Symptomatic Nonstenotic Carotids: A Topical Review.

Historically, the management of carotid artery disease has primarily focused on the degree of stenosis as the main indicator for assessing stroke etiology, risk, and need for intervention. However, accumulating evidence suggests that structural and biological features within the arterial wall, such as intraplaque hemorrhage, may have superior diagnostic, prognostic, and therapeutic values. Under current guidelines, unless an atheroma results in ≥50% stenosis, it is not considered the cause of a cerebrovascular event. This results in extensive and often unproductive diagnostic workup, prescription of ineffective medical therapy, and preclusion of patients from receiving revascularization procedures that have been shown to prevent recurrent cerebrovascular events in cases of ≥50% stenosis. A subset of embolic strokes of undetermined source, which account for up to 25% of all ischemic cerebrovascular events, are thought to be due to thromboembolic phenomena from undiagnosed plaque disruptions in nonstenotic arteries (<50% stenosis). Recently, it has been proposed to reclassify this subgroup of patients as symptomatic nonstenotic carotid if the carotid plaque ipsilateral to the cerebrovascular event presents with high-risk features including intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap, and ulceration. In this review, we first provide a historical overview of the chain of events and circumstances that resulted in the present management of carotid artery disease. Second, we embed the contemporary biomarkers of plaque vulnerability in a modern mechanistic paradigm of carotid plaque disruption and thromboembolization. Third, we review the clinically available imaging tools to detect these biomarkers, and how their use has started to shed light on the prevalence and natural history of this underdiagnosed condition. Fourth, we review recent clinical studies employing a contemporary definition of symptomatic nonstenotic carotid and discuss targeted treatments for this condition. Finally, we make a case to generate the much-needed high-level evidence to align the clinical management of patients with symptomatic nonstenotic carotid with a contemporary understanding of plaque disruption and thromboembolization.

Stroke thrombectomy for large infarcts with limited penumbra: Systematic review and meta-analysis of randomized trials.

BACKGROUND AND PURPOSE: Recent randomized trials have suggested that endovascular thrombectomy (EVT) is superior to medical management (MM) for stroke patients with large infarcts. However, whether or how perfusion metrics should be used to guide optimal patient selection for treatment is largely unknown. MATERIALS AND METHODS: This was a meta-analysis of randomized controlled trials reporting the effectiveness of EVT for large infarcts stratified by perfusion mismatch profiles. Patients with mismatch ratio 1.2-1.8 or penumbra volume 10-15cc (intermediate mismatch) or mismatch ratio <1.2 or volume <10cc (low mismatch) were included. Odds of 90-day modified Rankin scale (mRS) 0 to 3 (good) and 5 to 6 (poor) were calculated and effect sizes were pooled using Mantel-Haenszel fixed-effects models. RESULTS: Two trials - SELECT2 and ANGEL-ASPECT - were included; 140 intermediate mismatch (75 EVT and 65 MM) and 60 low mismatch patients (23 EVT and 37 MM) were identified. EVT was significantly associated with higher odds of mRS 0 to 3 for intermediate mismatch (pooled OR 2.77 [95%CI 1.11-6.89], p=0.028; Figure 1), but not low mismatch (pooled OR 1.47 [95%CI 0.444.94], p=0.54; Figure 1). Similarly, in terms of 90-day poor outcomes (mRS 5 or 6), EVT for intermediate mismatch patients was significantly associated with lower odds (OR 0.49 [95%CI 0.24 to 0.99], p=0.046; Figure 2), while EVT for the low mismatch cohort was not (OR 0.66 [95%CI 0.22 to 1.96], p=0.45; Figure 2). There was no significant inter-study heterogeneity observed across study estimates. CONCLUSIONS: For patients with large infarcts, EVT appears to be likely beneficial for patients with perfusion mismatch ratio and volume of at least 1.2 and 10cc, but not for those with mismatch ratio <1.2 or volume <10cc. These data generally support the continued use of perfusion imaging to select patients with large infarcts for EVT if it is available at the treating institution. Future studies and trials should consider investigating the efficacy and safety of EVT for patients with large infarcts and low mismatch profiles. ABBREVIATIONS: EVT = endovascular thrombectomy; MM = medical management; OR = odds ratio; CI = confidence interval.

