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BACKGROUND AND OBJECTIVES: There is growing evidence for endovascular thrombectomy (EVT) in patients with large ischemic core infarct and large vessel occlusion (LVO). The objective of this study was to compare the efficacy and safety of EVT vs medical management (MM) using a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs). METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to mechanical thrombectomy for large ischemic core from inception until February 10, 2023. The primary outcome was independent ambulation (modified Rankin Scale [mRS] 0-3). Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. The quality of articles was evaluated through the Cochrane risk assessment tool and the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42023396232). RESULTS: A total of 5,395 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded by review of the title, abstract, and full text. Finally, 3 RCTs and 10 cohort studies met the inclusion criteria. The RCT analysis showed that EVT improved the 90-day functional outcomes of patients with large ischemic core with high-quality evidence, including independent ambulation (mRS 0-3: RR 1.78, 95% CI 1.28-2.48, p < 0.001) and functional independence (mRS 0-2: RR 2.59, 95% CI 1.89-3.57, p < 0.001), but without significantly increasing the risk of symptomatic intracranial hemorrhage (sICH: RR 1.83, 95% CI 0.95-3.55, p = 0.07) or early mortality (RR 0.95, 95% CI 0.78-1.16, p = 0.61). Analysis of the cohort studies showed that EVT improved functional outcomes of patients without an increase in the incidence in sICH. DISCUSSION: This systematic review and meta-analysis indicates that in patients with LVO stroke with a large ischemic core, EVT was associated with improved functional outcomes over MM without increasing sICH risk. The results of ongoing RCTs may provide further insight in this patient population.

Endovascular thrombectomy (EVT) safety and efficacy in patients with large core infarcts receiving oral anticoagulants (OAC) are unknown. In the SELECT2 trial (NCT03876457), 29 of 180 (16%; vitamin K antagonists 15, direct OACs 14) EVT, and 18 of 172 (10%; vitamin K antagonists 3, direct OACs 15) medical management (MM) patients reported OAC use at baseline. EVT was not associated with better clinical outcomes in the OAC group (EVT 6 [4–6] vs MM 5 [4–6], adjusted generalized odds ratio 0.89 [0.53–1.50]), but demonstrated significantly better outcomes in patients without OAC (EVT 4 [3–6] vs MM 5 [4–6], adjusted generalized odds ratio 1.87 [1.45–2.40], p = 0.02). The OAC group had higher comorbidities, including atrial fibrillation (70% vs 17%), congestive heart failure (28% vs 10%), and hypertension (87% vs 72%), suggesting increased frailty. However, the results were consistent after adjustment for these comorbidities, and was similar regardless of the type of OACs used. Whereas any hemorrhage rates were higher in the OAC group receiving EVT (86% in OAC vs 70% in no OAC), no parenchymal hemorrhage or symptomatic intracranial hemorrhage were observed with OAC use in both the EVT and MM arms. Although we did not find evidence that the effect was due to excess hemorrhage or confounded by underlying cardiac disease or older age, OAC use alone should not exclude patients from receiving EVT. Baseline comorbidities and ischemic injury extent should be considered while making individualized treatment decisions. ANN NEUROL 2024;96:887–894 [ABSTRACT FROM AUTHOR]

Background Different studies have demonstrated the benefit of endovascular treatment (EVT) up to 24 hours after acute ischemic stroke (AIS) onset. Recent cohort observational studies suggest that patients with large vessel occlusion AIS may benefit from EVT beyond 24 hours from the last known well (LKW) when adequately selected. We aimed to examine the safety and efficacy of EVT beyond 24 hours from LKW using a meta-analysis of all the literature available. Methods A systematic search from inception to April 2023 was conducted for studies including AIS patients with EVT beyond 24 hours from LKW in Medline, Embase, Scopus, and Web of Science. Outcomes of interest included favorable functional outcome (90-day modified Rankin scale (mRS) 0-2), successful reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2b-3), symptomatic intracerebral hemorrhage (sICH), and 90- day mortality. Data were pooled using a random-effects model. Results Twelve studies with 894 patients were included. The rate of favorable functional outcome was 40% (95% CI 31% to 49%; I²=76%). The rate of successful reperfusion was 83% (95% CI 80% to 85%; I²=0%). The sICH rate was 7% (95% CI 5% to 9%; I²=0%) and the 90-day mortality rate was 28% (95% CI 24% to 33%; I²=0%). There was no significant difference in favorable outcomes (OR=0.69; 95% CI 0.41 to 1.14) and 90-day mortality (OR=1.35; 95% CI 0.90 to 2.00) among patients who underwent EVT <24 hours versus >24 hours. Conclusions EVT beyond 24 hours from LKW may achieve favorable clinical outcomes and high reperfusion rates, with acceptable intracranial hemorrhage rates in selected patients. Considering the current certainty of the evidence and heterogenous individual study results, larger prospective trials are warranted. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the benefit from endovascular thrombectomy for patients with large ischemic strokes caused by large vessel occlusion vary by the extent of presenting ischemic injury? Findings: In an exploratory analysis of a randomized clinical trial that included 336 participants, while functional outcomes worsened as baseline ischemic core volumes increased, endovascular thrombectomy was associated with better clinical outcomes across a wide spectrum of ischemic changes and penumbra profiles on various imaging modalities compared with medical management. Meaning: Endovascular thrombectomy, compared with medical management, improved clinical outcomes across a wide spectrum of ischemic core volumes and penumbral profiles; however, large ischemic core volume is an important prognostic factor to consider when individualizing treatment decisions. Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome—90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457 This exploratory analysis of the SELECT2 trial assesses the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and the association of mismatch with clinical outcomes and endovascular treatment effect in adult patients with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery and large ischemic core in 31 global centers between October 2019 and September 2022. [ABSTRACT FROM AUTHOR]

