Association between CT Perfusion Parameters and Hemorrhagic Transformation after Endovascular Treatment in Acute Ischemic Stroke: Results from the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Hemorrhagic transformation can occur as a complication of endovascular treatment for acute ischemic stroke. This study aimed to determine whether ischemia depth as measured by admission CTP metrics can predict the development of hemorrhagic transformation at 24 hours. MATERIALS AND METHODS: Patients with baseline CTP and 24-hour follow-up imaging from the ESCAPE-NA1 trial were included. RAPID software was used to generate CTP volume maps for relative CBF, CBV, and time-to-maximum at different thresholds. Hemorrhage on 24-hour imaging was classified according to the Heidelberg system, and volumes were calculated. Univariable and multivariable regression analyses assessed the association between CTP lesion volumes and hemorrhage/hemorrhage subtypes. RESULTS: Among 408 patients with baseline CTP, 142 (35%) had hemorrhagic transformation at 24-hour follow-up, with 89 (63%) classified as hemorrhagic infarction (HI1/HI2), and 53 (37%), as parenchymal hematoma (PH1/PH2). Patients with HI or PH had larger volumes of low relative CBF and CBV at each threshold compared with those without hemorrhage. After we adjustied for baseline and treatment variables, only increased relative CBF <30% lesion volume was associated with any hemorrhage (adjusted OR, 1.14; 95% CI, 1.02-1.27 per 10 mL), as well as parenchymal hematoma (adjusted OR, 1.23; 95% CI, 1.06-1.43 per 10 mL). No significant associations were observed for hemorrhagic infarction. CONCLUSIONS: Larger "core" volumes of relative CBF <30% were associated with an increased risk of PH following endovascular treatment. This particular metric, in conjunction with other clinical and imaging variables, may, therefore, help estimate the risk of post-endovascular treatment hemorrhagic complications.

Influence of Infarct Morphology and Patterns on Cognitive Outcomes After Endovascular Thrombectomy.

BACKGROUND: To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook Neglect Assessment Procedure for neglect, in large vessel occlusion stroke. METHODS: Secondary observational cohort study using data from the randomized-controlled ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke), in which patients with large vessel occlusion undergoing endovascular treatment were randomized to receive either intravenous Nerinetide or placebo. MOCA, Sunnybrook Neglect Assessment Procedure, and 15-item Boston Naming Test were obtained at 90 days. Total infarct volume, gray matter, and white matter infarct volumes were manually measured on 24-hour follow-up imaging. Infarcts were also visually classified as either involving the gray matter only or both the gray and white matter and scattered versus territorial. Associations of infarct variables and cognitive outcomes were analyzed using multivariable ordinal or binary logistic regression models. RESULTS: Of 1105 patients enrolled in ESCAPE-NA1, 1026 patients with visible infarcts on 24-hour follow-up imaging were included. MOCA and Sunnybrook Neglect Assessment Procedure were available for 706 (68.8%) patients and the 15-item Boston Naming Test was available for 682 (66.5%) patients. Total infarct volume was associated with worse MOCA scores (adjusted common odds ratio per 10 mL increase, 1.05 [95% CI, 1.04-1.06]). After adjusting for baseline variables and total infarct volume, mixed gray and white matter involvement (versus gray matter-only adjusted common odds ratio, 1.92 [95% CI, 1.37-2.69]), white matter infarct volume (adjusted common odds ratio per 10 mL increase 1.36 [95% CI, 1.18-1.58]) and territorial (versus scattered) infarct pattern (adjusted common odds ratio, 1.65 [95% CI, 1.15-2.38]) were associated with worse MOCA scores. Results for Sunnybrook Neglect Assessment Procedure and 15-item Boston Naming Test were similar, except for the territorial infarct pattern, which did not reach statistical significance in multivariable analysis. CONCLUSIONS: Besides total infarct volume, infarcts that involve the white matter and that show a territorial distribution were associated with worse cognitive outcomes, even after adjusting for total infarct volume.

Portable cerebral blood flow monitor to detect large vessel occlusion in patients with suspected stroke.

