Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

Association of Mismatch Profiles and Clinical Outcome from Endovascular Therapy in Large Infarct: A Post-Hoc Analysis of the ANGEL-ASPECT Trial.

OBJECTIVES: We investigated whether patients with large infarct and the presence or absence of perfusion mismatch are associated with endovascular treatment benefit. METHODS: This is a post-hoc analysis of the Endovascular Therapy in Anterior Circulation Large Vessel Occlusion with a Large Infarct (ANGEL-ASPECT) randomized trial, which enrolled patients within 24 hours of onset with ASPECTS 3 to 5 or ASPECTS 0 to 2 with an infarct core 70 to 100 ml. Mismatch ratio was defined as time-to-maximum (Tmax) >6 s cerebral volume/ischemic core volume, and mismatch volume was defined as Tmax >6 s volume minus ischemic core volume. We divided patients into mismatch ratio ≥1.2 and mismatch volume ≥10 ml, and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups. The primary outcome was the 90-day modified Rankin Scale score ordinal distribution. Safety outcomes were symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: There were 425 patients included. In both the mismatch ratio ≥1.2 and mismatch volume ≥10 ml (mismatch+, n = 395; mismatch-, n = 31) and mismatch ratio ≥1.8 and mismatch volume ≥15 ml groups (mismatch+, n = 346; mismatch-, n = 80), better 90-day modified Rankin Scale outcomes were found in the endovascular treatment group compared with the MM group (4 [2-5] vs 4 [3-5], common odds ratio [cOR], 1.9, 95% confidence interval [CI] 1.3-2.7, p = 0.001; 4 [2-5] vs 4 [3-5], cOR, 1.9, 95% CI 1.3-2.8, p = 0.001, respectively), but not in patients without mismatch ratio ≥1.2 and mismatch volume ≥10 ml (5 [3-6] vs 5 [4-6], cOR, 1.2, 95% CI 0.3-4.1, p = 0.83), and mismatch ratio ≥1.8 and mismatch volume ≥15 ml (4 [3-6] vs 5 [3-6], cOR, 1.2, 95% CI 0.6-2.7, p = 0.60). However, no interaction effect was found in both subgroups (p interaction >0.10). CONCLUSION: Endovascular treatment was more efficacious than MM in patients with mismatch profiles, but no treatment effect or interaction was noted in the no mismatch profile patients. However, the small sample size of patients with no mismatch may have underpowered our analysis. A pooled analysis of large core trials stratified by mismatch is warranted. ANN NEUROL 2024.

Differentiation Between the Low and High Trans-Stenotic Pressure Gradient in Patients With Idiopathic Intracranial Hypertension Using 4D Flow MRI-Derived Hemodynamic Parameters.

BACKGROUND: Trans-stenotic pressure gradient (TPG) measurement is essential for idiopathic intracranial hypertension (IIH) patients with transverse sinus (TS) stenosis. Four-D flow MRI may provide a noninvasive imaging method for differentiation of IIH patients with different TPG. PURPOSE: To investigate the associations between 4D flow parameters and TPG, and to evaluate the diagnostic performance of 4D flow parameters in differentiating patients with high TPG (GroupHP) from low TPG (GroupLP). STUDY TYPE: Prospective. POPULATION: 31 IIH patients with TS stenosis (age, 38 ± 12 years; 23 females) and 5 healthy volunteers (age, 25 ± 1 years; 2 females). FIELD STRENGTH/SEQUENCE: 3T, 3D phase contrast MR venography, and gradient recalled echo 4D flow sequences. ASSESSMENT: Scan-rescan reproducibility of 4D flow parameters were performed. The correlation between TPG and flow parameters was analyzed. The netflow and velocity difference between inflow plane, outflow plane, and the stenosis plane were calculated and compared between GroupHP and GroupLP. STATISTICAL TESTS: Pearson's correlation or Spearman's rank correlation coefficient, Independent samples t-test or Wilcoxon rank-sum test, Intra-class correlation coefficient (ICC), Bland-Altman analyses, Receiver operating characteristic curves. A P value <0.05 was considered significant. RESULTS: Significant correlations were found between TPG and netflow parameters including Favg,out-s, Favg,in-s, Fmax,out-s, and Fmax,in-s (r = 0.525-0.565). Significant differences were found in Favg,out-s, Fmax,out-s, Favg,in-s, and Fmax,in-s between GroupHP and GroupLP. Using the cut-off value of 2.19 mL/sec, the Favg,out-s showed good estimate performance in distinguishing GroupHP from GroupLP (AUC = 0.856). The ICC (ranged 0.905-0.948) and Bland-Altman plots indicated good scan-rescan reproducibility. DATA CONCLUSIONS: 4D flow MRI derived flow parameters showed good correlations with TPG in IIH patients with TS stenosis. Netflow difference between outflow and stenosis location at TS shows the good performance in differentiating GroupHP and GroupLP cases. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Outcomes of antiplatelet therapy before endovascular treatment of acute large vessel occlusion: Data from the ANGEL-ACT registry.

