Timing of Spot Sign Appearance, Spot Sign Volume, and Leakage Rate among Phases of Multiphase CTA Predict Intracerebral Hemorrhage Growth.

BACKGROUND AND PURPOSE: The presence of spot sign is associated with a high risk of hematoma growth. Our aim was to investigate the timing of the appearance, volume, and leakage rate of the spot sign for predicting hematoma growth in acute intracerebral hemorrhage using multiphase CTA. MATERIALS AND METHODS: In this single-center retrospective study, multiphase CTA in 3 phases was performed in acute intracerebral hemorrhage (defined as intraparenchymal ± intraventricular hemorrhages). Phases of the spot sign first appearance, spot sign volumes (microliter), and leakage rates among phases (microliter/second) were measured. Associations between baseline clinical and imaging variables including spot sign volume parameters (volume and leakage rate divided by median) and hematoma growth (>6 mL) were investigated using regression models. Receiver operating characteristic analysis was used as appropriate. RESULTS: Two hundred seventeen patients (131 men; median age, 70 years) were included. The spot sign was detected in 21.7%, 30.0%, and 29.0% in the first, second, and third phases, respectively, with median volumes of 19.7, 31.4, and 34.8 µl in these phases. Hematoma growth was seen in 44 patients (20.3%). By means of modeling, the following variables, namely the spot sign appearing in the first phase, first phase spot sign volume, spot sign appearing in the second or third phase, and spot sign positive and negative leakage rates, were associated with hematoma growth. Among patients with a spot sign, the absolute leakage rate accounting for both positive and negative leakage rates was also associated with hematoma growth (per 1-µl/s increase; OR, 1.26; 95% CI, 1.04-1.52). Other hematoma growth predictors were stroke history, baseline NIHSS score, onset-to-imaging time, and baseline hematoma volume (all P values < .05). CONCLUSIONS: The timing of the appearance of the spot sign, volume, and leakage rate were all associated with hematoma growth. Development of automated software to generate these spot sign volumetric parameters would be an important next step to maximize the potential of temporal intracerebral hemorrhage imaging such as multiphase CTA for identifying those most at risk of hematoma growth.

Combining Early Ischemic Change and Collateral Extent for Functional Outcomes After Endovascular Therapy: An Analysis From AcT Trial.

BACKGROUND: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients. METHODS: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction. RESULTS: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P<0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively). CONCLUSIONS: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

Workflow and Outcome of Thrombectomy in Late Time Window: A Pooled Multicenter Analysis.

BACKGROUND: We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window. METHODS: Individual patients' data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0-2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals. RESULTS: 608 patients were included. The median age was 70 years (IQR: 58-71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0-2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke. CONCLUSION: Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.

Use of Artificial Intelligence in Improving Outcomes in Heart Disease: A Scientific Statement From the American Heart Association.

A major focus of academia, industry, and global governmental agencies is to develop and apply artificial intelligence and other advanced analytical tools to transform health care delivery. The American Heart Association supports the creation of tools and services that would further the science and practice of precision medicine by enabling more precise approaches to cardiovascular and stroke research, prevention, and care of individuals and populations. Nevertheless, several challenges exist, and few artificial intelligence tools have been shown to improve cardiovascular and stroke care sufficiently to be widely adopted. This scientific statement outlines the current state of the art on the use of artificial intelligence algorithms and data science in the diagnosis, classification, and treatment of cardiovascular disease. It also sets out to advance this mission, focusing on how digital tools and, in particular, artificial intelligence may provide clinical and mechanistic insights, address bias in clinical studies, and facilitate education and implementation science to improve cardiovascular and stroke outcomes. Last, a key objective of this scientific statement is to further the field by identifying best practices, gaps, and challenges for interested stakeholders.

Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Physician Approaches to Antithrombotic Therapies for Recently Symptomatic Carotid Stenosis.

BACKGROUND: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. METHODS: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. RESULTS: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. CONCLUSION: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

Effect of Needle-To-Puncture Time on Reperfusion Outcome in Acute Ischemic Stroke.

