Effect of Mobile Stroke Unit Dispatch in all Patients with Acute Stroke or TIA.

OBJECTIVE: To determine the effect of additional mobile stroke unit (MSU) dispatch on functional outcomes among the full spectrum of stroke patients, regardless of subtype or potential contraindications to reperfusion therapies. METHODS: We used data from the nonrandomized Berlin-based B_PROUD study (02/2017 to 05/2019), in which MSUs were dispatched based solely on availability, and the linked B-SPATIAL stroke registry. All patients with final stroke or transient ischemic attack (TIA) diagnoses were eligible. The intervention under study was the additional dispatch of an MSU, an emergency physician-staffed ambulance equipped to provide prehospital imaging and thrombolytic treatment, compared to conventional ambulance alone. The primary outcome was the 3-month modified Rankin Scale (mRS) score, and the co-primary outcome was a 3-tiered disability scale. We identified confounders using directed acyclic graphs and obtained adjusted effect estimates using inverse probability of treatment weighting. RESULTS: MSUs were dispatched to 1,125 patients (mean age: 74 years, 46.5% female), while for 1,141 patients only conventional ambulances were dispatched (75 years, 49.9% female). After confounding adjustment, MSU dispatch was associated with more favorable 3-month mRS scores (common odds ratio [cOR] = 0.82; 95% confidence interval [CI]: 0.71-0.94). No statistically significant association was found with the co-primary outcome (cOR = 0.86; 9% CI: 0.72-1.01) or 7-day mortality (OR = 0.94; 95% CI: 0.59-1.48). INTERPRETATION: When considering the entire population of stroke/TIA patients, MSU dispatch improved 3-month functional outcomes without evidence of compromised safety. Our results are relevant for decision-makers since stroke subtype and treatment eligibility are unknown at time of dispatch. ANN NEUROL 2023;93:50-63.

Levels and dynamics of estimated glomerular filtration rate and recurrent vascular events and death in patients with minor stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Impaired kidney function is associated with an increased risk of vascular events in acute stroke patients, when assessed by single measurements of estimated glomerular filtration rate (eGFR). It is unknown whether repeated measurements provide additional information for risk prediction. METHODS: The MonDAFIS (Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke) study randomly assigned 3465 acute ischemic stroke patients to either standard procedures or an additive Holter electrocardiogram. Baseline eGFR (CKD-EPI formula) were dichotomized into values of < versus ≥60 ml/min/1.73 m2 . eGFR dynamics were classified based on two in-hospital values as "stable normal" (≥60 ml/min/1.73 m2 ), "increasing" (by at least 15% from baseline, second value ≥ 60 ml/min/1.73 m2 ), "decreasing" (by at least 15% from baseline of ≥60 ml/min/1.73 m2 ), and "stable decreased" (<60 ml/min/1.73 m2 ). The composite endpoint (stroke, major bleeding, myocardial infarction, all-cause death) was assessed after 24 months. We estimated hazard ratios in confounder-adjusted models. RESULTS: Estimated glomerular filtration rate at baseline was available in 2947 and a second value in 1623 patients. After adjusting for age, stroke severity, cardiovascular risk factors, and randomization, eGFR < 60 ml/min/1.73 m2 at baseline (hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.40-3.54) as well as decreasing (HR = 1.79, 95% CI = 1.07-2.99) and stable decreased eGFR (HR = 1.64, 95% CI = 1.20-2.24) were independently associated with the composite endpoint. In addition, eGFR < 60 ml/min/1.732 at baseline (HR = 3.02, 95% CI = 1.51-6.10) and decreasing eGFR were associated with all-cause death (HR = 3.12, 95% CI = 1.63-5.98). CONCLUSIONS: In addition to patients with low eGFR levels at baseline, also those with decreasing eGFR have increased risk for vascular events and death; hence, repeated estimates of eGFR might add relevant information to risk prediction.

[Comparison between chest pain units and stroke units : Essential components of the vascular emergency care system: comparison of structure, certification process, quality benchmarking and reimbursement]. / Vergleich von Chest Pain Units und Stroke Units : Elementare Bausteine der vaskulären Akutversorgung: Vergleich von Struktur, Zertifizierung, Qualitätserfassung und Vergütung.

