The Utility of Echocardiogram in the Workup of Ischemic Stroke Patients.

BACKGROUND: Cardiac sources of emboli can be identified by transthoracic echocardiogram (TTE). The Canadian Best Practice Guidelines recommend routine use of TTE in the initial workup of ischemic stroke when an embolic source is suspected. However, TTEs are commonly ordered for all patients despite insufficient evidence to justify cost-effectiveness. We aim to evaluate the TTE ordering pattern in the initial workup of ischemic stroke at a regional Stroke Center in Central South Ontario and determine the proportion of studies which led to a change in management and affected length of stay (LOS). METHODS: Hospital records of 520 patients with a discharge diagnosis of TIA or ischemic stroke between October 2016 and June 2017 were reviewed to gather information. RESULTS: 477 patients admitted for TIA or ischemic stroke met inclusion criteria. 67.9% received TTE, out of which 6.0% had findings of cardiac sources of emboli including left ventricular thrombus, atrial septal aneurysm, PFO, atrial myxoma, and valvular vegetation. 2.5% of all TTE findings led to change in medical management. The median LOS of patients who underwent TTE was 2 days longer (p < 0.00001). CONCLUSION: TTE in the initial workup of TIA or ischemic stroke remains common practice. The yield of TTEs is low, and the proportion of studies that lead to changes in medical management is minimal. TTE completion was associated with increased LOS and may result in increased healthcare spending; however, additional factors prolonging the LOS could not be excluded.

Thrombectomy in young adults with embolic stroke of undetermined source: Analysis of the Young ESUS study.

OBJECTIVES: Embolic Stroke of Undetermined Source (ESUS) is a distinct stroke entity that disproportionately affects young adults. We sought to describe characteristics, workup and outcomes of young adult ESUS patients who underwent thrombectomy, and compare outcomes to those reported in different age groups. MATERIALS AND METHODS: Young-ESUS is a multicenter longitudinal cohort study that enrolled consecutive patients aged 21-50 years at 41 stroke centers in 13 countries between 2017- 2019. Between-group comparisons were performed using Wilcoxon rank sum test for continuous variables or Fisher's exact test for binary variables. Distribution of functional outcomes after thrombectomy for our young adult cohort versus pediatric and older adult cohorts reported in the literature were described using the Kruskal-Wallis test. RESULTS: Of 535 patients enrolled in Young-ESUS, 65 (12.1%) were treated with endovascular thrombectomy. Patients who underwent thrombectomy were more likely to undergo in-depth cardiac testing than those who did not, but cardiac abnormalities were not detected more often in this group. Among thrombectomy patients, 35/63 (55.6%) had minimal to no functional disability at follow up. When adjusted for age, stroke severity and IV alteplase, the odds of achieving favorable outcome did not differ between treated versus untreated patients. CONCLUSIONS: Thrombectomy is not rare in young adults with ESUS. Despite extensive workup, cardiac abnormalities were not more prevalent in the thrombectomy group. More research to determine optimal workup, etiologic factors and favorable outcome of stroke across the lifespan is needed.

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.

Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

Novel Vascular Anastomoses and Moyamoya Disease in a Woman with Down Syndrome.

A 56-year-old woman with Down syndrome presented with right-sided weakness and dysarthria, and was found on CT/CTA to have a left middle cerebral artery infarct secondary to moyamoya disease. Her left posterior inferior cerebellar artery (PICA) was fed both by the left vertebral artery, and the left ascending pharyngeal artery (APA), with a variant origin from the internal carotid artery (ICA), then passing through the jugular foramen (Figure 1). Her right PICA originated exclusively from her right occipital artery, also via the jugular foramen (Figure 2). The left vertebral artery originated directly from the aortic arch, whereas the right vertebral artery originated from the brachiocephalic trunk. In addition, she had a trifurcated anterior cerebral artery (ACA), and just prior to this trifurcation, her left ACA was partially supplied by the left ICA, via a superior hypophyseal artery. This case is noteworthy for several reasons. First, though it is exceedingly rare to have the PICA supplied by the jugular branch of the APA, this is the first reported case with an ICA origin of that APA.1,2 The fact that both PICAs in this patient originate from the anterior circulation should remind clinicians that in unexplained posterior circulation infarctions, vascular anatomy should be explored, as carotid-vertebrobasilar anastomoses such as these are rare, but possible. Lastly, the conjunction of moyamoya disease and anomalies of the vertebrobasilar system in a patient with Down syndrome raises interesting questions about the influence of trisomy 21 on the developing vasculature. Connections from the APA to the vertebrobasilar system are hypothesized to result from a lack of regression of an embryological anastomosis, in line with the more common persistent trigeminal and persistent hypoglossal arteries.1 Patients with moyamoya disease have a significantly higher rate of persistent carotid-vertebrobasilar anastomoses than the general population,3 and are also 26 times more likely to have Down syndrome.4 Correspondingly, patients with Down syndrome have significantly higher levels of moyamoya disease, and are more than 10 times as likely as the general population to have abnormalities of the Circle of Willis5 and vertebral arteries.6 Several genes on chromosome 21 are known to affect angiogenesis, namely collagen XIII/endostatin (COL18A1), DYRK1A, and Down syndrome candidate region 1 (DSCR1), possibly through inhibition of VEGF activity.7 Whether additional copies of these genes are responsible for the anomalous vascular development seen in Down syndrome, in turn predisposing to the development of moyamoya disease, could benefit from further exploration.

