Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Clinical validation of in-hospital stroke diagnosis.

OBJECTIVE: In-hospital stroke cases occur during hospitalization for another diagnosis and reflect a clinically distinct cohort from community-onset stroke. The objective was to validate the diagnostic accuracy of in-hospital stroke identification in stroke audit data at a large teaching hospital. METHODS: A retrospective clinical validation of in-hospital stroke diagnoses from two linked data sources was completed for a 2-year period from January 1st 2020 to December 31st 2021. The linked data sources include the Hospital Inpatient Enquiry system which assigns coded stroke diagnoses at discharge and/or the local stroke audit coordinators who work clinically in stroke teams and input additional specific clinical data. Diagnostic sensitivity, specificity and the level of agreement using an unweighted Cohen's Kappa were calculated. RESULTS: There were 597 strokes admitted during the 2-year period. The median age was 72 years and 55% occurred in males. In total, 88 cases of in-hospital stroke were clinically validated yielding an in-hospital stroke rate of 15%. The clinical audit coordinator identified in-hospital stroke with higher sensitivity (86%; 95% CI 77%-93%) whereas the coding process was more specific at 96% (95% CI 85% to 99%). Levels of agreement with the clinically validated gold standard sample were moderate for the audit coordinator and coding process with κ = 0.57 and K = 0.42 respectively. When both data sources were combined the level of agreement was substantial (κ = 0.65; p < .000). CONCLUSIONS: Clinical validation studies are required to reinforce data quality within stroke registers. Combining clinical and administrative data sources improves diagnostic accuracy for in-hospital stroke identification.

Perspective: The Case for Acute Large Vessel Ischemic Stroke in COVID-19 Originating Within Thrombosed Pulmonary Venules.

The main burden of SARS-CoV-2 falls on the lungs but neurological manifestations, the most disabling of which are strokes and which correlate with disease severity, are common. We proffer a novel mechanism for acute COVID-19 stroke whereby pulmonary vein clots developing within the characteristic pulmonary intravascular thrombotic lesions can embolize to the brain. Appreciation of this mechanism requires an understanding of the tricompartmental model of lung parenchyma oxygenation (the alveolus, the bronchial artery, and the pulmonary artery), all of which are compromised in COVID-19. Of these 3 sources, the bronchial artery plays a crucial role in COVID-19 stroke because the unique collaterals from bronchial artery to pulmonary vein which exist under normal physiological conditions (and which maintain venous patency when the pulmonary artery is blocked by embolus) are occluded, thus leading to venular thrombosis in the presence of hypercoagulability. Dislodgement of clots from this source translocates the pathology to the brain and is a disease mechanism, formerly rare, which may account for many cases of large vessel occlusion stroke in COVID-19. This mechanism extends the concept of cardioembolic stroke from endocardium retrogradely into the pulmonary circulation with which the left cardiac chambers lie in direct continuity, and which is an accepted stroke mechanism under other circumstances such as lung lobectomy, where surgical ligation of the pulmonary vein creates a blind sac from which thrombi can embolize. The proposed model is supported by postmortem studies which have demonstrated venular thrombosis and by case reports of pulmonary vein thrombosis in COVID-19. This concept provides a more plausible cause for COVID-19 associated large vessel occlusion stroke than other putative mechanisms, such as cerebral endotheliitis, cytokine storm, and hypercoagulopathy, although it is acknowledged that the latter mechanism contributes to the genesis of pulmonary vein clots. Recognizing that extrapulmonary manifestations including stroke arise within thrombosed pulmonary veins is key to understanding of neurological manifestations of SARS-CoV-2 infection.

Atrial fibrillation and acceleration of frailty: findings from the Irish Longitudinal Study on Ageing.

