Large Vessel Occlusion Stroke Research Articles

Safety of Mechanical Thrombectomy for Acute Ischemic Stroke in Patients with Thrombocytopenia.

The impact of low platelet count on outcomes in patients with Acute Ischemic Stroke (AIS) undergoing Mechanical Thrombectomy (MT) is still unclear. In this study we have further explored the effect of thrombocytopenia on the safety and efficacy of MT in patients with anterior circulation Large Vessel Occlusion (LVO) stroke. Patients with AIS who underwent MT at our center between June 2015 and November 2021 were examined. Based on the platelet count recorded on admission patients were divided into two groups: those with thrombocytopenia (<150 × 109/L) and those without thrombocytopenia (≥ 150 × 109/L). Symptomatic Intracranial Hemorrhage (sICH) was the primary safety outcome. The efficacy outcome was functional independence defined as a 90-day modified Rankin Scale (mRS) score of 0-2. Multivariate logistic regression models were used to determine the risk factors for post-procedure sICH and 90-day functional outcomes. Among 302 patients included in the study, thrombocytopenia was detected in 111 (36.8%) cases. Univariate analysis showed age, the proportion of atrial fibrillation, the rates of sICH, 90-day poor outcomes, and mortality to be higher in patients with thrombocytopenia (all p &#60; 0.05). Multivariable analysis showed thrombocytopenia to be independently associated with a higher rate of sICH (OR 2.022, 95% CI 1.074-3.807, p =0.029) however, thrombocytopenia did not affect the 90-day functional outcomes (OR 1.045, 95%CI 0.490-2.230, p =0.909) and mortality (OR 1.389, 95% CI 0.467- 4.130 p = 0.554). Thrombocytopenia may increase the risk of sICH but not affect the 90-day functional outcomes and mortality in patients with AIS treated with MT.</p>.

Parallel activation of helicopter and ground transportation after dispatcher identification of suspected anterior large vessel occlusion stroke in rural areas: a proof-of-concept case with modeling from the LESTOR trial

BackgroundWhen stroke patients with suspected anterior large vessel occlusion (aLVO) happen to live in rural areas, two main options exist for prehospital transport: (i) the drip-and-ship (DnS) strategy, which ensures rapid access to intravenous thrombolysis (IVT) at the nearest primary stroke center but requires time-consuming interhospital transfer for endovascular thrombectomy (EVT) because the latter is only available at comprehensive stroke centers (CSC); and (ii) the mothership (MS) strategy, which entails direct transport to a CSC and allows for faster access to EVT but carries the risk of IVT being delayed or even the time window being missed completely. The use of a helicopter might shorten the transport time to the CSC in rural areas. However, if the aLVO stroke is only recognized by the emergency service on site, the helicopter must be requested in addition, which extends the prehospital time and partially negates the time advantage. We hypothesized that parallel activation of ground and helicopter transportation in case of aLVO suspicion by the dispatcher (aLVO-guided dispatch strategy) could shorten the prehospital time in rural areas and enable faster treatment with IVT and EVT.MethodsAs a proof-of-concept, we report a case from the LESTOR trial where the dispatcher suspected an aLVO stroke during the emergency call and dispatched EMS and HEMS in parallel. Based on this case, we compare the provided aLVO-guided dispatch strategy to the DnS and MS strategies regarding the times to IVT and EVT using a highly realistic modeling approach.ResultsWith the aLVO-guided dispatch strategy, the patient received IVT and EVT faster than with the DnS or MS strategies. IVT was administered 6 min faster than in the DnS strategy and 22 min faster than in the MS strategy, and EVT was started 47 min earlier than in the DnS strategy and 22 min earlier than in the MS strategy.ConclusionIn rural areas, parallel activation of ground and helicopter emergency services following dispatcher identification of stroke patients with suspected aLVO could provide rapid access to both IVT and EVT, thereby overcoming the limitations of the DnS and MS strategies.

Tenecteplase versus alteplase before stroke thrombectomy: outcomes after system-wide transitions in Pennsylvania.

