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Background: Cancer is associated with an increased risk of atrial fibrillation. Whether cancer is also associated with atrial cardiopathy, another atrial pathology associated with heightened ischemic stroke risk, is uncertain., Methods: We conducted a retrospective cross-sectional study among consecutive patients hospitalized with acute ischemic stroke at a quaternary care center in New York, United States from 2011 through 2016. The study exposure was active cancer. The study outcome was atrial cardiopathy, defined as a left atrial volume index ≥35 mL/m 2 on echocardiography. We used multivariable logistic regression, adjusting for baseline characteristics, to evaluate the relationship between cancer (active or historical) and atrial cardiopathy. We performed a subgroup analysis among patients with embolic stroke of undetermined source (ESUS)., Results: The final cohort included 1104 patients with acute ischemic stroke, of whom 10 % had active cancer and 47 % had atrial cardiopathy. Patients with atrial cardiopathy, compared to those without, were older (median age, 77 versus 68 years), and more frequently had hypertension, coronary disease, and atrial fibrillation. Active cancer was present in 9.6 % of patients with atrial cardiopathy (n = 50/520) and 10.4 % of patients without (n = 61/584). There was no association between active cancer and atrial cardiopathy among the overall ischemic stroke cohort (adjusted odds ratio [OR], 0.91; 95 % confidence interval [CI], 0.60-1.37) nor in patients with ESUS (aOR, 0.64; 95 % CI, 0.30-1.36). When the cancer exposure was broadened to include any history of cancer (n = 236, 21.4 %), there still was no significant association with atrial cardiopathy (aOR, 0.93; 95 % CI, 0.68-1.25)., Conclusions: When defining atrial cardiopathy by left atrial volume, we did not find an association between cancer and atrial cardiopathy in patients with ischemic stroke, including among those with ESUS. Future studies, evaluating other atrial cardiopathy biomarkers and settings, are needed to further investigate any potential link between cancer and atrial cardiopathy., Competing Interests: Declaration of competing interest Dr. Beyeler has received research support from the University of Bern, Switzerland. Dr. Navi has received personal fees for serving on an adjudication committee for MindRhythm Inc. Dr. Kamel reports serving as a PI for the ARCADIA trial (NIH/NINDSU01NS095869), which received in-kind study drug from the BMS-Pfizer Alliance for Eliquis® and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, U01NS106513); serving as Deputy Editor for JAMA Neurology; serving on clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; serving on endpoint adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group. The other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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; I 2 = 0%). In ESUS with PFO, anticoagulation was associated with significantly lower risk of ischemic stroke (RR 0.59, 95% CI 0.35-0.98; I 2 = 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; I 2 = 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.

Background: Ischaemic stroke remains one of the leading causes of death and disability worldwide. The population of Western Sydney has a unique demographic with lower socioeconomic status and a culturally and linguistically diverse population. This study aims to investigate the demographics and cardiovascular risk factors of patients in Western Sydney, focusing on the prevalence and profile of cardioembolic (CE) strokes and embolic strokes of undetermined source (ESUS)., Method: Prospective data were collected in 463 patients with ischaemic stroke presenting to a tertiary centre in Western Sydney, who underwent predischarge transthoracic echocardiography. Patients with haemorrhagic strokes or unclear stroke diagnosis were excluded. Analysis of stroke subtype (CE, ESUS, or non-embolic) and clinical characteristics was performed based on age, gender, and prior atrial fibrillation (AF) prevalence., Results: Of the 463 patients, 147 (32%) had CE strokes, and 147 (32%) had ESUS. Cardioembolic (CE) strokes were associated with older age (≥65 years) and a history of congestive cardiac failure. Older patients had higher rates of hypertension, ischaemic heart disease, AF, and congestive heart failure. History of AF was present in 67 patients (14.5%); however, only 51% received anticoagulation before admission despite a low bleeding risk. The transthoracic echocardiography characteristics of ESUS/non-embolic strokes differed from those of CE strokes; 20% of patients with ESUS had an enlarged left atrium, suggesting a subset of patients with ESUS with a left atrial myopathy., Conclusions: Patients with ischaemic stroke in Western Sydney have a high prevalence of cardiovascular risk factors which were often undertreated. Half of the patients with prior AF did not receive anticoagulation despite low bleeding risk, indicating a gap in optimal stroke prevention. There were distinct echocardiographic characteristics among stroke subtypes. Further analysis of left atrium parameters may provide greater insights into the pathogenesis and prevention of embolic strokes., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Patients with active endocarditis often suffer acute stroke, with increased risk for hemorrhagic conversion at the time of valve repair or replacement. Controversy persists about timing of operative intervention., Methods: An institutional Society of Thoracic Surgeons database of all patients with endocarditis was reviewed for patients undergoing valve surgery (2016-2024). Electronic medical records were reviewed for detailed stroke information and longitudinal follow-up. Descriptive statistics and Kaplan-Meier survival curves evaluated outcomes and survival., Results: Operations for acute active infective endocarditis were performed in 656 patients. Preoperative stroke occurred in 98 patients (14.9%); 86 strokes (87.8%) were embolic, and 16 patients (18.6%) had microhemorrhagic and 12 (12.2%) had hemorrhagic strokes. Median time between preoperative stroke diagnosis and surgery was 5.5 days. The overall incidence of postoperative stroke was 2.1% (14 of 656), with no statistically significant difference in postoperative stroke between patients with vs without preoperative stroke (n = 4 of 98 [4.1%] vs n = 10 of 558 [1.8%]; P = .148). However, the proportion of patients with postoperative hemorrhagic strokes was higher in the preoperative stroke group (3.1% vs 0.5%, P = .016). Finally, of patients with preoperative stroke, early surgery ≤72 hours (n= 38 [38.8%]) was not associated with increased stroke (2.6% vs 5.0%, P = .564)., Conclusions: These contemporary data highlight the feasibility of an early valve surgery strategy for acute endocarditis in the setting of acute stroke, with noninferior postoperative stroke risk., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: The susceptibility vessel sign, a hypointense signal on MR T2-weighted gradient-recalled echo images, is associated with erythrocyte-predominant thrombi, which are often present in cardioembolism. In contrast, cancer-associated hypercoagulability (CAH)-related stroke, which is presumably caused by fibrin-predominant thrombi, is associated with the absence of the susceptibility vessel sign. We hypothesized that the prevalence of the susceptibility vessel sign may be helpful in distinguishing CAH-related stroke from cardioembolism. This study attempted to validate this hypothesis and investigated the usefulness of the susceptibility vessel sign in differentiating CAH-related stroke from cardioembolism., Materials and Methods: We retrospectively studied patients with both CAH-related stroke (CAH group) and cardioembolism (cardioembolism group) who had major cerebral artery occlusion on MRA that was performed within 6 hours of stroke onset. All patients visited our department from 2015 to 2021. CAH-related stroke was defined as the following: 1) complication of active cancer, 2) pretreatment D-dimer value of >3 μg/mL, 3) multiple vascular territory infarctions, and 4) lack of any other specifically identified causes of stroke. We compared susceptibility vessel sign positivity rates within each group. Multivariable logistic regression analysis was used to assess the association between the absence of the susceptibility vessel sign and CAH-related stroke., Results: Of 691 patients with CAH-related stroke or cardioembolism, major cerebral artery occlusion was observed in 10 patients in the CAH group and 198 patients in the cardioembolism group. The absence of the susceptibility vessel sign was identified in 55 of 208 patients and was significantly more frequent in the CAH group versus the cardioembolism group (90% versus 24%, P  < .05). For predicting CAH-related stroke, the absence of the susceptibility vessel sign demonstrated a sensitivity of 90% (95% CI, 59%-99%), specificity of 78% (95% CI, 71%-83%), a positive predictive value of 18% (95% CI, 10-31), a negative predictive value of 99% (95% CI, 96%-99%), and a likelihood ratio of 4.06. Multivariable logistic regression analysis revealed that the absence of the susceptibility vessel sign was independently associated with CAH-related stroke (OR, 43; 95% CI, 6.8-863; P  < .01)., Conclusions: The absence of the susceptibility vessel sign was more frequent in CAH-related stroke than in cardioembolism. These findings could potentially be helpful for clinical management and differentiating cardioembolism and CAH-related stroke., (© 2024 by American Journal of Neuroradiology.)