BACKGROUND: Chest pain units (CPU) and stroke units (SU) have both become established as essential components of clinical emergency care. For both instances dedicated certification processes are installed. Up to summer 2020, 290 CPUs and 335 SUs have been successfully certified. OBJECTIVE: The aim of this review is to compare the structures and the current certification situation of CPUs and SUs. Also, the younger CPU certification process is compared to the long established SU certification standard. MATERIAL UND METHODS: The comparison includes the historical background, the certification process, quality benchmarking, possible additive structures, the current status of certification in Germany, the transfer of the concept to the European level as well as reimbursement issues. RESULTS: Both certification concepts show clear analogies. Evidence for SUs is supported by a positive Cochrane analysis and for CPUs there are many studies from the German CPU registry. The main differences include a uniform CPU system versus a multistep SU system of certification. Furthermore, SU have obligatory elements of quality documentation but only facultative quality indicator assessment for CPUs. From an economic viewpoint operation and procedural key (OPS) numbers guarantee a better reflection of the use of resources in the complex treatment of stroke, which could not yet be established for CPUs. CONCLUSION: The well-established CPU concept could additionally benefit from a superordinate quality control. Adequate quality benchmarking appears to be fundamental for gap analyses and for the establishment of a separate remuneration structure. In this respect the German Society for Cardiology as the certifying institution is required to establish an appropriate mechanism within the framework of regular updates of criteria.

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin.

Importance: Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective: To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure: Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures: The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results: Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance: In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

[Certification criteria for stroke units in Germany : Update 2018]. / Zertifizierungskriterien für Stroke-Units in Deutschland : Update 2018.

This article describes the revised criteria for certified stroke units (SU) in Germany that will apply from 1 October 2018. Due to the high level of quality only minor adjustments and specifications were necessary in many places and the majority of criteria remained unchanged. For the first time a uniform personnel quota of ≥1.75 full-time staff per monitor bed is defined, which is a better reflection of the treatment reality. The evidence-based process of acute vascular imaging using computed tomography angiography (CTA) and alternatively magnetic resonance angiography (MRA) is now defined as a minimum rate of≥20 % of all brain infarcts. In this way the timely identification of suitable candidates for endovascular thrombectomy (ET) should be accomplished. Ultrasound diagnostics of arteries supplying the brain remain an integral part of additional diagnostics after cerebral ischemia because this generates supplementary information. The extended detection of atrial fibrillation is newly included as a diagnostic minimum standard and necessitates measures that go beyond a single long-term electrocardiograph (ECG). In order to facilitate the certification of telemedically supplied SU (Tele-SU), the minimum standard of stroke patients was reduced to ≥200 per year. A Tele-SU in the immediate catchment area of a certified SU (<20 km) must provide proof of a regional treatment need in order for certification to be approved. Quality criteria in the audit reports have now a greater importance. They require a concrete plan of action, which must be tracked within the framework of the interim report and must be presented for the recertification. Furthermore, the SU are called upon not to limit the endeavors for quality only to the minimum requirements.

Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS): Rationale and design of a prospective randomized multicenter study.

BACKGROUND: Atrial fibrillation (AF) is estimated to account for approximately every fifth ischemic stroke. In routine clinical practice, detection of undiagnosed, clinically silent AF represents a major diagnostic challenge, and in up to 30% of patients with ischemic stroke, AF remains undetected. The MonDAFIS study has been designed to quantify the diagnostic yield and clinical relevance of systematic electrocardiogram (ECG) monitoring for patients with acute ischemic stroke during the subsequent in hospital stay. STUDY DESIGN: A prospective randomized multicenter study in 3,470 patients with acute ischemic stroke or transient ischemic attack and without known AF on hospital admission. Over a period of approximately 2years, patients will be enrolled in about 30 German-certified stroke units and randomized 1:1 to receive either usual stroke unit diagnostic procedures for detection of AF (control group) or usual stroke unit diagnostic procedures plus standardized and centrally analyzed Holter ECG recording for up to 7days in hospital (intervention group). Results of the ECG core laboratory analysis will be provided to the patients and treating physicians. All patients will be followed up for treatment and cardiovascular outcomes at 6, 12, and 24months after enrollment. OUTCOMES: The primary outcome of the randomized MonDAFIS study is the proportion of patients who receive anticoagulation therapy 12months after the index stroke. Secondary outcomes include the number of stroke patients with newly detected AF in hospital and the rate of recurrent stroke, major bleedings, myocardial infarction, or death 6, 12, and 24months after the index event. MonDAFIS will also explore patient-reported adherence to anticoagulants, the clinical relevance of short atrial tachycardia, or excessive supraventricular ectopic activity as well as cost-effectiveness of prolonged, centrally analyzed ECG recordings. CONCLUSION: MonDAFIS will be the largest study to date to evaluate whether a prolonged and systematic ECG monitoring during the initial in hospital stay has an impact on secondary stroke prevention. In addition, prognosis as well as adherence to medication up to 2 years after the index stroke will be analyzed. The primary results of the MonDAFIS study may have the potential to change the current guidelines recommendations regarding ECG workup after ischemic stroke.