INTRODUCTION: both atrial fibrillation (AF) and frailty are increasingly prevalent with age. Cross-sectional studies have suggested a relationship between AF and frailty, but longitudinal data are lacking. We explored if the presence of AF was associated with accelerated progression of frailty over 8 years in community-dwelling older adults. METHODS: a longitudinal retrospective case-control study was conducted using data from Waves 1 and 5 of the Irish Longitudinal Study on Ageing (TILDA). Participants with electrocardiographically detected AF at Wave 1 were matched to controls without AF (1:2) based on age and gender. Frailty was assessed using both the frailty phenotype (FP) and a 31-item frailty index (FI). Change in cases' and controls' FP and FI scores from Waves 1 to 5 were modelled using repeated measures analysis of variance (RM-ANOVA). RESULTS: one hundred eighteen TILDA participants with AF at Wave 1 were matched to 236 controls. By FP, participants with AF were not significantly more frail than controls at Wave 1 (P = 0.166) but were at Wave 5 (P = 0.011), and RM-ANOVA suggested that frailty progressed more in participants with AF between Waves 1 and 5 compared with controls (P = 0.033). By FI, participants with AF were significantly more frail at Wave 1 (P < 0.001) and 5 (P = 0.010), and RM-ANOVA did not show a difference in frailty progression between groups (P = 0.955). CONCLUSION: AF may drive the development of the FP. The FP is a pre-disability syndrome and hence may be better than the FI as a focus for disability prevention in adults with AF.

Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration.

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.

A Risk Score Including Carotid Plaque Inflammation and Stenosis Severity Improves Identification of Recurrent Stroke.

Background and Purpose- In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods- We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0-5) including 18F-fluorodeoxyglucose standardized uptake values (SUVmax <2 g/mL, 0 points; SUVmax 2-2.99 g/mL, 1 point; SUVmax 3-3.99 g/mL, 2 points; SUVmax ≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%-69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis. Results- In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score (P=0.002, C statistic 0.71 [95% CI, 0.56-0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2-4.5, P=0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9-5], P<0.001; C statistic 0.77 [95% CI, 0.67-0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58-12.93], P=0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46-0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66-0.97], P=0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39-5.39], P=0.004). Conclusions- The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.

Carotid Plaque Inflammation Imaged by 18F-Fluorodeoxyglucose Positron Emission Tomography and Risk of Early Recurrent Stroke.

Background and Purpose- Plaque inflammation contributes to stroke and coronary events. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identifies plaque inflammation-related metabolism. Almost no prospective data exist on the relationship of carotid 18F-FDG uptake and early recurrent stroke. Methods- We did a multicenter prospective cohort study BIOVASC (Biomarkers/Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease) of patients with carotid stenosis and recent stroke/transient ischemic attack with 90-day follow-up. On coregistered carotid 18F-FDG PET/computed tomography angiography, 18F-FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest slice. We then conducted a systematic review of similar studies and pooled unpublished individual-patient data with 2 highly similar independent studies (Dublin and Barcelona). We analyzed the association of SUVmax with all recurrent nonprocedural stroke (before and after PET) and with recurrent stroke after PET only. Results- In BIOVASC (n=109, 14 recurrent strokes), after adjustment (for age, sex, stenosis severity, antiplatelets, statins, diabetes mellitus, hypertension, and smoking), the hazard ratio for recurrent stroke per 1 g/mL SUVmax was 2.2 (CI, 1.1-4.5; P=0.025). Findings were consistent in the independent Dublin (n=52, hazard ratio, 2.2; CI, 1.1-4.3) and Barcelona studies (n=35, hazard ratio, 2.8; CI, 0.98-5.5). In the pooled cohort (n=196), 37 recurrent strokes occurred (29 before and 8 after PET). Plaque SUVmax was higher in patients with all recurrence ( P<0.0001) and post-PET recurrence ( P=0.009). The fully adjusted hazard ratio of any recurrent stroke was 2.19 (CI, 1.41-3.39; P<0.001) and for post-PET recurrent stroke was 4.57 (CI, 1.5-13.96; P=0.008). Recurrent stroke risk increased across SUVmax quartiles (log-rank P=0.003). The area under receiver operating curve for all recurrence was 0.70 (CI, 0.59-0.78) and for post-PET recurrence was 0.80 (CI, 0.64-0.96). Conclusions- Plaque inflammation-related 18F-FDG uptake independently predicted future recurrent stroke post-PET. Although further studies are needed, 18F-FDG PET may improve patient selection for carotid revascularization and suggest that anti-inflammatory agents may have benefit for poststroke vascular prevention.

Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals.

BACKGROUND: The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata. METHODS AND FINDINGS: A systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%-1.82%) and 0.41% (95% CI, 0.31%-0.53%) for <65-year-olds. New AF detection rate increased progressively with age from 0.34% (<60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (<60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60-64 years; and 1,089 for <60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples. CONCLUSIONS: People with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and >70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations.

Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Validation of two risk-prediction models for recurrent falls in the first year after stroke: a prospective cohort study.

Background: several multivariable models have been derived to predict post-stroke falls. These require validation before integration into clinical practice. The aim of this study was to externally validate two prediction models for recurrent falls in the first year post-stroke using an Irish prospective cohort study. Methodology: stroke patients with planned home-discharges from five hospitals were recruited. Falls were recorded with monthly diaries and interviews 6 and 12 months post-discharge. Predictors for falls included in two risk-prediction models were assessed at discharge. Participants were classified into risk groups using these models. Model 1, incorporating inpatient falls history and balance, had a 6-month outcome. Model 2, incorporating inpatient near-falls history and upper limb function, had a 12-month outcome. Measures of calibration, discrimination (area under the curve (AUC)) and clinical utility (sensitivity/specificity) were calculated. Results: 128 participants (mean age = 68.6 years, SD = 13.3) were recruited. The fall status of 117 and 110 participants was available at 6 and 12 months, respectively. Seventeen and 28 participants experienced recurrent falls by these respective time points. Model 1 achieved an AUC = 0.56 (95% CI 0.46-0.67), sensitivity = 18.8% and specificity = 93.6%. Model 2 achieved AUC = 0.55 (95% CI 0.44-0.66), sensitivity = 51.9% and specificity = 58.7%. Model 1 showed no significant difference between predicted and observed events (risk ratio (RR) = 0.87, 95% CI 0.16-4.62). In contrast, model 2 significantly over-predicted fall events in the validation cohort (RR = 1.61, 95% CI 1.04-2.48). Conclusions: both models showed poor discrimination for predicting recurrent falls. A further large prospective cohort study would be required to derive a clinically useful falls-risk prediction model for a similar population.

Cost-Effectiveness of a National Opportunistic Screening Program for Atrial Fibrillation in Ireland.

OBJECTIVES: To evaluate the cost-effectiveness of a national atrial fibrillation screening program in Ireland involving annual opportunistic pulse palpation of all those older than 65 years during general practitioner consultations, with an electrocardiogram being performed if an irregular pulse is detected. METHODS: A probabilistic Markov model was used to simulate costs and clinical outcomes in a hypothetical cohort of men and women with and without screening over the course of 25 years, using a societal perspective. RESULTS: Screening was associated with an incremental cost-effectiveness ratio of €23,004/quality-adjusted life-year compared with routine care. Nevertheless, if the relative risk of stroke and systematic embolism in screen-detected patients is more than 12% lower than that in patients with atrial fibrillation identified through routine practice, then screening would not be considered cost-effective at a willingness-to-pay threshold of €45,000/quality-adjusted life-year. An analysis comparing alternative combinations of start age and screening interval found that less frequent screening with a later start age may be more cost-effective than an annual screening from age 65 years. CONCLUSIONS: Annual opportunistic screening of men and women aged 65 years and older in primary care in Ireland is likely to be cost-effective using conventional willingness-to-pay thresholds, assuming that those detected through screening have a comparable stroke risk profile as those detected through routine practice. Raising the start age of screening or increasing the screening interval may improve the cost-effectiveness of a prospective screening program.

