Cardioembolic Stroke Research Articles

Abstract WP277: Stroke Etiology in Young Adults With Substance Abuse

Introduction: Recent public health trends suggest increasing rates of substance abuse among young people. Substance use has been associated with an increased risk of stroke, and specifically, cocaine use is known to more likely cause lacunar and cardioembolic strokes. However, less is known about the stroke etiology with other substances. Methods: We conducted a retrospective review of stroke patients between the ages of 18 to 50 years presenting to our Young Stroke Center between April 2022 through August 2023. For each case, data including basic demographics and medical history were collected, and stroke etiology was determined by a vascular neurologist. Patients with substance use at the time of stroke were compared to all non-substance use related stroke and analyzed with respect to TOAST stroke etiology. Substance use was defined as use of opioids, cocaine, marijuana, or alcohol abuse. Analysis was performed with logistic regression adjusting for age, sex, and race. Results: Of 187 patients in the registry, 25 patients had substance use at time of stroke compared with 162 patients with non-substance use related stroke. There were 10 marijuana, 4 opioid, 0 cocaine, 3 alcohol abuse and 8 polysubstance use (including 3 cocaine) cases. There were no significant differences in age at time of stroke (36.9 ± 7.1 vs. 38.8 ± 8.2 years) and race (50.0% vs. 53.4% Black) between substance use and non-substance use related stroke groups, respectively. There was a significantly higher proportion of males with substance use (62.5% vs. 31.9% male; OR [95% CI]: 4.0 [1.6-10.0]). In the substance use group, a higher proportion had cardioembolic stroke etiology (20.8% vs. 9.2%; OR [95% CI]: 4.1 [1.2-14.0]); however, there was no significant difference with respect to the other TOAST stroke etiologies. In patients with active substance use and cardioembolic stroke etiology, heart failure with reduced ejection fraction and atrial fibrillation were the etiologies found. Conclusion: Our findings indicate that among young individuals with active substance use at the time of their stroke, cardioembolic etiology appears to be more likely than in young stroke patients without substance use. This underscores the need for comprehensive cardiac evaluation in this population.

Abstract WP128: Using Clinical Data to Reclassify ESUS Patients to Either Large Artery Atherosclerotic or Cardioembolic Stroke Mechanisms

Introduction: Defining the specific underlying pathophysiology of ischemic stroke is critical for minimizing the risk of recurrent events with personalized secondary prevention treatments. A notable portion of ischemic strokes are classified as embolic stroke of undetermined source (ESUS), leaving these patients without optimal treatment tailored to their pathophysiology. Hypothesis: Standard clinically collected data can reliably reclassify a substantial portion of ESUS patients into either a large artery atherosclerotic (LAA) or cardioembolic (CE) cause. Methods: A statistical model was developed to discriminate LAA from CE using a retrospective cohort of ischemic stroke patients treated at the University of Washington. A total of 189 patients were included (79 CE and 61 LAA to train the model, 49 ESUS patients to assess reclassification). Sixteen candidate predictors were collected across several sources: clinical risk factors, blood tests, echocardiography, ECG, and neurovascular imaging (Table 1). The LASSO (least absolute shrinkage and selection operator) was used to select important predictors in a penalized logistic regression model with stroke etiology (LAA vs. CE) as the outcome. ESUS patients were considered reclassified if the model-based probability of CE or LAA was at least 75%. Results: Of 189 patients, the mean (SD) age was 68 (14) years and 40% were women. The LASSO selected 12 predictors to discriminate CE vs. LAA (Table 1), with a corresponding cross-validated C-statistic = 0.87 (95% CI: 0.82-0.94). When the model was applied to the 49 ESUS patients, 23 (47%) were reclassified to LAA and 6 (12%) to CE. Conclusions: A multivariate model based on standard clinical data can separate LAA from CE with a high degree of discrimination. Applying this model led to reclassification to either LAA or CE in 59% of ESUS patients. Such approaches may enable more personalized secondary prevention strategies, but need to be tested in future trials.

