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.

OBJECTIVE: Several clinical trials have provided evidence supporting the transcatheter closure of patent foramen ovale (PFO) in selected patients following a cryptogenic stroke. However, it remains unknown to what extent these guidelines have been implemented in everyday clinical practice and the familiarity of physicians from different specialties with PFO closure. The aim of our nationwide survey is to explore the implementation of transcatheter PFO occlusion in Greek clinical practice.
METHODS: Attending level cardiologists, internal medicine physicians and neurologists involved in the management of PFO-related strokes working in Greece were invited to complete an online questionnaire. The questionnaire consisted of 19 questions and was designed to obtain comprehensive data on provider demographics, PFO characteristics, and specific clinical scenarios.
RESULTS: A total of 51 physicians (56.9 % cardiologists, 25.5 % neurologists and 17.6 % internal medicine physicians) completed the survey, resulting in a response rate of 53 %. Cardiologists, internal medicine physicians and neurologists agree on several issues regarding PFO closure, such as PFO closure as first line treatment, management of patients with DVT or prior decompression sickness, and post-closure antithrombotic treatment, but different approaches were reported regarding closure in patients with thrombophilia treated with oral anticoagulation (p=0.012) and implantable loop recorder placement for atrial fibrillation exclusion (p=0.029 and p=0.020).
CONCLUSIONS: Our findings show that cardiologists, internal medicine physicians and neurologists agree in numerous issues, but share different views in the management of patients with thrombophilia and rhythm monitoring duration. These results highlight the significance of collaboration among physicians from different medical specialties for achieving optimal results.

BACKGROUND: Embolic stroke of unknown source (ESUS) accounts for 1 in 6 ischemic strokes. Current guidelines do not recommend routine cardiac magnetic resonance (CMR) imaging in ESUS, and beyond the identification of cardioembolic sources, there are no data assessing new clinical findings from CMR in ESUS. This study aimed to assess the prevalence of new cardiac and noncardiac findings and to determine their impact on clinical care in patients with ESUS.
RESULTS: In this prospective, multicenter, observational study, CMR imaging was performed within 3 months of ESUS. All scans were reported according to standard clinical practice. A new clinical finding was defined as one not previously identified through prior clinical evaluation. A clinically significant finding was defined as one resulting in further investigation, follow-up, or treatment. A change in patient care was defined as initiation of medical, interventional, surgical, or palliative care. From 102 patients recruited, 96 underwent CMR imaging. One or more new clinical findings were observed in 59 patients (61%). New findings were clinically significant in 48 (81%) of these patients. Of 40 patients with a new clinically significant cardiac finding, 21 (53%) experienced a change in care (medical therapy, n=15; interventional/surgical procedure, n=6). In 12 patients with a new clinically significant extracardiac finding, 6 (50%) experienced a change in care (medical therapy, n=4; palliative care, n=2).
CONCLUSIONS: CMR imaging identifies new clinically significant cardiac and noncardiac findings in half of patients with recent ESUS. Advanced cardiovascular screening should be considered in patients with ESUS.
BACKGROUND: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04555538.

(1) Background: Atrial cardiomyopathy constitutes an intrinsically prothrombotic atrial substrate that may promote atrial fibrillation and thromboembolic events, especially stroke, independently of the arrhythmia. Atrial reservoir strain is the echocardiography marker with the most robust evidence supporting its prognostic utility. The main aim of this study is to identify atrial cardiomyopathy by investigating the association between left atrial dysfunction in echocardiography and P-wave abnormalities in the surface electrocardiogram. (2) Methods: This is a community-based, multicenter, prospective cohort study. A randomized sample of 100 patients at a high risk of developing atrial fibrillation were evaluated using diverse echocardiography imaging techniques, and a standard electrocardiogram. (3) Results: Significant left atrial dysfunction, expressed by a left atrial reservoir strain < 26%, showed a relationship with the dilation of the left atrium (p < 0.001), the left atrial ejection fraction < 50% (p < 0.001), the presence of advanced interatrial block (p = 0.032), P-wave voltage in lead I < 0.1 mV (p = 0.008), and MVP ECG score (p = 0.036). (4) Conclusions: A significant relationship was observed between left atrial dysfunction and the presence of left atrial enlargement and other electrocardiography markers; all of them are non-invasive biomarkers of atrial cardiomyopathy.

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.
CaWeb 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.
Fifty-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.
To 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.

Accurate ischemic stroke etiologic determination and diagnosis form the foundation of excellent cerebrovascular care as from it stems initiation of the appropriate secondary prevention strategy as well as appropriate patient education regarding specific risk factors for that subtype. Recurrent stroke rates are highest among those patients who receive an incorrect initial stroke diagnosis. Patient distrust and patient reported depression are also higher. The cause of the ischemic stroke also informs predicted patient outcomes and the anticipated recovery trajectory. Finally, determining the accurate cause of the ischemic stroke provides the patient the opportunity to enroll in appropriate research studies studying mechanism, or targeting treatment approaches for that particular disease process. Advances in ischemic stroke research, imaging techniques, biomarkers, and the ability to rapidly perform genetic sequencing over the past decade have shown that classifying patients into large etiologic buckets may not always be appropriate and may represent one reason why some patients are labeled as cryptogenic, or for whom an underlying etiology is never found. Aside from the more traditional stroke mechanisms, there is new research emerging regarding clinical findings that are not normative, but the contributions to ischemic stroke are unclear. In this article, we first review the essential steps to accurate ischemic stroke etiologic classification and then transition to a discussion of embolic stroke of undetermined source (ESUS) and other new entities that have been postulated as causal in ischemic stroke (i.e., genetics and subclinical atherosclerosis). We also discuss the limitations that are inherent in the current ischemic stroke diagnostic algorithms and finally review the most recent studies regarding more uncommon diagnoses and the future of stroke diagnostics and classification.

