Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus.

BACKGROUND: Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology. METHODS: Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded. RESULTS: During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63 %) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p < 0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6 %, respectively; p = 0.1) and at latest follow-up (70.8 vs 50 %; p = 0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6 % vs 13.5 %; p = 0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2 %; p < 0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0 %; p = 0.1, respectively). Subgroup analysis comparing exclusive ACT vs Dual APT lead to similar results. CONCLUSION: Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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. TRIAL REGISTRATION INFORMATION: This study was registered at ClinicalTrials.gov under NCT04096248. CLASSIFICATION OF EVIDENCE: 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.

Subjects with carotid webs demonstrate pro-thrombotic hemodynamics compared to subjects with carotid atherosclerosis.

Carotid artery webs (CaW) are non-atherosclerotic projections into the vascular lumen and have been linked to up to one-third of cryptogenic strokes in younger patients. Determining how CaW affects local hemodynamics is essential for understanding clot formation and stroke risk. Computational fluid dynamics simulations were used to investigate patient-specific hemodynamics in carotid artery bifurcations with CaW, bifurcations with atherosclerotic lesions having a similar degree of lumen narrowing, and with healthy carotid bifurcations. Simulations were conducted using segmented computed tomography angiography geometries with inlet boundary conditions extracted from 2D phase contrast MRI scans. The study included carotid bifurcations with CaW (n = 13), mild atherosclerosis (n = 7), and healthy bifurcation geometries (n = 6). Hemodynamic parameters associated with vascular dysfunction and clot formation, including shear rate, oscillatory shear index (OSI), low velocity, and flow stasis were calculated and compared between the subject groups. Patients with CaW had significantly larger regions containing low shear rate, high OSI, low velocity, and flow stasis in comparison to subjects with mild atherosclerosis or normal bifurcations. These abnormal hemodynamic metrics in patients with CaW are associated with clot formation and vascular dysfunction and suggest that hemodynamic assessment may be a tool to assess stroke risk in these patients.

Early technique switch following failed passes during mechanical thrombectomy for ischemic stroke: should the approach change and when?

BACKGROUND: Fast and complete reperfusion in endovascular therapy (EVT) for ischemic stroke leads to superior clinical outcomes. The effect of changing the technical approach following initially unsuccessful passes remains undetermined. OBJECTIVE: To evaluate the association between early changes to the EVT approach and reperfusion. METHODS: Multicenter retrospective analysis of prospectively collected data for patients who underwent EVT for intracranial internal carotid artery, middle cerebral artery (M1/M2), or basilar artery occlusions. Changes in EVT technique after one or two failed passes with stent retriever (SR), contact aspiration (CA), or a combined technique (CT) were compared with repeating the previous strategy. The primary outcome was complete/near-complete reperfusion, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) of 2c-3, following the second and third passes. RESULTS: Among 2968 included patients, median age was 66 years and 52% were men. Changing from SR to CA on the second or third pass was not observed to influence the rates of eTICI 2c-3, whereas changing from SR to CT after two failed passes was associated with higher chances of eTICI 2c-3 (OR=5.3, 95% CI 1.9 to 14.6). Changing from CA to CT was associated with higher eTICI 2c-3 chances after one (OR=2.9, 95% CI 1.6 to 5.5) or two (OR=2.7, 95% CI 1.0 to 7.4) failed CA passes, while switching to SR was not significantly associated with reperfusion. Following one or two failed CT passes, switching to SR was not associated with different reperfusion rates, but changing to CA after two failed CT passes was associated with lower chances of eTICI 2c-3 (OR=0.3, 95% CI 0.1 to 0.9). Rates of functional independence were similar. CONCLUSIONS: Early changes in EVT strategies were associated with higher reperfusion and should be contemplated following failed attempts with stand-alone CA or SR.

Competitive leptomeningeal flow impact on thrombectomy reperfusion grade rating.