2024 Guideline for the Primary Prevention of Stroke: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2024 Guideline for the Primary Prevention of Stroke" replaces the 2014 "Guidelines for the Primary Prevention of Stroke." This updated guideline is intended to be a resource for clinicians to use to guide various prevention strategies for individuals with no history of stroke. METHODS: A comprehensive search for literature published since the 2014 guideline; derived from research involving human participants published in English; and indexed in MEDLINE, PubMed, Cochrane Library, and other selected and relevant databases was conducted between May and November 2023. Other documents on related subject matter previously published by the American Heart Association were also reviewed. STRUCTURE: Ischemic and hemorrhagic strokes lead to significant disability but, most important, are preventable. The 2024 primary prevention of stroke guideline provides recommendations based on current evidence for strategies to prevent stroke throughout the life span. These recommendations align with the American Heart Association's Life's Essential 8 for optimizing cardiovascular and brain health, in addition to preventing incident stroke. We also have added sex-specific recommendations for screening and prevention of stroke, which are new compared with the 2014 guideline. Many recommendations for similar risk factor prevention were updated, new topics were reviewed, and recommendations were created when supported by sufficient-quality published data.

Elevated triglycerides and treatment eligibility in patients with severe, asymptomatic carotid stenosis: CREST 2 Trials.

BACKGROUND: Data from the Centers for Disease Control show that approximately one-quarter of adults have elevated triglyceride (TG) levels. Some clinical trials, but not all, have demonstrated that pharmacologic treatment of high TG levels in patients already on statin therapy reduces the rate of major vascular events such as myocardial infarction and stroke. We assessed the prevalence of elevated TG levels in patients with asymptomatic carotid stenosis (CS), and medical conditions associated with high TG. METHODS: Baseline lipid profiles from patients enrolled in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST 2) were analyzed. to determine treatment eligibility for high TG levels using the criteria established by the REDUCE-IT trial (triglyceride levels ≥150 mg/dL with LDL managed by a statin to <100 mg/dL). Equally assessed was the percentage of patients who were using pharmacologic treatment for high TG levels at study entry. Demographic factors and baseline medical conditions associated with high (>150 mg/dl) TG values were also analyzed. Chi-square and t=tests were used to assess baseline factors and abnormal TG values. RESULTS: As of October 2023, of 2377 randomized CREST-2 patients, 2328 (98 %) (mean age 70.0 years, 63 % men) had baseline lipid profiles suitable for analysis. Among 1961 (84 %) patients who met REDUCE-IT criteria, analysis of lipid profiles revealed that 20.5 % of the patients were eligible for treatment of high triglycerides. Of the 1464 patients with fasting lipid profiles, 17.8 % were eligible for treatment. The median TG value was 205 (IQR 91) mg/dl in the total population. TG levels of 150 mg/dl or higher were strongly associated with hypertension, diabetes, obesity, high hemoglobin A1c, and reduced physical activity (all p<0.0001). CONCLUSIONS: Elevated TG levels are strongly associated with diabetes, hypertension, obesity, and reduced physical activity. Further research is needed on whether treatment of elevated TG levels in patients with asymptomatic carotid stenosis confers benefit.

Heterogeneity in measurement of NIHSS: a systematic review and meta-analysis.

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) is a pivotal clinical tool used to assess patients with acute stroke. However, substantial heterogeneity in the application and interpretation of stroke scale items can occur. This systematic review aimed to elucidate heterogeneity in measuring the NIHSS. MATERIAL AND METHODS: A literature search was performed on PubMed/OVID/Cochran's CENTRAL from inception to 2023. The references of the included papers were reviewed for further eligible articles. Clinical characteristic, NIHSS values, and sources of heterogeneity were recorded. Non-human and non-English language articles were excluded. The study quality was assessed using MINORS and GRADE. Meta-analysis and meta-regression were performed using a random-effects model to explore the sources of heterogeneity. RESULTS: Twenty-one papers for a total of 818 patients (mean per study: 39 ± 37) and 9696 NIHSS examinations (median per study: 8 [CI95% 2 to 42]) were included. Motor function had a higher ICC agreement (ranging from 0.85 ["Right Leg"] to 0.90 ["Right Arm"]) compared to the remaining items (ranging from 0.58 ["Facial Palsy"] to 0.85 ["Level of consciousness commands"]. The meta-regression showed a low effect size of covariates such as language version, remote evaluation, and retrospective analysis on NIHSS items (e.g., for "Level of consciousness commands," language effect was 0.30 [CI95% 0.20 to 0.48] and for "Visual", the retrospective assessment effect was -0.27 [CI95% -0.51 to -0.03]). CONCLUSION: The NIHSS scores showed moderate to excellent inter-rater agreement, with the highest heterogeneity in non-motor function evaluation. Using a non-English version, remote evaluation and retrospective analysis had small effects in terms of heterogeneity in the NIHSS scores.

