Extended Computed Tomography Angiography for the Successful Diagnosis of Cardioaortic Thrombus in Acute Ischemic Stroke and TIA: Study Protocol for a Randomized Controlled Trial.

INTRODUCTION: Cardiac imaging is one of the main components of the etiological investigation of ischemic strokes. However, basic and advanced cardiac imaging remain underused in most stroke centers globally. Computed tomography angiography (CTA) of the supra-aortic and intracranial arteries is the most frequent imaging modality applied during the evaluation of patients with acute ischemic stroke to identify the presence of a large vessel occlusion. Recent evidence from retrospective observational studies has shown a high detection of cardiac thrombi, ranging from 6.6 to 17.4%, by extending a CTA a few cm below the carina to capture cardiac images. However, this approach has never been prospectively compared against usual care in a randomized controlled trial. The Extended Computed Tomography Angiography for the Successful Screening of Cardioaortic Thrombus in Acute Ischemic Stroke and TIA (DAYLIGHT) prospective, randomized, controlled trial evaluates whether an extended CTA (eCTA) + standard-of-care stroke workup results in higher detection rates of cardiac and aortic source of embolism compared to standard-of-care CTA (sCTA) + standard-of-care stroke workup. METHODS: DAYLIGHT is a single-center, prospective, randomized, open-blinded endpoint trial, aiming to recruit 830 patients with suspected acute ischemic stroke or transient ischemic attack (TIA) being assessed under acute code stroke at the emergency department or at a dedicated urgent stroke prevention clinic. Patients are randomized 1:1 to eCTA versus sCTA. The eCTA expands image acquisition caudally, 6 cm below the carina. All patients receive standard-of-care cardiac imaging and diagnostic stroke workup. The primary efficacy endpoint is the diagnosis of a cardioaortic thrombus after at least 30 days of follow-up. The primary safety endpoint is door-to-CTA completion time. The diagnosis of a qualifying ischemic stroke or TIA is independently adjudicated by a stroke neurologist, blinded to the study arm allocation. Patients without an adjudicated ischemic stroke or TIA are excluded from the analysis. The primary outcome events are adjudicated by a board-certified radiologist with subspecialty training in cardiothoracic radiology and a cardiologist with formal training in cardiac imaging. The primary analysis is performed according to the modified intention-to-diagnose principle and without adjustment by logistic regression models. Results are presented with odds ratios and 95% confidence intervals. CONCLUSION: The DAYLIGHT trial will provide evidence on whether extending a CTA to include the heart results in an increased detection of cardioaortic thrombi compared to standard-of-care stroke workup.

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.

Differences between Atrial Fibrillation Detected before and after Stroke and TIA: A Systematic Review and Meta-Analysis.

BACKGROUND: Preliminary evidence suggests that patients with atrial fibrillation (AF) detected after stroke (AFDAS) may have a lower prevalence of cardiovascular comorbidities and lower risk of stroke recurrence than AF known before stroke (KAF). OBJECTIVE: We performed a systematic search and meta-analysis to compare the characteristics of AFDAS and KAF. METHODS: We searched PubMed, Scopus, and EMBASE for articles reporting differences between AFDAS and KAF until June 30, 2021. We performed random- or fixed-effects meta-analyses to evaluate differences between AFDAS and KAF in demographic factors, vascular risk factors, prevalent vascular comorbidities, structural heart disease, stroke severity, insular cortex involvement, stroke recurrence, and death. RESULTS: In 21 studies including 22,566 patients with ischemic stroke or transient ischemic attack, the prevalence of coronary artery disease, congestive heart failure, prior myocardial infarction, and a history of cerebrovascular events was significantly lower in AFDAS than KAF. Left atrial size was smaller, and left ventricular ejection fraction was higher in AFDAS than KAF. The risk of recurrent stroke was 26% lower in AFDAS than in KAF. There were no differences in age, sex, stroke severity, or death rates between AFDAS and KAF. There were not enough studies to report differences in insular cortex involvement between AF types. CONCLUSIONS: We found significant differences in the prevalence of vascular comorbidities, structural heart disease, and stroke recurrence rates between AFDAS and KAF, suggesting that they constitute different clinical entities within the AF spectrum. PROSPERO registration number is CRD42020202622.

COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals.

We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London's regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.

Atrial fibrillation diagnosed after stroke and dementia risk: cohort study of first-ever ischaemic stroke patients aged 65 or older.

AIMS: Atrial fibrillation (AF) is a risk factor for dementia among ischaemic stroke patients in whom the AF was known before the stroke (KAF). Atrial fibrillation detected after stroke (AFDAS) has a different profile compared to KAF, including less frequent cardiovascular comorbidities and lower CHA2-DS2-VASC scores. Currently, it is unknown if AFDAS is also associated with increased dementia risk. We assessed the association between AFDAS and the incident risk of dementia. We also evaluated whether the use of oral anticoagulants (OAC) was associated with lower dementia risk among AFDAS patients. METHODS AND RESULTS: In this cohort study, we classified 9791 first-ever ischaemic stroke patients from the Ontario Stroke Registry into four groups: (i) No AF, (ii) KAF, (iii) Inpatient AFDAS (diagnosed during admission), and (iv) Outpatient AFDAS (diagnosed after discharge). We used multivariable Cox proportional models to estimate hazard ratios (HR) for the association between AFDAS and incident dementia risk. Dementia was determined through administrative datasets based on previously validated algorithms. In adjusted analyses, the dementia risk was higher for inpatient AFDAS [HR 1.78, 95% confidence interval (CI) 1.51-2.10] and outpatient AFDAS (HR 1.74, 95% CI 1.47-2.05) relative to no AF. Oral anticoagulants use was associated with lower dementia risk among patients with inpatient AFDAS (HR 0.58, 95% CI 0.43-0.79) and outpatient AFDAS (HR 0.60, 95% CI 0.43-0.83). CONCLUSION: Atrial fibrillation detected after stroke was independently associated with higher risk of dementia relative to no AF. Among patients with AFDAS, the use of OACs was associated with lower dementia risk.

Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE): A Translational, Integrated, and Transdisciplinary Approach.

BACKGROUND: It has been hypothesized that ischemic stroke can cause atrial fibrillation. By elucidating the mechanisms of neurogenically mediated paroxysmal atrial fibrillation, novel therapeutic strategies could be developed to prevent atrial fibrillation occurrence and perpetuation after stroke. This could result in fewer recurrent strokes and deaths, a reduction or delay in dementia onset, and in the lessening of the functional, structural, and metabolic consequences of atrial fibrillation on the heart. METHODS: The Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE) study is an investigator-driven, translational, integrated, and transdisciplinary initiative. It comprises 3 complementary research streams that focus on atrial fibrillation detected after stroke: experimental, clinical, and epidemiological. The experimental stream will assess pre- and poststroke electrocardiographic, autonomic, anatomic (brain and heart pathology), and inflammatory trajectories in an animal model of selective insular cortex ischemic stroke. The clinical stream will prospectively investigate autonomic, inflammatory, and neurocognitive changes among patients diagnosed with atrial fibrillation detected after stroke by employing comprehensive and validated instruments. The epidemiological stream will focus on the demographics, clinical characteristics, and outcomes of atrial fibrillation detected after stroke at the population level by means of the Ontario Stroke Registry, a prospective clinical database that comprises over 23,000 patients with ischemic stroke. CONCLUSIONS: PARADISE is a translational research initiative comprising experimental, clinical, and epidemiological research aimed at characterizing clinical features, the pathophysiology, and outcomes of neurogenic atrial fibrillation detected after stroke.

Visual Aids for Improving Patient Decision Making in Severe Symptomatic Carotid Stenosis.

