The role of intravenous thrombolysis before mechanical Thrombectomy: A subgroup analysis of the RESILIENT trial.

BACKGROUND: Randomized trials have recently evaluated the non-inferiority of direct thrombectomy versus intravenous thrombolysis (IVT) followed by endovascular therapy in anterior circulation large vessel occlusion (LVO) stroke in patients eligible for IVT within 4.5 h from stroke onset with controversial results. We aimed to assess the effect of IVT on the clinical outcome of mechanical thrombectomy (MT) in the RESILIENT trial. METHODS: RESILIENT was a randomized, prospective, multicenter, controlled trial assessing the safety and efficacy of thrombectomy versus medical treatment alone. A total of 221 patients were enrolled. The trial showed a substantial benefit of MT when added to medical management. All eligible patients received intravenous tPA within the 4.5-h-window. Ordinal logistic and binary regression analyses using intravenous tPA as an interaction term were performed with adjustments for potential confounders, including age, baseline NIHSS score, occlusion site, and ASPECTS. A p-value <0.05 was considered statistically significant. RESULTS: Among 221 randomized patients (median NIHSS, 18 IQR [14-21]), 155 (70%) were treated with IVT. There was no difference in the mRS ordinal shift and frequency of functional independence between patients who received or not IV tPA; the odds ratio for the ordinal mRS shift was 2.63 [1.48-4.69] for the IVT group and 1.54 [0.63-3.74] for the no IVT group, with a p-value of 0.42. IVT also did not affect the frequency of good recanalization (TICI 2b or higher) and hemorrhagic transformation. CONCLUSIONS: The large effect size of MT on LVO outcomes was not significantly affected by IVT. TRIAL REGISTRATION: RESILIENT ClinicalTrials.gov number, NCT02216643.

Effects of intravenous thrombolysis on stent retriever and aspiration thrombectomy outcomes: a systematic review and meta-analysis of the randomized controlled trials.

BACKGROUND: Risks and benefits of intravenous thrombolysis (IVT) in patients undergoing mechanical thrombectomy (MT) have been a topic of interest. However, IVT's specific effects on stent retriever (SR) and aspiration thrombectomy (ASP) outcomes remain largely unexplored. In this meta-analysis, we aimed to investigate the effects of IVT on SR and ASP thrombectomy outcomes. METHODS: In accordance with PRISMA guidelines, a systematic literature review was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Center of Clinical Trials databases. Outcomes of interest included successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b), modified first pass efficacy (mFPE), functional independence (modified Rankin Scale (mRS) ≤2), symptomatic intracranial hemorrhage (sICH), and embolization to new territories (ENT). RESULTS: Four randomized controlled trials with 1176 patients were included. SR and ASP resulted in similar mTICI ≥2b, mFPE, and mRS 0-2 rates in patients with and without IVT administration. SR without IVT was associated with a significantly lower rate of mFPE compared with the SR+IVT (RR 0.85, 95% CI 0.74 to 0.97). Furthermore, ASP without IVT resulted in a lower rate of mRS 0-2 than the ASP+IVT with a strong trend towards significance (RR 0.78, 95% CI 0.60 to 1.01). Finally, bridging therapy did not increase sICH and ENT rates after ASP or SR thrombectomy. CONCLUSIONS: Our findings suggest that SR and ASP thrombectomy have comparable safety and efficacy profiles, regardless of prior IVT administration. Additionally, our results indicate that the addition of IVT may improve certain efficacy outcomes based on the employed first-line MT technique.

Safety Outcomes of Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions.