BACKGROUND: Early detection of large vessel occlusion (LVO) facilitates triage to an appropriate stroke center to reduce treatment times and improve outcomes. Prehospital stroke scales are not sufficiently sensitive, so we investigated the ability of the portable Openwater optical blood flow monitor to detect LVO. METHODS: Patients were prospectively enrolled at two comprehensive stroke centers during stroke alert evaluation within 24 hours of onset with National Institutes of Health Stroke Scale (NIHSS) score ≥2. A 70 s bedside optical blood flow scan generated cerebral blood flow waveforms based on relative changes in speckle contrast. Anterior circulation LVO was determined by CT angiography. A deep learning model trained on all patient data using fivefold cross-validation and learned discriminative representations from the raw speckle contrast waveform data. Receiver operating characteristic (ROC) analysis compared the Openwater diagnostic performance (ie, LVO detection) with prehospital stroke scales. RESULTS: Among 135 patients, 52 (39%) had an anterior circulation LVO. The median NIHSS score was 8 (IQR 4-14). The Openwater instrument had 79% sensitivity and 84% specificity for the detection of LVO. The rapid arterial occlusion evaluation (RACE) scale had 60% sensitivity and 81% specificity and the Los Angeles motor scale (LAMS) had 50% sensitivity and 81% specificity. The binary Openwater classification (high-likelihood vs low-likelihood) had an area under the ROC (AUROC) of 0.82 (95% CI 0.75 to 0.88), which outperformed RACE (AUC 0.70; 95% CI 0.62 to 0.78; P=0.04) and LAMS (AUC 0.65; 95% CI 0.57 to 0.73; P=0.002). CONCLUSIONS: The Openwater optical blood flow monitor outperformed prehospital stroke scales for the detection of LVO in patients undergoing acute stroke evaluation in the emergency department. These encouraging findings need to be validated in an independent test set and the prehospital environment.

Cost-Effectiveness of Late Endovascular Thrombectomy vs. Best Medical Management in a Clinical Trial Setting and Real-World Setting.

BACKGROUND AND PURPOSE: To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a "real-world" setting. METHODS: Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a "real-world" setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY. RESULTS: Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%-99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%-61.6%), but not the "real-world" setting (acceptability:32.9%-42.6%). CONCLUSION: EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and "real-world" setting, although this was largely related to baseline patient differences favoring the "real-world" EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.

Technique and impact on first pass effect primary results of the ASSIST global registry.

BACKGROUND: Patients treated with mechanical thrombectomy (MT) for acute ischemic strokes from large vessel occlusion (LVO) have better outcomes with effective reperfusion. However, it is unknown which technique leads to better technical and clinical success. We aimed to determine which technique yields the most effective first pass reperfusion during MT. METHODS: In a prospective, multicenter global registry we enrolled patients treated with operator preferred MT technique at 71 hospitals from January 2019 to January 2022. Three techniques were assessed: SR Classic with stent retriever (SR) and balloon guide catheter (BGC); SR Combination which employed SR with contact aspiration with or without BGC; and direct aspiration (DA) with or without BGC. The primary outcome was achieving an expanded Thrombolysis In Cerebral Infarction (eTICI) score of 2c or 3 on the first pass, with the primary technique as adjudicated by core lab. The primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. RESULTS: A total of 1492 patients were enrolled. Patients treated with SR Classic or SR Combination were more likely to achieve first pass eTICI 2c or 3 reperfusion (P=0.01). There was no significant difference in mRS 0-2 (P=0.46) or safety endpoints. CONCLUSIONS: The use of SR Classic or SR Combination was more likely to achieve first pass eTICI 2c or 3 reperfusion. There were no significant differences in clinical outcomes and safety endpoints.

Infarct Evolution on MR-DWI After Thrombectomy in Acute Stroke Patients Randomized to Nerinetide or Placebo: The REPERFUSE-NA1 Study