United States stroke systems are increasingly transitioning from alteplase (TPA) to tenecteplase (TNK). Real-world data on the safety and effectiveness of replacing TPA with TNK before large vessel occlusion (LVO) stroke endovascular treatment (EVT) are lacking. Four Pennsylvania stroke systems transitioned from TPA to TNK during the study period 01/2020-06/2023. LVO stroke patients who received intravenous thrombolysis with TPA or TNK before EVT were reviewed. Multivariate logistic analysis was conducted adjusting for age, sex, National Institute of Health Stroke Scale (NIHSS), occlusion site, last-known-well-to-intravenous thrombolysis time, interhospital-transfer and stroke system. Of 635 patients, 309 (48.7%) received TNK and 326 (51.3%) TPA prior to EVT. The site of occlusion was the M1 middle cerebral artery (MCA) (47.7%), M2 MCA (25.4%), internal carotid artery (14.0%), tandem carotid with M1 or M2 MCA (9.8%) and basilar artery (3.1%). A favorable functional outcome (90-day mRS ≤ 2) was observed in 47.6% of TNK and 49.7% of TPA patients (p = 0.132). TNK versus TPA groups had similar rates of early recanalization (11.9% vs. 8.4%, p = 0.259), successful endovascular reperfusion (93.5% vs. 89.3%, p = 0.627), symptomatic intracranial hemorrhage (3.2% vs. 3.4%, p = 0.218) and 90-day all-cause mortality (23.1% vs. 21.5%, p = 0.491). This U.S. multicenter real-world clinical experience demonstrated that switching from TPA to TNK before EVT for LVO stroke resulted in similar endovascular reperfusion, safety, and functional outcomes.

Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial

ObjectiveThe aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke.MethodsPost hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China.ResultsA total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0–2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947–0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807–0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869–0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665–0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991–0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705–25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke.ConclusionYounger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke.Chinese clinical trial registry identifierChiCTR-IOR-17014167.

Atrial fibrillation is associated with higher first pass effect following thrombectomy for large vessel occlusion

BackgroundFirst pass effect (FPE), defined as single-pass complete or near complete reperfusion during endovascular thrombectomy (EVT) for large vessel occlusion (LVO) strokes, is a critical performance metric. Atrial fibrillation (AF)-related...

Concurrent bacterial endocarditis is associated with worse inpatient outcomes for large vessel occlusions

BackgroundNeurological complications of bacterial endocarditis (BE) are common, including acute ischemic stroke (AIS). Although mechanical thrombectomy (MT) is effective for large vessel occlusion (LVO) stroke, data are limited on MT...

Higher blood glucose is associated with the severity of hemorrhagic transformation after endovascular therapy for stroke

ObjectivesHyperglycemia is associated with poor outcome in large vessel occlusion (LVO) stroke, with mechanism for this effect unknown. Materials and methodsWe used our prospective, multicenter, observational study, Blood Pressure After Endovascular Stroke Therapy (BEST), of anterior circulation LVO stroke undergoing endovascular therapy (EVT) from 11/2017-7/2018 to determine association between increasing blood glucose (BG) and intracerebral hemorrhage (ICH). Our primary outcome was degree of ICH, classified as none, asymptomatic ICH, or symptomatic ICH (≥4-point increase in National Institutes of Health Stroke Scale [NIHSS] at 24 h with any hemorrhage on imaging). Secondary outcomes included 24 h NIHSS, early neurologic recovery (ENR, NIHSS 0-1 or NIHSS reduction by ≥8 within 24 h), and 90-day modified Rankin Scale (mRS) using univariate and multivariable regression. ResultsOf 485 enrolled patients, increasing BG was associated with increasing severity of ICH (adjusted OR, aOR 1.06, 95 % CI 1.02-1.1, p < 0.001), higher 24 h NIHSS (aOR 1.22, 95 % CI 1.11-1.34, p < 0.001), ENR (aOR 0.90, 95 % CI 0.82-1.00, p < 0.002), and 90-day mRS (aOR 1.06, 95 % CI 1.03-1.09, p < 0.001) when adjusted for age, presenting NIHSS, ASPECTS, 24-hour peak systolic blood pressure, time from last known well, and successful recanalization. ConclusionsIn the BEST study, increasing BG was associated with greater odds of increasing ICH severity. Further study is warranted to determine whether treatment of will decrease ICH severity following EVT.