BACKGROUND: We aimed to describe the safety and efficacy of mechanical thrombectomy (MT) with or without intravenous thrombolysis (IVT) for patients with tandem lesions and whether using intraprocedural antiplatelet therapy influences MT's safety with IVT treatment. METHODS: This is a subanalysis of a pooled, multicenter cohort of patients with acute anterior circulation tandem lesions treated with MT from 16 stroke centers between January 2015 and December 2020. Primary outcomes included symptomatic intracranial hemorrhage (sICH) and parenchymal hematoma type 2. Additional outcomes included hemorrhagic transformation, successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3), complete reperfusion (modified Thrombolysis in Cerebral Infarction score 3), favorable functional outcome (90-day modified Rankin Scale score 0-2), excellent functional outcome (90-day modified Rankin Scale score 0-1), in-hospital mortality, and 90-day mortality. RESULTS: Of 691 patients, 512 were included (218 underwent IVT+MT and 294 MT alone). There was no difference in the risk of sICH (adjusted odds ratio [aOR], 1.22 [95% CI, 0.60-2.51]; P=0.583), parenchymal hematoma type 2 (aOR, 0.99 [95% CI, 0.47-2.08]; P=0.985), and hemorrhagic transformation (aOR, 0.95 [95% CI, 0.62-1.46]; P=0.817) between the IVT+MT and MT alone groups after adjusting for confounders. Administration of IVT was associated with an increased risk of sICH in patients who received intravenous antiplatelet therapy (aOR, 3.04 [95% CI, 0.99-9.37]; P=0.05). The IVT+MT group had higher odds of a 90-day modified Rankin Scale score 0 to 2 (aOR, 1.72 [95% CI, 1.01-2.91]; P=0.04). The odds of successful reperfusion, complete reperfusion, 90-day modified Rankin Scale score 0 to 1, in-hospital mortality, or 90-day mortality did not differ between the IVT+MT versus MT alone groups. CONCLUSIONS: Our study showed that the combination of IVT with MT for tandem lesions did not increase the overall risk of sICH, parenchymal hematoma type 2, or overall hemorrhagic transformation independently of the cervical revascularization technique used. However, intraprocedural intravenous antiplatelet therapy during acute stent implantation might be associated with an increased risk of sICH in patients who received IVT before MT. Importantly, IVT+MT treatment was associated with a higher rate of favorable functional outcomes at 90 days.

Association Between Intravenous Thrombolysis and Clinical Outcomes Among Patients With Ischemic Stroke and Unsuccessful Mechanical Reperfusion.

Importance: Clinical evidence of the potential treatment benefit of intravenous thrombolysis preceding unsuccessful mechanical thrombectomy (MT) is scarce. Objective: To determine whether intravenous thrombolysis (IVT) prior to unsuccessful MT improves functional outcomes in patients with acute ischemic stroke. Design, Setting, and Participants: Patients were enrolled in this retrospective cohort study from the prospective, observational, multicenter German Stroke Registry-Endovascular Treatment between May 1, 2015, and December 31, 2021. This study compared IVT plus MT vs MT alone in patients with acute ischemic stroke due to anterior circulation large-vessel occlusion in whom mechanical reperfusion was unsuccessful. Unsuccessful mechanical reperfusion was defined as failed (final modified Thrombolysis in Cerebral Infarction grade of 0 or 1) or partial (grade 2a). Patients meeting the inclusion criteria were matched by treatment group using 1:1 propensity score matching. Interventions: Mechanical thrombectomy with or without IVT. Main Outcomes and Measures: Primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2. Safety outcomes were the occurrence of symptomatic intracranial hemorrhage and death. Results: After matching, 746 patients were compared by treatment arms (median age, 78 [IQR, 68-84] years; 438 women [58.7%]). The proportion of patients who were functionally independent at 90 days was 68 of 373 (18.2%) in the IVT plus MT and 42 of 373 (11.3%) in the MT alone group (adjusted odds ratio [AOR], 2.63 [95% CI, 1.41-5.11]; P = .003). There was a shift toward better functional outcomes on the modified Rankin Scale favoring IVT plus MT (adjusted common OR, 1.98 [95% CI, 1.35-2.92]; P < .001). The treatment benefit of IVT was greater in patients with partial reperfusion compared with failed reperfusion. There was no difference in symptomatic intracranial hemorrhages between treatment groups (AOR, 0.71 [95% CI, 0.29-1.81]; P = .45), while the death rate was lower after IVT plus MT (AOR, 0.54 [95% CI, 0.34-0.86]; P = .01). Conclusions and Relevance: These findings suggest that prior IVT was safe and improved functional outcomes at 90 days. Partial reperfusion was associated with a greater treatment benefit of IVT, indicating a positive interaction between IVT and MT. These results support current guidelines that all eligible patients with stroke should receive IVT before MT and add a new perspective to the debate on noninferiority of combined stroke treatment.

Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial.

BACKGROUND: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. METHODS: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay. RESULTS: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. CONCLUSION: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors.

