Higher baseline blood glucose is associated with reduced likelihood for successful recanalization in patients with basilar artery occlusion

Purpose Evidence regarding the effect of mechanical thrombectomy (MT) of basilar artery occlusion (BAO) stroke is yet sparse. As successful recanalization has been suggested as major determinant of outcome, the early identification of modifiable factors associated with successful recanalization could be of importance to improve functional outcome. Hyperglycemia has been associated with enhanced thrombin generation and unfavorably altered clot features. Objective We hypothesized that serum baseline glucose is associated with likelihood of vessel recanalization mediated by collateral quality and clot burden in BAO stroke. Methods BAO stroke patients who received multimodal CT on admission were analyzed. The association of vessel recanalization defined using modified Thrombolysis in cerebral infarction scale (mTICI) scores 2b-3, and baseline imaging and clinical parameters were tested in logistic regression analyses. Collateral quality and clot burden were evaluated using the Basilar Artery on CT-Angiography (BATMAN) score. Results Out of 117 BAO patients, 91 patients (78%) underwent MT. In 70 patients (77%), successful recanalization could be achieved (mTICI 2b/3). In multivariable logistic regression analysis, only a higher BGL (aOR 0.97, 95% CI 0.96–0.99, p = 0.03) and higher BATMAN score (aOR 1.77, 95% CI 1.11–2.82, p = 0.02) were independently associated with vessel recanalization. Application of alteplase, or time from symptom onset-imaging revealed no independent association with recanalization status. Conclusion Higher BGL was significantly associated with reduced likelihood for recanalization success besides BATMAN score as a measure of collateral quality and clot burden. BGL could be tested as a modifiable parameter to increase likelihood for recanalization in BAO stroke, aiming to improve functional outcome.

Fibrinolytic Dysregulation Contributes to the Hypercoagulable State in Pulmonary Embolism Patients

Introduction: The multifactorial and complex pathophysiology of pulmonary embolism (PE) involves dysregulation of hemostatic system including fibrinolytic imbalance, endothelial compromise and generation of thrombotic mediators, along with cellular defects and hemodynamic derangement. It is estimated that 6000 cases of pulmonary embolism and DVT are reported yearly of which 1000 result in death. PE evolves from a pre-existing venous thrombus, obstructing pulmonary artery leading to pulmonary failure. The progression of clot formation results in increase in right ventricular pressure, systemic hypoperfusion, hypoxemia ischemia and eventually multi organ failure. Fibrinolytic dysregulation and generation of procoagulant mediators result in increased clot burden and lead to adverse outcomes. Profiling of the component of the fibrinolytic system for such mediators as the activators and inhibitors of fibrinolysis, vWF and cellular microparticles may provide additional insights into the pathogenesis of PE. The purpose of this study is to profile plasma samples from PE patients for various mediators of hemostatic dysregulation which contribute to the fibrinolytic dysregulation in PE patients. Material & Method: Seventy-eight patients of 18 years or older age, were included in this study through enrolment conducted in conjunction with an ongoing IRB approved project by the pulmonary embolism response team (PERT) registry. Diagnosis of PE was confirmed by computed tomography (CT), angiography or ventilation perfusion imaging. Blood samples were drawn with in 24 hours of confirmed diagnosis of acute PE in 3.2% sodium citrate tubes at the time of diagnosis, processed for platelet poor plasma and frozen. Control plasma samples were obtained from 50 healthy individuals. Both the patient and control plasma samples were analyzed for D-Dimer, PAI-1 antigen, tPA, TAFI-a, protein C, alpha-2 antiplasmin, microparticles and vWF using ELISA methods (Hypen Biomedical, Franklin, Ohio). A functional PAI-1 chromogenic substrate method and an ELISA based uPA antigen method was used (Biomedica, Halifax, Nova Scotia, Canada). Circulating levels of each of the individual biomarkers were compared to normal plasma, descriptive statistics including non-parametric Mann-Whitney t-test and spearman correlation coefficient analysis was carried out by using GraphPad Prism software. Percent Increase from the normal mean was calculated for each individual parameter. p value <0.05 was considered statistically significant. Result: In comparison to normal group, the PE patients exhibited varying levels of increase in the D-Dimer, tPA, uPA, PAI-1 antigen, PAI-1 functional, TAFI antigen, microparticles and vWF, whereas decreased levels were noted for protein C and alpha-2 antiplasmin as shown on Figure 1. D-Dimer showed the most pronounced increase (368.2-fold) followed by tPA (165.9-fold), PAI-1 antigen (3.91-fold), microparticles (2.14-fold), vWF (1.83-fold), uPA (0.5-fold), TAFI antigen (0.40-fold) and PAI-1 functional (0.34-fold). In correlation analysis, D-Dimer negatively correlated with TAFI antigen (r= -0.3106) and alpha-2 antiplasmin (r= -0.3056), functional PAI-1 levels positively correlated with tPA (r= 0.3117) and protein C (r= 0.4059), tPA negatively correlated with TAFI antigen (r= -0.4601), alpha-2 antiplasmin (r= -0.2460) and positively correlated with microparticles (r= 0.2456) , TAFI antigen positively correlated with protein C (r= 0.3612), alpha-2 antiplasmin (r= 0.3899) and negatively correlated with microparticles (r= -0.2470) whereas protein C showed a negative correlation with vWF (r= -0.2838). Conclusion: The markedly increased D-Dimer levels suggest increase clot burden in PE patients. tPA antigen is also markedly increased, whereas the uPA showed modest increase which may suggest compensatory upregulation, PAI-1 antigen levels were much higher in comparison to PAI-1 functional activity, suggesting consumption of this inhibitor. Decreased alpha-2 antiplasmin and protein C levels also suggest consumption. Increased TAFI antigen contribute to the clot resistant to fibrinolysis. Cellular consumption and endothelial dysfunction results in increased in vWF and microparticles promoting thrombogenesis. Measurement of these biomarkers may be useful in the understanding of the pathogenesis, risk stratification and clinical management of PE patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Prediction of persistent ventricular dilation by initial ventriculomegaly and clot volume in a porcine model

