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Specialised CT-equipped mobile stroke treatment units shorten time to intravenous thrombolysis in acute ischaemic stroke by starting treatment before hospital admission; however, direct effects of pre-hospital thrombolysis on clinical outcomes have not been shown. We aimed to compare 3-month functional outcomes after intravenous thrombolysis in patients with acute ischaemic who had received emergency mobile care or and conventional care. In this observational registry study, patients with ischaemic stroke received intravenous thrombolysis (alteplase) either within a stroke emergency mobile (STEMO) vehicle (pre-hospital care covering 1·3 million inhabitants of Berlin) or within conventional care (normal ambulances and in-hospital care at the Charité Campus Benjamin Franklin in Berlin). Patient data on treatment, outcome, and demographics were documented in STEMO (pre-hospital) or conventional care (in-hospital) registries. The primary outcome was the proportion of patients who had lived at home without assistance before stroke and had a 3-month modified Rankin Scale (mRS) score of 1 or lower. Our multivariable logistic regression was adjusted for demographics, comorbidities, and stroke severity. This study is registered with ClinicalTrials.gov, number NCT02358772. Between Feb 5, 2011, and March 5, 2015, 427 patients were treated within the STEMO vehicle and their data were entered into a pre-hospital registry. 505 patients received conventional care and their data were entered into an in-hospital thrombolysis registry. Of these, 305 patients in the STEMO group and 353 in the conventional care group met inclusion criteria and were included in the analysis. 161 (53%) patients in the STEMO group versus 166 (47%) in the conventional care group had an mRS score of 1 or lower (p=0·14). Compared with conventional care, adjusted odds ratios (ORs) for STEMO care for the primary outcome (OR 1·40, 95% CI 1·00–1·97; p=0·052) were not significant. Intracranial haemorrhage (p=0·27) and 7-day mortality (p=0·23) did not differ significantly between treatment groups. We found no significant difference between the proportion of patients with a mRS score of 1 or lower receiving STEMO care compared with conventional care. However, our results suggest that pre-hospital start of intravenous thrombolysis might lead to improved functional outcome in patients. This evidence requires substantiation in future large-scale trials. Zukunftsfonds Berlin, the Technology Foundation Berlin with EU co-financing by the European Regional Development Fund via Investitionsbank Berlin, and the German Federal Ministry for Education and Research via the Center for Stroke Research Berlin.

Cardiac complications are a frequent medical problem during the first few days after an ischaemic stroke, and patients present with a broad range of symptoms including myocardial injury, cardiac dysfunction, and arrhythmia, with varying overlap between these three conditions. Evidence from clinical and neuroimaging studies and animal research suggests that these cardiac disturbances share the same underlying mechanisms. Although the exact cascade of events has yet to be elucidated, stroke-induced functional and structural alterations in the central autonomic network, with subsequent dysregulation of normal neural cardiac control, are the assumed pathophysiology. This dysregulation can promote myocardial necrosis, microvascular dysfunction, coronary demand ischaemia, and arrhythmogenesis. These stroke-associated cardiac alterations can be summarised as a distinct so-called stroke–heart syndrome. Independent cohort studies have shown a strong association between this syndrome and unfavourable short-term prognosis; however, long-term consequences, including secondary cardiac events and death, are less well described and specific therapeutic targets are scarce. An integrated view of stroke–heart syndrome will offer opportunities to expedite research and inform clinical decision making.