BACKGROUND: Because of the large amount of information to process and the limited time of a clinical consult, choosing between carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS) can be confusing for patients with severe symptomatic internal carotid stenosis (ICA). GOAL: We aim to develop a visual aid tool to help clinicians and patients in the decision-making process of selecting between CEA and CAS. MATERIALS AND METHODS: Based on pooled analysis from randomized controlled trials including patients with symptomatic and severe ICA (SSICA), we generated visual plots comparing CEA with CAS for 3 prespecified postprocedural time points: (1) any stroke or death at 4 months, and (2) any stroke or death in the first 30 days and ipsilateral stroke thereafter at 5 years and (3) at 10 years. RESULTS: A total of 4574 participants (2393 assigned to CAS, and 2361 to CEA) were included in the analyses. For every 100 patients with SSICA, 6 would develop any stroke or death in the CEA group compared with 9 undergoing CAS at 4 months (hazard ratio [HR] 1.53; 95%CI 1.20-1.95). At 5 years, 7 patients in the CEA group would develop any periprocedural stroke or death and ipsilateral stroke thereafter versus 12 undergoing CAS (HR 1.72; 95%CI 1.24-2.39), compared with 10 patients in the CEA and 13 in the CAS groups at 10 years (HR 1.17; 95%CI 0.82-1.66). CONCLUSION: Visual aids presented in this study could potentially help patients with severe symptomatic internal carotid stenosis to better weigh the risks and benefits of CEA versus CAS as a function of time, allowing for the prioritization of personal preferences, and should be prospectively assessed.

Do elderly patients call 911 when presented with clinical scenarios suggestive of acute stroke? A cross-sectional study.

BACKGROUND AND PURPOSE: Among patients with acute stroke symptoms, delay in hospital admission is the main obstacle for the use of thrombolytic therapy and other interventions associated with decreased mortality and disability. The primary aim of this study was to assess whether an elderly clinical population correctly endorsed the response to call for emergency services when presented with signs and symptoms of stroke using a standardized questionnaire. METHODS: We performed a cross-sectional study among elderly out-patients (≥60 years) in Buenos Aires, Argentina randomly recruited from a government funded health clinic. The correct endorsement of intention to call 911 was assessed with the Stroke Action Test and the cut-off point was set at ≥75%. Knowledge of stroke and clinical and socio-demographic indicators were also collected and evaluated as predictors of correct endorsement using logistic regression. RESULTS: Among 367 elderly adults, 14% correctly endorsed intention to call 911. Presented with the most typical signs and symptoms, only 65% reported that they would call an ambulance. Amaurosis Fugax was the symptom for which was called the least (15%). On average, the correct response was chosen only 37% of the time. Compared to lower levels of education, higher levels were associated to correctly endorsed intention to call 911 (secondary School adjusted OR 3.53, 95% CI 1.59-7.86 and Tertiary/University adjusted OR 3.04, 95% CI 1.12-8.21). CONCLUSIONS: These results suggest the need to provide interventions that are specifically designed to increase awareness of potential stroke signs and symptoms and appropriate subsequent clinical actions.

Study protocol for a systematic review and meta-analysis of comorbidities and stroke characteristics associated with troponin elevation after acute stroke.

INTRODUCTION: It is unknown which comorbidities and stroke characteristics are associated with elevated cardiac troponin (cTn) levels after stroke. The main objective of this systematic review and meta-analysis is to assess the association of elevated cTn with preexisting cardiovascular comorbidities (eg, coronary artery disease, heart failure and structural heart disease), specific stroke characteristics (eg, infarct/haemorrhage size, stroke severity, insular cortex involvement) and renal failure after ischaemic stroke (IS) or intracranial haemorrhage (ICH). The secondary objective is to evaluate the association of elevated cTn with stroke recurrence and death. METHODS AND ANALYSIS: We will include all cross-sectional, case-control, cohort studies and clinical trials involving IS and ICH adult patients (≥18 years), published between 1 January 1990 and 31 December 2020 in English or Spanish, reporting the proportion with elevated cTn. We will search PubMed, EMBASE and Web of Science by applying predefined search terms. Two reviewers will independently screen titles and abstracts, retrieve full texts, extract the data in a predesigned form, and assess the risk of bias. We will apply random-effects or fixed-effects meta-analyses to estimate the association between cardiovascular comorbidities, stroke characteristics and renal failure with cTn elevation. We will report results as risk ratios or ORs. We will perform sensitivity analyses for subtypes of cTn (cTn-I and cTn-T), regular versus high-sensitivity assays, and type of stroke (IS vs ICH). We will estimate heterogeneity by using t2Q and I2 measures. We will use funnel plots, Rosenthal's Fail-Safe N, Duval and Tweedie's trim and fill procedure, and Egger's regression intercept to assess publication bias. ETHICS AND DISSEMINATION: This review will be based on published data and does therefore not require ethical clearance. The results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020203126.