OBJECTIVE While intraventricular hemorrhage (IVH) is associated with posthemorrhagic ventricular dilation (PHVD), not all infants affected by high-grade IVH develop PHVD. The authors aimed to determine clot-associated predictors of PHVD in a porcine model by varying the amount and rate of direct intraventricular injection of whole autologous blood. METHODS Seven 1-week-old piglets underwent craniectomy and injection of autologous blood into the right lateral ventricle. They survived for a maximum of 28 days. MRI was performed prior to injection, immediately postoperatively, and every 7 days thereafter. T1-weighted, T2-weighted, and susceptibility-weighted imaging (SWI) sequences were used to segment ventricular and clot volumes. Spearman correlations were used to determine the relationship between blood and clot volumes and ventricular volumes over time. RESULTS The maximum ventricular volume was up to 12 times that of baseline. One animal developed acute hydrocephalus on day 4. All other animals survived until planned endpoints. The interaction between volume of blood injected and duration of injection was significantly associated with clot volume on the postoperative scan (p = 0.003) but not the amount of blood injected alone (p = 0.38). Initial postoperative and day 7 clot volumes, but not volume of blood injected, were correlated with maximum (p = 0.007 and 0.014) and terminal (p = 0.014 and 0.036) ventricular volumes. Initial postoperative ventricular volume was correlated with maximum and terminal ventricular volume (p = 0.007 and p = 0.014). CONCLUSIONS Initial postoperative, maximum, and terminal ventricular dilations were associated with the amount of clot formed, rather than the amount of blood injected. This supports the hypothesis that PHVD is determined by clot burden rather than the presence of blood products and allows further testing of early clot lysis to minimize PHVD risk.

Abstract 1122‐000212: INARI FlowTriever system: First Endovascular Clinical Experience to Treat Diffuse Cerebral Venous Sinus Thrombosis