Impact and determinants of door in-door out time for stroke thrombectomy transfers in a large hub-and-spoke network.

The mantra "time is brain" cannot be overstated for patients suffering from acute ischemic stroke. This is especially true for those with large vessel occlusions (LVOs) requiring transfer to an endovascular thrombectomy (EVT) capable center. We sought to evaluate the spoke hospital door in-door out (DIDO) times for patients transferred to our hub center for EVT. Individuals who first presented with LVO to a spoke hospital and were then transferred to the hub for EVT were retrospectively identified from a prospectively maintained database from January 2019 to November 2022. DIDO was defined as the time between spoke hospital door in arrival and door out exit. Baseline characteristics, treatments, and outcomes were compared, dichotomizing DIDO at 90 minutes based in the American Heart Association goal for DIDO ≤90 minutes for 50% of transfers. Multivariable regression analyses were performed for determinants of the 90-day ordinal modified Rankin Scale (mRS) and DIDO. We identified 194 patients transferred for EVT with available DIDO. The median age was 67 years (IQR 57-80), and 46% were female. The median National Institutes of Health Stroke Scale (NIHSS) was 16 (10-20), 50% were treated with intravenous thrombolysis at a spoke, and TICI 2B-3 reperfusion was achieved in 87% at the hub. The median DIDO was 120 minutes (97-149), with DIDO ≤90 minutes achieved in 18%. DIDO was a significant determinant of 90-day ordinal mRS (B = 0.007, 95% CI = 0.001-0.012, p = 0.013), even when accounting for the last known well-to-spoke door in, spoke door out-to-hub arrival, hub arrival-to-puncture, puncture-to-first pass, age, NIHSS, intravenous thrombolysis, TICI 2B-3, and symptomatic intracranial hemorrhage. Importantly, determinants of DIDO included Black race or Hispanic ethnicity (B = 0.918, 95% CI = 0.010-1.826, p = 0.048), atrial fibrillation or heart failure (B = 0.793, 95% CI = 0.257-1.329, p = 0.004), and basilar LVO location (B = 2.528, 95% CI = 1.154-3.901, p < 0.001). Spoke DIDO was the most important period of time for long-term outcomes of LVO stroke patients treated with EVT. Targets were identified to reduce DIDO and improve patient outcomes.

A Deep Learning Approach to Predict Recanalization First-Pass Effect following Mechanical Thrombectomy in Patients with Acute Ischemic Stroke.

Following endovascular thrombectomy in patients with large-vessel occlusion stroke, successful recanalization from 1 attempt, known as the first-pass effect, has correlated favorably with long-term outcomes. Pretreatment imaging may contain information that can be used to predict the first-pass effect. Recently, applications of machine learning models have shown promising results in predicting recanalization outcomes, albeit requiring manual segmentation. In this study, we sought to construct completely automated methods using deep learning to predict the first-pass effect from pretreatment CT and MR imaging. Our models were developed and evaluated using a cohort of 326 patients who underwent endovascular thrombectomy at UCLA Ronald Reagan Medical Center from 2014 to 2021. We designed a hybrid transformer model with nonlocal and cross-attention modules to predict the first-pass effect on MR imaging and CT series. The proposed method achieved a mean 0.8506 (SD, 0.0712) for cross-validation receiver operating characteristic area under the curve (ROC-AUC) on MR imaging and 0.8719 (SD, 0.0831) for cross-validation ROC-AUC on CT. When evaluated on the prospective test sets, our proposed model achieved a mean ROC-AUC of 0.7967 (SD, 0.0335) with a mean sensitivity of 0.7286 (SD, 0.1849) and specificity of 0.8462 (SD, 0.1216) for MR imaging and a mean ROC-AUC of 0.8051 (SD, 0.0377) with a mean sensitivity of 0.8615 (SD, 0.1131) and specificity 0.7500 (SD, 0.1054) for CT, respectively, representing the first classification of the first-pass effect from MR imaging alone and the first automated first-pass effect classification method in CT. Results illustrate that both nonperfusion MR imaging and CT from admission contain signals that can predict a successful first-pass effect following endovascular thrombectomy using our deep learning methods without requiring time-intensive manual segmentation.

