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.

Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry.

AIMS: The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke. METHODS AND RESULTS: This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient. Within 2014 and 2016, 1080 patients gave written informed consent and 1048 patients were available for analysis. Median age was 77 years [interquartile range (IQR) 72-83], 503 (48%) patients were female, and 254 (24%) had a transient ischaemic attack (TIA). Overall, 470 (62%) out of 757 patients with known AF and a (pre-stroke) CHA2DS2-VASc ≥ 1 were anticoagulated at the time of stroke. At hospital discharge, 847 (81.3%) of 1042 patients were anticoagulated. Thereof 710 (68.1%) received a non-vitamin K-dependent oral anticoagulant (NOAC) and 137 (13.1%) a vitamin K antagonist (VKA). Pre-stroke intake of a NOAC [odds ratio (OR) 15.6 (95% confidence interval, 95% CI 1.97-122)] or VKA [OR 0.04 (95% CI 0.02-0.09)], an index TIA [OR 0.56 (95% CI 0.34-0.94)] rather than stroke, heart failure [OR 0.49 (95% CI 0.26-0.93)], and endovascular thrombectomy at hospital admission [OR 12.9 (95% CI 1.59-104)] were associated with NOAC prescription at discharge. Patients' age or AF type had no impact on OAC or NOAC use, respectively. CONCLUSION: About 60% of all registry patients with known AF received OAC at the time of stroke or TIA. At hospital discharge, more than 80% of AF patients were anticoagulated and about 80% of those were prescribed a NOAC.

Detection of Atrial Fibrillation in Cryptogenic Stroke.

PURPOSE OF REVIEW: To summarize the literature on the detection of atrial fibrillation (AF) in patients with "cryptogenic" stroke, a cohort including about 25% of all ischemic stroke patients and patients with embolic stroke of undetermined source (ESUS). RECENT FINDINGS: A first episode of AF is detected in up to one third of cryptogenic stroke and in up to one fourth of ESUS patients during long-term monitoring. AF prevalence correlates to patient selection, duration, and quality of ECG monitoring. Higher rates of AF were reported in stroke patients with left atrial pathology, specific ECG alterations, or increased natriuretic peptides. While AF detection impacts on medical stroke prevention in the vast majority of patients, patient selection for prolonged monitoring is largely left at the physician's discretion. AF detection after cryptogenic stroke or ESUS is a frequent, potentially causal condition. Whether subsequent oral anticoagulation may improve outcome remains open.

Somatosensory symptoms in unmedicated de novo patients with idiopathic Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative condition presenting with motor and non-motor symptoms including somatosensory disturbances. As neuropathic syndromes in advanced PD patients are supposed to be due to antiparkinsonian medication, we studied the presence of somatosensory symptoms and peripheral nerve function in drug naïve patients with PD as well as age-matched healthy controls. Somatosensory symptoms and signs were investigated in 39 de novo PD patients and 32 age-matched healthy controls using the modified Toronto Clinical Neuropathy Scale. To elucidate potential underlying mechanisms, peripheral nerve function was analyzed with sensory and motor neurography. About two thirds of de novo diagnosed levodopa naïve PD patients (66.7 %) reported somatosensory symptoms in comparison to one third of the control group (31.2 %) (p = 0.003). The presence of PD (p = 0.017) was a predictive factor for the occurrence of somatosensory symptoms among all participants. In contrast to the significantly higher frequency of somatosensory symptoms in patients with PD compared to controls, neurographically based peripheral nerve function did not differ between the groups. Our results indicate that somatosensory symptoms are a PD feature, which can be found when diagnosed first and independently of dopaminergic treatment. As the electrophysiologically determined peripheral nerve function was not different from that obtained in the control group, somatosensory symptoms are inherent in early PD and may be, at least partially, of central origin.

Safety of thrombolysis in patients with acute ischemic stroke and cerebral cavernous malformations.