A computational framework for the multiphysics simulation of microbubble-mediated sonothrombolysis using a forward-viewing intravascular transducer.

Sonothrombolysis is a technique that utilises ultrasound waves to excite microbubbles surrounding a clot. Clot lysis is achieved through mechanical damage induced by acoustic cavitation and through local clot displacement induced by acoustic radiation force (ARF). Despite the potential of microbubble-mediated sonothrombolysis, the selection of the optimal ultrasound and microbubble parameters remains a challenge. Existing experimental studies are not able to provide a complete picture of how ultrasound and microbubble characteristics influence the outcome of sonothrombolysis. Likewise, computational studies have not been applied in detail in the context of sonothrombolysis. Hence, the effect of interaction between the bubble dynamics and acoustic propagation on the acoustic streaming and clot deformation remains unclear. In the present study, we report for the first time the computational framework that couples the bubble dynamic phenomena with the acoustic propagation in a bubbly medium to simulate microbubble-mediated sonothrombolysis using a forward-viewing transducer. The computational framework was used to investigate the effects of ultrasound properties (pressure and frequency) and microbubble characteristics (radius and concentration) on the outcome of sonothrombolysis. Four major findings were obtained from the simulation results: (i) ultrasound pressure plays the most dominant role over all the other parameters in affecting the bubble dynamics, acoustic attenuation, ARF, acoustic streaming, and clot displacement, (ii) smaller microbubbles could contribute to a more violent oscillation and improve the ARF simultaneously when they are stimulated at higher ultrasound pressure, (iii) higher microbubbles concentration increases the ARF, and (iv) the effect of ultrasound frequency on acoustic attenuation is dependent on the ultrasound pressure. These results may provide fundamental insight that is crucial in bringing sonothrombolysis closer to clinical implementation.

Intraarterial urokinase for thrombus migration after mechanical thrombectomy for large vessel ischemic stroke.

BACKGROUND: Achieving rapid and complete reperfusion is the ultimate purpose for ischemic stroke with large vessel occlusion (LVO). Although mechanical thrombectomy (MT) had been a proverbially important procedure, medium vessel occlusion (MeVO) with thrombus migration can sporadically occur after MT. Moreover, the safe and effective approach for such had been unknown. We reported thrombolysis with intraarterial urokinase for MeVO with thrombus migration after MT. METHODS: We included 122 patients who were treated by MT with LVO stroke at our institution between April 2019 and March 2021. Of 26 patients (21.3%) who developed MeVO with thrombus migration after MT, 11 (9.0%) underwent additional MT (MT group) and 15 (12.3%) received intraarterial urokinase (UK group). The procedure time; angiographically modified Treatment in Cerebral Ischemia Scale (mTICI); functional independence, which was defined as modified Rankin Scale 0-2, on day 30 or upon discharge; and symptomatic and asymptomatic intracerebral hemorrhage (ICH) were compared between the UK and MT groups. RESULTS: The procedure time, mTICI, and asymptomatic ICH did not significantly differ between the groups. In the UK group, 8 of 15 (53.3%) patients obtained functional independence, and the functional independence rate was significantly higher in the UK group than in the MT group (p < 0.05). Symptomatic ICH did not occur in the UK group, and its incidence was significantly smaller than that in the MT group (p < 0.05). CONCLUSION: The results of this study suggest that intraarterial urokinase for MeVO with thrombus migration after MT may safely improve angiographic reperfusion.

In a hub-and-spoke network, spoke-administered thrombolysis reduces mechanical thrombectomy procedure time and number of passes.

