In AF, CHA2DS2-VASc 1 subgroups did not differ for predicting risk for arterial thromboembolism at 1 y.

SOURCE CITATION: Østergaard L, Olesen JB, Petersen JK, et al. Arterial thromboembolism in patients with atrial fibrillation and CHA2DS2-VASc 1: a nationwide study. Circulation. 2024;149:764-773. 38152890.

Toward More Personalized Management of Device-Detected Atrial Fibrillation.

This Viewpoint discusses the need to individualize the management of subclinical atrial fibrillation according to burden (among other factors) by modeling stroke risk.

Towards a new classification of atrial fibrillation detected after a stroke or a transient ischaemic attack.

Globally, up to 1·5 million individuals with ischaemic stroke or transient ischaemic attack can be newly diagnosed with atrial fibrillation per year. In the past decade, evidence has accumulated supporting the notion that atrial fibrillation first detected after a stroke or transient ischaemic attack differs from atrial fibrillation known before the occurrence of as stroke. Atrial fibrillation detected after stroke is associated with a lower prevalence of risk factors, cardiovascular comorbidities, and atrial cardiomyopathy than atrial fibrillation known before stroke occurrence. These differences might explain why it is associated with a lower risk of recurrence of ischaemic stroke than known atrial fibrillation. Patients with ischaemic stroke or transient ischaemic attack can be classified in three categories: no atrial fibrillation, known atrial fibrillation before stroke occurrence, and atrial fibrillation detected after stroke. This classification could harmonise future research in the field and help to understand the role of prolonged cardiac monitoring for secondary stroke prevention with application of a personalised risk-based approach to the selection of patients for anticoagulation.

World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

Atrial Fibrillation Detection and Load: Knowledge Gaps Related to Stroke Prevention.

Atrial fibrillation is a major cause of ischemic stroke. Technological advances now support prolonged cardiac rhythm monitoring using either surface electrodes or insertable cardiac monitors. Four major randomized controlled trials show that prolonged cardiac monitoring detects subclinical paroxysmal atrial fibrillation in 9% to 16% of patients with ischemic stroke, including in patients with potential alternative causes such as large artery disease or small vessel occlusion; however, the optimal monitoring strategy, including the target patient population and the monitoring device (whether to use an event monitor, insertable cardiac monitor, or stepped approach) has not been well defined. Furthermore, the clinical significance of very short duration paroxysmal atrial fibrillation remains controversial. The relevance of the duration of monitoring, burden of device-detected atrial fibrillation, and its proximity to the acute ischemic stroke will require more research to define the most effective methods for stroke prevention in this patient population.

Patent Foramen Ovale Management for Secondary Stroke Prevention: State-of-the-Art Appraisal of Current Evidence.

Patent foramen ovale (PFO) is frequently identified in young patients with ischemic stroke. Randomized controlled trials provide robust evidence supporting PFO closure in selected patients with cryptogenic ischemic stroke; however, several questions remain unanswered. This report summarizes current knowledge on the epidemiology of PFO-associated stroke, the role of PFO as a cause of stroke, and anatomic high-risk features. We also comment on breakthrough developments in patient selection algorithms for PFO closure in relation to the PFO-associated stroke causal likelihood risk stratification system. We further highlight areas for future research in PFO-associated stroke including the efficacy and safety of PFO closure in the elderly population, incidence, and long-term consequences of atrial fibrillation post-PFO closure, generalizability of the results of clinical trials in the real world, and the need for assessing the effect of neurocardiology teams on adherence to international recommendations. Other important knowledge gaps such as sex, race/ethnicity, and regional disparities in access to diagnostic technologies, PFO closure devices, and clinical outcomes in the real world are also discussed as priority research topics.

Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis.

BACKGROUND: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. METHODS: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. RESULTS: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. CONCLUSIONS: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03178864.

Current practice and attitudes of stroke physicians towards rhythm-control therapy for stroke prevention: results of an international survey.