Background: Stroke in young patients is frequently associated with a patent foramen ovale (PFO). Controversy exists over whether the PFO is a cause, a risk factor, or an incidental finding. Estimating the individualized risk of stroke recurrence has been difficult to ascertain. This has implications for aeromedical certification for pilots following stroke recovery., Case Report: A 28-yr-old male flight instructor presented with sudden onset unilateral facial paresthesia, hand weakness, and blurred vision, accompanied by gradual onset bilateral headache. While the cranial symptoms resolved, left hand weakness persisted for 3 d. MRI revealed two punctate ischemic foci in the right precentral gyrus and superior parietal lobe. A transesophageal echocardiogram revealed a PFO with a small bidirectional shunt. His cardiologist and neurologist advised the PFO was unlikely to have caused his stroke and estimated an annual recurrence rate of < 1.8%. He was treated medically and declined PFO closure. He was able to return to flying light-sport aircraft. However, an enduring copilot restriction for general aviation activities was placed on his Class 1 and 2 medical certificates., Discussion: This case highlights the difficulty in determining individualized recurrence risks for pilots recovering from a stroke associated with a PFO. While medical treatment does reduce the risk of recurrence, PFO closure provides marginal additional benefit in certain patients with a risk of side effects. Contemporary evidence-based risk scoring systems combined with echocardiography findings may be used together to better risk stratify patients and suitability for medical aviation recertification. Rengel AC, Gericke C. Embolic ischemic cortical stroke in a young flight instructor with a small patent foramen ovale. Aerosp Med Hum Perform. 2024; 95(10):784-787.

Background: In patients with embolic stroke of undetermined source (ESUS), underlying subclinical atrial fibrillation (AF) is often suspected. Previous studies identifying predictors of AF have been limited in their ability to diagnose episodes of AF. Implantable loop recorders enable prolonged, continuous, and therefore more reliable detection of AF. The aim of this study was to identify clinical and ECG parameters as predictors of AF in ESUS patients with implantable loop recorders., Methods: 101 ESUS patients who received an implantable loop recorder between 2012 and 2020 were included in this study. Patients were followed up regularly on a three-monthly outpatient interval., Results: During a mean follow-up of 647 ± 385 days, AF was detected in 26 patients (26%). Independent risk factors of AF were age ≥ 60 years (HR 2.753, CI 1.129-6.713, p = 0.026), P-wave amplitude in lead II ≤ 0.075 mV (HR 3.751, CI 1.606-8.761, p = 0.002), and P-wave duration ≥ 125 ms (HR 4.299, CI 1.844-10.021, p < 0.001). In patients without risk factors, the risk of developing AF was 16%. In the presence of one risk factor, the probability increased only slightly to 18%. With two or three risk factors, the risk of AF increased to 70%., Conclusion: AF was detected in about one in four patients after ESUS in this study. A comprehensive evaluation involving multiple parameters and the existence of multiple risk factors yields the highest predictive accuracy for detecting AF in patients with ESUS., (© 2024. The Author(s).)

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I 2  = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I 2  = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I 2  = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I 2  = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I 2  = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I 2  = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I 2  = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I 2  = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I 2  = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Atherosclerotic cervical internal carotid artery disease is one of the major causes of ischemic stroke and transient ischemic attacks. The risk of stroke from mild to moderate stenoses (i.e. <50% stenosis) might be underestimated. There is increasing evidence that plaque morphological features reflect plaque instability that may harbor high risk for embolization. In this narrative review, we will review the literature on plaque features that predict vulnerability beyond the degree of stenosis, discuss the clinical association with stroke, and evaluate the evidence that these lesions serve as a source for embolic stroke of unknown source (ESUS)., Methods: We performed a literature search using PubMed, EMBASE, and Web of Science. The terms "embolic stroke of undetermined source" and "plaque morphology" were used either alone or in combination with "non-flow limiting stenosis," "non-stenosing plaques," "high-risk plaque features" or "internal carotid artery plaque." Data on plaque morphology and ESUS were mainly taken from review articles, observational studies including retrospective cohort and cross-sectional studies, meta-analyses, and systematic reviews., Conclusion: Nonstenosing carotid artery plaques with high-risk features carry a remarkable risk for stroke occurrence and randomized clinical trials are warranted for further evaluation of using carotid artery stenting or carotid endarterectomy to mitigate the risk of stroke., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1-year outcomes., Methods and Results: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30-day Holter-ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1-year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2-dimensional and 3-dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m 2 , and 50.6±17.2 versus 34.0±15.4 mL/m 2 , respectively, P <0.001), lower 3-dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P =0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P <0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P <0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups., Conclusions: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long-term ECG monitoring in suspected cardiac sources.

