"Missing clot" during mechanical thrombectomy in acute stroke using Solitaire stent retrieval system.

Section Editors: Marc Fisher MD Antoni Davalos MD The Food and Drug Administration (FDA) evaluates applications for new human drugs, biologics, and complex medical devices. Companies must obtain FDA approval to legally market these products. In August, the FDA gave Concentric Medical clearance to market its Merci Retriever system to “remove blood clots from the brain in patients experiencing an ischemic stroke.” Given that the FDA is charged with “protecting the public health by assuring the safety, efficacy, and security of… biological products and medical devices…, ” “advancing public health by helping to speed innovations that make medicines … more effective, safer, and more affordable,” and “helping the public get the accurate, science-based information they need to use medicines … to improve their health,”1 the FDA’s decision to approve the Merci Retriever system is of concern. The pathways to approval are reviewed by Felten et al in the accompanying article and are outlined in Figure 1. Figure 1. Potential pathways for device approval. The decision to approve the Merci Retriever was based on data from the MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Trial; the approval was granted through the 510(k) process. The Merci Retriever system includes a flexible nickel titanium (nitinol) wire that obtains a helical shape once it is passed through the tip of the guidance catheter. In practice, the catheter/wire is passed distal to the thrombus, the catheter is removed, and the helical configuration assumed by the wire; the clot is then trapped in the helix and withdrawn from the vasculature (Figure 2). The 510(k) clearance means that the Merci Retriever was felt to be substantially equivalent to a predicate device. In this case, the predicate device was the Concentric Retriever, which itself received 510(k) clearance by the FDA in May 2001 for “use in …

Retrievable stent thrombectomy in acute ischemic stroke: Is it beneficial in the elderly?

The best approach between general anesthesia and conscious sedation to perform mechanical thrombectomy remains unknown. The goal of our study was to evaluate the feasibility, safety, and efficacy of mechanical thrombectomy under conscious sedation in patients with acute ischemic stroke, using the Solitaire FR device, in a prospective, single-center, single-arm study. The study included consecutive patients with acute ischemic stroke due to a large artery occlusion within 6 hours of symptom onset for the anterior circulation, and within 24 hours for the posterior circulation. After intravenous thrombolysis (when no contraindications), thrombectomy was performed with the Solitaire device in patients under conscious sedation. Primary efficacy and safety end points were good functional outcome (mRS ≤2) at 3 months and mortality at 3 months. Secondary end points were recanalization (TICI ≥2) and failure rate. From May 2010 to July 2011, 36 patients were treated. Median baseline NIHSS score was 17.5. The occlusion site was MCA in 21 patients (58.4%), ICA-MCA tandem occlusion in 9 patients (25.0%), terminal ICA in 2 patients (5.5%), and basilar artery in 4 patients (11.1%). Twenty-three patients (63.9%) received intravenous thrombolysis. Superselective catheterization of the occluded vessel was not feasible in 5/36 cases (13.9%). Successful revascularization was achieved in 28/36 patients (77.8%). After 3 months, 22 patients (61.1%) showed good functional outcome (mRS ≤2) and the median NIHSS score was 8.5. Overall mortality rate at 3 months was 22.2% (8/36). In acute ischemic stroke, mechanical thrombectomy while under conscious sedation is feasible in a large percentage of cases (86.1%) and is associated with a short procedure delay and a high percentage of good functional outcomes at 3 months (61.1%).

Mechanical Thrombectomy in Acute Stroke: Utilization Variances and Impact of Procedural Volume on Inpatient Mortality