OBJECTIVES: To investigate whether single or dual antiplatelet therapy (SAPT or DAPT) within 24 hours before endovascular treatment (EVT) could improve the clinical outcomes of patients with large vessel occlusion (LVO). METHODS: Patients from the ANGEL-ACT registry were divided into antiplatelet therapy (APT) and non-APT groups. The APT group was divided into SAPT and DAPT groups. Outcome measurement included 90-day modified Rankin Scale (mRS) distribution, change in the NIHSS at 7 days or discharge, number of passes, modified first pass effect (mFPE), symptomatic intracranial hemorrhage (SICH), and mortality within 90 days. To compare the outcomes, we performed multivariable analyses by adjusting for the propensity score calculated by the logistic regression model. RESULTS: Of 1611 patients, 1349 were in the non-APT group, while 262 (16.3 %) were in the APT group (122 [46.6 %] received SAPT, 140 [53.4 %] received DAPT). APT, SAPT or DAPT were not associated with a shift to better outcomes (non-APT vs. APT, 3[0-5] vs. 3[0-5], common odds ratio [OR], 1.04, 95 %confidence interval [CI]:0.82-1.34, P = 0.734). DAPT was associated with mFPE (OR,2.05, 95 %CI:1.39-3.01, P<0.001), more NIHSS reduction at 7 days or discharge (ß, -2.13, 95 %CI: -4.02--0.24, P = 0.028), lower number of passes (ß, -0.40, 95 %CI: -0.68--0.12, P=0.006), and shorter procedure duration (ß, -12.4, 95 %CI: -23.74--1.05, P = 0.032) without increasing odds of successful recanalization, PH within 24 hours and mortality with 90 days . CONCLUSIONS: APT before MT for AIS due to LVO does not affect clinical outcome in 90 days despite a tendency to reduce MT procedure time and number of passes. APT before MT in LVO does not increase SICH or mortality rates.

Sex-Related Differences in Outcomes of Endovascular Treatment for Anterior Circulation Large Vessel Occlusion.

BACKGROUND: Sex disparities in acute large vessel occlusion (LVO) following endovascular treatment (EVT) have been recently reported. However, there is uncertainty about the effect of sex differences on functional outcomes after EVT, particularly in an Asian population. The present study aimed to compare the clinical and safety outcomes between men and women with anterior circulation LVO treated with EVT. METHODS: We analyzed data from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke: a Prospective Multicenter Registry Study) Registry, which was conducted at 111 hospitals from 26 provinces in China between November 2017 and March 2019. Men and women with anterior circulation LVO treated with EVT were matched using propensity scores. After a 1:1 propensity score matching, we compared the clinical outcomes including 90-day ordinal modified Rankin Scale distribution (primary outcome), procedure duration, successful reperfusion, symptomatic intracranial hemorrhage, and mortality. Furthermore, we explored sex modification on the primary outcome in subgroup analysis. RESULTS: Of 1321 patients, 483 (36.6%) were women and 838 (63.4%) were men. The mean age for women and men were 68 and 62 years old, respectively. Among 578 patients identified after matching, there were no sex differences (men versus women) in 90-day ordinal modified Rankin Scale distribution (median [interquartile range], 4 [1-5] versus 3 [1-5], P=0.464), successful reperfusion (86.5% versus 91.0%, P=0.089), symptomatic intracranial hemorrhage (6.5% versus 7.9%, P=0.512), and mortality within 90 days (17.7% versus 17.0%, P=0.826). However, men had a longer median procedure duration than women (86 [52-128] versus 72 [48-110] minutes, ß=14.51, [95% CI, 4.19-24.84]; P=0.006). Subgroup analysis showed that in patients with National Institutes of Health Stroke Scale score <15, women tended to have a better outcome than men, whereas there was no gender effect in those with National Institutes of Health Stroke Scale score ≥15 (P for interaction=0.032). CONCLUSIONS: Overall, this matched-control study from the ANGEL-ACT study showed similar clinical outcomes between men and women with anterior circulation LVO treated with EVT. However, in the subgroup of patients presenting with lower stroke severity (ie, National Institutes of Health Stroke Scale score <15), women tended to have a better outcome than men highlighting a potential sex disparity for further investigation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03370939.

