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Background: Atrial fibrillation (AF) can be known before the stroke (KAF) or be newly detected after stroke (AFDAS). It is unknown whether the outcome of stroke differs between KAF and AFDAS. We performed a propensity-matched analysis to investigate the outcome of patients with AFDAS and their counterparts with KAF., Methods: We analysed a consecutive series of patients enrolled into the EIDASAF study, a single centre, retrospective study of ischemic stroke patients with a diagnosis of AF before or after the event who had been admitted to the Hyperacute Stroke Unit of Imperial College Healthcare NHS Trust between 2010 and 2017., Results: Overall, our cohort included 959 patients with AF and acute ischemic stroke. After propensity score matching, 547 patients were matched (404 KAF group and 143 AFDAS group). The rates of in hospital death and of haemorrhagic transformation were significantly higher in KAF patients compared to AFDAS patients. Logistic regression analysis did not reveal a statistically significant influence of AF subtypes on the outcome of death. However, in logistic regression analysis KAF was associated with increased probability of haemorrhagic transformation (OR 9.64; CI 1.29-71.68, p = 0.022) after the index event., Conclusion: KAF is associated with an increased risk of haemorrhagic transformation but not of death when compared to AFDAS., (© 2024. The Author(s).)

Pulse wave velocity (PWV) is as a reliable marker of arterial stiffness and vascular aging, surpassing traditional risk factors in predicting detrimental cardiovascular events. The present meta-analysis aims to investigate PWV thresholds and assess its prognostic value in outcomes of acute ischemic stroke (AIS). A search was conducted in PubMed, Cochrane, Web of Science, and Scopus for studies published up to January 2024, focusing on patients admitted with AIS, wherein arterial stiffness was assessed through PWV measurements during hospitalization. Identified studies reported PWV values in individuals with both favorable and unfavorable outcomes at the end of follow-up. Initially, 35 eligible studies provided data for weighted mean baPWV (11,953 AIS patients) and cfPWV (2,197 AIS patients) calculations. The average age was 67 years, with approximately 60% male, 67% hypertensive, 30% diabetic and 30% smoker participants. The weighted mean systolic blood pressure was approximately 150 mmHg. In AIS patients, the mean PWV was 10 m/s for standard cfPWV and 20 m/s for baPWV. Nine cohort studies (6,006 AIS patients) were included in the quantitative analysis of clinical outcomes. Higher PWV levels were associated with poorer functional outcomes (2.3 m/s higher, 95%CI:1.2-3.4, p < 0.001; I 2  = 87.4%). AIS patients with arterial stiffness/vascular aging (higher PWV) had approximately 46.2% increased risk of poor functional outcome, 12.7% higher risk of mortality, 13.9% greater risk of major adverse cardiovascular events, and 13.9% greater risk of stroke recurrence over the long term compared to those without arterial stiffness. Advanced vascular aging, as indicated by PWV, significantly predicts adverse outcomes in AIS patients. Integrating the assessment of vascular aging into clinical practice can improve risk perception in these patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

There is limited evidence on the outcomes and safety of mechanical thrombectomy (MT) among patients with acute ischemic stroke (AIS) in the context of cardiac diseases. Our study reviews MT in AIS within the context of cardiac diseases, aiming to identify existing and emerging needs and gaps. PubMed and Scopus were searched until December 31, 2023, using a combination of cardiological diseases and "mechanical thrombectomy" or "endovascular treatment" as keywords. Study design included case reports/series, observational studies, randomized clinical trials, and meta-analyses/systematic reviews. We identified 943 articles, of which 130 were included in the review. Results were categorized according to the cardiac conditions. MT shows significant benefits in patients with atrial fibrillation (n=139) but lacks data for stroke occurring after percutaneous coronary intervention (n=2) or transcatheter aortic valve implantation (n=5). MT is beneficial in AIS attributable to infective endocarditis (n=34), although functional benefit may be limited. Controversy surrounds the functional outcomes and mortality of patients with AIS with heart failure undergoing MT (n=11). Despite technical challenges, MT appears feasible in aortic dissection cases (n=4), and in patients with left ventricular assist device or total artificial heart (n=10). Data on AIS attributable to congenital heart disease (n=4) primarily focus on pediatric cases requiring technical modifications. Treatment outcomes of MT in patients with cardiac tumors (n=8) vary because of clot consistency differences. After cardiac surgery stroke, MT may improve outcomes with early intervention (n=13). Available data outline the feasibility of MT in patients with AIS attributable to large-vessel occlusion in the context of cardiac diseases.

