Search Results (27)

A significant portion of embolic strokes occurs without documented atrial fibrillation (AF), challenging the traditional paradigm of cardioembolism. This review addresses the emerging concept of “atrial cardiopathy” as a distinct clinical entity—an underlying atrial substrate abnormality, characterized by fibrosis and dysfunction, that promotes thromboembolism independent of AF. We posit that AF is often a late-stage manifestation of atrial cardiopathy, not the sole trigger for thrombosis. This paper synthesizes the growing evidence linking biomarkers of atrial cardiopathy to Embolic Stroke of Undetermined Source (ESUS). This new framework has profound clinical implications, suggesting a shift from arrhythmia detection to assessing atrial substrate health for stroke risk stratification. Recognizing atrial cardiopathy is fundamental for developing novel “upstream” therapies, such as targeted anticoagulation, aimed at preventing both AF and its devastating thromboembolic consequences. This review critically evaluates the evidence and translational gaps in the field, synthesizing the emerging role of advanced computational modeling as a key future tool for personalized risk stratification. Full article

Introduction/Aim: As the prevalence of atrial fibrillation (AF) increases with the aging population, the challenge of enhancing the detection rate of AF in embolic stroke of undetermined source (ESUS) has intensified. AF is often detected only after a debilitating or fatal cardioembolic stroke, underscoring the crucial need for early identification to prevent further ischemic stroke (IS). This study aims to assess the efficacy of AF detection in patients with ESUS using a single-lead patch (mobiCARE™; Seers Tech, Inc.) over a period of at least 72 h and up to 5 days, in comparison with standard 24 h Holter monitoring. Design: This multicenter, prospective, consecutive observational trial involves patients aged 18 years and older who have experienced an IS within the past six months. Study outcomes: The primary outcome is the initial detection of AF using either a single-lead wearable patch or 24 h Holter monitoring at both baseline and at a 6-month follow-up among patients diagnosed with ESUS stroke. Secondary outcomes include the first detection of AF among stroke patients with large-artery atherosclerosis or small-vessel occlusion, particularly those whose transthoracic echocardiography reveals a left atrial size of ≥44 mm, an echocardiographic marker of AF. Discussion: Prolonged cardiac monitoring increases the detection rate of paroxysmal AF, but the optimal method should be non-invasive, patient-friendly, and accurate. This new technology may reduce patient burden and socioeconomic impact by facilitating AF detection and preventing cardioembolic stroke, even in patients with non-cardiogenic stroke. Full article

Background: A persistent connection between the atria, known as a patent foramen ovale (PFO), is present in approximately 25% of the general population. PFO closure is indicated in patients under 60 years of age who have experienced an embolic stroke of undetermined source (ESUS) or transient ischemic attack (TIA) confirmed by neurological imaging, and in selected cases of peripheral embolism. Follow-up after the procedure is indicated to confirm the position of the occluder, assess the effectiveness of the closure, and evaluate any potential thrombus formation on the device. Methods: We analyzed data from 75 consecutive patients who underwent percutaneous PFO closure procedures and were followed up for at least one year. The procedure was performed under fluoroscopy and transesophageal echocardiography (TEE) guidance, and occluder size selection was made using TEE multiplanar imaging (MPR). All patients had standard transthoracic echocardiography (TTE) at 1 and 6–12 months after the procedure. To assess the long-term efficacy, contrast-enhanced transcranial Doppler (ce-TCD) was performed at 12 months to record high-intensity transient signals (HITSs). Cases with positive ce-TCD had TEE performed. Results: During follow-up evaluations after 1 and 6–12 months (TTE), we did not observe any device dislodgements, thrombi, or residual leaks visible in TTE. ce-TCD detected HITSs in eight patients, prompting additional TEE examinations performed in seven cases. In five out of seven patients, a leak around the occluder was identified, including two patients with grade 2 HITSs. Conclusions: Assessing the effectiveness of PFO occluder placement is crucial for the residual embolic risk and thus the necessity of antithrombotic therapy. Even low grades of HITSs observed in ce-TCD help to identify patients with residual leaks confirmed in TEE. Full article