Heart failure, recurrent vascular events and death in patients with ischemic stroke-results of the MonDAFIS study.

Heart failure (HF) is associated with poor outcome after stroke, but data from large prospective trials are sparse.We assessed the impact of HF on clinical endpoints in patients hospitalized with acute ischemic stroke or transient ischemic attack (TIA) enrolled in the prospective, multicenter Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke (MonDAFIS) trial. HF was defined as left ventricular ejection fraction (LVEF) < 55% or a history of HF on admission. The composite of recurrent stroke, major bleeding, myocardial infarction, and all-cause death, and its components during the subsequent 24 months were assessed. We used estimated hazard ratios in confounder-adjusted models. Overall, 410/2562 (16.0%) stroke patients fulfilled the HF criteria (i.e. 381 [14.9%] with LVEF < 55% and 29 [1.9%] based on medical history). Patients with HF had more often diabetes, coronary and peripheral arterial disease and presented with more severe strokes on admission. HF at baseline correlated with myocardial infarction (HR 2.21; 95% CI 1.02-4.79), and all-cause death (HR 1.67; 95% CI 1.12-2.50), but not with major bleed (HR 1.93; 95% CI 0.73-5.06) or recurrent stroke/TIA (HR 1.08; 95% CI 0.75-1.57). The data were adjusted for age, stroke severity, cardiovascular risk factors, and randomization. Patients with ischemic stroke or TIA and comorbid HF have a higher risk of myocardial infarction and death compared with non-HF patients whereas the risk of recurrent stroke or major hemorrhage was similar. Trial registration number Clinicaltrials.gov NCT02204267.

Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source.

BACKGROUND: Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial. METHODS: The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods. RESULTS: Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3-11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02-5.93) times higher risk of stroke recurrence than patients with a score of 0-4. The cumulative probability of stroke recurrence in the low-(0-4), intermediate-(5-6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1). CONCLUSIONS: This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model's performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS. TRIAL REGISTRATION: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267 .

Extent of routine diagnostic cardiac work-up at certified German stroke units participating in the prospective MonDAFIS study.

BACKGROUND: About 25% of all ischaemic strokes are related to cardio-embolism, most often due to atrial fibrillation (AF). Little is known about the extent and standardization of routine cardiac diagnostic work-up at certified stroke-units in Germany. METHODS: The MonDAFIS study included non-AF patients with acute ischaemic stroke or transient ischaemic attack (TIA) at 38 certified stroke-units in Germany. Here, we analysed routine diagnostic work-up and disregarded study-related Holter-ECG monitoring. We compared duration of stroke-unit stay, number of 24-h Holter-ECGs, and echocardiography performed between university-based comprehensive stroke centres (UCSC, 12 hospitals, 1606 patients), non university-based comprehensive stroke centres (nUCSC, 14 hospitals, 892 patients), and primary stroke centres at non-university hospitals (PCS, 12 hospitals, 933 patients) using multivariable mixed regression analyses. Detection of a first AF episode in-hospital was also compared between hospitals of different stroke-unit levels. RESULTS: In 3431 study patients (mean age 66.2 years, 39.5% female, median NIHSS = 2 on admission), median duration of the stroke-unit stay was 72 h (IQR 42-86). Stroke-unit stay was longer (categorised ≤ 24/ > 24- ≤ 72/ > 72 h) for patients with severe stroke (NIHSS score ≥ 5/ < 5: OR = 1.6, 95%CI 1.3-2.0) and for patients with ischaemic stroke vs. TIA (OR = 1.7, 95%CI 1.4-2.1). Overall, 2149/3396 (63.3%) patients underwent at least one additional 24-h Holter-ECG (median 1 [IQR 0-1], range 0-7). Holter-ECG rate was 47% in UCSC, 71% in nUCSC, and 84% in PCS. Compared to PCS, AF was less often detected in-hospital in UCSC (OR = 0.65, 95%CI 0.45-0.93) and nUCSC (OR = 0.69, 95%CI 0.46-1.04). Transoesophageal echocardiography (TEE) only was performed in 513/3391 (15.1%) study patients, transthoracic echocardiography (TTE) only in 1228/3391 (36.2%), and TEE combined with TTE in 1020/3391 (30.1%) patients. Patients younger than 60 years (vs. ≥ 60 years) underwent TEE more often than those older than 60 years (OR = 3.44, 95%CI 2.67-4.42). TEE (IQR 34-65%) and TTE rate (IQR 40-85%) varied substantially among study centres. Echocardiography rate (TTE and/or TEE) was 74.0% in UCSC, 85.4% in nUCSC, and 90.3% in PSC, respectively. CONCLUSIONS: In the MonDAFIS study, the routine use of echocardiography and Holter-ECG monitoring varied in participating stroke centres and at stroke-unit level, if grouped according to stroke-unit certification grade and hospitals´ university status. Trial registration Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267 .