Background Iron deficiency (ID) is a common co‐morbidity in patients with cardiovascular disease and contributes to impaired functional capacity. The relevance of ID in patients in recovery after acute stroke is not known. We assessed the prevalence of ID and anaemia in relation to functional capacity and to recovery during early rehabilitation after stroke. Methods This observational study enrolled consecutively 746 patients with ischaemic or haemorrhagic stroke at in‐patient early rehabilitation (age 68 ± 13 years, female 47%, ischaemic stroke 87%). Functional capacity was assessed before and after rehabilitation using Barthel index (reha‐BI), motricity index (MI), trunk control test (TCT), and functional ambulatory category (FAC). ID was defined as ferritin <100 μg/L or as transferrin saturation (TSAT) < 20% if ferritin was 100‐ < 300 μg/L or if CrP > 5 mg/L. Anaemia was defined as Hb < 12 g/dL (women) and <13 g/dL (men). Results The prevalence of ID and anaemia before rehabilitation were 45% and 46%, respectively, and remained high at discharge (after 27 ± 17 days) at 40% and 48%, respectively. Patients with ID had lower functional capacity compared with patients without ID (reha‐BI 20 [±86] vs. 40 [±80], MI 64 [±66] vs. 77 [±41], TCT 61 [±76] vs. 100 [±39], FAC 1 [±4] vs. 4 [±4]; median [IQR], all P < 0.001). ID was related to inflammation (OR 2.68 [95% CI 1.98–3.63], P < 0.001), female sex (OR 2.13 [95% CI 1.59–2.85], P < 0.001), haemorrhagic stroke (OR 1.70 [95% CI 1.11–2.61], P = 0.015), initial treatment on stroke unit (OR 3.59 [95% CI 1.08–11.89], P < 0.001), and anaemia (OR 2.94 [95% CI 2.18–3.96], P < 0.001), while age, BMI, and renal function were not related to ID. In adjusted analysis, ID was associated with low functional capacity in all functional scores: reha‐BI (OR 1.66 [95% CI 1.08–2.54], P = 0.02), motricity index (OR 1.94 [95% CI 1.36–2.76], P < 0.001), trunk control test (OR 2.34 [95% CI] 1.64–3.32, P < 0.001) and functional ambulatory category (OR 1.77 [95% CI 1.2–2.63], P < 0.02). Functional capacity improved during rehabilitation regardless of presence of ID, but functional outcome remained significantly lower in patients with ID at the end of rehabilitation (rehab BI and MI, both P < 0.001). Conclusions Iron deficiency and anaemia are common and persistent findings in patients after acute stroke. ID and anaemia are independently related to lower functional capacity after acute stroke and to poor functional outcome after rehabilitation. Regular assessment of iron status may identify patients at risk of low functional recovery.

ObjectivesTo investigate the association between acute and chronic ischaemic lesions in a multiple territory lesion pattern (MTLP) detected by 3-Tesla MRI and stroke aetiology, specifically atrial fibrillation-associated stroke.MethodsWe analysed data from the 1000+ study – a prospective, observational 3-Tesla MRI cohort study of consecutively included acute stroke patients. Acute and chronic lesions were detected by DWI and fluid-attenuated inversion recovery, respectively. Observers blinded to clinical data allocated lesions to the right anterior, left anterior or posterior circulation. Lesion pattern was categorised as MTLPa/c when more than one territory was affected by either acute or chronic lesions or as MTLPa when more than one territory was affected by acute lesions alone.ResultsOf the 1,000 included patients, an MTLPa/c was found in 43% and MTLPa in 24%. Advanced age (aOR=1.21 per 10 years, 95% CI 1.06–1.39), atrial fibrillation (aOR=1.44, 95% CI 1.06–1.94), aortic arch atherosclerosis (aOR=2.52, 95% CI 1.10–5.77), malignant disease (aOR=1.99, 95% CI 1.25–3.16) and lower estimated glomerular filtration rate (eGFR) (aOR=0.90 per 10 ml, 95% CI 0.84–0.97) were associated with MTLPa/c. Only malignant disease (aOR=2.03, 95% CI 1.27–3.23) and lower eGFR (aOR=0.91 per 10 ml, 95% CI 0.85–0.97) were associated with MTLPa.ConclusionsAn MRI-detected multiple territory lesion pattern of acute and chronic ischaemic lesions is frequent and more often present in older patients and patients with atrial fibrillation, aortic arch atherosclerosis, malignant disease and lower eGFR. Considering not only acute but also chronic ischaemic lesions may facilitate identifying atrial fibrillation-associated or aorto-embolic stroke.Key Points• Brain imaging with MRI may help to determine the aetiology of stroke.• Of 1,000 stroke patients undergoing 3-Tesla MRI, 43% had acute and chronic ischaemic lesions in multiple cerebral vascular territories.• Atrial fibrillation, aortic arch atherosclerosis and malignant disease were associated with a multiple territory lesion pattern.