BACKGROUND AND OBJECTIVES: The neuroprotectant nerinetide has shown promise in reducing infarct volumes in primate models of ischemia reperfusion. We hypothesized that early secondary infarct growth after endovascular therapy (EVT) (1) may be a suitable surrogate biomarker for testing neuroprotective compounds, (2) is feasible to assess in the acute setting using sequential MRI, and (3) can be modified by treatment with nerinetide. METHODS: REPERFUSE-NA1 was a prospective, multisite MRI substudy of the randomized controlled trial ESCAPE-NA1 (ClinicalTrials.gov NCT02930018) that involved patients with acute disabling large vessel occlusive stroke undergoing EVT within 12 hours of onset who were randomized to receive intravenous nerinetide or placebo. Patients enrolled in REPERFUSE-NA1 underwent sequential MRI <5 hours post-EVT (day 1) and at 24 hours (day 2). The primary outcome was total diffusion-weighted MRI infarct growth early after EVT, defined as the lesion volume difference between day 2 and day 1. The secondary outcome was region-specific infarct growth in different brain tissue compartments. Statistical analyses were performed using the Mann-Whitney U test and multiple linear regression. RESULTS: Sixty-seven of 71 patients included had MRI of sufficient quality. The median infarct volume post-EVT was 12.98 mL (IQR, 5.93-28.08) in the nerinetide group and 10.80 mL (IQR, 3.11-24.45) in the control group (p = 0.59). Patients receiving nerinetide showed a median early secondary infarct growth of 5.92 mL (IQR, 1.09-21.30) compared with 10.80 mL (interquartile range [IQR], 2.54-21.81) in patients with placebo (p = 0.30). Intravenous alteplase modified the effect of nerinetide on region-specific infarct growth in white matter and basal ganglia compartments. In patients with no alteplase, the infarct growth rate was reduced by 120% (standard error [SE], 60%) in the white matter (p = 0.03) and by 340% (SE, 140%) in the basal ganglia (p = 0.02) in the nerinetide group compared with placebo after adjusting for confounders. DISCUSSION: This study highlights the potential of using MR imaging as a biomarker to estimate the effect of a neuroprotective agent in acute stroke treatment. Patients with acute large vessel occlusive stroke exhibited appreciable early infarct growth both in the gray matter and the white matter after undergoing EVT. Acknowledging relatively small overall infarct volumes in this study, treatment with nerinetide was associated with slightly reduced percentage infarct growth in the white matter and basal ganglia compared with placebo in patients not receiving intravenous alteplase and had no effect on the total early secondary infarct growth. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT02930018. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute large vessel ischemic stroke undergoing EVT, nerinetide did not significantly decrease early post-EVT infarct growth compared with placebo.

Modeling diffusion-weighted imaging lesion expansion between 2 and 24 h after endovascular thrombectomy in acute ischemic stroke.

PURPOSE: Diffusion-weighted imaging (DWI) lesion expansion after endovascular thrombectomy (EVT) is not well characterized. We used serial diffusion-weighted magnetic resonance imaging (MRI) to measure lesion expansion between 2 and 24 h after EVT. METHODS: In this single-center observational analysis of patients with acute ischemic stroke due to large vessel occlusion, DWI was performed post-EVT (< 2 h after closure) and 24-h later. DWI lesion expansion was evaluated using multivariate generalized linear mixed modeling with various clinical moderators. RESULTS: We included 151 patients, of which 133 (88%) had DWI lesion expansion, defined as a positive change in lesion volume between 2 and 24 h. In an unadjusted analysis, median baseline DWI lesion volume immediately post-EVT was 15.0 mL (IQR: 6.6-36.8) and median DWI lesion volume 24 h post-EVT was 20.8 mL (IQR: 9.4-66.6), representing a median change of 6.1 mL (IQR: 1.5-17.7), or a 39% increase. There were no significant associations among univariable models of lesion expansion. Adjusted models of DWI lesion expansion demonstrated that relative lesion expansion (defined as final/initial DWI lesion volume) was consistent across eTICI scores (0-2a, 0.52%; 2b, 0.49%; 2c-3, 0.42%, p = 0.69). For every 1 mL increase in lesion volume, there was 2% odds of an increase in 90-day mRS (OR: 1.021, 95%CI [1.009, 1.034], p < 0.001). CONCLUSION: We observed substantial lesion expansion post-EVT whereby relative lesion expansion was consistent across eTICI categories, and greater absolute lesion expansion was associated with worse clinical outcome. Our findings suggest that alternate endpoints for cerebroprotectant trials may be feasible.

Symptomatic Non-stenotic Carotid Disease in Embolic Stroke of Undetermined Source : Analysis of the ESCAPE-NA1 Trial.