Prediction of Large Vessel Occlusion Stroke Using Clinical Registries for Research.

A reliable method of predicting large vessel occlusion (LVO) stroke in data sets without neuroimaging could be retrospectively applied to expand research efforts. We conducted a retrospective, cross-sectional cohort analysis of the Get With The Guidelines (GWTG)-Stroke registry. We included adult patients with a final diagnosis of ischemic stroke from 2016 to 2021 who had brain and vascular imaging and excluded those with missing data or posterior circulation stroke. We included 416,022 patients of which 125,381 (30.1%) had LVO. The mean age was 71 years, and 48.2% were female. The area under the receiver operating curve (AUC) for the final model, including age, sex, hypertension, dyslipidemia, atrial fibrillation, diabetes, TOAST stroke mechanism, and NIH Stroke Scale (NIHSS), was 0.79 (95% CI 0.79-0.80). Without TOAST mechanism, the AUC was 0.74. The specificity did not exceed 0.5 using different cut points for the NIHSS. We found that 30% of adult acute ischemic stroke patients in GWTG-Stroke have LVO and that the combination of clinical covariates and NIHSS is only moderately predictive of LVO status. These results are consistent with previous studies and suggest it may not be possible to retrospectively predict LVO with high accuracy in data sets without vascular neuroimaging.

Efficacy and safety of combined stent retriever and contact aspiration vs. stent retriever alone on revascularization in patients with acute ischemic stroke: a systematic review and meta-analysis.

Whether the efficacy of combined stent retriever and contact aspiration (S + A) is superior to stent retriever (S) alone for revascularisation in patients with large vessel occlusive stroke remains uncertain. The aim of this meta-analysis was to assess the safety and efficacy of combined stent retriever and contact aspiration for the treatment of acute ischaemic stroke with large vessel occlusion by comparing it with stent retriever alone. We systematically searched the PubMed, Embase, Web of Science, and The Cochrane Library databases for randomised controlled trials and observational studies (case-control and cohort studies) published before 1 October 2023 comparing the efficacy of combined stent retriever and contact aspiration versus tent retriever alone in patients with large vessel occlusive stroke. The end point of the primary efficacy observed in this meta-analysis study was the rate of first pass nearly complete or complete recanalisation (mTICI 2c-3). Secondary effectiveness nodes were: rate of first pass successful recanalisation (mTICI 2b-3), rate of near-complete or complete recanalisation of the postoperative vessel, rate of successful recanalisation of the postoperative vessel, and MRS 0-2 within 90 days. Safety endpoints were interoperative embolism, symptomatic intracranial haemorrhage, and mortality within 90 days. A total of 16 studies were included in the literature for this meta-analysis, with a total of 7,320 patients (S + C group: 3,406, S group: 3,914). A comprehensive analysis of the included literature showed that combined stent retriever and contact aspiration had a higher rate of near-complete or complete recanalisation of the postoperative vessel [OR = 1.53, 95% CI (1.24, 1.88), p < 0.0001] and rate of successful recanalisation of the postoperative vessel compared to stent retriever alone [OR = 1.83, 95% CI (1.55, 2.17), p < 0.00001]; there were no statistically significant differences between the two groups in terms of the rate of first pass nearly complete or complete recanalisation [OR = 1.00, 95% CI (0.83, 1.19), p = 0.96], rate of first pass successful recanalisation [OR = 1.02, 95% CI (0.85, 1.24), p = 0.81], interoperative embolism [OR = 0.93, 95% CI (0.72, 1.20), p = 0.56], symptomatic intracranial haemorrhage [OR = 1.14, 95% CI (0.87, 1.48), p = 0.33], MRS 0-2 within 90 days [OR = 0.89, 95% CI (0.76, 1.04), p = 0.14] and mortality within 90 days [OR = 1.11, 95% CI (0.94, 1.31), p = 0.22]. Combined stent retriever and contact aspiration has a higher rate of postprocedural revascularisation (mTICI 2c-3/mTICI 2b-3) compared with stent retriever alone in patients with large vessel occlusion stroke. In addition, it was not superior to stenting alone in terms of the rate of first pass recanalisation (mTICI 2c-3/mTICI 2b-3), interoperative embolisation, symptomatic intracranial haemorrhage, good functional prognosis within 90 days and mortality within 90 days.

