Embolic Stroke Of Unknown Source Research Articles

Abstract TP223: Predicting Atrial Fibrillation in Embolic Stroke of Unknown Source

Background: A considerable portion of patients with embolic stroke of unknown source(ESUS)are later found to have occult atrial fibrillation (AF). Studies have shown that prolonged outpatient cardiac monitoring increases the chances of AF detection and impacts choice of antithrombotic therapy. The Brown ESUS-AF Score, a prediction tool utilizing age and left atrial enlargement has previously shown promise in predicting AF in ESUS patients. In this study we aimed to externally validate the Brown ESUS-AF score and compare its performance against a random forest classifier. Methods: We included all patients with ESUS who underwent an inpatient stroke evaluation followed by outpatient cardiac monitoring between October 9,2015-March 31,2023. To validate the Brown ESUS-AF score, our cohort was divided between those who developed AF during follow-up versus those who did not. To develop the random forest classifier, we included demographics, medical comorbidities, lab records, echocardiographic and electrocardiographic findings. We did 80/20 train-test split to fine tune the model, and we identified features that had the greatest performance contribution. Results: Of 468 patients, 97(20.7%) patients had occult AF. AF patients were older(68.6±13.0 vs 60.1±15.6;p=0.0001), had a higher left atrial (LA) volume index(30.6±12.3 vs 26.2±10.0;p=0.0001) and larger LA diameter(3.8 ± 0.7 vs 3.5 ± 0.7;p=0.002) compared to those who did not develop AF. We found that a Brown ESUS-AF score of≥2 had lower sensitivity in our patient cohort than the original development cohort (42%vs63%). In comparing our random forest classifier to the Brown ESUS-AF score, our model had higher c-statistic (0.71vs0.64). The most important features we identified are age, LAVI, PR and QT Interval, triglyceride level and platelets. Conclusion: Our machine learning model incorporating 52 variables performed better than the Brown ESUS-AF score in predicting AF in our large and diverse ESUS cohort.

The usefulness of global longitudinal peak strain and left atrial volume index in predicting atrial fibrillation in patients with ischemic stroke.

Detection of atrial fibrillation (AF) is crucial for preventing recurrence in patients with ischemic stroke. We aimed to examine whether the left atrial volume index (LAVI) and global longitudinal peak strain (GLPS) are associated with AF in patients with ischemic stroke. We prospectively analyzed 678 consecutive patients with ischemic stroke. LAVI and GLPS were assessed using three-dimensional transthoracic echocardiography with speckle-tracking imaging. Multiple logistic regression was used to evaluate the association of AF with LAVI and GLPS. To evaluate the predictive value of LAVI and GLPS for the presence of AF, we used optimism-corrected c-statistics calculated by 100 bootstrap repetitions and the net reclassification improvement (NRI). The mean patient age was 68 ± 13 years (men, 60%). Patients with AF (18%) were a higher LAVI (41.7 ml/m2 vs. 74.9 ml/m2, P < 0.001) and a higher GLPS than those without AF (-14.0 vs. -17.3, P < 0.001). Among the 89 patients classified with embolic stroke of unknown source, the probable cardioembolic group had higher GLPS (n= 17, -14.6 vs. -18.6, respectively; P= 0.014) than the other groups (n= 72). Adding GLPS to age, hypertension, and the LAVI significantly improved the NRI, with an overall NRI improvement of 6.1% (P= 0.03). The LAVI andGLPS with speckle-tracking imaging echocardiography may help identify patients with AF.

Sex-Specific Risk Factors of Nonstenotic Carotid Plaque in Embolic Stroke of Unknown Source: A Case-Control Study.