In-Hospital Delays for Acute Stroke Treatment Delivery During the COVID-19 Pandemic.

BACKGROUND: We investigated the impact of regionally imposed social and healthcare restrictions due to coronavirus disease 2019 (COVID-19) to the time metrics in the management of acute ischemic stroke patients admitted at the regional stroke referral site for Central South Ontario, Canada. METHODS: We compared relevant time metrics between patients with acute ischemic stroke receiving intravenous tissue plasminogen activator (tPA) and/or endovascular thrombectomy (EVT) before and after the declared restrictions and state of emergency imposed in our region (March 17, 2020). RESULTS: We identified a significant increase in the median door-to-CT times for patients receiving intravenous tPA (19 min, interquartile range (IQR): 14-27 min vs. 13 min, IQR: 9-17 min, p = 0.008) and/or EVT (20 min, IQR: 15-33 min vs. 11 min, IQR: 5-20 min, p = 0.035) after the start of social and healthcare restrictions in our region compared to the previous 12 months. For patients receiving intravenous tPA treatment, we also found a significant increase (p = 0.005) in the median door-to-needle time (61 min, IQR: 46-72 min vs. 37 min, IQR: 30-50 min). No delays in the time from symptom onset to hospital presentation were uncovered for patients receiving tPA and/or endovascular reperfusion treatments in the first 1.5 months after the establishment of regional and institutional restrictions due to the COVID-19 pandemic. CONCLUSION: We detected an increase in our institutional time to treatment metrics for acute ischemic stroke patients receiving tPA and/or endovascular reperfusion therapies, related to delays from hospital presentation to the acquisition of cranial CT imaging for both tPA- and EVT-treated patients, and an added delay to treatment with tPA.

Délais dans le traitement en milieu hospitalier des AVC aigus dans le contexte de la pandémie de COVID-19. CONTEXTE: Nous nous sommes penchés, dans le contexte de la pandémie de COVID-19, sur l'impact de restrictions régionales imposées dans le domaine social et dans les soins de santé sur les délais de prise en charge de patients victimes d'un AVC aigu. À noter que ces patients ont été admis dans un centre régional de traitement des AVC situé dans le centre-ouest de l'Ontario (Canada). MÉTHODES: Nous avons comparé entre eux les délais de prise en charge de patients ayant bénéficié d'activateurs tissulaires du plasminogène par intraveineuse (tPA) et/ou d'une procédure de thrombectomie endovasculaire (TE) avant et après la mise sur pied de restrictions et l'imposition d'un état d'urgence sanitaire dans notre région (17 mars 2020). RÉSULTATS: Après la mise sur pied de ces restrictions, nous avons identifié, par rapport aux 12 mois précédent, une augmentation notable des délais médians entre l'arrivée à l'hôpital et un examen de tomodensitométrie dans le cas de patients bénéficiant de tPA (19 minutes, EI : 14­27 minutes contre 13 minutes, EI : 9­17 minutes ; p = 0,008) et/ou d'une procédure de TE (20 minutes, EI : 15­33 minutes contre 11 minutes, EI : 5­20 minutes ; p = 0,035). Pour ce qui est des patients bénéficiant de tPA, nous avons également observé une augmentation importante (p = 0,005) des délais médians entre leur arrivée à l'hôpital et l'injection d'un traitement (61 minutes, EI : 46­72 minutes contre 37 minutes, EI : 30­50 minutes). Enfin, dans le premier mois et demi suivant la mise sur pied des restrictions régionales et institutionnelles attribuables à la pandémie de COVID-19, aucun délai supplémentaire entre l'apparition des premiers symptômes d'un AVC et l'arrivée à l'hôpital n'a été remarqué pour des patients bénéficiant de tPA et/ou d'une procédure de TE. CONCLUSION: En somme, nous avons détecté une augmentation de nos délais de traitement dans le cas de patients victimes d'un AVC aigu ayant bénéficié de tPA et/ou d'une procédure de TE. Cela peut être attribué à une augmentation des délais de présentation à l'hôpital mais aussi à des délais dans l'obtention d'images de tomodensitométrie pour des patients traités avec des tPA et une procédure de TE, sans compter des délais accrus pour bénéficier d'un traitement de tPA.