The use of percutaneous left atrial appendage occluder device in a patient with prior surgical ligation with incomplete exclusion: a case report

Abstract Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and the most common cause of cardioembolic stroke. The left atrial appendage (LAA) is the main source of thrombus formation in patients with AF. Therapies include use of percutaneous LAA closure devices, or surgical LAA occlusion (LAAO). Despite these options, complete closure of the LAA is not always achieved, and residual communication between the LAA and atrium may result in increased thrombus formation. Although studies have analysed the use of percutaneous measures such as coils, plugs, or second occluder device deployment in LAA with peri-device leak (PDL), use of percutaneous occlude devices in surgically occluded LAA is far less studied. Case summary We present a case of a 79-year-old female patient who underwent LAAO device deployment within a surgically occluded LAA with PDL. She underwent 27 mm LAAO device (WATCHMANTM) deployment and all the P.A.S.S. (Position, Anchor, Size, and Seal) criteria were satisfied. Only 1.4 mm PDL was present. She was continued on apixaban and aspirin post-operatively. Post-operative transoesophageal echocardiogram at 6 weeks demonstrated trivial PDL measuring 1.49 mm. Patient was continued on aspirin and clopidogrel, with discontinuation of apixaban. Discussion Percutaneous LAAO device deployment in previously surgically ligated LAA with incomplete exclusion is a potential therapeutic option for patients with AF and a high bleeding risk seeking a minimally invasive strategy, in an attempt to de-escalate anticoagulation therapy.

Update of Anticoagulation Use in Cardioembolic Stroke With a Special Reference to Endovascular Treatment.

Cardioembolic stroke is a major cause of morbidity, with a high risk of recurrence, and anticoagulation represents the mainstay of secondary stroke prevention in most patients. The implementation of endovascular treatment in routine clinical practice complicates the decision to initiate anticoagulation, especially in patients with early hemorrhagic transformation who are considered at higher risk of hematoma expansion. Late hemorrhagic transformation in the days and weeks following stroke remains a potentially serious complication for which we still do not have any established clinical or radiological prediction tools. The optimal time to initiate therapy is challenging to define since delaying effective secondary prevention treatment exposes patients to the risk of recurrent embolism. Consequently, there is clinical equipoise to define and individualize the optimal timepoint to initiate anticoagulation combining the lowest risk of hemorrhagic transformation and ischemic recurrence in cardioembolic stroke patients. In this narrative review, we will highlight and critically outline recent observational and randomized relevant evidence in different subtypes of cardioembolic stroke with a special focus on anticoagulation initiation following endovascular treatment. We will refer mainly to the commonest cause of cardioembolism, non-valvular atrial fibrillation, and examine the possible risk and benefit of anticoagulation before, during, and shortly after the acute phase of stroke. Other indications of anticoagulation after ischemic stroke will be briefly discussed. We provide a synthesis of available data to help clinicians individualize the timing of initiation of oral anticoagulation based on the presence and extent of hemorrhagic transformation as well as stroke severity.

Gut Microbiome and Stroke: a Bidirectional Mendelian Randomisation Study in East Asian and European Populations.

Observational studies have implicated the involvement of gut microbiome in stroke development. Conversely, stroke may disrupt the gut microbiome balance, potentially causing systemic infections exacerbated brain infarction. However, the causal relationship remains controversial or unknown. To investigate bidirectional causality and potential ethnic differences, we conducted a bidirectional two-sample Mendelian randomisation (MR) study in both East Asian (EAS) and European (EU) populations. Leveraging the hitherto largest genome-wide association study (GWAS) summary data from the MiBioGen Consortium (n=18 340, EU) and BGI (n=2524, EAS) for the gut microbiome, stroke GWAS data from the GIGASTROKE Consortium(264 655 EAS and 1 308 460 EU), we conducted bidirectional MR and sensitivity analyses separately for the EAS and EU population. We identified nominally significant associations between 85 gut microbiomes taxa in EAS and 64 gut microbiomes taxa in EU with stroke or its subtypes. Following multiple testing, we observed that genetically determined 1 SD increase in the relative abundance of species Bacteroides pectinophilus decreased the risk of cardioembolic stroke onset by 28% (OR 0.72 (95% CI 0.62 to 0.84); p=4.22e-5), and that genetically determined 1 SD increase in class Negativicutes resulted in a 0.76% risk increase in small vessel stroke in EAS. No significant causal association was identified in the EU population and the reverse MR analysis. Our study revealed subtype-specific and population-specific causal associations between gut microbiome and stroke risk among EAS and EU populations. The identified causality holds promise for developing a new stroke prevention strategy, warrants further mechanistic validation and necessitates clinical trial studies.

Association between gastroesophageal reflux disease and stroke: a bidirectional Mendelian randomization study.