The effect of inadvertent systemic hypothermia after mechanical thrombectomy in patients with large-vessel occlusion stroke.

Postinterventional hypothermia is a frequent complication in patients with large-vessel occlusion strokes (LVOS) after mechanical thrombectomy (MT). This inadvertent hypothermia might potentially have neuroprotective but also adverse effects on patients' outcomes. The aim of the study was to determine the rate of hypothermia in patients with LVOS receiving MT and its influence on functional outcome. We performed a monocentric, retrospective study using a prospectively derived databank, including all LVOS patients receiving MT between 2015 and 2021. Predictive values of postinterventional body temperature and body temperature categories (hyperthermia (≥38°C), normothermia (35°C-37.9°C), and hypothermia (<35°C)) on functional outcome were analyzed using multivariable Bayesian logistic regression models. Favorable outcome was defined as modified Rankin Scale (mRS) ≤3. Of the 480 included LVOS patients with MT (46.0% men; mean ± SD age 73 ± 12.9 years), 5 (1.0%) were hyperthermic, 382 (79.6%) normothermic, and 93 (19.4%) hypothermic. Postinterventional hypothermia was significantly associated with unfavorable functional outcome (mRS > 3) after 90 days (OR 2.06, 95% CI 1.01-4.18, p = 0.045). For short-term functional outcome, patients with hypothermia had a higher discharge NIHSS (OR 1.38, 95% CI 1.06 to 1.79, p = 0.015) and a higher change of NIHSS from admission to discharge (OR 1.35, 95% CI 1.03 to 1.76, p = 0.029). Approximately a fifth of LVOS patients in this cohort were hypothermic after MT. Hypothermia was an independent predictor of unfavorable functional outcomes. Our findings warrant a prospective trial investigating active warming during MT.

Dynamic Evolution of Infarct Volumes at MRI in Ischemic Stroke Due to Large Vessel Occlusion.

The typical infarct volume trajectories in stroke patients, categorized as slow or fast progressors, remain largely unknown. This study aimed to reveal the characteristic spatiotemporal evolutions of infarct volumes caused by large vessel occlusion (LVO) and show that such growth charts help anticipate clinical outcomes. We conducted a secondary analysis from prospectively collected databases (FRAME, 2017-2019; ETIS, 2015-2022). We selected acute MRI data from anterior LVO stroke patients with witnessed onset, which were divided into training and independent validation datasets. In the training dataset, using Gaussian mixture analysis, we classified the patients into 3 growth groups based on their rate of infarct growth (diffusion volume/time-to-imaging). Subsequently, we extrapolated pseudo-longitudinal models of infarct growth for each group and generated sequential frequency maps to highlight the spatial distribution of infarct growth. We used these charts to attribute a growth group to the independent patients from the validation dataset. We compared their 3-month modified Rankin scale (mRS) with the predicted values based on a multivariable regression model from the training dataset that used growth group as an independent variable. We included 804 patients (median age 73.0 years [interquartile range 61.2-82.0 years]; 409 men). The training dataset revealed nonsupervised clustering into 11% (74/703) slow, 62% (437/703) intermediate, and 27% (192/703) fast progressors. Infarct volume evolutions were best fitted with a linear (r = 0.809; p < 0.001), cubic (r = 0.471; p < 0.001), and power (r = 0.63; p < 0.001) function for the slow, intermediate, and fast progressors, respectively. Notably, the deep nuclei and insular cortex were rapidly affected in the intermediate and fast groups with further cortical involvement in the fast group. The variable growth group significantly predicted the 3-month mRS (multivariate odds ratio 0.51; 95% CI 0.37-0.72, p < 0.0001) in the training dataset, yielding a mean area under the receiver operating characteristic curve of 0.78 (95% CI 0.66-0.88) in the independent validation dataset. We revealed spatiotemporal archetype dynamic evolutions following LVO stroke according to 3 growth phenotypes called slow, intermediate, and fast progressors, providing insight into anticipating clinical outcome. We expect this could help in designing neuroprotective trials aiming at modulating infarct growth before EVT.