Many ischemic strokes are diagnosed as embolic strokes of undetermined source (ESUS). Recent evidence suggests that nonstenotic carotid plaque (nsCP) may be a substantial contributor to the risk for ESUS. We aimed to investigate the risk factor profile associated with nsCP in ESUS and defined stroke etiologies. In this retrospective case-control study, we investigated consecutive patients with acute ischemic stroke due to ESUS, small-vessel disease, or cardioembolism proven by magnetic resonance imaging. The association of vascular risk factors age, arterial hypertension, diabetes, dyslipoproteinemia, body mass index, alcohol consumption, tobacco use, kidney failure, and history of stroke with the presence of nsCP was investigated using binary logistic regression analysis and further stratified by stroke etiology and sex. In total, 609 patients (median age, 76 years; 46% women) who were treated from 2018 to 2020 were considered. In patients with ESUS, sex played a more important role for the prevalence of nsCP than in defined etiologies. Female patients with ESUS had lower odds of exhibiting nsCP compared with male patients with ESUS (adjusted odds ratio, 0.36 [95% CI, 0.15-0.86]). In male patients with ESUS, we observed that age (adjusted odds ratio per 10-year increase, 2.55 [95% CI, 1.26-5.17]) and hypertension (adjusted odds ratio, 2.49 [95% CI, 0.56-11.1]) were the main risk factors for nsCP, whereas in female patients with ESUS also tobacco use was particularly relevant (adjusted odds ratio, 3.71 [95% CI, 0.61-22.5]). These results were in line with a sensitivity analysis in nsCP located ipsilateral to the infarct. Sex differences play an important role in nsCP prevalence in patients with ESUS. These findings may have important implications for the management in targeted secondary prevention following ESUS.

Impact of high-resolution intracranial vessel wall magnetic resonance imaging on diagnosis in patients with embolic stroke of unknown source

BackgroundThe mechanism responsible for stroke in patients with embolic stroke of unknown source (ESUS) often remains unknown despite extensive investigations. We aimed to test whether high-resolution intracranial vessel wall MR imaging (icVWI) can add to the diagnostic yield in these patients. Patients and methodsPatients with ESUS were prospectively included into an ongoing registry. Patients that underwent icVWI as part of their diagnostic workup were compared to those that did not have an icVWI. Patients with icVWI positive for intracranial vulnerable plaques were than compared to those without evidence of plaque vulnerability on VWI. ResultsA total of 179 patients with ESUS were included and 48 of them (27%) underwent icVWI. Patients that had an icVWI scan were significantly younger, had lower rates of ischemic heart disease and prior disability as well as significantly lower stroke severity. On regression analysis the only factor that remained associated with not obtaining an icVWI scan was increasing age (Odds ratio [OR] 0.97/year, 95% confidence intervals [CI] 0.95–0.97). Among patients that had an icVWI scan 28 (58%) had evidence of plaque enhancement on VWI in the same distribution of the stroke and the remaining 20 studies were negative. The relative proportion of stroke presumed to be secondary to intracranial non-stenotic atheromatous disease increased from 15% in patients without icVWI scans to 58% among patients with icVWI scans (p = 0.001). On regression analysis the only factor that was associated with vulnerable plaques on icVWI was smoking (OR 11.05 95% CI 1.88–65.17). ConclusionsicVWI can add significant information relevant to stroke pathogenesis and treatment in patients with ESUS and a negative initial exhaustive diagnostic workup.

EMBOLIC STROKE OF UNKNOWN SOURCE: A TREATMENT CONUNDRUM

EMBOLIC STROKE OF UNKNOWN SOURCE: A TREATMENT CONUNDRUM

Experience and insights from a prolonged electrocardiographic monitorization with a wearable system after an embolic stroke of unknown source.

