Cardiac Contributions to Brain Health: A Scientific Statement From the American Heart Association.

The burden of neurologic diseases, including stroke and dementia, is expected to grow substantially in the coming decades. Thus, achieving optimal brain health has been identified as a public health priority and a major challenge. Cardiovascular diseases are the leading cause of death and disability in the United States and around the world. Emerging evidence shows that the heart and the brain, once considered unrelated organ systems, are interdependent and linked through shared risk factors. More recently, studies designed to unravel the intricate pathogenic mechanisms underpinning this association show that people with various cardiac conditions may have covert brain microstructural changes and cognitive impairment. These findings have given rise to the idea that by addressing cardiovascular health earlier in life, it may be possible to reduce the risk of stroke and deter the onset or progression of cognitive impairment later in life. Previous scientific statements have addressed the association between cardiac diseases and stroke. This scientific statement discusses the pathogenic mechanisms that link 3 prevalent cardiac diseases of adults (heart failure, atrial fibrillation, and coronary heart disease) to cognitive impairment.

Anticoagulation vs Antiplatelets Across Subgroups of Embolic Stroke of Undetermined Source: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: The term "embolic stroke of undetermined source" (ESUS) encompasses a substantial but heterogeneous population of patients with ischemic stroke, underscoring the importance of identifying personalized treatment strategies. In subgroups of patients randomized in ESUS trials, we evaluated the effectiveness of anticoagulation compared with antiplatelet therapy in secondary ischemic stroke prevention. METHODS: A study-level meta-analysis was conducted on randomized controlled trials of patients with ESUS, comparing anticoagulation with antiplatelet therapy. The primary efficacy outcome was recurrent ischemic stroke, and safety outcomes were major bleeding and death. Subgroups assessed were age, sex, presence of patent foramen ovale (PFO), left atrial enlargement (LAE), and atrial cardiopathy. Pooled risk ratios (RRs) were meta-analyzed. Cochrane Risk of Bias Tool 2.0 was used for risk-of-bias assessment. RESULTS: A total of 7 randomized controlled trials involving 14,804 patients were analyzed, with 7,406 patients treated with anticoagulation and 7,398 treated with antiplatelet therapy. Compared with antiplatelet therapy, anticoagulation was associated with a similar rate of recurrent ischemic stroke (RR 0.91, 95% CI 0.80-1.05; I2 = 0%). In ESUS with PFO, anticoagulation was associated with significantly lower risk of ischemic stroke (RR 0.59, 95% CI 0.35-0.98; I2 = 0%). Heterogeneity was present in those with LAE: antiplatelet therapy was superior in trials allowing cardiac monitoring after randomization (RR 6.65, 95% CI 1.26-35.08; I2 = 0%), but anticoagulation was superior in trials prohibiting cardiac monitoring after randomization (RR 0.25 95% CI 0.07-0.89). Subgroups based on age, sex, or presence of atrial cardiopathy did not benefit from anticoagulation over antiplatelet therapy. DISCUSSION: In this meta-analysis, an empiric anticoagulation approach is not beneficial for patients with ESUS. This finding highlights the importance of an individualized treatment strategy. Such a strategy should include prolonged cardiac monitoring for atrial fibrillation, particularly in patients with moderate-to-severe LAE. Anticoagulation treatment showed promise in patients with medically treated PFO. Other subgroups did not benefit from anticoagulation therapy. Large prospective studies within ESUS subgroups are needed to validate our findings.

Comparison of Risk Factors for Early Seizures Between Angiogram-Negative and Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Early-onset seizures are common in aneurysmal subarachnoid hemorrhage (aSAH), with risk factors that have been explored. However, early-onset seizures in patients with angiogram-negative nonperimesencephalic SAH (an-SAH) are less understood. We sought to compare the incidence and risk factors of early-onset seizures between these groups. METHODS: We conducted a retrospective study of a cohort of consecutive patients admitted to an academic center between July 2016 and July 2023. Patients were categorized into aSAH or an-SAH based on imaging findings. Clinical data and electroencephalogram findings were retrieved and analyzed. Multivariable logistic regression analysis was used to determine risk factors for clinical or electrographic seizures, as well as other epileptic features. RESULTS: We included 473 patients (63% female) in the final analysis, of whom 79 had an-SAH and 394 had aSAH. Patients with an-SAH were older (mean age 61.9 years [standard deviation 15.9] vs. 56.7 [standard deviation 13.4]; p = 0.02). The rate of clinical or electrographic seizures was similar between the two groups (13% in aSAH vs. 11% in an-SAH; p = 0.62). Highly epileptic features (electrographic seizures, ictal-interictal continuum, and periodic epileptic discharges) occurred more frequently in the aSAH group compared with the an-SAH group, although this difference was not significant (15% vs. 8%; p = 0.09). Risk factors for seizures in aSAH were Hunt and Hess grade (odds ratio [OR] 1.25 per grade increase, 95% confidence interval [CI] 1.05-1.49; p = 0.011), modified Fisher score (OR 1.64 per point increase, 95% CI 1.25-2.15; p < 0.001), cerebral infarct (OR 3.64, 95% CI 2.13-6.23; p < 0.001), and intracerebral hemorrhage (OR 10, 95% CI 1.35-76.9; p = 0.017). However, none of these factors were associated with seizures in an-SAH. CONCLUSIONS: Early-onset seizures occur at similar rates in patients with an-SAH and aSAH. However, seizure risk factors appear to differ between these groups. Larger prospective studies are needed to identify predictors of seizures in patients with an-SAH.