Introduction : Cerebral Venous Sinus Thrombosis (CVST) is a rare stroke with a wide range of symptomatology at presentation ranging from headache, focal weakness, and coma. Anticoagulation remains the mainstay of treatment. However, in a subset of patients endovascular treatment can be potentially beneficial. Here we describe the first clinical experience using the INARI FlowTriever system to treat a patient presented with focal weakness and found to have diffuse cerebral venous sinus thrombosis. Methods : Case report of CSVT treated with INARI FlowTriever system. Results : A 78‐year‐old female with past medical history of Autoimmune hepatitis and hypothyroidism, was brought to the hospital with left arm weakness. CT head revealed left temporoparietal intraparenchymal hemorrhage and right frontal subarachnoid hemorrhage. CTA of the head and neck revealed extensive CVST involving superior sagittal sinus, bilateral transverse and sigmoid sinuses. She was started on heparin drip. Patient was taken for venous thrombectomy due to persistent left‐sided weakness and multicompartment bleeding while being on anticoagulation for 48 hours. She underwent successful endovascular venous thrombectomy using the INARI FlowTriever system with large clot burden extracted. She was switched to novel oral anticoagulation prior to discharge. During the 3 months follow‐up–MRI brain with and without contrast revealed near complete resolution of the clot burden in the superior sagittal sinus and left transverse/sigmoid complex and her modified Rankin score was at 0. Conclusions : Here we discussed a case of diffuse CVST who was treated initially with heparin drip then underwent endovascular venous thrombectomy using INARI FlowTriever system with large clot burden aspirated with a reasonable safety profile. The INARI medical FlowTriever system is the only mechanical thrombectomy system indicated for the treatment of pulmonary embolism. It is specifically designed for venous clots. It is composed of a trackable large bore aspiration catheter. The INARI FlowTriever Catheter; has 3 expanding nitinol mesh disks; designed to engage and disrupt venous clots and subsequently deliver it to the large bore aspiration catheter. Its larger size makes it an attractive candidate for venous sinus clot retrieval. This study illustrates the first clinical use of INARI thrombectomy device in CVST with a reasonable safety profile. Anticoagulation is the mainstay first line treatment for CVST. However, a small subset of patients would potentially benefit from endovascular treatment but it still uncertain how to select these patients and what is the best timeline to offer early endovascular treatment. Various neuro endovascular techniques has been attempted to treat cerebral venous sinus thrombosis. However; it is unclear which approach and device provides the optimal restoration of venous blood flow. Current neuro endovascular techniques and devices are not particularly designed for CVST pathology treatment and there is need for further innovation and new devices.

Abstract 1122‐000168: Hyperacute Stenting and Angioplasty for Isolated Non‐tandem Cervical ICA Strokes within the First 48 Hours

Introduction : Acute stroke that involves complete and isolated occlusion of extracranial cervical ICA segment with no intracranial clot burden account for a minority of stroke cases. Since endarterectomy is not recommended in the hyperacute phase (first 48 hours), management of these strokes includes administration of IV‐tPA as part of standard medical therapy. This makes endovascular intervention with acute carotid artery stenting (CAS) with or without balloon angioplasty a viable treatment option during the hyperacute phase of the disease. We aim to present our two‐decade long experience of endovascular management of complete and isolated cervical ICA occlusive strokes in the hyperacute phase, and attempt to evaluate the clinical efficacy and safety of this treatment modality. Methods : A prospectively maintained database was retrospectively searched for patients who presented from Jan 2000 – Dec 2020 with acute cervical ICA stroke confirmed on angiography. Only patients who had 100% occlusion of cervical ICA segment and who underwent acute CAS within the first 48 hours of symptom onset were included. Patients who had an intracranial or tandem lesion or those with <100% EC‐ICA stenosis were excluded. Information on demographics, co‐morbidities, procedural details, and complications was recorded. Rate of adequate revascularization and follow up were also recorded. Results : A total of 46 patients with acute cervical ICA occlusive stroke were included in the study. Mean age was 68.9 years, and 32 (69.6%) were male. Median NIH Stroke Scale at admission was 8 (IQR 7) with a perfusion deficit seen in 78.3% of cases. IV‐tPA was administered in 41.3% of cases with median time from symptom onset to puncture 14.4 hours. Stenting was performed in all patients with pre‐ and/or post‐angioplasty done in 78.3% of cases. Successful recanalization was achieved in 82.6% cases. One patient (2.2%) suffered a symptomatic intracerebral hemorrhage (sICH) post‐procedure. Outcome measures were reported as stable or improved NIHSS at discharge in 86.9% of cases, with good outcome (functional independence at 90‐day‐mRS <2) at 78.3% and a mortality rate of 6.5%. Conclusions : Emergent stenting and angioplasty for acute cervical ICA occlusive strokes within the first 48 hours (hyperacute phase) can be performed successfully with good clinical outcomes and an impressive rate of recanalization.