Embolic cerebrovascular events that remain of unknown etiology after a thorough diagnostic evaluation, are known as Embolic Strokes of Undetermined Source (ESUS). Subclinical atrial fibrillation (AF) represents a significant underlying cause of ESUS. Our aims were to examine the overall diagnostic yield of a prolonged cardiac monitoring wearable system (PCMw) after an ESUS to detect AF and factors associated with it, including the time frame from the ESUS event to PCMw initiation. Additionally, to evaluate the frequency of unexpected arrhythmic events (UAE) and their prognostic implications. We retrospectively analyzed 200 ECG recordings (3-leads, 30days duration) by means of a PCMw in patients with an ESUS to detect AF lasting longer than 30s, between 2017 and 2021. UAE were defined as arrhythmia events that were not correlated to the main reason of prolonged cardiac monitoring. AF was detected in 21 patients (10.5%). Patients with AF had more left atrial enlargement (OR=4.22 [1.59-6.85]; p=.01) and atrial arrythmias in the initial 24-h Holter during hospitalization (OR=5.73 [2.03-16.49]; p=.001). The detection of AF was significatively higher if the PCMw was worn within the first 30days after the ESUS compared to beyond 30days (17% vs. 10.3%; p=.002). Fifty three patients (26.5%) had UAE during PCMw. In six of them these findings led to targeted treatment. PCMw represents a feasible non-invasive device that could reliably detect subclinical AF episodes after an ESUS. Diagnostic yield was significatively higher when used within the first 30days after the event, especially in selected patients. UAE were common, but did not impact prognosis.

Symptomatic carotid webs require aggressive intervention

ObjectiveCarotid web (CaWeb) is a rare form of fibromuscular dysplasia that can produce embolic stroke. Misdiagnosis of symptomatic CaWeb as “cryptogenic stroke” or “embolic stroke of unknown source” is common and can lead to recurrent, catastrophic neurologic events. Reports of CaWeb in the literature are scarce, and their natural history is poorly understood. Appropriate management remains controversial. MethodsCaWeb was defined as a single, shelf-like, linear projection in the posterolateral carotid bulb causing a filling defect on computed tomography angiography (CTA) or cerebral angiography. Cases of symptomatic CaWeb at a single institution with a high-volume stroke center were identified through collaborative evaluation by vascular neurologists and vascular surgeons. ResultsFifty-two patients with symptomatic CaWeb were identified during a 6-year period (2016-2022). Average age was 49 years (range, 29-73 years), 35 of 52 (67%) were African American, and 18 of 52 (35%) were African American women under age 50. Patients initially presented with stroke (47/52; 90%) or transient ischemic attack (5/52; 10%). Stenosis was <50% in 49 of 52 patients (94%) based on NASCET criteria, and 0 of 52 (0%) CaWebs were identified with carotid duplex. Definitive diagnosis was made by CTA examined in multiple planes or cerebral angiography examined in a lateral projection to adequately assess the posterolateral carotid bulb, where 52 of 52 (100%) of CaWebs were seen. Early in our institutional experience, 10 of 52 patients (19%) with symptomatic CaWeb were managed initially with dual antiplatelet and statin therapy or systemic anticoagulation; all suffered ipsilateral recurrent stroke at an average interval of 43 months (range, 1-89 months), and five were left with permanent deficits. Definitive treatment included carotid endarterectomy in 27 of 50 (56%) or carotid stenting in 23 of 50 (46%). Two strokes were irrecoverable, and intervention was deferred. Web-associated thrombus was observed in 20 of 50 (40%) on angiography or grossly upon carotid exploration. Average interval from initial stroke to intervention was 39 days. After an average follow-up of 38 months, there was no reported postintervention stroke or mortality. ConclusionsTo our knowledge, this is the largest single-institution analysis of symptomatic CaWeb yet reported. Our series demonstrates that carotid duplex is inadequate for diagnosis, and that medical management is unacceptable for symptomatic CaWeb. Recurrent stroke occurred in all patients managed early in our experience with medical therapy alone. We have since adopted an aggressive interventional approach in cases of symptomatic CaWeb, with no postoperative stroke reported over an average follow-up of 38 months. In younger patients presenting with cryptogenic stroke, especially African American women, detailed review of lateral cerebral angiography or multi-planar, fine-cut CTA images is required to accurately rule out or diagnose CaWeb and avoid recurrent neurologic events.