In-Hospital ECG Findings, Changes in Medical Management, and Cardiovascular Outcomes in Patients With Acute Stroke or Transient Ischemic Attack.

Background In patients with acute ischemic stroke, little is known regarding the frequency of abnormal ECG findings other than atrial fibrillation and their association with cardiovascular outcomes. We aim to analyze the frequency and type of abnormal ECG findings, subsequent changes in medical treatment, and their association with cardiovascular outcomes in patients with acute ischemic stroke. Methods and Results In the investigator-initiated multicenter MonDAFIS (impact of standardized monitoring for detection of atrial fibrillation in ischemic stroke) study, 3465 patients with acute ischemic stroke or transient ischemic attack and without known atrial fibrillation were randomized 1:1 to receive Holter-ECG for up to 7 days in-hospital with systematic evaluation in a core cardiology laboratory (intervention group) or standard diagnostic care (control group). Outcomes included predefined abnormal ECG findings (eg, pauses, atrial fibrillation, brady-/tachycardias), medical management in the intervention group, and combined vascular end point (recurrent stroke, myocardial infarction, major bleeds, or all-cause death) and mortality at 24 months in both randomization groups. Predefined abnormal ECG findings were detected in 326 of 1693 (19.3%) patients in the intervention group. Twenty of these 326 patients (6.1%) received a pacemaker, and 62 of 326 (19.0%) patients had newly initiated or discontinued ß-blocker medication. Discontinuation of ß-blockers was associated with a higher death rate in the control group than in the intervention group during 24 months after enrollment (adjusted hazard ratio, 11.0 [95% CI, 2.4-50.4]; P=0.025 for interaction). Conclusions Systematic in-hospital Holter ECG reveals abnormal findings in 1 of 5 patients with acute stroke, and mortality was lower at 24 months in patients with systematic ECG recording in the hospital. Further studies are needed to determine the potential impact of medical management of abnormal ECG findings. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02204267.

Association of stroke lesion shape with newly detected atrial fibrillation - Results from the MonDAFIS study.

Paroxysmal Atrial fibrillation (AF) is often clinically silent and may be missed by the usual diagnostic workup after ischemic stroke. We aimed to determine whether shape characteristics of ischemic stroke lesions can be used to predict AF in stroke patients without known AF at baseline. Lesion shape quantification on brain MRI was performed in selected patients from the intervention arm of the Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS) study, which included patients with ischemic stroke or TIA without prior AF. Multiple morphologic parameters were calculated based on lesion segmentation in acute brain MRI data. Multivariate logistic models were used to test the association of lesion morphology, clinical parameters, and AF. A stepwise elimination regression was conducted to identify the most important variables. A total of 755 patients were included. Patients with AF detected within 2 years after stroke (n = 86) had a larger overall oriented bounding box (OBB) volume (p = 0.003) and a higher number of brain lesion components (p = 0.008) than patients without AF. In the multivariate model, OBB volume (OR 1.72, 95%CI 1.29-2.35, p < 0.001), age (OR 2.13, 95%CI 1.52-3.06, p < 0.001), and female sex (OR 2.45, 95%CI 1.41-4.31, p = 0.002) were independently associated with detected AF. Ischemic lesions in patients with detected AF after stroke presented with a more dispersed infarct pattern and a higher number of lesion components. Together with clinical characteristics, these lesion shape characteristics may help in guiding prolonged cardiac monitoring after stroke.