BACKGROUND: Competitive leptomeningeal flow (CLF) can be observed immediately after mechanical thrombectomy (MT) reperfusion with retrograde contrast clearing of the distal leptomeningeal branches from non-contrast opacified flow through different vascular territories. We aim to evaluate the frequency of the CLF phenomenon, to determine if it has an association with the degree of leptomeningeal collateral status, and to understand the potentia impact it may have on the final expanded Treatment in Cerebral Ischemia (eTICI) score rating. METHODS: Retrospective analysis of a prospective MT database spanning November 2020 to December 2021. Consecutive cases of intracranial internal carotid (i-ICA) or middle cerebral artery (MCA) M1 occlusions were included. CLF was defined by the observation of retrograde clearing of distal MCA branches that were previously opacified by antegrade reperfusion. The clearance of the distal branches is presumed to occur due to CLF via non-contrast opacified posterior cerebral artery or anterior cerebral artery flow. The washout was considered CLF if it cleared abruptly with or without forward reconstitution of antegrade opacification. RESULTS: A total of 125 patients met the inclusion criteria. The median age was 64 years (IQR 52.5-75) and 64 (51%) were men. The baseline median National Institutes of Health Stroke Scale score was 17 (IQR 12-22) and the Alberta Stroke Program Early CT Score was 9 (IQR 8-10). Median last known well time to puncture was 7 hours (IQR 4-13.1) and 30.4% received tissue plasminogen activator. Final eTICI 2c-3 was achieved in 80%. CLF was present in 32 (25.6%) patients, who had comparable baseline characteristics to patients without CLF. Twelve (37.5%) patients had regional CLF and 20 (62.5%) had focal CLF. The CLF arm had better leptomeningeal single-phase CTA collaterals than the non-CLF arm (P=0.01). The inter-rater agreement for the eTICI score was moderate when CLF was present and strong in its absence (Krippendorf's alpha=0.65 and 0.81, respectively). There was minimal agreement (Kappa=0.3) for the presence versus absence of CLF between the two operators, possibly related to reader experience. CONCLUSION: CLF was observed in 32% of patients, was associated with better collateral flow, and impacted the reported procedural eTICI rating.

Thrombectomy With the pRESET vs Solitaire Stent Retrievers as First-Line Large Vessel Occlusion Stroke Treatment: A Randomized Clinical Trial.

Importance: Stent retriever-based thrombectomy is highly beneficial in large vessel occlusion (LVO) strokes. Many stent retriever designs are currently available, but comparison of these technologies in well-conducted studies is lacking. Objective: To determine whether thrombectomy for LVO stroke with the pRESET stent retriever is noninferior to treatment with the Solitaire stent retriever. Design, Setting, and Participants: This study was a multicenter, prospective, randomized, controlled, open-label, adaptive, noninferiority trial with blinded primary end point evaluation. Between October 2019 and February 2022, multicenter participation occurred across 19 research hospitals and/or universities in the US and 5 in Germany. Patients with LVO stroke were enrolled and included up to 8 hours after symptom onset. Interventions: Patients underwent 1:1 randomization to thrombectomy with the pRESET or Solitaire stent retriever. Main Outcomes and Measures: The primary outcome was the difference in the rate of 90-day functional independence across the 2 devices, using a -12.5% noninferiority margin for the lower bound of the 1-sided 95% CI of the difference between pRESET and Solitaire retrievers. Results: Of 340 randomized patients, 170 (50.0%) were female, and the median (IQR) age was 73.0 (64.0-82.0) years. The study procedure was completed in 322 of the 340 randomized patients. The primary end point of 90-day functional independence was achieved by 95 patients (54.9%; 95% CI, 48.7-61.1) in the pRESET group and in 96 (57.5%; 95% CI, 51.2-63.8) in the Solitaire group (absolute difference, -2.57%; 95% CI, -11.42 to 6.28). As the lower bound of the 95% CI was greater than -12.5%, the pRESET retriever was deemed noninferior to the Solitaire retriever. The noninferiority of pRESET over Solitaire was also observed in the secondary clinical end point (90-day shift in modified Rankin Scale score) and in both angiographic end points (Expanded Treatment in Cerebral Infarction [eTICI] score of 2b50 or greater within 3 passes: 146 of 173 [84.4%] vs 149 of 167 [89.2%]; absolute difference, -4.83%; 95% CI, -10.84 to 1.19; eTICI of 2c or greater following the first pass: 76 of 173 [43.7%] vs 74 of 167 [44.3%]; absolute difference, -0.63%; 95% CI, -9.48 to 8.21). Symptomatic intracranial hemorrhage occurred in 0 patients in the pRESET group and 2 (1.2%) in the Solitaire group. Mortality occurred in 25 (14.5%) in the pRESET group and in 24 (14.4%) in the Solitaire group at 90 days. Findings of the per-protocol and as-treated analyses were in concordance with findings of the intention-to-treat analysis. Conclusions and Relevance: In this study, among patients with LVO stroke, thrombectomy with the pRESET stent retriever was noninferior to thrombectomy with the Solitaire stent retriever. Findings suggest that pRESET offers a safe and effective option for flow restoration and disability reduction in patients with LVO stroke.

Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

Optical Coherence Tomography in the Evaluation of Suspected Carotid Webs.

BACKGROUND: Carotid web (CaW) is a subtype of fibromuscular dysplasia that predominantly involves the intimal layer of the arterial wall and is commonly overlooked as a separate causative entity for recurrent strokes. CaW is defined as a shelf-like lesion at the carotid bulb, although different morphological features have been reported. Optical coherence tomography (OCT) has been described in the literature as a useful microscopic and cross-sectional tomographic imaging tool. This study aimed to evaluate the potential utility of OCT in characterizing the wall structure features of patients with suspected CaW. METHODS: Retrospective analysis of patients with suspected CaW who underwent digital subtraction angiography (DSA) coupled with OCT of the carotid bulb from 2018 to 2021 in a single comprehensive stroke center. RESULTS: Sixteen patients were included. The median age was 56 years (IQR 46-61) and 50% were women. OCT corroborated the diagnosis of CaW in 12/16 (75%) cases and ruled it out in 4/16 (25%) patients in whom atherosclerotic disease was demonstrated. Five of the 12 lesions demonstrated a thick fibrotic ridge consistent with CaW but also showed atherosclerotic changes in the vicinity of the carotid bulb (labeled as "CaW+"). In 4/16 (25%) patients, microthrombi adhered to the vessel wall were noted on OCT (inside the CaW pocket or just distal to the web), none of which were observed on CT angiography or DSA. CONCLUSIONS: OCT may have value as a complementary imaging tool in the investigation of patients with suspected CaW and atypical morphological features. Further studies are warranted.

Primary results from the CLEAR study of a novel stent retriever with drop zone technology.

BACKGROUND: Challenges to revascularization of large vessel occlusions (LVOs) persist. Current stent retrievers have limited effectiveness for removing organized thrombi. The NeVa device is a novel stent retriever designed to capture organized thrombi within the scaffold during retrieval. OBJECTIVE: To evaluate the safety and effectiveness of revascularization of acute LVOs with the NeVa device. METHODS: Prospective, international, multicenter, single-arm, Investigational Device Exemption study to evaluate the performance of the NeVa device in recanalizing LVOs including internal carotid artery, M1/M2 middle cerebral artery, and vertebrobasilar arteries, within 8 hours of onset. Primary endpoint was rate of expanded Treatment in Cerebral Ischemia (eTICI) score 2b-3 within 3 NeVa passes, tested for non-inferiority against a performance goal of 72% with a -10% margin. Additional endpoints included first pass success and 90-day modified Rankin Scale (mRS) score 0-2. Primary composite safety endpoint was 90-day mortality and/or 24-hour symptomatic intracranial hemorrhage (sICH). RESULTS: From April 2021 to April 2022, 139 subjects were enrolled at 25 centers. Median National Institutes of Health Stroke Scale (NIHSS) score was 16 (IQR 12-20). In the primary analysis population (n=107), eTICI 2b-3 within 3 NeVa passes occurred in 90.7% (97/107; non-inferiority P<0.0001; post hoc superiority P<0.0001). First pass eTICI 2b-3 was observed in 73.8% (79/107), with first pass eTICI 2b67-3 in 69.2% (74/107) and eTICI 2c-3 in 48.6% (52/107). Median number of passes was 1 (IQR 1-2). Final eTICI 2b-3 rate was 99.1% (106/107); final eTICI 2b67-3 rate was 91.6% (98/107); final eTICI 2c-3 rate was 72.9% (78/107). Good outcome (90-day mRS score 0-2) was seen in 65.1% (69/106). Mortality was 9.4% (13/138) with sICH in 5.0% (7/139). CONCLUSIONS: The NeVa device is highly effective and safe for revascularization of LVO strokes and demonstrates superior first pass success compared with a predicate performance goal. TRIAL REGISTRATION NUMBER: NCT04514562.