PURPOSE: Non-stenotic (< 50%) carotid disease may play an important etiological role in ischemic stroke classified as embolic stroke of undetermined source (ESUS). We aimed to assess the prevalence of non-stenotic carotid disease and its association with ipsilateral ischemic stroke. METHODS: Data are from ESCAPE-NA1, a randomized controlled trial investigating the neuroprotectant nerinetide in patients with acute ischemic stroke and large vessel occlusion (LVO). The degree of stenosis of the extracranial internal carotid artery (ICA) and high-risk plaque features were assessed on baseline computed tomography (CT) angiography. We evaluated the association of non-stenotic carotid disease and ipsilateral stroke by age-adjusted and sex-adjusted logistic regression and calculated the attributable risk of ipsilateral stroke caused by non-stenotic carotid disease. RESULTS: After excluding patients with non-assessable imaging, symptomatic > 50% carotid stenosis and extracranial dissection, 799/1105 (72.1%) patients enrolled in ESCAPE-NA1 remained for this analysis. Of these, 127 (15.9%) were classified as ESUS. Non-stenotic carotid disease occurred in 34/127 ESUS patients (26.8%) and was associated with the presence of ipsilateral ischemic stroke (odds ratio, OR 1.6, 95% confidence interval, CI 1.0-2.6, p = 0.049). The risk of ipsilateral ischemic stroke attributable to non-stenotic carotid disease in ESUS was estimated to be 19.7% (95% CI -5.7% to 39%), the population attributable risk was calculated as 4.3%. Imaging features such as plaque thickness, plaque irregularity or plaque ulceration were not different between non-stenotic carotids with vs. without ipsilateral stroke. CONCLUSION: Non-stenotic carotid disease frequently occurs in patients classified as ESUS and is associated with ipsilateral ischemic stroke. Our findings support the role of non-stenotic carotid disease as stroke etiology in ESUS, but further prospective research is needed to prove a causal relationship.

Predicting outcome in acute stroke with large vessel occlusion-application and validation of MR PREDICTS in the ESCAPE-NA1 population.

BACKGROUND: Predicting outcome after endovascular treatment for acute ischemic stroke is challenging. We aim to investigate differences between predicted and observed outcomes in patients with acute ischemic stroke treated with endovascular treatment and to evaluate the performance of a validated outcome prediction score. PATIENTS AND METHODS: MR PREDICTS is an outcome prediction tool based on a logistic regression model designed to predict the treatment benefit of endovascular treatment based on the MR CLEAN and HERMES populations. ESCAPE-NA1 is a randomized trial of nerinetide vs. placebo in patients with acute stroke and large vessel occlusion. We applied MR PREDICTS to patients in the control arm of ESCAPE-NA1. Model performance was assessed by calculating its discriminative ability and calibration. RESULTS: Overall, 556/1105 patients (50.3%) in the ESCAPE-NA1-trial were randomized to the control arm, 435/556 (78.2%) were treated within 6 h of symptom onset. Good outcome (modified Rankin scale 0-2) at 3 months was achieved in 275/435 patients (63.2%), the predicted probability of good outcome was 52.5%. Baseline characteristics were similar in the study and model derivation cohort except for age (ESCAPE-NA1: mean: 70 y vs. HERMES: 66 y), hypertension (72% vs. 57%), and collaterals (good collaterals, 15% vs. 44%). Compared to HERMES we observed higher rates of successful reperfusion (TICI 2b-3, ESCAPE-NA1: 87% vs. HERMES: 71%) and faster times from symptom onset to reperfusion (median: 201 min vs. 286 min). Model performance was good, indicated by a c-statistic of 0.76 (95%confidence interval: 0.71-0.81). CONCLUSION: Outcome-prediction using models created from HERMES data, based on information available in the emergency department underestimated the actual outcome in patients with acute ischemic stroke and large vessel occlusion receiving endovascular treatment despite overall good model performance, which might be explained by differences in quality of and time to reperfusion. These findings underline the importance of timely and successful reperfusion for functional outcomes in acute stroke patients.

Infarcts in a New Territory: Insights From the ESCAPE-NA1 Trial.