Atrial Cardiopathy and Nonstenosing Large Artery Plaque in Patients With Embolic Stroke of Undetermined Source.

Background and Purpose- Atrial cardiopathy and atherosclerotic plaque are two potential mechanisms underlying embolic strokes of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. A better understanding of their association may inform targeted secondary prevention strategies. Methods- We examined the association between atrial cardiopathy and atherosclerotic plaque in the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), which enrolled 7213 patients with recent ESUS during 2014 to 2017. For this analysis, we included patients with data on left atrial dimension, location of brain infarction, and cervical large artery plaque. The variables of primary interest were left atrial diameter and cervical plaque ipsilateral to brain infarction. Secondary markers of atrial cardiopathy were premature atrial contractions on Holter monitoring and newly diagnosed atrial fibrillation. For descriptive purposes, left atrial enlargement was defined as ≥4.7 cm. Multivariable logistic regression was used to examine the association between atrial cardiopathy markers and ipsilateral plaque after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, current smoking, and hyperlipidemia. Results- Among 3983 eligible patients, 235 (5.9%) had left atrial enlargement, 939 (23.6%) had ipsilateral plaque, and 94 (2.4%) had both. Shared risk factors for left atrial enlargement and ipsilateral plaque were male sex, white race, hypertension, tobacco use, and coronary artery disease. Despite shared risk factors, increasing left atrial dimension was not associated with ipsilateral plaque after adjustment for covariates (odds ratio per cm, 1.1 [95% CI, 1.0-1.2]; P=0.08). We found no consistent associations between secondary markers of atrial cardiopathy and ipsilateral plaque. Conclusions- In a large population of patients with ESUS, we did not observe a notable association between atrial cardiopathy and atherosclerotic plaque, and few patients had both conditions. These findings suggest that atrial cardiopathy and atherosclerotic plaque may be distinct, nonoverlapping risk factors for stroke among ESUS patients.

Intracranial and systemic atherosclerosis in the NAVIGATE ESUS trial: Recurrent stroke risk and response to antithrombotic therapy.

BACKGROUND: Non-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis. METHODS: Exploratory analysis of the international NAVIGATE ESUS randomized trial comparing rivaroxaban 15mg daily with aspirin 100mg daily in 7213 patients with recent ESUS. Among participants with results of intracranial arterial imaging with either computed tomographic angiography (CTA) or magnetic resonance angiography (MRA), the frequency and predictors of non-stenotic intracranial and systemic atherosclerosis and responses to antithrombotic therapy were assessed. RESULTS: Among 4723 participants with available intracranial CTA or MRA results (65% of the trial cohort), the prevalence of intracranial atherosclerosis was 16% (n=739). Patient features independently associated with intracranial atherosclerosis included East Asian region (odds ratio 2.7, 95%CI 2.2,3.3) and cervical carotid plaque (odds ratio 2.3, 95%CI 1.9,2.7), among others. The rate of recurrent ischemic stroke averaged 4.8%/year among those with intracranial atherosclerosis vs. 5.0.%/year for those without (HR 0.95, 95%CI 0.65, 1.4). Among those with intracranial atherosclerosis, the recurrent ischemic stroke rate was higher if assigned to rivaroxaban (5.8%/year) vs. aspirin (3.7%/year), but the difference was not statistically significant (HR 1.6, 95%CI 0.78, 3.3). There was trend for the effect of antithrombotic treatments to be different according to the presence or absence of intracranial atherosclerosis (pinteraction=0.09). Among participants with evidence of systemic atherosclerosis by either history or imaging (n=3820), recurrent ischemic stroke rates were similar among those assigned to rivaroxaban (5.5%/year) vs. aspirin (4.9%/year)(HR 1.1, 95%CI 0.84, 1.5). CONCLUSIONS: East Asia region was the strongest factor associated with intracranial atherosclerosis. There were no statistically significant differences between rivaroxaban and aspirin prophylaxis for recurrent ischemic stroke in patients with non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.