Large vessel occlusion prediction scale thresholds that are sensitive for DAWN Trial patients.

BACKGROUND: Large vessel occlusion (LVO) prediction scales are used to triage prehospital suspected stroke patients with a high probability of LVO stroke to endovascular therapy centers. The sensitivities of these scales in the 6-to-24-h time window are unknown. Higher scale score thresholds are typically less sensitive and more specific. Knowing the highest scale score thresholds that remain sensitive could inform threshold selection for clinical use. Sensitivities may also vary between left and right-sided LVOs. METHODS: LVO prediction scale scores were retrospectively calculated using the National Institutes of Health Stroke Scale (NIHSS) scores of patients enrolled in the DAWN Trial. All patients had last known well times between 6 and 24 h, NIHSS scores ≥ 10, intracranial internal carotid artery or proximal middle cerebral artery occlusions, and mismatches between their clinical severities and infarct core volumes. Scale thresholds with sensitivities ≥ 85% were identified, along with scores ≥ 5% more sensitive for left or right-sided LVOs. Specificities could not be calculated because all patients had LVOs. RESULTS: A total of 201 out of 206 patients had the required NIHSS subitem scores. CPSS = 3, C-STAT ≥ 2, FAST-ED ≥ 4, G-FAST ≥ 3, RACE ≥ 5, and SAVE ≥ 3 were the highest thresholds that were still 85% sensitive for DAWN Trial LVO stroke patients. RACE ≥ 5 was the only typically used score threshold more sensitive for right-sided LVOs, though similar small differences were seen for other scales at higher thresholds. CONCLUSIONS: Our findings likely represent the maximum sensitivities of the LVO prediction scales tested for ideal thrombectomy candidates in the 6-to-24-h time window because NIHSS scores were documented in hospitals during a clinical trial rather than in the prehospital setting. Patients with NIHSS scores < 10 or more distal LVOs would lower sensitivities further. Selecting even higher scale thresholds for LVO triage would lead to many missed LVO strokes.

Emergent use of ticagrelor during endovascular reperfusion in large arterial occlusions.

OBJECTIVE: Given many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes. METHODS: This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any. RESULTS: 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03). CONCLUSION: We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Higher Procedural Volumes Are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVE: We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). METHODS: This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016 to December 31, 2019 in the Get with the Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment National Institutes of Health Stroke Scale (NIHSS) < 6, onset-to-treatment time > 6 hours, and interhospital transfers. There were 2 secondary cohorts: (1) the EVT metrics cohort excluded patients with missing data on time from door to arterial puncture and (2) the intravenous thrombolysis (IVT) metrics cohort only included patients receiving IVT ≤4.5 hours after onset. RESULTS: The primary cohort (mean ± standard deviation age = 70.7 ± 14.8 years; 51.2% female; median [interquartile range] baseline NIHSS = 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case increase in volume) of discharge to home (1.03 [1.02-1.04]), functional independence at discharge (1.02 [1.01-1.04]), and lower rates of in-hospital mortality (0.96 [0.95-0.98]). All secondary measures were also associated with procedural volumes. INTERPRETATION: Among AIS patients primarily presenting to EVT-capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality. ANN NEUROL 2023.

Assessment of Complex Flow Patterns in Patients With Carotid Webs, Patients With Carotid Atherosclerosis, and Healthy Subjects Using 4D Flow MRI.