Mediators of sex-specific differences in rates of stroke mimics among patients treated with intravenous thrombolysis: A nationwide analysis of 174,995 patients.

INTRODUCTION: Women are at higher risk of stroke mimics; however, the underlying reasons are unclear. METHODS: In this retrospective cohort study of the 2016-2020 National Inpatient Sample database, we identified patients treated with intravenous thrombolysis (IVT). Demographic information, vascular risk factors, comorbidities, and presence of known risk factors for stroke mimics (seizures, migraines, demyelinating diseases, psychiatric illnesses, and functional neurological disorders [FND]) were identified using ICD-10 codes. Rates of no cerebral infarction (NCI) were compared between men and women. Mediation analyses were conducted to identify significant drivers of sex-specific differences in the rate of NCI. RESULTS: 174,995 IVT-treated patients were identified; 41,605 (23.8 %) had NCI. Female patients had significantly higher rates of NCI compared to men (26.2 % vs. 20.9 %, p < 0.001). Women had significantly higher rates of stroke mimic risk factors (seizures, migraines, demyelinating disease, anxiety, depression, FND, and electrolyte derangements; all p < 0.001). Mediation analyses revealed that 39.8 %, 19.1 % of female sex's association with higher rates of NCI were mediated by higher rates of migraines and FND among women, respectively (both p < 0.001). CONCLUSIONS: IVT-treated women were more likely to have NCI than men. This relationship was largely mediated by higher rates of migraine and FND among women.

Endovascular Stroke Thrombectomy for Patients With Large Ischemic Core: A Review.

Importance: Recently, 6 randomized clinical trials-RESCUE-Japan-LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial), ANGEL-ASPECT (Trial of Endovascular Therapy for Acute Ischemic Stroke With Large Infarct), SELECT2 (Trial of Endovascular Thrombectomy for Large Ischemic Strokes), TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke), TENSION (Endovascular Thrombectomy for Acute Ischemic Stroke With Established Large Infarct), and LASTE (Large Stroke Therapy Evaluation)-have concluded their investigations on the efficacy and safety of endovascular thrombectomy (EVT) for the treatment of patients with ischemic stroke, anterior-circulation large vessel occlusions, and large areas of ischemic changes defined as an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 5 or less. Overall, the results appeared to be positive, with 5 of the 6 trials meeting their primary efficacy end point, and 1 trial that was a near miss. However, questions remain regarding how these trial results should be interpreted and incorporated into routine clinical practice. Observations: In this narrative review and analysis of published trials, important nuances of the available clinical data were identified, and important areas of lingering uncertainty were highlighted, including the efficacy and safety of EVT for patients with a low ASPECTS score in late treatment windows and those with large core volumes. Also emphasized was the possibly important role of advanced neuroimaging modalities such as perfusion and magnetic resonance imaging when making EVT treatment decisions for select patients with low ASPECTS scores. Conclusions and Relevance: Recent trial data provide strong evidence that EVT is safe and effective for patients with anterior, large vessel-occlusion stroke and low ASPECTS scores who present within 6 hours from stroke onset. However, patient outcomes often remain poor despite EVT treatment. The efficacy and safety of EVT for patients with low ASPECTS scores who present beyond 6 hours of stroke onset remain uncertain, and the current trial data seem too scarce to justify forgoing advanced stroke imaging during this extended time window. Furthermore, the efficacy and safety of EVT for patients with large core volumes (100 mL or greater) or M2 occlusions (ie, occlusions of the second segment of the middle cerebral artery) remain uncertain. Future research to better identify patients likely to meaningfully respond to EVT is needed to further optimize the stroke triage process and health care resource utilization.

UltraAIGenomics: Artificial Intelligence-Based Cardiovascular Disease Risk Assessment by Fusion of Ultrasound-Based Radiomics and Genomics Features for Preventive, Personalized and Precision Medicine: A Narrative Review.