Clinical and radiological predictive factors of silent AF in ESUS stroke

A quarter of cerebral infarctions remain without etiology (ESUS: embolic stroke of unknown source) with a risk of recurrence under anti-platelet therapy greater than 4% per year. In this population, the challenge is the detection of subclinical atrial fibrillation (AF), the incidence of which could reach 25%. The efficacy of the probabilistic anticoagulation strategy has not been demonstrated in this population making it necessary to identify ESUS patients at high risk of subclinical AF. The aim of this study is to determine clinical and radiological predictive factors of silent AF in ESUS stroke. Monocentric descriptive and analytical historical cohort study conducted at the Neurology Department between January 2016 and December 2020. Three hundred Esus patients were included. In our study 42/300 (14%) patients had at least one episode of AF (> 30 s). In univariate analysis, the variables significantly associated with slower AF in ESUS-type stroke were age greater than or equal to 60 years (P = 0.004, OR = 3.76), female gender (P = 0.045, OR = 1.94), coronary artery disease (P = 0.008, OR = 3.43), previous stroke (P = 0.007, OR = 2.67), stroke of different territory or age (P = 0.031, OR = 2.65), stroke on awakening (P < 10−3, OR = 5.95), higher NIHSS score on admission (P = 0.023, OR = 1.08), lower NIHSS score on discharge (P = 0.031, OR = 0.89), older cerebellar stroke (P < 10−3, OR = 14.16). In multivariate analysis, higher NIHSS score at admission (P = 0.023, OR = 1.08), and lower NIHSS score (P = 0.031, OR = 0.89) at discharge appeared as independent predictors of the occurrence of a subclinical AF episode. In this cohort of ESUS patients, several factors appeared to be predictive of subclinical AF. The subgroup of ESUS patients with these factors appeared to benefit from probabilistic anticoagulation in preventing recurrent cerebral infarction. A therapeutic trial should confirm this hypothesis.

Association of non-sustained atrial tachycardia and its duration in 24-h Holter monitoring with embolic stroke of unknown source.

Although supraventricular ectopic beats (SVE), including premature atrial contractions (PACs) and non-sustained atrial tachycardia (NSAT), are frequent in the general population, some study results indicate that they are pathologic. SVE may predict undiagnosed atrial fibrillation or be associated with the embolic pattern of ischemic stroke. The aim of this study was to identify the indicators most associated with embolic stroke among the parameters that suggest the burden of SVE. A total of 1920 consecutive acute ischemic stroke (AIS) patients were enrolled from two university hospitals. We defined embolic stroke of unknown source (ESUS) and small vessel occlusion (SVO) etiologies using stricter criteria than the existing conventional criteria. We enrolled 426 (SVO: 310 vs. ESUS: 116) patients who met the inclusion criteria. In the 24-h Holter monitoring parameters, total number of PACs and PAC-to-total beat ratio were not significantly different between the two groups. However, NSATs were more frequent, and the duration of the longest NSAT was longer in the ESUS group. Multivariate logistic regression revealed that high brain natriuretic peptide levels, presence of NSAT, history of previous stroke, and the longest NSAT duration significantly correlated with the ESUS etiology. The presence of NSAT and its duration are more important indicators of embolic stroke than the frequency of PACs is. Therefore, considering secondary prevention in AIS patients with ESUS, 24-h Holter monitoring parameters, such as the presence of NSAT and its duration, could be considered as potential sources of cardio-embolism.

390 Real World Analysis of Outcomes After Revascularization Surgery for Symptomatic Non-stenotic Carotid (SyNC) Artery Disease

