High-Sensitivity Cardiac Troponin T and Cognitive Function Over 12 Months After Stroke-Results of the DEMDAS Study.

BACKGROUND: Subclinical myocardial injury in form of hs-cTn (high-sensitivity cardiac troponin)  levels has been associated with cognitive impairment and imaging markers of cerebral small vessel disease (SVD) in population-based and cardiovascular cohorts. Whether hs-cTn is associated with domain-specific cognitive decline and SVD burden in patients with stroke remains unknown. METHODS AND RESULTS: We analyzed patients with acute stroke without premorbid dementia from the prospective multicenter DEMDAS (DZNE [German Center for Neurodegenerative Disease]-Mechanisms of Dementia after Stroke) study. Patients underwent neuropsychological testing 6 and 12 months after the index event. Test results were classified into 5 cognitive domains (language, memory, executive function, attention, and visuospatial function). SVD markers (lacunes, cerebral microbleeds, white matter hyperintensities, and enlarged perivascular spaces) were assessed on cranial magnetic resonance imaging to constitute a global SVD score. We examined the association between hs-cTnT (hs-cTn T levels) and cognitive domains as well as the global SVD score and individual SVD markers, respectively. Measurement of cognitive and SVD-marker analyses were performed in 385 and 466 patients with available hs-cTnT levels, respectively. In analyses adjusted for demographic characteristics, cardiovascular risk factors, and cognitive status at baseline, higher hs-cTnT was negatively associated with the cognitive domains "attention" up to 12 months of follow-up (beta-coefficient, -0.273 [95% CI, -0.436 to -0.109]) and "executive function" after 12 months. Higher hs-cTnT was associated with the global SVD score (adjusted odds ratio, 1.95 [95% CI, 1.27-3.00]) and the white matter hyperintensities and lacune subscores. CONCLUSIONS: In patients with stroke, hs-cTnT is associated with a higher burden of SVD markers and cognitive function in domains linked to vascular cognitive impairment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01334749.

Sex Differences in Outcomes of Acute Myocardial Injury After Stroke.

BACKGROUND: Sex differences in presentation, treatment, and prognosis of cardiovascular disorders are well recognized. Although an association between acute myocardial injury and mortality after ischemic stroke has been demonstrated, it is unclear whether prevalence and outcome of poststroke acute myocardial injury differ between women and men. METHODS AND RESULTS: We prospectively screened consecutive patients with acute ischemic stroke and serial high-sensitivity cardiac troponin T measurements admitted to our center. Acute myocardial injury was defined as at least 1 high-sensitivity cardiac troponin T value above the upper reference limit (14 ng/L) with a rise/fall of >20%. Rates of acute myocardial injury were also calculated using sex-specific high-sensitivity cardiac troponin T cutoffs (women upper reference limit, 9 ng/L; men upper reference limit, 16 ng/L). Logistic regression analyses were performed to evaluate the association between acute myocardial injury and outcomes. Of 1067 patients included, 494 were women (46%). Women were older, had a higher rate of known atrial fibrillation, were more likely to be functionally dependent before admission, had higher stroke severity, and more often had cardioembolic strokes (all P values <0.05). The crude prevalence of acute myocardial injury differed by sex (29% women versus 23% men, P=0.024). Statistically significant associations between acute myocardial injury and outcomes were observed in women (7-day in-hospital mortality: adjusted odds ratio [aOR], 3.2 [95% CI, 1.07-9.3]; in-hospital mortality: aOR, 3.3 [95% CI, 1.4-7.6]; modified Rankin Scale score at discharge: aOR, 1.6 [95% CI, 1.1-2.4]) but not in men. The implementation of sex-specific cutoffs did not increase the prognostic value of acute myocardial injury for unfavorable outcomes. CONCLUSIONS: The prevalence of acute myocardial injury after ischemic stroke and its association with mortality and greater disability might be sex-dependent. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03892226.

Machine learning using multimodal and autonomic nervous system parameters predicts clinically apparent stroke-associated pneumonia in a development and testing study.

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.

World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

Heart rate turbulence in acute ischemic stroke.

