Second-generation Stent Retriever Research Articles

Mechanical thrombectomy and intravascular imaging for cerebral venous sinus thrombosis: a preclinical model.

Although the majority of patients with cerebral venous sinus thrombosis (CVST) will improve with anticoagulation therapy, a portion of patients will either present in a comatose state or continue to deteriorate clinically despite early anticoagulation. In these cases, along with treating the underlying thrombophilia, timely thrombolysis may be beneficial. Repurposed arterial thrombectomy devices may not perform as expected in the cerebral venous sinus, and there are currently no preclinical endovascular thrombectomy (EVT) models for CVST. Contrary to arterial stroke research, preclinical models utilized to test various endovascular techniques and devices are lacking. The purpose of this research was to develop a reliable preclinical animal model for the testing of endovascular strategies to treat CVST. Five consecutive male Yorkshire swine weighing 45 kg were utilized. Thrombosis of the superior sagittal sinus was induced with a bovine thrombin injection via a microcatheter under distal balloon occlusion for 15 minutes. Combined arterial injections and superselective sinus injections confirmed the extent of thrombosis. EVT was subsequently performed using a second-generation stent retriever, followed by intravascular optical coherence tomography (OCT) imaging to assess the luminal environment after thrombectomy. Thrombosis of the superior sagittal sinus, EVT, and subsequent OCT imaging were technically successful in 4 of the 5 swine. Recanalization of the sinus with a second-generation stent retriever was successful after one attempt in 3 of 4 swine (75%), and 1 swine required two attempts. OCT imaging after thrombectomy revealed regions of residual sinus luminal thrombus despite complete angiographic recanalization. Thrombosed bridging cortical veins were also observed before draining into the sinus, along with patent cortical veins. The authors describe a preclinical model to assess endovascular techniques and devices for the treatment of CVST. Repurposed devices from arterial stroke may not perform as expected, given the unique features of venous sinus thrombosis. Residual bridging cortical vein thrombus and residual sinus thrombus, visualized on intravascular OCT, may be present despite complete sinus recanalization on angiography, and this may be the etiology of the poor clinical outcome despite technical success. In the setting of bridging cortical vein thrombus after successful sinus thrombectomy, direct chemical thrombolysis may be warranted to dissolve the remaining clot. This model may be helpful in developing and testing a new generation of devices designed specifically for CVST treatment.

Endovascular Treatment of Acute Ischemic Stroke.

This article reviews the actual indications for mechanical thrombectomy in patients with acute ischemic stroke and how the opportunities for endovascular therapy can be expanded by using the concept of clinical-imaging or perfusion-imaging mismatch (as a surrogate for salvageable tissue) rather than time of ischemia. Six randomized controlled trials undoubtedly confirmed the benefits of using endovascular thrombectomy on the clinical outcome of patients with stroke with large vessel occlusion within 6 hours from symptom onset compared with those receiving only standard medical care. In a meta-analysis of individual patient data, the number needed to treat with endovascular thrombectomy to reduce disability by at least one level on the modified Rankin Scale for one patient was 2.6. Recently, the concept of "tissue window" versus time window has proved useful for selecting patients for mechanical thrombectomy up to 24 hours from symptom onset. The DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention) trial included patients at a median of 12.5 hours from onset and showed the largest effect in functional outcome ever described in any acute stroke treatment trial (35.5% increase in functional independence). In DEFUSE 3 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 3), patients treated with mechanical thrombectomy at a median of 11 hours after onset had a 28% increase in functional independence and an additional 20% absolute reduction in death or severe disability. For patients with acute ischemic stroke and a large vessel occlusion in the proximal anterior circulation who can be treated within 6 hours of stroke symptom onset, mechanical thrombectomy with a second-generation stent retriever or a catheter aspiration device should be indicated regardless of whether the patient received treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA) in patients with limited signs of early ischemic changes on neuroimaging. Two clinical trials completely disrupted the time window concept in acute ischemic stroke, showing excellent clinical outcomes in patients treated up to 24 hours from symptom onset. Time of ischemia is, on average, a good biomarker for tissue viability; however, the window of opportunity for treatment varies across different individuals because of a range of compensatory mechanisms. Adjusting time to the adequacy of collateral flow leads to the concept of tissue window, a paradigm shift in stroke reperfusion therapy.

