Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper.

BACKGROUND: With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention. METHODS AND RESULTS: The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample. Based on the results of a systematic literature search followed by an analysis of a simple pooling of five retrieved clinical studies, the test strip has a high sensitivity and an acceptably high negative predictive value when compared with levels measured with liquid chromatography tandem mass spectrometry or calibrated chromogenic assays to reliably exclude plasma DOAC concentrations ≥30 ng/mL. CONCLUSION: Based on these data, a simple algorithm is proposed to enhance medical decision-making in acute care indications useful primarily in hospitals not having readily available quantitative tests and 24/7. This algorithm not only determines DOAC exposure but also differentiates between factor Xa and thrombin inhibitors to better guide clinical management.

Performance of Thrombectomy-Capable, Comprehensive, and Primary Stroke Centers in Reperfusion Therapies for Acute Ischemic Stroke: Report from the Get With The Guidelines Stroke Registry: Stroke Outcomes Per Hospital Certification Status.

Background: The thrombectomy-capable stroke center (TSC) is a recently introduced intermediate tier of accreditation for hospitals caring for patients with acute ischemic stroke (AIS). The comparative quality and clinical outcomes of reperfusion therapies at TSCs, primary stroke centers (PSCs), and comprehensive stroke centers (CSCs) has not been well delineated. Methods: We conducted a retrospective, observational, cohort study from 2018-2020 that included patients with AIS who received endovascular (EVT) and/or intravenous (IVT) reperfusion therapies at CSC, TSC, or PSC. Participants were recruited from Get With The Guidelines-Stroke registry. Study endpoints included timeliness of IVT and EVT, successful reperfusion, discharge destination, discharge mortality, and functional independence at discharge. Results: Among 84,903 included patients, 48,682 received EVT, of whom 73% were treated at CSCs, 22% at PSCs, and 4% at TSCs. The median annual EVT volume was 76 for CSCs, 55 for TSCs, and 32 for PSCs. Patient differences by center status included higher NIHSS, longer onset-to-arrival time, and higher transfer-in rates for CSC/TSC/PSC, respectively. In adjusted analyses, the likelihood of achieving the goal door-to-needle time was higher in CSCs compared to PSCs (OR 1.39; 95% CI 1.17-1.66) and in TSCs compared to PSCs (OR 1.45; 95% CI 1.08-1.96). Similarly, the odds of achieving the goal door-to-puncture time were higher in CSCs compared to PSCs (OR 1.58; 95% CI 1.13-2.21). CSCs and TSCs also demonstrated better clinical efficacy outcomes compared to PSCs. The odds of discharge to home or rehabilitation were higher in CSCs compared to PSCs (OR 1.18; 95% CI 1.06-1.31), while the odds of in-hospital mortality/discharge to hospice were lower in both CSCs compared to PSCs (OR 0.87; 95% CI 0.81-0.94) and TSCs compared to PSCs (OR 0.86; 95% CI 0.75-0.98). There were no significant differences in any of the quality-of-care metrics and clinical outcomes between TSCs and CSCs. Conclusions: In this study representing national US practice, CSCs and TSCs exceeded PSCs in key quality-of-care reperfusion metrics and outcomes, whereas TSCs and CSCs demonstrated similar performance. Considering that over one-fifth of all EVT procedures during the study period were conducted at PSCs, it may be desirable to explore national initiatives aimed at facilitating the elevation of eligible PSCs to a higher certification status.

Borderzone Infarcts and Recurrent Cerebrovascular Events in Symptomatic Intracranial Arterial Stenosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration. METHODS: As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated. RESULTS: A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52-2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38-3.18). For isolated BZI, RR was 2.59 (95% CI 1.24-5.41). RR was 2.96 (95% CI 1.71-5.12) for studies only including anterior circulation stroke patients. CONCLUSION: This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.

Intra-arterial Thrombolysis for Acute Retinal Ischemia: A Retrospective, Observational, Cohort Study.