Cardiovascular disease (CVD) diagnosis and treatment are challenging since symptoms appear late in the disease's progression. Despite clinical risk scores, cardiac event prediction is inadequate, and many at-risk patients are not adequately categorised by conventional risk factors alone. Integrating genomic-based biomarkers (GBBM), specifically those found in plasma and/or serum samples, along with novel non-invasive radiomic-based biomarkers (RBBM) such as plaque area and plaque burden can improve the overall specificity of CVD risk. This review proposes two hypotheses: (i) RBBM and GBBM biomarkers have a strong correlation and can be used to detect the severity of CVD and stroke precisely, and (ii) introduces a proposed artificial intelligence (AI)-based preventive, precision, and personalized ( aiP 3 ) CVD/Stroke risk model. The PRISMA search selected 246 studies for the CVD/Stroke risk. It showed that using the RBBM and GBBM biomarkers, deep learning (DL) modelscould be used for CVD/Stroke risk stratification in the aiP 3 framework. Furthermore, we present a concise overview of platelet function, complete blood count (CBC), and diagnostic methods. As part of the AI paradigm, we discuss explainability, pruning, bias, and benchmarking against previous studies and their potential impacts. The review proposes the integration of RBBM and GBBM, an innovative solution streamlined in the DL paradigm for predicting CVD/Stroke risk in the aiP 3 framework. The combination of RBBM and GBBM introduces a powerful CVD/Stroke risk assessment paradigm. aiP 3 model signifies a promising advancement in CVD/Stroke risk assessment.

Surgical Management for Primary Intracerebral Hemorrhage.

The incidence of primary intracerebral hemorrhage (ICH) is increasing, particularly in younger patients, in part, because of increased prescription of anticoagulants. The ICH incidence rate from 2016 to 2018 in the United States was nearly 79 per 100,000 person-years and as high as 367 per 100,000 person-years among those 75 years or older. Worldwide, ICH comprises 28% of all new strokes, but a higher disease burden than ischemic stroke because of its higher morbidity and mortality. While mortality seems to be decreasing, functional outcomes are not improving. After negative trials of open surgical evacuation, recent trials of medical management strategies including intensive blood pressure control and prothrombotic agents intended to reduce hematoma expansion failed to demonstrate efficacy. Concomitantly, continued interest in minimally invasive surgical approaches arose from appreciation of secondary iatrogenic injury incurred to subcortical white matter tracts from open surgical techniques. A positive trial of minimally invasive surgery for lobar hemorrhage has recently been reported, bringing new optimism and demanding a reconsideration of surgical management of ICH. In this narrative review, we summarize the landmark studies, review recent literature, and consider the outstanding questions surrounding surgical management of ICH.

Artificial intelligence for cardiovascular disease risk assessment in personalised framework: a scoping review.

Background: The field of precision medicine endeavors to transform the healthcare industry by advancing individualised strategies for diagnosis, treatment modalities, and predictive assessments. This is achieved by utilizing extensive multidimensional biological datasets encompassing diverse components, such as an individual's genetic makeup, functional attributes, and environmental influences. Artificial intelligence (AI) systems, namely machine learning (ML) and deep learning (DL), have exhibited remarkable efficacy in predicting the potential occurrence of specific cancers and cardiovascular diseases (CVD). Methods: We conducted a comprehensive scoping review guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Our search strategy involved combining key terms related to CVD and AI using the Boolean operator AND. In August 2023, we conducted an extensive search across reputable scholarly databases including Google Scholar, PubMed, IEEE Xplore, ScienceDirect, Web of Science, and arXiv to gather relevant academic literature on personalised medicine for CVD. Subsequently, in January 2024, we extended our search to include internet search engines such as Google and various CVD websites. These searches were further updated in March 2024. Additionally, we reviewed the reference lists of the final selected research articles to identify any additional relevant literature. Findings: A total of 2307 records were identified during the process of conducting the study, consisting of 564 entries from external sites like arXiv and 1743 records found through database searching. After 430 duplicate articles were eliminated, 1877 items that remained were screened for relevancy. In this stage, 1241 articles remained for additional review after 158 irrelevant articles and 478 articles with insufficient data were removed. 355 articles were eliminated for being inaccessible, 726 for being written in a language other than English, and 281 for not having undergone peer review. Consequently, 121 studies were deemed suitable for inclusion in the qualitative synthesis. At the intersection of CVD, AI, and precision medicine, we found important scientific findings in our scoping review. Intricate pattern extraction from large, complicated genetic datasets is a skill that AI algorithms excel at, allowing for accurate disease diagnosis and CVD risk prediction. Furthermore, these investigations have uncovered unique genetic biomarkers linked to CVD, providing insight into the workings of the disease and possible treatment avenues. The construction of more precise predictive models and personalised treatment plans based on the genetic profiles of individual patients has been made possible by the revolutionary advancement of CVD risk assessment through the integration of AI and genomics. Interpretation: The systematic methodology employed ensured the thorough examination of available literature and the inclusion of relevant studies, contributing to the robustness and reliability of the study's findings. Our analysis stresses a crucial point in terms of the adaptability and versatility of AI solutions. AI algorithms designed in non-CVD domains such as in oncology, often include ideas and tactics that might be modified to address cardiovascular problems. Funding: No funding received.