In-hospital recurrent stroke in ipsilateral carotid web patients undergoing thrombectomy.

OBJECTIVE: Carotid artery web is a possible cause of ischemic stroke, especially in young patients who lack conventional risk factors. The immediate and long-term outcomes are not well studied. We aimed to determine the association between an ipsilateral carotid web and in-hospital stroke recurrence. METHODS: We analyzed data from adult patients admitted with an acute anterior circulation large vessel occlusion at a Comprehensive Stroke Center between July 2015 and March 2023. The primary outcome was in-hospital stroke recurrence and secondary outcome was in-hospital recurrent LVO. Multivariable logistic regression was performed to examine the association between ipsilateral carotid web and recurrent ischemic stroke and recurrent LVO. RESULTS: Of the 1463 patients with anterior circulation large vessel occlusion, 27 (1.8%) had an ipsilateral carotid artery web. Patients with carotid web were younger (median age (IQR), 60 years (53-67 years) versus 74 years (62-84 years), P < 0.01) and less likely to be Caucasian (60% vs. 80%, p = 0.014). Of the 27 patients with carotid web, 18 (70%) had no identifiable competing stroke mechanism. When compared to patients without ipsilateral carotid web, those with an ipsilateral carotid web had a higher risk of recurrent ischemic stroke (adjusted RR: 4.38, 95% CI: 1.38-13.85) and recurrent ipsilateral large vessel occlusion (adjusted RR: 4.49, 95% CI: 1.41-14.21). INTERPRETATION: Carotid webs are an under recognized cause of acute large vessel occlusion and are associated with higher risk of early recurrence. Studies are needed to validate our findings and test early revascularization strategies in patients with symptomatic carotid artery webs.

Risk factors for MACE and bleeding in atrial fibrillation patients undergoing surgery: Insights from the bridge trial.

INTRODUCTION: Patients with atrial fibrillation (AF) undergoing elective procedures are at risk for Major Adverse Cardiovascular Events (MACE) and symptomatic bleeding. We aimed to identify risk factors to guide perioperative risk stratification. METHODS: We conducted a post-hoc analysis of the "Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery" randomized trial. The primary outcomes were MACE and symptomatic bleeding. Our statistical approach encompassed standard univariate analysis, logistic stepwise regression, and Cox regression models. Additional interaction analyses evaluated the interplay between low-molecular-weight heparin bridge therapy and other identified risk factors. RESULTS: Among a total of 1,813 participants (mean age 71.6 ± 8.8, 73.3 % male), MACE occurred in 25 (1.4 %) individuals, with pre-procedure clopidogrel use (adjusted hazard ratio [aHR] 7.73, 95 % CI 2.63-22.72, p < 0.001) and CHA2DS2-VASc score ≥ 5 (aHR 2.89, 95 % CI 1.26-6.63, p = 0.012) identified as risk factors. Symptomatic bleeding occurred in 57 (3.1 %) individuals, with bridge therapy (aHR 1.84, 95 % CI 1.07-3.19, p = 0.029), renal disease (aHR 2.50, 95 % CI 1.34-4.67, p = 0.004), post-procedure aspirin use (aHR 2.86, 95 % CI 1.66-4.91, p < 0.001), post-procedure nonsteroidal anti-inflammatory drug use excluding aspirin (aHR 3.40, 95 % CI 1.22-9.43, p = 0.019), and major surgery (aHR 3.94, 95 % CI 2.26-6.85, p < 0.001) identified as risk factors. The interactions between risk factors and bridging therapy on MACE and symptomatic bleeding outcomes were not significant (p > 0.05). CONCLUSION: We identified predictors for MACE and symptomatic bleeding in AF patients undergoing elective procedures. These insights may help guide perioperative decisions to reduce the risk of adverse outcomes.