BACKGROUND: To determine whether intra-arterial thrombolysis (IAT) within 16 hours after the onset of symptoms is feasible and associated with better visual outcomes in patients with acute retinal ischemia (ARI). METHODS: The retrospective cohort study was performed from January 2014 to December 2021 in the Xuanwu Hospital of Capital Medical University. Patients with ARI who initially presented visual acuity of 20/100 or worse were screened in the study. Visual end points were evaluated at one week and at final visit after treatment. Serious adverse events were recorded during operation and within 1 week after IAT treatment. RESULTS: The amount of clinically significant visual improvement (≥0.3 logarithm of the minimum angle of resolution) in the IAT group was significantly higher than that in the conservative treatment group at one week after the treatment (47.8% vs 16.7%; P = 0.014) and at final visit (52.2% vs 20%; P = 0.014). After controlling confounding factors, ARI treatment was the only factor significantly associated with the amount of clinically significant visual improvement (OR, 4.364; 95 CI, 1.298-14.667; P = 0.017). A patient (4.3%) experienced retinal hemorrhage without symptom within 1 week after IAT treatment. No patients experienced new symptomatic cerebral infarction, intracranial hemorrhage, TIA, artery dissection, vascular perforation, and distal embolization during operation and within 1 week after IAT treatment. CONCLUSIONS: IAT may be associated with better visual improvement within 16 hours after the onset of symptoms. Besides, IAT is feasible and associated with a low risk of periprocedural complications for ARI. This study will aid in feasibility testing and sample size calculations in advance of future, fully-powered efficacy studies for ARI.

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study.

BACKGROUND: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. METHODS: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. RESULTS: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7]). CONCLUSIONS: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Prolonged Cardiac Monitoring and Stroke Recurrence: A Meta-analysis.

BACKGROUND AND OBJECTIVES: Prolonged poststroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of patients with ischemic stroke (IS) with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We evaluated the association between PCM and the institution of stroke preventive strategies and stroke recurrence. METHODS: We searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or TIA receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random effects model. To explore for differences between the monitoring strategies, we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT). RESULTS: We included 8 studies (5 RCTs, 3 observational; 2,994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in RCTs (risk ratio [RR] 3.91, 95% CI 2.54-6.03; RR 2.16, 95% CI 1.66-2.80, respectively) and observational studies (RR 2.06, 95% CI 1.57-2.70; RR 2.01, 95% CI 1.43-2.83, respectively). PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR 0.29, 95% CI 0.15-0.59), but not in RCTs (RR 0.72, 95% CI 0.49-1.07). In indirect analyses of RCTs, the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with Holter monitors and external loop recorders. DISCUSSION: PCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.

How I do it: endarterectomy for carotid web.

BACKGROUND: The carotid web is an important and under recognized etiology for recurrent cryptogenic strokes. A management option for a symptomatic carotid web is a carotid endarterectomy (CEA) with surgical microdissection and removal of the intimal luminal defect. METHODS: We describe some of the technical nuances involved in successfully performing a carotid endarterectomy for resection of a carotid web. CONCLUSION: Utilizing a familiar approach to an understudied pathology, this procedure can be safely performed and provides the patient with lasting protection against recurrent infarcts through removal of the thromboembolic nidus.

Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System.

BACKGROUND AND PURPOSE: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. METHODS: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. RESULTS: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. CONCLUSION: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.

The Effect of Hyperglycemia on Infarct Growth after Reperfusion: An Analysis of the DEFUSE 3 trial.

BACKGROUND AND PURPOSE: Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied. MATERIALS AND METHODS: This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core. RESULTS: We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03). CONCLUSION: In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.

The impact of delirium on withdrawal of life-sustaining treatment after intracerebral hemorrhage.

OBJECTIVE: To determine the impact of delirium on withdrawal of life-sustaining treatment (WLST) after intracerebral hemorrhage (ICH) in the context of established predictors of poor outcome, using data from an institutional ICH registry. METHODS: We performed a single-center cohort study on consecutive patients with ICH admitted over 12 months. ICH features were prospectively adjudicated, and WLST and corresponding hospital day were recorded retrospectively. Patients were categorized using DSM-5 criteria as never delirious, ever delirious (either on admission or later during hospitalization), or persistently comatose. We determined the impact of delirium on WLST using Cox regression models adjusted for demographics and ICH predictors (including Glasgow Coma Scale score), then used logistic regression with receiver operating characteristic curve analysis to compare the accuracy of ICH score-based models with and without delirium category in predicting WLST. RESULTS: Of 311 patients (mean age 70.6 ± 15.6, median ICH score 1 [interquartile range 1-2]), 50% had delirium. WLST occurred in 26%, and median time to WLST was 1 day (0-6). WLST was more frequent in patients who developed delirium (adjusted hazard ratio 8.9 [95% confidence interval (CI) 2.1-37.6]), with high rates of WLST in both early (occurring ≤24 hours from admission) and later delirium groups. An ICH score-based model was strongly predictive of WLST (area under the curve [AUC] 0.902 [95% CI 0.863-0.941]), and the addition of delirium category further improved the model's accuracy (AUC 0.936 [95% CI 0.909-0.962], p = 0.004). CONCLUSION: Delirium is associated with WLST after ICH regardless of when it occurs. Further study on the impact of delirium on clinician and surrogate decision-making is warranted.