INTRODUCTION: The aim of the study was to investigate the impact of time interval between start of intravenous thrombolysis (IVT) to start of endovascular thrombectomy (EVT) on stroke outcomes. METHODS: Data from the Quality Improvement and Clinical Research (QuICR) provincial stroke registry from Alberta, Canada, were used to identify stroke patients who received IVT and EVT from January 2015 to December 2019. We assessed the impact of the time interval between IVT bolus to EVT puncture (needle-to-puncture times [NPT]) on outcomes. Radiological outcomes included successful initial recanalization (revised Arterial Occlusive Lesion 2b-3), successful initial and final reperfusion (modified thrombolysis in cerebral infarction 2b-3). Clinical outcomes were 90-day modified Rankin Scale (mRS) and mortality. RESULTS: Of the 680 patients, 233 patients (median age: 73, 41% females) received IVT + EVT. Median NPT was 38 min (IQR, 24-60). Arrival during working hours was independently associated with shorter NPT (p < 0.001). Successful initial recanalization and initial and final reperfusion were observed in 12%, 10%, and 83% of patients, respectively. NPT was not associated with initial successful recanalization (OR 0.97 for every 10-min increase of NPT, 95% CI: 0.91-1.04), initial successful reperfusion (OR 1.01, 95% CI: 0.96-1.07), or final successful reperfusion (OR: 1.03, 95% CI: 0.97-1.08). Every 10-min delay in NPT was associated with lower odds of functional independence at 90 days (mRS ≤2; OR: 0.93; 95% CI, 0.88-0.97). Patients with shorter NPT (≤38 min) had lower 90-day mRS scores (median 1 vs. 3; OR: 0.54 [0.31-0.91]) and had lower mortality (6.1% vs. 21.2%; OR, 0.23 [0.10-0.57]) than the longer NPT group. CONCLUSION: Shorter NPT did not impact reperfusion outcomes but was associated with better clinical outcome.

Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial.

BACKGROUND: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion. AIMS: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL. METHODS: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed. RESULTS: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group. CONCLUSION: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase.

Predicting outcome in acute stroke with large vessel occlusion-application and validation of MR PREDICTS in the ESCAPE-NA1 population.

BACKGROUND: Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate the performance of a validated outcome prediction score. PATIENTS AND METHODS: MR PREDICTS is an outcome prediction tool based on a logistic regression model designed to predict the treatment benefit of endovascular treatment based on the MR CLEAN and HERMES populations. ESCAPE-NA1 is a randomized trial of nerinetide vs. placebo in patients with acute stroke and large vessel occlusion. We applied MR PREDICTS to patients in the control arm of ESCAPE-NA1. Model performance was assessed by calculating its discriminative ability and calibration. RESULTS: Overall, 556/1105 patients (50.3%) in the ESCAPE-NA1-trial were randomized to the control arm, 435/556 (78.2%) were treated within 6 h of symptom onset. Good outcome (modified Rankin scale 0-2) at 3 months was achieved in 275/435 patients (63.2%), the predicted probability of good outcome was 52.5%. Baseline characteristics were similar in the study and model derivation cohort except for age (ESCAPE-NA1: mean: 70 y vs. HERMES: 66 y), hypertension (72% vs. 57%), and collaterals (good collaterals, 15% vs. 44%). Compared to HERMES we observed higher rates of successful reperfusion (TICI 2b-3, ESCAPE-NA1: 87% vs. HERMES: 71%) and faster times from symptom onset to reperfusion (median: 201 min vs. 286 min). Model performance was good, indicated by a c-statistic of 0.76 (95%confidence interval: 0.71-0.81). CONCLUSION: Outcome-prediction using models created from HERMES data, based on information available in the emergency department underestimated the actual outcome in patients with acute ischemic stroke and large vessel occlusion receiving endovascular treatment despite overall good model performance, which might be explained by differences in quality of and time to reperfusion. These findings underline the importance of timely and successful reperfusion for functional outcomes in acute stroke patients.

Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial.

PURPOSE: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilateral ischemic stroke. METHODS: Data are from ESCAPE-NA1, a randomized controlled trial investigating the neuroprotectant nerinetide in patients with acute ischemic stroke and large vessel occlusion (LVO). The degree of stenosis of the extracranial internal carotid artery (ICA) and high-risk plaque features were assessed on baseline computed tomography (CT) angiography. We evaluated the association of non-stenotic carotid disease and ipsilateral stroke by age-adjusted and sex-adjusted logistic regression and calculated the attributable risk of ipsilateral stroke caused by non-stenotic carotid disease. RESULTS: After excluding patients with non-assessable imaging, symptomatic > 50% carotid stenosis and extracranial dissection, 799/1105 (72.1%) patients enrolled in ESCAPE-NA1 remained for this analysis. Of these, 127 (15.9%) were classified as ESUS. Non-stenotic carotid disease occurred in 34/127 ESUS patients (26.8%) and was associated with the presence of ipsilateral ischemic stroke (odds ratio, OR 1.6, 95% confidence interval, CI 1.0-2.6, p = 0.049). The risk of ipsilateral ischemic stroke attributable to non-stenotic carotid disease in ESUS was estimated to be 19.7% (95% CI -5.7% to 39%), the population attributable risk was calculated as 4.3%. Imaging features such as plaque thickness, plaque irregularity or plaque ulceration were not different between non-stenotic carotids with vs. without ipsilateral stroke. CONCLUSION: Non-stenotic carotid disease frequently occurs in patients classified as ESUS and is associated with ipsilateral ischemic stroke. Our findings support the role of non-stenotic carotid disease as stroke etiology in ESUS, but further prospective research is needed to prove a causal relationship.

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial.

BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (Pinteraction=0.161) or door-to-needle time (Pinteraction=0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic. CLINICALTRIALS: gov; Unique identifier: NCT03889249.

Prevalence of high-risk aortic arch atherosclerosis features on computed tomography angiography in embolic stroke of undetermined source.

INTRODUCTION: Embolic stroke of undetermined source (ESUS) comprises a heterogenous group. There is a need to further identify etiologies within this group to guide management strategies. We examined the prevalence of aortic arch atherosclerosis (AAA) on CT angiography (CTA) in patients with embolic stroke of undetermined source (ESUS) to characterize high-risk plaque features. METHODS: All patients from two prospective multicenter acute ischemic stroke studies (INTERRSeCT and PRove-IT) were included if the CTA adequately imaged the proximal aortic arch and the stroke etiology was recorded. Three readers blinded to stroke etiology analyzed the following AAA plaque features on baseline CTA at the time of stroke: 1) thickness in millimetres (mm); 2) morphology (none, smooth, ulcerated, or protruding); 3) location within the aortic arch (proximal, transverse, or distal); and 4) calcification (none, single small, multiple small, single large, or diffuse extensive). RESULTS: We included 1063 patients, of which 293 (27.6%) had ESUS (mean age 67.5 years; 46.4% men; median NIHSS 12; 80.6% large vessel occlusion). Mean AAA thickness was significantly larger in ESUS patients (3.8 mm) compared to non-ESUS patients (3.0 mm; p<0.0001) and to a subgroup of patients with large artery atherosclerosis (2.9 mm; p=0.003). ESUS patients had a significantly higher proportion of ulcerated or protruding plaques (17.4% vs 10.3%; risk ratio 1.7, 95% C.I. 1.2-2.4, p=0.002). The location of AAA in the ESUS group was the ascending aorta in 37.9%, transverse arch in 42.3%, and descending aorta in 84.6%. Although AAA was mostly located in the distal aortic arch, ulcerated or protruding plaques were least common in the distal arch (p=0.002). There was no difference between ESUS and non-ESUS patients in plaque location (p=0.23) or calcification grade (p=0.092). CONCLUSION: ESUS patients in our study had thicker AAA and a higher prevalence of ulcerated or protruding plaques located more proximally within the aortic arch. High-risk plaque features may suggest a causal role of AAA in the ESUS population with visible intracranial occlusions.