Outcomes of Endovascular Thrombectomy for Basilar Artery Occlusion.

Large prospective observational studies have cast doubt on the common assumption that endovascular thrombectomy (EVT) is superior to intravenous thrombolysis for patients with acute basilar artery occlusion (BAO). The purpose of this study was to retrospectively review our experience for patients with BAO undergoing EVT with modern endovascular devices. All consecutive patients undergoing EVT with either a second-generation stent retriever or direct aspiration thrombectomy for BAO at our regional stroke center from January 1, 2013 to March 1, 2019 were included. The primary outcome measure was functional outcome at 1 month using the modified Rankin Scale (mRS) score. Multivariable logistic regression was used to assess the association between patient characteristics and dichotomized mRS. A total of 43 consecutive patients underwent EVT for BAO. The average age was 67 years with 61% male patients. Overall, 37% (16/43) of patients achieved good functional outcome. Successful reperfusion was achieved in 72% (31/43) of cases. The median (interquartile range) stroke onset to treatment time was 420 (270-639) minutes (7 hours) for all patients. The procedure-related complication rate was 9% (4/43). On multivariate analysis, posterior circulation Alberta stroke program early computed tomography score and Basilar Artery on Computed Tomography Angiography score were associated with improved functional outcome. EVT appears to be safe and feasible in patients with BAO. Our finding that time to treatment and successful reperfusion were not associated with improved outcome is likely due to including patients with established infarcts. Given the variability of collaterals in the posterior circulation, the paradigm of utilizing a tissue window may assist in patient selection for EVT. Magnetic resonance imaging may be a reasonable option to determine the extent of ischemia in certain situations.

Optical coherence tomography imaging after endovascular thrombectomy: a novel method for evaluating vascular injury in a swine model.

Although studies have shown that some degree of iatrogenic endothelial injury occurs during endovascular thrombectomy (EVT), the clinical significance of such injury is uncertain. Furthermore, it is likely that iatrogenic effects such as endothelial denudation, intimal dissection, and tunica media edema will have varying clinical implications. The purpose of this study was to assess the feasibility of endovascular optical coherence tomography (OCT) in quantifying vessel injury in real time after EVT, correlate vessel injury with histological findings, and perform imaging at varying time intervals after EVT to assess the impact of prolonged direct exposure of the vessel to the thrombus. Yorkshire swine weighing 35-40 kg were selected for use as the animal model, with a total of 9 vessels from 3 swine examined. Thrombectomy was performed using a second-generation stent retriever 1, 3, and 6 hours after thrombus deposition. The presence and degree of denudation of the endothelium, detachment and separation of the layers of the tunic media, hemorrhage within the media, dissection of the vessels, and thrombus within the lumina were assessed using OCT images acquired immediately after EVT. Bland-Altman analysis indicated that these OCT findings were correlated with postmortem histological findings. OCT image acquisition was technically successful in all cases. Endothelial denudation was present in 65% ± 16%, 87% ± 8%, and 93% ± 7% of the vessel surface 1, 3, and 6 hours, respectively, after thrombus deposition and subsequent EVT. Residual intraluminal thrombus was present in vessels at all time intervals despite complete angiographic revascularization. Bland-Altman plots showed good agreement between OCT and histological analysis with respect to the degree of endothelial denudation and elevation, separation of the tunica media, and hemorrhage within the media. OCT appears to be more specific than histological analysis in detecting endothelial elevation. OCT is a feasible method that can be used to assess vascular injury after EVT with histological accuracy. Varying degrees of vessel injury occur after EVT, and residual luminal thrombus can be present despite complete angiographic revascularization.