Estimation of venous sinus pressure drop in patients with idiopathic intracranial hypertension using 4D-flow MRI.

OBJECTIVE: We aimed to explore a non-invasive estimate of pressure drop in patients who undergo venous sinus stenting to treat idiopathic intracranial hypertension (IIH). METHODS: This prospective study included 28 IIH patients scheduled for venous stenting. 4D-flow MRI was acquired 24-48 h before venous manometry. Manometry-obtained pressure drop (Mp) was dichotomized into low (Lp: 0-8 mmHg) and high (Hp: 8-30 mmHg) groups. Hemodynamic indices were compared between Lp and Hp. Trans-stenotic pressure drop was estimated by work-energy equation, simplified Bernoulli equation, vorticity magnitude, and velocity difference between inlet and outlet and was compared with Mp. Measurement agreement, correlation, and accuracy were evaluated using the κ coefficient, Pearson's r, and confusion matrix-derived accuracy. RESULTS: Among 28 patients (mean age 38.8 ± 12.7), 19 (67.9%) were female. Work-energy equation-estimated pressure drop (WEp) had strong correlation (r = 0.91, 95% confidence interval [CI]: 0.81-0.96, p < 0.001) and high agreement (intraclass correlation coefficient = 0.90, 95% CI: 0.78-0.95, p < 0.001) with Mp. WEp classified Lp and Hp with an accuracy of 0.96. The κ value between WEp and Mp was 0.92 (95% CI: 0.78-1.00). In the work-energy equation, the viscosity energy term (Ve) had the largest weights, and the ratio of Ve to the summation of the three energy terms was 0.93 ± 0.07. Ve had strong correlation with mVort (r = 0.93, 95% CI: 0.85-0.97, p < 0.001), and mean vorticity magnitude was significantly elevated in Hp compared to that in Lp (259.8 vs. 174.9 mL/s, p < 0.001). CONCLUSION: Trans-stenotic pressure drop in IIH can be estimated using the work-energy equation with favorable accuracy. KEY POINTS: • Trans-stenotic pressure drop in patients with idiopathic intracranial hypertension can be estimated accurately with the work-energy equation using the 4D-flow MRI full velocity field. • Compared with traditional venous sinus manometry, the 4D-flow MRI-derived pressure drop is totally non-invasive and cost-saving. • 4D-flow MRI may help neurointerventionalist to select IIH patients suitable for venous sinus stenting.

The Effects of Pressure Gradient on Papilledema Improvement After Venous Sinus Stenting in Idiopathic Intracranial Hypertension.

PURPOSE: This study aimed to evaluate the impact of the pressure gradient on papilledema after stenting in patients with idiopathic intracranial hypertension (IIH) patients and venous sinus stenosis (VSS). MATERIALS AND METHODS: In this prospective cohort study, we examined 121 patients with IIH and VSS who underwent stenting. The papilledema Frisen grade at the 1-month follow-up was used as a grouping factor (favorable outcome: 0-1; unfavorable outcome: 2-5). We used multivariable logistic regression modeling to determine independent predictors of favorable outcome. The performance of the prediction model was evaluated using a receiver operating characteristic (ROC) analysis. RESULTS: A total of 96 patients had papilledema grades 0 to 1, and 25 patients had papilledema grades 2 to 5. Patients with the first group had significantly lower gradient pressures preoperatively (15.2 mmHg vs. 21.4 mmHg, p=0.001) and postoperatively (2 mmHg vs. 3.3 mmHg, p=0.002) relative to those in the second group. Multivariate analysis indicated that preoperative pressure gradient (odds ratio [OR] = 1.119; 95% confidence interval [CI] = 1.034-1.211]) and postoperative pressure gradient (OR = 1.498; 95% CI = 1.147-1.957) were independent predictors of favorable outcome. In the ROC analysis, the cut-off pressure gradient for the highest sensitivity (0.44) and specificity (0.874) was 22.75 mmHg, with a Youden's index of 0.314. Survival analysis demonstrated that patients with a preoperative pressure gradient <22.75 mmHg had more rapid improvement of papilledema than did those with a pressure gradient >22.75 mmHg (mean+SD: 2.639+0.382 [95% CI: 1.890-3.388] versus mean+SD: 3.882+0.884 [95% CI: 2.149-5.616]; p=0.004). CONCLUSION: A significant reduction in the pressure gradient appears to be strongly correlated with the success of VSS in patients with IIH. A higher preoperative pressure gradient may reduce stenting efficacy in patients with IIH. CLINICAL IMPACT: Venous sinus stenting has the potential to yield substantial clinical advantages in individuals diagnosed with idiopathic intracranial hypertension with venous sinus stenosis. Nevertheless, a heightened preoperative pressure gradient could lead to less favorable results. Thus, the early adoption of venous sinus stenting is advised to avert additional irreversible clinical deterioration among idiopathic intracranial hypertension patients with venous sinus stenosis.