Mechanical Thrombectomy in Ischemic Stroke Patients with Severe Pre-Stroke Disability.

Frequency and outcomes of mechanical thrombectomy (MT) in clinical practice for patients with severe pre-stroke disability are largely unknown. In this case series, we aim to describe the disability make-up and outcomes of 33 patients with severe pre-stroke disability undergoing MT. Patients with a permanent, severe, pre-stroke disability (modified Rankin Score, mRS, 4-5) were identified from a prospectively-maintained database of consecutive, MT-treated, anterior circulation acute ischemic stroke patients at two comprehensive stroke centers in the United States. We present details on the cause of disability and socio-demographic status as well as procedural and functional outcomes. This study, despite the lack of inferential testing due to limited sample size, provides insight into demographics and outcomes of MT-treated patients with severe pre-stroke disability. Rate of return to functional baseline as well as rates of procedural success and complications were comparable to that reported in the literature for patients without any pre-existing disability.

Hypoperfusion Distal to Anterior Circulation Intracranial Atherosclerosis is Associated with Recurrent Stroke.

BACKGROUND AND PURPOSE: In patients with symptomatic vertebrobasilar intracranial atherosclerotic disease (ICAD), impaired distal flow predicts recurrent stroke, but limited data exist on the association between perfusion status and recurrent stroke in anterior circulation ICAD. METHODS: This is a retrospective study of patients hospitalized for symptomatic ICAD with 50-99% stenosis of the intracranial carotid or middle cerebral artery. The primary outcome is recurrent symptomatic ischemic stroke in the territory of the artery with ≥50% stenosis within 90 days. The primary predictor is distal hypoperfusion on magnetic resonance (MR) or computed tomography (CT) perfusion, defined as a ≥15 mL volume of territory of the symptomatic artery with Tmax >6 seconds. RESULTS: Fifty patients met inclusion criteria, including 15 (30%) with recurrent stroke and 15 (30%) with distal hypoperfusion. Distal hypoperfusion was present in 10 of 15 (66.7%) with recurrent stroke versus 5 of 35 (14.3%) without recurrent stroke (P < .001). The hazard ratio for recurrent stroke in patients with distal hypoperfusion was 6.80 (95% confidence interval [CI] 2.31-20.0). CONCLUSION: Distal hypoperfusion in acutely symptomatic ICAD with 50-99% stenosis is associated with stroke recurrence. Distal hypoperfusion could be used to enrich future trials of secondary stroke prevention in ICAD patients.

Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation.

BACKGROUND AND PURPOSE: Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. RESULTS: Of the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were women. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10-2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06-3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. CONCLUSION: Small stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes.

Increased Left Atrial Appendage Density on Computerized Tomography is Associated with Cardioembolic Stroke.

BACKGROUND AND PURPOSE: While studies have stratified cardioembolic (CE) stroke risk by qualitative left atrial appendage (LAA) morphology and biomarkers of atrial dysfunction, the quantitative properties that underlie these observations are not well established. Accordingly, we hypothesized that LAA volume and contrast density (attenuation) on computerized tomography (CT) may capture the structural and hemodynamic processes that underlie CE stroke risk. METHODS: Data were collected from a single center prospective ischemic stroke database over 18 months and included all patients with ischemic stroke who previously underwent routine, nongated, contrast enhanced thin-slice (≤2.5 mm) chest CT. Stroke subtype was determined based on the inpatient diagnostic evaluation. LAA volume and attenuation were determined from CT studies performed for various clinically appropriate indications. Univariate and multivariable analyses were performed to determine factors associated with ischemic stroke subtype, including known risk factors and biomarkers, as well as LAA density and morphologic measures. RESULTS: We identified 311 patients with a qualifying chest CT (119 CE subtype, 109 Embolic Stroke of Undetermined Source (ESUS), and 83 non-CE). In unadjusted models, there was an association between CE (versus non-CE) stroke subtype and LAA volume (OR per mL increase 1.15, 95% CI 1.07-1.24, P < .001) and LAA density (4th quartile versus 1st quartile; OR 2.95, 95% CI 1.28-6.80, P = .011), but not with ESUS (versus non-CE) subtype. In adjusted models, only the association between LAA density and CE stroke subtype persisted (adjusted OR 3.71, 95% CI 1.37-10.08, P = .010). CONCLUSION: The LAA volume and density values on chest CT are associated with CE stroke subtype but not ESUS subtype. Patients with ESUS and increased LAA volume or attenuation may be a subgroup where the mechanism is CE and anticoagulation can be tested for secondary stroke prevention.