BACKGROUND: Patients with ischemic stroke and atrial fibrillation (AF) are at particularly high risk for recurrent stroke and cardiovascular events. Early rhythm control has been shown to be superior to usual care for the prevention of stroke and cardiovascular events for people with early AF. There are no data on the willingness to use rhythm control for patients with AF and acute ischemic stroke in clinical practice. METHODS: An online survey was carried out among stroke physicians to assess current practice and attitudes toward rhythm control in patients with AF and acute ischemic stroke between December 22nd 2021 and March 24th 2022. RESULTS: The survey was completed by 277 physicians including 237 from 15 known countries and 40 from unspecified countries. 79% (210/266) reported that they do not regularly apply treatment for rhythm control by ablation or antiarrhythmic drugs at all or only in small numbers (≤ 10%) of patients with AF and acute ischemic stroke. In those patients treated with rhythm-control therapy, antiarrhythmic drugs were used by the majority of respondents (89%), while only a minority reported using AF ablation (11%). 88% of respondents (221/250) stated that they would be willing to randomize patients with AF after acute ischemic stroke to either early rhythm control or usual care in a clinical trial. CONCLUSION: Despite its potential benefit, few patients with AF and acute ischemic stroke appear to be treated with rhythm control, which may result from uncertainty regarding potential complications of antiarrhythmic therapy in patients with acute stroke. Together with recent data on the effectiveness of early rhythm control in patients with a history of stroke, these results call for a randomized clinical trial to assess the efficacy of early rhythm control in patients with acute ischemic stroke and AF.

Ultraearly repeated systemic thrombolysis in recurrent ischemic stroke - A multicentre case study.

OBJECTIVE: We analysed outcomes of patients who received off-label repeated thrombolysis with recombinant tissue plasminogen activator for ischemic stroke recurrence within 10 days (ultraearly repeated thrombolysis, UERT). METHOD: We identified patients receiving UERT from the prospective telestroke network of South-East Bavaria (TEMPiS) registry and by database search (Pubmed, Google scholar). Corresponding authors were contacted for further details. Baseline demographic data and clinical, laboratory, and imaging findings were analysed in a multicentric case study. RESULTS: Sixteen patients receiving UERT were identified. The median time between first and second thrombolysis was 3.5 days. In patients with available data, second thrombolysis achieved an early clinical improvement (NIHSS reduction ≥4 points) in 12 of 14 (85.7%) and a favourable outcome (mRS 0-2 after 3 months) in 11 of 16 (68.8%) patients. Intracerebral haemorrhage (ICH) occurred in 4 patients (25.0%) with one fatal large parenchymatous haemorrhage (6.3%). Neither allergic reactions nor other immunoreactive events were observed. CONCLUSIONS: In our analysis UERT led to early clinical improvement and a favourable clinical outcome in a high percentage of patients with ICH rates comparable to prior publications. UERT might be considered in patients with early recurrent stroke under careful risk-benefit assessment.

Differences in Stroke Recurrence Risk Between Atrial Fibrillation Detected on ECG and 14-Day Cardiac Monitoring.