Background: While arterial stiffening is a known risk factor for cardiovascular diseases, it remains unclear whether there is an early vascular aging (EVA) in patients who have experienced acute ischemic stroke (AIS). This systematic review and meta-analysis aims to investigate whether patients with AIS exhibit EVA through pulse wave velocity (PWV) measurements shortly after the stroke onset, shedding light on the relationship between arterial stiffness, hypertension, and stroke., Methods: Thirteen case-control studies were included, comparing PWV measurements between AIS patients and non-AIS individuals. A meta-analysis was performed to compare PWV levels, age, blood pressure, and the prevalence of different cardiovascular risk factors among 1711 AIS patients and 1551 controls., Results: Despite AIS patients showing higher PWV compared to controls (mean difference: 1.72 m/s, 95 % CI: 1.05-2.38, p < 0.001; I 2 = 88.3 %), their age did not significantly differ (95 % CI: -0.47-0.94, p = 0.519; I 2 = 0 %), suggesting EVA in AIS patients. Moreover, AIS patients exhibited elevated systolic and diastolic blood pressure and had higher odds of smoking, hypertension, diabetes, and male gender compared to controls., Conclusions: This study's findings underscore the presence of EVA in AIS patients, evident through increased PWV measurements shortly after stroke onset. Notably, smoking, hypertension, and diabetes mellitus emerge as substantial factors contributing to accelerated arterial stiffness within this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed a holistic integrated care management approach for stroke patients, to improve cardiovascular outcomes. The impact of implementing the ABC stroke pathway 'concept' on clinical outcomes has never been estimated before. In order to investigate the potential effect of ABC stroke pathway adherence to cardiovascular outcomes post stroke, we performed a post-hoc analysis from the Athens Stroke Registry., Methods and Results: This analysis was performed in the Athens Stroke Registry, which includes all consecutive patients with acute first-ever ischemic stroke. The Kaplan-Meier product limit was used to estimate the cumulative hazard of each outcome according to adherence with the ABC stroke pathway. We studied 2513 patients [median (IQR) age 71 (62-78) years; 37.7 % female] with ischemic stroke with median follow-up period of 30 (6-75) months. Full adherence to the ABC pathway was identified in 156 (6.2 %) of the patients, while 192 (7.6 %) did not adhere to any of the therapeutic pillars of ABC stroke . Full adherence to ABC treatment pathway was associated with significant reduction of stroke recurrence, compared to patients with no or partial adherence (aHR: 0.61; 95 %CI: 0.37-0.99), as well as a lower risk of MACE (HR: 0.59; 0.39-0.88) and death (aHR: 0.22; 95 %CI: 0.12-0.41)., Conclusion: Full adherence to the ABC stroke pathway based on the current guidelines was evident in only 6.2 % of our ischaemic stroke cohort but was independently associated with lower risks of stroke recurrence, major cardiovascular events and mortality. This highlights a potential opportunity to improve clinical outcomes post-stroke with a holistic or integrated care management approach., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Ischemic strokes in orally anticoagulated patients pose challenges for acute management and secondary prevention but the characteristics of these strokes are poorly understood. We examined the clinical and imaging features, the presumed underlying etiology and the subsequent antithrombotic management., Methods: We analyzed a consecutive series of patients enrolled into the EIDASAF study, a single center, observational study of ischemic stroke patients with a diagnosis atrial fibrillation (AF) prior to the index event who had been admitted to the Hyperacute Stroke Unit of Imperial College London between 2010 and 2017. We compared patients with oral anticoagulation therapy prior admission (OAC prior ) with those without anticoagulation (OAC naive ). Brain imaging was analyzed centrally., Results: 763 patients were included in the analysis. 481 (63%) were OAC naive while 282 (37%) were OAC prior . Patients with OAC prior were younger, more often had a previous history of stroke or transient ischemic attack (TIA), and more often suffered from hypertension and diabetes. In OAC naive, patients, large and deep middle cerebral artery infarcts occurred more often than in OAC prior patients. The groups differed significantly in the distribution of competing etiologies underlying their stroke. At discharge, OAC prior more frequently were (re)-anticoagulated compared to OAC naive patients. Within the OAC prior group, patients with recurrent strokes did not differ from those with a first stroke regarding clinical characteristics and pattern of cerebral infarction but they were less frequently anticoagulated., Conclusions: Ischemic strokes on OAC represent a significant proportion of AF-related strokes. There is an unmet need to better understand the causes underlying these strokes and to optimize the medical management., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Since the onset of the COVID-19 pandemic, a substantial proportion of COVID-19 patients had documented thrombotic complications and ischemic stroke. Several mechanisms related to immune-mediated thrombosis, the renin angiotensin system and the effect of SARS-CoV-2 in cardiac and brain tissue may contribute to the pathogenesis of ischemic stroke in patients with COVID-19. Simultaneously, significant strains on global healthcare delivery, including ischemic stroke management, have made treatment of stroke in the setting of COVID-19 particularly challenging. In this review, we summarize the current knowledge on epidemiology, clinical manifestation, and pathophysiology of ischemic stroke in patients with COVID-19 to bridge the gap from bench to bedside and clinical practice during the most challenging global health crisis of the last decades., (© 2021 European Academy of Neurology.)