BACKGROUND AND PURPOSE: Data on safety of intravenous thrombolysis with recombinant tissue-type plasminogen activator for acute ischemic stroke in patients with coexisting cerebral cavernous malformations (CCMs) are scarce. We assessed the risk of thrombolysis-associated hemorrhage in these patients. METHODS: We searched our tertiary care hospital thrombolysis register for patients with CCM confirmed by MRI (3 T, Siemens, TimTrio) before thrombolysis for acute ischemic stroke. CCMs were graded into subtypes according to the Zabramski classification on the basis of their MRI appearance. The primary end point was symptomatic intracerebral hemorrhage according to European Cooperative Acute Stroke Study III (ECASS III) criteria. The secondary end point was any parenchymal hemorrhage. RESULTS: In a total of 350 patients (median age, 76 years; interquartile range, 68-84; median National Institutes of Health Stroke Scale score, 8; interquartile range, 5-14; 51.4% women), CCMs were found in 9 patients (2.6%). Seven patients had a single CCM, and 2 patients had multiple CCMs with a total number of 12 CCMs in all patients. The subtype of CCMs was type III in 9 cases and type I in 3 cases. Symptomatic intracerebral hemorrhage occurred in 1 of 9 patients with CCM versus 11 of 341 patients without CCM (P=0.27). Parenchymal hemorrhage occurred in 2 of 9 patients with CCM versus 27 of 341 patients (P=0.17) without CCM. CONCLUSIONS: Given the limitations of our study (mainly low number of patients with CCM), the risk of thrombolysis-associated hemorrhage in patients with CCM remains uncertain. Although our data do not suggest an increased hazard from thrombolysis in patients with CCM, larger studies are necessary to determine definitively the influence of CCMs on parenchymal hemorrhage and symptomatic intracerebral hemorrhage.

Dose-related effects of statins on symptomatic intracerebral hemorrhage and outcome after thrombolysis for ischemic stroke.

BACKGROUND AND PURPOSE: The aim of our study was to assess whether statins have dose-dependent effects on risk of symptomatic intracerebral hemorrhage (sICH) and outcome after intravenous thrombolysis for ischemic stroke. METHODS: We pooled data from 2 European intravenous thrombolysis registries. Statin doses were stratified in 3 groups according to the attainable lowering of cholesterol levels (low dose: simvastatin 20 mg or equivalent; medium dose: simvastatin 40 mg or equivalent; and high dose: simvastatin 80 mg or equivalent). sICH was defined according to the European Cooperative Acute Stroke Study. Modified Rankin Scale score 0 to 2 at 3 months was considered a favorable outcome. RESULTS: Among 1446 patients analyzed (median age, 75 years; median initial National Institutes of Health Stroke Scale score, 11; 54% men), 317 (22%) used statins before intravenous thrombolysis. Of them, 120 patients had low-dose, 134 medium-dose, and 63 high-dose statin therapy. sICH occurred in 4% of patients (n=53). Frequency of sICH was 2%, 6%, and 13% in patients with low-, medium-, and high-dose statin treatment, respectively (P<0.01). Adjusted odds ratio (OR) for sICH was 2.4 (95% confidence interval [CI], 1.1-5.3) and 5.3 (95% CI, 2.3-12.3) for patients with medium- and high-dose statins compared with non-statin users. Statin users more often achieved favorable outcome compared with non-statin users (58% versus 51%; P=0.03). An independent association of statin use with favorable outcome was detected (adjusted OR, 1.8; 95% CI, 1.3-2.5). The association was maintained when stratifying for statin dose, although it was not significant in the high-dose group anymore (OR, 1.7; 95% CI, 0.9-3.2). CONCLUSIONS: We observed an association between increasing dose of statin use and risk of sICH after intravenous thrombolysis. Nevertheless, there was an overall beneficial effect of previous statin use on favorable 3-month outcome.

Endovascular procedures versus intravenous thrombolysis in stroke with tandem occlusion of the anterior circulation.