Anticoagulation Versus Antiplatelets in Spontaneous Cervical Artery Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P=0.02; I2=0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P=0.03, I2=0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

Fostering Psychological Safety and Supporting Mental Health Among Cardiovascular Health Care Workers: A Science Advisory From the American Heart Association.

The psychological safety of health care workers is an important but often overlooked aspect of the rising rates of burnout and workforce shortages. In addition, mental health conditions are prevalent among health care workers, but the associated stigma is a significant barrier to accessing adequate care. More efforts are therefore needed to foster health care work environments that are safe and supportive of self-care. The purpose of this brief document is to promote a culture of psychological safety in health care organizations. We review ways in which organizations can create a psychologically safe workplace, the benefits of a psychologically safe workplace, and strategies to promote mental health and reduce suicide risk.

Importance of sex and gender differences in enrollment and interpretation of stroke clinical trials.

OBJECTIVES: This review aims to reinforce the importance of improving sex balance in preclinical trials and sex and gender diversity and proportional balance in clinical trials enrollment and how this influences interpretation of stroke clinical trials. It also aims to identify strategies for improvement in data collection. MATERIALS AND METHODS: A PubMed search was conducted of publications in English, using MeSH terms sex, sex characteristics, gender identity, transgender, gender-nonconforming persons, clinical trials as topic, stroke. Of 249 search results, 217 were human or animal studies related to stroke, the majority of which were reviews, secondary analyses of stroke clinical trials, meta analyses, or retrospective studies, subject to the methods of sex and gender acquisition per the primary data source. Articles were reviewed, noting inclusion or absence of sex and gender definitions and trial design. Selected articles were supplemented with United States Food and Drug Administration, National Institutes of Health, and National Academy of Science, Engineering, and Medicine publications. RESULTS: The majority of preclinical studies continue to report sex as a binary variable, and the majority of stroke clinical trials report sex and gender as interchangeable and binary. Mindful trial design and statistical analysis can improve accuracy in the interpretation of sex and gender differences. Guidance exists to improve reporting on currently accepted sex and gender definitions, recommended data collection instruments, and appropriate statistical analyses. CONCLUSIONS: Despite acknowledgement of having failed to achieve diverse and proportionally balanced enrollment, sex and gender imbalance across the research continuum remains prevalent. Responsible incorporation of sex and gender in stroke clinical trials can be achieved through thoughtful study design, use of contemporary sex and gender definitions, inclusive prospective data collection, balanced enrollment with prespecified goals, and appropriate statistical analysis.

Predictors of hospital length of stay and long-term care facility placement in aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is frequently associated with complications, extended hospital length of stay (LOS) and high health care related costs. We sought to determine predictors for hospital LOS and discharge disposition to a long-term care facility (LTCF) in aSAH patients. Methods: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic referral center from 2016 to 2021. Multiple linear regression was performed to identify predictors for hospital LOS. We then created a 10-point scoring system to predict discharge disposition to a LTCF. Results: In a cohort of 318 patients with confirmed aSAH, mean age was 57 years (SD 13.7), 61% were female and 70% were white. Hospital LOS was longer for survivors (median 19 days, IQR 14-25) than for non-survivors (median 5 days, IQR 2-8; p < 0.001). Main predictors for longer LOS for this cohort were ventriculoperitoneal shunt (VPS) requirement (p < 0.001), delayed cerebral ischemia (p = 0.026), and pneumonia (p = 0.014). The strongest predictor for LTCF disposition was age older than 60 years (OR 1.14, 95% CI 1.07-1.21; p < 0.001). LTCF score had high accuracy in predicting discharge disposition to a LTCF (area under the curve [AUC] 0.83; 95% CI 0.75-0.91). Forty-one percent of patients who were discharged to a LTCF had significant functional recovery at 3 months post-discharge. Conclusions: VPS requirement and aSAH related complications were associated with longer hospital LOS compared to other factors. LTCF score has high accuracy in predicting discharge disposition to a LTCF.