BACKGROUND: The utility of intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT) in large vessel occlusion stroke (LVO) is controversial. Some data suggest IVT increases MT technical difficulty. Within our hub-and-spoke telestroke network, we examined how spoke-administered IVT affected hub MT procedure time and pass number. METHODS: Patients presenting to 25 spoke hospitals who were transferred to the hub and underwent MT from 2018 to 2020 were identified from a prospectively maintained database. MT procedure time, fluoroscopy time, and pass number were obtained from operative reports. RESULTS: Of 107 patients, 48 received IVT at spokes. Baseline characteristics and NIHSS were similar. The last known well (LKW)-to-puncture time was shorter among IVT patients (4.3 ± 1.9 h vs. 10.5 ± 6.5 h, p < 0.0001). In patients that received IVT, mean MT procedure time was decreased by 18.8 min (50.5 ± 29.4 vs. 69.3 ± 46.7 min, p = 0.02) and mean fluoroscopy time was decreased by 11.3 min (21.7 ± 15.8 vs. 33.0 ± 30.9 min, p = 0.03). Furthermore, IVT-treated patients required fewer MT passes (median 1 pass [IQR 1.0, 1.80] vs. 2 passes [1.0, 2.3], p = 0.0002) and were more likely to achieve reperfusion in ≤2 passes (81.3% vs. 59.3%, p = 0.01). An increased proportion of IVT-treated patients achieved TICI 2b-3 reperfusion after MT (93.9% vs. 83.8%, p = 0.045). There were no associations between MT procedural characteristics and LKW-to-puncture time. CONCLUSION: Within our network, hub MT following spoke-administered IVT was faster, required fewer passes, and achieved improved reperfusion. This suggests spoke-administered IVT does not impair MT, but instead may enhance it.

Influence of prior intravenous thrombolysis in patients treated with mechanical thrombectomy for M2 occlusions: insight from the Endovascular Treatment in Ischemic Stroke (ETIS) registry.

BACKGROUND: Intravenous thrombolysis (IVT) for patients treated with mechanical thrombectomy (MT) for proximal occlusions has recently been questioned through randomized trials. However, few patients with M2 occlusions were included. We investigated the influence of prior IVT for patients presenting M2 occlusions treated with MT in comparison with MT alone. METHODS: We conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry, a multicenter observational study. Data from consecutive patients treated with MT for M2 occlusions between January 2015 and January 2022 at 26 comprehensive stroke centers were analyzed. The primary endpoint was 90-day modified Rankin Scale score of 0-2. Outcomes were compared using propensity score approaches. We also performed sensitivity analysis in relevant subgroups of patients. RESULTS: Among 1132 patients with M2 occlusions treated with MT, 570 received prior IVT. The two groups were comparable after propensity analysis. The rate of favorable functional outcome was significantly higher in the IVT+MT group compared with the MT alone group (59.8% vs 44.7%; adjusted OR 1.38, 95% CI 1.10 to 1.75, P=0.008). Hemorrhagic and procedural complications were similar in both groups. In sensitivity analysis excluding patients with anticoagulation treatment, favorable recanalization was more frequent in the IVT+MT group (OR 1.37, 95% CI 1.11 to 1.70, P=0.004). CONCLUSIONS: In cases of M2 occlusions, prior IVT combined with MT resulted in better functional outcome than MT alone, without increasing the rate of hemorrhagic or procedural complications. These results suggest the benefit of IVT in patients undergoing MT for M2 occlusions.

Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial.

BACKGROUND: A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. METHODS: SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. RESULTS: Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. CONCLUSION: Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT03192332.

European Stroke Organisation (ESO)-European Society for Minimally Invasive Neurological Therapy (ESMINT) expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion.

Six randomized controlled clinical trials have assessed whether mechanical thrombectomy (MT) alone is non-inferior to intravenous thrombolysis (IVT) plus MT within 4.5 hours of symptom onset in patients with anterior circulation large vessel occlusion (LVO) ischemic stroke and no contraindication to IVT. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted with the European Society of Minimally Invasive Neurological Therapy (ESMINT) according to ESO standard operating procedure based on the GRADE system. We identified two relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if insufficient evidence was available to provide recommendations based on the GRADE approach.For stroke patients with anterior circulation LVO directly admitted to a MT-capable center ('mothership') within 4.5 hours of symptom onset and eligible for both treatments, we recommend IVT plus MT over MT alone (moderate evidence, strong recommendation). MT should not prevent the initiation of IVT, nor should IVT delay MT. In stroke patients with anterior circulation LVO admitted to a center without MT facilities and eligible for IVT ≤4.5 hours and MT, we recommend IVT followed by rapid transfer to a MT capable-center ('drip-and-ship') in preference to omitting IVT (low evidence, strong recommendation). Expert consensus statements on ischemic stroke on awakening from sleep are also provided. Patients with anterior circulation LVO stroke should receive IVT in addition to MT if they have no contraindications to either treatment.

Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients.