PURPOSE: Stroke with tandem occlusion within the anterior circulation presents a lower probability of recanalization and good clinical outcome after intravenous (IV) thrombolysis than stroke with single occlusion. The present study describes the impact of endovascular procedures (EPs) compared with IV thrombolysis alone on recanalization and clinical outcome. MATERIALS AND METHODS: Thirty patients with symptom onset less than 4.5 hours and tandem occlusion within the anterior circulation were analyzed retrospectively. Recanalization was assessed per Thrombolysis In Cerebral Infarction (TICI) classification on computed tomography, magnetic resonance imaging, or digital subtraction angiography within 24 hours. Infarct size was detected on follow-up imaging as a dichotomized variable, ie, more than one third of the territory of the middle cerebral artery. Clinical outcomes were major neurologic improvement, independent outcome (90-d modified Rankin Scale [mRS] score), symptomatic intracerebral hemorrhage (sICH; per European Cooperative Acute Stroke Study criteria), and death within 7 days. RESULTS: Patients treated with EPs (n = 14) were significantly younger and had a history of arterial hypertension more frequently than patients treated with IV thrombolysis alone (n = 16). Recanalization (ie, TICI score 2b/3; EP, 64%; IV, 19%; P = .01), major neurologic improvement (EP, 64%; IV, 19%; P = .01), and independent outcome (mRS score ≤ 2; EP, 54% IV, 13%; P = .02) occurred more often in the EP group, whereas infarct sizes greater than one third of the MCA territory (EP, 43%; IV, 81%; P = .03) were observed less often. Rates of sICH (P = .12) and death within 7 days (P = .74) did not differ significantly. CONCLUSIONS: Higher recanalization rate, smaller infarct volume, and better clinical outcome in the EP group should encourage researchers to include this subgroup of patients in prospective randomized trials comparing IV thrombolysis versus EP in 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.

Severe renal impairment is associated with symptomatic intracerebral hemorrhage after thrombolysis for ischemic stroke.

BACKGROUND AND PURPOSE: Patients with renal impairment (RI) have an increased risk of both thrombotic and hemorrhagic events. We aimed to clarify whether RI increases the risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis with recombinant tissue plasminogen activator. METHODS: Patients who received intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 hours of symptom onset were retrospectively analyzed. Creatinine levels on admission served to calculate glomerular filtration rate (GFR) to estimate RI according to International Classification of Diseases criteria. Effect of RI on symptomatic ICH (sICH) was assessed using dichotomized (GFR <90 and <30 mL/min) and continuous GFR (centered data to test for linear and centered and squared data to test for curvilinear association). RESULTS: Of the 740 patients included, 83% had any RI (GFR <90 mL/min) and 5% had severe RI (GFR <30 mL/mL); 4.6% experienced sICH. Univariate comparisons revealed higher prevalence of sICH in patients with severe RI (P<0.01) but not with any RI. GFR as a continuous variable (centered and squared) was also associated with sICH (P=0.02), but GFR on its own was not. Severe RI and GFR (centered and squared) remained independently associated with sICH in multiple regression analyses. CONCLUSIONS: Severe RI (GFR <30 mL/min) is associated with sICH after intravenous thrombolysis with recombinant tissue plasminogen activator. The association is curvilinear. Severe RI must be taken into account when balancing the risk-benefit ratio of intravenous thrombolysis with recombinant tissue plasminogen activator.

Preclusion of ischemic stroke patients from intravenous tissue plasminogen activator treatment for mild symptoms should not be based on low National Institutes of Health Stroke Scale Scores.

BACKGROUND: Intravenous tissue plasminogen activator (IV tPA) improves neurologic outcome after stroke, but is not recommended for patients with minor neurologic deficits commonly classified by a lower cutoff on the National Institutes of Health Stroke Scale (NIHSS). Because not all stroke signs are captured on the NIHSS, the use of a strict cutoff may exclude functionally impaired stroke patients from IV tPA treatment. METHODS: We described functional impairment, safety, and clinical outcome in patients derived from our hospital thrombolysis database who had stroke that was considered disabling despite a neurologic deficit that was considered mild. We used 2 cutoffs: NIHSS score ≤ 4 and ≤ 3. Functional impairment was assessed with the modified Rankin Scale (mRS). RESULTS: Between 2008 and 2011, a total of 670 acute ischemic stroke patients received IV tPA in our institution. 107 (16%) of these patients presented with a NIHSS score ≤ 4; 65 (10%) patients presented with a NIHSS score ≤ 3. All of these patients were considered functionally impaired (mRS score ≥ 2). The most frequent symptoms were language impairment (two-thirds), distal (hand) paresis (one-third), and gait disorder in both groups. Symptomatic intracerebral hemorrhage occurred in 1 patient with a NIHSS score of 4 (1%). Despite IV tPA therapy, 26% had a nonfavorable outcome (mRS score 0-1) after 3 months, and 52% had persisting symptoms in both groups. CONCLUSIONS: Language impairment, distal (hand) paresis, and gait disorder are common disabling deficits in patients with low NIHSS scores. Judgment of whether a stroke is disabling should not be based on the NIHSS score but on the assessment of the individual neurologic deficits and their impact on functional impairment.