BACKGROUND: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide. METHODS: Data are from ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in subjects with acute ischemic stroke who underwent endovascular thrombectomy within 12 hours from onset. Concurrent treatment and outcomes were collected as part of the trial protocol. INTs were identified on core lab imaging review of follow-up brain imaging and defined by the presence of infarct in a new vascular territory, outside the baseline target occlusion(s) on follow-up brain imaging (computed tomography or magnetic resonance imaging). INTs were classified by maximum diameter (<2, 2-20, and >20 mm), number, and location. The association between INT and clinical outcomes (modified Rankin Scale and death) was assessed using standard descriptive techniques and adjusted estimates of effect were derived from Poisson regression models. RESULTS: Among 1092 patients, 103 had INT (9.3%, median age 69.5 years, 49.5% females). There were no differences in baseline characteristics between those with versus without INT. Most INTs (91/103, 88.3%) were not associated with visible occlusions on angiography and 39 out of 103 (37.8%) were >20 mm in maximal diameter. The most common INT territory was the anterior cerebral artery (27.8%). Almost half of the INTs were multiple (46 subjects, 43.5%, range, 2-12). INT was associated with poorer outcomes as compared to no INT on the primary outcome of modified Rankin Scale score of 0 to 2 at 90 days (adjusted risk ratio, 0.71 [95% CI, 0.57-0.89]). Infarct volume in those with INT was greater by a median of 21 cc compared with those without, and there was a greater risk of death as compared to patients with no INT (adjusted risk ratio, 2.15 [95% CI, 1.48-3.13]). CONCLUSIONS: Infarcts in a new territory are common in individuals undergoing endovascular thrombectomy for acute ischemic stroke and are associated with poorer outcomes. Optimal therapeutic approaches, including technical strategies, to reduce INT represent a new target for incremental quality improvement of endovascular thrombectomy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02930018.

Long-term effect of field triage on times to endovascular treatment for emergent large vessel occlusion.

BACKGROUND: Delays to endovascular therapy (EVT) for stroke may be mitigated with direct field triage to EVT centers. We sought to compare times to treatment over a 5.5 year span between two adjacent states, one with field triage and one without, served by a single comprehensive stroke center (CSC). METHODS: During the study period, one of the two states implemented severity-based triage for suspected emergent large vessel occlusion, while in the other state, patients were transported to the closest hospital regardless of severity. We compared times to treatment and clinical outcomes between these two states. We also performed a matched pairs analysis, matching on date treated and distance from field to CSC. RESULTS: 639 patients met the inclusion criteria, 407 in State 1 (with field triage) and 232 in State 2 (without field triage). In State 1, scene to EVT decreased 6% (or 8.13 min, p=0.0004) every year but no decrease was observed for State 2 (<1%, p=0.94). Cumulatively over 5.5 years, there was a reduction of 43 min in time to EVT in State 1, but no change in State 2. Lower rates of disability were seen in State 1, both for the entire cohort (all OR 1.22, 95% CI 1.07 to 1.40, p=0.0032) and for those independent at baseline (1.36, 95% CI 1.15 to 1.59, p=0.0003). CONCLUSIONS: Comparing adjacent states over time, the implementation of severity-based field triage significantly reduced time to EVT.

Discordance in tests used to detect inhibition of the P2Y12 receptor in patients undergoing interventional neuroradiology procedures.

BACKGROUND: Clopidogrel is an inhibitor of the P2Y12 platelet receptor but testing to demonstrate a drug effect is controversial since there are often discordant results between different tests methods. METHODS: Samples from patients taking clopidogrel prior to intracranial flow-diversion procedures were tested using light transmission aggregometry (LTA), whole blood impedance aggregometry (WBIA) and the VerifyNow device (VND). Samples were classified as concordant if all test results were either responsive (inhibition) or resistant. Discordant results were separated using the VND into those with a responsive versus a resistant test result. RESULTS: Samples from 96 patients were studied. Concordance for all three tests was seen in 53/96 (55%) of samples, of which 41 (43%) were responsive and 12 (12%) were resistant. Discordance was observed in 43 samples (45%), 37 (28%) of which were caused by responsive VND and either a resistant WBIA or LTA and 6 (7%) of which were caused by a resistant VND but a responsive test result using either WBIA or LTA. These two discordant groups differed in both platelet count and hematocrit, but no such difference was present between the two concordant groups. CONCLUSION: Discordance in P2Y12 inhibition testing may be partly explained by sample platelet count and hematocrit.