BACKGROUND: Heart rate turbulence (HRT), an ECG-based marker of autonomic cardiac regulation, has shown high prognostic value in patients with established cardiovascular diseases, while data in patients with acute ischemic stroke are scarce. PATIENTS AND METHODS: The HRT parameters turbulence onset and turbulence slope were analyzed using Holter-ECG recordings from patients with acute ischemic stroke, consecutively enrolled in the prospective observational HEBRAS study. HRT was categorized as normal (category 0; both parameters normal), abnormal (category 1; one parameter abnormal), or severely abnormal (category 2; both parameters abnormal). Outcomes of interest were functional outcome according to modified Rankin Scale (mRS) score at 3 months, mortality at 1 year, newly detected atrial fibrillation (AF), and evidence of focal myocardial fibrosis on cardiovascular MRI. RESULTS: HRT was assessed in 335 patients in sinus rhythm (median age 69 years, 37% female, median NIHSS score 2 on admission), including 262 (78%) with normal HRT, 47 (14%) with abnormal and 26 (8%) with severely abnormal HRT. Compared with normal HRT, severely abnormal HRT was associated with increased disability [higher mRS] at 3 months (adjusted odds ratio [aOR]: 2.9, 95% confidence interval [CI]: 1.3-6.6), new AF (aOR: 3.5, 95% CI: 1.1-10.6), MRI-detected myocardial fibrosis (aOR: 5.8, 95% CI: 1.3-25.9), but not with mortality at 1 year after stroke (aOR: 3.0, 95% CI: 0.7-13.9). Abnormal HRT was not associated with the analyzed outcomes. CONCLUSIONS: Severely abnormal HRT was associated with increased disability and previously unknown cardiac comorbidities. The potential role of HRT in selecting patients for extended AF monitoring and cardiac imaging should be further investigated.

Datawarehouse-enabled quality control of atrial fibrillation detection in the stroke unit setting.

Objective: (1) To assess the accuracy of a standard operating procedure (SOP) regarding the utilization of atrial fibrillation (AF) alarms in everyday clinical practice, and (2) to evaluate the performance of automated continuous surveillance for atrial fibrillation (AF) in hospitalized acute stroke patients. Design: Retrospective cohort study. Setting: Two stroke units from two tertiary care hospitals in Berlin, Germany. Participants: We identified 635 patients with ischemic stroke diagnosis for the time period between 01. January and 30. September 2021 of which 176 patients had recorded AF alarms during monitoring. Of those, 115 patients were randomly selected for evaluation. After excluding 6 patients with hemorrhagic stroke in their records, 109 patients (mean age: 79.1 years, median NIHSS at admission: 6, 57% female) remained for analysis. Intervention: Using a clinical data warehouse for comprehensive data storage we retrospectively downloaded and visualized ECG data segments of 65 s duration around the automated AF alarms. We restricted the maximum number of ECG segments to ten per patient. Each ECG segment plot was uploaded into a REDCap database and categorized as either AF, non-AF or artifact by manual review. Atrial flutter was subsumed as AF. These classifications were then matched with 1) medical history and known diseases before stroke, 2) discharge diagnosis, and 3) recommended treatment plan in the medical history using electronic health records. Main outcome measures: The primary outcome was the proportion of previously unknown AF diagnoses correctly identified by the monitoring system but missed by the clinical team during hospitalization. Secondary outcomes included the proportion of patients in whom a diagnosis of AF would likely have led to anticoagulant therapy. We also evaluated the accuracy of the automated detection system in terms of its positive predictive value (PPV). Results: We evaluated a total of 717 ECG alarm segments from 109 patients. In 4 patients (3.7, 95% confidence interval [CI] 1.18-9.68%) physicians had missed AF despite at least one true positive alarm. All four patients did not receive long-term secondary prevention in form of anticoagulant therapy. 427 out of 717 alarms were rated true positives, resulting in a positive predictive value of 0.6 (CI 0.56-0.63) in this cohort. Conclusion: By connecting a data warehouse, electronic health records and a REDCap survey tool, we introduce a path to assess the monitoring quality of AF in acute stroke patients. We find that implemented standards of procedure to detect AF during stroke unit care are effective but leave room for improvement. Such data warehouse-based concepts may help to adjust internal processes or identify targets of further investigations.

Safety and effectiveness of IV Thrombolysis in retinal artery occlusion: A multicenter retrospective cohort study.