Some previous studies have suggested a potential link between stroke and gastroesophageal reflux disease (GERD). We used a two-sample bidirectional Mendelian randomization (MR) method to explore the causal relationship between stroke and GERD. Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. Single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for stroke (n = 446,696) and its common subtypes ischemic stroke (IS) (n = 440,328), large vessel stroke (LVS) (n = 410,484), small vessel stroke (SVS) (n = 198,048), and cardioembolic stroke (CES) (n = 413,304) were obtained from the MEGASTROKE consortium. The data on intracerebral hemorrhage (ICH) (n = 721,135) come from the UK Biobank. Instrumental variables (IVs) for lacunar stroke (LS) (n = 474,348) and GERD (n = 602,604) were screened from publicly available genetic summary data. The inverse variance weighted (IVW) method was used as the main MR method. Pleiotropy was detected by the MR-Egger intercept test, MR pleiotropy residual sum and outlier, and leave-one-out analysis. Cochran Q statistics were used as supplements to detect pleiotropy. We found that GERD can causally increase the risk of stroke [IVW odds ratio (OR): 1.22, 95% confidence interval (CI): 1.13-1.32, p = 1.16 × 10-6] and its common subtypes IS (OR: 1.19, 95% CI: 1.10-1.30, p = 3.22 × 10-5), LVS (OR: 1.49, 95% CI: 1.21-1.84, p = 1.47 × 10-4), and LS (OR: 1.20, 95% CI: 1.001-1.44, p = 0.048). Several important risk factors for stroke have also been implicated in the above causal relationship, including type 2 diabetes, sleep apnea syndrome, high body mass index, high waist-to-hip ratio, and elevated serum triglyceride levels. In reverse MR analysis, we found that overall stroke (OR: 1.09, 95% CI: 1.004-1.19, p = 0.039) and IS (OR: 1.10, 95% CI: 1.03-1.17, p = 0.007) have the causal potential to enhance GERD risk. This MR study provides evidence supporting a causal relationship between GERD and stroke and some of its common subtypes. We need to further explore the interconnected mechanisms between these two common diseases to better prevent and treat them.

Radon Exposure, Clonal Hematopoiesis, and Stroke Susceptibility in the Women's Health Initiative.

Studies suggest that clonal hematopoiesis of indeterminate potential (CHIP) may increase risk of hematologic malignancy and cardiovascular disease, including stroke. However, few studies have investigated plausible environmental risk factors for CHIP such as radon, despite the climate-related increases in and documented infrequency of testing for this common indoor air pollutant.The purpose of this study was to estimate the risk of CHIP related to radon, an established environmental mutagen. We linked geocoded addresses of 10,799 Women's Health Initiative Trans-Omics for Precision Medicine (WHI TOPMed) participants to US Environmental Protection Agency-predicted, county-level, indoor average screening radon concentrations, categorized as follows: Zone 1 (>4 pCi/L), Zone 2 (2-4 pCi/L), and Zone 3 (<2 pCi/L). We defined CHIP as the presence of one or more leukemogenic driver mutations with variant allele frequency >0.02. We identified prevalent and incident ischemic and hemorrhagic strokes; subtyped ischemic stroke using Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria; and then estimated radon-related risk of CHIP as an odds ratio (OR) and 95% CI using multivariable-adjusted, design-weighted logistic regression stratified by age, race/ethnicity, smoking status, and stroke type/subtype. The percentages of participants with CHIP in Zones 1, 2, and 3 were 9.0%, 8.4%, and 7.7%, respectively (ptrend = 0.06). Among participants with ischemic stroke, Zones 2 and 1 were associated with higher estimated risks of CHIP relative to Zone 3: 1.39 (1.15-1.68) and 1.46 (1.15-1.87), but not among participants with hemorrhagic stroke: 0.98 (0.68-1.40) and 1.03 (0.70-1.52), or without stroke: 1.04 (0.74-1.46) and 0.95 (0.63-1.42), respectively (pinteraction = 0.03). Corresponding estimates were particularly high among TOAST-subtyped cardioembolism: 1.78 (1.30-2.47) and 1.88 (1.31-2.72), or other ischemic etiologies: 1.37 (1.06-1.78) and 1.50 (1.11-2.04), but not small vessel occlusion: 1.05 (0.74-1.49) and 1.00 (0.68-1.47), respectively (pinteraction = 0.10). Observed patterns of association among strata were insensitive to attrition weighting, ancestry adjustment, prevalent stroke exclusion, separate analysis of DNMT3A driver mutations, and substitution with 3 alternative estimates of radon exposure. The robust elevation of radon-related risk of CHIP among postmenopausal women who develop incident cardioembolic stroke is consistent with a potential role of somatic genomic mutation in this societally burdensome form of cerebrovascular disease, although the mechanism has yet to be confirmed.