Heart rate monitoring on the stroke unit. What does heart beat tell about prognosis? An observational study.

BACKGROUND: Guidelines recommend maintaining the heart rate (HR) of acute stroke patients within physiological limits; data on the frequency and predictors of significant deviations from these limits are scarce. METHODS: Demographical data, stroke risk factors, NIH stroke scale score, lesion size and location, and ECG parameters were prospectively assessed in 256 patients with ischemic stroke. Patients were continuously monitored for at least 24 hours on a certified stroke unit. Tachycardia (HR ≥ 120 bpm) and bradycardia (HR <45 bpm) and cardiac rhythm (sinus rhythm or atrial fibrillation) were documented. We investigated the influence of risk factors on HR disturbances and their respective influence on dependence (modified Rankin Scale ≥ 3 after three months) and mortality. RESULTS: HR ≥ 120 bpm occurred in 39 patients (15%). Stroke severity (larger lesion size/higher NIHSS-score on admission), atrial fibrillation and HR on admission predicted its occurrence. HR <45 bpm occurred in 12 patients (5%) and was predicted by lower HR on admission. Neither HR ≥ 120 nor HR <45 bpm independently predicted poor outcome at three moths. Stroke location had no effect on the occurrence of HR violations. Clinical severity and age remained the only consistent predictors of poor outcome. CONCLUSIONS: Significant tachycardia and bradycardia are frequent phenomena in acute stroke; however they do not independently predict clinical course or outcome. Continuous monitoring allows detecting rhythm disturbances in stroke patients and allows deciding whether urgent medical treatment is necessary.

Systematic monitoring for detection of atrial fibrillation in patients with acute ischaemic stroke (MonDAFIS): a randomised, open-label, multicentre study.

BACKGROUND: Systematic electrocardiogram (ECG) monitoring improves detection of covert atrial fibrillation in stroke survivors but the effect on secondary prevention is unknown. We aimed to assess the effect of systematic ECG monitoring of patients in hospital on the rate of oral anticoagulant use after 12 months. METHODS: In this investigator-initiated, randomised, open-label, parallel-group multicentre study with masked endpoint adjudication, we recruited patients aged at least 18 years with acute ischaemic stroke or transient ischaemic attack without known atrial fibrillation in 38 certified stroke units in Germany. Patients were randomly assigned (1:1) to usual diagnostic procedures for atrial fibrillation detection (control group) or additional Holter-ECG recording for up to 7 days in hospital (intervention group). Patients were stratified by centre using a random permuted block design. The primary outcome was the proportion of patients on oral anticoagulants at 12 months after the index event in the intention-to-treat population. Secondary outcomes included the number of patients with newly diagnosed atrial fibrillation in hospital and the composite of recurrent stroke, major bleeding, myocardial infarction, or death after 6 months, 12 months, and 24 months. This trial was registered with ClinicalTrials.gov, NCT02204267, and is completed and closed for participants. FINDINGS: Between Dec 9, 2014, and Sept 11, 2017, 3465 patients were randomly assigned, 1735 (50·1%) to the intervention group and 1730 (49·9%) to the control group. Oral anticoagulation status was available in 2920 (84·3%) patients at 12 months (1484 [50·8%] in the intervention group and 1436 [49·2%] in the control group). For the primary outcome, at 12 months, 203 (13·7%) of 1484 patients in the intervention group versus 169 (11·8%) of 1436 in the control group were on oral anticoagulants (odds ratio [OR] 1·2 [95% CI 0·9-1·5]; p=0·13). Atrial fibrillation was newly detected in patients in hospital in 97 (5·8%) of 1714 in the intervention group versus 68 (4·0%) of 1717 in the control group (hazard ratio [HR] 1·4 [95% CI 1·0-2·0]; p=0·024). The composite of cardiovascular outcomes and death did not differ between patients randomly assigned to the intervention group versus the control group at 24 months (232 [13·5%] of 1714 vs 249 [14·5%] of 1717; HR 0·9 [0·8-1·1]; p=0·43). Skin reactions due to study ECG electrodes were reported in 56 (3·3%) patients in the intervention group. All-cause death occured in 73 (4·3%) patients in the intervention group and in 103 (6·0%) patients in the control group (OR 0·7 [0·5-0·9]). INTERPRETATION: Systematic core centrally reviewed ECG monitoring is feasible and increases the detection rate of atrial fibrillation in unselected patients hospitalised with acute ischaemic stroke or transient ischaemic attack, if added to usual diagnostic care in certified German stroke units. However, we found no effect of systematic ECG monitoring on the rate of oral anticoagulant use after 12 months and further efforts are needed to improve secondary stroke prevention. FUNDING: Bayer Vital. TRANSLATION: For the German translation of the abstract see Supplementary Materials section.

