-90 days, and 91-180 days). First, we performed univariate analyses comparing in-hospital outcomes between separate mRS or time-to-intervention cohorts for all carotid intervention methods. Afterward, multivariable logistic regression was used to adjust for demographics and comorbidities across groups, and outcomes between the various intervention methods were compared. Primary outcome was the in-hospital stroke/death rate. RESULTS: We identified 4260 patients who underwent tfCAS, 3130 patients who underwent TCAR, and 20,012 patients who underwent CEA. Patients were most likely to have minimal disability (mRS, 0-1 [61%]) and least likely to have severe disability (mRS, 5 [1.5%]). Patients most often underwent revascularization in 3 to 14 days (45%). Across all intervention methods, increasing preoperative mRS was associated with higher procedural in-hospital stroke/death (all P < .03), whereas increasing time to intervention was associated with lower stroke/death rates (all P < .01). After adjustment for demographics and comorbidities, undergoing tfCAS was associated with higher stroke/death compared with undergoing CEA (adjusted odds ratio, 1.6; 95% confidence interval, 1.3-1.9; P < .01) or undergoing TCAR (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.8; P = .03). CONCLUSIONS: In patients with preoperative stroke, optimal timing for carotid revascularization varies with stroke severity. Increasing preoperative mRS was associated with higher procedural in-hospital stroke/death rates, whereas increasing time to-intervention was associated with lower stroke/death rates. Overall, patients undergoing CEA were associated with lower in-hospital stroke/deaths. To determine benefit for delayed intervention, these results should be weighed against the risk of recurrent stroke during the interval before intervention.

Real-world use of medical therapy in moderate asymptomatic carotid stenosis.

OBJECTIVE: Despite level 1 evidence demonstrating the benefit of carotid endarterectomy for the prevention of stroke in patients with severe asymptomatic carotid stenosis (ACS), there has been a trend toward recommending optimal medical therapy (OMT) alone. This recommendation has been promulgated based on the observation that modern advances in OMT reduce the overall stroke risk in the general population, but the success of this treatment strategy is dependent on patient and provider adherence. In current practice, patients with moderate ACS are nearly all treated with OMT alone. The objective of this study was to evaluate adherence to OMT in a cohort of patients with moderate ACS undergoing treatment with OMT alone. METHODS: Consecutive carotid duplex ultrasound examinations were reviewed for the years 2019 and 2020. Those with moderate (50%-69%) ACS based on Society for Vascular Surgery guidelines were included in the study. Patients were assessed for OMT at the time of the index duplex, the first follow-up visit, and at each subsequent follow-up visit until the end of the study. OMT was defined as abstinence from smoking, aspirin or other antiplatelet use, and statin or other lipid-lowering therapy. Patients were stratified based on their ability to achieve OMT, and each component was evaluated to identify shortfalls in therapy. RESULTS: A total of 323 duplex ultrasound examinations with moderate ACS in 255 patients were identified. Of the 255 patients, 143 (56.1%) were on OMT at the time of the first duplex; that number increased to 163 (63.9%) by the first follow-up visit and 175 (68.6%) by the completion of the study. There were 112 (43.9%) patients who were not on OMT at the time of the index duplex, 43 (38.4%) of whom achieved OMT over a median follow-up time of 2.7 years. By the end of follow-up, 86 (76.8%) were taking aspirin or another antiplatelet medication, 93 (83.0%) were on statin or other lipid-lowering therapy, and 74 (66.1%) were abstinent from smoking. Pre-duplex smoking was independently associated with failure to achieve OMT (hazard ratio: 0.452, P = .017). CONCLUSIONS: Among patients with moderate ACS who were not previously on OMT, the rate of OMT achievement is poor. Although advances in lipid management through statin therapy have been praised for their role in improving the effectiveness of OMT, smoking cessation represents an important target for improving uptake and as a result effectiveness of OMT.

Investigation of the weekend effect on perioperative complications and mortality after carotid revascularization.