Whether treatment with intravenous alteplase prior to mechanical thrombectomy (MT) in acute ischemic stroke patients with large vessel occlusion is beneficial remains unclear. To determine whether patients experiencing acute ischemic stroke due to occlusion of the intracranial internal carotid artery or the M1 segment of the middle cerebral artery who are referred to an endovascular stroke center and who are candidates for intravenous alteplase will have non-inferior functional outcome at 90 days when treated with MT alone (direct MT) with stent retrievers compared to patients treated with combined intravenous thrombolysis (IVT) with alteplase plus MT (IVT + MT) with stent retrievers. To randomize 404 patients 1:1 to direct MT or combined IVT+MT. A multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial utilizing an adaptive statistical design. The primary efficacy endpoint is functional independence (modified Rankin Scale 0-2) at 90 days. Secondary clinical efficacy outcomes include change in National Institutes of Health Stroke Scale score from baseline to day 1 and health-related quality of life at 90 days. Secondary technical efficacy outcomes include successful reperfusion prior to start of MT and time from randomization to successful reperfusion. Safety outcomes include all serious adverse events, symptomatic intracranial hemorrhage, and mortality up to 90 days. SWIFT DIRECT will inform physicians whether direct MT in acute ischemic stroke patients with large vessel occlusion is equally or more efficacious than combined treatment with intravenous alteplase and MT. ClinicalTrials.gov Identifier: NCT03192332.

Direct to Thrombectomy.

Impact of recanalisation by mechanical thrombectomy in mild acute ischemic stroke with large anterior vessel occlusion.

Purpose: Pre-treatment NIHSS has been shown to be the strongest predictor of outcome after endovascular therapy in acute ischemic stroke. However, it is not clear if sequential changes in NIHSS scores have any predictive value after mechanical thrombectomy cases. Methods: Prospective (Pivotal N=119, PICS N=219, START N=124) and retrospective/registry (POST N=95, RetroSTART N=168) cases using the Penumbra System were pooled. All were IV tPA-ineligible or refractory with treatment at <8 h. The association of NIHSS pre- and post-treatment and good clinical outcome (mRS 0-2 at 90 days) was tested. Results: Among 725 patients, mean age was 66 ± 15 and median admission NIHSS score was 17 (IQR 13-21). Median NIHSS improved to 11 at 7 days. NIHSS scores at 7 days showed a stronger relationship with good outcome (correlation 0.84; p<0.001) than baseline (correlation 0.37; p<0.001). Furthermore, serial NIHSS scores (baseline minus 7 day) also predicted good outcome (correlation -0.69; p<0.001). Age (correlation 0.39, p < 0.001), pre-treatment ASPECTS score (correlation -0.19; p < 0.001) but not reperfusion to TIMI 2-3/TICI 2b-3 also demonstrated associations with good outcome. Conclusion: In this pooled Penumbra cohort, post treatment improvement in neurological status significantly predicted good clinical and functional outcomes, independent of reperfusion status.

Early neurological deterioration (END) is associated with a poor survival after mechanical thrombectomy (MT) in acute ischemic stroke (AIS). To assess risk factors and functional outcomes of END after MT in patients, we analyzed data from 79 patients who received MT with large-vessel occlusion. END after MT in patients is defined as an increase of two points or more in the National Institute of Health Stroke Scale (NIHSS) score, compared with the best neurological status within 7 days. The mechanism of END can be classified into: AIS progression, sICH, and encephaledema. A total of 32 AIS patients (40.5%) had END after MT. Risk factors for END after MT included: history of oral antiplatelet and/or anticoagulation drugs before MT (OR = 9.56,95% CI = 1.02-89.57), higher NIHSS score when admitted to hospital (OR = 1.24, 95% CI = 1.04-1.48), under the subtype of atherosclerotic stroke (OR = 17.36, 95% CI = 1.51-199.56), ASITN/SIR< 2 (OR = 15.78, 95% CI = 1.65-151.26), and prolonged period from AIS onset to the first revascularization (OR = 1.01, 95% CI = 1.00-1.02). AIS patients who had END at early stages were more likely to experience poor outcomes (Modified Rankin Scale [mRS] >2) at 90 days after MT (OR = 6.829, 95% CI = 1.573-29.655). Thus, AIS patients who had experienced END at early stages were more likely to have poor outcomes (mRS >2) at 90 days after MT, and the risk factors of END were connected to the mechanism of END.