BACKGROUND: Retinal artery occlusion (RAO) may lead to irreversible blindness. For acute RAO, intravenous thrombolysis (IVT) can be considered as treatment. However, due to the rarity of RAO, data about IVT safety and effectiveness is limited. METHODS: From the multicenter database ThRombolysis for Ischemic Stroke Patients (TRISP), we retrospectively analyzed visual acuity (VA) at baseline and within 3 months in IVT and non-IVT treated RAO patients. Primary outcome was difference of VA between baseline and follow up (∆VA). Secondary outcomes were rates of visual recovery (defined as improvement of VA ⩾ 0.3 logMAR), and safety (symptomatic intracranial hemorrhage (sICH) according to ECASS II criteria, asymptomatic intracranial hemorrhage (ICH) and major extracranial bleeding). Statistical analysis was performed using parametric tests and a linear regression model adjusted for age, sex and baseline VA. RESULTS: We screened 200 patients with acute RAO and included 47 IVT and 34 non-IVT patients with complete information about recovery of vision. Visual Acuity at follow up significantly improved compared to baseline in IVT patients (∆VA 0.5 ± 0.8, p < 0.001) and non-IVT patients (∆VA 0.40 ± 1.1, p < 0.05). No significant differences in ∆VA and visual recovery rate were found between groups at follow up. Two asymptomatic ICH (4%) and one (2%) major extracranial bleeding (intraocular bleeding) occurred in the IVT group, while no bleeding events were reported in the non-IVT group. CONCLUSION: Our study provides real-life data from the largest cohort of IVT treated RAO patients published so far. While there is no evidence for superiority of IVT compared to conservative treatment, bleeding rates were low. A randomized controlled trial and standardized outcome assessments in RAO patients are justified to assess the net benefit of IVT in RAO.

Safety and Healthcare Resource Utilization in Patients Undergoing Left Atrial Appendage Closure-A Nationwide Analysis.

Percutaneous left atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative for stroke prevention in patients with atrial fibrillation (AF) not suitable for anticoagulation therapy. Real-world data on peri-procedural outcomes are limited. The aim of this study was to analyze outcomes of peri-procedural safety and healthcare resource utilization in 11,240 adult patients undergoing LAAC in the United States between 2016 and 2019. Primary outcomes (safety) were in-hospital ischemic stroke or systemic embolism (SE), pericardial effusion (PE), major bleeding, device embolization and mortality. Secondary outcomes (resource utilization) were adverse discharge disposition, hospital length of stay (LOS) and costs. Logistic and Poisson regression models were used to analyze outcomes by adjusting for 10 confounders. SE decreased by 97% between 2016 and 2019 [95% Confidence Interval (CI) 0-0.24] (p = 0.003), while a trend to lower numbers of other peri-procedural complications was determined. In-hospital mortality (0.14%) remained stable. Hospital LOS decreased by 17% (0.78-0.87, p < 0.001) and adverse discharge rate by 41% (95% CI 0.41-0.86, p = 0.005) between 2016 and 2019, while hospital costs did not significantly change (p = 0.2). Female patients had a higher risk of PE (OR 2.86 [95% CI 2.41-6.39]) and SE (OR 5.0 [95% CI 1.28-43.6]) while multi-morbid patients had higher risks of major bleeding (p < 0.001) and mortality (p = 0.031), longer hospital LOS (p < 0.001) and increased treatment costs (p = 0.073). Significant differences in all outcomes were observed between male and female patients across US regions. In conclusion, LAAC has become a safer and more efficient procedure. Significant sex differences existed across US regions. Careful considerations should be taken when performing LAAC in female and comorbid patients.

Enhanced diagnostic workup increases pathological findings in patients with acute ischaemic stroke: results of the prospective HEBRAS study.

BACKGROUND: Stroke 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. METHODS: Hospitalised 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. RESULTS: Among 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. CONCLUSIONS: Enhanced 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.

Data lake-driven analytics identify nocturnal non-dipping of heart rate as predictor of unfavorable stroke outcome at discharge.

BACKGROUND: Post-stroke heart rate (HR) and heart rate variability (HRV) changes have been proposed as outcome predictors after stroke. We used data lake-enabled continuous electrocardiograms to assess post-stroke HR and HRV, and to determine the utility of HR and HRV to improve machine learning-based predictions of stroke outcome. METHODS: In this observational cohort study, we included stroke patients admitted to two stroke units in Berlin, Germany, between October 2020 and December 2021 with final diagnosis of acute ischemic stroke or acute intracranial hemorrhage and collected continuous ECG data through data warehousing. We created circadian profiles of several continuously recorded ECG parameters including HR and HRV parameters. The pre-defined primary outcome was short-term unfavorable functional outcome after stroke indicated through modified Rankin Scale (mRS) score of > 2. RESULTS: We included 625 stroke patients, 287 stroke patients remained after matching for age and National Institute of Health Stroke Scale (NIHSS; mean age 74.5 years, 45.6% female, 88.9% ischemic, median NIHSS 5). Both higher HR and nocturnal non-dipping of HR were associated with unfavorable functional outcome (p < 0.01). The examined HRV parameters were not associated with the outcome of interest. Nocturnal non-dipping of HR ranked highly in feature importance of various machine learning models. CONCLUSIONS: Our data suggest that a lack of circadian HR modulation, specifically nocturnal non-dipping, is associated with short-term unfavorable functional outcome after stroke, and that including HR into machine learning-based prediction models may lead to improved stroke outcome prediction.

Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration.

OBJECTIVE: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection. METHODS: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging. RESULTS: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (ORadjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (ORadjusted 1.01, 95% CI 0.83-1.22), and mortality (ORadjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; ORadjusted 0.51, 95% CI 0.33-0.79). INTERPRETATION: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

New Cerebral Microbleeds After Catheter-Based Structural Heart Interventions: An Exploratory Analysis.

Background Cerebral microbleeds (CMBs) are increasingly recognized as "covert" brain lesions indicating increased risk of future neurological events. However, data on CMBs in patients undergoing catheter-based structural heart interventions are scarce. Therefore, we assessed occurrence and predictors of new CMBs in patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Methods and Results We conducted an exploratory analysis using data derived from 2 prospective, observational studies. Eligible patients underwent cerebral magnetic resonance imaging (3 Tesla) examinations and cognitive tests (using the Montreal Cognitive Assessment) before and after catheter-based left atrial appendage closure and percutaneous mitral valve repair. Forty-seven patients (53% men; median age, 77 years) were included. New CMBs occurred in 17 of 47 patients (36%) following catheter-based structural heart interventions. Occurrences of new CMBs did not differ significantly between patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair (7/25 versus 10/22; P=0.348). In univariable analysis, longer procedure time was significantly associated with new CMBs. Adjustment for heparin attenuated this association (adjusted odds ratio [per 30 minutes]: 1.77 [95% CI, 0.92-3.83]; P=0.090). Conclusions New CMBs occur in approximately one-third of patients after catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Our data suggest that longer duration of the procedure may be a risk factor for new CMBs. Future studies in larger populations are needed to further investigate their clinical relevance. Clinical Trial Registration German Clinical Trials Register: DRKS00010300 (https://drks.de/search/en/trial/DRKS00010300); ClinicalTrials.gov : NCT03104556 (https://clinicaltrials.gov/ct2/show/NCT03104556?term=NCT03104556&draw=2&rank=1).

Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants.

Importance: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC). Objective: To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion. Design, Setting, and Participants: This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021. Exposures: Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation. Main Outcomes and Measures: The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses. Results: Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion. Conclusions and Relevance: In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

High-Sensitivity Cardiac Troponin T and Cognitive Decline in Older Adults: Results of the Berlin Aging Study II.

INTRODUCTION: There is evidence of an association between markers of cardiac injury and cognition in patients with cardiovascular disease. We hypothesized that levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with cognitive performance and cognitive decline in a population of predominantly healthy older adults. METHODS: We included 1,226 predominantly healthy adults ≥60 years from the Berlin Aging Study II. Participants were recruited from the general population of the Berlin metropolitan area from 2009 to 2014. At baseline, participants underwent measurement of hs-cTnT and cognitive testing using the extended Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) battery. In addition, the Digit Symbol Substitution Test (DSST) was performed at baseline and at follow-up (7.3 ± 1.4 years after the baseline visit). The CERAD test results were summarized into four cognitive domains (processing speed, executive function, visuo-construction, and memory). After summing-up the respective raw scores, we calculated standardized z scores. We performed unadjusted and adjusted linear regression models to assess links between hs-cTnT and cognitive domains. We used linear mixed models to analyze associations between hs-cTnT and cognitive decline according to changes in DSST scores over time. RESULTS: The mean age of study participants at baseline was 68.5 (±3.6) years, 49% were female, and median hs-cTnT levels were 6 ng/L (IQR 4-8 ng/L). We detected no significant association between hs-cTnT and different cognitive domains at baseline after adjustment for age, sex, education, and cardiovascular risk factors. Hs-cTnT was associated with cognitive decline, which remained statistically significant after full adjustment (adjusted beta-coefficient -0.82 (-1.28 to -0.36), p = 0.001). After stratification for sex, the association with hs-cTnT remained statistically significant in men but not in women. CONCLUSION: Higher hs-cTnT levels in older men are associated with cognitive decline measured with the DSST.

Elevation of cardiac biomarkers in stroke is associated with pathological findings on cardiac MRI-results of the HEart and BRain interfaces in Acute Stroke study.