Dual antiplatelet use in the management of COVID-19 associated acute ischemic stroke reocclusion.

INTRO: SARS-CoV-2 (COVID-19) infection is associated with acute ischemic stroke (AIS), which may be due to a prothrombotic state. Early reports have suggested high rates of reocclusion following mechanical thrombectomy (MT) with poor radiographic and clinical outcomes. We report our early experience using intra-procedural antithrombotics to address SARS-CoV-2 reocclusion. METHODS: We identified 6 patients that experienced early reocclusion after MT for COVID-19-associated AIS through retrospective chart review abstracting their basic demographics, COVID-19 status, and stroke management. All these patients were treated after reocclusion with aspirin and cangrelor intra-procedurally, the latter of which was converted to ticagrelor post-procedurally. Some patients additionally received argatroban infusion intraprocedurally. RESULTS: Mean age was 54. There were 3 post-procedural and 3 intra-procedural re-occlusions. After repeat thrombectomy and treatment with aspirin and cangrelor, those with post-procedure reocclusion did not show further reocclusion, while those with intra-procedural reocclusion showed radiographic improvement with intraprocedural cangrelor administration. Outcomes for these patients were poor, with a median mRS of 4. Two patients developed petechial hemorrhage of their stroke which was managed conservatively, and one developed a retroperitoneal hemorrhage from femoral access requiring transfusion. There were no patients who developed new parenchymal hematomas. CONCLUSION: COVID-19 AIS may be associated with a hypercoagulable state which risks malignant reocclusion complicating MT. We found antithrombotic treatment periprocedural cangrelor with or without argatroban transitioned to oral aspirin with ticagrelor to be a viable method for management of these patients.

Safety of Sheathless Transradial Balloon Guide Catheter Placement for Acute Stroke Thrombectomy.

BACKGROUND: Transradial access has been described for mechanical thrombectomy in acute stroke, and proximal balloon occlusion has been shown to improve recanalization and outcomes. However, sheathed access requires a larger total catheter diameter at the access site. We aimed to characterize the safety of sheathless transradial balloon guide catheter use in acute stroke intervention. METHODS: Consecutive patients who underwent sheathless right-sided transradial access for thrombectomy with a balloon guide catheter were identified in a prospectively collected dataset from 2019 to 2021. Demographics, procedure details, and short-term outcomes were collected and reported with descriptive statistics. RESULTS: A total of 48 patients (20 women) with a mean age of 72.3 years were identified. Of patients, 56.3% had occlusions in the left-sided circulation; 35 (72.9%) had M1 occlusions, 7 (14.6%) had M2 occlusions, and 6 (12.5%) had internal carotid artery occlusions. Tissue plasminogen activator was administered to 16 (33.3%) patients. Five (10.4%) patients underwent intraprocedural carotid stenting. The cohort had successful reperfusion after a median of 1 (interquartile range: 1, 2) pass. Median time from access to recanalization was 31 (interquartile range: 25, 53) minutes. A postprocedural Thrombolysis In Cerebral Infarction score of ≥2b was achieved in 46 (95.8%) patients. Five patients had wrist access site hematomas. All hematomas resolved with warm compresses, and no further intervention was required. CONCLUSIONS: Sheathless radial access using a balloon guide catheter may be safely performed for acute ischemic stroke with excellent radiographic outcomes. Further investigation is warranted to evaluate the comparative effectiveness of sheathless compared with sheathed transradial balloon guide access.

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study.

BACKGROUND: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. METHODS: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. RESULTS: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7]). CONCLUSIONS: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Association of Stent-Retriever Characteristics in Establishing Successful Reperfusion During Mechanical Thrombectomy : Results from the ESCAPE-NA1 Trial.

BACKGROUND: Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial. METHODS: Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built. RESULTS: Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46). CONCLUSION: The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion.

Predictors and clinical impact of infarct progression rate in the ESCAPE-NA1 trial.

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 (ß: -0.81 (95% CI -1.20 to -0.41)), Alberta Stroke Program Early CT Score (ASPECTS, ß: -0.34 (95% CI -0.46 to -0.23)), blood glucose(ß: 0.09 (95% CI 0.02 to 0.16)), and National Institutes of Health Stroke Scale (NIHS score (ß: 0.07 (95% CI 0.04 to 0.10)) were associated with log-transformed 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 near-complete 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.