Embolic Stroke of Undetermined Source: New Data and New Controversies on Cardiac Monitoring and Anticoagulation.

Embolic strokes of undetermined source (ESUS) represent 9%-25% of all ischemic strokes. Based on the suspicion that a large proportion of cardioembolic sources remain undetected among embolic stroke of undetermined source patients, it has been hypothesized that a universal approach of anticoagulation would be better than aspirin for preventing recurrent strokes. However, 4 randomized controlled trials (RCTs), with different degrees of patient selection, failed to confirm this hypothesis. In parallel, several RCTs consistently demonstrated that prolonged cardiac monitoring increased atrial fibrillation detection and anticoagulation initiation compared with usual care in patients with ESUS, and later in individuals with ischemic stroke of known cause (e.g., large or small vessel disease). However, none of these trials or subsequent meta-analyses of all available RCTs have shown a reduction in stroke recurrence associated with the use of prolonged cardiac monitoring. In this article, we review the clinical and research implications of recent RCTs of antithrombotic therapy in patients with ESUS and in high-risk populations with and without stroke, with device-detected asymptomatic atrial fibrillation.

Deep learning approach for cardiovascular disease risk stratification and survival analysis on a Canadian cohort.

The quantification of carotid plaque has been routinely used to predict cardiovascular risk in cardiovascular disease (CVD) and coronary artery disease (CAD). To determine how well carotid plaque features predict the likelihood of CAD and cardiovascular (CV) events using deep learning (DL) and compare against the machine learning (ML) paradigm. The participants in this study consisted of 459 individuals who had undergone coronary angiography, contrast-enhanced ultrasonography, and focused carotid B-mode ultrasound. Each patient was tracked for thirty days. The measurements on these patients consisted of maximum plaque height (MPH), total plaque area (TPA), carotid intima-media thickness (cIMT), and intraplaque neovascularization (IPN). CAD risk and CV event stratification were performed by applying eight types of DL-based models. Univariate and multivariate analysis was also conducted to predict the most significant risk predictors. The DL's model effectiveness was evaluated by the area-under-the-curve measurement while the CV event prediction was evaluated using the Cox proportional hazard model (CPHM) and compared against the DL-based concordance index (c-index). IPN showed a substantial ability to predict CV events (p < 0.0001). The best DL system improved by 21% (0.929 vs. 0.762) over the best ML system. DL-based CV event prediction showed a ~ 17% increase in DL-based c-index compared to the CPHM (0.86 vs. 0.73). CAD and CV incidents were linked to IPN and carotid imaging characteristics. For survival analysis and CAD prediction, the DL-based system performs superior to ML-based models.

Sex discrepancies in the population incidence of stroke and hemorrhage related to atrial fibrillation or flutter.