INTRODUCTION: Symptomatic non-stenotic carotid (SyNC) artery disease is emerging as one of the primary causes of embolic stroke of unknown source. The optimal secondary prevention strategies including medical therapy and revascularization (Carotid Endarterectomy (CEA) versus Carotid Artery Stenting (CAS)) continue to be controversial. METHODS: The National Surgical Quality Improvement Program (NSQIP) targeted dataset for CEA and CAS was queried for symptomatic patients with &lt;50% stenosis of the ipsilateral carotid artery undergoing CEA and CAS between 2012-2019. Data analysis for continuous and categorical variables was carried out. RESULTS: A total of 363 symptomatic patients with &lt;50% stenosis of the ipsilateral carotid artery were identified of which 22 underwent CAS and 341 underwent CEA. Statistical analysis showed that patients undergoing CEA were more likely to be male as compared to those undergoing CAS (68% vs 54.5%, p &lt; 0.001). Additionally, patients in the CAS group were more likely to present with high-risk anatomy features compared to patients in the CEA group (31.8% vs 11.7%, p = 0.007) whereas patients undergoing CEA were more likely to have &lt;50% stenosis contralateral ICA stenosis when compared to patients undergoing CAS (65.1% vs 36.4%, p = 0.001). Furthermore, patients undergoing CAS were more likely to experience post procedural stroke at 30 days compared to those undergoing CEA (13.6% vs 3.8%, p = 0.03). Upon multivariable analysis, CEA was associated with lower odds of post procedural stroke as compared to CAS (OR = 0.17, 95% CI 0.033-0.82, p = 0.027). CONCLUSIONS: Carotid revascularization for SyNC is being performed despite current guidelines and CEA is associated with lower odds of post-procedural stroke compared to CAS.

Abstract Number ‐ 267: The Role of Non‐stenosing Carotid Artery Plaques in ESUS, is it a Silent Offender?

Introduction The secondary prevention of Acute ischemic stroke (AIS)varies based on the root cause of the initial event; thus, determining the cause of an individual AIS is critical for implementing effective care. The well‐described TOAST classification is used to classify stroke etiology, and according to this paradigm, the presence of large vessel disease is considered a high risk for subsequent stroke only if &gt;50% carotid artery stenosis is present. Cryptogenic strokes represent around 30% of all AIS and Embolic stroke of unknown source (ESUS) is a subcategory of the cryptogenic strokes and is characterized as a non‐lacunar ischemic stroke presumed to be of an embolic origin with no evidence of an obvious source of emboli. Here we discuss the most important and latest evidence on the relationship between ESUS and high‐risk plaque features not causing significant stenosis per NASCET criteria. Methods N/A Results The Relationship Between ESUS and Non‐stenosing Carotid Artery Plaques is mainly illustrated in the following points: Plaque vulnerability Researchers have described the following high‐risk features of plaques that may lead to stroke (Table). Plaque vulnerability is a plaque’s susceptibility to rupture and is a proposed determinant of high risk for superimposed thrombosis. According to a meta‐analysis conducted by Kamtchum‐Tatuene et al, high‐risk plaque features were three times more prevalent in patients with symptomatic versus asymptomatic carotid stenosis.3 Laterality of cartid plaques and stroke A meta‐analysis of 8 studies that assessed 323 patients with ESUS showed that mild carotid stenosis with high‐risk plaque features was more commonly located ipsilateral to the stroke side (32.5%) versus being contralaterally located (4.6%).4 Knight‐Greenfield et al evaluated plaque features by CTA in patients with AIS who did not have hemodynamic stenosis. It was also found that ESUS patients had a higher total plaque thickness ipsilateral to the stroke side when compared to the contralateral stroke‐free hemisphere.5 Clot composition and stroke etiology Fibrin/platelet component was dominant in cardioembolic thrombi and cryptogenic stroke, while red blood cells were seen more frequently in non‐cardioembolic thrombi. This supports the hypothesis that plaque histological features play a major role in causing large vessel occlusion despite the absence of significant stenosis.8 Conclusions Despite the evidence that high‐risk plaque features can predict a recurrent stroke, adoption of this principle and its integration into the medical guidelines have not yet been established. This reflects a lack of clinical trials that have utilized detailed plaque characterization for assessing risk of stroke.

Gapless Electrocardiogram-Monitoring in stroke at high risk of atrial fibrillation.