UNASSIGNED: Initiation of anticoagulation therapy in ischemic stroke patients is contingent on a clinical diagnosis of atrial fibrillation (AF). Results from previous studies suggest thromboembolic risk may predate clinical manifestations of AF. Early identification of this cohort of patients may allow early initiation of anticoagulation and reduce the risk of secondary stroke.
UNASSIGNED: This study aims to produce a substrate-based predictive model using cardiac magnetic resonance imaging (CMR) and baseline noninvasive electrocardiographic investigations to improve the identification of patients at risk of future thromboembolism.
UNASSIGNED: CARM-AF is a prospective, multicenter, observational cohort study. Ninety-two patients will be recruited following an embolic stroke of unknown source (ESUS) and undergo atrial CMR followed by insertion of an implantable loop recorder (ILR) as per routine clinical care within 3 months of index stroke. Remote ILR follow-up will be used to allocate patients to a study or control group determined by the presence or absence of AF as defined by ILR monitoring.
UNASSIGNED: Baseline data collection, noninvasive electrocardiographic data analysis, and imaging postprocessing will be performed at the time of enrollment. Primary analysis will be performed following 12 months of continuous ILR monitoring, with interim and delayed analyses performed at 6 months and 2 and 3 years, respectively.
UNASSIGNED: The CARM-AF Study will use atrial structural and electrocardiographic metrics to identify patients with AF, or at high risk of developing AF, who may benefit from early initiation of anticoagulation.

We evaluated the performance of implantable loop recorders (ILRs) with different detection algorithms and looked for artifacts and therapeutic consequences and their dependence on patient factors.
586 RevealLinq™ ILRs (first generation (NT): n = 335; second generation with TruRhythm™ (TR): n = 251) were implanted during 2014-2021 (syncope n = 206; embolic stroke of unknown source (ESUS) n = 380). Automatically detected EGM episodes (n = 18,650) were classified as correct or incorrect for asystole (AS), atrial fibrillation (AF) or tachycardia (TA). Incorrect episodes were caused by loss of signal (LO), noise (NO), extrasystole (ES) and T-wave oversensing (TWO). Left directed R axes, lower R-amplitudes and older age were related to artifacts. Results were separated by indication. In ESUS patients TR reduced total median artifact episodes: 0.6 (0-7) vs 0 (0-5) (p < 0.03) and median artifact examination time: 0.3 (0-3.5) vs 0 (0-2.5) (p = 0.03) per patient-year. This benefit is caused by significant reductions in total AS and ES-AS artifacts. The total positive predictive value (PPV) improved only in syncope patients (45 vs 71%, p = 0.002). Accordingly in syncope patients with TR more therapeutic consequences could be established (log rank 0.003).
Patients R-axis and measured R-amplitudes during implantation predicted artifacts. This should be taken into account during ILR implantation. Total artifacts, AS artifacts and time spent for artifact analysis was reduced by the new TR detection algorithm in ESUS patients, whereas total artifacts remained unchanged in syncope patients despite reduction of AS artifacts. However TR had no effect on AF and TA episode detection and therefore has to be improved.

Approximately one-third of ischemic strokes are classified as cryptogenic strokes. The risk of stroke recurrence in these patients is significantly elevated with up to one-third of patients with cryptogenic stroke experiencing a further stroke within 10 years. While anticoagulation is the mainstay of treatment for secondary stroke prevention in the context of documented atrial fibrillation (AF), it is estimated that up to 25% of patients with cryptogenic stroke have undiagnosed AF. Furthermore, the historical acceptance of a causal relationship between AF and stroke has recently come under scrutiny, with evidence to suggest that embolic stroke risk may be elevated even in the absence of documented atrial fibrillation attributable to the presence of electrical and structural changes constituting an atrial cardiomyopathy. More recently, the term embolic stroke of unknown source has garnered increasing interest as a subset of patients with cryptogenic stroke in whom a minimum set of diagnostic investigations has been performed, and a nonlacunar infarct highly suspicious of embolic etiology is suspected but in the absence of an identifiable secondary cause of stroke. The ongoing ARCADIA (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) randomized trial and ATTICUS (Apixiban for Treatment of Embolic Stroke of Undetermined Source) study seek to further define this novel term. This review summarizes the relationship between AF, embolic stroke, and atrial cardiomyopathy and provides an overview of the clinical relevance of cardiac imaging, electrocardiographic, and serum biomarkers in the assessment of AF and secondary stroke risk. The implications of these findings on therapeutic considerations is considered and gaps in the literature identified as areas for future study in risk stratifying this cohort of patients.

Recent trials within the past few years have influenced not only how we treat patients immediately after acute ischaemic stroke, but also how we investigate for aetiology. With the advent of improved medications, procedures and monitoring devices, modern stroke prevention strategies are more individualised, but the decision-making process is more complex. We provide an approach to navigating these management options.