1891 Role of telemetry in detecting atrial fibrillation in acute ischaemic stroke

Abstract Introduction Atrial Fibrillation (AF) causes 15% of ischaemic strokes. The National Clinical Guideline for Stroke recommends at least 24 hours of cardiac monitoring and a longer duration if cardio-embolic stroke is suspected. The British Heart Rhythm Society suggests up to 72 hours of cardiac monitoring. Currently, there is little data on the use of telemetry in detecting AF in acute strokes. Our study aims to evaluate the detection rate of new onset AF in acute stroke with telemetry and to determine if there was any correlation between the duration of telemetry and the detection rate of AF. Method All patients with ischaemic stroke who were admitted to stroke ward over a 3-month period were retrospectively analysed. Exclusion criteria were patients who were known to have AF, had new AF on admission electrocardiogram, patients receiving palliative care, patients who were discharged home early without having a telemetry and patients with missing records. Results 61 patients met the inclusion criteria and 5 (8.2%) had AF on telemetry. Two patients had AF on day 1, one on day 2 and two on day 3. All of these patients were anticoagulated. The duration of telemetry ranged between 1- 19 days however no AF was detected beyond the third day of this study. Conclusions AF was detected in 8% of patients with ischaemic stroke within the first 72 hours of admission. Among the patients in whom AF was detected, 5% were detected between 24 hours and 72 hours of admission. Studies (EMBRACE and CRYSTAL trials) have shown that prolonged cardiac monitoring (30 days and 6 months to a year respectively) resulted in higher detection rates of AF. This study suggests that patients with ischaemic stroke should be monitored for at least 72 hours due to a higher detection rate of AF.

Seasonal Variations in Stroke and a Comparison of the Predictors of Unfavorable Outcomes among Patients with Acute Ischemic Stroke and Cardioembolic Stroke.

We investigated the seasonal variations in stroke in 4040 retrospectively enrolled patients with acute ischemic stroke (AIS) admitted between January 2011 and December 2022, particularly those with cardioembolic (CE) stroke, and compared predictors of unfavorable outcomes between AIS patients and CE stroke patients. The classification of stroke subtypes was based on the Trial of ORG 10172 in Acute Stroke Treatment. Stroke occurrence was stratified by seasons and weekdays or holidays. Of all AIS cases, 18% were of CE stroke. Of all five ischemic stroke subtypes, CE stroke patients were the oldest; received the most thrombolysis and thrombectomy; had the highest initial National Institutes of Stroke Scale (NIHSS) and discharge modified Rankin Scale (mRS) scores; and had the highest rate of in-hospital complications, unfavorable outcomes (mRS > 2), and mortality. The highest CE stroke prevalence was noted in patients aged ≥ 85 years (30.9%); moreover, CE stroke prevalence increased from 14.9% in summer to 23.0% in winter. The main predictors of death in patients with CE stroke were age > 86 years, heart rate > 79 beats/min, initial NIHSS score > 16, neutrophil-to-lymphocyte ratio (NLR) > 6.4, glucose > 159 mg/dL, cancer history, in-hospital complications, and neurological deterioration (ND). The three most dominant factors influencing death, noted in not only patients with AIS but also those with CE stroke, are high initial NIHSS score, ND, and high NLR. We selected the most significant factors to establish nomograms for predicting fatal outcomes. Effective heart rhythm monitoring, particularly in older patients and during winter, may help develop stroke prevention strategies and facilitate early AF detection.

About chronic cerebrovascular insufficiency caused by cardiac pathology (literature review)

The widespread introduction of cardiological diagnostic methods in clinical angioneurology has significantly enriched the data on the role of cardiovascular diseases in the development of cerebrovascular pathology. Various cardiac disorders play a significant role in the development of cardioembolic and haemodynamic ischaemic strokes. It has been scientifically proven that chronic heart failure, along with hypertension, is a risk factor for the occurrence of a chronic form of cerebrovascular disease — chronic cerebrovascular insufficiency. The characteristic feature of all types of cardiovascular insufficiency is the inability of the circulatory system to deliver to the organs, systems, tissues, including the brain, the amount of blood necessary for their normal functioning, both at rest and especially during exertion. In their daily practice, neurologists encounter patients with chronic heart failure and symptoms of cerebrovascular disease (memory loss, reduced performance, depression). Underestimation of these conditions can result in a shortened life due to irreversible damage to target organs (heart, brain, kidneys). In the absence of adequate treatment, death is possible within the first 5 years after the onset of heart failure. The degree of disease progression depends on many factors: clinical and pathogenetic variant of chronic heart failure, the rate of the pathological process, the presence of myocardial damage and remodeling, complications from target organs. In this article, we tried to analyse the literature data of domestic and foreign authors on the pathogenetic mechanisms of chronic heart failure, the impact on its development and the course of its complications, and, above all, brain damage in the form of chronic cerebrovascular insufficiency.