Background Stratification of cardiovascular risk in patients with ischemic stroke is important as it may inform management strategies. We aimed to develop a machine-learning-derived prognostic model for the prediction of cardiovascular risk in ischemic stroke patients., Materials and Methods: Two prospective stroke registries with consecutive acute ischemic stroke patients were used as training/validation and test datasets. The outcome assessed was major adverse cardiovascular event, defined as non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death during 2-year follow-up. The variables selection was performed with the LASSO technique. The algorithms XGBoost (Extreme Gradient Boosting), Random Forest and Support Vector Machines were selected according to their performance. The evaluation of the classifier was performed by bootstrapping the dataset 1000 times and performing cross-validation by splitting in 60% for the training samples and 40% for the validation samples., Results: The model included age, gender, atrial fibrillation, heart failure, peripheral artery disease, arterial hypertension, statin treatment before stroke onset, prior anticoagulant treatment (in case of atrial fibrillation), creatinine, cervical artery stenosis, anticoagulant treatment at discharge (in case of atrial fibrillation), and statin treatment at discharge. The best accuracy was measured by the XGBoost classifier. In the validation dataset, the area under the curve was 0.648 (95%CI:0.619-0.675) and the balanced accuracy was 0.58 ± 0.14. In the test dataset, the corresponding values were 0.59 and 0.576., Conclusions: We propose an externally validated machine-learning-derived model which includes readily available parameters and can be used for the estimation of cardiovascular risk in ischemic stroke patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Hemorrhagic transformation (HT) after stroke, related to atrial fibrillation (AF), is a frequent complication, and it can be associated with a delay in the (re-)initiation of oral anticoagulation therapy. We investigated the effect of the presence and severity of white matter disease (WMD) on early HT after stroke related to AF., Methods: A consecutive series of patients with recent (<4 weeks) ischemic stroke and AF, treated at the Hyper Acute Stroke Unit of the Imperial College London between 2010 and 2017, were enrolled. Patients with brain MRI performed 24-72 h from stroke onset and not yet started on anticoagulant treatment were included. WMD was graded using the Fazekas score., Results: Among the 441 patients eligible for the analysis, 91 (20.6%) had any HT. Patients with and without HT showed similar clinical characteristics. Patients with HT had a larger diffusion-weighted imaging (DWI) infarct volume compared to patients without HT (p < .001) and significant difference in the distribution of the Fazekas score (p = .001). On multivariable analysis, HT was independently associated with increasing DWI infarct volume (odd ratio (OR), 1.03; 95% confidence interval (CI), 1.01-1.05; p < .001), higher Fazekas scores (OR, 1.94; 95% CI, 1.47-2.57; p < .001) and history of previous intracranial hemorrhage (OR, 4.80; 95% CI, 1.11-20.80; p = .036)., Conclusions: Presence and severity of WMD is associated with increased risk of development of early HT in patients with stroke and AF. Further evidence is needed to provide reliable radiological predictors of the risk of HT in cardioembolic stroke., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

This document presents the consensus recommendations of the Hellenic Stroke Organization and the Hellenic Atherosclerosis Society for lipid modification in patients with ischemic stroke or transient ischemic attack. This clinical guide summarizes the current literature on lipid management and can be of assistance to the physicians treating stroke patients in clinical practice.

