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Purpose: Endovascular treatment (EVT) of acute ischemic stroke can be complicated by vessel perforation. We studied the incidence and determinants of vessel perforations. In addition, we studied the association of vessel perforations with functional outcome, and the association between location of perforation on digital subtraction angiography (DSA) and functional outcome, using a large EVT registry. Methods: We included all patients in the MR CLEAN Registry who underwent EVT. We used DSA to determine whether EVT was complicated by a vessel perforation. We analyzed the association with baseline clinical and interventional parameters using logistic regression models. Functional outcome was measured using the modified Rankin Scale at 90 days. The association between vessel perforation and angiographic imaging features and functional outcome was studied using ordinal logistic regression models adjusted for prognostic parameters. These associations were expressed as adjusted common odds ratios (acOR). Results: Vessel perforation occurred in 74 (2.6%) of 2794 patients who underwent EVT. Female sex (aOR 2.0 (95% CI 1.2–3.2)) and distal occlusion locations (aOR 2.2 (95% CI 1.3–3.5)) were associated with increased risk of vessel perforation. Functional outcome was worse in patients with vessel perforation (acOR 0.38 (95% CI 0.23–0.63)) compared to patients without a vessel perforation. No significant association was found between location of perforation and functional outcome. Conclusion: The incidence of vessel perforation during EVT in this cohort was low, but has severe clinical consequences. Female patients and patients treated at distal occlusion locations are at higher risk. [ABSTRACT FROM AUTHOR]

Background: A considerable proportion of acute ischemic stroke patients treated with endovascular thrombectomy (EVT) are dead or severely disabled at 3 months despite successful reperfusion. Ischemic core imaging biomarkers may help to identify patients who are more likely to have a poor outcome after endovascular thrombectomy (EVT) despite successful reperfusion. We studied the association of CT perfusion-(CTP), CT angiography-(CTA), and non-contrast CT-(NCCT) based imaging markers with poor outcome in patients who underwent EVT in daily clinical practice. Methods: We included EVT-treated patients (July 2016–November 2017) with an anterior circulation occlusion from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry with available baseline CTP, CTA, and NCCT. We used multivariable binary and ordinal logistic regression to analyze the association of CTP ischemic core volume, CTA-Collateral Score (CTA-CS), and Alberta Stroke Program Early CT Score (ASPECTS) with poor outcome (modified Rankin Scale score (mRS) 5-6) and likelihood of having a lower score on the mRS at 90 days. Results: In 201 patients, median core volume was 13 (IQR 5-41) mL. Median ASPECTS was 9 (IQR 8-10). Most patients had grade 2 (83/201; 42%) or grade 3 (28/201; 14%) collaterals. CTP ischemic core volume was associated with poor outcome [aOR per 10 mL 1.02 (95%CI 1.01–1.04)] and lower likelihood of having a lower score on the mRS at 90 days [aOR per 10 mL 0.85 (95% CI 0.78–0.93)]. In multivariable analysis, neither CTA-CS nor ASPECTS were significantly associated with poor outcome or the likelihood of having a lower mRS. Conclusion: In our population of patients treated with EVT in daily clinical practice, CTP ischemic core volume is associated with poor outcome and lower likelihood of shift toward better outcome in contrast to either CTA-CS or ASPECTS. [ABSTRACT FROM AUTHOR]

Background: Endovascular treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO.Methods: MR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS < 3 with an LVO confirmed on CT angiography/MR angiography eligible for both IVT and EVT are randomized to receive either IVT (0.9 mg/kg) followed by EVT, or direct EVT in a 1:1 ratio. The primary objective is to assess superiority of direct EVT. Secondarily, non-inferiority of direct EVT compared to IVT before EVT will be explored. The primary outcome is the score on the modified Rankin Scale at 90 days. Ordinal regression with adjustment for prognostic variables will be used to estimate treatment effect. Secondary outcomes include reperfusion graded with the eTICI scale after EVT and stroke severity (National Institutes of Health Stroke Scale) at 24 h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included.Discussion: IVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT.Trial Registration: www.isrctn.com : ISRCTN80619088 . Registered on 31 October 2017. [ABSTRACT FROM AUTHOR]

Background and purpose: Direct presentation of patients with acute ischemic stroke to a comprehensive stroke center (CSC) reduces time to endovascular treatment (EVT), but may increase time to treatment for intravenous thrombolysis (IVT). This dilemma, however, is not applicable to patients who have a contraindication for IVT. We examined the effect of direct presentation to a CSC on outcomes after EVT in patients not eligible for IVT. Methods: We used data from the MR CLEAN Registry (2014–2017). We included patients who were not treated with IVT and compared patients directly presented to a CSC to patients transferred from a primary stroke center. Outcomes included treatment times and 90-day modified Rankin Scale scores (mRS) adjusted for potential confounders. Results: Of the 3637 patients, 680 (19%) did not receive IVT and were included in the analyses. Of these, 389 (57%) were directly presented to a CSC. The most common contraindications for IVT were anticoagulation use (49%) and presentation > 4.5 h after onset (26%). Directly presented patients had lower baseline NIHSS scores (median 16 vs. 17, p = 0.015), higher onset-to-first-door times (median 105 vs. 66 min, p < 0.001), lower first-door-to-groin times (median 93 vs. 150 min; adjusted β = − 51.6, 95% CI: − 64.0 to − 39.2) and lower onset-to-groin times (median 220 vs. 230 min; adjusted β = − 44.0, 95% CI: − 65.5 to − 22.4). The 90-day mRS score did not differ between groups (adjusted OR: 1.23, 95% CI: 0.73–2.08). Conclusions: In patients who were not eligible for IVT, treatment times for EVT were better for patients directly presented to a CSC, but without a statistically significant effect on clinical outcome. [ABSTRACT FROM AUTHOR]

