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Background: We evaluated the association of reperfusion quality and different patterns of achieved reperfusion with clinical and radiological outcomes in the ESCAPE NA1 trial., Methods: Data are from the ESCAPE-NA1 trial. Good clinical outcome [90-day modified Rankin Scale (mRS) 0-2], excellent outcome (90-day mRS0-1), isolated subarachnoid hemorrhage, symptomatic hemorrhage (sICH) on follow-up imaging, and death were compared across different levels of reperfusion defined by expanded Treatment in Cerebral Infarction (eTICI) Scale. Comparisons were also made between patients with (a) first-pass eTICI 2c3 reperfusion vs multiple-pass eTICI 2c3; (b) final eTICI 2b reperfusion vs eTICI 2b converted-to-eTICI 2c3; (c) sudden reperfusion vs gradual reperfusion if >1 pass was required. Multivariable logistic regression was used to test associations of reperfusion grade and clinical outcomes., Results: Of 1037 included patients, final eTICI 0-1 was achieved in 46 (4.4%), eTICI 2a in 76 (7.3%), eTICI 2b in 424 (40.9%), eTICI 2c in 284 (27.4%), and eTICI 3 in 207 (20%) patients. The odds for good and excellent clinical outcome gradually increased with improved reperfusion grades (adjOR ranging from 5.7-29.3 and 4.3-17.6) and decreased for sICH and death. No differences in outcomes between first-pass versus multiple-pass eTICI 2c3, eTICI 2b converted-to-eTICI 2c3 versus unchanged eTICI 2b and between sudden versus gradual eTICI 2c3 reperfusion were observed., Conclusion: Better reperfusion degrees significantly improved clinical outcomes and reduced mortality, independent of the number of passes and whether eTICI 2c3 was achieved suddenly or gradually., Competing Interests: Declaration of conflicting interestThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Financial interests: PC reports honoraria from ESMINT, outside the submitted work. JO reports consultancy fee from NicoLab. ADM received grants from NoNO; honoraria from Medtronic; patent Circle NVI. MT is CEO of NoNO; patents owned by NoNO. BKM has stock options in Circle NVI and has consulted for Biogen and Boehringer Ingelheim. AYP has received a project research grant from Stryker and honoraria from BMS-Pfizer. MDH has received consulting fees from Sun Pharma and Brainsgate and has stock options in Circle NVI. MG reports consultancy for Medtronic, Stryker, Microvention, GE Healthcare, Mentice, outside the submitted work. All other authors have nothing to disclose. Nonfinancial interests: ADM is a member of the editorial board at International Journal of Stroke (Editor). AYP is PI of EASI-TOC study. BKM is a member of the editorial board at Stroke (Assistant Editor). MDH is Director, Board of Circle Neurovascular, Director, Board of the Canadian Neuroscience Federation, and Director, Board of the Canadian Stroke Consortium. MG is a member of the editorial board at Stroke (Consulting Editor).