Phenotypes of atrial fibrillation diagnosed before-versus-after ischaemic stroke and TIA: study protocol for a systematic review and meta-analysis.

INTRODUCTION: The underlying pathophysiology of atrial fibrillation (AF) detected after stroke (AFDAS) is relatively unknown. Preliminary evidence suggests AFDAS has a lower prevalence of cardiovascular comorbidities and higher incidence of insular cortex involvement than AF known to exist before stroke occurrence (KAF). This favours a neurogenic AF substrate (autonomic dysregulation) in which the presence of underlying heart disease is not necessary for AF to occur. The main objective of this systematic review and meta-analysis is to compare the prevalence of cardiovascular comorbidities and echocardiographic abnormalities in patients with AFDAS, KAF and no AF (NAF). Secondary objectives are to compare the proportion with insular cortex involvement, stroke recurrence and death in the three rhythm groups. METHODS AND ANALYSIS: We will perform a systematic review including cross-sectional, case-control, cohort studies and clinical trials involving ≥18 years patients, with ischaemic stroke or transient ischaemic attack published between inception and 31 December 2020 in any language, and reporting the proportion of patients with AFDAS, KAF and NAF. We will search PubMed, EMBASE and Scopus by applying predefined search terms. Two reviewers will independently screen titles and abstracts and retrieve full texts, extract data in a predesigned form, and assess the risk of bias. We will perform a meta-analysis of all included studies and we will report the results of the main outcome as proportions. We will report results of secondary outcomes as risk ORs. We will estimate heterogeneity across studies by using t2, Q and I2 measures. We will use funnel plots, Rosenthal's Fail-Safe N and Egger's regression intercept to assess publication bias. ETHICS AND DISSEMINATION: This study will be based on published data and does therefore not require ethical clearance. The results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42020202622.

Stroke risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases.

OBJECTIVES: To investigate the hypothesis that strokes occurring in patients with coronavirus disease 2019 (COVID-19) have distinctive features, we investigated stroke risk, clinical phenotypes, and outcomes in this population. METHODS: We performed a systematic search resulting in 10 studies reporting stroke frequency among patients with COVID-19, which were pooled with 1 unpublished series from Canada. We applied random-effects meta-analyses to estimate the proportion of stroke among COVID-19. We performed an additional systematic search for cases series of stroke in patients with COVID-19 (n = 125), and we pooled these data with 35 unpublished cases from Canada, the United States, and Iran. We analyzed clinical characteristics and in-hospital mortality stratified into age groups (<50, 50-70, >70 years). We applied cluster analyses to identify specific clinical phenotypes and their relationship with death. RESULTS: The proportions of patients with COVID-19 with stroke (1.8%, 95% confidence interval [CI] 0.9%-3.7%) and in-hospital mortality (34.4%, 95% CI 27.2%-42.4%) were exceedingly high. Mortality was 67% lower in patients <50 years of age relative to those >70 years of age (odds ratio [OR] 0.33, 95% CI 0.12-0.94, p = 0.039). Large vessel occlusion was twice as frequent (46.9%) as previously reported and was high across all age groups, even in the absence of risk factors or comorbid conditions. A clinical phenotype characterized by older age, a higher burden of comorbid conditions, and severe COVID-19 respiratory symptoms was associated with the highest in-hospital mortality (58.6%) and a 3 times higher risk of death than the rest of the cohort (OR 3.52, 95% CI 1.53-8.09, p = 0.003). CONCLUSIONS: Stroke is relatively frequent among patients with COVID-19 and has devastating consequences across all ages. The interplay of older age, comorbid conditions, and severity of COVID-19 respiratory symptoms is associated with an extremely elevated mortality.

Diagnosis and management of carotid free-floating thrombus: A systematic literature review.