Endovascular Treatment for Acute Large Vessel Occlusion Due to Underlying Intracranial Atherosclerotic Disease.

Intracranial atherosclerotic disease (ICAD) is one of the most common causes of acute ischemic stroke worldwide. Patients with acute large vessel occlusion due to underlying ICAD (ICAD-LVO) often do not achieve successful recanalization when undergoing mechanical thrombectomy (MT) alone, requiring rescue treatment, including intra-arterial thrombolysis, balloon angioplasty, and stenting. Therefore, early detection of ICAD-LVO before the procedure is important to enable physicians to select the optimal treatment strategy for ICAD-LVO to improve clinical outcomes. Early diagnosis of ICAD-LVO is challenging in the absence of consensus diagnostic criteria on noninvasive imaging and early digital subtraction angiography. In this review, we summarize the clinical and diagnostic criteria, prediction of ICAD-LVO prior to the procedure, and EVT strategy of ICAD-LVO and provide recommendations according to the current literature.

High-resolution magnetic resonance imaging-based radiomic features aid in selecting endovascular candidates among patients with cerebral venous sinus thrombosis.

OBJECTIVES: Cerebral venous sinus thrombosis (CVST) can cause sinus obstruction and stenosis, with potentially fatal consequences. High-resolution magnetic resonance imaging (HRMRI) can diagnose CVST qualitatively, although quantitative screening methods are lacking for patients refractory to anticoagulation therapy and who may benefit from endovascular treatment (EVT). Thus, in this study, we used radiomic features (RFs) extracted from HRMRI to build machine learning models to predict response to drug therapy and determine the appropriateness of EVT. MATERIALS AND METHODS: RFs were extracted from three-dimensional T1-weighted motion-sensitized driven equilibrium (MSDE), T2-weighted MSDE, T1-contrast, and T1-contrast MSDE sequences to build radiomic signatures and support vector machine (SVM) models for predicting the efficacy of standard drug therapy and the necessity of EVT. RESULTS: We retrospectively included 53 patients with CVST in a prospective cohort study, among whom 14 underwent EVT after standard drug therapy failed. Thirteen RFs were selected to construct the RF signature and CVST-SVM models. In the validation dataset, the sensitivity, specificity, and area under the curve performance for the RF signature model were 0.833, 0.937, and 0.977, respectively. The radiomic score was correlated with days from symptom onset, history of dyslipidemia, smoking, fibrin degradation product, and D-dimer levels. The sensitivity, specificity, and area under the curve for the CVST-SVM model in the validation set were 0.917, 0.969, and 0.992, respectively. CONCLUSIONS: The CVST-SVM model trained with RFs extracted from HRMRI outperformed the RF signature model and could aid physicians in predicting patient responses to drug treatment and identifying those who may require EVT.

Predictors of poor outcome after endovascular treatment for acute vertebrobasilar occlusion: data from ANGEL-ACT registry.

PURPOSE: Acute vertebrobasilar artery occlusion (VBAO) is a catastrophic disease for patients. There is evidence that the eventual patient outcome depends on patient-specific and procedural factors. This study aimed to identify the incidence and independent predictors of the 90-day poor outcome in VBAO after endovascular treatment (EVT). METHODS: Subjects were selected from the ANGEL-ACT registry. The 90-day poor outcome was defined as a 90-day modified Rankin Scale (mRS) of 4 to 6. Logistic regression analyses were performed to determine the independent predictors of the 90-day poor outcome. RESULTS: Of the 347 enrolled patients with acute VBAO undergoing EVT, 176 (50.7%) experienced the 90-day poor outcome. Multivariate logistic regression indicated that only the use of general anesthesia (GA) (odds ratio [OR] = 2.04; 95% confidence interval [CI], 1.23-3.37; P = 0.006) and heparin during the procedure (OR =1.74; 95% CI, 1.06-2.86; P = 0.028), admission National Institute of Health Stroke Scale (NIHSS) ≥ 26 (OR=3.96; 95% CI, 2.37-6.61; P < 0.001), and time from onset to puncture (OTP) ≥ 395 min (OR=1.91; 95% CI, 1.14-3.20; P = 0.014) and procedure duration ≥ 102 min (OR = 1.70; 95% CI, 1.04-2.79; P = 0.036) were independent predictors of the 90-day poor outcome after EVT. Furthermore, admission NIHSS (OR > 36 vs. ≤ 11 = 9.01, P for trend < 0.001), OTP (OR > 441min vs. ≤ 210 min = 2.71, P for trend = 0.023), and procedure duration (OR > 145 min vs. ≤ 59 min = 2.77, P for trend = 0.031) were significantly associated with increasing risk of the 90-day poor outcome. CONCLUSIONS: Poor outcome after EVT at 90 days occurred in 50.7% of acute VBAO patients from the ANGEL-ACT registry. Our study found several predictors of the 90-day poor outcome which should be highly considered in daily practice to improve acute VBAO management. CLINICAL TRIAL REGISTRATION : http://www. CLINICALTRIALS: gov . Unique identifier: NCT03370939.