Previous studies investigating prolonged electrocardiogram (ECG)-monitoring after ischemic stroke had significant gaps between the index event and the beginning of long-term monitoring. Atrial fibrillation (AF) detection might be higher if prolonged cardiac rhythm documentation is performed with a gapless approach without any interruption of monitoring time. This investigator-initiated, prospective study included patients with acute ischemic stroke or transient ischemic attack at three study centers. Participants received gapless ECG-monitoring via telemetry during stroke-unit admission until implantation of an insertable cardiac monitor (ICM) within the first days after the index event. Patients acted as their own controls and also received standard 24-72-h Holter ECG. A total of 110 patients were included, of whom 86 (78.2%) had an embolic stroke of unknown source, 14 (12.7%) had small-vessel disease, and 10 (9.1%) had large-artery disease. AF was newly diagnosed in 17 (15.5%) patients via ICM monitoring, compared to one (0.9%) patient via Holter ECG during 6 months of follow-up (p< 0.001). The detection rate of AF within the first 30 days was 10.0%, which accounted for 64% of all new AF diagnoses. The median duration of the detected episodes was 1.7 (interquartile range=0.2-4.7) h. All patients with new onset AF were treated with oral anticoagulation. Gapless ECG-monitoring is an effective strategy to significantly increase the detection rate of AF after ischemic stroke. This finding supports the use of long-term ECG-monitoring with a gapless approach without any interruption in monitoring time as the gold standard for clinical practice.

Abstract TP94: Optimizing The Utilization Of Cardiac Computed Tomography Angiography Among Patients With Ischemic Stroke

Background: The current AHA guidelines recommend (class IIb) advanced cardiac imaging in embolic stroke of unknown source (ESUS). We aim to better characterize the role of cardiac CTA (cCTA) in the evaluation of stroke patients. Method: A retrospective review of stroke patients at a comprehensive stroke center, who had cCTA between 12/2016 and 11/2020 was conducted using institutional registries. Ischemic stroke patients with ESUS, cryptogenic (with ESUS as a competing etiology) and cardio-embolic etiologies were included. Only cardioembolic etiologies in which a suspicion of intracardiac thrombus with either a known diagnosis of atrial fibrillation or presence of LVAD were included. Cases with TIA, large vessel disease, small vessel disease, dissection or hemodynamic etiologies were excluded. TTE and cCTA results from all cases were reviewed for remarkable findings, most notably intracardiac thrombus, and analyzed if a change in anti-thrombotic therapy was directly attributable to cCTA results. Results: As per our criteria, 96 cases (Female 42.7%, Black 37.5%, Age mean: 63.7 years) were included, of whom 45 (46.9%) were ESUS, 21 (21.9%) were cryptogenic, and 30 (31.2%) were cardioembolic. cCTA revealed intracardiac thrombus in 5 (5.2%) cases, all with LA thrombus. Of these, 3 (60%) had escalation of anti-thrombotic therapy. Interestingly, in one patient who had both cMRI and cCTA imaging, the cMRI revealed an apical LV thrombus which was not detected on cCTA. Conclusion: In this retrospective analysis of 96 select stroke cases, escalation of anti-thrombotic therapy from anti-platelets to full dose anti-coagulation was indicated in 3 patients (3.1%) with addition of cCTA. Compared to a similar cohort of patients from the same institutional registry using cMRI as the advanced cardiac imaging modality, cCTA did not reveal any LV thrombi and even missed a case of LV thrombus seen on cMRI suggesting lower sensitivity for cCTA to detect LV thrombus. Further analysis of data is in process to determine the subset of stroke patients who would benefit the most from cCTA.

Symptomatic Carotid Web Requires Aggressive Intervention

Carotid web (CaWeb) is a rare form of fibromuscular dysplasia that can produce embolic stroke. Misdiagnosis of symptomatic CaWeb as “cryptogenic stroke” or “embolic stroke of unknown source” is common and can lead to recurrent, catastrophic neurologic events. Reports of CaWeb in the literature are scarce, and their natural history is poorly understood. Appropriate management remains controversial.