Lipid Profiles and Atrial Fibrillation in Ischemic Stroke Patients Treated with Thrombectomy: Experience from a Tertiary Italian Stroke Hospital.

To assess acute lipid profiles, atrial fibrillation and other cardiovascular risk factors in patients undergoing treatments by thrombectomy (EVT) with acute ischemic stroke (AIS). We performed a retrospective analysis of the lipid profile and vascular risk factor in 1639 consecutive patients with acute ischemic stroke between January 2016 and December 2021. To assess lipid profiles, laboratory tests, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were obtained the day after admission. We also examined the association between lipid profile, AF and EVT in multivariate logistic regression analysis. Median age of patients was 74 years, 54.9% were males (95% CI 52.5-57.4%), and 26.8% (95% CI, 24.7-29.0%) had AF. EVT patients (n = 370; 22.57 %; 95% CI, 20.6-24.7) showed no difference in age (median 73 years (IQR; 63-80) versus 74 years (IQR; 63-82)), HbA1c levels (median 5.8 (IQR; 5.4-6.2) versus 5.9 (IQR; 5.4-6.4)), TG/HDL ratio (median 2.40 (IQR; 1.65-3.48) versus 2.51 (IQR; 1.73-3.64)), diabetes (OR 0.82; 95% CI 0.61 to 1.08), hypertension (OR 0.87; 95% CI 0.68 to 1.12) and obesity (OR 1.06; 95% CI 0.78 to 1.42) compared to non-EVT patients. Conversely, EVT patients showed lower levels of TC (160 mg/dl (IQR; 139- 187) versus 173 mg/dl (IQR; 148-202); p <0.001), LDL-C (105 mg/dl (IQR; 80-133) versus 113 mg/dl (IQR; 88-142); p <0.01), TG (98 mg/dl (IQR; 76-126) versus 107 mg/dl (IQR; 85-139); p <0.001), non-HDL-C (117 mg/dl (IQR; 94-145) versus 127 mg/dl (IQR; 103-154); p <0.001), HC (8.3 mmol/l (IQR; 6-11) versus 10 mmol/l (IQR; 7.3-13.5); p <0.001) than non-EVT patients. Multivariate logistic regression analysis showed an independent association of EVT with TC (OR 0.99, 95% CI 0.98-0.99), AF (OR 1.79, 95% CI 1.34-2.38), age (OR 0.98, 95% CI 0.96-0.99), and NIHSS (OR 1.17, 95% CI 0.14-1.19). Total cholesterol and all cholesterol-related measures were significantly lower in patients undergoing thrombectomy than in other stroke patients. Conversely, we found that AF was significantly high in patients with EVT, suggesting that hypercholesterolemia could be mainly linked to small-vessel occlusion stroke while large vessel occlusion (LVO) stroke could show different causes. AIS patients may have different pathogenesis and their understanding may improve the discovery of specific and tailored preventive treatments.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Noncontrast CT Selected Thrombectomy vs Medical Management for Late-Window Anterior Large Vessel Occlusion.