Background: Incomplete reperfusion (IR) after mechanical thrombectomy (MT) can be a consequence of residual occlusion, no-reflow phenomenon, or collateral counterpressure. Data on the impact of these phenomena on clinical outcome are limited., Methods: Patients from the ESCAPE-NA1 trial with IR (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b) were compared with those with complete or near-complete reperfusion (eTICI 2c-3) on the final angiography run. Final runs were assessed for (a) an MT-accessible occlusion, or (b) a non-MT-accessible occlusion pattern. The primary clinical outcome was modified Rankin Scale (mRS) 0-2 at 90 days. Our imaging outcome was infarction in IR territory on follow-up imaging. Unadjusted and adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI) were obtained., Results: Of 1105 patients, 443 (40.1%) with IR and 506 (46.1%) with complete or near-complete reperfusion were included. An MT-accessible occlusion was identified in 147/443 patients (33.2%) and a non-MT-accessible occlusion in 296/443 (66.8%). As compared with patients with near-complete/complete reperfusion, patients with IR had significantly lower chances of achieving mRS 0-2 at 90 days (aIRR 0.82, 95% CI 0.74 to 0.91). Rates of mRS 0-2 were lower in the MT-accessible occlusion group as compared with the non-MT-accessible occlusion pattern group (aIRR 0.71, 95% CI 0.60 to 0.83, and aIRR 0.89, 95% CI 0.81 to 0.98, respectively). More patients with MT-accessible occlusion patterns developed infarcts in the non-reperfused territory as compared with patients with non-MT occlusion patterns (68.7% vs 46.3%)., Conclusion: IR was associated with worse clinical outcomes than near-complete/complete reperfusion. Two-thirds of our patients with IR had non-MT-accessible occlusion patterns which were associated with better clinical and imaging outcomes compared with those with MT-accessible occlusion patterns., Competing Interests: Competing interests: PC reports honoraria from A-care Medical, outside the submitted work. JO reports consultancy fee from NicoLab. ADM received grants from NoNO; honoraria from Medtronic; patent Circle NVI. MT is CEO of NoNO; patents owned by NoNO. MDH received grants from Canadian Institutes for Health Research, Alberta Innovates, NoNO, Heart & Stroke Foundation of Canada, National Institutes of Neurological Disorders and Stroke, Covidien, Boehringer-Ingleheim, Stryker, and Medtronic; fees from Merck; patent for systems of acute stroke diagnosis; a patent issued and licensed to US Patent office Number: 62/086,077; stock in Calgary Scientific. MG reports consultancy for Medtronic, Stryker, Microvention, GE Healthcare, Mentice, outside the submitted work. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Meaningful delays occurred in the Interventional Management of Stroke (IMS) III trial. Analysis of the work flow will identify factors contributing to the in-hospital delays., Methods and Results: In the endovascular arm of the IMS III trial, the following time intervals were calculated: stroke onset to emergency department arrival; emergency department to computed tomography (CT); CT to intravenous tissue plasminogen activator start; intravenous tissue plasminogen activator start to randomization; randomization to groin puncture; groin puncture to thrombus identification; thrombus identification to start of endovascular therapy; and start of endovascular therapy to reperfusion. The effects of enrollment time, CT angiography use, interhospital transfers, and intubation on work flow were evaluated. Delays occurred notably in the time intervals from intravenous tissue plasminogen activator initiation to groin puncture (median 84 minutes) and start of endovascular therapy to reperfusion (median 85 minutes). The CT to groin puncture time was significantly shorter during working hours than after. Times from emergency department to reperfusion and groin puncture to reperfusion decreased over the trial period. Patients with CT angiography had shorter emergency department to reperfusion and onset to reperfusion times. Transfer of patients resulted in a longer onset to reperfusion time compared with those treated in the same center. Age, sex, National Institutes of Health Stroke Scale score, and intubation did not affect delays., Conclusions: Important delays were identified before reperfusion in the IMS III trial. Delays decreased as the trial progressed. Use of CT angiography and endovascular treatment in the same center were associated with time savings. These data may help in optimizing work flow in current and future endovascular trials., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00359424., (© 2014 American Heart Association, Inc.)

Background and Purpose: The shorter the time interval between the estimation of the ischemic core by imaging and reperfusion, the more likely that core expansion is minimized. We aimed to assess the feasibility of achieving an ultrashort imaging to reperfusion time in routine clinical practice., Methods: The study subjects were a prospective cohort of patients with acute ischemic stroke treated with endovascular therapy in a tertiary center in whom an imaging to reperfusion time of <60 min was achieved., Results: Imaging to reperfusion time of <60 min was accomplished in 11 patients. The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 11 and the median baseline Alberta Stroke Program Early CT Score (ASPECTS) was 8. The median time interval from imaging to endovascular reperfusion was 47 min. The median ASPECTS score on the 24 h CT scan was also 8 and the median 24 h NIHSS score was 1. Upon discharge, 82% of patients achieved a modified Rankin scale score of ≤ 1., Conclusions: An imaging to endovascular reperfusion time of <60 min is feasible and resulted in minimal core expansion on follow-up imaging in patients with 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. [ABSTRACT FROM AUTHOR]

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 (β ± 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. [ABSTRACT FROM AUTHOR]