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO+ cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.

Treatment Strategies for Proximal Deep Vein Thrombosis: A Network Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To investigate the outcomes of treatment strategies for proximal and iliofemoral deep vein thrombosis (DVT). METHODS: Randomised controlled trials (RCTs) investigating outcomes of catheter directed thrombolysis (CDT), ultrasound assisted CDT (USCDT), percutaneous aspiration thrombectomy (PAT), and best medical therapy (BMT) for proximal DVT from 2000 onwards were considered. MEDLINE, EMBASE, and CINAHL were searched using the Healthcare Databases Advanced Search interface developed by the National Institute for Health and Care Excellence. The primary outcome was the rate of post-thrombotic syndrome (PTS), which was defined using the Villalta scoring system (score of ≥5). Secondary outcomes included vessel patency, recurrence, bleeding, and mortality. The network of evidence was summarised using network plots, and random effects network meta-analyses were performed. The certainty of evidence was assessed using the Certainty In Network Meta-Analysis (CINeMA) approach. RESULTS: Seven RCTs meeting the inclusion criteria were identified. There were direct comparisons between medical therapy, CDT, and USCDT across outcomes, except for patency. There were no direct comparisons between medical therapy and PAT (except for patency), and USCDT and PAT. There was no significant difference observed in PTS between the treatment modalities for proximal and iliofemoral DVT (low certainty). There was a significant difference in patency rates between medical therapy and USCDT (odds ratio [OR] 9.46, 95% confidence interval [CI] 3.05 - 29.35; low certainty) and CDT (OR 2.03, 95% CI 1.46 - 2.80; low certainty) in favour of USCDT and CDT, respectively, for proximal DVT. USCDT significantly improved patency rates compared with CDT (OR 4.67, 95% CI 1.58 - 13.81; very low certainty) for proximal DVT. There was no significant difference in DVT recurrence, bleeding, or mortality between treatment groups for proximal and iliofemoral DVT (low to moderate certainty for most comparisons). CONCLUSION: USCDT may improve patency rates compared with BMT and the other interventional treatment modalities used for the management of proximal DVT. However, no treatment modality showed superiority with regard to a reduction in PTS, and overall, the quality of available evidence is poor.

Stent Opening Visualization During Mechanical Thrombectomy; Relationship with the Retrieved Clot and Procedural Success.

PURPOSE: The angiographic visualization of the stent during mechanical thrombectomy (MT) may provide information regarding the characteristics of the underlying occluding clot, device-clot interaction, and recanalization. The purpose of this study was to evaluate the open stent sign in relation to the retrieved clot and recanalization. METHODOLOGY: 78 patients treated with the stent retriever for acute stroke were retrospectively reviewed. The open stent sign was defined as full opening (>80% of normal vessel diameter) of the stent on DSA after deployment across the occlusion. The retrieved clot was visually classified as red or non-red clots. The relationship between the open stent sign and the patient characteristics, recanalization, retrieved clot, and clinical outcome were analyzed. RESULTS: Overall successful recanalization and good outcome was achieved in 68 (87.2%) and 35 (44.9%) patients, respectively. Open stent sign was seen in 52 patients (66.7%). Occlusions showing positive open stent sign was associated with significantly higher first pass effect (44.2% vs 19.2%, p=0.044) and successful recanalization rate (94.2% vs 73.1%, p=0.013) compared to negative open stent sign. The open stent sign was associated with higher incidence of red clot (75.0% vs 38.9%, p=0.008). On multivariate analysis, the open stent sign (OR 22.721, 95% CI 1.953-264.372, p=0.013) was a predictor of successful recanalization. CONCLUSIONS: The visualization of the open stent during MT of acute ischemic stroke may provide added information in terms of clot characteristics and procedural success. The open stent sign is associated with red clots, higher first pass effect and successful recanalization.

Cerebral blood volume Alberta Stroke Program Early Computed Tomography Score predicts intracranial hemorrhage after thrombectomy in patients with acute ischemic stroke in an extended time window.