BACKGROUND: Carotid webs (CaWs) are fibromuscular projections in the internal carotid artery (ICA) that cause mild luminal narrowing (<50%), but may be causative in up to one-third of seemingly cryptogenic strokes. Understanding hemodynamic alterations caused by CaWs is imperative to assessing stroke risk. Time-Average Wall Shear Stress (TAWSS) and Oscillatory Shear Index (OSI) are hemodynamic parameters linked to vascular dysfunction and thrombosis. PURPOSE: To test the hypothesis: "CaWs are associated with lower TAWSS and higher OSI than mild atherosclerosis or healthy carotid bifurcation." STUDY TYPE: Prospective study. POPULATION: A total of 35 subjects (N = 14 bifurcations with CaW, 11F, age: 49 ± 10, 10 mild atherosclerosis 6F, age: 72 ± 9, 11 healthy 9F, age: 42 ± 13). FIELD STRENGTH/SEQUENCE: 4D flow/STAR-MATCH/3D TOF/3T MRI, CTA. ASSESSMENT: 4D Flow velocity data were analyzed in two ways: 1) 3D ROI in the ICA bulbar segment (complex flow patterns are expected) was used to quantify the regions with low TAWSS and high OSI. 2) 2D planes were placed perpendicular to the centerline of the carotid bifurcation for detailed analysis of TAWSS and OSI. STATISTICAL TESTS: Independent-samples Kruskal-Wallis-H test with 0.05 used for statistical significance. RESULTS: The percent surface area where low TAWSS was present in the ICA bulb was 12.3 ± 8.0% (95% CI: 7.6-16.9) in CaW subjects, 1.6 ± 1.9% (95% CI: 0.2-2.9) in atherosclerosis, and 8.5 ± 7.7% (95% CI: 3.6-13.4) in healthy subjects, all differences were statistically significant (ƞ2 = 0.3 [95% CI: 0.05-0.5], P-value CaW vs. healthy = 0.2). OSI had similar values in the CCA between groups (ƞ2 = 0.07 [95% CI: 0.0-0.2], P-value = 0.5), but OSI was significantly higher downstream of the bifurcation in CaW subjects compared to atherosclerosis and normal subjects. OSI returned to similar values between groups 1.5 diameters distal to the bifurcation (ƞ2 = 0.03 [95% CI: 0.0-0.2], P-value = 0.7). CONCLUSION: Lower TAWSS and higher OSI are present in the ICA bulb in patients with CaW when compared to patients with atherosclerotic or healthy subjects. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Rescue intracranial stenting for failed posterior circulation thrombectomy: analysis from the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study.

BACKGROUNDS: Recent trials have shown improved outcomes after mechanical thrombectomy (MT) for vertebrobasilar occlusion (VBO) stroke. However, there is a paucity of data regarding safety and outcomes of rescue intracranial stenting (RS) after failed MT (FRRS+) for posterior circulation stroke. We sought to compare RS to failed reperfusion without RS (FRRS-). METHODS: This is a retrospective analysis of the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study, a multicenter collaboration involving prospectively collected databases. Patients were included if they had posterior circulation stroke and failed MT. The cohort was divided into two groups: FRRS+ and FRRS- (defined as modified Thrombolysis In Cerebral Infarction (mTICI) score 0-2a). The primary outcome was a shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included mRS 0-2 and mRS 0-3 at 90 days. Safety measures included rates of symptomatic intracranial hemorrhage (sICH), procedural complications, and 90-day mortality. Sensitivity and subgroup analyses were performed to identify outcomes in a matched cohort and in those with VBO, respectively. RESULTS: A total of 152 failed thrombectomies were included in the analysis. FRRS+ (n=84) was associated with increased likelihood of lower disability (acOR 2.24, 95% CI 1.04 to 4.95, P=0.04), higher rates of mRS 0-2 (26.8% vs 12.5%, aOR 4.43, 95% CI 1.22 to 16.05, P=0.02) and mRS 0-3 (35.4% vs 18.8%, aOR 3.13, 95% CI 1.08 to 9.10, P=0.036), and lower mortality (42.7% vs 59.4%, aOR 0.40, 95% CI 0.17 to 0.97, P=0.04) at 90 days compared with FRRS- (n=68). The rates of sICH and procedural complications were comparable between the groups. Sensitivity and subgroup analyses showed similar results. CONCLUSION: In patients with posterior circulation stroke who had failed MT, RS resulted in better functional outcomes with comparable safety profile to procedure termination.