The association between socioeconomic status and acute ischemic stroke treatments remain uncertain, particularly in countries with universal health care systems. This study aimed to investigate the association between neighborhood-level material deprivation and the odds of receiving IV thrombolysis or thrombectomy for acute ischemic stroke within a single-payer, government-funded health care system. We conducted a population-based cohort study using linked administrative data from Ontario, Canada. This study involved all community-dwelling adult Ontario residents hospitalized with acute ischemic stroke between 2017 and 2022. Neighborhood-level material deprivation, measured in quintiles from least to most deprived, was our main exposure. We considered the receipt of thrombolysis or thrombectomy as the primary outcome. We used multivariable logistic regression models adjusted for baseline differences to estimate the association between material deprivation and outcomes. We performed a sensitivity analysis by additionally adjusting for hospital type at initial assessment. Furthermore, we tested whether hospital type modified the associations between deprivation and outcomes. Among 57,704 patients, those in the most materially deprived group (quintile 5) were less likely to be treated with thrombolysis or thrombectomy compared with those in the least deprived group (quintile 1) (16.6% vs 19.6%, adjusted odds ratio [aOR] 0.76, 95% CI 0.63-0.93). The association was consistent when evaluating thrombolysis (13.0% vs 15.3%, aOR 0.78, 95% CI 0.64-0.96) and thrombectomy (6.4 vs 7.8%, aOR 0.73, 95% CI 0.59-0.90) separately. There were no statistically significant differences between the middle 3 quintiles and the least deprived group. These associations persisted after additional adjustment for hospital type, and there was no interaction between material deprivation and hospital type (p interaction >0.1). We observed disparities in the use of thrombolysis or thrombectomy for acute ischemic stroke by socioeconomic status despite access to universal health care. Targeted health care policies, public health messaging, and resource allocation are needed to ensure equitable access to acute stroke treatments for all patients.

Transradial access for thrombectomy in acute stroke: A systematic review and meta-analysis

Background: In acute ischemic stroke (AIS) patients due to intracranial atherosclerosis-related occlusions (ICAS-O), despite successful reperfusion with mechanical thrombectomy (MT), unexpected early reocclusion sometimes occurs and worsens clinical outcome. We investigated prevalence, outcomes, and predictors of early reocclusion within 48 hours of MT in AIS due to ICAS-O. Methods: In 557 consecutive AIS patients who underwent MT from January, 2016 to March, 2019 in two stroke centers, 71 patients due to ICAS-O were retrospectively evaluated. We divided them into two groups: patients with early reocclusion and those without. Clinical and angiographical findings and outcomes were compared between the 2 groups. Multivariable logistic regression analysis was used to investigate predictors of early reocclusion after MT. Results: Of 71 patients (aged 72 ± 10 years; 23 women; median NIHSS score, 15), early reocclusion was observed in 11 (15%). The first procedure for recanalization was stent retriever in 25 patients (35%), Penumbra system in 25 patients (35%), and balloon angioplasty in 21 patients (30%). Of these, 63 patients (88%) received rescue therapy (balloon angioplasty, 50; intracranial stenting, 13). In the early reocclusion group, more number of intraprocedural reocclusion (median [IQR], 3 [2-3] vs. 1 [0-1], p &lt; 0.001), a higher rate of remaining stenosis on the final angiography (67.6 ± 5.9% vs 57.3 ± 15.9%, p = 0.044), and a higher rate of procedure-related adverse events (27% vs 5%, p = 0.043) were observed compared to the other group. On logistic regression analysis, a total number of intraprocedural reocclusion was independently associated with early reocclusion (odds ratio, 31.4; 95% confidence interval, 2.6-375.2). Early reocclusion was related to a low rate of favorable outcome at 90 days (modified Rankin Scale ≤ 2, 9% vs 54%, p = 0.007). Conclusions: In AIS patients due to ICAS-O, early reocclusion within 48 hours was not rare and associated with unfavorable outcome. Patients with repeated intraprocedural reocclusion are at high risk for early reocclusion; they might need follow-up angiographical assessment and intensive antithrombotic treatment.