Introduction: Variations in the left atrial appendage (LAA) morphology are associated with different embolic risk in patients with atrial fibrillation (AF). Data are scarce regarding the association between LAA morphology and Embolic stroke of undetermined source (ESUS)., Patients and Methods: Using cardiac computed tomography (CCT) scans, LAA morphology was categorized as either chicken wing (CW), cactus, windsock, or cauliflower. Furthermore, we examined the presence of large secondary lobes arising from the main lobe, considering their existence as indicative of a complex LAA morphology. LAA morphologies were compared between ESUS ( n  = 134) and AF patients ( n  = 120); and between ESUS patients with ( n  = 24) and without ( n  = 110) subsequent AF diagnosis during long-term follow-up., Results: ESUS patients had a significantly higher prevalence of cauliflower morphology compared to AF group (52% vs 34%, respectively, p  = 0.01); however, no significant difference was found between the groups when categorizing LAA morphology to either CW or non-CW. ESUS patients had significantly higher prevalence of large secondary lobes compared with AF patients (50% vs 29%, respectively, p  = 0.001). When comparing ESUS patients with and without AF diagnosis during follow-up (20-48 months of follow-up, median 31 months), there were no significant differences in the prevalence of the "classical" morphologies, but large secondary lobes were significantly more prevalent among those without subsequent AF diagnosis., Conclusion: ESUS patients have a high prevalence of complex LAA morphology, which might be associated with an increased risk for thrombus formation even in the absence of AF., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Artificial intelligence (AI)-enabled sinus rhythm (SR) electrocardiogram (ECG) interpretation can aid in identifying undiagnosed paroxysmal atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS)., Objective: The purpose of this study was to assess the efficacy of an AI model in identifying AF based on SR ECGs in patients with ESUS., Methods: A transformer-based vision AI model was developed using 737,815 SR ECGs from patients with and without AF to detect current paroxysmal AF or predict the future development of AF within a 2-year period. Probability of AF was calculated from baseline SR ECGs using this algorithm. Its diagnostic performance was further tested in a cohort of 352 ESUS patients from 4 tertiary hospitals, all of whom were monitored using an insertable cardiac monitor (ICM) for AF surveillance., Results: Over 25.1-month follow-up, AF episodes lasting ≥1 hour were identified in 58 patients (14.4%) using ICMs. In the receiver operating curve (ROC) analysis, the area under the curve for the AI algorithm to identify AF ≥1 hour was 0.806, which improved to 0.880 after integrating the clinical parameters into the model. The AI algorithm exhibited greater accuracy in identifying longer AF episodes (ROC for AF ≥12 hours: 0.837, for AF ≥24 hours: 0.879) and a temporal trend indicating that the AI-based AF risk score increased as the ECG recording approached the AF onset (P for trend <.0001)., Conclusions: Our AI model demonstrated excellent diagnostic performance in predicting AF in patients with ESUS, potentially enhancing patient prognosis through timely intervention and secondary prevention of ischemic stroke in ESUS cohorts., Competing Interests: Disclosures Dr Joonghee Kim developed the algorithm and founded a start-up company ARPI Inc. He is the CEO of the company. Dr Youngjin Cho works for the company as a research director. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: While statins have been widely used in patients with large-artery atherosclerotic stroke, their effectiveness in patients with cardioembolic large vessel occlusion (CE-LVO) undergoing endovascular treatment (EVT) remains unclear. This study aimed to evaluate whether combining statin therapy with EVT could improve clinical outcomes in patients with acute ischemic stroke caused by CE-LVO in the anterior circulation., Methods: We performed a retrospective screening on patients with CE-LVO in the anterior circulation who underwent EVT in 27 hospitals across China between 2018 and 2021. The primary outcome measure was functional independence, defined as a 90-day modified Rankin Scale (mRS) score of 0 to 2. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH)., Results: A total of 510 patients with CE-LVO in the anterior circulation undergoing EVT were included in this study. Of these, 404 (79.2%) patients received statin treatment (statin group), while 106 (20.8%) did not (non-statin group). Statin treatment was significantly associated with improved functional independence (adjusted OR (aOR) 2.072, 95% CI 1.197 to 3.586, P=0.009). Moreover, statin use was associated with a lower rate of 90-day mortality (aOR 0.343, 95% CI 0.197 to 0.596, P<0.001) and a lower rate of sICH (aOR 0.153, 95% CI 0.072 to 0.325, P<0.001)., Conclusion: Statin treatment was associated with improved clinical outcomes and reduced risks of mortality and sICH in patients with CE-LVO in the anterior circulation undergoing EVT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardioembolism accounts globally for around 25% of ischemic strokes and is more often associated with higher rates of morbidity and mortality. Potential sources of cardioembolism into the intracranial circulation include paradoxic embolism, dysrhythmias, structural heart disease, and valvular heart disease. To identify the etiology of a patient's ischemic stroke, thorough investigation of the intracardiac structures, assessment of dysrhythmias, and consideration of high-risk events such as cardiac surgery are crucial. Treatment after cardioembolic stroke can be personalized based on the underlying cardioembolic source to minimize the risk of recurrent cerebral ischemic events., Competing Interests: Disclosure M.Y Yu and F.Z Caprio have no relevant disclosure. R.A. Bernstein has been a speaker and consultant for Medtronic, Astra Zeneca, Bristo Myers Squibb, Boehringer Ingelheim, and Abbott., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Stump syndrome is defined as a clinical syndrome resulting from a distal intracranial vessel embolic stroke due to an extracranial vessel occlusion. Similar to the anterior circulation, the recurrence of ischemic strokes in territories supplied by the posterior circulation in the presence of vertebral artery occlusion is termed Vertebral Artery Stump Syndrome (VASS)., Material and Methods: We conducted a literature review, identifying 72 patients with transient ischemic attacks (TIAs) or ischemic strokes attributed to VASS, according to Kawano criteria. We categorized all patients in two groups focusing on the therapeutic management those who underwent primary medical treatment and those who received endovascular or surgical treatment either in acute or chronic phase., Results: In the anticoagulant therapy group, only 1 patient had a stroke recurrence. Among the 4 on antiplatelets, all had recurrences, but 3 benefited from switching to anticoagulants or endovascular therapy. In the endovascular therapy group, worse outcomes were linked to acute large vessel occlusion. Endovascular treatment of the vertebral artery, in a chronic phase, was explored in literature for recurrent TIAs or minor strokes suggesting that this could be a viable therapeutic alternative when medical treatment failed in preventing recurrence of ischemic stroke., Conclusions: Some studies suggest that anticoagulant medical therapy may be beneficial for VASS and endovascular therapy has also been reported for selected patients. However, data on treatment outcomes and prognosis are still underreported, making treatment decisions challenging. Randomized Controlled Trials are needed to establish the optimal treatment approach., Competing Interests: Declaration of competing interest We declare that we have no conflicts of interest to disclose regarding the manuscript entitled "Vertebral Artery Stump Syndrome: A Comprehensive Review of Diagnosis and Management," submitted for consideration for publication in Journal of Stroke Cerebrovascular Disease. We have no financial interests, research funding, employment or leadership roles, intellectual property rights, consultancies, or personal relationships that could potentially influence or be perceived to influence the content of this manuscript. We affirm that the work is original, has not been previously published or submitted elsewhere, and that we have not received any financial support or compensation for the preparation, writing, or submission of this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Embolic Stroke of Undetermined Source (ESUS) is a distinct stroke entity that disproportionately affects young adults. We sought to describe characteristics, workup and outcomes of young adult ESUS patients who underwent thrombectomy, and compare outcomes to those reported in different age groups., Materials and Methods: Young-ESUS is a multicenter longitudinal cohort study that enrolled consecutive patients aged 21-50 years at 41 stroke centers in 13 countries between 2017- 2019. Between-group comparisons were performed using Wilcoxon rank sum test for continuous variables or Fisher's exact test for binary variables. Distribution of functional outcomes after thrombectomy for our young adult cohort versus pediatric and older adult cohorts reported in the literature were described using the Kruskal-Wallis test., Results: Of 535 patients enrolled in Young-ESUS, 65 (12.1%) were treated with endovascular thrombectomy. Patients who underwent thrombectomy were more likely to undergo in-depth cardiac testing than those who did not, but cardiac abnormalities were not detected more often in this group. Among thrombectomy patients, 35/63 (55.6%) had minimal to no functional disability at follow up. When adjusted for age, stroke severity and IV alteplase, the odds of achieving favorable outcome did not differ between treated versus untreated patients., Conclusions: Thrombectomy is not rare in young adults with ESUS. Despite extensive workup, cardiac abnormalities were not more prevalent in the thrombectomy group. More research to determine optimal workup, etiologic factors and favorable outcome of stroke across the lifespan is needed., Competing Interests: Declaration of competing interest Dr Perera received grants from Bayer, which provided partial funding to Young ESUS, during the conduct of the study. Dr. Häusler reports personal fees from Bayer, which provided partial funding to Young ESUS study, during the conduct of the study. None of the other authors report any relevant competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cardioembolic stroke is one of the most devastating complications of nonischemic dilated cardiomyopathy (NIDCM). However, in clinical trials of primary prevention, the benefits of anticoagulation are hampered by the risk of bleeding. Indices of cardiac blood stasis may account for the risk of stroke and be useful to individualize primary prevention treatments. We performed a cross-sectional study in patients with NIDCM and no history of atrial fibrillation (AF) from two sources: 1 ) a prospective enrollment of unselected patients with left ventricular (LV) ejection fraction <45% and 2 ) a retrospective identification of patients with a history of previous cardioembolic neurological event. The primary end point integrated a history of ischemic stroke or the presence intraventricular thrombus, or a silent brain infarction (SBI) by imaging. From echocardiography, we calculated blood flow inside the LV, its residence time ( T R ) maps, and its derived stasis indices. Of the 89 recruited patients, 18 showed a positive end point, 9 had a history of stroke or transient ischemic attack (TIA) and 9 were diagnosed with SBIs in the brain imaging. Averaged T R , [Formula: see text] performed well to identify the primary end point [AUC (95% CI) = 0.75 (0.61-0.89), P = 0.001]. When accounting only for identifying a history of stroke or TIA, AUC for [Formula: see text] was 0.92 (0.85-1.00) with odds ratio = 7.2 (2.3-22.3) per cycle, P < 0.001. These results suggest that in patients with NIDCM in sinus rhythm, stasis imaging derived from echocardiography may account for the burden of stroke. NEW & NOTEWORTHY Patients with nonischemic dilated cardiomyopathy (NIDCM) are at higher risk of stroke than their age-matched population. However, the risk of bleeding neutralizes the benefit of preventive oral anticoagulation. In this work, we show that in patients in sinus rhythm, the burden of stroke is related to intraventricular stasis metrics derived from echocardiography. Therefore, stasis metrics may be useful to personalize primary prevention anticoagulation in these patients.