Objectives: While traditionally, carotid plaques with significant stenosis have been considered major embolic sources, recent evidence suggests that even non-stenotic small plaques with a <50% stenosis rate may contribute to cerebral infarction. Herein, we evaluated the relationship between non-stenotic small plaques and embolic stroke of undetermined source (ESUS) using computed tomography angiography (CTA). Materials and Methods: We retrospectively reviewed our single-institutional database of hospitalized patients with stroke between April 2017 and December 2022 and enrolled them with ESUS. We evaluated the presence or absence of non-stenotic carotid artery plaque lesions ipsilateral and contralateral to the cerebral infarction lesion using CTA. A neurologist, blinded to the stroke side and all other clinical information, reviewed each CTA and viewed the axial and sagittal CTA source images. In each image, a line perpendicular to the vessel wall was drawn and the plaque diameter was measured. The largest part was considered as the maximum plaque diameter. Results: A total of 951 patients with stroke were hospitalized during the study period. Among these, 35 patients with unilateral anterior circulation ESUS were enrolled. Plaque prevalence > 3 mm was compared between the carotid artery on the ESUS side and contralateral carotid artery. The prevalences were 31% and 8% on the ESUS and contralateral sides, respectively. Plaques > 3 mm were often found on the ESUS side. Conclusions: Patients with ESUS were more likely to exhibit non-stenotic plaques of ≥3 mm in the infarcted carotid artery than in the contralateral carotid artery. Thus, small non-stenotic plaques may be the embolization source in ESUS, and CT angiography is useful for these evaluations. Full article

Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure and arrhythmic mortality; yet, its association with cerebrovascular events, particularly in the absence of atrial fibrillation (AF), remains insufficiently explored. Purpose: This study aimed to determine the prevalence, mechanisms, and anatomical distribution of stroke in patients with DCM and to assess the role of AF and structural remodeling in stroke risk. Methods: We retrospectively analyzed 471 patients who died with DCM at the Emergency County Clinical Hospital of Bihor between 1 January 2022 and 31 December 2024. Clinical records, neuroimaging, autopsy reports, and histopathological data were reviewed. Stroke subtypes were classified according to TOAST criteria (large artery atherosclerosis, cardioembolic, small vessel disease, other determined, undetermined) and hemorrhagic categories (intracerebral, subarachnoid). Demographic, echocardiographic, and comorbidity data were compared between patients with and without cerebrovascular events. Results: Of 471 patients with DCM, 45 (9.6%) had concomitant stroke: pure ischemic in 32 (71.1%), 7 (15.6%) showed ischemic with hemorrhagic transformation, and primary hemorrhagic in 6 (13.3%). The parietal lobe was most frequently affected. AF was present in 26 patients (57.8%) and was significantly associated with ischemic stroke (p = 0.004), though embolic strokes also occurred in sinus rhythm. Patients with stroke had significantly lower left ventricular ejection fraction (28.0 ± 13.7% vs. 34.0 ± 11.2%, p = 0.007) and larger atrial dimensions. Histopathological findings confirmed acute and chronic ischemic injury patterns, including “red neurons,” white matter vacuolization, and gliotic scarring. Conclusions: Stroke is a frequent and often underdiagnosed complication in DCM, predominantly ischemic and embolic in nature. Importantly, embolic events were observed even in patients without AF, suggesting that atrial remodeling in DCM may independently predispose to cerebrovascular risk. These results underscore the need for refined preventive strategies, including careful atrial assessment and exploration of whether anticoagulation may benefit selected high-risk DCM patients without AF, a question that requires confirmation in prospective trials. Potential embolic sources in DCM include atrial cardiopathy and left ventricular thrombus in the setting of severe systolic dysfunction; therefore, careful ventricular as well as atrial assessment is warranted in high-risk DCM. Full article

Embolic stroke of undetermined source (ESUS) was proposed in 2014 as a clinical category to subgroup non-lacunar cryptogenic ischemic strokes that appear embolic but lack an identifiable cause despite thorough investigation. The initial hypothesis was that anticoagulation might offer superior secondary prevention compared to antiplatelet therapy, prompting several large clinical trials. This review synthesizes current knowledge on ESUS. ESUS represents about 17% of ischemic strokes and often affects younger patients with fewer traditional risk factors. Although these patients lack major cardioembolic sources (e.g., atrial fibrillation) or significant arterial stenosis, many have covert embolic substrates. Major trials—NAVIGATE ESUS, RE-SPECT ESUS, and the atrial cardiopathy-focused ARCADIA—found no benefit of anticoagulants over aspirin, challenging the original ESUS framework. These results highlight the heterogeneity within ESUS and underscore the need for individualized diagnostic and therapeutic strategies. Full article

Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations. Full article

Background/Objectives: Previously undiagnosed atrial fibrillation (PUAF) is a significant cause of embolic stroke of undetermined source (ESUS). This study aimed to determine whether early heart rhythm monitoring with a Holter ECG after acute stroke enhances the detection of PUAF compared to standard ambulatory monitoring in ESUS patients, assuming that early cardiac monitoring would lead to a higher detection rate of PUAF. Methods: This cohort study included 100 patients aged 50 and older diagnosed with ESUS and exhibiting sinus rhythm for at least 24 h. All participants were hospitalized in a stroke unit and underwent 48 h of Holter ECG monitoring. A group of 100 ESUS patients who underwent outpatient delayed Holter ECG monitoring served as controls. Results: This study revealed a significantly higher detection rate of AF in the hospitalized group compared to the outpatient group (20% vs. 5%; p = 0.001). The mean age and distribution of risk factors, including hypertension, diabetes, hyperlipidemia, ischemic heart disease, heart failure, chronic kidney disease, smoking, previous stroke, and malignancy, did not differ between the groups. There were no significant differences in initial stroke severity or in outcomes between the groups. Conclusions: Early Holter ECG monitoring in the hospitalized ESUS patients significantly increased the detection rate of PUAF compared to ambulatory monitoring, highlighting the importance of timely cardiac assessment in stroke management. Full article

Background/Objectives: An embolic stroke of undetermined source (ESUS) is a subtype of ischemic stroke characterized by a non-lacunar infarct in the absence of a clearly identifiable embolic source, despite comprehensive diagnostic evaluation. While ESUS patients are typically younger, have fewer cardiovascular comorbidities, and experience milder strokes than those with cardioembolic strokes (CEs), their functional recovery remains underexplored. Methods: We retrospectively analyzed data from 374 ischemic stroke patients (n = 94 ESUS, n = 280 CE) admitted to the Department of Neurology, University of Pécs, between February 2023 and September 2024. Functional recovery was assessed using the modified Rankin Scale (mRS). Propensity score matching (PSM) was performed to balance the baseline characteristics, and the mRS-shift was compared between groups. Independent predictors of mRS-shift were identified using Huber regression and extreme gradient boosting (XGBoost). Results: The ESUS patients were significantly younger (60.7 ± 13.8 years vs. 75.1 ± 11.3 years, p < 0.001), had lower pre-morbid modified Rankin Scale (pre-mRS) scores (0.34 ± 0.91 vs. 0.81 ± 1.23, p < 0.001), were less likely to have hypertension (75.5% vs. 86.1%, p = 0.027) and diabetes (23.4% vs. 36.8%, p = 0.024), and presented with milder strokes (National Institutes of Health Stroke Scale [NIHSS] score at admission: 5.4 ± 4.5 vs. 8.1 ± 6.3, p < 0.001, and 72 h post-stroke: 3.0 ± 4.4 vs. 6.5 ± 6.3, p < 0.001) compared to the CE patients. After adjusting for baseline differences, the ESUS patients demonstrated significantly greater functional recovery than the CE patients (adjusted mRS-shift: 1.84 ± 1.14 vs. 2.53 ± 1.69, p = 0.022). Age, pre-mRS score, and NIHSS score at 72 h post-stroke were the strongest predictors of mRS-shift, with an older age, a higher pre-mRS score, and a greater stroke severity significantly decreasing the odds of recovery. Conclusions: The ESUS patients showed superior functional recovery compared to the CE patients, even after accounting for baseline differences. These findings highlight the need for further research into the pathomechanisms underlying ESUSs and the development of optimal treatment strategies to improve patient outcomes. Full article