Abstract 1: Optical Coherence Tomography Imaging in Acute Ischemic Stroke: Preliminary Animal and Human Results

Background: Studies evaluating endothelial injury after EVT have been done by means of retrieved human thrombus, MR vessel-wall imaging, and animal histopathologic studies. These techniques have limitations, as MR imaging has insufficient spatial resolution to directly visualize endothelium, and histopathologic examinations are ex-vivo and unable to provide real-time patterns of injury. Objective: Endovascular imaging after EVT using optical coherence tomography (OCT) to examine for vessel injury in real-time. Methodology: Three swine weighing 35-40kg were selected for the animal model. Autologous venous whole-blood was used to create thrombus. A second-generation stent retriever was used for EVT. Next, three consecutive patients with basilar artery occlusion underwent EVT and endovascular OCT imaging. Results: In the animal model, revascularization and OCT imaging was successful for all 9 vessels. Endothelial injury was observed in 4/9 (44%) of vessels, and residual thrombus was observed in 4/9 (44%) of vessels despite complete angiographic revascularization. All vessels undergoing EVT after 6 hours had evidence of endothelial injury, and 2/3 (66%) had residual thrombus. Two basilar stroke patients (2/3) 66% had significant residual thrombus despite complete angiographic revascularization. The residual thrombus was also not visible on CT angiography or MR imaging done within 24 hours of EVT. Conclusions: Endothelial injury and residual thrombus despite complete revascularization is present after EVT and can be observed in real-time using OCT. It is possible that the longer occlusive thrombus is present, the more endothelial injury will occur during EVT.

Noninferiority Margins in Trials of Thrombectomy Devices for Acute Ischemic Stroke: Is the Bar Being Set Too Low?

Background and Purpose- Novel endovascular thrombectomy (EVT) devices for acute ischemic stroke are often cleared by regulatory agencies on the basis of noninferiority trials. The relation between the noninferiority margins used in trials and the minimal clinically important differences (MCIDs) determined by experts have not been systematically investigated. Methods- Systematic searches were performed to identify (1) all noninferiority design or noninferiority-presented stroke-EVT trials for acute ischemic stroke, (2) all studies determining the MCIDs for the same outcomes, and (3) all noninferiority coronary revascularization trials. Stroke-EVT trial results were reanalyzed using the broad noninferiority margins originally used and narrower noninferiority margins derived from formal MCID studies. Results- We identified 7 noninferiority-designed or noninferiority-interpreted stroke-EVT controlled trials, enrolling 1766 patients, variously comparing coil retrievers, first- and second-generation stent retrievers, and aspiration devices. In 6 trials, the primary outcome was achievement of reperfusion, using noninferiority margins of 15% (3 trials), 10% (2 trials), and 8% (1 trial). In contrast, a stroke expert survey identified the MCID for reperfusion as 3.1% to 5%, and cardiac trials used noninferiority margins of 3.5% to 4.4%. In one stroke-EVT trial, the primary outcome was functional independence, using a noninferiority margin of 15%. However, 2 stroke expert survey studies identified MCIDs for functional independence as having lower values, 5% and 1% to 1.5%. For both reperfusion and functional independence outcomes, all 7 trials demonstrated noninferiority with the broadest noninferiority margin, but only 4 and 3 trials demonstrated noninferiority with actual expert-derived margins for reperfusion and functional independence, respectively. Conclusions- Noninferiority margins used in EVT device trials have regularly exceeded the MCIDs determined by stroke experts, as well as margins used for cardiac devices. New approaches, such as the use of reasonably adequate performance margins, rather than noninferiority margins, are needed to optimize stroke-EVT trial design integrity and trial performance feasibility.