A patient presenting with acute ischemic stroke associated with patent foramen ovale (PFO) had concurrent deep vein thrombosis, pulmonary embolism, and new-onset atrial fibrillation. Upon initiation of anticoagulation therapy, the patient developed hemorrhagic transformation of the stroke. The patient's multiple potential sources of embolic stroke were treated with concomitant left atrial appendage occlusion and PFO closure through the PFO, made possible by using the Steerable Amulet Sheath under 3D-intracardiac echocardiography guidance., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Objectives: First, this registry-based study aimed to comprehensively analyze patients' medical histories and treatments based on ischemic strokes' etiology. We focused on the management of atrial fibrillation among patients diagnosed with cardioembolic stroke. Then, our objective was to identify prognostic factors associated with 28-day mortality., Materials and Methods: All ischemic strokes occurring in adults between 2014 and 2021 in Lille, France, were categorized using the TOAST classification. Comparative analyses of patients' medical characteristics were conducted across subtypes. Survival rates within 28 days post-stroke were assessed, and factors influencing mortality were identified using a multivariate Cox model., Results: 1912 ischemic strokes were recorded, due to cardioembolism (36%), large-artery atherosclerosis (9%), small-artery occlusion (9%), other determined causes (6%), or undetermined causes (39%). The median NIHSS score after cardioembolic stroke (6, IQR: 3-13) was twice that after small-artery occlusion (3, IQR: 2-5). Among patients with cardioembolic stroke, 26% were diagnosed post-admission with atrial fibrillation. For the 42% diagnosed pre-admission, only 54% had prior prescriptions for oral anticoagulants. Reperfusion therapies were administered in 21% of cases, with significant variations across subtypes. Mortality rates were higher after cardioembolic strokes (17%) than after small-artery occlusions (3%). Prognostic factors included etiology, high NIHSS score, atrial fibrillation, and previous heparin prescription., Conclusions: While atrial fibrillation was underdiagnosed and undertreated, patients with cardioembolic stroke exhibited high severity and elevated mortality rates. Etiology emerged as an independent predictor of early mortality, regardless of NIHSS score upon admission. These findings underscore the importance of targeted prevention to improve patient outcomes after ischemic stroke., Competing Interests: Declaration of competing interest The Authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Embolic stroke of undetermined source (ESUS) results in significant morbidity. A left atrial (LA) myopathy is implicated in a proportion of these patients. We hypothesized that LA shape varies by cause of stroke [CE (cardioembolic) vs. ESUS]., Methods and Results: A total of 236 ischaemic stroke and atrial fibrillation (AF) patients and controls were recruited prospectively. AF was classified as paroxysmal AF (PAF) or persistent AF (PersAF). Stroke patients comprised CE stroke secondary to AF and ESUS. There were 81 AF (47 PAF, 34 PersAF), 50 ESUS, 57 CE patients [subdivided into CE with PAF (CEpaf) and CE with PersAF (CEpers)], and 48 controls. Echocardiographic parameters including LA volume, function, and shape/sphericity (3D LA sphericity and 2D-derived LA circularity, ellipticity, sphericity, and eccentricity indices) were evaluated. Increased LA volume and sphericity with LA dysfunction were present in CE, AF, and ESUS groups compared with controls. K-means cluster analysis demonstrated a spectrum of LA myopathy with controls at the lowest and CEpers and PersAF at the upper extremes, with ESUS, PAF, and CEpaf being similar and falling between these extremes. After adjusting for age, sex, and left ventricular (LV) and LA parameters, LA sphericity markers differentiated ESUS from controls (P < 0.01)., Conclusion: Alterations in LA shape are present in ESUS, AF, and CE patients, particularly increased spherical remodelling. The novel markers of LA sphericity proposed may identify LA myopathy in ESUS patients and potentially guide management for secondary prevention., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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.

