Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

Early prediction of final infarct volume with material decomposition images of dual-energy CT after mechanical thrombectomy.

PURPOSE: Evaluation of water material density images (wMDIm) of dual-energy CT (DECT) for earlier prediction of final infarct volume (fiV) in follow-up single-energy CT (SECT) and correlation with clinical outcome. METHODS: Fifty patients (69 years, ± 12.1, 40-90, 50% female) with middle cerebral artery (MCA) occlusions were included. Early infarct volumes were analyzed in monoenergetic images (MonoIm) and wMDIm at 60 keV and compared with the fiV in SECT 4.9 days (± 4) after thrombectomy. Association between infarct volume and functional outcome was tested by linear regression analysis. RESULTS: wMDIm shows a prior visible infarct demarcation (60.7 ml, ± 74.9 ml) compared with the MonoIm (37.57 ml, ± 76.7 ml). Linear regression analysis, Bland-Altman plots and Pearson correlation coefficients show a close correlation of infarct volume in wMDIm to the fiV in SECT (r = 0.86; 95% CI 0.76-0.92), compared with MonoIm and SECT (r = 0.81; 95% CI 0.69-0.89). The agreement with SECT is substantially higher in patients with infarct volumes < 70 ml (n = 33; 66%). Coefficients were smaller with r = 0.59 (95% CI 0.31; 0.78) for MonoIm and SECT compared with r = 0.77 (95% CI 0.57; 0.88) for wMDIm and SECT. At admission, the mean NIHSS score and mRS were 17.02 (± 4.7) and 4.9 (± 0.2). mRS ≤ 2 was achieved in 56% at 90 days with a mean mRS of 2.5 (± 0.8) at discharge. CONCLUSION: Material decomposition allows earlier visibility of the final infarct volume. This promises an earlier evaluation of the dimension and severity of infarction and may lead to faster initiation of secondary stroke prophylaxis.

Influence of vessel morphology and variations on technical and clinical success in mechanical thrombectomy: -In vivo and in vitro analyses.

PURPOSE: To determine the impact of vessel variation and anatomical features on technical and clinical success. MATERIALS AND METHODS: In vitro blood clots (n=100) were introduced into a silicon carotid-T flow model of 2, 3 or 4mm. The ICA/M1angle varied at 45°, 90°, 135° and 180°. Peripheral embolism was measured. In vivo 50 pat. (73.5 yrs.,±15) with MCA occlusion were examined for siphon variation, ICA morphology, vessel diameter and angles. The patients were divided according to the clinical success (mRS): group A: mRS≤2 after 90 day and group B: mRS≥3. Furthermore the technical success (TICI) and number of retrieval (n) were analysed. RESULTS: In vitro with larger vessel diameter the migrated thrombus load decreased (P=.001). The steeper the M1/ICA angles, the higher thrombus weighs (180°: 2.94mg; 135°: 6.32mg; 90°: 8.65mg, 45°: 10.69mg; P<.001). In vivo patients with mRS≤2 had significantly lower NIHSS (16.5 vs 20, P=.009) and higher ASPECTS (9 vs 6, P<.05). TICI≥2b was more often achieved (86.6 vs 40% P=.002). The procedure time was lower (45 vs. 80min, P<.05) with smaller number of retrieval (1.5 vs 4, P<05). Proximal ICA stenosis offers a trend to unfavourable outcome (P=.073). Siphon variation "D" is associated with less retrieval manoeuvre. CONCLUSION: While in vitro there is a close correlation between embolism and vascular anatomy, in vivo carotid artery stenosis and siphon variation influence clinical and technical success.

Initial clinical experience with the micromesh Roadsaver carotid artery stent for the treatment of patients with symptomatic carotid artery disease.