Optical Coherence Tomography Imaging in Acute Ischemic Stroke: Preliminary Animal and Human Results

Abstract INTRODUCTION Studies evaluating endothelial injury after endovascular thrombectomy (EVT) have been done by means of retrieved human thrombus, magnetic resonance (MR) vessel-wall imaging, and animal histopathologic studies. These techniques have limitations, as MR imaging has insufficient spatial resolution to directly visualize endothelium, and histopathologic examinations are ex vivo and unable to provide real-time patterns of injury. The aim of the current study is intraluminal imaging after EVT using optical coherence tomography (OCT). We describe our animal model for thrombus preparation, vessel occlusion, mechanical thrombectomy, and subsequent endovascular OCT imaging. Furthermore, we describe the first human endovascular OCT imaging after EVT in 2 stroke patients. METHODS A total of 3 swine weighing 35 to 40 kg were selected for the animal model. Autologous venous whole blood drawn 48 h before the procedure was used to create thrombus. The bilateral superficial cervical arteries and right internal thoracic artery were used for occlusion given their diameters of 2 to 3 mm and 3 to 4 mm, respectively. A second-generation stent retriever was used for EVT. Thrombi were retrieved after 1, 3, and 6 h with subsequent intraluminal OCT imaging. Next, 2 consecutive patients with basilar artery occlusion underwent EVT and endovascular OCT imaging. RESULTS In the animal model, revascularization and OCT imaging was successful for all 9 vessels. Endothelial injury was observed in 4/9 (44%) of vessels, and residual thrombus was observed in 4/9 (44%) of vessels despite complete revascularization. All vessels undergoing EVT after 6 h had evidence of endothelial injury, and 2/3 (66%) had residual thrombus. Both basilar stroke patients had significant residual thrombus despite complete angiographic revascularization. CONCLUSION Endothelial injury and residual thrombus despite complete revascularization is present after EVT and can be observed in real time using intravascular OCT. It is possible that the longer occlusive thrombus is present, the more endothelial injury will occur during EVT.

Long-term outcomes of acute ischemic stroke patients treated with endovascular thrombectomy: A real-world experience

Background and purposeLong-term follow-up of large trials have confirmed the superiority of endovascular thrombectomy (ET) for treating acute ischemic stroke (AIS). However, it is still unknown whether these results can be generalized to clinical practice. In this study, we aimed to determine the long-term outcomes of AIS post-ET in the real-world clinical practice. MethodsThis observational study is based on a single-center prospective registry study. AIS patients were treated with second-generation stent retrievers from December 2012 to April 2016. The primary outcome was modified Ranks scale (mRS) at the time of the latest assessment. Favorable outcome was defined as mRS scores 0–2, and the unfavorable outcome was defined as mRS scores 3–6. ResultsEighty-nine AIS subjects with large artery occlusion in anterior circulation undergoing ET were eligible for analysis. Median follow-up duration was 20 months (interquartile range 6–32), and 47 subjects (53%) achieved favorable outcome whereas 17 subjects (19%) were functional dependence and 25 subjects (28%) died. Independent predicators for long-term unfavorable outcome were higher baseline National Institutes of Health Stroke Scale (NIHSS) score (odd ratio:1.21;95% confidence interval 1.09–1.35; p < 0.001) and symptomatic intracerebral hemorrhage (sICH) (odd ratio:16.45;95% confidence interval 1.34–193.44; p = 0.026). More subjects of large-artery-atherosclerosis underwent permanent intracranial stenting (22%vs.10%) as compared with those of cardioembolism, while subjects of cardioembolism were more likely to experience sICH (13%vs.8%) and died (32%vs.16%). ConclusionsOver half of AIS patients can achieve favorable long-term outcomes post-ET. Higher baseline NIHSS scores and sICH are independently associated with unfavorable outcome. Overall, clinical practice in this single canter can replicate the long-term outcomes from the published endovascular clinical trials.