BACKGROUND: There is no consensus regarding the management of carotid free-floating thrombi in patients with acute ischemic stroke and transient ischemic attack. AIMS: This systematic review aims to (1) describe the current imaging methods for diagnosis of carotid free-floating thrombi and its associated risk factors, (2) estimate the proportion of carotid free-floating thrombi diagnosed in stroke patients, (3) estimate the proportion of carotid free-floating thrombi patients treated medically and surgically, and (4) evaluate 30-day outcomes. METHODS: We searched MEDLINE, EMBASE, and manually for references reporting carotid free-floating thrombi from 1960 until June 2017. We estimated the frequency of carotid free-floating thrombi and evaluated 30-day outcomes using Cox regression. We defined the timing of surgical intervention as early (less than 72 h) and delayed (more or equal to 72 h). SUMMARY OF REVIEW: We retrieved 525 carotid free-floating thrombi cases from 58 case series and 83 case reports. Carotid free-floating thrombi were present in 1.53% of stroke patients. Carotid free-floating thrombi diagnosis was made by digital subtraction angiography (38.1%), carotid duplex ultrasound (29.5%), and computed tomography angiography (29.5%). The 30-day risk of transient ischemic attack, silent brain ischemia, any stroke or death was 17.1%. In multivariate analyses, there were no differences in outcome for any anticoagulation regime or timing of revascularization procedure. CONCLUSIONS: The diagnosis of carotid free-floating thrombi is more common due to the increased use of early noninvasive vascular imaging in transient ischemic attack and stroke. It poses a high short-term risk of stroke and death, but there is as yet no established treatment. The low quality of evidence in the carotid free-floating thrombi literature limits the interpretation of our results and warrants a large-scale prospective cohort study in carotid free-floating thrombi.

Dystextia and dystypia as modern stroke symptoms: A case series and literature review.

Stroke recognition remains a barrier to care in cerebrovascular disease. Despite an increasing reliance on digital communication, the clinical utility of deficits relating to technology remains unexplored. Dystextia and dystypia, terms used to refer to impairments in texting and typing, respectively, may serve as modern indicators of stroke and provide information regarding stroke duration, symptomatology, and etiological diagnosis. In this report, we describe two cases in which dystextia and dystypia were involved in stroke presentation and perform a literature review surrounding these signs. Four out of six cases identified on literature review in which stroke etiology was described, in addition to both of our presented cases, were found to be embolic in origin. While shared lesion topography involving the left posterior upper insular cortex and superior longitudinal fasciculus was identified in our cases, additional research is required for proper symptom-lesion mapping. Further characterization of dystextia and dystypia, and their corresponding localization, may assist in stroke diagnosis and guide investigations.

Atrial fibrillation detected after stroke is related to a low risk of ischemic stroke recurrence.

OBJECTIVE: To compare the risk of 1-year ischemic stroke recurrence between atrial fibrillation (AF) diagnosed after stroke (AFDAS) and sinus rhythm (SR) and investigate whether underlying heart disease is as frequent in AFDAS as it is in AF known before stroke (KAF). METHODS: In this retrospective cohort study, we included all ischemic stroke patients admitted to institutions participating in the Ontario Stroke Registry from July 1, 2003, to March 31, 2013. Based on heart rhythm assessed during admission, we classified patients as AFDAS, KAF, or SR. We modeled the relationship between heart rhythm groups and 1-year ischemic stroke recurrence by using Cox regression adjusted for multiple covariates (e.g., oral anticoagulants). We compared the prevalence of coronary artery disease, myocardial infarction, and heart failure among the 3 groups. RESULTS: Among 23,376 ischemic stroke patients, 15,885 had SR, 587 AFDAS, and 6,904 KAF. At 1 year, 39 (6.6%) patients with AFDAS, 661 (9.6%) with KAF, and 1,269 (8.0%) with SR had recurrent ischemic strokes (p = 0.0001). AFDAS-related ischemic stroke recurrence adjusted risk was not different from that of SR (hazard ratio 0.90 [95% confidence interval 0.63, 1.30]; p = 0.57). Prevalence of coronary artery disease (18.2% vs 34.7%; p < 0.0001), myocardial infarction (11.6% vs 20.5%; p < 0.0001), and heart failure (5.5% vs 16.8%; p < 0.0001) were lower in AFDAS relative to KAF. CONCLUSIONS: The lack of difference in 1-year ischemic stroke recurrence between AFDAS and SR and the lower prevalence of heart disease in AFDAS compared to KAF suggest that the underlying pathophysiology of AFDAS may differ from that of KAF.