PURPOSE: To assess the effectiveness, technical aspects, handling, and safety of the micromesh Roadsaver Carotid Artery Stent in the treatment of atherosclerotic carotid artery stenosis and tandem lesions in ischemic stroke patients. METHODS: Seven patients (5 men; mean age 75±11.4 years, range 53-86) suffering from symptomatic internal carotid artery (ICA) stenosis (mean 76% diameter reduction) were treated with the dual layer closed-cell stent without embolic protection. Postdilation was performed in 6 of 7 patients. Two patients were treated in the context of ischemic stroke and concurrent middle cerebral artery occlusion. Mean National Institutes of Health Stroke Scale score at admission was 12.8±5. RESULTS: All devices were deployed satisfactorily. One wall-adherent thromboembolus in a proximal ICA was covered with the Roadsaver stent in a tandem lesion setting. The modified Rankin Scale (mRS) declined from 3.7±0.7 to 2.4±0.8 in hospital, showing an improvement in clinical symptoms. No complications were detected during or after the procedure. The 30-day mRS was 1.7±1.1. At 6 months, ultrasound examination demonstrated patency of stents and the external carotid arteries. CONCLUSION: The Roadsaver double layer micromesh stent seems to be safe and effective in the treatment of extracranial ICA stenosis and in the context of tandem lesions in ischemic stroke. Further studies with larger populations are warranted.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.

BACKGROUND: Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial. METHODS: TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed. FINDINGS: We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99]). INTERPRETATION: In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients. FUNDING: European Union Horizon 2020 Research and Innovation Programme.

An Update on Drug-eluting Technology in Peripheral Arteries to Treat Peripheral Arterial Disease.

For the treatment of peripheral arterial disease, drug-eluting technology is a widely accepted therapeutic option, with significant reduction in intimal hyperplasia and, consequently, use of target lesion revascularization. Nevertheless, the reputation of such devices was damaged after a meta-analysis, published in December 2018, showed increased mortality in patients receiving paclitaxel-eluting devices. Although subsequent studies have failed to establish such correlation, the use of paclitaxel-eluting devices remains heavily restricted. As such, other options and drugs have been developed, for instance sirolimus. In this article we present the available data on drug-eluting technology.

Eluvia drug-eluting vascular stent system for the treatment of symptomatic femoropopliteal lesions.

Endovascular options are increasingly recognized as primary treatments for lower extremity peripheral arterial disease inadequately responsive to noninvasive therapy. Options include balloon angioplasty and stent implantation, and newer technologies incorporate drug coatings to prevent restenosis and reduce the need for reintervention. The Eluvia drug-eluting vascular stent system (Boston Scientific, MA, USA) was designed with a biocompatible fluoropolymer coating to allow for drug elution over time. Initial clinical results demonstrate promising efficacy in terms of sustained femoropopliteal artery patency along with a good safety profile. This review summarizes the existing clinical literature on treatment of femoropopliteal artery lesions with Eluvia, and outlines the continuing research program.

Drug-coated balloons: what is the evidence?

Having evolved at a rapid pace, the therapy options for percutaneous treatment of peripheral arterial disease in the lower limbs, especially percutaneous transluminal angioplasty in combination with stent-technology, are able to deliver a rate where at least 80% of the treated patients remain free from reintervention after the first years under ideal study conditions, meaning that defined and often restrict in- and exclusion criteria were fulfilled and mid-term dual platelet therapy is warranted. This is somewhat a huge leap when compared to the 50-60% in the 1980s and 1990s, but we now face an era of an increasingly demanding clientele, where the industry also strives to cover this final 20% with newer technologies. As recent studies with drug-eluting stents (DES) suggests, nowadays it is possible to achieve up to 90% patency in the short- and mid-term, but this comes accompanied by remarkably increased therapy costs, making it almost impossible to most centers to implant it as the standard therapy option. Trying to fill this gap between the low-patency of the plain old balloon angioplasty and the higher costs of the DES, drug-coated balloon technology has found its niche, knowing that reimbursement shows a broad variation across the countries and continents.