Blood pressure threshold violations in the first 24 hours after admission for acute stroke: frequency, timing, predictors, and impact on clinical outcome.

BACKGROUND AND PURPOSE: Admission blood pressure (BP) and significant decreases in BP after acute stroke have been correlated with outcome. Few data are available on the impact of extreme values at any time point within the first 24 hours. METHODS: BP was measured hourly for 24 hours in 325 consecutive patients with acute ischemic stroke. Predefined endpoints were systolic BP >or=200, diastolic BP >or=110, or systolic BP <100 mm Hg during the first 24 hours, and significant systolic BP decreases by >26 mm Hg within 4 hours after admission. Multiple logistic regression analysis identified independent predictors of each end point and determined the impact on dependency at 3 months defined as modified Rankin scale score >or=3. RESULTS: Upper threshold violations occurred in 70% of cases during the admission process, and more frequently in patients arriving early after stroke; 30% of cases exhibited such values at a later time point. History of hypertension (P<0.01) and higher NIHSS on admission (P<0.05) were independent predictors. Systolic BP <100 mm Hg occurred at random and was associated with younger age (P<0.05). Night time admission was the strongest independent predictor of systolic BP decreases >26 mm Hg (P<0.0001). Diabetes, NIHSS on admission, and age were associated with adverse outcome at 3 months, whereas threshold violations and decreases were not. There was a trend for administration of antihypertensives being associated with poor outcome (P<0.1). CONCLUSIONS: External stimuli, premorbid risk factors, diurnal BP variations, and disease-immanent mechanisms all influence the course of BP after acute stroke. Monitoring should precede any medical BP treatment.

Fiberoptic endoscopic Dysphagia severity scale predicts outcome after acute stroke.

BACKGROUND AND PURPOSE: Fiberoptic endoscopic evaluation of swallowing (FEES) is a suitable method for dysphagia assessment after acute stroke. Recently, we developed the fiberoptic endoscopic dysphagia severity scale (FEDSS) for acute stroke patients, grading dysphagia into 6 severity codes (1 to 6; 1 being best). The purpose of this study was to investigate the impact of the FEDSS as a predictor of outcomes at 3 months and intermediate complications during acute treatment. METHODS: A total of 153 consecutive first-ever acute stroke patients were enrolled. Dysphagia was classified according to the FEDSS, assessed within 24 h after admission. Intermediate outcomes were pneumonia and endotracheal intubation. Functional outcome was measured by the modified Rankin Scale (mRS) at 3 months. Multivariate regression analysis was used to identify whether the FEDSS was an independent predictor of outcome and intercurrent complications. Analyses were adjusted for sex, age and National Institutes of Health Stroke Scale (NIH-SS) on admission. RESULTS: The FEDSS was found to predict the mRS at 3 months as well as but independent from the NIH-SS. For each additional point on the FEDSS, the likelihood of dependency at 3 months (mRS > or = 3) raised by approximately 50%. Each increase of 1 point on the FEDSS conferred a more than 2-fold increased chance of developing pneumonia. The odds for the necessity of endotracheal intubation raised by a factor of nearly 2.5 with each additional point on the FEDSS. CONCLUSIONS: The FEDSS strongly and independently predicts outcome and intercurrent complications after acute stroke. Thus, a baseline FEES examination provides valuable prognostic information for the treatment of acute stroke patients.

Microembolic signals on transcranial Doppler ultrasound are correlated with platelet activation markers, but not with platelet-leukocyte associates: a study in patients with acute stroke and in patients with asymptomatic carotid stenosis.