Left atrial reservoir strain is a superior discriminator of cardioembolism in ischaemic stroke.

Echocardiographic measures of left heart size and function have long been associated with cardioembolic mechanisms of stroke development, however, the diagnostic performance and comparison of measures of atrial function in this context has not been well studied. We sought to evaluate the diagnostic performance of left atrial reservoir strain (LASr) in identification of cardioembolism in the ischaemic stroke population relative to traditional measures of left heart size and function. Consecutive patients admitted to our institution with ischaemic stroke or transient ischaemic attack were recruited and underwent comprehensive transthoracic echocardiography. Strokes were classified by aetiology with comparison undertaken between cardioembolic and non-cardioembolic types. Four hundred and eighteen consecutive stroke patients with a cardioembolic (n = 229) or non-cardioembolic (n = 189) stroke aetiology were analysed. LASr was impaired in cardioembolic compared with non-cardioembolic strokes (16.7 ± 8.2% vs. 26.0 ± 5.5%, P < 0.01) and provided greatest discrimination [area under the curve (AUC) 0.813, 95%CI 0.773-0.858] in differentiating stroke subtypes when compared with LVEF (AUC difference 0.150, P < 0.01), LAVI (AUC difference 0.083, P < 0.01), and E/e' (AUC difference 0.163, P < 0.01). Inclusion of LASr in a model with conventional left heart echocardiographic factors improved model performance with a net reclassification improvement of 1.083 (95%CI 0.945-1.220, P < 0.01). Further, a proposed user-defined model-based clinical algorithm with LASr demonstrated improved diagnostic accuracy of the identification of cardioembolic stroke subtypes which was best appreciated in patients without atrial fibrillation. LASr may provide enhanced diagnostic accuracy beyond conventional echocardiographic measures to discriminate cardioembolic from non-cardioembolic stroke mechanisms, in particular amongst those without comorbid atrial fibrillation.

Genetically predicted chronic rhinosinusitis and the risk of stroke: a two-sample Mendelian randomization study.

The causal association between chronic rhinosinusitis (CRS) and stroke remains uncertain due to the susceptibility of observational studies to confounding and the possibility of reverse causality. This study aims to examine the potential causal relationship between CRS and the risk of stroke, encompassing various subtypes. In this research, we utilized genome-wide association study (GWAS) data for CRS from FinnGen. We identified significant single-nucleotide polymorphisms (SNPs) associated with CRS and used them as instrumental variables (IVs). GWAS data for any ischemic stroke (AIS), ischemic stroke (IS), large-artery atherosclerotic stroke (LAS), small-vessel strokes (SVS), cardioembolic strokes (CES), intracerebral hemorrhage (ICH), lobar ICH, and non-lobar ICH came from multi-ancestry GWAS datasets. We conducted two-sample Mendelian randomization (MR) analyses using inverse variance weighting (IVW), weighted median, and MR-Egger regression methods to investigate potential causal relationships between CRS and stroke. Both heterogeneity and pleiotropy were evaluated by sensitivity analyses. The IVW analysis revealed no significant associations between CRS and AIS (OR = 0.99, 95% CI [0.93-1.05], p = 0.73), IS (OR = 0.97, 95% CI [0.81-1.17], p = 0.09), SVS (OR = 0.96, 95% CI [0.82-1.12], p = 0.58), LAS (OR = 0.91, 95% CI [0.77-1.08], p = 0.09), CES (OR = 0.97, 95% CI [0.81-1.17], p = 0.79), ICH (OR = 1.28, 95% CI [0.74-2.22], p = 0.28), lobar ICH (OR = 1.22, 95% CI [0.60-2.50], p = 0.28), and non-lobar ICH (OR = 1.25, 95% CI [0.65-2.40], p = 0.79). Sensitivity analysis found no evidence of horizontal pleiotropy. According to genetic evidence, this Mendelian randomization (MR) study does not indicate a causal relationship between CRS and stroke in European populations. However, further studies are necessary to comprehensively evaluate the potential association between CRS and stroke.

Gender Predicts Differences in Acute Ischemic Cardioembolic Stroke Profile: Emphasis on Woman-Specific Clinical Data and Early Outcome-The Experience of Sagrat Cor Hospital of Barcelona Stroke Registry.