Background Current guidelines recommend measurement of troponin in acute ischemic stroke (AIS) patients. In AIS patients, troponin elevation is associated with increased mortality and worse outcome. However, uncertainty remains regarding the underlying pathophysiology of troponin elevation after stroke, particularly regarding diagnostic and therapeutic consequences. Troponin elevation may be caused by coronary artery disease (CAD) and more precisely acute coronary syndrome (ACS). Both have a high prevalence in stroke patients and contribute to poor outcome. Therefore, better diagnostic algorithms are needed to identify those AIS patients likely to have ACS or other manifestations of CAD. Methods/design The primary goal of the “PRediction of Acute coronary syndrome in acute Ischemic StrokE” (PRAISE) study is to develop a diagnostic algorithm for prediction of ACS in AIS patients. The primary hypothesis will test whether dynamic high-sensitivity troponin levels determined by repeat measurements (i.e., “rise or fall-pattern”) indicate presence of ACS when compared to stable (chronic) troponin elevation. PRAISE is a prospective, multicenter, observational trial with central reading and predefined endpoints guided by a steering committee. Clinical symptoms, troponin levels as well as findings on electrocardiogram, echocardiogram, and coronary angiogram will be recorded and assessed by central academic core laboratories. Diagnosis of ACS will be made by an endpoint adjudication committee. Severe adverse events will be evaluated by a critical event committee. Safety will be judged by a data and safety monitoring board. Follow-up will be conducted at three and twelve months and will record new vascular events (i.e., stroke and myocardial infarction) as well as death, functional and cognitive status. According to sample size calculation, 251 patients have to be included. Discussion PRAISE will prospectively determine the frequency of ACS and characterize cardiac and coronary pathologies in a large, multicenter cohort of AIS patients with troponin elevation. The findings will elucidate the origin of troponin elevation, shed light on its impact on necessary diagnostic procedures and provide data on the safety and diagnostic yield of coronary angiography early after stroke. Thereby, PRAISE will help to refine algorithms and develop guidelines for the cardiac workup in AIS. Trial registration NCT03609385 registered 1st August 2018.

BackgroundStroke aetiology remains cryptogenic in a relevant proportion of patients with acute ischaemic stroke (AIS). We assessed whether enhanced diagnostic workup after AIS yields a higher rate of prespecified pathological findings compared with routine diagnostic care in-hospital.MethodsHospitalised patients with AIS were prospectively enrolled in the investigator-initiated observational HEart and BRain Interfaces in Acute Ischaemic Stroke (HEBRAS) study at the Charité, Berlin, Germany. Patients with AIS without known atrial fibrillation (AF) underwent cardiovascular MR imaging (CMR), MR-angiography of the aortic arch and prolonged Holter-ECG monitoring on top of routine diagnostic care.ResultsAmong 356 patients with AIS (mean age 66 years, 37.6% female), enhanced workup yielded a higher rate of prespecified pathological findings compared with routine care (17.7% vs 5.3%; p<0.001). Consequently, fewer patients were classified as cryptogenic after enhanced diagnostic workup (38.5% vs 45.5%, p<0.001). Routine care included echocardiography in 228 (64.0%) patients. CMR was successfully performed in 292 (82.0%) patients and revealed more often a prespecified pathological finding compared with routine echocardiography (16.1% vs 5.3%). Furthermore, study-related ECG monitoring (median duration 162 hours (IQR 98–210)) detected AF in 16 (4.5%) patients, while routine monitoring (median duration 51 hours (IQR 34–74)) detected AF in seven (2.0%) patients.ConclusionsEnhanced diagnostic workup revealed a higher rate of prespecified pathological findings in patients with AIS compared with routine diagnostic care and significantly reduced the proportion of patients with cryptogenic stroke.Trial registration number NCT02142413.