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.

Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry.

AIMS: We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. METHODS: The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. RESULTS: At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01]. CONCLUSION: At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge. CLINICAL TRIAL REGISTRATION: NCT02306824.

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.

Non-invasive telemedical care in heart failure patients and stroke: post hoc analysis of TIM-HF and TIM-HF2 trials.

AIMS: Patients with chronic heart failure (CHF) have an increased risk of ischaemic stroke. We aimed to identify the incidence rate and factors associated with ischaemic stroke or transient ischaemic attack (TIA) in CHF patients as well as the impact of non-invasive telemedical care (NITC) on acute stroke/TIA. METHODS AND RESULTS: We retrospectively analysed baseline characteristics of 2248 CHF patients enrolled to the prospective multicentre Telemedical Interventional Monitoring in Heart Failure study (TIM-HF) and Telemedical Interventional Management in Heart Failure II study (TIM-HF2), randomizing New York Heart Association (NYHA) II/III patients 1:1 to NITC or standard of care. Hospitalizations due to acute ischaemic stroke or TIA during a follow-up of 12 months were analysed. Old age, hyperlipidaemia, lower body mass index, and peripheral arterial occlusive disease (PAOD) were independently associated with present cerebrovascular disease on enrolment. The stroke/TIA rate was 1.5 per 100 patients-years within 12 months after randomization (n = 32, 1.4%). Rate of stroke/TIA within 12 months was in the intervention group similar compared with the control group (50.0% vs. 49.8%; P = 0.98) despite that the rate of newly detected atrial fibrillation (AF) was higher in the intervention group (14.1% vs. 1.6%; P < 0.001). A history of PAOD (OR 2.7, 95% CI 1.2-6.2; P = 0.02) and the highest tertile (OR 3.0, 95% CI 1.1-8.3) of N-terminal pro-brain natriuretic peptide (NT-proBNP) on enrolment were associated with stroke/TIA during follow-up. In patients who suffered acute stroke or TIA during follow-up, echocardiography was part of the diagnostic workup in only 56% after hospital admission. CONCLUSIONS: Annual rate of ischaemic stroke/TIA in NYHA II/III patients is low but higher in those with elevated NT-proBNP levels and history of PAOD at baseline. NITC showed no impact on the stroke rate during 1 year follow-up despite a significantly higher rate of newly detected AF. Irrespective of known CHF, echocardiography was often missing during in-hospital diagnostic workup after acute stroke/TIA.

A Score for Risk of Thrombolysis-Associated Hemorrhage Including Pretreatment with Statins.

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis with recombinant tissue-plasminogen activator (rt-PA) for acute ischemic stroke is associated with a poor functional outcome. We aimed to develop a score assessing risk of sICH including novel putative predictors-namely, pretreatment with statins and severe renal impairment. METHODS: We analyzed our local cohort (Berlin) of patients receiving rt-PA for acute ischemic stroke between 2006 and 2016. Outcome was sICH according to ECASS-III criteria. A multiple regression model identified variables associated with sICH and receiver operating characteristics were calculated for the best discriminatory model for sICH. The model was validated in an independent thrombolysis cohort (Basel). RESULTS: sICH occurred in 53 (4.0%) of 1,336 patients in the derivation cohort. Age, baseline National Institutes of Health Stroke Scale, systolic blood pressure on admission, blood glucose on admission, and prior medication with medium- or high-dose statins were associated with sICH and included into the risk of intracranial hemorrhage score. The validation cohort included 983 patients of whom 33 (3.4%) had a sICH. c-Statistics for sICH was 0.72 (95% CI 0.66-0.79) in the derivation cohort and 0.69 (95% CI 0.60-0.77) in the independent validation cohort. Inclusion of severe renal impairment did not improve the score. CONCLUSION: We developed a simple score with fair discriminating capability to predict rt-PA-related sICH by adding prior statin use to known prognostic factors of sICH. This score may help clinicians to identify patients with higher risk of sICH requiring intensive monitoring.