Association between blood pressure and endovascular treatment outcomes differs by baseline perfusion and reperfusion status.

We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by baseline perfusion and recanalization status. We identified 388 ICA or M1 occlusion patients who underwent EVT ≤ 24 h from onset with successful recanalization (TICI ≥ 2b). BP was measured at 5-min intervals from arrival and during the procedure. Systolic BPs (SBP) were summarized as dropmax (the maximal decrease over two consecutive measurements), incmax (the maximal increase), mean, coefficient of variation (cv), and standard deviation. Adequate baseline perfusion was defined as hypoperfusion intensity ratio (HIR) ≤ 0.5; infarct proportion as the volume ratio of final infarcts within the Tmax > 6 s region. In the adequate perfusion group, infarct proportion was closely associated with SBPdropmax (ß ± SE (P-value); 1.22 ± 0.48, (< 0.01)), SBPincmax (1.12 ± 0.33, (< 0.01)), SBPcv (0.61 ± 0.15 (< 0.01)), SBPsd (0.66 ± 0.08 (< 0.01)), and SBPmean (0.71 ± 0.37 (0.053) before recanalization. The associations remained significant only in SBPdropmax, SBPincmax, and SBPmean after recanalization. SBPincmax, SBPcv and SBPsd showed significant associations with modified Rankin Scale score at 3 months in the pre-recanalization period. In the poor perfusion group, none of the SBP indices was associated with any stroke outcomes regardless of recanalization status. BP may show differential associations with stroke outcomes by the recanalization and baseline perfusion status.

Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke: A Prespecified Secondary Analysis of the ACT Randomized Clinical Trial.

Importance: It is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke. Objective: To examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke. Design, Setting, and Participants: This was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) randomized clinical trial that enrolled patients from 22 primary and comprehensive stroke centers across Canada between December 10, 2019, and January 25, 2022. Patients 18 years and older with a disabling ischemic stroke within 4.5 hours of symptom onset were randomly assigned (1:1) to either intravenous tenecteplase or alteplase and were monitored for up to 120 days. Patients with baseline intracranial internal carotid artery (ICA), M1-middle cerebral artery (MCA), M2-MCA, and basilar occlusions were included in this analysis. A total of 1600 patients were enrolled, and 23 withdrew consent. Exposures: Intravenous tenecteplase (0.25 mg/kg) vs intravenous alteplase (0.9 mg/kg). Main Outcomes and Measures: The primary outcome was the proportion of modified Rankin scale (mRS) score 0-1 at 90 days. Secondary outcomes were an mRS score from 0 to 2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were successful reperfusion (extended Thrombolysis in Cerebral Infarction scale score 2b-3) on first and final angiographic acquisitions. Multivariable analyses (adjusting for age, sex, National Institute of Health Stroke Scale score, onset-to-needle time, and occlusion location) were carried out. Results: Among 1577 patients, 520 (33.0%) had LVO (median [IQR] age, 74 [64-83] years; 283 [54.4%] women): 135 (26.0%) with ICA occlusion, 237 (45.6%) with M1-MCA, 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. The primary outcome (mRS score 0-1) was achieved in 86 participants (32.7%) in the tenecteplase group vs 76 (29.6%) in the alteplase group. Rates of mRS 0-2 (129 [49.0%] vs 131 [51.0%]), symptomatic intracerebral hemorrhage (16 [6.1%] vs 11 [4.3%]), and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively. No difference was noted in successful reperfusion rates in the first (19 [9.2%] vs 21 [10.5%]) and final angiogram (174 [84.5%] vs 177 [88.9%]) among 405 patients who underwent thrombectomy. Conclusions and Relevance: The findings in this study indicate that intravenous tenecteplase conferred similar reperfusion, safety, and functional outcomes compared to alteplase among patients with LVO.