Cardiac troponin is a specific and sensitive biomarker to identify and quantify myocardial injury. Myocardial injury is frequently detected after acute ischemic stroke and strongly associated with unfavorable outcomes. Concomitant acute coronary syndrome is only one of several possible differential diagnoses that may cause elevation of cardiac troponin after stroke. As a result, there are uncertainties regarding the correct interpretation and optimal management of stroke patients with myocardial injury in clinical practice. Elevation of cardiac troponin may occur as part of a ‘Stroke-Heart Syndrome’. The term ‘Stroke-Heart Syndrome’ subsumes a clinical spectrum of cardiac complications after stroke including cardiac injury, dysfunction, and arrhythmia which may relate to disturbances of autonomic function and the brain–heart axis. In this review, we provide an up-to-date overview about prognostic implications, mechanisms, and management of elevated cardiac troponin levels in patients with acute ischemic stroke.

Cardiovascular alterations are common in patients who had ischaemic stroke, haemorrhagic stroke and other acute brain disorders such as seizures. These cardiac complications are important drivers of morbidity and mortality and comprise blood-based detection of cardiomyocyte damage, ECG changes, heart failure and arrhythmia. Recently, the concept of a distinct ‘stroke-heart syndrome’ has been formulated as a pathophysiological framework for poststroke cardiac complications. The concept considers cardiac sequelae after stroke to be the result of a stroke-induced disturbance of the brain–heart axis. In this review, we describe the spectrum of cardiac changes secondary to ischaemic stroke and other acute brain disorders. Furthermore, we focus on Takotsubo syndrome secondary to acute brain disorders as a model disease of disturbed brain–heart interaction. Finally, we aim to provide an overview of the anatomical and functional links between the brain and the heart, with emphasis on the autonomic network and the role of inflammation. Given the clinical relevance of the deleterious impact of acute brain injury on the heart, we call for clinical awareness and for starting joint efforts combining expertise of neurology and cardiology to identify specific therapeutic interventions.

ObjectiveTo investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).MethodsWe analysed consecutive patients with AF with an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.ResultsAmong 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.ConclusionsStroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.Trial registration numberISRCTN48292829.

Background Stroke-associated pneumonia (SAP) is a preventable determinant for poor outcome after stroke. Machine learning (ML) using large-scale clinical data warehouses may be able to predict SAP and identify patients for targeted interventions. The aim of this study was to develop a prediction model for identifying clinically apparent SAP using automated ML. Methods The ML model used clinical and laboratory parameters along with heart rate (HR), heart rate variability (HRV), and blood pressure (BP) values obtained during the first 48 h after stroke unit admission. A logistic regression classifier was developed and internally validated with a nested-cross-validation (nCV) approach. For every shuffle, the model was first trained and validated with a fixed threshold for 0.9 sensitivity, then finally tested on the out-of-sample data and benchmarked against a widely validated clinical score (A2DS2). Results We identified 2390 eligible patients admitted to two-stroke units at Charité between October 2020 and June 2023, of whom 1755 had all parameters available. SAP was diagnosed in 96/1755 (5.5%). Circadian profiles in HR, HRV, and BP metrics during the first 48 h after admission exhibited distinct differences between patients with SAP diagnosis vs. those without. CRP, mRS at admission, leukocyte count, high-frequency power in HRV, stroke severity at admission, sex, and diastolic BP were identified as the most informative ML features. We obtained an AUC of 0.91 (CI 0.88–0.95) for the ML model on the out-of-sample data in comparison to an AUC of 0.84 (CI 0.76–0.91) for the previously established A2DS2 score ( p  < 0.001). The ML model provided a sensitivity of 0.87 (CI 0.75–0.97) with a corresponding specificity of 0.82 (CI 0.78–0.85) which outperformed the A2DS2 score for multiple cutoffs. Conclusions Automated, data warehouse-based prediction of clinically apparent SAP in the stroke unit setting is feasible, benefits from the inclusion of vital signs, and could be useful for identifying high-risk patients or prophylactic pneumonia management in clinical routine.