Introduction: The impact of body mass index (BMI) on outcomes after mechanical thrombectomy (MT) for large vessel occlusion acute ischemic stroke (LVOS) has been a subject of controversy, mainly due to the so-called obesity paradox. The obesity paradox refers to the phenomenon where, contrary to expectations, overweight or obese individuals seem to have better clinical outcomes in certain disease states. This study aimed to investigate the relationship between BMI and the clinical prognosis of patients with LVOS treated with endovascular thrombectomy (EVT) combined with or without intravenous alteplase in DIRECT-MT (Direct Intra-arterial Thrombectomy to Revascularize Acute Ischemic Stroke Patients with Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: A Multicenter Randomized Clinical Trial). Methods: This is a post hoc analysis of the DIRECT-MT randomized trial. Patients were randomly allocated to undergo EVT after alteplase intravenous thrombolysis (IVT) (IVT+EVT group) or EVT alone (EVT group) at a 1:1 ratio. Among 656 randomized patients, 645 with baseline BMI information were included. The BMI was analyzed as a categorical variable, and all patients were categorized according to their BMI into 3 groups: 18.5 ≤ BMI <24 kg/m2 (normal weight), 24 ≤ BMI <28 kg/m2 (overweight), and BMI ≥28 kg/m2 (obese). The primary outcome was the 90-day modified Rankin Scale (mRS) score analyzed as a continuous variable. Multivariable ordinal logistic regression with an interaction term was used to estimate treatment allocation and the BMI subgroups. Results: A total of 645 patients were enrolled in this study, 373 (57.8%) were normal weight, 208 (32.2%) were overweight, and 64 (10.0%) were obese. In all, 175 (46.9%) normal-weight patients, 114 (54.8%) overweight patients, and 31 (48.4%) obese patients underwent direct EVT. Patients in the three groups were statistically different in age (71 versus 68, 66), time from randomization to groin puncture (31 versus 32, 39.5), time from randomization to revascularization (101.5 versus 92, 116), and time from admission to groin puncture (84 versus 83, 98.5). Other baseline and procedural characteristics were comparable. No significant difference for the ordinal mRS or 90-day mortality was observed by BMI (adjusted common odds ratio [acOR] was 0.92 [95% CI 0.64 to 1.32] for normal weight, 1.36 [95% CI 0.83 to 2.22] for overweight, and 1.09 [95% CI 0.45 to 2.64] for obese) and treatment allocation interaction (the adjusted p value for interaction was 0.335 [normal weight versus overweight], 0.761 [normal weight versus obese], and 0.733 [overweight versus obese]). For the procedural complications and other clinical and imaging outcomes, no significant differences were observed between the BMI and treatment allocation. Conclusion: The results demonstrated that BMI had no association with the final outcome whether the patient with LVOS underwent EVT alone or plus IVT for Chinese adults. Thus, the obesity paradox does not appear to pertain to EVT alone or plus IVT. Further studies are needed to confirm the finding.

Introduction: A large proportion of mechanical thrombectomies (MT) in acute stroke include patients transferred from an outside hospital to thrombectomy capable centers. However, patient characteristics associated with the odds of transfer is unknown. We explored the US national claims database to explore predictors of interfacility transfer in MT hospitalizations using a nationally representative sample. Methods: National Inpatient Sample database was retrospectively explored from 2016 to 2020 for stroke hospitalizations with EVT. The primary outcome was transfer status from the presenting emergency department of MT-capable hospital. Multivariable logistic regression models with multiple robustness checks were performed to determine patient characteristics with the odds of transfer. Results: This study included 100,865 patients with MT, of whom 32,685 patients (32.4%) were transferred (median [IQR] age, 71 [60-81] years; 16775 women [51.2%]; 23090 White individuals [74.9%]; 3715 Black individuals [12.1%]; 1875 Hispanic individuals [6.1%]; 895 Asian individuals [2.9%]). White race, higher baseline NIHSS, hospital size and status (urban teaching vs rural), and hospital location were independent predictors of interfacility transfer for MT. Conclusion: Nearly one in 3 MTs in the US is performed in patients presenting following transfer from another acute care hospital. Analysis of population level data utilizing the National Inpatient Sample database shows disparities in the transfer of patients with minority backgrounds (Black, Hispanic, Asian) for MT. Urban teaching centers, larger hospitals, higher baseline NIHSS, and hospital location (northeast and midwest) were more likely to receive Interhospital MT transfers regardless of race.

Mechanical thrombectomy for acute ischemic stroke with large vessel occlusion in pregnancy with mechanical heart valves： A case report