INTRODUCTION: Cardiac biomarkers, such as high-sensitivity cardiac troponin T (hs-cTnT), are frequently elevated in ischemic stroke patients but the mechanisms underlying this elevation are insufficiently understood. We determined the presence of cardiac damage, assessed using cardiac magnetic resonance imaging (CMR), in stroke patients with elevated hs-cTnT and brain natriuretic peptide (BNP). METHODS: This is a post hoc analysis of the prospective, investigator-initiated, cross-sectional HEart and BRain interfaces in Acute Stroke (HEBRAS) study. All patients underwent the measurement of hs-cTnT and BNP as well as gadolinium-enhanced CMR in the acute phase of ischemic stroke. We performed unadjusted and adjusted logistic regression models to assess the association between hs-cTnT and BNP elevation and the presence of pathological CMR findings. RESULTS: Two hundred and thirty-three stroke patients (median age 67 years, 33% female) were included, of whom 43 (21%) had elevated hs-cTnT and 109 (47%) had elevated BNP. Hundred of the 233 (43%) patients had pathological findings on CMR had focal fibrosis as detected by late-gadolinium enhancement (LGE) in 51 (23%), left-ventricular hypertrophy (LVH) in 38 (16%), reduced LVEF in 32 (14%), and left-atrial dilatation in 34 (15%). After adjustment for potential confounders, both hs-cTnT (adjOR 5.0 (95%CI 2.1-11.7), p < 0.001) and BNP (adjOR 4.1 (95%CI 2.3-7.3), p < 0.001) were significantly associated with pathological findings on CMR. Hs-cTnT was associated with LGE, LVEF, and LVH, whereas BNP was associated with left-atrial dilatation and LVEF, LVH. CONCLUSION: Elevated cardiac biomarkers in acute stroke including CMR are strongly associated with pathological findings on CMR. In acute stroke patients, the elevation of cardiac biomarkers may identify patients who require a more thorough cardiology work-up.

Frequency, associated variables, and outcomes of acute myocardial injury according to the fourth Universal Definition of Myocardial Infarction in patients with acute ischemic stroke.

Background: Myocardial injury as indicated by elevation of cardiac troponin levels is common after acute ischemic stroke (AIS) and linked to poor outcomes. Previous studies rarely reported on serial hs-cTn measurements to distinguish whether myocardial injury is acute or chronic. Thus, little is known about frequency, associated variables, and outcome of acute myocardial injury in AIS. Methods and patients: In this single-centered observational cohort study, from 01/2019 to 12/2020, consecutive patients with neuroimaging-confirmed AIS <48 h after symptom onset, and serial troponin measurements within the first 2 days after admission (Roche Elecsys®, hs-cardiac troponin T) were prospectively registered. Acute myocardial injury was defined according to the fourth Universal Definition of Myocardial Infarction (troponin above the upper reference limit and rise/fall>20%). Outcomes of interest were in-hospital mortality and unfavorable functional status at discharge (modified Rankin Scale >1). Results: Out of 1067 analyzed patients, 25.3% had acute myocardial injury, 40.4% had chronic myocardial injury and 34.3% had no myocardial injury. Older age, higher stroke severity, thrombolytic treatment, and impaired kidney function were independently associated with acute myocardial injury. In-hospital mortality was higher in patients with acute myocardial injury than in those without (13% vs 3%, adjusted OR, 2.9% [95% CI, 1.6-5.5]). Compared with no myocardial injury, both acute and chronic myocardial injury were associated with unfavorable functional status at discharge (adjusted OR, 1.6 [95% CI, 1.1-2.5] and OR, 1.7 [95% CI, 1.2-2.4], respectively). Conclusions: A quarter of patients with AIS have evidence of acute myocardial injury according to the fourth Universal Definition of Myocardial Infarction. The strong association with in-hospital mortality highlights the need for clinical awareness and future studies on underlying mechanisms.

Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration.

BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Stroke-Heart Syndrome: Recent Advances and Challenges.

After ischemic stroke, there is a significant burden of cardiovascular complications, both in the acute and chronic phase. Severe adverse cardiac events occur in 10% to 20% of patients within the first few days after stroke and comprise a continuum of cardiac changes ranging from acute myocardial injury and coronary syndromes to heart failure or arrhythmia. Recently, the term stroke-heart syndrome was introduced to provide an integrated conceptual framework that summarizes neurocardiogenic mechanisms that lead to these cardiac events after stroke. New findings from experimental and clinical studies have further refined our understanding of the clinical manifestations, pathophysiology, and potential long-term consequences of the stroke-heart syndrome. Local cerebral and systemic mediators, which mainly involve autonomic dysfunction and increased inflammation, may lead to altered cardiomyocyte metabolism, dysregulation of (tissue-resident) leukocyte populations, and (micro-) vascular changes. However, at the individual patient level, it remains challenging to differentiate between comorbid cardiovascular conditions and stroke-induced heart injury. Therefore, further research activities led by joint teams of basic and clinical researchers with backgrounds in both cardiology and neurology are needed to identify the most relevant therapeutic targets that can be tested in clinical trials.