Background: The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS., Methods: CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that objectively compared ticagrelor plus aspirin and clopidogrel plus aspirin in patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles in China. All study participants were classified into ESUS and non-ESUS groups for the prespecified exploratory analysis. Cox proportional hazards models were used to assess the interaction of the state of ESUS with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin, adjusting for sociodemographic and clinical factors., Results: The subgroup analysis comprised 5796 participants (90.4% of the total 6412 participants) in the CHANCE-2 trial, with a median age of 64.9 years (range, 57.0-71.4 years), of whom 1964 (33.9%) were female. These participants underwent diffusion-weighted imaging as part of the study protocol. After systematic evaluation, 15.2% of patients (881/5796) were deemed to have ESUS. The incidence of stroke recurrence in patients with ESUS was found to be 5.6% in the ticagrelor-aspirin group and 9.2% in the clopidogrel-aspirin group (hazard ratio, 0.57 [95% CI, 0.33-0.99]; P =0.04). In patients without ESUS, the respective incidence rates were 5.6% and 7.5% (hazard ratio, 0.72 [95% CI, 0.58-0.90]; P <0.01). The P value was 0.56 for the treatment × ESUS status interaction effect., Conclusions: In this prespecified exploratory analysis, ticagrelor with aspirin was superior to clopidogrel with aspirin for preventing stroke at 90 days in patients with acute ischemic stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles and were classified as ESUS., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737., Competing Interests: Disclosures Dr Johnston has received support from SANOFI US SERVICES Inc, compensation from Johnson and Johnson International, AstraZeneca AB, and Bristol Myers Squibb Company for consultant services. Dr Bath reports compensation from DiaMedica, F. Hoffmann-La Roche AG, and Phagenesis for consultant services, and World Stroke Organisation for other services; stock options in CoMind; employment by University Of Nottingham; and grants from British Heart Foundation and National Institute for Health and Care Research. The other authors report no conflicts.

Background: The association between hypothyroidism and stroke remains controversial and the association between hypothyroidism and stroke subtypes has not been satisfactorily researched. This study aimed to explore the causal effect of hypothyroidism on the risk of stroke and its subtypes by Mendelian randomization (MR) analysis., Methods: Single nucleotide polymorphisms (SNPs) were selected from published genome-wide association studies (GWAS) meta-analysis as instrumental variables (IVs) for hypothyroidism. As outcomes, summary GWAS data for stroke and its subtypes were obtained from two other large GWAS meta-analyses, including any stroke (AS), any ischemic stroke (AIS), large vessel stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), and intracranial hemorrhage (ICH). Univariate Mendelian randomization (UVMR) and multivariate Mendelian randomization (MVMR) were used to assess the causal effect of hypothyroidism on stroke and its subtypes., Results: In UVMR, genetically predicted hypothyroidism was significantly associated with LAS (OR = 1.14, 95CI = 1.02-1.27) and SVS (OR = 1.14, 95CI = 1.04-1.25), but not with AS, AIS, CES, and ICH. The results of the MVMR showed that after adjusting for smoking, alcohol consumption, hypertension, diabetes, low-density lipoprotein cholesterol (LDL-c), and body mass index (BMI), the causal association between hypothyroidism and SVS remained significant, while the association between hypothyroidism and LAS became nonsignificant., Conclusion: Hypothyroidism is causally associated with risk for LAS and SVS, but not for other stroke subtypes. Hypothyroidism may be an independent risk factor for SVS, and vascular risk factors play an important role in hypothyroidism causing LAS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The D-dimer-to-fibrinogen ratio (DFR) is a good indicator of thrombus activity in thrombotic diseases, but its clinical role in acute ischaemic stroke (AIS) patients with different etiologies has not been studied. We evaluated the diagnostic value of the DFR for different subtypes of AIS., Methods: We conducted a single-center retrospective study of 269 patients with AIS who were referred to our stroke center within 4.5 h from Jan 2017 to Oct 2019. Coagulation data including DFRs were compared among the different stroke subtypes, and a separate retrospective validation sample was utilized to evaluate the prediction efficiency of the DFR for subtype diagnosis., Results: A higher DFR was observed in patients with cardioembolism than in those with large artery atherosclerosis (LAA) (odds ratio (OR) per 0.1 increase of the DFR: 1.49 [1.01-2.18]) after we adjusted for vascular risk factors. The diagnostic value of the DFR for detecting cardioembolism (AUC = 0.722, 95 % CI = 0.623-0.820) exceeded that of isolated D-dimer or fibrinogen. The validation sample (n = 117) further supported the notion that a diagnosis of cardioembolism was more common in patients with a DFR > 0.11 (multivariable risk ratio = 3.11[1.33-7.31], P = 0.009)., Conclusion: High DFRs were associated with cardioembolism in patients with AIS. The utilization of DFR can be beneficial for distinguishing a cardiac embolic source from atherosclerotic stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring., Methods: We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised., Results: A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting., Conclusion: Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