BACKGROUND: Higher baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was associated with a lower probability of hemorrhagic transformation in patients with acute ischemic stroke (AIS). PURPOSE: To investigate the predictive value of cerebral blood volume (CBV)-ASPECTS of intracranial hemorrhage (ICH) in AIS treated with thrombectomy selected by computed tomographic perfusion (CTP) in an extended time window. MATERIAL AND METHODS: A total of 91 consecutive patients with AIS with large vessel occlusion in the anterior circulation after thrombectomy in an extended time window were enrolled between January 2018 and September 2019. ICH was diagnosed according to Heidelberg Bleeding Classification. CBV-ASPECTS was assessed by evaluating each ASPECTS region for relatively low CBV value compared with the mirror region in the contralateral hemisphere. Demographic characteristics, clinical data, CBV-ASPECTS, and procedure process and results were compared between patients with ICH and those without. RESULTS: ICH occurred in 31/91 (34.1%) patients with AIS. Symptomatic ICH (sICH) was observed in 4 (4.4%) patients, while asymptomatic ICH (aICH) was seen in 27 (29.7%). In univariate analysis, both ICH and aICH were associated with high admission NIHSS score (P<0.001 and P<0.001, respectively), more passes of retriever (P = 0.007 and P = 0.019, respectively), low NCCT-ASPECTS (P = 0.013 and P = 0.034, respectively), and low CBV-ASPECTS (P < 0.001 and P < 0.001, respectively). After multivariable analysis, low CBV-ASPECTS remained an independent predictor of ICH (odds ratio [OR] 0.521, 95% confidence interval [CI] 0.371-0.732, P < 0.001) and aICH (OR 0.532, 95% CI 0.376-0.752, P < 0.001), respectively. CONCLUSION: Low CBV-ASPECTS independently predicts ICH in patients with AIS treated with thrombectomy selected by CTP in an extended time window.

Mechanical thrombectomy of COVID-19 DVT with congenital heart disease leading to phlegmasia cerulea dolens: a case report.

BACKGROUND: COVID-19 and Fontan physiology have each been associated with an elevated risk of venous thromboembolism (VTE), however little is known about the risks and potential consequences of having both. CASE PRESENTATION: A 51 year old male with tricuspid atresia status post Fontan and extracardiac Glenn shunt, atrial flutter, and sinus sick syndrome presented with phlegmasia cerulea dolens (PCD) of the left lower extremity in spite of supratherapeutic INR in the context of symptomatic COVID-10 pneumonia. He was treated with single session, catheter directed mechanical thrombectomy that was well-tolerated. CONCLUSIONS: This report of acute PCD despite therapeutic anticoagulation with a Vitamin K antagonist, managed with emergent mechanical thrombectomy, calls to attention the importance of altered flow dynamics in COVID positive patients with Fontan circulation that may compound these independent risk factors for developing deep venous thrombosis with the potential for even higher morbidity.

Endovascular Therapy Versus Anticoagulation for Treatment of Cerebral Venous Sinus Thrombosis: A Meta-Analysis.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that mainly affects the young. Anticoagulation (AC) with heparin is the mainstay of treatment for CVST. Although highly anticipated, endovascular therapy (ET) including local thrombolysis and mechanical thrombectomy has been controversial. REVIEW SUMMARY: To compare the effectiveness and safety of ET with AC for patients with confirmed CVST, we systematically searched PubMed, Embase, and Cochrane Library from the earliest date to February 2020. Data on the total number of patients in each treatment group and the exact number of patients for each outcome were separately extracted from 10 studies with 891 patients.Our Results show that ET has a higher mortality rate compared with AC [odds ratio (OR)=1.95; 95% confidence interval (CI), 1.19-3.18; P=0.008<0.01] and has lower probability of good outcome (OR=0.48; 95% CI, 0.23-1.02; P=0.056). ET leads to a higher risk of complications than AC (OR=5.29; 95% CI, 1.17-23.95; P=0.030<0.05). No difference was found in recurrence rate between 2 treatments (OR=0.85; 95% CI, 0.31-2.35; P=0.761). CONCLUSIONS: ET is related to a higher mortality, fewer good outcome and possibly more complications compared with AC. The risks of ET should be weighed in every individualized therapeutic decision.

Effect of Intravenous Thrombolysis on Clot Survival during Mechanical Thrombectomy in Acute Large Vessel Occlusion Strokes.