Exploring sex differences for acute ischemic stroke clinical, imaging and thrombus characteristics in the INTERRSeCT study.

Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01-1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden.

Predicting DWI-FLAIR mismatch on NCCT: the role of artificial intelligence in hyperacute decision making.

Background: The presence of diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch was used to determine eligibility for intravenous thrombolysis in clinical trials. However, due to the restricted availability of MRI and the ambiguity of image assessment, it is not widely implemented in clinical practice. Methods: A total of 222 acute ischemic stroke patients underwent non-contrast computed tomography (NCCT), DWI, and FLAIR within 1 h of one another. Human experts manually segmented ischemic lesions on DWI and FLAIR images and independently graded the presence of DWI-FLAIR mismatch. Deep learning (DL) models based on the nnU-net architecture were developed to predict ischemic lesions visible on DWI and FLAIR images using NCCT images. Inexperienced neurologists evaluated the DWI-FLAIR mismatch on NCCT images without and with the model's results. Results: The mean age of included subjects was 71.8 ± 12.8 years, 123 (55%) were male, and the baseline NIHSS score was a median of 11 [IQR, 6-18]. All images were taken in the following order: NCCT - DWI - FLAIR, starting after a median of 139 [81-326] min after the time of the last known well. Intravenous thrombolysis was administered in 120 patients (54%) after NCCT. The DL model's prediction on NCCT images revealed a Dice coefficient and volume correlation of 39.1% and 0.76 for DWI lesions and 18.9% and 0.61 for FLAIR lesions. In the subgroup with 15 mL or greater lesion volume, the evaluation of DWI-FLAIR mismatch from NCCT by inexperienced neurologists improved in accuracy (from 0.537 to 0.610) and AUC-ROC (from 0.493 to 0.613). Conclusion: The DWI-FLAIR mismatch may be reckoned using NCCT images through advanced artificial intelligence techniques.

Impact of vessel tortuosity and radiological thrombus characteristics on the choice of first-line thrombectomy strategy: Results from the ESCAPE-NA1 trial.

INTRODUCTION: Despite improvements in device technology, only one-third of stroke patients undergoing endovascular thrombectomy (EVT) achieve first-pass effect (FPE). We investigated the effect of arterial tortuosity and thrombus characteristics on the relationship between first-line EVT strategy and angiographic outcomes. PATIENTS AND METHODS: Patients with thin-slice baseline CT-angiography from the ESCAPE-NA1 trial (Efficacy and safety of nerinetide for the treatment of acute ischemic stroke) were included. Tortuosity was estimated using the tortuosity index extracted from catheter pathway, and radiological thrombus characteristics were length, non-contrast density, perviousness and hyperdense artery sign. We assessed the association of first-line EVT strategy (stent-retriever [SR] versus contact aspiration [CA] versus combined SR+CA) with FPE (eTICI score 2c/3 after one pass), final eTICI 2b/3, number of passes and procedure duration using multivariable regression. Interaction of tortuosity and thrombus characteristics with first-line technique were assessed using interaction terms. RESULTS: Among 520 included patients, SR as a first-line modality was used in 165 (31.7%) patients, CA in 132 (25.4%), and combined SR+CA in 223 (42.9%). FPE was observed in 166 patients (31.9%). First-line strategy was not associated with FPE. Tortuosity had a significant effect on FPE only in the CA group (aOR = 0.90 [95% CI 0.83-0.98]) compared with stent-retrievers and combined first-line approach (p interaction = 0.03). There was an interaction between thrombus length and first-line strategy for number of passes (p interaction = 0.04). Longer thrombi were associated with higher number of passes only in the CA group (acOR 1.03 [95% CI 1.00-1.06]). CONCLUSION: Our study suggests that vessel tortuosity and longer thrombi may negatively affect the performance of first-line contact aspiration catheters in acute stroke patients undergoing EVT.