Changes in anticoagulation practice in subjects admitted with stroke associated with atrial fibrillation, following introduction of direct oral anticoagulants over 2013-2021.

BACKGROUND: The adoption of direct oral anticoagulants (DOACs) has changed practice in prevention of stroke in atrial fibrillation (AF). We used Irish data national data on stroke and anticoagulation therapy over 9 years to investigate changes in anticoagulation practice and potential consequences on stroke prevalence and thrombolysis. METHODS: AF, anticoagulation, thrombolysis, and stroke data from the Irish National Audit of Stroke (INAS) 2013-2021 were reviewed. The proportion of patients with ischemic stroke (IS) and intracerebral hemorrhage (IH) with known AF admitted on anticoagulation was determined. Effects on age distribution in the population and thrombolysis practice were assessed. RESULTS: AF data were available on 34,630 of 35,241 individuals (98.3%) included in INAS; median age was 74 years and 56% were male. AF was found in 10,016 (28.9%, 9059 IS, 957 IH). 6313 had known AF prior to stroke (63.1%). The proportion all total IS due to AF decreased by 15.3% (31.3%-26.5%, chi-square = 24.6, p < 0.0001). The proportion of IH did not change significantly (21.6%-20.2%, chi-square = 1.8, p = 0.18). Over the 9 years, 3875 (38.6%) of the subjects with AF were recorded as receiving anticoagulants at admission. In 2013, 4.4% of AF-associated strokes were admitted on a DOAC and 21.4% on warfarin; by 2021, 44.1% were receiving a DOAC and 6.2% warfarin. There was a strong inverse correlation between the proportion of anticoagulated stroke patients and the total proportion of AF-associated strokes over time (r = -0.82, p = 0.006). In contrast, no correlation was found between increasing DOAC usage and IH (r = 0.14, p = 0.71). Increased anticoagulation usage correlated with a reduction in patients ⩾ 80 years (r = -0.83, p = 0.006) and also correlated with a relative reduction of 30.1% in subjects thrombolysed <4 h from onset (r = -0.89, p = 0.001). CONCLUSION: DOACs have led to increased use of anticoagulation, but warfarin use fell by two-thirds. There has been a reduction in the proportion of AF-associated IS without a noticeable increase in IH. Increased anticoagulation correlated with reduced numbers of strokes in those >80 years and in the proportion of patients thrombolysed.

A single-site retrospective review of in-hospital stroke.

BACKGROUND: In-hospital stroke refers to a stroke arising in a patient during hospital admission for another condition. Between 2 and 17% of all inpatient strokes are in-hospital strokes. AIM: To compare the outcomes and performance on quality-of-care stroke measures of in-hospital stroke cases with community-onset strokes. METHODS: Data collected for the Irish Annual Audit of Stroke from an Irish university teaching hospital was analysed for a 2-year period from 1st January 2020 to 31st December 2021. A retrospective cohort study was conducted to compare baseline characteristics, outcomes, and performance on standardised quality-of-care measures between the cohorts. RESULTS: The rate of IHS was 15.6%. Median age was 73 years and 72 years for in-hospital and community-onset strokes respectively. Amongst in-hospital strokes, COVID-19 co-diagnosis (9.1% versus 1.3%; p = .0004), admission to intensive care (52.3% versus 5.3%; p < .0001), discharge to long term care (6.8% versus 2.3%; p = .04), mortality (12.5% versus 7.6%; p = .13), and modified Rankin score of two or more at discharge (58.0% versus 38.1%; p = .001), were more likely compared to community-onset strokes. Thrombolysis rates were lower (7.3% versus 12.0%; p = .22) and thrombectomy rates higher (9.8% versus 6.6;% p = .32), albeit non-significantly. Median time to thrombolysis was slower amongst in-hospital strokes (105 min versus 66 min; p = .03) and they were less likely to be admitted to the stroke unit (43.2% versus 78.5%; p < .0001). CONCLUSIONS: When compared with community-onset stroke, in-hospital stroke represents a distinct stroke subgroup with poorer outcomes and delays to thrombolysis emphasising the need for standardised approaches to evaluation and management.