Predictors of Recurrent Ischemic Stroke in Patients with Embolic Strokes of Undetermined Source and Effects of Rivaroxaban Versus Aspirin According to Risk Status: The NAVIGATE ESUS Trial.

BACKGROUND: Embolic stroke of undetermined source (ESUS) identifies patients with cryptogenic ischemic stroke presumed due to embolism from several unidentified sources. Among patients with recent ESUS, we sought to determine independent predictors of recurrent ischemic stroke during treatment with aspirin or rivaroxaban and to assess the relative effects of these treatments according to risk. METHODS: Exploratory analyses of 7213 participants in the NAVIGATE ESUS international trial who were randomized to aspirin 100 mg/day or rivaroxaban 15 mg/day and followed for a median of 11 months, during which time there were 309 first recurrent ischemic strokes (4.6% per year). Baseline features were correlated with recurrent stroke by multivariate analysis. RESULTS: The 7 independent predictors of recurrent stroke were stroke or transient ischemic attack (TIA) prior to the qualifying stroke (hazard ratio [HR] 2.03 95% confidence internal [CI] 1.58-2.60), current tobacco user (HR 1.62, 95% CI 1.24-2.12), age (HR 1.02 per year increase, 95%CI 1.01-1.03), diabetes (HR 1.28, 95% CI 1.01-1.64), multiple acute infarcts on neuroimaging (HR 1.49, 95% CI 1.09-2.02), aspirin use prior to qualifying stroke (HR 1.34, 95% CI 1.02-1.70), and time from qualifying stroke to randomization (HR .98, 95% CI .97-.99). The rate of recurrent stroke rate was 2.6% per year for participants without any of these risk factors, and increased by an average of 45% for each independent predictor (P < .001). There were no significant interactions between treatment effects and independent stroke predictors or stroke risk status. CONCLUSIONS: In this large cohort of ESUS patients, several features including prior stroke or TIA, advanced age, current tobacco user, multiple acute infarcts on neuroimaging, and diabetes independently identified those with an increased risk of ischemic stroke recurrence. The relative effects of rivaroxaban and aspirin were similar across the spectrum of independent stroke predictors and recurrent stroke risk status.

Stroke type and severity in patients with subclinical atrial fibrillation: An analysis from the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT).

BACKGROUND: The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) demonstrated that subclinical atrial fibrillation (SCAF) was associated with a 2.5-fold increased risk of stroke. However, the absolute stroke rate was only 1.7% per year and fewer than 20% patients with stroke had SCAF in the preceding 30 days. This raises the possibility that SCAF is merely a risk marker for stroke rather than the cause. Systematic characterization of stroke subtypes among patients with SCAF would help clarify this issue. METHODS: All ischemic strokes that occurred in the ASSERT trial were blindly adjudicated by stroke neurologists, classified as cortical versus subcortical, and subtyped using modified TOAST criteria. Stroke severity was measured using the modified Rankin Score. RESULTS: Of the 44 participants who had an ischemic stroke, 14 had SCAF before stroke. Among patients with SCAF who had stroke, 57% of strokes (n = 8) were judged to be cardioembolic, 36% to be lacunar (n = 5), and 7% (n = 1) to be large artery disease. However, of 5 patients who had SCAF detected within 30 days before their index stroke, 4 patients had a cardioembolic stroke. The average duration of SCAF in these 4 patients was 6.0 ± 6.1 h/d. The modified Rankin score at 30 days was similar between patients with (2.7 ± 2.3) and without SCAF (2.3 ± 2.0; P = .68). CONCLUSIONS: In patients with SCAF and stroke, SCAF seems probably causal in many cases; however, in more than 40%, it seems to be acting only as a risk marker.