BACKGROUND: The in vivo correlates of microembolic signals (MES) are still unknown. Platelet-associates (PA) with monocytes or granulocytes or platelet aggregates only may represent these correlates. METHODS: Thirty patients with asymptomatic carotid stenosis >50% and 16 patients with acute (<4 days) atherothrombotic stroke were investigated. PA, P-selectin and thrombospondin expressions on platelets were assessed by flow cytometry. Soluble P-selectin (sPS) levels were assessed. MES detections were performed by transcranial Doppler sonography for 1 hour. PA, P-selectin and thrombospondin expressions on platelets and sPS levels were compared between MES-positive (MES+) and MES-negative (MES-) patients. RESULTS: Eight patients (27%) with asymptomatic carotid stenosis had 1-26 MES/h. Degree of stenosis was 78 +/- 10% in MES- and 88 +/- 8% in the MES+ (p=0.01). There were no differences in percentages of PA. P-selectin and thrombospondin surface expression was lower in MES+, but this was not significant. sPS levels were higher in MES+ (122 +/- 27 ng/ml versus 80 +/- 25 ng/ml in MES-, p=0.01). Seven (44%) patients with stroke had 1-39 MES/h. There were no differences in percentages of PA. MES+ had higher sPS levels (178 +/- 43 versus 121 +/- 44 ng/ml, p=0.02) and less P-selectin surface expression than MES- (9.0 +/- 3.4 versus 4.5 +/- 1.6%, p=0.004). CONCLUSION: High levels of sPS in MES+ and lower expression of platelet activation markers on platelets' surface suggest shedding of activation markers from the platelets' surface and thus enhanced activation of platelets of MES+ compared with MES-. PA are probably not the clinical correlates of MES, but platelets seem to be the main cellular element of solid cerebral microemboli.

Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): multicentre, randomised controlled, endpoint blinded trial.

OBJECTIVE: To determine the safety and efficacy of aerobic exercise on activities of daily living in the subacute phase after stroke. DESIGN: Multicentre, randomised controlled, endpoint blinded trial. SETTING: Seven inpatient rehabilitation sites in Germany (2013-17). PARTICIPANTS: 200 adults with subacute stroke (days 5-45 after stroke) with a median National Institutes of Health stroke scale (NIHSS, range 0-42 points, higher values indicating more severe strokes) score of 8 (interquartile range 5-12) were randomly assigned (1:1) to aerobic physical fitness training (n=105) or relaxation sessions (n=95, control group) in addition to standard care. INTERVENTION: Participants received either aerobic, bodyweight supported, treadmill based physical fitness training or relaxation sessions, each for 25 minutes, five times weekly for four weeks, in addition to standard rehabilitation therapy. Investigators and endpoint assessors were masked to treatment assignment. MAIN OUTCOME MEASURES: The primary outcomes were change in maximal walking speed (m/s) in the 10 m walking test and change in Barthel index scores (range 0-100 points, higher scores indicating less disability) three months after stroke compared with baseline. Safety outcomes were recurrent cardiovascular events, including stroke, hospital readmissions, and death within three months after stroke. Efficacy was tested with analysis of covariance for each primary outcome in the full analysis set. Multiple imputation was used to account for missing values. RESULTS: Compared with relaxation, aerobic physical fitness training did not result in a significantly higher mean change in maximal walking speed (adjusted treatment effect 0.1 m/s (95% confidence interval 0.0 to 0.2 m/s), P=0.23) or mean change in Barthel index score (0 (-5 to 5), P=0.99) at three months after stroke. A higher rate of serious adverse events was observed in the aerobic group compared with relaxation group (incidence rate ratio 1.81, 95% confidence interval 0.97 to 3.36). CONCLUSIONS: Among moderately to severely affected adults with subacute stroke, aerobic bodyweight supported, treadmill based physical fitness training was not superior to relaxation sessions for maximal walking speed and Barthel index score but did suggest higher rates of adverse events. These results do not appear to support the use of aerobic bodyweight supported fitness training in people with subacute stroke to improve activities of daily living or maximal walking speed and should be considered in future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT01953549.

Prevalence and prognostic impact of microembolic signals in arterial sources of embolism. A systematic review of the literature.