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

INTRODUCTION: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. MATERIALS AND METHODS: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. RESULTS: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). DISCUSSION: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. CONCLUSIONS: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

Redefining Early Neurological Improvement After Reperfusion Therapy in Stroke.

BACKGROUND AND PURPOSE: Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. We hypothesized that ENI defined as a percentage change in the National Institute of Health Stroke Scale (NIHSS) score (percent change NIHSS score) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS score (delta NIHSS score) at 24 hours. METHODS: Retrospective analysis of prospectively collected single-center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. We examined delta NIHSS score and percent change NIHSS score in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). RESULTS: Among 586 patients who met the inclusion criteria, 194 (33.1%) had a favorable outcome at 3 months. In fully adjusted models, both delta NIHSS score (OR per point decrease 1.27; 95% confidence interval [CI] 1.19-1.36) and percent change NIHSS score (OR per 10 percent decrease 1.17; 95% CI 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS score (.755) was greater than delta NIHSS score (.613) or admission NIHSS (.694). CONCLUSIONS: Percentage change in NIHSS score may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.

Prolonged Cardiac Rhythm Monitoring and Secondary Stroke Prevention in Patients With Cryptogenic Cerebral Ischemia.

Background and Purpose- Although prolonged cardiac rhythm monitoring (PCM) can reveal a substantial proportion of ischemic stroke (IS) patients with atrial fibrillation not detected by conventional short-term monitoring, current guidelines indicate an uncertain clinical benefit for PCM. We evaluated the impact of PCM on secondary stroke prevention using data from available to date randomized clinical trials and observational studies. Methods- We performed a comprehensive literature search in MEDLINE, SCOPUS, CENTRAL (Cochrane Central Register of Controlled Trial), and conference proceedings to identify studies reporting stroke recurrence rates in patients with history of cryptogenic IS or transient ischemic attack (TIA) receiving PCM compared with patients receiving conventional (non-PCM) cardiac monitoring. Results- We included 4 studies (2 randomized clinical trials and 2 observational studies), including a total of 1102 patients (mean age: 68 years, 41% women). We documented an increased incidence of atrial fibrillation detection (risk ratio=2.46; 95% CI, 1.61-3.76) and anticoagulant initiation (risk ratio=2.07; 95% CI, 1.36-3.17) and decreased risk of recurrent stroke (risk ratio=0.45; 95% CI, 0.21-0.97) and recurrent stroke/TIA (risk ratio=0.49; 95% CI, 0.30-0.81) during follow-up for IS/TIA patients who underwent PCM compared with IS/TIA patients receiving conventional cardiac monitoring. In the subgroup analysis, according to study type, atrial fibrillation detection, anticoagulant initiation, and IS/TIA recurrence rates were comparable between PCM and non-PCM in randomized clinical trials and observational studies. No evidence of heterogeneity (I2<12%) was documented across all the aforementioned subgroups. Conclusions- We provide preliminary evidence for a potential impact of PCM on secondary stroke prevention, as patients with cryptogenic IS/TIA undergoing PCM had higher rates of atrial fibrillation detection, anticoagulant initiation, and lower stroke recurrence.

Infarct Pattern, Perfusion Mismatch Thresholds, and Recurrent Cerebrovascular Events in Symptomatic Intracranial Stenosis.

BACKGROUND AND PURPOSE: Studies have shown an association between infarct patterns and recurrent stroke in patients with symptomatic intracranial stenosis (sICAS) but there are limited data on associations with perfusion imaging mismatch profile. We aim to determine the association between infarct pattern, optimal mismatch profile definition, and recurrent cerebrovascular events (RCVE) in patients with anterior circulation sICAS. METHODS: This is a retrospective study of consecutive patients with acutely sICAS admitted to a comprehensive stroke center over 18 month's period. Patients with sICAS underwent magnetic resonance perfusion (MRP) imaging within 24 hours from admission. Infarct patterns (internal BZ [IBZ], cortical BZ [CBZ], and core/perforator [C/P]) and RCVE within 90 days, were independently adjudicated by two reviewers. We compared mismatch profiles and recurrent event rates across infarct patterns. RESULTS: Twenty-five patients met inclusion criteria; 28% had IBZ infarcts and overall RCVE rate was 32.0%. When compared to patients without IBZ infarcts, those with IBZ infarcts were more likely to have a target mismatch profile using Tmax > 6 seconds (60% vs. 6.7%, P = .007) and RCVE (62.5% vs. 11.8%, P = .01). There were no associations between CBZ and C/P infarcts and target mismatch profiles and RCVE. CONCLUSION: IBZ infarcts may be a surrogate marker of distal perfusion status and RCVE risk. Larger multicenter, prospective, core-lab blindly adjudicated studies are needed to confirm our findings.