Background Determining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication. Objective To estimate infarct progression rate in patients with AIS with large vessel occlusion (LVO) and determine its predictors and impact on clinical outcome. Methods Data are from the ESCAPE-NA1 Trial. Patients with AIS with time from last known well to randomization <6 hours and near-complete reperfusion following endovascular treatment were included. Infarct growth rate (mL/h) was estimated by dividing 24 hour infarct volume (measured by non-contrast CT or diffusion-weighted magnetic resonance imaging) by time from last known well to reperfusion. Multivariable linear regression was used to assess the association of patient baseline variables with log-transformed infarct progression rate. The association of infarct progression rate and good outcome (modified Rankin Scale score 0-2) was determined using multivariable logistic regression. Results Four hundred and nine patients were included in the study. Median infarct progression rate was 4.74 mL/h (IQR 1.25-14.84). Collateral status (β: -0.81 (95% CI -1.20 to -0.41)), Alberta Stroke Program Early CT Score (ASPECTS, β: -0.34 (95% CI -0.46 to -0.23)), blood glucose(β: 0.09 (95% CI 0.02 to 0.16)), and National Institutes of Health Stroke Scale (NIHS score (β: 0.07 (95% CI 0.04 to 0.10)) were associated with logtransformed infarct progression rate. Clinical and imaging baseline variables explained 23% of the variance in infarct progression rate. Infarct progression rate was significantly associated with good outcome (aOR per 1 mL/h increase: 0.96 (95% CI 0.95 to 0.98)). Conclusion In this sample of patients presenting within the early time window with LVO and nearcomplete recanalization, infarct progression rate was significantly associated with good outcome. A significant association between ASPECTS, collateral status, blood glucose, and NIHSS score was observed, but baseline imaging and clinical characteristics explained only a small proportion of the interindividual variance. More research on measurable factors affecting infarct growth is needed. [ABSTRACT FROM AUTHOR]

Background and purpose: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management. Methods: We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0–2a. Proportions of good outcome (modified Rankin scale 0–2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained. Results: We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81–2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56–2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00–22.97). Conclusion: Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management [ABSTRACT FROM AUTHOR]

Background The DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1. Methods Aggregate data on baseline characteristics, workflow, reperfusion quality, final infarct volume, and clinical outcomes (modified Rankin Score [mRS] at 90 days) in subjects enrolled in the DAWN and DEFUSE-3 EVT arms were compared with similar data from the ESCAPE-NA1 control arm (EVT-only arm) presenting beyond 6 hours from LKW using descriptive statistics. Results Baseline characteristics among late-window patients in the ESCAPE NA1 trial were similar to those in the DAWN and DEFUSE-3 EVT arms. Median time from LKW-to-puncture in subjects enrolled in the ESCAPE NA1 trial was 9 hrs (IQR: 7.5--11 hours) when compared with DAWN (n=107; 12.8 hours, IQR: 10.6--16.7 hours) and DEFUSE-3 (n=92; 11.5 hours, IQR: 9.2--12.8 hours). Median post-treatment infarct-volume was largest in the ESCAPE NA1-patients (47 mL [IQR: 19--146] vs median 8 mL [IQR: 0--48] in the DAWN group and 35 mL [IQR: 18--82] in DEFUSE-3), while % mRS 0--2 at 90 days were similar across the three trials (ESCAPE NA1: 50/111 [45%], DAWN: 52/107 [49%], DEFUSE-3: 41/92 [45%]). Conclusion Patients enrolled beyond 6 hours from LKW in the ESCAPE-NA1 trial based on NCCT-ASPECTS and mCTA had similar clinical outcomes when compared with patients selected by perfusion imaging in the DAWN and DEFUSE-3 trials. [ABSTRACT FROM AUTHOR]

Since 2015, endovascular therapy (EVT) has become the standard of care for acute ischemic stroke (AIS) due to large vessel occlusion. It is a safe and highly effective treatment, and its number needed to treat of 2.6 is one of the highest throughout medicine. The ultimate goal when performing EVT is to maximize chances of good outcome through achievement of fast first-pass complete reperfusion, as incomplete and delayed reperfusion increases complication rates and negatively affects outcome. Since EVT has been established as standard of care, new devices have been developed and treatment techniques have been refined. This review provides a brief overview about the rationale for and history of EVT, followed by a detailed step-by-step description of how to perform EVT using the BADDASS (BAlloon guide with large bore Distal access catheter with Dual Aspiration with Stent-retriever as Standard approach), a combined technique, which is in our opinion the safest and most effective way to achieve fast first-pass complete reperfusion. We also discuss treatment strategies for patients with simultaneous high-grade carotid stenosis/pseudoocclusion/occlusion and gaining carotid access in challenging arch anatomy, as these are commonly encountered situations in AIS, and conclude with an outlook on new technologies and future directions of EVT. [ABSTRACT FROM AUTHOR]