Background: Endovascular treatment (EVT) with or without intravenous thrombolysis (IVT) is effective and safe in is-chemic stroke caused by large vessel occlusion, but IVT might delay time to EVT or increase risk of intracranial hemorrhage (ICH). We assessed the influence of prior IVT on time to treatment and risk of ICH in patients treated with EVT. Methods: We analyzed data from the MR CLEAN Registry and included patients with an anterior circulation occlusion treated with EVT who presented directly to an intervention center, between 2014 and 2017. Primary endpoint was the door to groin time. Secondary outcomes were workflow time intervals and safety outcomes. We compared patients who received EVT only with patients who received IVT prior to EVT. Results: We included 1,427 patients directly referred to an intervention center of whom 1,023 (72%) received IVT + EVT. Adjusted door to CT imaging and door to groin time were shorter in IVT + EVT patients (difference 5.7 min [95% CI: 4.6–6.8] and 7.0 min [95% CI: 2.4–12], respectively) while CT imaging to groin time was similar between the groups. Early recanalization on digital subtraction angiography before EVT was seen more often after prior IVT (11 vs. 5.2%, aOR 2.4 [95% CI: 1.4–4.2]). Rates of symptomatic ICH were similar. Conclusion: Prior IVT did not delay door to groin times and was associated with higher rates of early recanalization, without increasing the risk of ICH. Our results do not warrant withholding IVT prior to EVT. [ABSTRACT FROM AUTHOR]

Background collateral status modified the effect of endovascular treatment (EVT) for stroke in several randomized trials. We assessed the association between collaterals and functional outcome in EVT treated patients and investigated if this association is time dependent. Methods We included consecutive patients from the Multicenter Randomized clinical Trial of Endovascular Treatment for Acute Ischemic stroke in The Netherlands (MR cLEAN) Registry (March 2014-June 2016) with an anterior circulation large vessel occlusion undergoing EVT. Functional outcome was measured on the modified Rankin scale (MRS) at 90 days. We investigated the association between collaterals and mRs in the MR CLEAN Registry with ordinal logistic regression and if this association was time dependent with an interaction term. Additionally, we determined modification of EVT effect by collaterals compared with MR cLEAN controls, and also investigated if this was time dependent with multiplicative interaction terms. Results 1412 patients were analyzed. Functional independence (mRs score of 0-2) was achieved in 13% of patients with grade 0 collaterals, in 27% with grade 1, in 46% with grade 2, and in 53% with grade 3. collaterals were significantly associated with mRs (adjusted common OR 1.5 (95% ci 1.4 to 1.7)) and significantly modified EVT benefit (P=0.04). None of the effects were time dependent. Better collaterals corresponded to lower mortality (P<0.001), but not to lower rates of symptomatic intracranial hemorrhage Conclusion In routine clinical practice, better collateral status is associated with better functional outcome and greater treatment benefit in EVT treated acute ischemic stroke patients, independent of time to treatment. Within the 6 hour time window, a substantial proportion of patients with absent and poor collaterals can still achieve functional independence. [ABSTRACT FROM AUTHOR]

Background: Randomized, clinical trials in selected acute ischemic stroke patients reported that for every hour delay of endovascular treatment (EVT), chances of functional independence diminish by up to 3.4%. These findings may not be fully generalizable to clinical practice because of strict in- and exclusion criteria in these trials. Therefore, we aim to assess the association of time to EVT with functional outcome in current, everyday clinical practice.Methods: The MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) is an ongoing, prospective, observational study in all centers that perform EVT in The Netherlands. Data were analyzed from patients treated between March 2014 and June 2016. In the primary analysis we assessed the association of time from stroke onset to start of EVT and time from stroke onset to successful reperfusion with functional outcome (measured with the modified Rankin Scale), by means of ordinal logistic regression.Results: We analyzed 1488 patients with acute ischemic stroke who underwent EVT. An increased time to start of EVT was associated with worse functional outcome (adjusted common odds ratio, 0.83 per hour; 95% confidence interval, 0.77-0.89) and a 2.2% increase in mortality. Every hour increase from stroke onset to EVT start resulted in a 5.3% decreased probability of functional independence (modified Rankin Scale, 0-2). In the 742 patients with successful reperfusion, every hour increase from stroke onset to reperfusion was associated with a 7.7% decreased probability of functional independence.Conclusions: Time to EVT for acute ischemic stroke in current clinical practice is strongly associated with functional outcome. Our data suggest that this association might be even stronger than previously suggested in reports on more selected patient populations from randomized, controlled trials. These findings emphasize that functional outcome of EVT patients can be greatly improved by shortening onset to treatment times. [ABSTRACT FROM AUTHOR]