Cardiac Biomarkers Predict Large Vessel Occlusion in Patients with Ischemic Stroke.

BACKGROUND AND PURPOSE: Cardiac biomarkers may help identify stroke mechanisms and may aid in improving stroke prevention strategies. There is limited data on the association between these biomarkers and acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). We hypothesized that cardiac biomarkers (cardiac troponin and left atrial diameter [LAD]) would be associated with the presence of LVO. METHODS: Data were abstracted from a single center prospective AIS database over 18 months and included all patients with AIS with CT angiography of the head and neck. The presence of LVO was defined as proximal LVO of the internal carotid artery terminus, middle cerebral artery (M1 or proximal M2), or basilar artery. Univariate analyses and predefined multivariable models were performed to determine the association between cardiac biomarkers (positive troponin [troponin ≥0.1 ng/mL] and LAD on transthoracic echocardiogram) and LVO adjusting for demographic factors (age and sex), risk factors (hypertension, diabetes, hyperlipidemia, history of stroke, congestive heart failure, coronary heart disease, and smoking), and atrial fibrillation (AF). RESULTS: We identified 1234 patients admitted with AIS; 886 patients (71.8%) had vascular imaging to detect LVO. Of those with imaging available, 374 patients (42.2%) had LVO and 207 patients (23.4%) underwent thrombectomy. There was an association between positive troponin and LVO after adjusting for age, sex and other risk factors (adjusted OR 1.69 [1.08-2.63], P = .022) and this association persisted after including AF in the model (adjusted OR 1.60 [1.02-2.53], P = 0.043). There was an association between LAD and LVO after adjusting for age, sex, and risk factors (adjusted OR per mm 1.03 [1.01-1.05], P = 0.013) but this association was not present when AF was added to the model (adjusted OR 1.01 [0.99-1.04], P = .346). Sensitivity analyses using thrombectomy as an outcome yielded similar findings. CONCLUSIONS: Cardiac biomarkers, particularly serum troponin levels, are associated with acute LVO in patients with ischemic stroke. Prospective studies are ongoing to confirm this association and to test whether anticoagulation reduces the risk of recurrent embolism in this patient population.

The Addition of Atrial Fibrillation to the Los Angeles Motor Scale May Improve Prediction of Large Vessel Occlusion.

BACKGROUND AND PURPOSE: There is evidence suggesting that Los Angeles Motor Scale (LAMS) ≥ 4 predicts large vessel occlusion (LVO). We aim to determine whether atrial fibrillation (AF) can improve the ability of LAMS in predicting LVO. METHODS: We included consecutive patients with a discharge diagnosis of ischemic stroke admitted within 24 hours from last known normal time who underwent emergent vascular imaging using a computerized tomography angiography (CTA) of the head and neck. LVO was defined as intracranial internal carotid artery, proximal middle cerebral artery (M1 or proximal M2 segment), or basilar occlusion. LAMS was determined in the emergency department upon arrival. Univariate and multivariable models were performed to identify predictors of LVO and to determine whether AF improves the ability of LAMS to predict LVO. RESULTS: Among 1,234 patients admitted with ischemic stroke, 862 underwent emergent vascular imaging (69.8%) out of which 374 (43.4%) had evidence of LVO and 207 (24%) underwent mechanical thrombectomy. In multivariable models, predictors of LVO were LAMS (OR 1.42 per one point increase 95% CI 1.29-1.57) and AF (OR 1.95 95% CI 1.26-3.02, P < .001). We developed the LAMS-AF that includes the LAMS score and adds two points if AF is present. In this analysis, LAMS-AF (AUC .78) had improved prediction over LAMS (AUC .76) in predicting LVO and lead to reclassification of 8/68 patients (11.8%) with LAMS = 3 group into the high-risk LVO group. CONCLUSION: In patients with LAMS = 3, using the LAMS-AF score may improve the ability of LAMS in predicting LVO. Larger studies are needed to confirm our findings.