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Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship.In a pooled, patient-level analysis of EXTEND-IA trials and SELECT study, we employed a mediation analysis framework to quantify infarct growth and cerebral edema(midline shift) mediation effect on successful reperfusion(mTICI≥2b) association with functional outcome(mRS distribution). Further, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift.542/665(81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful vs unsuccessful reperfusion. Median(IQR) infarct growth was 12.3(1.8-48.4)ml and median(IQR) midline shift was 0(0,2.2)mm. Of 249(37%) demonstrating a midline shift of ≥1mm, median(IQR) shift was 2.75(1.89, 4.21)mm). Successful reperfusion was associated with reductions in both predefined mediators; infarct growth (β, -1.19; 95%CI, -1.51to-0.88;p0.001) and midline shift (aOR:0.36,95%CI:0.23-0.57,p0.001). Successful reperfusion association with improved functional outcome (acOR:2.68; 95%CI:1.86-3.88,p0.001), became insignificant (acOR:1.39, 95%CI:0.95-2.04,p=0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect. Analysis considering alternative hypothesis demonstrated consistent results.In this mediation analysis from a pooled, patient-level cohort, a significant proportion(~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect and identify novel therapeutic targets to further enhance reperfusion benefits. This article is protected by copyright. All rights reserved.

Background: Limited data are available on endovascular thrombectomy (EVT) efficacy and safety in large vessel occlusion (LVO) patients presenting >24hr from last known well (LKW). We compared outcomes between patients receiving EVT and best medical management (MM) in a multicenter international cohort. Methods: Consecutive patients with anterior circulation LVO presenting >24h after LKW from 13 centers from 7/2012-4/2021 were analyzed. Multivariable models for 90d mRS distribution and symptomatic ICH were adjusted for age, NIHSS, glucose, IV tPA, transfer status, clot location, time from LKW, CT ASPECTS and ischemic core (rCBF6s volumes. Results: Of 240 patients with a median (IQR) LKW to presentation 28.3h (24.9-38.2), 153 (64%) received EVT. Baseline characteristics were similar except for NIHSS (EVT: 13 (8-20) vs MM: 17 (10-22), p=0.005), CT ASPECTS (EVT: 8(6-9) vs MM: 4(3-6), p Conclusions: EVT may be associated with better functional outcomes, despite numerically increased risk of sICH in patients presenting with anterior circulation LVO beyond 24 hours. Further prospective studies are warranted.

Background: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. Methods: In a pooled patient level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II and SELECT, EVT Functional outcomes (mRS distribution) were compared between general anesthesia (GA) vs non-general anesthesia (non-GA). Further, we assessed the impact of collateral flow on perfusion imaging evaluated by hypoperfusion intensity ratio (HIR) - Tmax10 sec/Tmax6 sec) on the association between anesthesia type and EVT outcomes. Results: Of 731 treated with EVT, 305 (42%) received GA and 426 (58%) non-GA. The baseline characteristics were similar, except for presentation NIHSS (median [IQR] GA 18 [13-22], non-GA 16[11-20], p Conclusion: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals. These findings have implications for randomized trials of GA vs non-GA.

ImportanceThe role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well.ObjectiveTo evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well.Design, Setting, and ParticipantsThis retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well.InterventionsEndovascular thrombectomy or medical management (control).Main Outcomes and MeasuresPrimary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)–weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts.ResultsOf 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02).Conclusions and RelevanceIn this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation.

There is a growing interest in performing pulmonary vein isolation (PVI) with concomitant posterior wall isolation (PWI) using the cryoballoon for the treatment of patients with persistent atrial fibrillation (AF). However, there is little known about the long-term durability of PWI using this approach.In this multicenter study, we retrospectively examined the durability of PVI + PWI using the 28-mm cryoballoon by investigating the outcomes from consecutive patients referred for repeat catheter ablation.Altogether, 81/519 patients (15.6%) were referred for repeat catheter ablation. Repeat ablation was associated with a longer AF duration, hypertension, heart failure, multiple cardioversions, and antiarrhythmic therapy as well as larger left atrial (LA) diameters (49 ± 4 mm versus 43 ± 5 mm; P0.001) and greater need for "touch-up" (adjunct) radiofrequency ablation (44.4% versus 18.3%; P0.001). LA diameter also emerged as a significant predictor for adjunct radiofrequency ablation (P0.001). Durable PVI was observed in 66/81 patients (81.5%) and PWI in 67/81 patients (82.7%). Those with incomplete PWI exhibited larger LA diameters, particularly48 mm (negative predictive value = 89.7%). Lastly, an atypical LA posterior wall/roof flutter represented the third most common cause of arrhythmia recurrence and essentially every patient with incomplete PWI exhibited such an arrhythmia.PWI performed using a 28-mm cryoballoon in conjunction with PVI exhibits long-term durability in the vast majority of patients with persistent AF. While LA diameter (particularly48 mm) is a significant predictor for the need for adjunct radiofrequency ablation when performing this technique, those with incomplete PWI invariably present with an atypical flutter using this substrate.