Comparison of the Effects of Blood Pressure Parameters on Rebleeding and Outcomes in Unsecured Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated systolic blood pressure (SBP) has been linked to preprocedural rebleeding risk and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study seeks to compare the effects of SBP and mean arterial pressure (MAP) on rebleeding and functional outcomes in aSAH patients. METHODS: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic center in 2016-2023. Binary regression analysis was used to determine the association between BP parameters and outcomes including rebleeding and poor outcome defined as modified Rankin Scale 4-6 at 3 months postdischarge. RESULTS: The cohort included 324 patients (mean age 57 years [standard deviation 13.4], 61% female). Symptomatic rebleeding occurred in 34 patients (11%). Higher BP measurements were recorded in patients with rebleeding and poor outcome, however, only MAP met statistical significance for rebleeding (odds ratio {OR} 1.02 for 1 mmHg increase in MAP, 95% confidence interval {CI}: 1.001-1.03, P = 0.043; OR 1 per 1 mmHg increase in SBP, 95% CI 0.99-1.01; P = 0.06)) and for poor outcome (OR 1.01 for 1 mmHg increase in MAP, 95% CI: 1.002-1.025, P = 0.025; OR 1 for 1 mmHg increase in SBP, 95% CI: 0.99-1.02, P = 0.23) independent of other predictors. CONCLUSIONS: MAP may appear to be slightly better correlated with rebleeding and poor outcomes in unsecured aSAH compared to SBP. Larger prospective studies are needed to identify and mitigate risk factors for rebleeding and poor outcome in aSAH patients.

IV Thrombolysis for central retinal artery occlusion - Real-world experience from a comprehensive stroke center.

OBJECTIVES: Central retinal artery occlusion (CRAO) is a stroke of the retina potentially amenable to intravenous thrombolysis (IVT). We aimed to determine feasibility of an emergency treatment protocol and risk profile of IVT for CRAO in a comprehensive stroke center (CSC). METHODS: We performed a retrospective, observational cohort study including patients with acute CRAO admitted to a CSC over 4 years. Patients are offered IVT if they present with acute vision loss of ≤ 20/200 in the affected eye, have no other cause of vision loss (incorporating a dilated ophthalmologic exam), and meet criteria akin to acute ischemic stroke. We collected socio-demographic data, triage data, time from onset to presentation, IVT candidacy, and rates of symptomatic intracranial hemorrhage (sICH)- or extracranial hemorrhage. RESULTS: 36 patients presented within the study period, mean (standard deviation (SD)) age of 70.7 (10), 52 % female, and median time (Q1, Q3) to ED presentation of 13.5 (4.3, 18.8) h. Patients within 4.5 h from onset presented more commonly directly to our ED (66.6 % vs 37.1 %, p = 0.1). Nine patients (25 %) presented within the 4.5 h window. Of those eligible, 7 (77 %) received IVT. There were no events of intracranial or extracranial hemorrhage. CONCLUSIONS: Our study confirmed that IVT for acute CRAO is feasible. We found a high rate of treatment with IVT of those eligible. However, because 75 % of patients presented outside the treatment window, continued educational efforts are needed to improve rapid triage to emergency departments to facilitate evaluation for possible candidacy with IVT.

Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association.

Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy.

A reassessment of hemoglobin and hematoma expansion in intracerebral hemorrhage.

BACKGROUND: In patients with spontaneous intracerebral hemorrhage (ICH), prior studies identified an increased risk of hematoma expansion (HE) in those with lower admission hemoglobin (Hgb) levels. We aimed to reproduce these findings in an independent cohort. METHODS: We conducted a cohort study of patients admitted to a Comprehensive Stroke Center for acute ICH within 24 hours of onset. Admission laboratory and CT imaging data on ICH characteristics including HE (defined as >33% or >6 mL), and 3-month outcomes were collected. We compared laboratory data between patients with and without HE and used multivariable logistic regression to determine associations between Hgb, HE, and unfavorable 3-month outcomes (modified Rankin Scale 4-6) while adjusting for confounders including anticoagulant use, and laboratory markers of coagulopathy. RESULTS: Among 345 patients in our cohort (mean [SD] age 72.9 [13.7], 49% male), 71 (21%) had HE. Patients with HE had similar Hgb versus those without HE (mean [SD] 13.1 [1.8] g/dl vs. 13.1 [1.9] g/dl, p=0.92). In fully adjusted multivariable models, Hgb was not associated with HE (OR per 1g/dl 1.01, 95% CI 0.86 -1.17, p = 0.94), however higher admission Hgb levels were associated with lower odds of unfavorable 3-month outcome (OR 0.83 per 1 g/dl Hgb, 95% CI 0.72-0.96, p=0.01). CONCLUSION: We did not confirm a previously reported association between admission Hgb and HE in patients with ICH, although Hgb and HE were both associated with poor outcome. These findings suggest that the association between Hgb and poor outcome is mediated by other factors.