Comparative analysis of stenting for carotid web and atherosclerotic disease.

INTRODUCTION: Carotid Web (CaW) is an increasingly recognized etiology of ischemic stroke, and has been shown to be amenable to endovascular stenting. The technical complexity of stenting for CaW may be lower than for carotid atherosclerotic disease (CAD). We aimed to assess procedural characteristics of stenting for CaW as compared to CAD. METHODS: We retrospectively analyzed a cohort of consecutive patients at a single comprehensive stroke center from 2014 to 2021, who had undergone elective endovascular stent placement for symptomatic CAD or CaW. RESULTS: In total, 118 patients underwent elective stent placement following ischemic stroke/transient ischemic attack; 88 patients had CAD and 30 patients had CaW. CAD patients were older (63.2 vs 51.2 years, p < 0.001), less likely to be female (28.4% vs 73.3%, p < 0.001), and more likely to have pre-existing vascular risk factors. Procedure time (73.0 vs 57.5 min, p = 0.007), radiation exposure (1482 vs 1125 milliGray, p = 0.03), filter time (24 vs 14 min, p = 0.04), and use of pre-stent (68.2% vs 0%, p < 0.001) and post-stent (34.1% vs 3.3%, p < 0.001) balloon angioplasty were higher in CAD cases. There was no significant difference between groups in the rate of periprocedural complications such as hypotension, use of vasopressors, or bradycardia. Recurrent stroke/TIA was reported in five CAD patients and 0 CaW patients by the end of the follow-up period (8.3% vs 0%, p = 0.12). In-stent restenosis was detected in seven CAD patients and 0 CaW patients (10.1% vs 0%, p = 0.09) at a median follow-up of 4 vs 16 months (p = 0.01), respectively. Periprocedural intracranial hemorrhage was not observed in either group. CONCLUSION: Stenting for CaW was found to be technically simpler than CAD and not to confer increased risk of baroreceptor dysregulation. Intimal hyperplasia was uncommon in CaW cases.

Comparison of CT Perfusion Software Packages for Thrombectomy Eligibility.

INTRODUCTION: Computed tomography perfusion (CTP) has played an important role in patient selection for mechanical thrombectomy (MT) in acute ischemic stroke. We aimed to investigate the agreement between perfusion parametric maps of 3 software packages - RAPID (RapidAI-IschemaView), Viz CTP(Viz.ai), and e-CTP(Brainomix) - in estimating baseline ischemic core volumes of near completely/completely reperfused patients. METHODS: We retrospectively reviewed a prospectively maintained MT database to identify patients with anterior circulation large vessel occlusion strokes (LVOS) involving the internal carotid artery or middle cerebral artery M1-segment and interpretable CTP maps treated during September 2018 to November 2019. A subset of patients with near-complete/complete reperfusion (expanded thrombolysis in cerebral infarction [eTICI] 2c-3) was used to compare the pre-procedural prediction of final infarct volumes. RESULTS: In this analysis of 242 patients with LVOS, RAPID and Viz CTP relative cerebral blood flow (rCBF) < 30% values had substantial agreement (ρ = 0.767 [95% confidence interval [CI] = 0.71-0.81]) as well as for RAPID and e-CTP (ρ = 0.668 [95% CI = 0.61-0.71]). Excellent agreement was seen for time to maximum of the residue function (Tmax ) > 6 seconds between RAPID and Viz CTP (ρ = 0.811 [95% CI = 0.76-0.84]) and substantial for RAPID and e-CTP (ρ = 0.749 [95% CI = 0.69-0.79]). Final infarct volume (FIV) prediction (n = 136) was substantial in all 3 packages (RAPID ρ = 0.744; Viz CTP ρ = 0.711; and e-CTP ρ = 0.600). CONCLUSION: Perfusion parametric maps of the RAPID, Viz CTP, and e-CTP software have substantial agreement in predicting final infarct volume in near-completely/completely reperfused patients. ANN NEUROL 2023;94:848-855.