Embolic Stroke of Undetermined Source: A Systematic Review and Clinical Update.

BACKGROUND AND PURPOSE: Embolic stroke of undetermined source (ESUS) designates patients with nonlacunar cryptogenic ischemic strokes in whom embolism is the likely stroke mechanism. It has been hypothesized that anticoagulation is more efficacious than antiplatelet therapy for secondary stroke prevention in ESUS patients. We review available information about ESUS. METHODS: Systematic literature review to assess the frequency of ESUS, patient features, and prognosis using PubMed from 2014 to present, unrestricted by language. RESULTS: On the basis of 9 studies, the reported frequency of ESUS ranged from 9% to 25% of ischemic strokes, averaging 17%. From 8 studies involving 2045 ESUS patients, the mean age was 65 years and 42% were women; the mean NIH stroke score was 5 at stroke onset (4 studies, 1772 ESUS patients). Most (86%) ESUS patients were treated with antiplatelet therapy during follow-up, with the annualized recurrent stroke rate averaging 4.5% per year during a mean follow-up of 2.7 years (5 studies, 1605 ESUS patients). CONCLUSIONS: ESUS comprises about 1 ischemic stroke in 6. Patients with ischemic stroke meeting criteria for ESUS were relatively young compared with other ischemic stroke subtypes and had, on average, minor strokes, consistent with small emboli. Retrospective methods of available studies limit confidence in stroke recurrence rates but support a substantial (>4% per year) rate of stroke recurrence during (mostly) antiplatelet therapy. There is an important need to define better antithrombotic prophylaxis for this frequently occurring subtype of ischemic stroke.

Global Survey of the Frequency of Atrial Fibrillation-Associated Stroke: Embolic Stroke of Undetermined Source Global Registry.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is increasingly recognized as the single most important cause of disabling ischemic stroke in the elderly. We undertook an international survey to characterize the frequency of AF-associated stroke, methods of AF detection, and patient features. METHODS: Consecutive patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19 stroke research centers in 19 different countries. Data were analyzed by global regions and World Bank income levels. RESULTS: Of 2144 patients with ischemic stroke, 590 (28%; 95% confidence interval, 25.6-29.5) had AF-associated stroke, with highest frequencies in North America (35%) and Europe (33%) and lowest in Latin America (17%). Most had a history of AF before stroke (15%) or newly detected AF on electrocardiography (10%); only 2% of patients with ischemic stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The mean age and 30-day mortality rate of patients with AF-associated stroke (75 years; SD, 11.5 years; 10%; 95% confidence interval, 7.6-12.6, respectively) were substantially higher than those of patients without AF (64 years; SD, 15.58 years; 4%; 95% confidence interval, 3.3-5.4; P<0.001 for both comparisons). There was a strong positive correlation between the mean age and the frequency of AF (r=0.76; P=0.0002). CONCLUSIONS: This cross-sectional global sample of patients with recent ischemic stroke shows a substantial frequency of AF-associated stroke throughout the world in proportion to the mean age of the stroke population. Most AF is identified by history or electrocardiography; the yield of conventional short-duration cardiac rhythm monitoring is relatively low. Patients with AF-associated stroke were typically elderly (>75 years old) and more often women.

Chronic ischemic lesions and presence of patent foramen ovale in young adults with embolic stroke of undetermined source: Results of the young ESUS patient registry.

BACKGROUND: Chronic ischemic lesions (CILs) are frequent findings in patients with acute ischemic stroke, but their phenotypes and relevance in young adults with embolic stroke of undetermined source (Y-ESUS) remains uncertain. We aimed to compare Y-ESUS patients with CIL to those without CIL and assessed the association of CIL and its phenotypes with the presence of patent foramen ovale (PFO). METHODS: This prospective longitudinal, multicenter cohort study enrolled consecutive patients 50 years and younger with ESUS from October 2017 to October 2019 in 41 stroke research centers in 13 countries. Local investigators adjudicated presence and phenotypes of CIL on routine brain imaging (either magnetic resonance imaging (MRI) or computed tomography (CT)). RESULTS: Overall, 535 patients were enrolled (mean age = 40.4 (standard deviation (SD) = 7.3) years, 238 (44%) female). CILs were present in 76/534 (14.2%) patients with a median count CIL count of 1.0 (interquartile range (IQR) = 1-2), 42/76 (55%) had at least one cortical phenotype and 38/76 (50%) at least one non-cortical phenotype. Y-ESUS with CIL were less often female (32% vs 47% in non-CIL Y-ESUS), were older (mean 43 vs 40 years), had more often hypertension (42% vs 19%), diabetes (17% vs 7%), and hyperlipidemia (34% vs 18%). CIL Y-ESUS were independently associated with lower stroke recurrence (relative risk (RR) = 0.17 (0.05-0.61)). In Y-ESUS with PFO, CILs were less frequent in probable pathogenic PFO than with probable non-pathogenic PFO (6.1% vs 30% p< 0.001). CONCLUSION: One in seven Y-ESUS patients has additional CIL. CILs were associated with several vascular risk factors, lower probability of a pathogenic PFO, and lower stroke recurrence.