Symptomatic Carotid Atheroma Inflammation Lumen-stenosis score compared with Oxford and Essen risk scores to predict recurrent stroke in symptomatic carotid stenosis.

BACKGROUND: The Oxford Carotid Stenosis tool (OCST) and Essen Stroke Risk Score (ESRS) are validated to predict recurrent stroke in patients with and without carotid stenosis. The Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score combines stenosis and plaque inflammation on fluorodeoxyglucose positron-emission tomography (18FDG-PET). We compared SCAIL with OCST and ESRS to predict ipsilateral stroke recurrence in symptomatic carotid stenosis. PATIENTS AND METHODS: We pooled three prospective cohort studies of patients with recent (<30 days) non-severe ischaemic stroke/TIA and internal carotid artery stenosis (>50%). All patients had carotid 18FDG-PET/CT angiography and late follow-up, with censoring at carotid revascularisation. RESULTS: Of 212 included patients, 16 post-PET ipsilateral recurrent strokes occurred in 343 patient-years follow-up (median 42 days (IQR 13-815)).Baseline SCAIL predicted recurrent stroke (unadjusted hazard ratio [HR] 1.96, CI 1.20-3.22, p = 0.007, adjusted HR 2.37, CI 1.31-4.29, p = 0.004). The HR for OCST was 0.996 (CI 0.987-1.006, p = 0.49) and for ESRS was 1.26 (CI 0.87-1.82, p = 0.23) (all per 1-point score increase). C-statistics were: SCAIL 0.66 (CI 0.51-0.80), OCST 0.52 (CI 0.40-0.64), ESRS 0.61 (CI 0.48-0.74). Compared with ESRS, addition of plaque inflammation (SUVmax) to ESRS improved risk prediction when analysed continuously (HR 1.51, CI 1.05-2.16, p = 0.03) and categorically (ptrend = 0.005 for risk increase across groups; HR 3.31, CI 1.42-7.72, p = 0.006; net reclassification improvement 10%). Findings were unchanged by further addition of carotid stenosis. CONCLUSIONS: SCAIL predicted recurrent stroke, had discrimination better than chance, and improved the prognostic utility of ESRS, suggesting that measuring plaque inflammation may improve risk stratification in carotid stenosis.

Association of Plaque Inflammation With Stroke Recurrence in Patients With Unproven Benefit From Carotid Revascularization.

BACKGROUND AND OBJECTIVES: In pooled analyses of endarterectomy trials for symptomatic carotid stenosis, several subgroups experienced no net benefit from revascularization. The validated symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score includes stenosis severity and inflammation measured by PET and improves the identification of patients with recurrent stroke compared with lumen-stenosis alone. We investigated whether the SCAIL score improves the identification of recurrent stroke in subgroups with uncertain benefit from revascularization in endarterectomy trials. METHODS: We did an individual-participant data pooled analysis of 3 prospective cohort studies (Dublin Carotid Atherosclerosis Study [DUCASS], 2008-2011; Biomarkers and Imaging of Vulnerable Atherosclerosis in Symptomatic Carotid Artery Disease [BIOVASC], 2014-2018; Barcelona Plaque Study, 2015-2018). Eligible patients had a recent nonsevere (modified Rankin Scale score ≤3) anterior circulation ischemic stroke/TIA and ipsilateral mild carotid stenosis (<50%); ipsilateral moderate carotid stenosis (50%-69%) plus at least 1 of female sex, age <65 years, diabetes mellitus, TIA, or delay >14 days to revascularization; or monocular loss of vision. Patients underwent coregistered carotid 18F-fluorodeoxyglucosePET/CT angiography (≤7 days from inclusion). The primary outcome was 90-day ipsilateral ischemic stroke. Multivariable Cox regression modeling was performed. RESULTS: We included 135 patients. All patients started optimal modern-era medical treatment at admission, and 62 (45.9%) underwent carotid revascularization (36 within the first 14 days and 26 beyond). At 90 days, 18 (13.3%) patients had experienced at least 1 stroke recurrence. The risk of recurrence increased progressively according to the SCAIL score (0.0% in patients scoring 0-1, 15.1% scoring 2-3, and 26.7% scoring 4-5; p = 0.04). The adjusted (age, smoking, hypertension, diabetes, carotid revascularization, antiplatelets and statins) hazard ratio for ipsilateral recurrent stroke per 1-point SCAIL increase was 2.16 (95% CI 1.32-3.53; p = 0.002). A score ≥2 had a sensitivity of 100% for recurrence. DISCUSSION: The SCAIL score improved the identification of early recurrent stroke in subgroups who did not experience benefit in endarterectomy trials. Randomized trials are needed to test whether a combined stenosis-inflammation strategy will improve selection for carotid revascularization when benefit is currently uncertain. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, in patients with recent anterior circulation ischemic stroke who do not benefit from carotid revascularization, the SCAIL score accurately distinguishes those at risk for recurrent ipsilateral ischemic stroke.