Delayed neurological improvement after endovascular treatment for acute large vessel occlusion: data from ANGEL-ACT registry.

BACKGROUND: A subgroup of patients with acute large vessel occlusion (ALVO) may experience delayed neurological improvement (DNI) after endovascular treatment (EVT). Our study aimed to investigate the incidence and independent predictors of DNI in patients with ALVO after EVT. METHODS: We selected subjects from ANGEL-ACT Registry. The definition of DNI is patients with ALVO who did not experience early neurological improvement (ENI) despite complete recanalization after EVT. These patients achieved a 90-day favorable outcome assessed by a modified Rankin Scale (mRS) score. We defined ENI as a ≥ 4-point decrease in the National Institutes of Health Stroke Scale (NIHSS) between baseline and 24 h or NIHSS of 0 or 1 at 24 h, with complete recanalization after EVT. We performed logistic regression analyses to determine the independent predictors of DNI. RESULTS: Among the 1056 enrolled patients, 406 (38.4%) did not experience ENI. 106 (26.1%) patients without ENI achieved DNI. On Multivariate analysis, lower admission NIHSS score (odds ratio [OR] = 1.17,95% confidence interval [CI]: 1.11-1.23, P < 0.001), underlying ICAD (OR = 2.03, 95% CI: 1.07-3.85, P = 0.029) and absence of general anesthesia (OR = 2.13, 95% CI: 1.24-3.64, P = 0.006) were independent predictors of DNI. CONCLUSION: DNI occurred in 26.1% of patients with ALVO who did not experience ENI after EVT. Our study identified several independent predictors of DNI that should be highly considered in daily clinical practice to improve ALVO management.

Pial arteriovenous fistula resembling the vein of Galen aneurysmal malformation, treated with staged endovascular embolization: a case report.

A 41-month-old boy was presented to our hospital because of an intracranial mass suspected of cerebrovascular malformation. He was admitted and received cerebral angiography. The angiography result confirmed the intracranial mass was the dilated vein of Galen resulting from a pial arteriovenous fistula, which quite resembling the vein of Galen aneurysmal malformation. Considering one-time embolization of the fistula may greatly change the distribution of intracranial blood flow, we decided to perform staged embolization. In the first stage, we partially embolized the fistula, resulting in a sharp decrease in blood flow to the lesion. The second intervention was performed one month later, and completely embolized the fistula. The boy recoverd well and returned to normal childhood without any neurological deficits. Follow-up MR images obtained at 10 months after the last procedure showing total obliteration of the pAVF, gradually shrinking of the varix, and remodeling of the vein of Galen.

Association of Stroke Subtype With Hemorrhagic Transformation Mediated by Thrombectomy Pass: Data From the ANGEL-ACT Registry.

BACKGROUND: The role of stroke etiology subtype in patients with acute large vessel occlusion on the occurrence of hemorrhagic transformation (HT) after endovascular treatment is poorly studied, and which factors mediate their relationship remains largely unknown. We utilized nationwide registry data to explore the association of stroke subtype (cardioembolism versus large artery atherosclerosis) with HT and to identify the possible mediators. METHODS: A total of 1015 subjects were selected from the ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke)-a prospective consecutive cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals in China between November 2017 and March 2019-and divided into large artery atherosclerosis (n=538) and cardioembolism (n=477) according to the Trial of ORG 10172 in Acute Stroke Treatment criteria. The types of HT included any intracerebral hemorrhage (ICH), parenchymal hematoma, and symptomatic ICH within 24 hours after endovascular treatment. The association between stroke subtype and HT was analyzed using a logistic regression model. Mediation analysis was done to assess how much of the effect of stroke subtype on HT was mediated through the identified mediators. RESULTS: Stroke subtype (cardioembolism versus large artery atherosclerosis) was associated with increased risk of any ICH (29.8% versus 16.5%; odds ratio, 2.03 [95% CI, 1.22-3.36]), parenchymal hematoma (14.3% versus 5.4%; odds ratio, 2.90 [95% CI, 1.38-6.13]), and symptomatic ICH (9.9% versus 4.7%; odds ratio, 2.59 [95% CI, 1.09-6.16]) after adjustment for potential confounders. The more thrombectomy passes in cardioembolism patients had a significant mediation effect on the association of stroke subtype with increased risk of HT (any ICH, 15.9%; parenchymal hematoma, 13.4%; symptomatic ICH, 14.2%, respectively). CONCLUSIONS: Stroke subtype is an independent risk factor for HT within 24 hours following endovascular treatment among acute large vessel occlusion patients. Mediation analyses propose that stroke subtype contributes to HT partly through thrombectomy pass, suggesting a possible pathomechanistic link. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03370939.