Background: Four randomized controlled trials (RCTs) did not show a benefit of direct oral anticoagulant (DOAC) treatment compared with antiplatelet therapy for the prevention of recurrent strokes in patients with embolic stroke of undetermined source (ESUS). However, the balance between efficacy and safety in subgroups needs to be better defined. We aimed to assess the relative benefits of DOACs in key subgroups of adult patients with ESUS. Methods: We searched major databases (PubMed, Embase, CENTRAL, and Web of Science) for RCTs published from inception to 16 June 2024. The primary outcome was recurrent stroke, and the main safety outcomes were major bleeding and clinically relevant non-major bleeding (CRNB). We assessed the risk of bias using the Cochrane Risk of Bias tool 2. Results: We identified four RCTs, involving a total of 13,970 patients with ESUS. Compared to antiplatelet therapy, treatment with DOAC did not reduce the risk of recurrent stroke (RR 0.95, 95% CI 0.83–1.08, p = 0.45) or ischemic stroke (RR 0.92, 95% CI 0.80–1.05, p = 0.22) or increase major bleeding (RR 1.57, 95% CI 0.87–2.83; p = 0.14). DOAC treatment was associated with a significantly higher risk of CRNMB compared to aspirin (RR 1.52, 95% CI: 1.22–1.90; p = 0.0002). The subgroup analysis demonstrated that use of DOACs was associated with a significant protective effect in patients aged 75 or older (RR 0.76, 95% CI 0.60–0.97, p = 0.03) and when the time from index stroke to randomization was ≥8 days (RR 0.80, 95% CI 0.66–0.97, p = 0.02) in preventing recurrency of any type of stroke. Conclusions: Our meta-analysis showed lack of overall benefit of anticoagulation with DOAC compared to antiplatelet therapy for recurrent stroke prevention in adult patients with ESUS. However, the subgroup analyses suggest the possibility of interactions between age and timing of randomization since stroke and treatment with an DOAC in terms of recurrent stroke prevention. Further research toward tailoring the antithrombotic strategy according to patient characteristics is needed. Full article

Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring. Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by inpatient transthoracic echocardiogram (TTE), and stroke etiology was adjudicated by the neurologist per the consensus criteria. Patients with cardioembolic stroke and those with indeterminate diastolic function on TTE were excluded. Baseline patient characteristics and clinical variables were compared among patients with and without LVDD and elevated LVFP. Multivariable regression models were used to assess the associations between diastolic dysfunction, ESUS, and AF detection in ESUS patients. Results: We identified 509 patients with ESUS and NCE stroke who had reported diastolic function. The mean age was 64.19 years, 45.19% were female, and 146 had LVDD with available LVFP data. LVDD was not associated with ESUS (adjusted OR: 1.43, 95% CI: 0.90–2.27, p = 0.130) or atrial fibrillation (AF) detection on cardiac monitoring (adjusted OR: 1.88, 95% CI: 0.75–4.72, p = 0.179). However, LVDD with elevated LVFP was borderline associated with ESUS (adjusted OR: 2.17, 95% CI: 0.99–4.77, p = 0.054) and significantly associated with AF detection (adjusted OR: 3.59, 95% CI: 1.07–12.06, p = 0.038). Conclusions: Our data suggest that LVDD with elevated LVFP is borderline associated with ESUS and significantly associated with AF detection on follow-up cardiac monitoring. Therefore, the presence of LVDD with an increased probability of elevated LVFP may help identify a subset of stroke patients more likely to have ESUS, potentially due to atrial cardiopathy with underlying occult AF. Further studies are needed to confirm our findings and to evaluate the safety and efficacy of anticoagulation in patients with ESUS and LVDD with elevated LVFP. Full article

Introduction: Atrial fibrillation (AF), apart from non-stenotic supracardiac atherosclerosis and neoplastic disease, is the leading cause of cryptogenic stroke, including embolic stroke of un-determined source (ESUS). The aim of our study was to determine the prevalence of AF in ESUS patients based on 30-day telemetric heart rate monitoring initiated within three months after stroke onset. Another aim was to identify factors that increase the likelihood of detecting subsequent AF among ESUS patients. Material and Methods: patients with first-ever stroke classified as per the ESUS definition were eligible for this study. All patients underwent outpatient 30-day telemetric heart rate monitoring. Results: In the period between 2020 and 2022, 145 patients were included. The mean age of all qualified patients was 54; 40% of eligible patients were female. Six patients (4.14%), mostly male patients (4 vs. 2), were diagnosed with AF within the study period. In each case, the diagnosis related to a patient whose stroke occurred in the course of large vessel occlusion. Episodes of AF were detected between day 1 and 25 after starting ECG monitoring. Out of the analyzed parameters that increase the probability of, A.F.; only supraventricular extrasystoles proved to be an independent factor regarding an increased risk of AF [OR 1.046, CI 95% 1.016–1.071, p-value < 0.01]. Conclusions: The use of telemetry heart rhythm monitoring in an outpatient setting can detect AF in 4% of ESUS patients who have undergone prior diagnostic procedures for cardiogenic embolism. Supraventricular extrasystoles significantly increases the likelihood of AF detection in patients with ESUS within three months following stroke. Comorbid coronary artery disease, diabetes and hypertension, rather than a single-factor clinical burden, increase the likelihood of AF detection in older ESUS patients. ESUS in the course of large vessel occlusion is probably associated with an increased likelihood of cardiogenic embolism. Full article