Exact Basilar Artery Occlusion Location Indicates Stroke Etiology and Recanalization Success in Patients Eligible for Endovascular Stroke Treatment

IntroductionEndovascular stroke treatment (EST) is commonly performed for acute basilar artery occlusion (BAO). We aimed to identify the role of the exact location of BAO in patients receiving EST regarding the stroke etiology, recanalization success and prediction of favorable clinical outcome.MethodsRetrospective analysis of 191 consecutive patients treated for BAO with EST from 01/2013 until 06/2021 in a tertiary stroke center. Groups were defined according to exact location of BAO in I: proximal third, II: middle third, III: distal third and IV: tip of the basilar artery. Univariate and multivariate analyses were performed for BAO location comparing stroke etiology, recanalization result and favorable clinical outcome according to mRS 0–3 90 days after stroke onset.ResultsOcclusion sides types I–IV were evenly distributed (37, 36, 60 and 58 patients). Types I and II were more often associated with large artery atherosclerosis (50 vs. 10 patients, p < 0.001). Distal/tip occlusion (types III/IV) occurred mostly in cardiac embolism or embolic stroke of unknown source (89 vs. 12 in types I/II, p < 0.001). Occlusion site correlated with the underlying stroke etiology (AUC [Area under the curve] 0.89, p < 0.0001, OR [odds ratio] for embolism in type IV: 245). Recanalization rates were higher in patients with distal occlusions (type III/IV OR 3.76, CI [95% confidence interval] 1.51–9.53, p = 0.0076). The BAO site is not predicting favorable clinical outcome.ConclusionThe exact basilar artery occlusion site in patients eligible for endovascular stroke treatment reflects the stroke etiology and is associated with differing recanalization success but does not predict favorable clinical outcome.

The role of non-stenosing carotid artery plaques in embolic stroke of undetermined source, is it a silent offender? A review of literature.

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). 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. 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.

Abstract 15227: Decreased Left Atrial Emptying Fraction is Associated With Increased Odds of Diagnosing Atrial Fibrillation Within 1 Year of ESUS

Introduction: A significant proportion of patients with embolic stroke of unknown source (ESUS) are subsequently diagnosed with atrial fibrillation (AF). Left atrial myopathy characterized by mechanical left atrial dysfunction has been associated with development of AF. Hypothesis: Decreased left atrial emptying fraction (LAEF) is independently associated with AF in patients with ESUS. Methods: Patients admitted at a tertiary care medical center for ESUS treated with implantable loop recorders from 2015-2022 were included. Patients were excluded for lack of an interpretable transthoracic echocardiogram during sinus rhythm and electrocardiogram with 6 months of ESUS. Patients were also excluded for lack of clinical follow-up. Co-variates (table) were ascertained from chart review. LAEF was calculated by Simpson’s method of discs. Results: 153 patients were included. The mean(standard deviation) LAEF of patients who developed and did not develop AF within 1 year post ESUS was 48.0%(17.0%) and 57.6%(13.1%), respectively (P&lt;0.001). The odds of diagnosing atrial fibrillation within 1 year post ESUS were 7.18-fold greater in patients with LAEF&lt;40%. Conclusions: LAEF is independently associated with increased odds of AF within 1 year post ESUS. Future research is needed to validate these findings.

152 EXPLORATORY ANALYSIS OF TROPONIN AS BIOMARKER OF ACUTE ISCHAEMIC STROKE SUBTYPES IN A GROUP OF PATIENTS RECRUITED TO THE MIND STUDY