Mechanical Thrombectomy in Acute Terminal Internal Carotid Artery Occlusions Using a Large Manually Expandable Stentretriever (Tiger XL Device): Multicenter Initial Experience

Background: The recently introduced Tigertriever XL Device for treatment of cerebral vessel occlusions combines manual adjustability and maximum length in one device. In this study, we report our initial experience with the Tigertriever XL in terminal ICA occlusions. Methods: Retrospective multicenter analysis of acute terminal ICA occlusions treated by mechanical thrombectomy using the Tigertriever XL Device. Results: 23 patients were treated using the Tigetriever XL due to an acute occlusion of the terminal ICA. The overall successful reperfusion rate after a median of two maneuvers using the Tigertriever XL Device was 78.3% (mTICI 2b-3). In 43.5% (10/23) additional smaller devices were applied to treat remaining occlusions in downstream territories, which resulted in a final successful reperfusion rate of 95.7%. Device related complications did not occur. Two symptomatic intracerebral hemorrhages (sICH) were observed. Conclusions: The Tigertriever XL Device might be a helpful tool in the treatment of ICA terminus occlusions with large clot burden resulting in high reperfusion rates. This is mainly related to the manual adjustability of the device combined with the maximum length.

Practical use and underlying physics of the BENCHMARK™ BMX™ 96 for large-bore aspiration thrombectomy: Case report of initial institutional experience

Endovascular thrombectomy (EVT) is part of first-line intervention for acute ischemic stroke management. Recent technological advances have demonstrated that large-bore catheters are an attractive approach for EVT. A multitude of approaches such as A Direct Aspiration first Pass Technique (ADAPT) or in conjunction with stent retrieval (Solumbra technique) have been developed with increasingly large-bore catheters, demonstrating safety and efficacy. Furthermore, these techniques have demonstrated promise for the intervention of cerebral venous thrombosis as well as posterior circulation ischemic events. Recently, advances in neurointerventional catheters have focused on improved maneuverability to navigate the neurovasculature, as well as larger inner diameters for improved procedural versatility, including aspiration. We describe a case report highlighting our early institutional experience with the recently developed large-bore catheter, the BENCHMARK™ BMX™ 96. The case report entails near complete occlusion of the internal carotid artery from acute thrombus and the utility of the BMX™ 96 catheter for treatment of such extensive clot burden. The applicability of large-bore aspiration catheters, with an emphasis on recent advances, for mechanical thrombectomy in arterial as well as venous systems is discussed. To our knowledge, this is the first reported case of use of the BENCHMARK™ BMX™ 96 access system for EVT in acute ischemic stroke. Such new-generation large-bore catheters are a promising advance in neurointervention, and our early institution experience highlights the ease of use and versatility for neurointerventional procedures such as EVT.

Decreased clot burden is associated with factor XIII Val34Leu polymorphism and better functional outcomes in acute ischemic stroke patients treated with intravenous thrombolysis

Background Intravenous thrombolysis using recombinant tissue plasminogen activator remains the mainstay treatment of acute ischemic stroke (AIS), although endovascular treatment is becoming standard of care in case of large vessel occlusions (LVO). To quantify the thrombus burden in LVO, a semiquantitative CT angiography (CTA) grading system, the clot burden score (CBS) can be used. Here we aimed to study the association between CBS and various hemostasis parameters, and to evaluate which parameters are major determinants of thrombolysis outcome. Methods In this single-centered prospective observational case-control study, 200 anterior circulation AIS patients receiving intravenous thrombolysis treatment without thrombectomy were enrolled: 100 AIS patients with LVO (CBS 0–9) and 100 age- and sex-matched AIS patients without LVO (CBS 10). Fibrinogen, α2-plasmin inhibitor, plasminogen, factor XIII and D-dimer were assessed from blood samples taken before and 24 h after thrombolysis, and FXIII-A Val34Leu was genotyped. CBS was calculated using admission CTA. Short-term outcomes were defined based on the change in NIHSS by day 7, long-term outcomes were assessed according to the modified Rankin scale at 3 months post-event. Results Poor outcomes were significantly more frequent in the CBS 0–9 group. Plasminogen activity on admission was significantly higher in the CBS 0–9 group. In a univariate analysis, significant protective effect of the Leu34 allele against developing larger clots (CBS 0–9) could be demonstrated (OR:0.519; 95%CI:0.298–0.922, p = 0.0227). Multivariate regression analysis revealed that CBS is an independent predictor of short- and long-term functional outcomes, while such effect of the studied hemostasis parameters could not be demonstrated. Conclusions CBS was found to be a significant independent predictor of thrombolysis outcomes. FXIII-A Leu34 carrier status was associated with smaller thrombus burden, which is consistent with the in vitro described whole blood clot mass reducing effects of the allele, but the polymorphism had no effect on thrombolysis outcomes.