Background and Objectives: Acute ischemic cardioembolic stroke (CS) is a clinical condition with a high risk of death, and can lead to dependence, recurrence, and dementia. Materials and Methods: In this study, we evaluated gender differences and female-specific clinical data and early outcomes in 602 women diagnosed with CS from a total of 4600 consecutive acute stroke patients in a single-center hospital stroke registry over 24 years. A comparative analysis was performed in women and men in terms of demographics, cerebrovascular risk factors, clinical data, and early outcomes. Results: In a multivariate analysis, age, hypertension, valvular heart disease, obesity, and internal capsule location were independent variables associated with CS in women. The overall in-hospital mortality rate was similar, but the group of women had a greater presence of neurological deficits and a higher percentage of severe limitation at hospital discharge. After the multivariate analysis, age, altered consciousness, limb weakness, and neurological, respiratory, gastrointestinal, renal, cardiac and peripheral vascular complications were independent predictors related to early mortality in women. Conclusions: Women with CS showed a differential demographic and clinical profile and worse early outcomes than men. Advanced age, impaired consciousness, and medical complications were predictors of stroke severity in women with CS.

Clinical characteristics of stroke in SARS-CoV-2 infected patients in Japan: A prospective nationwide study

IntroductionWe investigated the clinical characteristics and outcomes of stroke in SARS-CoV-2 infected patients in Japan. MethodsThis prospective, multicenter observational study of stroke in patients with SARS-CoV-2 infection involving 563 primary stroke centers across Japan was conducted between July 2020, and May 2022. We included 159 stroke cases (131 ischemic stroke, 2 transient ischemic attack (TIA), 21 intracranial hemorrhage, and 5 subarachnoid hemorrhage) and collected their clinical characteristics. Ischemic stroke and TIA (n = 133) were analyzed separately. ResultsThe mean age of the 159 patients was 70.6 years, with 66% being men. Poor outcomes (modified Rankin Scale score 5–6) occurred in 40% (63/159) at discharge. Among patients with ischemic stroke and TIA, 30%, 18%, 10%, and 42% had cardioembolism, large-artery atherosclerosis, small-vessel occlusion, and cryptogenic stroke or embolic stroke of undetermined source, respectively. One-third (34%) presented with large vessel occlusion (LVO) of the internal carotid, middle cerebral M1, or basilar arteries. Poor outcomes included age (adjusted odds ratio (aOR): 1.06, 95%CI: 1.01–1.12), ischemic heart disease (IHD) history (aOR: 13.00, 95%CI: 1.51–111.70), moderate to severe pneumonia (aOR: 7.78, 95%CI: 1.18–51.42), an National Institutes of Health Stroke Scale score at baseline (aOR: 1.10, 95%CI: 1.03–1.17), LVO (aOR: 14.88, 95%CI: 2.33–94.97), and log10 D-dimer (aOR: 3.38, 95%CI: 1.01–11.26). ConclusionUpon discharge, 40% of SARS-CoV-2 infected patients with ischemic stroke and TIA had poor outcomes. Poor outcomes were associated with older age, IHD history, moderate to severe pneumonia, higher NIHSS scores, LVO, and higher log10 D-dimer.Registration: UMIN Clinical Trials Registry: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041226.

Exploring the shared biomarkers between cardioembolic stroke and atrial fibrillation by WGCNA and machine learning.

Cardioembolic Stroke (CS) and Atrial Fibrillation (AF) are prevalent diseases that significantly impact the quality of life and impose considerable financial burdens on society. Despite increasing evidence of a significant association between the two diseases, their complex interactions remain inadequately understood. We conducted bioinformatics analysis and employed machine learning techniques to investigate potential shared biomarkers between CS and AF. We retrieved the CS and AF datasets from the Gene Expression Omnibus (GEO) database and applied Weighted Gene Co-Expression Network Analysis (WGCNA) to develop co-expression networks aimed at identifying pivotal modules. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the shared genes within the modules related to CS and AF. The STRING database was used to build a protein-protein interaction (PPI) network, facilitating the discovery of hub genes within the network. Finally, several common used machine learning approaches were applied to construct the clinical predictive model of CS and AF. ROC curve analysis to evaluate the diagnostic value of the identified biomarkers for AF and CS. Functional enrichment analysis indicated that pathways intrinsic to the immune response may be significantly involved in CS and AF. PPI network analysis identified a potential association of 4 key genes with both CS and AF, specifically PIK3R1, ITGAM, FOS, and TLR4. In our study, we utilized WGCNA, PPI network analysis, and machine learning to identify four hub genes significantly associated with CS and AF. Functional annotation outcomes revealed that inherent pathways related to the immune response connected to the recognized genes might could pave the way for further research on the etiological mechanisms and therapeutic targets for CS and AF.