Abstract Background Stroke is a major common cause of acquired disability and death worldwide. Atrial dysfunction or cardiomyopathy, defined by the presence of specific serum biomarkers, ECG findings, or echocardiographic findings, increases the risk of atrial fibrillation, which has been implicated as a key risk factor for ischaemic stroke. There is now growing body of evidence which suggests that early positive troponin after ischaemic stroke may be independently associated with a cardiac embolic source. miRNA as Novel Diagnostic biomarker (MiND) is a current Irish-led research study whose aim is to discover a unique highly diagnostic and prognostic biomarker expressed in acute ischaemic stroke. Methods Data were retrospectively extracted from patients recruited to the MiND study with confirmed diagnosis of acute ischaemic stroke within 12 hours of symptoms onset having also undergone high-sensitivity troponin testing from July 2019 to November 2021. Stroke subtypes were classified as per ESUS criteria. Statistical analysis was carried out using STATA/SE, version 16.0. Results We identified 52 patients who had troponin performed within 12 hours of symptoms onset. Twenty-two patients were identified as having cardioembolic stroke (CE), 17 as non-cardioembolic stroke (NCE) and 13 as Embolic stroke of unknown source (ESUS). The mean age for each group was 77.5 (±9.8), 65.5 (±12.8) and 66.3 (±11.7) years, respectively. The rate of troponin positivity for each group was 55% (12/22), 29% (5/17) and 15% (2/13), respectively. The unadjusted logistic analysis revealed a positive association between CE stroke subtype and elevated troponin (OR 3.94, 95% 1.20-12.98, p = 0.024) and an inverse association between ESUS stroke subtype and elevated troponin (OR 0.24, 95% CI 0.05-1.21, p = 0.083). Conclusion Our analysis reveals that early positive troponin after ischaemic stroke is a strong predictor of CE stroke subtype but not of ESUS stroke subtype.

Utility of P-wave abnormalities for distinguishing embolic stroke from non-embolic stroke

BackgroundOur aim was to analyze the incidence of P-wave abnormalities in embolic and non-embolic strokes, and evaluate its clinical usefulness for predicting stroke etiology. MethodsWe included 376 consecutive patients hospitalized for acute ischemic stroke from January 2015 to September 2021. Among the patients in sinus rhythm at admission, 31 had ischemic stroke due to atrial fibrillation (AF)-related embolism, 59 had embolic stroke of unknown source (ESUS), and 143 had non-embolic stroke. P-wave abnormalities were defined as 1. P-wave axis abnormality (PWAA); 2. P-wave terminal force in V1 (PTFV1) ≤ -4000 μV*ms; 3. advanced inter-atrial block (A-IAB). ResultsThe prevalence of each type of abnormality was consistently lower in patients with non-embolic stroke than in those with AF-related embolism (AF-related vs. ESUS vs. non-embolic; PWAA, 45% vs. 20% vs. 14%; PTFV1, 36% vs. 37% vs. 15%; and A-IAB, 55% vs. 31% vs. 13%, respectively). The identification of at least one type of P-wave abnormality improved the sensitivity compared to using a single abnormality parameter (sensitivity 72%, specificity 62%), while at least two types of abnormality had low sensitivity, but high specificity (sensitivity 29%, specificity 95%). Multivariate regression analysis revealed that identification of at least one type of P-wave abnormality was independently associated with embolic stroke (odds ratio 3.11, 95%CI 1.46–6.63). ConclusionsThe incidence of each type of P-wave abnormality was significantly lower in patients with non-embolic stroke. A combination of PWAA, PTFV1, and A-IAB parameters could be useful for distinguishing embolic from non-embolic stroke.

Management of Patients with Embolic Stroke of Unknown Source: Interpreting the Evidence in the Light of Clinical Judgement

To assess the validity of the belief that anticoagulation is not beneficial in patients with embolic stroke of unknown source (ESUS), and to asssess the benefits and safety of direct-acting oral anticoagulants (DOACs). The failure of randomized trials to show benefit of anticoagulation in ESUS is probably due to misclassification of large artery atherosclerosis (LAA) as ESUS, as defined by a stenosis ≥ 50%. There are important differences among DOACs. There are a number of problems with dabigatran, and rivaroxaban and edoxaban are not suitable for once-daily dosing. Recent evidence from real-world practice indicates that apixaban is more effective and safer than rivaroxaban. Plaque burden should be included in the definition of LAA. Patients in whom a cardioembolic source is strongly suspected should be anticoagulated; antiplatelet agents are not significantly safer than DOACs, and are not effective in cardioembolic stroke.