BACKGROUND: The benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke is uncertain. Conventional metrics of final modified thrombolysis in cerebral ischemia (mTICI) score and 90-d modified Rankin Scale may be insensitive to IVT effects on procedural complexity and duration. OBJECTIVE: To study the effect of IVT prior to MT on clot survival. METHODS: We performed a single-center retrospective analysis of 257 acute stroke patients with LVO undergoing MT and analyzed the effect of IVT prior to MT using a novel, pass-by-pass clot survival methodology. RESULTS: The use of IVT was associated with a significantly lower number of passes to attain mTICI 2B or greater (P = .002) or mTICI 3 (P = .039) reperfusion. The number of patients who achieved mTICI 2B or greater after the first pass was significantly higher in the IVT group (P = .003). This increased rate of reperfusion persisted into subsequent passes. CONCLUSION: IVT prior to MT reduces the number of thrombectomy passes required to achieve mTICI 2B or mTICI 3 reperfusion. This information should be considered as the merits of IVT prior to MT are debated.

ADAPT First-Line Strategy for MCA Mainstem Occlusion; Analysis for Optimal Salvage Therapy and its Related Factor.

OBJECTIVES: A direct first-pass aspiration technique (ADAPT) is an attractive interventional technique for mechanical thrombectomy (MT), which could achieve recanalization quickly and safely at a small amount of material resources. To clarify its usefulness, our ADAPT first-line strategy for middle cerebral artery (MCA)-mainstem occlusion was retrospectively analyzed. MATERIALS AND METHODS: We reviewed 54 consecutive patients who underwent MT for MCA-mainstem occlusion using ADAPT first-line strategy. A salvage procedure was concurrently conducted in cases that failed to achieve successful recanalization by ADAPT attempt alone. Procedural and clinical outcome were assessed in both ADAPT alone and Salvage groups. Further investigation was performed in cases that required salvage procedure to determine the reason, risk factors, and optimal procedure. RESULTS: Forty-one patients (75.9%) were able to achieve successful recanalization with ADAPT technique alone. In salvage group, the procedural time was longer, and rates of successful recanalization were lower than in ADAPT-alone group. No significant difference in the rates of favorable outcomes was observed. Among 13 patients who required salvage therapy, the major reason (eight cases) was intra-procedural "thrombus distal migration". Failure of recanalization was seen in two cases due to "inaccessibility". In patients who had "thrombus distal migration", occlusion in the proximal portion was more frequently observed than in patients who did not (p = 0.032, 63.6% vs. 23.3%). CONCLUSIONS: Our ADAPT first-line strategy for MCA-mainstem occlusion demonstrated favorable procedural and clinical outcomes, even in cases that required additional procedures. Further investigation and better understanding are required to refine this promising procedure.

A Direct Aspiration First Pass Technique for Vertebra-Basilar Occlusion: A Retrospective Comparison to Stent Retriever.

OBJECTIVES: This study aimed to assess the clinical usefulness of a direct aspiration first pass technique as a first-line strategy for mechanical thrombectomy in posterior circulation. MATERIALS AND METHODS: We examined 34 consecutive patients treated with mechanical thrombectomy for acute vertebrobasilar artery occlusion. Procedural and clinical outcomes were assessed and compared between patients treated with a direct aspiration first pass technique first-line strategy (ADAPT group) and stent retriever system first-line strategy (stent retriever group). RESULTS: Overall, successful reperfusion, complete reperfusion, and first-pass effects were achieved in 94.1%, 61.8%, and 50% of patients with acute ischemic stroke in vertebra-basilar artery occlusion treated with mechanical thrombectomy, respectively. The ADAPT group required a significantly shorter procedural time (p=.015) and fewer attempts (p=.0498) to achieve successful recanalization than the stent retriever group. The ADAPT group also tended to show better recanalization rates and first-pass effects than the stent retriever group. The rates of favorable outcomes seemed to be better, although insignificant, in the ADAPT group than in the stent retriever group (52.2% vs. 27.3%, p=.217). However, a significant correlation between the time required for reperfusion and clinical outcome was detected, and this will serve as the rationale for encouraging a direct aspiration first pass technique as a first-line strategy in the acute vertebra-basilar artery. CONCLUSIONS: The a direct aspiration first pass technique first-line strategy for mechanical thrombectomy in posterior circulation may achieve successful recanalization with fewer attempts and shorter durations than the stent retriever first-line strategy.