Background/Objectives: Paroxysmal atrial fibrillation (PAF) is an important cause that is thought main potential factor in Embolic stroke of undetermined source (ESUS). Extended Holter ECG is an expensive and time-consuming examination. It needs another tools for predicting PAF in ESUS patients. In this study, serum galectin-3 levels, ECG parameters (PR interval, P wave time and P wave peak time) LA volume index, LA global peak strain and atrial electromechanical conduction time values were investigated for predicting PAF. Methods: 150 patients with ESUS and 30 volunteers for the control group were recruited to study. 48–72 h Holter ECG monitoring was used for detecting PAF. Patients were divided into two groups (ESUS + PAF and ESUS-PAF) according to the development of PAF in Holter ECG monitoring. Results: 30 patients with ESUS whose Holter ECG monitoring showed PAF, were recruited to the ESUS + PAF group. Other 120 patients with ESUS were recruited to the ESUS-PAF group. PA lateral, PA septum, and PA tricuspid were higher in the ESUS + PAF group (p < 0.001 for all). Serum galectin-3 levels were significantly higher in ESUS + PAF than in ESUS-PAF and control groups (479.0 pg/mL ± 435.8 pg/mL, 297.8 pg/mL ± 280.3 pg/mL, and 125.4 ± 87.0 pg/mL, p < 0.001, respectively). Serum galectin-3 levels were significantly correlated with LAVI, PA lateral, and global peak LA strain (r = 0.246, p = 0.001, p = 0.158, p = 0.035, r = −0.176, p = 0.018, respectively). Conclusion: Serum galectin-3 levels is found higher in ESUS patients which developed PAF and Serum galectin-3 levels are associated LA adverse remodeling in patients with ESUS. Full article

Background: In patients with embolic stroke of undetermined source (ESUS), occult atrial fibrillation (AF) has been implicated as a key source of cardioembolism. However, only a minority acquire implantable cardiac loop recorders (ILRs) to detect occult paroxysmal AF, partly due to financial cost and procedural inconvenience. Without the initiation of appropriate anticoagulation, these patients are at risk of increased ischemic stroke recurrence. Hence, cost-effective and accurate methods of predicting AF in ESUS patients are highly sought after. Objective: We aimed to incorporate clinical and echocardiography data into machine learning (ML) algorithms for AF prediction on ILRs in ESUS. Methods: This was a single-center cohort study that included 157 consecutive patients diagnosed with ESUS from October 2014 to October 2017 who had ILR evaluation. We developed four ML models, with hyperparameters tuned, to predict AF detection on an ILR. Results: The median age of the cohort was 67 (IQR 59–74) years old and the median monitoring duration was 1051 (IQR 478–1287) days. Of the 157 patients, 32 (20.4%) had occult AF detected on the ILR. Support vector machine predicted for AF with a 95% confidence interval area under the receiver operating characteristic curve (AUC) of 0.736–0.737, multilayer perceptron with an AUC of 0.697–0.708, XGBoost with an AUC of 0.697–0.697, and random forest with an AUC of 0.663–0.674. ML feature importance found that age, HDL-C, and admitting heart rate were important non-echocardiography variables, while peak mitral A-wave velocity and left atrial volume were important echocardiography parameters aiding this prediction. Conclusion: Machine learning modeling incorporating clinical and echocardiographic variables predicted AF in ESUS patients with moderate accuracy. Full article

While tumor emboli are a rare cause of stroke in cancer patients, they highlight the importance of gross observations and pathological assessments in the evaluation of clots. In this case report, a 70-year-old male with type 2 diabetes mellitus and coronary artery disease presented with acute left-sided weakness. He was clinically diagnosed with stroke and given alteplase at 1.5 h from last known normal. He then underwent CT angiography that showed right internal carotid artery occlusion and immediate thrombectomy. The recovered clot was white and lipid-like; due to its atypical appearance, it was sent for pathological assessment, where it was shown to bear features of malignancy. Subsequent imaging identified masses indicating malignancy in the left gluteus, right pleural hilum, and spine. Tumor embolic stroke is a rare pathology. Embolic diseases such as strokes and pulmonary embolisms are common in patients with cancer. Embolic stroke of undetermined source (ESUS) represents a significant portion of cancer strokes. Tumor emboli, though rare, may be an underappreciated source of ESUS in cancer patients. We intend for this case to demonstrate the value of pathological assessment for atypical thrombi as well as highlight the etiology of tumor embolic strokes. Full article