Background: Although pulmonary vein isolation (PVI) remains the cornerstone of catheter ablation of atrial fibrillation (AF), several studies have illustrated clinical benefits associated with PVI with posterior wall isolation (PWI). Methods: This retrospective study investigated the outcomes of PVI alone versus PVI+PWI performed using the cryoballoon in patients with cardiac implantable electronic devices (CIEDs) and paroxysmal AF (PAF) or persistent AF (PersAF). Results: Acute PVI was achieved in all patients using cryoballoon ablation. Compared to PVI alone, PVI+PWI was associated with longer cryoablation, fluoroscopy, and total procedure times. Adjunct radiofrequency was required to complete PWI in 29/77 patients (37.7%). Adverse events were similar with PVI alone versus PVI+PWI. But at 24 ± 7 months of follow‐up, not only cryoballoon PVI+PWI was associated with improved freedom from recurrent AF (74.3% vs. 46.0%, P =.007) and all atrial tachyarrhythmias (71.4% vs. 38.1%, P =.001) in patients with PersAF, cryoballoon PVI+PWI also yielded greater freedom from AF (88.1% vs. 63.7%, P =.003) and all atrial tachyarrhythmias (83.3% vs. 60.8%, P =.008) in those with PAF. Additionally, PVI+PWI was associated with higher reductions in atrial tachyarrhythmia burden (97.9% vs. 91.6%, P <.001), need for cardioversion (5.2% vs. 23.6%, P <.001) and repeat catheter ablation (10.4% vs. 26.1%, P =.005), and a longer time‐to‐arrhythmia recurrence (16 ± 6 months vs. 8 ± 5 months, P <.001) in both PersAF and PAF patients. Conclusion: In CIED patients with PersAF or PAF, cryoballoon PVI+PWI is associated with a greater freedom from recurrent AF and atrial tachyarrhythmias, as compared to PVI alone during long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: In a pooled, patient‐level analysis of the EXTEND‐IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. Results: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8–48.4), and median midline shift was 0mm (IQR = 0–2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89–4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (β = −1.19, 95% confidence interval [CI] = −1.51 to −0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23–0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86–3.88, p < 0.001) 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, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. Interpretation: 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. ANN NEUROL 2023;93:793–804 [ABSTRACT FROM AUTHOR]

Background Sex disparities in acute ischemic stroke outcomes are well reported with IV thrombolysis. Despite several studies, there is still a lack of consensus on whether endovascular thrombectomy (EVT) outcomes differ between men and women. Objective To compare sex differences in EVT outcomes at 90-day follow-up and assess whether progression in functional status from discharge to 90-day follow-up differs between men and women. Methods From the Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) prospective cohort study (2016-2018), adult men and women (≥18 years) with anterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery M1/M2) treated with EVT up to 24 hours from last known well were matched using propensity scores. Discharge and 90-day modified Rankin Scale (mRS) scores were compared between men and women. Furthermore, we evaluated the improvement in mRS scores from discharge to 90 days in men and women using a repeated-measures, mixed-effects regression model. Results Of 285 patients, 139 (48.8%) were women. Women were older with median (IQR) age 69 (57-81) years vs 64.5 (56-75), p=0.044, had smaller median perfusion deficits (Tmax >6 s) 109 vs 154 mL (p<0.001), and had better collaterals on CT angiography and CT perfusion but similar ischemic core size (relative cerebral blood flow <30%: 7.6 (0-25.2) vs 11.4 (0-38) mL, p=0.22). In 65 propensity-matched pairs, despite similar discharge functional independence rates (women: 42% vs men: 48%, aOR=0.55, 95% CI 0.18 to 1.69, p=0.30), women exhibited worse 90-day functional independence rates (women: 46% vs men: 60%, aOR=0.41, 95% CI 0.16 to 1.00, p=0.05). The reduction in mRS scores from discharge to 90 days also demonstrated a significantly larger improvement in men (discharge 2.49 and 90 days 1.88, improvement 0.61) than in women (discharge 2.52 and 90 days 2.44, improvement 0.08, p=0.036). Conclusion In a propensity-matched cohort from the SELECT study, women had similar discharge outcomes as men following EVT, but the improvement from discharge to 90 days was significantly worse in women, suggesting the influence of post-discharge factors. [ABSTRACT FROM AUTHOR]