OBJECTIVE: To compile available studies using microembolic signal (MES) detection by transcranial Doppler sonography in varying sources of arterial brain embolism. We investigated prevalences of MES and whether MES detection is of proven use for risk stratification. METHOD: Studies reporting prevalences of MES and the risk of cerebral ischemic events were pooled for patients with symptomatic or asymptomatic carotid stenosis, intracranial artery stenosis, cervical artery dissection, and aortic embolism. RESULTS: MES were reported in 43% of 586 patients with symptomatic and in 10% of 1066 patients with asymptomatic carotid stenosis. Presence of one MES indicated an increased risk of future events [odds ratio (OR): 7.5, 95% confidence interval (CI): 3.6-15.4, p<0.0001 for symptomatic, and OR: 13.4, 95% CI: 6.5-27.4, p<0.0001 for asymptomatic disease). MES were reported in 25% of 220 patients with symptomatic vs. 0% of 86 patients with asymptomatic intracranial stenosis (p<0.0001), Of 82 patients with cervical artery dissection presenting with TIA or stroke, 50% had MES compared with 13% of 16 patients with local symptoms (p=0.006), In patients with aortic embolism, patients with plaques >or= 4 mm more frequently had MES compared with patients with smaller plaques (p=0.04), Data were insufficient to reliably predict future events in patients with intracranial stenosis, cervical artery dissection, and aortic embolism. CONCLUSION: MES are a frequent finding in varying sources of arterial brain embolism, MES detection is useful for risk stratification in patients with carotid stenosis.

Neurosonographical follow-up in patients with spontaneous cervical artery dissection.

OBJECTIVE: Neurovascular ultrasound (nUS) is widely used as a screening and monitoring tool in patients with spontaneous cervical artery dissection (sCAD). The aim of the study was to describe the sonographical course of the affected arteries in patients with a MRI-proven sCAD by repetitive nUS. METHODS: Thirty-seven consecutive patients aged<60 years with 1.5 T MRI-proven sCAD were prospectively investigated by nUS, and within 48 hours after admission before MRI. The patients were re-investigated after 6 months and again after a period>12 months. RESULTS: Forty-nine sCAD were detected in 37 patients; 24 lesions (49%) were located in the internal carotid arteries (ICA), and 25 (51%) in the vertebral arteries (VA). An arterial occlusion was found in 13 arteries (27%). The recanalization rate of occluded arteries was 62%. Regression of stenosis/occlusion within the first 6 months was found in 34 (69%) of the affected arteries, while between 6 and >12 months, the improvement rate was lower (19%). A complete recanalization without residual stenosis after 6 months was found in 39%. In only one artery, initial high grade ICA stenosis progressed to complete persistent occlusion (2%). DISCUSSION: The course of arterial stenosis or occlusion caused by sCAD is highly dynamic during the first 6 month after the event. The vast majority of arteries show regression of stenosis or recanalization of initial occlusion. Only a minority of patients experience a persistent deterioration of the vessel status.

Positional sleep apnea in patients with ischemic stroke.

BACKGROUND: In non-stroke patients, the severity of sleep apnea (SA) is known to be frequently related to the sleeping position, a condition called positional SA. In the present study, we investigated whether in acute stroke the occurrence of apneas was related to the positioning of patients, and whether a similar finding could be observed after rehabilitation. With the purpose of identifying patients potentially being in need of a SA treatment beyond rehabilitation, we furthermore looked for epidemiologic and clinical parameters being related to persistent SA 6 months after stroke. PATIENTS AND METHODS: Fifty-five acute stroke patients underwent cardiorespiratory polygraphy within 72 hours after onset of neurological symptoms and after 6 months. Apart from the total AHI (AHITOT), the AHI with the patient in supine position and the AHI with the patient in other positions were determined. In all patients, demographic data, NIH-stroke scale score and cumulative vascular risk factors were assessed. RESULTS: In the initial sleep study, 78% of patients had an AHI>or=10/h, of whom 65% fulfilled the criteria of positional SA. On follow-up, the incidence of SA declined to 49% with positional SA being present in 33%. Multivariate logistic regression analysis identified AHITOT on admission [OR=1.07 (1.002-1.13)] and cumulative vascular risk factors [OR=3.48 (1.34-9.05)] as independent predictors of persistent SA 6 months after stroke. CONCLUSION: According to our results, positional SA is a predominant feature in acute stroke and its incidence decreases significantly during the following months. These findings may have implications for SA treatment in patients with acute stroke.