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single entity, regardless of how it is diagnosed. We hypothesized that ECG-detected AF is associated with a higher risk of stroke recurrence than AF detected on 14-day Holter (PCM-detected AF). METHODS: We conducted a retrospective, registry-based, cohort study of consecutive patients with ischemic stroke and TIA included in the London Ontario Stroke Registry between 2018 and 2020, with ECG-detected and PCM-detected AF lasting ≥30 seconds. We quantified PCM-detected AF burden. The primary outcome was recurrent ischemic stroke, ascertained by systematically reviewing all medical records until November 2022. We applied marginal cause-specific Cox proportional hazards models adjusted for qualifying event type (ischemic stroke versus TIA), CHA2DS2-VASc score, anticoagulation, left ventricular ejection fraction, left atrial size, and high-sensitivity troponin T to estimate adjusted hazard ratios for recurrent ischemic stroke. RESULTS: We included 366 patients with ischemic stroke and TIA with AF, 218 ECG-detected, and 148 PCM-detected. Median PCM duration was 12 (interquartile range, 8.8-14.0) days. Median PCM-detected AF duration was 5.2 (interquartile range, 0.3-33.0) hours, with a burden (total AF duration/total net monitoring duration) of 2.23% (interquartile range, 0.13%-12.25%). Anticoagulation rate at the end of follow-up or at the first event was 83.1%. After a median follow-up of 17 (interquartile range, 5-34) months, recurrent ischemic strokes occurred in 16 patients with ECG-detected AF (13 on anticoagulants) and 2 with PCM-detected AF (both on anticoagulants). Recurrent ischemic stroke rates for ECG-detected and PCM-detected AF groups were 4.05 and 0.72 per 100 patient-years (adjusted hazard ratio, 5.06 [95% CI, 1.13-22.7]; P=0.034). CONCLUSIONS: ECG-detected AF was associated with 5-fold higher adjusted recurrent ischemic stroke risk than PCM-detected AF in a cohort of ischemic stroke and TIA with >80% anticoagulation rate.

A systematic review and synthesis of global stroke guidelines on behalf of the World Stroke Organization.

BACKGROUND: There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke, the World Stroke Organization (WSO) Guideline committee, under the auspices of the WSO, reviewed available guidelines. AIMS: To systematically review the literature to identify stroke guidelines (excluding primary stroke prevention and subarachnoid hemorrhage) since 1 January 2011, evaluate quality (The international Appraisal of Guidelines, Research and Evaluation (AGREE II)), tabulate strong recommendations, and judge applicability according to stroke care available (minimal, essential, advanced). SUMMARY OF REVIEW: Searches identified 15,400 titles; 911 texts were retrieved, 200 publications scrutinized by the three subgroups (acute, secondary prevention, rehabilitation), and recommendations extracted from most recent version of relevant guidelines. For acute treatment, there were more guidelines about ischemic stroke than intracerebral hemorrhage; recommendations addressed pre-hospital, emergency, and acute hospital care. Strong recommendations were made for reperfusion therapies for acute ischemic stroke. For secondary prevention, strong recommendations included establishing etiological diagnosis; management of hypertension, weight, diabetes, lipids, and lifestyle modification; and for ischemic stroke, management of atrial fibrillation, valvular heart disease, left ventricular and atrial thrombi, patent foramen ovale, atherosclerotic extracranial large vessel disease, intracranial atherosclerotic disease, and antithrombotics in non-cardioembolic stroke. For rehabilitation, there were strong recommendations for organized stroke unit care, multidisciplinary rehabilitation, task-specific training, fitness training, and specific interventions for post-stroke impairments. Most recommendations were from high-income countries, and most did not consider comorbidity, resource implications, and implementation. Patient and public involvement was limited. CONCLUSION: The review identified a number of areas of stroke care where there was strong consensus. However, there was extensive repetition and redundancy in guideline recommendations. Future guideline groups should consider closer collaboration to improve efficiency, include more people with lived experience in the development process, consider comorbidity, and advise on implementation.

Microembolism and Other Links Between Migraine and Stroke: Clinical and Pathophysiologic Update.

Migraine and stroke are highly prevalent diseases with a high effect on quality of life, with multiple epidemiologic, pathophysiologic, clinical, and prognostic areas of overlap. Migraine is a risk factor for stroke. This risk is explained by common risk factors, migraine-specific mechanisms, and non-migraine-specific mechanisms that have a relevant role in patients with migraine with aura (e.g., atrial fibrillation and paradoxical embolism through a patent foramen ovale). Another important link between migraine aura and ischemic stroke is cardiac embolism. Cardioembolism is the most frequent cause of ischemic stroke, and increasing evidence suggests that microembolism, predominantly but not exclusively originating in the heart, is a contributing mechanism to the development of migraine aura. In this review, we discuss epidemiologic aspects of the association between migraine and ischemic stroke, the clinical presentation of ischemic strokes in patients with migraine, and the differentiation between migrainous and nonmigrainous infarctions. After that, we review migraine-specific and non-migraine-specific stroke mechanisms. We then review updated preclinical and clinical data on microembolism as a cause of migraine aura. In the last section, we summarize knowledge gaps and important areas to explore in future research. The review includes a clinical vignette with a discussion of the most relevant topics addressed.