Lesion-Related Carotid Angioplasty and Stenting with Closed-Cell Design without Embolic Protection Devices in High-Risk Elderly Patients-Can This Concept Work Out? A Single Center Experience Focusing on Stent Design.

To compare the performance differences of three carotid artery stents in high-risk elderly patients without embolic protection devices (EPDs) on the basis of stent design, procedure-related complications, conveniences in handling, in-stent restenosis, 30-day outcome, and long-term follow-up. A total of 101 symptomatic internal carotid stenoses of 94 patients were prospectively treated with stent-protected angioplasty to 94 patients. Three closed-cell stents, one of those being hybrid cell design, were chosen depending on vascular anatomy: curved vessel, lesion length > 1 cm: 64 Carotid Wallstent (Boston Scientific, Natick, MA); curved vessel, lesion length < 1 cm: 21 Cristallo Ideale (Invatec, Roncadelle, Italy); straight vessel, lesion length > 1 cm: 16 Xact (Vascular Abbott, Santa Clara, CA). Comparisons of demographics, procedures, and outcomes were performed. The mean age of patients was 73.1 years (standard deviation [SD], ± 7.9; range, 58-87 years), 71% of the patients were older than 70 years and 20% were octogenarians. Male/female ratio was 3.1:1. About 13.9% (14/101) had contralateral internal carotid artery occlusion. Overall peri-interventional complication rate was 2.9% and 30-day mortality rate was 1%. During the long-term follow-up (34 months, range 1-59) no ipsilateral stroke was documented. Ten deaths (three after MI) were recognized. Two in-stent restenosis were detected (> 70% North American Symptomatic Carotid Endarterectomy Trial) during follow-up, one patient was detected with previous carotid endarterectomy. Especially, if individual anatomical variance is considered, lesion-related stent-protected carotid angioplasty with lesion-adapted closed-cell design is an effective, reliable, safe, and comprehensible treatment option in symptomatic patients. Even without EPDs, the rate of complications is low, when compared with symptomatic carotid artery stenosis described in the literature. In-stent restenosis seems to play no significant role in follow-up.

Frameless navigated biopsy with the BrainLAB® VarioGuide system: a technical note.

OBJECTIVE: Implementation of a new neuronavigation system in the department included the opportunity to change the brain biopsy procedures from a frame-based system to a frameless system--the BrainLAB® VarioGuide. We report our first 20 consecutive procedures within 2 years, analyzing the effectiveness of this new tool. PATIENTS, MATERIALS, AND METHODS: 15 men and 5 women with various intracerebral lesions were biopsied. Their average age was 62 years (range, 41-83 years). Preoperative planning was performed using computed tomography (CT) or magnetic resonance imaging (MRI) data provided by a radiological picture archiving and communication system (PACS) sent to the planning station. Planning was based on either MRI or CT in 14 and 4 cases, respectively, and a combination of both in 2 cases. RESULTS: The lesions had a mean maximal diameter of 42.97 mm (range, 5.8-109.8 mm). 19 lesions were supratentorial, 1 of those intraventricular, and 1 lesion was infratentorial, within the cerebellar peduncle and brainstem. During surgery, the samples were sent to neuropathological examination, and the procedure was completed after confirmation that pathological tissue was obtained. In 18 of 20 cases, definitive pathological tissue was harvested. Histopathology confirmed 8 glioblastomas, 1 oligoastrocytoma, 4 anaplastic astrocytomas, 1 astrocytoma, and 2 primary central nervous system lymphomas, as well as 1 encephalitis and 1 necrotic tissue of unknown origin. In 3 cases, including the case of necrotic tissue, there was no final diagnosis possible. Referencing the BrainLAB® navigation system and software-wizard guided sterile adjustment of the VarioGuide arm over the entry point took 5 to 10 minutes. The mean operation time was 49 minutes (range, 24-69 minutes) including the time until first neuropathological examination was completed. No adverse events occurred during or after the operation.