Importance: The concept of embolic stroke of undetermined source (ESUS) unifies a subgroup of cryptogenic strokes based on neuroimaging, a defined minimum set of diagnostic tests, and exclusion of certain causes. Despite an annual stroke recurrence rate of 5%, little is known about the etiology underlying recurrent stroke after ESUS., Objective: To identify the stroke subtype of recurrent ischemic strokes after ESUS, to explore the interaction with treatment assignment in each category, and to examine the consistency of cerebral location of qualifying ESUS and recurrent ischemic stroke., Design, Setting, and Participants: The NAVIGATE-ESUS trial was a randomized clinical trial conducted from December 23, 2014, to October 5, 2017. The trial compared the efficacy and safety of rivaroxaban and aspirin in patients with recent ESUS (n = 7213). Ischemic stroke was validated in 309 of the 7213 patients by adjudicators blinded to treatment assignment and classified by local investigators into the categories ESUS or non-ESUS (ie, cardioembolic, atherosclerotic, lacunar, other determined cause, or insufficient testing). Five patients with recurrent strokes that could not be defined as ischemic or hemorrhagic in absence of neuroimaging or autopsy were excluded. Data for this secondary post hoc analysis were analyzed from March to June 2019., Interventions: Patients were randomly assigned to receive rivaroxaban, 15 mg/d, or aspirin, 100 mg/d., Main Outcomes and Measures: Association of recurrent ESUS with stroke characteristics., Results: A total of 309 patients (205 men [66%]; mean [SD] age, 68 [10] years) had ischemic stroke identified during the median follow-up of 11 (interquartile range [IQR], 12) months (annualized rate, 4.6%). Diagnostic testing was insufficient for etiological classification in 39 patients (13%). Of 270 classifiable ischemic strokes, 156 (58%) were ESUS and 114 (42%) were non-ESUS (37 [32%] cardioembolic, 26 [23%] atherosclerotic, 35 [31%] lacunar, and 16 [14%] other determined cause). Atrial fibrillation was found in 27 patients (9%) with recurrent ischemic stroke and was associated with higher morbidity (median change in modified Rankin scale score 2 [IQR, 3] vs 0 (IQR, 1]) and mortality (15% vs 1%) than other causes. Risk of recurrence did not differ significantly by subtype between treatment groups. For both the qualifying and recurrent strokes, location of infarct was more often in the left (46% and 54%, respectively) than right hemisphere (40% and 37%, respectively) or brainstem or cerebellum (14% and 9%, respectively)., Conclusions and Relevance: In this secondary analysis of randomized clinical trial data, most recurrent strokes after ESUS were embolic and of undetermined source. Recurrences associated with atrial fibrillation were a minority but were more often disabling and fatal. More extensive investigation to identify the embolic source is important toward an effective antithrombotic strategy., Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.

Background and Aims: To reassess the effect of statin-based lipid-lowering therapy on ischemic stroke in primary and secondary prevention trials with regard to achieved levels of low-density lipoprotein-cholesterol in view of the availability of novel potent hypolipidemic agents., Methods: English literature was searched (up to November 2018) for publications restricted to trials with a minimum enrolment of 1000 and 500 subjects for primary and secondary prevention, respectively, meeting the following criteria: adult population, randomized controlled design, and recorded outcome data on ischemic stroke events. Data were meta-analyzed and curve-estimation procedure was applied to estimate regression statistics and produce related plots., Results: Four primary prevention trials and four secondary prevention trials fulfilled the eligibility criteria. Lipid-lowering therapy was associated with a lower risk of ischemic stroke in primary (risk ratio, RR 0.70, 95% confidence interval, CI, 0.60-0.82; p  < 0.001) and in the secondary prevention setting (RR 0.80, 95% CI 0.70-0.90; p  < 0.001). Curve-estimation procedure revealed a linear relationship between the absolute risk reduction of ischemic stroke and active treatment-achieved low-density lipoprotein-cholesterol levels in secondary prevention (adjusted R-square 0.90) in support of "the lower the better" hypothesis for stroke survivors. On the other hand, the cubic model followed the observed data well in primary prevention (adjusted R-square 0.98), indicating greater absolute risk reduction in high-risk cardiovascular disease-free individuals., Conclusions: Statin-based lipid-lowering is effective both for primary and secondary prevention of ischemic stroke. Most benefit derives from targeting disease-free individuals at high cardiovascular risk, and by achieving low treatment targets for low-density lipoprotein-cholesterol in stroke survivors.