Abstract TP35: Asymptomatic Hemorrhagic Transformation in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy is Associated With Poor Outcome

Introduction: Asymptomatic hemorrhagic transformation (AHT) is a common complication in acute ischemic stroke (AIS) patients treated with endovascular therapy. However, whether AHT has impact on the functional outcome of this patient’s populations is unclear, especially in patients treated with endovascular thrombectomy (ET). In this study, we aim to evaluate the influence of AHT on the functional outcome of AIS patients treated with ET. Methods: This observational study based on a prospective registry study. AIS patients with anterior circulation large artery occlusion and underwent ET with second-generation stent retrievers (i.e., Solitaire FR and Trevo) were recruited. AHT was diagnosed by CT according to the Heidelberg Bleeding Clarification. Head CT was performed 12-24 hours and 5-7 days post-treatment. The primary outcome was functional outcome at 3 months post-treatment assessed by modified Rankin Scale (mRS). Results: One hundred and two consecutive AIS patients (aged 61.1 years old) were recruited. 39 patients (38.2%) had AHT on post-treatment CT. Patients with AHT were more likely to receive post-procedures sedation (69.2% vs. 23.8%, p &lt;0.001). Less patients with AHT achieved favorable outcome (mRS&lt;3) at 3 months follow up (35.9% vs. 61.9%, p =0.011). Compared with 7 of 63 subjects (11.1%) died in no AHT group, 14 of 39 subjects (35.9%) died in AHT group, which was significantly higher ( p =0.003). The median length of follow-up was 19 (IQR 3.5-32) months. In long-term follow up, less patients with AHT achieved favorable outcome (30.8% vs. 66.7%, p &lt;0.001). 15 of 26 subjects (57.7%) died in AHT group, as compared with 8 of 50 subjects (16.0%) died in no AHT group, which was significant higher ( p &lt;0.001). On multivariate analysis, AHT was an independent predictor for both short- and long-term functional outcome and mortality. Conclusions: In AIS patients undergoing ET with second-generation stent retrievers, AHT is associated with increased risk of poor outcome.

Low-Dose Tirofiban Improves Functional Outcome in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy.

Chinese patients largely experience acute ischemic stroke (AIS) because of large artery atherosclerosis rather than cardioembolism, and whether tirofiban is safe and effective in these patients treated with endovascular thrombectomy (ET) is unknown. This study evaluated the safety and efficacy of tirofiban in Chinese patients with AIS treated with ET. This observational study is based on a single-center prospective registry study. Patients with AIS undergoing ET with second-generation stent retrievers from January 2013 to February 2017 were treated with ET alone or ET plus low dose of tirofiban. The primary outcome was symptomatic intracerebral hemorrhage (sICH). The secondary outcomes included rate of early reocclusion, any ICH, fatal ICH, and 3-month and long-term functional outcomes. One hundred eighty AIS subjects were included in the analysis, including 90 subjects treated with tirofiban and 90 subjects without tirofiban. Sixty-three subjects (35%) had any ICH, 19 of them (11%) were sICH, and 9 of them (5%) were fatal ICH. Ten subjects (11%) treated with tirofiban experienced sICH and 9 subjects (10%) not given tirofiban experienced sICH, not a significant difference (P=0.808). Early reocclusion happened in 4 of 90 subjects (4.4%) treated with tirofiban and 8 of 90 subjects (8.9%) not treated with tirofiban (P=0.370). One hundred sixty-one subjects (89%) completed long-term follow-up, subjects treated tirofiban were associated with lower odds of death (23% versus 44%, P=0.005) when compared with those who were not treated. Additionally, tirofiban was associated with better odds of long-term functional independence (adjusted odds ratio, 4.37; 95% confidence interval, 1.13-16.97; P=0.033). In patients with AIS undergoing ET, tirofiban is not associated with higher sICH, it seems to lead to lower odds of deaths and better odds of long-term functional independence. Further investigations are needed to determine the efficacy of tirofiban in preventing early reocclusion, the underlying mechanisms, and its optimal treatment protocol.