There is uncertainty whether patients with large vessel occlusion (LVO) presenting in the late 6-hour to 24-hour time window can be selected for endovascular therapy (EVT) by noncontrast CT (NCCT) and CT angiography (CTA) for LVO detection. We evaluated the clinical outcomes of patients selected for EVT by NCCT compared with those medically managed in the extended time window. This multinational cohort study was conducted at 66 sites across 10 countries. Consecutive patients with proximal anterior LVO stroke selected for EVT by NCCT or medically managed and presenting within 6-24 hours of time last seen well (TSLW) from January 2014 to May 2022 were included. The primary end point was the 90-day ordinal shift in the modified Rankin Scale (mRS) score. Inverse probability treatment weighting (IPTW) and multivariable methods were used. Of 5,098 patients screened, 839 patients were included, with a median (interquartile range) age of 75 (64-83) years; 455 (54.2%) were women. There were 616 patients selected to undergo EVT by NCCT (73.4%) and 223 (26.6%) who were medically managed. In IPTW analyses, there was a more favorable 90-day ordinal mRS shift in patients selected by NCCT to EVT vs those who were medically managed (odds ratio [OR] 1.99, 95% CI 1.53-2.59; p < 0.001). There were higher rates of 90-day functional independence (mRS 0-2) in the EVT group (40.1% vs 18.4%, OR 3.31, 95% CI 2.11-5.20; p < 0.001). sICH was nonsignificantly higher in the EVT group (8.5% vs 1.4%, OR 3.77, 95% CI 0.72-19.7, p = 0.12). Mortality at 90 days was lower in the EVT vs MM group (23.9% vs 32.3%, OR 0.61, 95% CI 0.45-0.83, p = 0.002). In patients with proximal anterior LVO in the extended time window, there was a lower rate of disability and mortality in patients selected with NCCT and CTA to EVT compared with those who were medically managed. These findings support the use of NCCT as a simpler and more inclusive approach to patient selection in the extended window. This study was registered at ClinicalTrials.gov under NCT04096248. This study provides Class III evidence that for patients with proximal anterior circulation occlusion presenting with ischemic stroke from 6 to 24 hours, compared with medical management, those undergoing thrombectomy based on NCCT have reduced disability and mortality at 90 days.

Association of functional outcomes between intravenous tirofiban and endovascular thrombectomy in imaging-screened patients with large vessel occlusion stroke: a secondary analysis of randomized clinical trial.

In the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Stroke Patients with Large Vessel Occlusion) trial, enrollment in extended time window was based on non-contrast computed tomography. To assess whether perioperative intravenous tirofiban would further enhance the clinical benefit of endovascular therapy in the RESCUE BT trial according to advanced imaging criteria based on current American Heart Association/American Stroke Association (AHA/ASA) guidelines. This is a secondary analysis of the RESCUE BT trial. Patients who were eligible for endovascular thrombectomy in the 6-hour window and met the criteria of the DAWN or DEFUSE 3 trials in the extended window according to the AHA/ASA guidelines were analyzed. The primary outcome was the distribution of the 90-day modified Rankin Scale (mRS) scores. Safety outcomes included the incidence of symptomatic intracranial hemorrhage (sICH) within 48 hours and 90-day mortality. A total of 652 patients (319 in tirofiban group and 333 in placebo group) who meeting the AHA/ASA guidelines were included in this analysis, with median (IQR) age of 68 (58-75) years, 278 (42.6%) were women. The median 90-day mRS score was 3 (IQR, 1-4) in the tirofiban group, and 3 (IQR, 1-4) in the placebo group. The adjusted common odds ratio (OR) for a lower level of disability with tirofiban than with placebo was 1.08 (95% confidence interval [CI], 0.83-1.42). The incidence of sICH (10.1% versus 6.3%; adjusted OR 1.70; [95% CI, 0.95-3.04]) was not significantly different between groups. However, intravenous tirofiban might be associated with lower disability level (adjusted common OR, 1.74 [95% CI, 1.14-2.65]; P=0.01) in patients with large artery atherosclerosis. There was no significant difference in the severity of disability at 90 days with intravenous tirofiban compared to placebo in patients who underwent endovascular therapy according to AHA/ASA guidelines. We observed potential benefits of tirofiban in patients with large artery atherosclerosis, but there was an increased risk of sICH in patients with cardioembolism stroke.

The lesion core extent modulates the impact of early perfusion mismatch imaging on outcome variability after thrombectomy in stroke.