Transcranial Doppler ultrasound to evaluate the risk of hyperperfusion after endovascular stroke thrombectomy.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) has been reported in up to 50% of acute ischemic stroke (AIS) patients with a large vessel occlusion (LVO) treated with endovascular thrombectomy (EVT). HT may be driven by postrecanalization hyperperfusion injury and is independently associated with worse functional outcomes. Strategies to identify patients at risk for HT may assist in developing preventive therapies. METHODS: We prospectively included adult AIS patients with an anterior circulation LVO achieving successful recanalization after EVT. Consenting participants received transcranial Doppler ultrasound (TCD) within 18 hours of procedure completion. We compared flow velocities according to the presence of HT on the computed tomography scan performed within the first 24±12 hours from the end of EVT. We also evaluated the association of flow velocities with systemic blood pressure (BP) readings at the time of insonation. RESULTS: A total of 48 patients consented to participate in the study. Six (12%) were excluded due to the absence of temporal windows. HT was detected in 20 participants (48%). Those with HT had higher peak systolic velocities on the middle cerebral arteries compared to those without HT for both the symptomatic (107±42 vs. 82±25 cm/second, p = .024) and asymptomatic (97±21 vs. 81±25 cm/second, p = .040) sides. No correlation of flow velocities on either the symptomatic or asymptomatic side and BP measurements at the time of insonation was detected. CONCLUSION: TCD can identify patients at risk of HT following successful EVT. TCD could serve as an inexpensive ancillary test to guide participant selection for clinical trials targeting postprocedural reperfusion injury.

Are Factor Xa Inhibitors Efficacious for Ischemic Stroke Prevention in Patients Without Atrial Fibrillation? Evidence From Randomized Clinical Trials.

BACKGROUND: Clinical trials provide conflicting evidence regarding oral factor Xa inhibitors for prevention of ischemic stroke in patients without a history of atrial fibrillation (AF). METHODS: We performed a critical appraisal of randomized clinical trials that tested oral factor Xa inhibitors in patients without AF that reported ischemic stroke. RESULTS: Considering the 11 trials that reported > 10 ischemic strokes during follow-up (97,578 participants, 1195 ischemic strokes), 1 tested apixaban (57 strokes), 1 betrixaban (52 strokes), and 9 rivaroxaban (1086 strokes). In 7 trials with placebo comparisons, numerically fewer ischemic strokes occurred among those assigned factor Xa inhibitors in 7 of 8 randomized comparisons (range of hazard ratios [HRs], 0.89-0.51), including statistically significant reductions in 2 trials that compared rivaroxaban 2.5 mg twice daily vs placebo on a background of aspirin in patients with cardiovascular disease, COMPASS (HR, 0.51; 95% confidence interval [CI], 0.38-0.68) and COMMANDER-HF (HR, 0.64; 95% CI, 0.43-0.95). Compared with aspirin in 4 trials, oral factor Xa inhibitors were associated with fewer ischemic strokes in 2, with statistically significant reduction in 1 (rivaroxaban 5 mg twice daily in COMPASS; HR, 0.69; 95% CI, 0.53-0.90). Major bleeding was increased by oral factor Xa inhibitors in all 7 placebo-controlled trials (HR range, 1.42-4.08), with statistically significant increases reported in 5 trials, and in all 4 aspirin-controlled trials (all statistically significant increases; HR range, 1.52-2.72). CONCLUSIONS: Aggregate evidence on the basis of placebo comparisons from randomized trials supports the potential for oral factor Xa inhibitors to reduce ischemic stroke in patients without AF, but major bleeding is increased.