Combined Approach to Eptifibatide and Thrombectomy in Acute Ischemic Stroke Because of Large Vessel Occlusion: A Matched-Control Analysis.

BACKGROUND: In patients undergoing mechanical thrombectomy (MT), adjunctive antithrombotic might improve angiographic reperfusion, reduce the risk of distal emboli and reocclusion but possibly expose patients to a higher intracranial hemorrhage risk. This study evaluated the safety and efficacy of combined MT plus eptifibatide for acute ischemic stroke. METHODS: This was a propensity-matched analysis of data from 2 prospective trials in Chinese populations: the ANGEL-ACT trial (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) in 111 hospitals between November 2017 and March 2019, and the EPOCH trial (Eptifibatide in Endovascular Treatment of Acute Ischemic Stroke) in 15 hospitals between April 2019 and March 2020. The primary efficacy outcome was good outcome (modified Rankin Scale score 0-2) at 3 months. Secondary efficacy outcomes included the distribution of 3-month modified Rankin Scale scores and poor outcome (modified Rankin Scale score 5-6) and successful recanalization. The safety outcomes included any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 3-month mortality. Mixed-effects logistic regression models were used to account for within-hospital clustering in adjusted analyses. RESULTS: Eighty-one combination arm EPOCH subjects were matched with 81 ANGEL-ACT noneptifibatide patients. Compared with the no eptifibatide group, the eptifibatide group had significantly higher rates of successful recanalization (91.3% versus 81.5%; P=0.043) and 3-month good outcomes (53.1% versus 33.3%; P=0.016). No significant difference was found in the remaining outcome measures between the 2 groups. All outcome measures of propensity score matching were consistent with mixed-effects logistic regression models in the total population. CONCLUSIONS: This matched-control study demonstrated that MT combined with eptifibatide did not raise major safety concerns and showed a trend of better efficacy outcomes compared with MT alone. Overall, eptifibatide shows potential as a periprocedural adjunctive antithrombotic therapy when combined with MT. Further randomized controlled trials of MT plus eptifibatide should be prioritized. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03844594 (EPOCH), NCT03370939 (ANGEL-ACT).

Effects of blood lipids and lipid-modifying drugs on intracranial aneurysms.

BACKGROUND AND PURPOSE: We used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-modifying drugs on intracranial aneurysm (IA). METHODS: Genetic variants for the effects of high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B, and triglycerides and targets for lipid-modifying drugs were selected from the genome-wide discovery analyses of the UK Biobank. Summary-level data on IAs were obtained from the International Stroke Genetics Consortium. Univariate and multivariate MR analyses were performed. RESULTS: Univariate MR analyses showed that the HDL-C was negatively correlated with IA (odds ratio [OR] = 0.816, 95% confidence interval [CI] = 0.715-0.932, p = 0.003) and ruptured IA (rIA; OR = 0.775, 95% CI = 0.663-0.906, p = 0.001). The multivariate MR-inverse variance weighted analysis showed that the HDL-C was negatively correlated with IA (OR = 0.655, 95% CI = 0.434-0.988, p = 0.043) and rIA (OR = 0.563, 95% CI = 0.347-0.913, p = 0.02), and the LDL-C was negatively correlated with IA (OR = 0.402, 95% CI = 0.191-0.848, p = 0.017) and rIA (OR = 0.376, 95% CI = 0.160-0.883, p = 0.025). Using genetic proxies of known lipid-modifying drugs, we found that the increased HDL-C with cholesterol ester transfer protein proxies was associated with a decreased risk of rIA (OR = 0.852, 95% CI = 0.747-0.973, p = 0.018), and the decreased LDL-C with 3-hydroxy-3-methylglutaryl-coenzyme A reductase proxies was associated with increased risk of IA (OR = 1.772, 95% CI = 1.080-2.908, p = 0.024) and rIA (OR = 1.856, 95% CI = 1.022-3.371, p = 0.042). CONCLUSIONS: Genetically determined HDL-C and LDL-C reduce the risk of IA and rIA. The effects of different lipid-modifying drugs on IA need to be further investigated.