ESCAPE is a prospective, multicenter, randomized clinical trial that will enroll subjects with the following main inclusion criteria: less than 12 h from symptom onset, age > 18, baseline NIHSS >5, ASPECTS score of >5 and CTA evidence of carotid T/ L or M1 segment MCA occlusion, and at least moderate collaterals by CTA. The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with standard medical therapy alone. Patient populations that are eligible include those receiving IV tPA, tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal. The primary end-point, based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days assessed using a proportional odds model. The projected maximum sample size is 500 subjects. Randomization is stratified under a minimization process using age, gender, baseline NIHSS, baseline ASPECTS (8-10 vs. 6-7), IV tPA treatment and occlusion location ( ICA vs. MCA) as covariates. The study will have one formal interim analysis after 300 subjects have been accrued. Secondary end-points at 90 days include the following: mRS 0-1; mRS 0-2; Barthel 95-100, EuroQOL and a cognitive battery. Safety outcomes are symptomatic ICH, major bleeding, contrast nephropathy, total radiation dose, malignant MCA infarction, hemicraniectomy and mortality at 90 days. [ABSTRACT FROM AUTHOR]

The advent of stentrievers provided momentum for endovascular stroke therapy. Hopes were dampened after three randomized trials showed no clear benefit of endovascular therapy. This review discusses the results of these trials results and shortcomings. A detailed discussion will follow on the design, conduct and analysis of current and future endovascular stroke trials. Steps to improve the workflow of acute stroke cases from the time they enter the emergency department until endovascular reperfusion is achieved can significantly shorten the time from onset to successful reperfusion. These factors in addition to using novel approaches to analyze data and minimize delays caused by the consent process are perceived to be sufficient to demonstrate the efficacy of endovascular stroke therapy. [ABSTRACT FROM AUTHOR]

Rapid reperfusion of the entire territory distal to vascular occlusions is the aim of stroke interventions. Recent studies defined successful reperfusion as establishing some perfusion with distal branch filling of <50% of territory visualized (Thrombolysis In Cerebral Infarction "TICI" 2a) or more. We investigate the importance of the quality of final reperfusion and whether a revision of the successful reperfusion definition is warranted. We retrospectively evaluated a prospective database of anterior circulation strokes treated using stentrievers to assess the quality of final reperfusion using two scores: the traditional TICI score and a modified TICI score. The modified TICI score includes an additional category (TICI 2c): near complete perfusion except for slow flow or distal emboli in a few distal cortical vessels. We compared different cut-off definitions of reperfusion (TICI 2a – 3 vs. TICI-2b-3 vs. TICI 2c-3) using the area under the curve to identify their correlation with a favorable 90-day outcome (mRS≤2). In our cohort of 110 patients, 90% achieved TICI 2a-3 reperfusion with 80% achieving TICI 2b-3 and 55.5% achieving TICI 2c-3. The proportion of patients with a favorable 90- day outcome was higher in the TICI 2c (62.5%) compared to TICI 2b (44.4%) or TICI 2a (45.5%) but similar to the TICI 3 group (75.9%). A TICI 2c-3 reperfusion had a better predictive value than TICI 2b-3 for 90-day mRS 0-1. Defining successful reperfusion as TICI 2c/3 has merits. In this cohort, there was evidence toward faster recovery and better outcomes in patients with the TICI 2c vs. the traditional TICI 2b grade. [ABSTRACT FROM AUTHOR]

Introduction: Quicker recanalization results in better clinical outcomes in patients with acute ischemic strokes. We describe our experience with the use of a self-expanding, fully retrievable stent in acute intracranial occlusions. Methods: Patients who underwent intra-arterial procedures with a self-expanding, fully retrievable stent for acute ischemic strokes at our center in 2009 were included in this study. The primary outcome was recanalization [Thrombolysis in Myocardial Infarction (TIMI) grade 2/3] at end of procedure. Secondary endpoints were procedural interval times, incidence of vasospasm, rupture of vessels, device-related complications, groin complications, postprocedural intracerebral hemorrhage (ICH) on noncontrast CT, and all-cause mortality. Results: Fourteen patients (mean age 62.1 years, range 34-81 years; six males) were included in the study. Sites of occlusion are as follows: M1 middle cerebral artery (MCA, n = 8), M2 MCA ( n = 1), proximal basilar artery ( n = 1), and distal basilar artery ( n = 4). An additional device or technique was used in 9 of 14 patients prior to the use of the retrievable stent. Twelve out of 14 (85.7%) achieved TIMI 2-3 recanalization with 4 of 14 (28.6%) achieving TIMI 3. Eight of 14 (57.1%) patients had modified Rankin Scale (0-2) at 3 months or discharge. ICH on follow-up CT was noted in 28.6% (4 of 14) of patients. All-cause mortality was 2 of 14 (14.3%). Conclusion: Use of a novel self-expanding, fully retrievable stent resulted in fast and very high recanalization rates in acute ischemic strokes with intravascular occlusions. [ABSTRACT FROM AUTHOR]