This study aimed to investigate the relationship between complex aortic plaque (CAP) and short-term as well as long-term outcomes following cardioembolic stroke. CAP is a known risk factor for occurrence and recurrence of ischemic stroke. However, the association of CAP on cardioembolic stroke remains unclear. This was retrospective study using prospective cohort of consecutive patients with cardioembolic stroke who underwent transesophageal echocardiography. The functional outcome was evaluated using the modified Rankin Scale score at 3 months, and long-term outcomes were assessed by recurrence of ischemic stroke and occurrence of major adverse cardiovascular events (MACE). Among 759 patients with cardioembolic stroke, 91 (12.0%) had CAP. Early ischemic stroke recurrence within 3 months was associated with CAP (p = 0.025), whereas CAP was not associated with functional outcome at 3 months (odd ratio  1.01, 95% confidence interval [CI]  0.57-1.84, p = 0.973). During a median follow-up of 3.02 years, CAP was significantly associated with ischemic stroke recurrence (hazard ratio = 2.68, 95% CI 1.48-4.88, p = 0.001) and MACE occurrence (hazard ratio = 1.61, 95% CI 1.03-2.51, p = 0.039). In conclusion, CAP was associated with early ischemic stroke recurrence and poor long-term outcomes in patients with cardioembolic stroke. It might be helpful to consider transesophageal echocardiography for patients with cardioembolic stroke to identify CAP., (© 2024. The Author(s).)

Competing Interests: Conflict of interest: None declared.

Background: There is no defined cause for cryptogenic stroke/embolic stroke of undetermined source (CS-ESUS). As atrial fibrillation (AF) develops in a significant proportion of these patients, it has been suggested that left atrial (LA) myopathy may predispose to CS-ESUS. We investigated alterations in echocardiographic measures of LA size and function in patients with CS-ESUS., Methods: A systematic literature review and meta-analysis was performed. PubMed, EMBASE, Cochrane Library, Web of Science and SCOPUS were searched for articles published between 1 January 1990 and 10 February 2023. All observational studies of adult CS-ESUS patients with LA volume or function measurements performed by transthoracic echocardiogram were included. Individual random effects meta-analyses were performed on LA measurements in the CS-ESUS patients using subgroup analysis of comparator groups., Results: We included 29 articles with 3927 CS-ESUS patients. Analysis of weighted mean differences showed CS-ESUS patients had altered LA structure and function parameters, with a larger maximum indexed LA volume, reduced LA emptying fraction and/or LA reservoir strain, compared to healthy controls and noncardioembolic stroke patients. Conversely, CS-ESUS patients had a smaller left atrium with better function, compared to cardioembolic stroke patients and CS-ESUS patients who subsequently developed atrial fibrillation., Conclusions: LA volume and function are altered in CS-ESUS patients compared to healthy controls and other stroke aetiologies. An underlying atrial myopathy in a subset of CS-ESUS patients may be involved in both thrombogenesis and dysrhythmia (specifically AF). While LA functional assessment is not currently recommended following stroke, it may offer an opportunity for recurrent stroke risk stratification., (© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Purpose: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilateral ischemic stroke., Methods: Data are from ESCAPE-NA1, a randomized controlled trial investigating the neuroprotectant nerinetide in patients with acute ischemic stroke and large vessel occlusion (LVO). The degree of stenosis of the extracranial internal carotid artery (ICA) and high-risk plaque features were assessed on baseline computed tomography (CT) angiography. We evaluated the association of non-stenotic carotid disease and ipsilateral stroke by age-adjusted and sex-adjusted logistic regression and calculated the attributable risk of ipsilateral stroke caused by non-stenotic carotid disease., Results: After excluding patients with non-assessable imaging, symptomatic > 50% carotid stenosis and extracranial dissection, 799/1105 (72.1%) patients enrolled in ESCAPE-NA1 remained for this analysis. Of these, 127 (15.9%) were classified as ESUS. Non-stenotic carotid disease occurred in 34/127 ESUS patients (26.8%) and was associated with the presence of ipsilateral ischemic stroke (odds ratio, OR 1.6, 95% confidence interval, CI 1.0-2.6, p = 0.049). The risk of ipsilateral ischemic stroke attributable to non-stenotic carotid disease in ESUS was estimated to be 19.7% (95% CI -5.7% to 39%), the population attributable risk was calculated as 4.3%. Imaging features such as plaque thickness, plaque irregularity or plaque ulceration were not different between non-stenotic carotids with vs. without ipsilateral stroke., Conclusion: Non-stenotic carotid disease frequently occurs in patients classified as ESUS and is associated with ipsilateral ischemic stroke. Our findings support the role of non-stenotic carotid disease as stroke etiology in ESUS, but further prospective research is needed to prove a causal relationship., (© 2023. The Author(s).)

Cardioembolic stroke accounts for over 20% of ischemic strokes and is associated with worse outcomes than other types of strokes. Atrial fibrillation (AF) is the most common risk factor for cardioembolic stroke. In this narrative review, we present an update about cardioembolic stroke mainly related to AF and atrial cardiopathy. Direct oral anticoagulants (DOACs) have revolutionized stroke prevention in patients with AF; however, their efficacy in preventing recurrent embolic stroke of unknown source remains uncertain. Various cardiac monitoring methods are used to detect AF, which is crucial for preventing stroke recurrence. DOACs are preferred over warfarin for AF-related stroke prevention; however, the timing of initiation after acute ischemic stroke is debated. Resuming anticoagulation after intracerebral hemorrhage in AF patients requires careful assessment of the risks. While catheter ablation may reduce the incidence of cardiovascular events, its effect on stroke prevention is unclear, especially in heart failure patients. Atrial cardiopathy is the emerging cause of embolic stroke of unknown source, which indicates atrial structural and functional disorders that can precede AF. Future research should focus on refining stroke risk prediction models, optimizing AF detection, understanding the roles of ablation and anticoagulation in stroke prevention, and establishing atrial cardiopathy as a therapeutic target, which could significantly reduce the burden of stroke.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cardioembolic stroke, characterized by severe illness, poor prognosis, and high recurrence rate, is one of the important causes of ischemic stroke. In the field of genetic research, numerous genes associated with cardioembolic stroke have been identified, and their potential in predicting disease risk and evaluating risk factors has been progressively explored. Here, we provide an overview of the latest advancements in genetics for cardioembolic stroke, including genome-wide association studies, copy number variation studies, whole-genome sequencing studies. Furthermore, we also summarize the application of genetic datasets in polygenic risk score and Mendelian randomization. The aim of this overview is to provide insights and references from multiple perspectives for future investigations on the genetic information for cardioembolic stroke.