Embolic Stroke of Undetermined Source: Current Perspectives on Diagnosis, Investigations, and Management.

In 2014, Hart et al. introduced the concept of "embolic stroke of undetermined source" (ESUS) to the clinical-research stroke community. The hypothesis underlying the development of the ESUS construct was that this potentially heterogenous group of stroke mechanisms were largely thromboembolic, and would thus benefit from anticoagulation over antiplatelet for secondary prevention. Since then, 2 large clinical trials have shown that, to date, there is not a clear uniform antithrombotic strategy for secondary prevention after ESUS as it was originally broadly defined. However, this work has yielded valuable information about the patient phenotypes that experience ESUS strokes, as well as hypothesis-generating substudies that have given rise to the next generation of secondary prevention trials aimed at more personalized approaches for different suspected mechanisms of embolic stroke. In parallel with the evolution of ESUS, several studies aimed at screening for atrial fibrillation in the secondary stroke prevention population have generated additional questions about the mechanistic relevance of atrial fibrillation detected after stroke, and how this should inform poststroke workup, and secondary prevention strategies. Herein, we provide a synthesis of the current understanding surrounding the patient phenotypes that experience ESUS strokes, and previous, ongoing, and anticipated clinical trials that will guide earlier and later secondary prevention strategies and poststroke cardiac investigations.

Epilepsy Surgery in Adult Stroke Survivors with New-Onset Drug-Resistant Epilepsy.

BACKGROUND: Despite its effectiveness, surgery for drug-resistant epilepsy is underutilized. However, whether epilepsy surgery is also underutilized among patients with stroke-related drug-resistant epilepsy is unclear. Therefore, our objectives were to estimate the rates of epilepsy surgery assessment and receipt among patients with stroke-related drug-resistant epilepsy and to identify factors associated with these outcomes. METHODS: We used linked health administrative databases to conduct a population-based retrospective cohort study of adult Ontario, Canada residents discharged from an Ontario acute care institution following the treatment of a stroke between January 1, 1997, and December 31, 2020, without prior evidence of seizures. We excluded patients who did not subsequently develop drug-resistant epilepsy and those with other epilepsy risk factors. We estimated the rates of epilepsy surgery assessment and receipt by March 31, 2021. We planned to use Fine-Gray subdistribution hazard models to identify covariates independently associated with our outcomes, controlling for the competing risk of death. RESULTS: We identified 265,081 patients who survived until discharge following inpatient stroke treatment, 1,902 (0.7%) of whom subsequently developed drug-resistant epilepsy (805 women; mean age: 67.0 ± 13.1 years). Fewer than six (≤0.3%) of these patients were assessed for or received epilepsy surgery before the end of follow-up (≤55.5 per 100,000 person-years). Given that few outcomes were identified, we could not proceed with the multivariable analyses. CONCLUSIONS: Patients with stroke-related drug-resistant epilepsy are infrequently considered for epilepsy surgery that could reduce morbidity and mortality.

Readmissions After Left Atrial Appendage Closure in Patients With Previous Ischemic Stroke or Transient Ischemic Attack.