A comparison between different endovascular treatment strategies for acute large vessel occlusion due to intracranial artery atherosclerosis: data from ANGEL-ACT Registry.

PURPOSE: The aim of our study is to compare the characteristics and clinical outcomes among the different endovascular treatment (EVT) strategies for large vessel occlusion underlying intracranial atherosclerosis (ICAS-LVO) in a recent nationwide registry. METHODS: Patients with isolated ICAS-LVO were enrolled in our analysis and were categorized into three groups: first-line mechanical thrombectomy (MT) with rescue angioplasty and/or stenting (MT + RS), direct angioplasty and/or stenting without thrombectomy (DA), and MT alone. Baseline and periprocedural characteristics, successful recanalization, and 90-day functional outcomes were compared. RESULTS: Of 396 patients with isolated ICAS-LVO in our study, successful recanalization was achieved in 94.5%, 100%, and 90.9% of patients in the MT + RS, DA, and MT groups, respectively. The 90-day functional independence in the three groups was 50.8%, 59.0%, and 45.1%. The main efficacy and safety outcomes showed no significant differences among the groups. First-pass recanalization (FPR) was more observed in the MT group (43.4%), the recanalization rate per attempt in the MT group gradually decreased until the fourth attempt, and further maneuvers showed recanalization rates of ≈0% per attempt. MT + RS (adjusted odds ratio [aOR] 0.10, p < 0.0001) and DA (aOR 0.18, p = 0.0013) were associated with lower FPR rate than MT alone in the multivariable logistic regression. CONCLUSIONS: The technical feasibility and favorable outcomes of several EVT strategies for ICAS-LVO were established in our study. First-line MT with a bailout angioplasty is a reasonable option for ICAS-LVO, and DA is an effective option for the cases when ICAS-LVO is strongly suspected before EVT procedure.

Effect of changes in serum uric acid on the risk of stroke and its subtypes.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in stroke remains controversial and analyses of changes in SUA and stroke are limited. The objective of the study was to investigate the associations of changes in SUA with stroke and its subtypes (ischemic and hemorrhagic stroke). METHODS AND RESULTS: A total of 51 441 participants (mean age 52.69 ± 11.71 years) without history of myocardial infarction or stroke were enrolled. Participants were divided into four groups based on SUA level changes during 2006 and 2010: stable low, increasing, decreasing, and stable high. SUA score was quantified on a 3-point scale with 1 point awarded for hyperuricemia at either year 2006, 2008 or 2010. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs). During 7.03-year follow up, 1611 stroke (1410 ischemic stroke, 199 hemorrhagic stroke, and 47 subarachnoid hemorrhage) were identified. Participants with stable high SUA had higher risk of hemorrhagic stroke, the HR was 1.93 (95% CI: 1.06-3.51), compared to those with stable low SUA. Furthermore, cumulative high SUA exposure also increased the risk of hemorrhagic stroke, the HR (95%CI) was 2.99 (1.55-5.74), compared with cumulative low SUA exposure. However, no significant evidence indicated changes in SUA was associated with the risk of total and ischemic stroke, the HRs (95% CIs) were 0.98 (0.74-1.29) and 0.88 (0.65-1.19), respectively. CONCLUSIONS: Stable high SUA was positively associated with the risk of hemorrhagic stroke, but not with total and ischemic stroke risk.

Predictors of symptomatic intracranial hemorrhage after endovascular treatment for acute large vessel occlusion: data from ANGEL-ACT registry.