OBJECTIVE: Outcomes for weekend surgical interventions are associated with higher rates of mortality and complications than weekday interventions. Although prior investigations have reported the "weekend effect" for carotid endarterectomy (CEA), this association remains unclear for transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS). We investigated the weekend effect for all three carotid revascularization methods. METHODS: We queried the Vascular Quality Initiative for patients who underwent CEA, TCAR, and TFCAS between 2016 and 2022. χ2 and logistic regression modeling analyzed outcomes including in-hospital stroke, death, myocardial infarction, and 30-day mortality by weekend vs weekday intervention. Backward stepwise regression was used to identify significant confounding variables and was ultimately included in each final logistic regression model. Logistic regression of outcomes was substratified by symptomatic status. Secondary multivariable analysis compared outcomes between the three revascularization methods by weekend vs weekday interventions. RESULTS: A total of 155,962 procedures were analyzed including 103,790 CEA, 31,666 TCAR, and 20,506 TFCAS. Of these, 1988 CEA, 246 TCAR, and 820 TFCAS received weekend interventions. Logistic regression demonstrated no significant differences for TCAR and increased odds of in-hospital stroke/death/myocardial infarction for CEA (odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.04-1.65) and TFCAS (OR: 1.46, 95% CI: 1.09-1.96) weekend procedures. Asymptomatic TCAR patients had nearly triple the odds of 30-day mortality (OR: 2.85, 95% CI: 1.06-7.68, P = .038). Similarly, odds of in-hospital death were nearly tripled for asymptomatic CEA (OR: 2.89, 95% CI: 1.30-6.43, P = .009) and asymptomatic TFCAS (OR: 2.78, 95% CI: 1.34-5.76, P = .006) patients. Secondary analysis demonstrated that CEA and TCAR had no significant differences for all outcomes. TFCAS was associated with increased odds of stroke and death compared with CEA and TCAR. CONCLUSIONS: In this observational cohort study, we found that weekend carotid revascularization is associated with increased odds of complications and mortality. Furthermore, asymptomatic weekend patients perform worse in the CEA and TFCAS procedural groups. Among the three revascularization methods, TFCAS is associated with the highest odds of perioperative stroke and mortality. As such, our findings suggest that TFCAS procedures should be avoided over the weekend in favor of CEA or TCAR. In patients who are poor candidates for CEA, TCAR offers the lowest morbidity and mortality for weekend procedures.

Seven years of the transcarotid artery revascularization surveillance project, comparison to transfemoral stenting and endarterectomy.

OBJECTIVE: This study utilizes the latest data from the Vascular Quality Initiative (VQI), which now encompasses over 50,000 transcarotid artery revascularization (TCAR) procedures, to offer a sizeable dataset for comparing the effectiveness and safety of TCAR, transfemoral carotid artery stenting (tfCAS), and carotid endarterectomy (CEA). Given this substantial dataset, we are now able to compare outcomes overall and stratified by symptom status across revascularization techniques. METHODS: Utilizing VQI data from September 2016 to August 2023, we conducted a risk-adjusted analysis by applying inverse probability of treatment weighting to compare in-hospital outcomes between TCAR vs tfCAS, CEA vs tfCAS, and TCAR vs CEA. Our primary outcome measure was in-hospital stroke/death. Secondary outcomes included myocardial infarction and cranial nerve injury. RESULTS: A total of 50,068 patients underwent TCAR, 25,361 patients underwent tfCAS, and 122,737 patients underwent CEA. TCAR patients were older, more likely to have coronary artery disease, chronic kidney disease, and undergo coronary artery bypass grafting/percutaneous coronary intervention as well as prior contralateral CEA/CAS compared with both CEA and tfCAS. TfCAS had higher odds of stroke/death when compared with TCAR (2.9% vs 1.6%; adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.65-2.06; P < .001) and CEA (2.9% vs 1.3%; aOR, 2.21; 95% CI, 2.01-2.43; P < .001). CEA had slightly lower odds of stroke/death compared with TCAR (1.3% vs 1.6%; aOR, 0.83; 95% CI, 0.76-0.91; P < .001). TfCAS had lower odds of cranial nerve injury compared with TCAR (0.0% vs 0.3%; aOR, 0.00; 95% CI, 0.00-0.00; P < .001) and CEA (0.0% vs 2.3%; aOR, 0.00; 95% CI, 0.0-0.0; P < .001) as well as lower odds of myocardial infarction compared with CEA (0.4% vs 0.6%; aOR, 0.67; 95% CI, 0.54-0.84; P < .001). CEA compared with TCAR had higher odds of myocardial infarction (0.6% vs 0.5%; aOR, 1.31; 95% CI, 1.13-1.54; P < .001) and cranial nerve injury (2.3% vs 0.3%; aOR, 9.42; 95% CI, 7.78-11.4; P < .001). CONCLUSIONS: Although tfCAS may be beneficial for select patients, the lower stroke/death rates associated with CEA and TCAR are preferred. When deciding between CEA and TCAR, it is important to weigh additional procedural factors and outcomes such as myocardial infarction and cranial nerve injury, particularly when stroke/death rates are similar. Additionally, evaluating subgroups that may benefit from one procedure over another is essential for informed decision-making and enhanced patient care in the treatment of carotid stenosis.

The effect of controlled vs uncontrolled hypertension on outcomes of carotid revascularization procedures.