Background: We examined the frequency and risk factors associated with readmission after left atrial appendage closure (LAAC) in patients with and without previous ischemic stroke and/or transient ischemic attack (TIA). Methods: Hospitalizations for LAAC were identified from the US National Readmission Database, 2016-2018. The primary outcome was the first unplanned readmission after LAAC, with readmission times stratified into those occurring within 0 to 30 days vs within 31 to 180 days. Patients were stratified based on the history of previous stroke and/or TIA. Results: Of 12,901 discharges after LAAC, 28% had previous stroke and/or TIA, and 8.2% had a readmission within 30 days while 18% had a readmission within 31 to 180 days. The rates of in-hospital complications and readmissions at both periods were not significantly different between individuals with vs without previous stroke and/or TIA. Cardiac causes accounted for 28% of readmissions within 30 days and 32% of those within 31 to 180 days, and congestive failure, bleeding, and infections were the most common readmission diagnoses. New stroke and/or TIA accounted for 4% and 6% of the total noncardiac readmissions within 30 days and 31 to 180 days, respectively, and the incidence was higher among those with previous stroke and/or TIA. Female sex and index hospitalization length of stay (LOS) > 1 day were factors independently associated with readmission within 30 days, whereas LOS, diabetes, renal disease, chronic obstructive pulmonary disease, and anemia were among the factors associated with readmissions within 31 to 180 days. Conclusions: Unplanned rehospitalizations were common after LAAC and had similar frequency for patients with vs without previous ischemic stroke and/or TIA. Female sex and index hospitalization LOS > 1 day were among the strongest factors that were independently associated with readmission within 30 days.

Contexte: Nous avons examiné la fréquence et les facteurs de risque des réadmissions consécutives à une fermeture de l'appendice auriculaire gauche (FAOG) chez les patients ayant ou non subi un accident vasculaire cérébral (AVC) ischémique et/ou un accident ischémique transitoire (AIT). Méthodologie: Les hospitalisations pour une FAOG ont été recensées au moyen de la US National Readmission Database (base de données nationale des réadmissions aux États-Unis) pour la période 2016-2018. Le critère d'évaluation principal était la première réadmission non prévue après une FAOG, avec stratification du moment de la réadmission selon que celle-ci était survenue de 0 à 30 jours ou de 31 à 180 jours après l'intervention. Les patients ont été stratifiés en fonction des antécédents d'AVC et/ou d'AIT. Résultats: Parmi les 12 901 patients ayant reçu leur congé de l'hôpital après une FAOG, 28 % avaient des antécédents d'AVC et/ou d'AIT; 8,2 % des patients admissibles ont été réadmis dans les 30 jours et 18 %, entre le 31e et le 180e jour suivant l'intervention. Aucune différence significative n'a été observée entre les patients ayant subi un AVC et/ou un AIT et les patients qui n'en avaient pas subi en ce qui concerne les taux de complications hospitalières et de réadmission durant ces deux périodes. Les causes cardiaques représentaient 28 % des réadmissions dans les 30 jours et 32 % des réadmissions entre le 31e et le 180e jour. L'insuffisance cardiaque congestive, les hémorragies et les infections ont été les causes les plus fréquentes de réadmission. Les nouveaux cas d'AVC et/ou d'AIT ont respectivement été à l'origine de 4 % et de 6 % de l'ensemble des réadmissions de cause non cardiaque dans les 30 jours, et entre le 31e et le 180e jour, et leur fréquence a été plus élevée chez les patients ayant des antécédents d'AVC et/ou d'AIT. Le sexe féminin et une durée d'hospitalisation initiale > 1 jour ont été des facteurs indépendants associés aux réadmissions dans les 30 jours, tandis que la durée de l'hospitalisation, un diabète, une néphropathie, une maladie pulmonaire obstructive chronique et une anémie faisaient partie des facteurs associés aux réadmissions entre le 31e et le 180e jour. Conclusions: Les réhospitalisations non prévues ont été courantes après une FAOG, et leur fréquence a été similaire en présence ou en l'absence d'antécédents d'AVC ischémique et/ou d'AIT. Le sexe féminin et une durée d'hospitalisation initiale > 1 jour ont été les facteurs les plus importants associés aux réadmissions dans les 30 jours.