Progressive resistance training in a post-acute, older, inpatient setting: A randomised controlled feasibility study.

OBJECTIVES: Progressive resistance training can successfully target functional decline in healthy older community-dwelling adults. There are concerns about the safety and acceptance of its use in frail older populations. The aim of this study was to evaluate the feasibility of using progressive resistance training in an older, post-acute, inpatient setting. METHODS: A randomised controlled feasibility study was conducted. Appropriate older inpatients undergoing post-acute rehabilitation were recruited. Feasibility measures examined were safety, recruitment, outcome measurement, adherence and retention rates and satisfaction. A range of clinical measures were used to capture changes in body structure and function, activity and participation. Assessments were performed on admission to the study and six weeks later. RESULTS: A sample of 33 patients were included and randomised to the treatment group (n=16) or the control group (n=17). There were no serious adverse events, adherence rates were 63% and retention rates were 82%. While both groups improved between time 1 and 2, there were no significant differences in clinical measures between the groups. CONCLUSION: Progressive resistance training is a safe and acceptable intervention for use with this population. Further work on the effectiveness of progressive resistance training in this setting is now required.

Development of a national stroke audit in Ireland: scoping review protocol.

Introduction Recent advances in stroke management and care have resulted in improved survival and outcomes. However, providing equitable access to acute care, rehabilitation and longer-term stroke care is challenging. Recent Irish evidence indicates variation in stroke outcomes across hospitals, and a need for continuous audit of stroke care to support quality improvement. The aim of this project is to develop a core minimum dataset for use in the new Irish National Audit of Stroke (INAS), which aims to improve the standard of stroke care in Ireland. This paper outlines the protocol for conducting a scoping review of international practice and guidelines in auditing acute and non-acute stroke care. Objective Identify data items that are currently collected by stroke audits internationally, and identify audit guidelines that exist for recommending inclusion of content in stroke audit datasets. Methods and analysis This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). We will search the following databases: Medline Ovid; Embase; CINAHL EBSCOHost. Grey literature will also be searched for relevant materials, as will relevant websites. Study selection and review will be carried out independently by two researchers, with discrepancies resolved by a third. Data charting and synthesis will involve sub-dividing relevant sources of evidence, and synthesising data into three categories: i) acute stroke care; ii) non-acute stroke care; and iii) audit data collection procedures and resourcing. Data will be charted using a standardised form specific to each category. Consultation with knowledge users will be conducted at all stages of the scoping review. Discussion This scoping review will contribute to a larger project aimed at developing an internationally benchmarked stroke audit tool that will be used prospectively to collect data on all stroke admissions in Ireland, encompassing both acute and non-acute data items.