No genetic association between iron deficiency anemia and ischemic stroke and its subtypes: a bidirectional two-sample Mendelian randomization study.

Observational researches have suggested a connection between iron deficiency anemia (IDA) and an increased likelihood of ischemic stroke (IS), yet establishing causality is challenging owing to the inherent limitations of such studies, including their vulnerability to confounding factors and the potential for reverse causation. This study employs a bidirectional two-sample Mendelian randomization (MR) approach to assess the causal linkage between IDA and IS and its subtypes. Identifiable single nucleotide polymorphisms (SNPs) with significant links to either IDA or IS and its subtypes were employed as instrumental variables (IVs). The relationship between IDA and any IS, small vessel stroke (SVS), cardioembolic stroke (CES), and large artery stroke (LAS), was quantified using the inverse variance weighted (IVW) method. Complementary analyses utilizing MR-Egger and weighted median methods further supplemented the IVW findings. Moreover, the leave-one-out analysis, MR-Egger intercept test, MR-PRESSO global test, and Cochrane's Q test were conducted for sensitivity analyses. This study revealed no correlation between IDA and any IS (IVW method: OR [95% CI] = 0.977 [0.863-1.106]; p = 0.716), LAS (OR [95% CI] = 1.158 [0.771-1.740]; p = 0.479), CES (OR [95% CI] = 1.065 [0.882-1.285]; p = 0.512), or SVS (OR [95% CI] = 1.138 [0.865-1.498]; p = 0.357). Conducting a reverse MR analysis, it was determined that there is no causal connection between any IS, LAS, CES, SVS, and IDA (all p > 0.05). Sensitivity analysis indicated that heterogeneity was not significant and no evidence of horizontal pleiotropy was detected. This MR study suggested no causal effect of IDA on IS, LAS, CES, and SVS. Through reverse MR analyses, it was determined that IS and its subtypes did not exert a causal impact on IDA.

Clinical Benefits of Oral Anticoagulants for Elderly Patients With Cardioembolic Stroke at High Bleeding Risk.

The relationship between the severity of cardioembolic stroke (CES) and oral anticoagulant (OAC) treatment before stroke onset in very elderly (≥80 years) patients with nonvalvular atrial fibrillation (NVAF) at high bleeding risk remains unknown. A total of 364 consecutive patients (≥80 years) with CES and NVAF within 48 h following stroke onset were investigated. High bleeding risk was defined as follows: Bleeding history, renal dysfunction (creatinine clearance <30 ml/min), low body weight (≤45 kg), and antiplatelet or nonsteroidal anti-inflammatory drug use. Patients were divided into two groups: High bleeding risk (n=214) and non-high bleeding risk (n=150). We assessed stroke severity and functional outcome between the two groups, and evaluated the effect of therapy with direct OAC (DOAC) on stroke severity in the high-risk group. The high-risk group had a worse modified Rankin Scale (mRS) at discharge than the non-high-risk group [median: 4 (range=2-5) vs. 3 (range=1-4); p=0.02]. Patients in the high-risk group were categorized according to OAC treatment before stroke onset: No OAC (n=148), warfarin (n=46), and DOAC (n=20). The numbers of patients with National Institutes of Health Stroke Scale score (NIHSS) ≥8 on admission in these groups were 104 (70%), 30 (65%), and 8 (40%) (p=0.03), respectively. Multivariate analysis confirmed that DOAC therapy had a lower odds ratio (OR) for severe stroke (NIHSS ≥8) on admission (OR relative to no OAC=0.22, 95% confidence interval=0.08-0.62; p=0.005) and poor functional outcome (mRS ≥4) at discharge (OR=0.31, 95% confidence interval=0.11-0.90; p=0.03). Very elderly patients with CES at high bleeding risk have unfavorable functional outcomes. DOAC administration may be associated with reduced stroke severity.