Borderzone Infarcts and Recurrent Cerebrovascular Events in Symptomatic Intracranial Arterial Stenosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration. METHODS: As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated. RESULTS: A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52-2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38-3.18). For isolated BZI, RR was 2.59 (95% CI 1.24-5.41). RR was 2.96 (95% CI 1.71-5.12) for studies only including anterior circulation stroke patients. CONCLUSION: This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.

Perioperative Acute Ischemic Stroke in Patients with Atrial Fibrillation.

OBJECTIVE: Anticoagulation therapy is commonly interrupted in patients with atrial fibrillation (AF) for elective procedures. However, the risk factors of acute ischemic stroke (AIS) during the periprocedural period remain uncertain. We performed a nationwide analysis to evaluate AIS risk factors in patients with AF undergoing elective surgical procedures. METHODS: Using the Nationwide Readmission Database, we included electively admitted adult patients with AF and procedural Diagnosis-Related Group codes from 2016 to 2019. Diagnoses were identified based on International Classification of Disease, 9th revision-Clinical Modification (ICD-10 CM) codes. We constructed a logistic regression model to identify risk factors and developed a new scoring system incorporating CHA2 DS2 VASc to estimate periprocedural AIS risk. RESULTS: Of the 1,045,293 patients with AF admitted for an elective procedure, the mean age was 71.5 years, 39.2% were women, and 0.70% had a perioperative AIS during the index admission or within 30 days of discharge. Active cancer (adjusted OR [aOR] = 1.58, 95% confidence interval [CI] = 1.42-1.76), renal failure (aOR = 1.14, 95% CI = 1.04-1.24), neurological surgery (aOR = 4.51, 95% CI = 3.84-5.30), cardiovascular surgery (aOR = 2.74, 95% CI = 2.52-2.97), and higher CHA2 DS2 VASc scores (aOR 1.25 per point, 95% CI 1.22-1.29) were significant risk factors for periprocedural AIS. The new scoring system (area under the receiver operating characteristic curve [AUC] = 0.68, 95% CI = 0.67 to 0.79) incorporating surgical type and cancer outperformed CHA2 DS2 VASc (AUC = 0.60, 95% CI = 0.60 to 0.61). INTERPRETATION: In patients with AF, periprocedural AIS risk increases with the CHA2 DS2 VASc score, active cancer, and cardiovascular or neurological surgeries. Studies are needed to devise better strategies to mitigate perioperative AIS risk in these patients. ANN NEUROL 2023;94:321-329.

Recurrence risk in symptomatic intracranial stenosis treated medically in the real world.

BACKGROUND: The risk of early recurrence in medically treated patients with intracranial atherosclerotic stenosis (ICAS) may differ in clinical trials versus real-world settings. Delayed enrollment may contribute to lower event rates in ICAS trials. We aim to determine the 30-day recurrence risk in a real-world setting of symptomatic ICAS. METHODS: We used a comprehensive stroke center stroke registry to identify hospitalized patients with acute ischemic stroke or TIA due to symptomatic 50-99% ICAS. The outcome was recurrent stroke within 30 days. We used adjusted Cox regression models to identify factors associated with increased recurrence risk. We also performed a comparison of 30-day recurrent stroke rates in real world cohorts and clinical trials. RESULTS: Among 131 hospitalizations with symptomatic 50-99% ICAS over 3 years, 80 hospitalizations of 74 patients (mean age 71.6 years, 55.41% men) met the inclusion criteria. Over 30 days, 20.6 % had recurrent stroke; 61.5% (8/13) occurred within first 7 days. The risk was higher in patients not receiving dual antiplatelet therapy (HR 3.92 95% CI 1.30-11.84, p = 0.015) and hypoperfusion mismatch volume >3.5 mL at a T max>6 s threshold (HR 6.55 95% CI 1.60-26.88, p < 0.001). The recurrence risk was similar to another real world ICAD cohort (20.2%), and higher than that seen in clinical trials (2.2%-5.7%), even in those treated with maximal medical treatment or meeting inclusion criteria for trials. CONCLUSIONS: In patients with symptomatic ICAS, the real-world recurrence of ischemic events is higher than that seen in clinical trials, even in subgroups receiving the same pharmacological treatment strategies.

Subsequent ischemic stroke and tobacco smoking: A secondary analysis of the POINT trial.

Background: The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively. Results: Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97-1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56-0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37-1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40-7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08-6.21), p = 0.032), p for interaction = 0.613. Conclusions: In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.