Association Between 18-FDG Positron Emission Tomography and MRI Biomarkers of Plaque Vulnerability in Patients With Symptomatic Carotid Stenosis.

Purpose: Pathologic studies suggest that unstable plaque morphology and inflammation are associated with cerebrovascular events. 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) is a validated technique for non-invasive imaging of inflammation-related plaque metabolism, and MRI can identify morphologic features of plaque instability. The aim of this study was to investigate the association of selected imaging characteristics of plaque vulnerability measured with MRI and PET in patients with symptomatic carotid stenosis. Methods: Patients from the BIOVASC study were selected based on the following inclusion criteria: (1) age ≥ 50 years; (2) recent (<30 days) ischaemic stroke (modified Rankin scale ≤3) or motor/speech/vision TIA; (3) ipsilateral internal carotid artery stenosis (≥5 0% lumen-narrowing); (4) carotid PET/CTA and MRI completed. Semi-automated plaque analysis of MRI images was performed to quantify morphologic features of plaque instability. PET images were co-registered with CTA and inflammation-related metabolism expressed as maximum standardised uptake value (SUVmax). Results: Twenty-five patients met inclusion criteria (72% men, mean age 65 years). MRI-measured plaque volume was greater in men (1,708-1,286 mm3, p = 0.03), patients who qualified with stroke (1,856-1,440 mm3, p = 0.05), and non-statin users (1,325-1,797 mm3, p = 0.03). SUVmax was associated with MRI-measured plaque lipid-rich necrotic core (LRNC) in the corresponding axial slice (r s = 0.64, p < 0.001) and was inversely associated with whole-plaque fibrous cap thickness (r s = -0.4, p = 0.02) and calcium volume (r s = -0.4, p = 0.03). Conclusion: This study demonstrated novel correlations of non-invasive imaging biomarkers of inflammation-related plaque metabolism with morphological MRI markers of plaque instability. If replicated, our findings may support the application of combined MRI and PET to detect vulnerable plaque in future clinical practise and randomised trials.

von Willebrand Factor Antigen, von Willebrand Factor Propeptide, and ADAMTS13 in Carotid Stenosis and Their Relationship with Cerebral Microemboli.

BACKGROUND: The relationship between von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio, ADAMTS13 activity, and microembolic signal (MES) status in carotid stenosis is unknown. METHODS: This prospective, multicenter study simultaneously assessed plasma VWF:Ag levels, VWFpp levels and ADAMTS13 activity, and their relationship with MES in asymptomatic versus symptomatic moderate-to-severe (≥50-99%) carotid stenosis patients. One-hour transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES+ve or MES-ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the "early phase" (≤4 weeks) and 37 patients in the "late phase" (≥3 months) after transient ischemic attack (TIA)/ischemic stroke. VWF:Ag levels were higher (p = 0.049) and VWFpp/VWF:Ag ratios lower (p = 0.006) in early symptomatic than in asymptomatic patients overall, and in early symptomatic versus asymptomatic MES-ve subgroups (p ≤0.02). There were no intergroup differences in VWFpp expression or ADAMTS13 activity (p ≥0.05). VWF:Ag levels and ADAMTS13 activity decreased (p ≤ 0.048) and VWFpp/VWF:Ag ratios increased (p = 0.03) in symptomatic patients followed up from the early to late phases after TIA/stroke. Although there were no differences in the proportions of symptomatic and asymptomatic patients with blood group O, a combined analysis of early symptomatic and asymptomatic patients revealed lower median VWF:Ag levels in patients with blood group O versus those without blood group O (9.59 vs. 12.32 µg/mL, p = 0.035). DISCUSSION: VWF:Ag expression, a marker of endothelial ± platelet activation, is enhanced in recently symptomatic versus asymptomatic carotid stenosis patients, including in MES-ve patients, and decreases with ADAMTS13 activity over time following atherosclerotic TIA/ischemic stroke.