INTRODUCTION: Atrial fibrillation or flutter (AF) is a well-known risk factor for ischemic stroke. While female sex has been associated with higher stroke risk among AF patients, overall sex-specific real-world burdens of AF-related strokes and hemorrhages are unknown. METHODS: The 2016-2020 National Inpatient Sample was queried for hospitalizations, morbidity, and mortality due to AF-related ischemic strokes and bleeds. Patient demographic information, vascular risk factors, comorbidities, and stroke characteristics were extracted using ICD-10 codes. Overall incidences were calculated using total population estimates provided by the United States Census Bureau, and relative risk was calculated by comparing annual incidences between men and women. RESULTS: 2,420,870 ischemic stroke hospitalizations were identified; 542,635 (22.4%) were associated with AF. Overall, women had similar risk of hospitalization due to AF-related ischemic strokes compared to men; however, women had a higher risk of morbidity and mortality (RR 1.13 and 1.17, respectively; both p<0.001). In contrast, women had lower incidences of hospitalization, morbidity, and mortality due to AF-related bleeds (RR 0.82, 0.94, and 0.74, respectively; all p<0.001). Among patients with AF-related ischemic strokes, women had lower rates of anticoagulation use, higher rates of large vessel occlusion, and higher stroke severity (all p<0.001). These trends persisted among patients 80 years or older (all p<0.001). CONCLUSION: Women in the United States have higher incidences of morbidity and mortality from AF-related ischemic strokes than men. Future studies should investigate strategies to reduce morbidity and mortality due to AF-related strokes in women.

The impact of sex on stroke care: From epidemiology to outcome.

BACKGROUND: Carotid stenosis and atrial fibrillation are key risk factors for development of hemispheric strokes. In this review we aim to identify sex-specific differences in the pathophysiology and treatment of these risk factors and areas for future study. KEY FINDINGS: Women are underrepresented in research studies of stroke in patients with carotid disease and atrial fibrillation. However, key differences have been found between men and women that suggest that the development of carotid disease and atrial fibrillation occur at later stages of life and are associated with higher severity of stroke. Some treatments, including surgical treatment, seem to have different rates of efficacy and women and women are at higher risk of surgical complications. This suggests that treatment recommendations may need to be sex specific. CONCLUSION: Efforts should be made to address research and treatment gaps in women with stroke risk factors. This may lead to the development of sex-specific recommendations for stroke prevention and treatment.

Optimal Angiographic Goal and Number of Passes for Octogenarians Undergoing Endovascular Stroke Thrombectomy.

BACKGROUND: The optimal recanalization goal and number of endovascular thrombectomy (EVT) passes for elderly patients with large vessel occlusion strokes is unclear. METHODS: Consecutive patients 80 years or older undergoing EVT were identified from 2016 to 2022 at a single center. Clinical information, procedural details, and modified treatment in cerebral ischemia (mTICI) scores were collected. Primary outcome was modified Rankin scale (mRS) at 90 days. Bivariate and multivariable analyses were conducted to assess associations between mTICI scores, EVT passes, and 90-day outcomes. RESULTS: One hundred twenty-six patients were identified. At 90 days, mTICI 2b recanalization resulted in high rates of poor outcomes (8.7% functional independence and 60.9% mortality) not significantly different from mTICI 0, 1 or 2a (median mRS 6 vs. 6, P = 0.61). Complete recanalization (mTICI 2c or 3) led to significantly better mRS outcomes at 90 days compared to mTICI 2b (median mRS 4 vs. 6, adjusted P = 0.038), with 26.8% functional independence and 37.8% mortality. In multivariable analysis, complete recanalization was significantly associated with better 90-day outcomes than mTICI 2b or lower recanalization (odds ratio 4.24 [95% Confidence interval 1.46-12.3]; P = 0.002), while the number of passes was not independently associated with worse outcomes (P = 0.98). CONCLUSIONS: For octogenarians, mTICI 2b recanalization yields limited clinical benefit and results in poor 90-day outcomes. In contrast, complete recanalization is independently associated with significantly better outcomes. Thus, once the decision is made to pursue EVT in the elderly, mTICI 2c or better recanalization should be the angiographic goal. Providers should not withhold thrombectomy passes based on age alone.

Transcarotid Arterial Revascularization of Symptomatic Internal Carotid Artery Disease: A Systematic Review and Study-Level Meta-Analysis.