BACKGROUND: Hypertension (HTN) has been implicated as a strong predictive factor for poorer outcomes in patients undergoing various vascular procedures. However, limited research is available that examines the effect of uncontrolled HTN (uHTN) on outcomes after carotid revascularization. We aimed to determine which carotid revascularization procedure yields the best outcome in this patient population. METHODS: We studied patients undergoing carotid endarterectomy (CEA), transfemoral carotid artery stenting (TFCAS), or transcarotid artery revascularization (TCAR) from April 2020 to June 2022 using data from the Vascular Quality Initiative. Patients were stratified into two groups: those with cHTN and those with uHTN. Patients with cHTN were those with HTN treated with medication and a blood pressure of <130/80 mm Hg. Patients with uHTN had a blood pressure of ≥130/80 mm Hg. Our primary outcomes were in-hospital stroke, death, myocardial infarction (MI), and 30-day mortality. Our secondary outcomes were postoperative hypotension or HTN, reperfusion syndrome, prolonged length of stay (LOS) (>1 day), stroke/death, and stroke/death/MI. We used logistic regression models for the multivariate analysis. RESULTS: A total of 34,653 CEA (uHTN, 11,347 [32.7%]), 8199 TFCAS (uHTN, 2307 [28.1%]), and 17,309 TCAR (uHTN, 4990 [28.8%]) patients were included in this study. There was no significant difference in age between patients with cHTN and patients with uHTN for each carotid revascularization procedure. However, compared with patients with cHTN, patients with uHTN had significantly more comorbidities. uHTN was associated with an increased risk of combined in-hospital stroke/death/MI after CEA (adjusted odds ratio [aOR], 1.56; 95% confidence interval [CI], 1.30-1.87; P < .001), TFCAS (aOR, 1.59; 95% CI, 1.21-2.08; P < .001), and TCAR (aOR, 1.39; 95% CI, 1.12-1.73; P = .003) compared with cHTN. Additionally, uHTN was associated with a prolonged LOS after all carotid revascularization methods. For the subanalysis of patients with uHTN, TFCAS was associated with an increased risk of stroke (aOR, 1.82; 95% CI, 1.39-2.37; P < .001), in-hospital death (aOR, 3.73; 95% CI, 2.25-6.19; P < .001), reperfusion syndrome (aOR, 6.24; 95% CI, 3.57-10.93; P < .001), and extended LOS (aOR, 1.87; 95% CI, 1.51-2.32; P < .001) compared with CEA. There was no statistically significant difference between the outcomes of TCAR compared with CEA. CONCLUSIONS: The results from this study show that patients with uHTN are at a higher risk of stroke and death postoperatively compared with patients with cHTN, highlighting the importance of treating HTN before undergoing elective carotid revascularization. Additionally, in patients with uHTN, TFCAS yields the worst outcomes, whereas CEA and TCAR proved to be safer interventions. Patients with uTHN with symptomatic carotid disease treated with CEA or TCAR have better outcomes compared with those treated with TFCAS.

Multi-center experience with intravascular lithotripsy for treatment of severe calcification during transcarotid artery revascularization for high-risk patients.

OBJECTIVE: Transcarotid artery revascularization (TCAR) offers a safe alternative to carotid endarterectomy (CEA), but severe calcification is currently considered a contraindication in carotid artery stenting. This study aims to describe the safety and effectiveness of TCAR with intravascular lithotripsy (IVL) in patients with traditionally prohibitive calcific disease. METHODS: All consecutive patients who underwent TCAR+IVL from 2018-2022 at nine institutions were identified. IVL was combined with pre-dilatation angioplasty to treat calcified vessels before stent deployment. The primary outcome was a new ipsilateral stroke within 30 days. Secondary outcomes included any new ipsilateral neurologic event (stroke/transient ischemic attack [TIA]) at 30 days, technical success, and <30% residual stenosis. RESULTS: Fifty-eight patients (62% male; mean age, 78 ± 6.6 years) underwent TCAR+IVL, with 22 (38%) for symptomatic disease. Fifty-seven patients (98%) met high-risk anatomical or physiologic criteria for CEA. Forty-seven patients had severely calcific lesions. Fourteen patients (30%) had isolated eccentric plaque, 20 patients (43%) had isolated circumferential plaque, and 13 (27%) had eccentric and circumferential calcification. Mean procedure and flow reversal times were 87 ± 27 minutes and 25 ± 14 minutes. The median number of lithotripsy pulses per case was 90 (range, 30-330), and mean contrast usage was 29 mL. No patients had electroencephalogram changes or new deficits observed intraoperatively. Technical success was achieved in 100% of cases, with 98% having <30% residual stenosis on completion angiography. One patient had an in-hospital post-procedural stroke (1.72%). Four patients total had any new ipsilateral neurologic event (stroke/TIA) within 30 days for an overall rate of 6.8%. One TIA and one stroke occurred during the index hospitalization, and two TIAs occurred after discharge. Preoperative mean stenosis in patients with any postoperative neurologic event was 93% (vs 86% in non-stroke/TIA patients; P = .32), and chronic renal insufficiency was higher in patients who had a new neurologic event (75% vs 17%; P = .005). No differences were observed in calcium, procedural, or patient characteristics between the two groups. The mean follow-up was 132 days (range, 19-520 days). Three stents developed recurrent stenosis (5%) on follow-up duplex; the remainder were patent without issue. There were no reported interventions for recurrent stenosis during the study period. CONCLUSIONS: IVL sufficiently remodels calcified carotid arteries to facilitate TCAR effectively in patients with traditionally prohibitive calcific disease. One patient (1.7%) suffered a stroke within 30 days, although four patients (6.8%) sustained any new neurological event (stroke/TIA). These results raise concerns about the risks of TCAR+IVL and whether it is an appropriate strategy for patients who could potentially undergo CEA.