Management and outcome of patients with acute ischemic stroke and tandem carotid occlusion in the ESCAPE-NA1 trial.

BACKGROUND: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial. METHODS: ESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling. RESULTS: Among 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0-2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0-2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1). CONCLUSIONS: Tandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

Assessment of Discrepancies Between Follow-up Infarct Volume and 90-Day Outcomes Among Patients With Ischemic Stroke Who Received Endovascular Therapy.

Importance: Some patients have poor outcomes despite small infarcts after endovascular therapy (EVT), while others with large infarcts do well. Understanding why these discrepancies occur may help to optimize EVT outcomes. Objective: To validate exploratory findings from the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial regarding pretreatment, treatment-related, and posttreatment factors associated with discrepancies between follow-up infarct volume (FIV) and 90-day functional outcome. Design, Setting, and Participants: This cohort study is a post hoc analysis of the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, a double-blind, randomized, placebo-controlled, international, multicenter trial conducted from March 2017 to August 2019. Patients who participated in ESCAPE-NA1 and had available 90-day modified Rankin Scale (mRS) scores and 24-hour to 48-hour posttreatment follow-up parenchymal imaging were included. Exposures: Small FIV (volume ≤25th percentile) and large FIV (volume ≥75th percentile) on 24-hour computed tomography/magnetic resonance imaging. Baseline factors, outcomes, treatments, and poststroke serious adverse events (SAEs) were compared between discrepant cases (ie, patients with 90-day mRS score ≥3 despite small FIV or those with mRS scores ≤2 despite large FIV) and nondiscrepant cases. Main Outcomes and Measures: Area under the curve (AUC) and goodness of fit of prespecified logistic models, including pretreatment (eg, age, cancer, vascular risk factors) and treatment-related and posttreatment (eg, SAEs) factors, were compared with stepwise regression-derived models for ability to identify small FIV with higher mRS score and large FIV with lower mRS score. Results: Among 1091 patients (median [IQR] age, 70.8 [60.8-79.8] years; 549 [49.7%] women; median [IQR] FIV, 24.9 mL [6.6-92.2 mL]), 42 of 287 patients (14.6%) with FIV of 7 mL or less (ie, ≤25th percentile) had an mRS score of at least 3; 65 of 275 patients (23.6%) with FIV of 92 mL or greater (ie, ≥75th percentile) had an mRS score of 2 or less. Prespecified models of pretreatment factors (ie, age, cancer, vascular risk factors) associated with low FIV and higher mRS score performed similarly to models selected by stepwise regression (AUC, 0.92 [95% CI, 0.89-0.95] vs 0.93 [95% CI, 0.90-0.95]; P = .42). SAEs, specifically infarct in new territory, recurrent stroke, pneumonia, and congestive heart failure, were associated with low FIV and higher mRS scores; stepwise models also identified 24-hour hemoglobin as treatment-related/posttreatment factor (AUC, 0.92 [95% CI, 0.90-0.95] vs 0.94 [95% CI, 0.91-0.96]; P = .14). Younger age was associated with high FIV and lower mRS score; stepwise models identified absence of diabetes and higher baseline hemoglobin as additional pretreatment factors (AUC, 0.76 [95% CI, 0.70-0.82] vs 0.77 [95% CI, 0.71-0.83]; P = .82). Absence of SAEs, especially stroke progression, symptomatic intracerebral hemorrhage, and pneumonia, was associated with high FIV and lower mRS score2; stepwise models also identified 24-hour hemoglobin level, glucose, and diastolic blood pressure as posttreatment factors associated with discrepant cases (AUC, 0.80 [95% CI, 0.74-0.87] vs 0.79 [95% CI, 0.72-0.86]; P = .92). Conclusions and Relevance: In this study, discrepancies between functional outcome and post-EVT infarct volume were associated with differences in pretreatment factors, such as age and comorbidities, and posttreatment complications related to index stroke evolution, secondary prevention, and quality of stroke unit care. Besides preventing such complications, optimization of blood pressure, glucose levels, and hemoglobin levels are potentially modifiable factors meriting further study.