Arterial spin-labeling magnetic resonance imaging (ASL-MRI) is widely used for evaluating collateral development in patients with acute ischemic stroke (AIS). This study aimed to characterize the findings of multiphase ASL-MRI between embolic and atherosclerotic large vessel occlusion (LVO) to aid in the differential diagnosis. Among 982 patients with AIS, 44 who were diagnosed with acute, symptomatic, and unilateral occlusion of the horizontal segment of the middle cerebral artery (MCA) were selected and categorized into embolic stroke (ES) and atherosclerosis (AT) groups. Using ASL-MRI (postlabeling delay [PLD] of 1.5, 2.0, and 2.5 s) at admission, the ipsilateral to contralateral ratio (ICR) of the signal intensity and its time-course increasing rate (from PLD 1.5 to 2.0 and 2.5, ΔICR) were measured and compared between the two groups. The mean ICR was significantly higher in the AT group than in the ES group (AT vs. ES: 0.49 vs. 0.27 for ICR 1.5 , 0.73 vs. 0.32 for ICR 2.0 , and 0.92 vs. 0.37 for ICR 2.5 ). The ΔICR of PLD 1.5-2.0 (ΔICR 2.0 ) and 2.5 (ΔICR 2.5 ) were also significantly higher in the AT group than in the ES group (AT vs. ES: 50.9% vs. 26.3% for ΔICR 2.0 , and 92.6% vs. 42.9% for ΔICR 2.5 ). Receiver operating characteristic curves showed moderate-to-strong discriminative abilities of each ASL-MRI parameter in predicting MCA occlusion etiology. In conclusion, multiphase ASL-MRI parameters may aid in differentiating intracranial LVO etiology during the acute phase. Thus, it is applicable to AIS management.

Paradoxical embolism is a medical condition characterized by the migration of an embolus from a venous source into the systemic circulation. This occurs through a specific cardiac abnormality known as a right-to-left shunt, ultimately resulting in the possibility of arterial embolism. Patent foramen ovale (PFO) is the most common cause of intracardiac shunting. We reported a rare case of a 56-year-old man on hemodialysis with PFO and arteriovenous fistula dysfunction who suffered a paradoxical embolic ischemic stroke after percutaneous transluminal angioplasty. This case emphasized the potential risk of paradoxical embolism in hemodialysis patients with vascular access problems. We aimed to highlight the importance of searching for PFO, as it may serve as a possible source of embolism in these patients., (© 2024 Wiley Periodicals LLC.)

The prognosis of patients with embolic stroke of undetermined source (ESUS) may vary according to the underlying cause. Therefore, we aimed to divide ESUS into subtypes and assess the long-term outcomes. Consecutive patients with acute ischemic stroke who underwent a comprehensive workup, including transesophageal echocardiography and prolonged electrocardiography monitoring, were enrolled. We classified ESUS into minor cardioembolic (CE) ESUS, arteriogenic ESUS, two or more causes ESUS, and no cause ESUS. Arteriogenic ESUS was sub-classified into complex aortic plaque (CAP) ESUS and non-stenotic (< 50%) relevant artery plaque (NAP) ESUS. A total of 775 patients were enrolled. During 1286 ± 748 days follow-up, 116 major adverse cardiovascular events (MACE) occurred (4.2 events/100 patient-years). Among the ESUS subtypes, CAP ESUS was associated with the highest MACE frequency (9.7/100 patient-years, p = 0.021). Cox regression analyses showed that CAP ESUS was associated with MACE (hazard ratio 2.466, 95% confidence interval 1.305-4.660) and any stroke recurrence (hazard ratio 2.470, 95% confidence interval, 1.108-5.508). The prognosis of ESUS varies according to the subtype, with CAP ESUS having the worst prognosis. Categorizing ESUS into subtypes could improve patient care and refine clinical trials., (© 2024. The Author(s).)

Introduction and Aim: The advances and the wide use of brain imaging have considerably increased the prevalence of silent brain infarctions (SBI). We aim in this study to determine the prevalence of SBI in patients presenting with acute cardioembolic stroke and the predictive cardiovascular risk factors., Methods: This retrospective study included 267 patients presenting with acute cardioembolic stroke in the emergency and/or neurology departments of the Hassan II University Hospital Center. Clinical, biological and echocardiographic characteristics were recorded. All patients were screened for SBI by brain imaging., Results: The prevalence of SBI in our series was 46%. A group of 203 non-valvular patients and a group of 64 valvular patients were distinguished. In non-valvular group, the average age was 72.97±10.53years. The prevalence of SBI was 45.3%. Forty-four percent of patients with SBI had atrial fibrillation (AF). In multivariate regression analysis, the history of previous stroke, CHA 2 DS 2 -VASc Score≥4, enlarged left atrium (LA), the association of AF with enlarged LA and the lability of International Normalized Ratio in patients initially treated with anticoagulants were significantly associated with the occurrence of SBI (P=0.013, P=0.032, P=0.0001, P=0.01, P=0.03, respectively). Territorial location was significantly the most frequent (P=0.007). In valvular group, the average age was 57.19±14.38years. The prevalence of SBI was 48.4%. In multivariate regression analysis, SBI were significantly associated with moderate or severe mitral stenosis (P=0.02) and with the enlarged LA (P=0.02). In all patients, Modified Rankin Scale at 3 months of discharge from the acute stroke was significantly higher (mRS≥3) in patients with SBI (P=0.04)., Conclusions: SBI requires good management of associated cardiovascular risk factors in a population presenting with initial cardioembolic stroke., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Cryptogenic stroke refers to a stroke of undetermined etiology. It accounts for approximately one-fifth of ischemic strokes and has a higher prevalence in younger patients. Embolic stroke of undetermined source (ESUS) refers to a subgroup of patients with nonlacunar cryptogenic strokes in whom embolism is the suspected stroke mechanism. Under the classifications of cryptogenic stroke or ESUS, there is wide heterogeneity in possible stroke mechanisms. In the absence of a confirmed stroke etiology, there is no established treatment for secondary prevention of stroke in patients experiencing cryptogenic stroke or ESUS, despite several clinical trials, leaving physicians with a clinical dilemma. Both conventional and advanced MRI techniques are available in clinical practice to identify differentiating features and stroke patterns and to determine or infer the underlying etiologic cause, such as atherosclerotic plaques and cardiogenic or paradoxical embolism due to occult pelvic venous thrombi. The aim of this review is to highlight the diagnostic utility of various MRI techniques in patients with cryptogenic stroke or ESUS. Future trends in technological advancement for promoting the adoption of MRI in such a special clinical application are also discussed., (© RSNA, 2024.)