Symptomatic intracranial hemorrhage (SICH) is a catastrophic complication of endovascular treatment (EVT) for large vessel occlusion (LVO). We aimed to investigate the incidence and predictors of SICH after EVT. Patients were selected from the ANGEL-ACT registry. We diagnosed SICH according to the Heidelberg Bleeding Classification. Logistic regression analyses were performed to determine the independent predictors of SICH. Of the 1283 patients, SICH was observed in 116 patients (9.0%). On multivariable analysis, admission National Institutes of Health Stroke Scale (NIHSS) > 12 (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.11-3.11, P = 0.018), admission Alberta Stroke Program Early CT Score (ASPECTS) < 6 (OR = 2.98, 95%CI: 1.68-5.29, P < 0.001), general anesthesia (OR = 1.81, 95%CI: 1.20-2.71, P = 0.004), prior intravenous thrombolysis (OR = 1.58, 95%CI: 1.04-2.40, P = 0.031), number of mechanical thrombectomy passes > 2 (OR = 1.68, 95%CI: 1.10-2.57, P = 0.016), and procedure duration > 96 min (OR = 1.82, 95%CI: 1.20-2.77, P = 0.005) were associated with high risk of SICH, whereas SICH was negatively associated with underlying intracranial atherosclerotic disease (OR = 0.45, 95%CI: 0.26-0.79, P = 0.021). The incidence of SICH after EVT for anterior LVO was 9.0% in ANGEL-ACT registry. Our study identified some predictors, which may assist doctors in identifying LVO patients with a high risk of SICH and making the optimal peri-procedural management strategies for such patients.

Evolution of the Flow Patterns After Endovascular Treatment in Patients with High-Grade Carotid Artery Stenosis - the Clinical Value of Insonation of the Supratrochlear Artery and Alternating Flow.

AIM: We aimed to describe the evolution of flow pattern in the ophthalmic artery (OA) and supratrochlear artery (SA) by transcranial Doppler (TCD) ipsilateral to a severe proximal carotid artery stenosis before and after staged endovascular treatment (EVT). METHODS: We insonated and recorded the flow patterns of OA and SA in 63 patients with ≥ 80% carotid artery stenosis before and after staged carotid angioplasty and stenting at 2-4 weeks apart. Based on the direction of OA and SA blood flow, we categorized patients into (1) reversed, (2) alternating, or (3) forward flow, groups. We evaluated the evolving sonographic flow patterns in OA and SA at the 3-time points and correlated them with the stenotic and flow velocity change. RESULTS: Despite the disconcordance between OA and SA, the evolution of flow direction were evoluted from reversed to alternating or from alternating to forward in both OA and SA. OA and SA's disagreement rate at three-time points was 19.1%, 49.2%, and 28.6%, respectively. After angioplasty alone, we detected an alternating flow in 21 (33.3%) and 46 (73.0%) patients in OA and SA, respectively. Alternating flow patterns in SA persisted in 20 patients (31.7%) after stenting. The post-angioplasty residual stenosis did not differ between the three flow pattern groups (p>0.05). CONCLUSIONS: An alternating flow in OA or SA might mark the hemodynamic recovery after EVT. Insonation of SA may provide supporting evidence for hemodynamic change in patients with carotid artery stenosis undergoing EVT.

Prediction of intracranial atherosclerotic acute large vessel occlusion by severe hypoperfusion volume growth rate.

BACKGROUND AND PURPOSE: We aimed to investigate whether the time elapsed from stroke onset to imaging (OTI) combined with the parameters generated by automated computed tomography perfusion (CTP) could predict large vessel occlusion (LVO) patients with underlying intracranial atherosclerotic disease (ICAD) before endovascular treatment (EVT). METHODS: We performed a prospective cohort of LVO patients with automated CTP before EVT from two comprehensive stroke centers. Severe hypoperfusion volume growth rate was defined as the Time-to-Maximum (Tmax) > 10s divided by OTI. We performed receiver operating characteristic analyses to assess the ICAD prediction performance of all the automated CTP parameters, Delong test to compare the area under the curve (AUC) of severe hypoperfusion volume growth rate with the AUC of the other parameters, and logistic regression analysis to find the independent predictors of LVO with underlying ICAD. RESULTS: Of the 204 enrolled LVO patients, 95 ICAD patients and 109 non-ICAD patients were identified. The AUC of severe hypoperfusion volume growth rate was 0.86 (95% confidence interval [CI] 0.81 - 0.91, P < 0.001), the cut-off value with the highest Youden Index was ≤ 11.2 mL/h (sensitivity, 78.95%; specificity, 77.06%; accuracy 77.94%), which was larger than the other parameters except for hypoperfusion intensity ratio (HIR) (All P for Delong test < 0.05). Atrial fibrillation (odds ratio [OR]: 0.09, 95%CI: 0.03 - 0.26, P < 0.001), admission ASPECTS (1-point increased OR: 1.25, 95%CI: 1.03 - 1.53, P = 0.024), and severe hypoperfusion volume growth rate (1 mL/h increased OR: 0.94, 95%CI: 0.90 - 0.98, P = 0.003) were associated with underlying ICAD independently. CONCLUSIONS: Severe hypoperfusion volume growth rate showed the best performance for LVO with underlying ICAD prediction. Future larger studies for external validation are needed.