Clot composition and recanalization outcomes in mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy (MT) has become standard for large vessel occlusions, but rates of complete recanalization are suboptimal. Previous reports correlated radiographic signs with clot composition and a better response to specific techniques. Therefore, understanding clot composition may allow improved outcomes. METHODS: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin-eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of first-pass effect (FPE, modified Thrombolysis in Cerebral Infarction 2c/3) and the number of passes. RESULTS: A total of 1430 patients of mean±SD age 68.4±13.5 years (median (IQR) baseline National Institutes of Health Stroke Scale score 17.2 (10.5-23), IV-tPA use 36%, stent-retrievers (SR) 27%, contact aspiration (CA) 27%, combined SR+CA 43%) were included. The median (IQR) number of passes was 1 (1-2). FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for red blood cell (RBC)-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes than RBC-rich and mixed clots (median 2 and 1.5 vs 1, respectively; P=0.02). CA showed a trend towards a higher number of passes with fibrin-rich clots (2 vs 1; P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots. CONCLUSIONS: Despite the lack of correlation between clot histology and FPE, our study adds to the growing evidence supporting the notion that clot composition influences recanalization treatment strategy outcomes.

Tissue Clock Beyond Time Clock: Endovascular Thrombectomy for Patients With Large Vessel Occlusion Stroke Beyond 24 Hours.

BACKGROUND AND PURPOSE: Randomized trials proved the benefits of mechanical thrombectomy (MT) for select patients with large vessel occlusion (LVO) within 24 hours of last-known-well (LKW). Recent data suggest that LVO patients may benefit from MT beyond 24 hours. This study reports the safety and outcomes of MT beyond 24 hours of LKW compared to standard medical therapy (SMT). METHODS: This is a retrospective analysis of LVO patients presented to 11 comprehensive stroke centers in the United States beyond 24 hours from LKW between January 2015 and December 2021. We assessed 90-day outcomes using the modified Rankin Scale (mRS). RESULTS: Of 334 patients presented with LVO beyond 24 hours, 64% received MT and 36% received SMT only. Patients who received MT were older (67±15 vs. 64±15 years, P=0.047) and had a higher baseline National Institutes of Health Stroke Scale (NIHSS; 16±7 vs.10±9, P<0.001). Successful recanalization (modified thrombolysis in cerebral infarction score 2b-3) was achieved in 83%, and 5.6% had symptomatic intracranial hemorrhage compared to 2.5% in the SMT group (P=0.19). MT was associated with mRS 0-2 at 90 days (adjusted odds ratio [aOR] 5.73, P=0.026), less mortality (34% vs. 63%, P<0.001), and better discharge NIHSS (P<0.001) compared to SMT in patients with baseline NIHSS ≥6. This treatment benefit remained after matching both groups. Age (aOR 0.94, P<0.001), baseline NIHSS (aOR 0.91, P=0.017), Alberta Stroke Program Early Computed Tomography (ASPECTS) score ≥8 (aOR 3.06, P=0.041), and collaterals scores (aOR 1.41, P=0.027) were associated with 90-day functional independence. CONCLUSION: In patients with salvageable brain tissue, MT for LVO beyond 24 hours appears to improve outcomes compared to SMT, especially in patients with severe strokes. Patients' age, ASPECTS, collaterals, and baseline NIHSS score should be considered before discounting MT merely based on LKW.

Bailout technique for entangled stent retriever and carotid stent during tandem large vessel occlusion endovascular therapy.