Background: Embolic stroke of undetermined source (ESUS) refers to ischemic stroke where the underlying cause of thromboembolism cannot be found despite the recommended diagnostic workup. Unidentified source of emboli hinders clinical decision-making and patient management with detrimental consequences on long-term prognosis. The rapid development and versatility of magnetic resonance imaging (MRI) make it an appealing addition to the diagnostic routine of patients with ESUS for the assessment of potential vascular and cardiac embolic sources., Aims: To review the use of MRI in the identification of cardiac and vascular embolic sources in ESUS and to assess the reclassification value of MRI examinations added to the conventional workup of ESUS., Summary of Review: We reviewed the use of cardiac and vascular MRI for the identification of a variety of embolic sources associated with ESUS, including atrial cardiomyopathy, left ventricular pathologies, and supracervical atherosclerosis in carotid and intracranial arteries and in distal thoracic aorta. The additional reclassification after MRI examinations added to the workup of patients with ESUS ranged from 6.1% to 82.3% and varied depending on the combination of imaging modalities., Conclusion: MRI techniques allow us to identify additional cardiac and vascular embolic sources and may further decrease the prevalence of patients with the diagnosis of ESUS., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The annualized recurrent stroke rate in patients with Embolic Stroke of Undetermined Source (ESUS) under antiplatelet therapy is around 4.5%. Only a fraction of these patients will develop atrial fibrillation (FA), to which a stroke can be attributed retrospectively. The challenge is to identify patients at risk of occult AF during follow-up., Objective: This work aims to determine clinical factors and electrocardiographic and ultrasound parameters that can predict occult AF in patients with ESUS and build a simple predictive score applicable worldwide., Methods: This is a single-center, registry-based retrospective study conducted at the stroke unit of Sahloul University Hospital, Sousse, Tunisia, between January 2016 and December 2020. Consecutive patients meeting ESUS criteria were monitored for a minimum of one year, with a standardized follow-up consisting of outpatient visits, including ECG every three months and a new 24-hour Holter monitoring in case of palpitations. We performed multivariate stepwise regression to identify predictors of new paroxysmal AF among initial clinical, electrocardiographic (ECG and 24-hour Holter monitoring) and echocardiographic parameters. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integerbased point-scoring system., Results: Three hundred patients met the criteria for ESUS. Among them, 42 (14%) patients showed at least one episode of paroxysmal AF during a median follow-up of two years. In univariate analysis, age, gender, coronary artery disease, history of ischemic stroke, higher NIHSS at admission and lower NIHSS at discharge, abnormal P -wave axis, prolonged P -wave duration, premature atrial contractions (PAC) frequency of more than 500/24 hours, and left atrial (LA) mean area of more than 20 cm 2 were associated with the risk of occurrence of paroxysmal AF. We proposed an AF predictive score based on (1.771 x NIHSS score at admission) + (10.015 x P -wave dispersion; coded 1 if yes and 0 if no) + (9.841x PAC class; coded 1 if ≥500 and 0 if no) + (9.828x LA class surface; coded 1 if ≥20 and 0 if no) + (0.548xNIHSS score at discharge) + 0.004. A score of ≥33 had a sensitivity of 76% and a specificity of 93%., Conclusion: In this cohort of patients with ESUS, NIHSS at both admission and discharge, Pwave dispersion, PAC≥500/24h on a 24-hour Holter monitoring, and LA surface area≥20 cm 2 provide a simple AF predictive score with very reasonable sensitivity and specificity and is applicable almost worldwide. An external validation of this score is ongoing., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: We utilized data from the Third China National Stroke Registry to investigate the prevalence of atrial cardiopathy markers in patients with embolic stroke of undetermined source (ESUS) and to assess their association with death and stroke recurrence., Methods: In China, patients experiencing transient ischemic attack or ischemic stroke were recruited consecutively by the Third China National Stroke Registry. We compared atrial cardiopathy markers, such as left atrial (LA) enlargement, increased P-wave terminal force in lead V1 (PTFV1), premature atrial contractions, paroxysmal supraventricular tachycardia, advanced interatrial block, prolonged PR interval, prolonged P-wave dispersion, and prolonged P-wave duration between ESUS patients and those with small vessel disease and large artery atherosclerosis strokes. The association between these markers and the recurrence of stroke as well as mortality risk in ESUS patients was evaluated using Cox regression analysis., Results: Of 8,528 ischemic stroke patients who underwent a standard diagnostic workup, 2,415 were identified as having ESUS. Multivariable analysis revealed a significant association between elevated PTFV1 and an increased risk of stroke recurrence (HR: 2.50; 95% CI: 1.53-4.09; p &lt; 0.01) as well as mortality (HR: 3.76; 95% CI: 1.58-8.91; p &lt; 0.01) at 1 year in patients with ESUS. Furthermore, we observed that moderate-severe LA enlargement slightly increased the risk of stroke recurrence in patients with ESUS (HR: 1.95; 95% CI: 0.90-4.26; p = 0.09). Both LA diameter (HR: 1.03; 95% CI: 1.00-1.06; p = 0.03) and the top quartile of the LA diameter index (HR: 1.56; 95% CI: 1.03-2.40; p = 0.04) were associated with stroke recurrence in patients with ESUS., Conclusions: PTFV1 was independently associated with an elevated risk of stroke recurrence and mortality in ESUS patients. Additionally, a trend toward a correlation between LA enlargement and high stroke recurrence risk after ESUS was observed., (© 2023 S. Karger AG, Basel.)