Effects of preceding antiplatelet agents on severity of ischemic stroke in patients with a history of stroke

IntroductionAntiplatelet agents are effective for secondary prevention of ischemic stroke and can reduce the severity of first-ever ischemic stroke. However, it is uncertain if prophylactic antiplatelet therapy reduces the severity of recurrent ischemic stroke. The aim of this study was to determine the effect of preceding antiplatelet treatment on the severity of thrombotic stroke (TS) in patients with a prior history of stroke. MethodsFrom a prospective hospital registry of 1338 consecutive patients with acute ischemic stroke, we identified patients with a prior history of stroke who were admitted for cardioembolic stroke (CE); TS including large-artery atherosclerosis, small vessel occlusion, and branch atheromatous disease; or other cause or cryptogenic stroke (OCS). Cases in each subtype were categorized based on preceding medication: antiplatelet agents (AP) and none (N). Severity of stroke (National Institutes of Health Stroke Scale: NIHSS) on admission was compared between AP and N cases. ResultsThe total cohort of 252 patients included 83 with CE, 102 with TS, and 67 with OCS. After excluding those with prior anticoagulants, the median NIHSS on admission was lower in AP cases than in N cases (3 vs. 5, p = 0.002). In multivariate analysis, preceding AP treatment was independently associated with minor stroke (NIHSS ≤4) on admission in CE group (OR 8.48, 95% CI 1.71–62.9, p = 0.008) and TS group (OR 4.24, 95% CI 1.44–13.4, p = 0.009). ConclusionPreceding antiplatelet treatment in patients with a prior history of stroke may reduce the severity of subsequent thrombotic and cardiogenic stroke.

Left Atrial Expansion Index for Ischemic Stroke Prediction in Patients with Atrial Fibrillation.

The efficacy of the left atrial (LA) expansion index (LAEI) to predict cerebral ischemic events in patients with atrial fibrillation (AF) is unknown. We enrolled 177 patients with AF (88 with paroxysmal AF and 89 with persistent AF) and a baseline CHA2DS2-VASc score (at enrollment) of 3.6 ± 2.3. Comprehensive echocardiography was performed at enrollment. The LAEI was calculated as (Volmax - Volmin) × 100%/Volmin, where Volmax and Volmin denoted maximal and minimal LA volumes, respectively. The study endpoint was ischemic stroke. Stroke subtypes were classified into cardioembolic stroke (CE), non-CE with determined mechanism (NCE), embolic stroke of undetermined source (ESUS), or transient ischemic attack (TIA). Over a mean 9.9-year follow-up period, 44 (24.9%) of the patients reached the endpoint (24 with CE, 4 with NCE, 6 with ESUS, and 10 with TIA). The LAEI was lower in the stroke group than in the non-stroke group. Stroke incidence in the lowest LAEI quartile was much higher than that in the other LAEI quartiles; the 10-year cumulative stroke risk was 15.9% (14/88) and 33.7% (30/89) in the patients with paroxysmal and persistent AF, respectively. An LAEI of < 35% predicted the presence of stroke with 77% sensitivity and 78% specificity. In multivariable analysis, the LAEI was independently associated with ischemic stroke (hazard ratio 0.952 per 1% increase, 95% confidence interval 0.932-0.971, p < 0.0001). The LAEI is a useful predictor of ischemic stroke in patients with AF.

Genetically predicted small dense low-density lipoprotein cholesterol and ischemic stroke subtype: multivariable Mendelian randomization study.

Small dense low-density lipoprotein cholesterol (S-LDL-C) has been suggested as a particularly atherogenic factor for ischemic stroke (IS) in observational studies, but the causality regarding the etiological subtype remains unclear. This study aims to explore the causal effects of small dense low-density lipoprotein cholesterol (S-LDL-C), medium (M-LDL-C) and large (L-LDL-C) subfractions on the lifetime risk of ischemic stroke (IS) and main subtypes using two-sample Mendelian randomization (TSMR) design. We identified genetic instruments for S-LDL-C, M-LDL-C and L-LDL-C from a genome-wide association study of 115 082 UK Biobank participants. Summary-level data for genetic association of any ischemic stroke (AIS), large artery stroke (LAS), small vessel stroke (SVS) and cardioembolic stroke (CES) were obtained from MEGASTROKE consortium. Accounting for the pleiotropic effects of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), we conducted multivariable TSMR analysis. In univariable TSMR, we found a causal association between genetically predicted S-LDL-C and LAS (IVW-FE: odds ratio (OR) = 1.481, 95% confidence interval (CI): 1.117-1.963, P = 0.006, q = 0.076) but not AIS, SVS or CES. No causal effects were observed for M-LDL-C or L-LDL-C in terms of AIS and IS subtype. In multivariable analysis, the causal association between S-LDL-C and LAS remained significant (IVE-MRE: OR = 1.329, 95% CI: 1.106-1.597, P = 0.002). Findings supported a causal association between S-LDL-C and LAS. Further studies are warranted to elucidate the underlying mechanism and clinical benefit of targeting S-LDL-C.