Despite profitable group effects on functional outcomes after mechanical thrombectomy (MT) in large vessel occlusion (LVO), many patients with successful reperfusion show a non-favorable long-term outcome, highlighting the necessity to identify potential biomarkers predicting outcome variability. In this regard, the role of perfusion mismatch imaging for outcome variability in the early time window within 6 h after symptom onset is a matter of debate. We attempted to investigate under which conditions early perfusion mismatch imaging accounts for variability in functional outcomes after mechanical thrombectomy. In a retrospective single-center study, we examined 190 consecutive patients with LVO who were admitted to the Medical Center Lübeck within 6 h after symptom onset, all of whom underwent MT. Perfusion mismatch was quantified by applying the Alberta Stroke Program Early CT score (ASPECTS) on CT-measured cerebral blood flow (CBF-ASPECTS) and subtracting it from an ASPECTS application on cerebral blood volume (CBV-ASPECTS), i.e., ASPECTS mismatch. Using multivariate ordinal regression models, associations between ASPECTS mismatch and modified Rankin Scale (mRS) after 90 days were assessed. Furthermore, the interaction between ASPECTS mismatch and the core lesion volume was calculated to evaluate conditional associations. ASPECTS mismatch did not correlate with functional outcomes when corrected for multiple influencing covariables. However, interactions between ASPECTS mismatch and CBV-ASPECTS [OR: 1.12 (1.06-1.18), p-value < 0.001], as well as NCCT-ASPECTS [OR: 1.15 (1.06-1.25), p-value < 0.001], did show a significant association with functional outcomes. Model comparisons revealed that, profoundly, in patients with large core lesion volumes (CBV-ASPECTS < 6 or NCCT-ASPECTS < 6), perfusion mismatch showed a negative correlation with the mRS. Perfusion mismatch imaging within the first 6 h of symptom onset provides valuable insights into the outcome variability of LVO stroke patients receiving thrombectomy but only in patients with large ischemic core lesions.

How Clot Composition Influences Fibrinolysis in the Acute Phase of Stroke: A Proteomic Study of Cerebral Thrombi.

The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA). In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression. FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080). Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.

Effect of heart rate on poor outcome in stroke patients treated with intra-arterial thrombectomy

Background and purposeThe relationship between heart rate and the prognosis of patients with large vessel occlusion strokes treated with mechanical thrombectomy (MT) is not well established. This study aimed to evaluate the association of mean heart rate and heart rate variability (HRV) with the clinical outcomes after MT therapy.MethodsAcute ischemic stroke patients undergoing MT therapy were prospectively recruited from March 2020 to November 2022. Their heart rate was collected every hour for the initial 72 h after MT procedure, and the variability of heart rate was measured by standard deviation (SD) and coefficient of variation (CV). All-cause mortality and worsening of functional outcome (change in modified Rankin Scale (mRS) score) at 3-month were captured. Binary logistic regression was used to evaluate the association between heart rate indicators and all-cause mortality. Ordinal logistic regression was used to evaluate the association between heart rate indicators and worsening of functional outcome.ResultsAmong 191 MT-treated patients, 51(26.7%) patients died at 3-month after stroke. Increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were all associated with the increased risk of mortality (adjusted hazard ratio [aHR] with 95% CI: 1.29 [1.09–1.51], 1.19 [1.07–1.32], 1.14 [1.03–1.27]; respectively). Patients in the highest tertile of heart rate SD had an increased risk of mortality (4.62, 1.70-12.52). After using mRS as a continuous variable, we found increased mean heart rate per 10-bpm, heart rate SD and CV per 5-unit were associated with the worsening of functional outcome (adjusted odds ratio [aOR] with 95% CI: 1.35 [1.11–1.64], 1.27 [1.05–1.53], 1.19 [1.02–1.40]; respectively). A linear relationship was observed between mean heart rate or heart rate SD and mortality; while all of the heart rate measures in this study showed a linear relationship with the worsening of functional outcome.ConclusionsHigher mean heart rate and HRV were associated with the increased risk of 3-month all-cause mortality and worse functional outcome after MT therapy for AIS patients.