BACKGROUND: Transcarotid artery revascularization (TCAR) is an interventional therapy for symptomatic internal carotid artery disease. Currently, the utilization of TCAR is contentious due to limited evidence. In this study, we evaluate the safety and efficacy of TCAR in patients with symptomatic internal carotid artery disease compared with carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: A systematic review was conducted, spanning from January 2000 to February 2023, encompassing studies that used TCAR for the treatment of symptomatic internal carotid artery disease. The primary outcomes included a 30-day stroke or transient ischemic attack, myocardial infarction, and mortality. Secondary outcomes comprised cranial nerve injury and major bleeding. Pooled odds ratios (ORs) for each outcome were calculated to compare TCAR with CEA and CAS. Furthermore, subgroup analyses were performed based on age and degree of stenosis. In addition, a sensitivity analysis was conducted by excluding the vascular quality initiative registry population. RESULTS: A total of 7 studies involving 24 246 patients were analyzed. Within this patient cohort, 4771 individuals underwent TCAR, 12 350 underwent CEA, and 7125 patients underwent CAS. Compared with CAS, TCAR was associated with a similar rate of stroke or transient ischemic attack (OR, 0.77 [95% CI, 0.33-1.82]) and myocardial infarction (OR, 1.29 [95% CI, 0.83-2.01]) but lower mortality (OR, 0.42 [95% CI, 0.22-0.81]). Compared with CEA, TCAR was associated with a higher rate of stroke or transient ischemic attack (OR, 1.26 [95% CI, 1.03-1.54]) but similar rates of myocardial infarction (OR, 0.9 [95% CI, 0.64-1.38]) and mortality (OR, 1.35 [95% CI, 0.87-2.10]). CONCLUSIONS: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

The BAND score: A simple model for upfront prediction of poor outcomes despite successful stroke thrombectomy.

BACKGROUND: While endovascular thrombectomy (EVT) is beneficial for patients with acute large vessel occlusion ischemic strokes, a significant portion of patients still do poorly despite successful recanalization. Identifying patients at high risk for poor outcomes can be helpful for future clinical trial design and optimizing acute stroke triage. METHODS: Consecutive EVT patients were identified from 2016 to 2021 at a Comprehensive Stroke Center, and clinical information was recorded. Poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 or greater despite achieving a modified thrombolysis in cerebral infarction (mTICI) score of 2b or greater. Multivariable regression analyses were used to identify risk factors for poor outcomes, and a scoring system was constructed. RESULTS: 483 patients with successful recanalization were identified. From a randomly selected training cohort (n = 357), the 10-point BAND score was constructed from independent risk factors for poor outcomes: baseline disability (1 point: baseline mRS ≥ 2), age (1 point: 60-69 years, 2 points: 70-79 years, 3 points: 80-84 years, 4 points: 85 years or older), NIHSS (2 points: 13-17, 3 points: 18-22, and 4 points: ≥ 23), and delay from last known normal (1 point: ≥ 6 h). The BAND score was significantly associated with rates of poor outcomes (p < 0.001), and it achieved an area under the receiver-operating characteristic curve (AUC) of 0.80 (95 %CI 0.76-0.85) in our training cohort and 0.78 (95 %CI 0.70-0.86) in our validation cohort (n = 126). Overall, the BAND score had a significantly higher AUC value than the widely validated THRIVE score and the THRIVE-EVT calculation (p = 0.001 and 0.029, respectively). Among patients with high BAND scores (7 or higher), 88.2 % had poor outcomes. CONCLUSION: The BAND score is a simple tool to predict poor outcomes despite successful recanalization. Future studies are needed to confirm the BAND score's external validity.

Inflammatory Biomarkers and Stroke Subtype: An Important New Frontier

Inflammation is an established pathway in the formation, growth, and rupture of atherosclerotic plaques. Inflammation is thus essential to the pathogenesis of coronary heart disease and some types of ischemic stroke.1 The benefit of anti-inflammatory therapies, such as colchicine2 and the anti-IL1ß canakinumab,3 is proven in patients with coronary heart disease, yet it remains unproven for patients with ischemic stroke. Compared with coronary heart disease, the etiology of stroke is more heterogeneous. Besides arterio-arterial atherogenic embolism, possible etiologies are penetrator artery occlusion, cardioembolism, and other mechanisms. Finding a stroke etiology remains elusive in up to 30%-40% of patients despite a full evaluation. Understanding whether the stroke etiology modifies the association between inflammatory markers and recurrence risk is an important step to improve selection of patients for randomized trials on anti-inflammatory agents. IL-6 and high-sensitive CRP (hs-CRP) have been implicated in a higher recurrence risk after ischemic stroke by both an individual participant data meta-analysis4 and a Mendelian randomization study,5 but granular, in vivo results stratified by stroke etiology are lacking.