BACKGROUND AND IMPORTANCE: Endovascular thrombectomy for patients with tandem occlusions could be challenging. Exposure to potential technical complications and bailout rescue techniques are of utmost importance. CLINICAL PRESENTATION: A 73-year-old woman with tandem internal carotid artery and middle cerebral artery lesions underwent an unsuccessful retrograde revascularization approach in the setting of tortuous anatomy. Antegrade approach revascularization was then pursued. Following cervical internal carotid artery revascularization, a triaxial system of aspiration catheter, microcatheter and micro guidewire was navigated through the stented curved cervical ICA and intracranial stent retriever pass was performed. Upon retrieving the clot-incorporated stent retriever with the intention to retrieve the entire stent retriever into the locally placed aspiration catheter, the triaxial system collapsed into the distal common carotid artery. Large thrombus was recovered from the aspiration catheter aspirate however the proximal end of stent retriever and distal internal carotid artery stent got tangled. After unsuccessful maneuvering to disentangle stent retriever from the internal carotid artery stent, we decided to attempt safe separation of the stent retriever from its pusher wire and leave behind the patent internal carotid artery stent/stent retriever metal construct in place. Gradual pulling pressure was applied to the stent retriever wire while maintaining distal exchange-length microwire access and fully inflated extracranial balloon over the entangled portion to ensure continuous vascular access. The stent retriever wire was then safely separated from the stent retriever and fully retracted outside the body. Delayed angiographic runs continued to demonstrate full patency of the internal carotid artery lumen. No residual dissection, spasm, or thrombus was noted. CONCLUSION: This case illustrates a novel bailout endovascular salvage technique that could be considered in such cases. These techniques minimize intraoperative complication, focus on patient safety, and promote efficiency for endovascular thrombectomy in unfavorable anatomy.

Optimization of 4D Flow MRI Spatial and Temporal Resolution for Examining Complex Hemodynamics in the Carotid Artery Bifurcation.

BACKGROUND: Three-dimensional, ECG-gated, time-resolved, three-directional, velocity-encoded phase-contrast MRI (4D flow MRI) has been applied extensively to measure blood velocity in great vessels but has been much less used in diseased carotid arteries. Carotid artery webs (CaW) are non-inflammatory intraluminal shelf-like projections into the internal carotid artery (ICA) bulb that are associated with complex flow and cryptogenic stroke. PURPOSE: Optimize 4D flow MRI for measuring the velocity field of complex flow in the carotid artery bifurcation model that contains a CaW. METHODS: A 3D printed phantom model created from computed tomography angiography (CTA) of a subject with CaW was placed in a pulsatile flow loop within the MRI scanner. 4D Flow MRI images of the phantom were acquired with five different spatial resolutions (0.50-2.00  mm3) and four different temporal resolutions (23-96 ms) and compared to a computational fluid dynamics (CFD) solution of the flow field as a reference. We examined four planes perpendicular to the vessel centerline, one in the common carotid artery (CCA) and three in the internal carotid artery (ICA) where complex flow was expected. At these four planes pixel-by-pixel velocity values, flow, and time average wall shear stress (TAWSS) were compared between 4D flow MRI and CFD. HYPOTHESIS: An optimized 4D flow MRI protocol will provide a good correlation with CFD velocity and TAWSS values in areas of complex flow within a clinically feasible scan time (~ 10 min). RESULTS: Spatial resolution affected the velocity values, time average flow, and TAWSS measurements. Qualitatively, a spatial resolution of 0.50  mm3 resulted in higher noise, while a lower spatial resolution of 1.50-2.00  mm3 did not adequately resolve the velocity profile. Isotropic spatial resolutions of 0.50-1.00  mm3 showed no significant difference in total flow compared to CFD. Pixel-by-pixel velocity correlation coefficients between 4D flow MRI and CFD were > 0.75 for 0.50-1.00  mm3 but were < 0.5 for 1.50 and 2.00  mm3. Regional TAWSS values determined from 4D flow MRI were generally lower than CFD and decreased at lower spatial resolutions (larger pixel sizes). TAWSS differences between 4D flow and CFD were not statistically significant at spatial resolutions of 0.50-1.00  mm3 but were different at 1.50 and 2.00 mm3. Differences in temporal resolution only affected the flow values when temporal resolution was > 48.4 ms; temporal resolution did not affect TAWSS values. CONCLUSION: A spatial resolution of 0.74-1.00  mm3 and a temporal resolution of 23-48 ms (1-2 k-space segments) provides a 4D flow MRI protocol capable of imaging velocity and TAWSS in regions of complex flow within the carotid bifurcation at a clinically acceptable scan time.