REACT Aspiration Catheters: Clinical Experience and Technical Considerations

Catheter; Mechanical aspiration; StrokeCatéter; Aspiración mecánica; IctusCatèter; Aspiració mecànica; IctusAspiration catheters are widely used in mechanical thrombectomy procedures to treat acute ischemic stroke due to large vessel occlusion. The key performance requirements for aspiration catheters are ease of navigation and effective aspiration. In this work, we review the clinical experience and in vitro studies of REACT aspiration catheters (Medtronic, Minneapolis, MN, USA). In vitro experiments showed that REACT catheters exhibit solid performance in navigation and aspiration. Previous studies reported that the recanalization capacity of the aspiration catheters can be influenced by the devices’ inner diameter and tip distensibility, the catheter-to-vessel diameter ratio, the negative pressure delivered by the vacuum generator, the cyclical aspiration mode, the proximal flow arrest, and the angle of interaction between catheter and clot. REACT catheters can be navigated through the vasculature without any support from a microcatheter/ microwire in favorable anatomical configurations. In challenging situations, mostly encountered when crossing the ophthalmic segment of the internal carotid artery, the use of the stentriever anchoring technique or delivery assist catheter can facilitate the navigation. Three clinical studies reporting on 299 patients who underwent mechanical thrombectomy with REACT catheters were included in this review. Successful recanalization (modified treatment in cerebral ischemia score 2b–3) was achieved in 89–96% of cases, no procedural complications related to REACT catheters were reported, and functional independence (modified Rankin Scale 0–2) at 90-days was 24–36%. In vitro experimental evaluations and clinical studies support the safety and effectiveness of the REACT catheters

Influencia de los inhibidores endógenos de la fibrinolisis sobre el tratamiento trombolítico del ictus con t-PA

Consultable des del TDXTítol obtingut de la portada digitalitzadaIntroducción Los inhibidores endógenos de la fibrinolisis juegan un papel esencial en el balance coagulación/fibrinolisis pudiendo estar involucrados en la respuesta al tratamiento trombolítico del ictus. Mientras que por una parte pueden inducir resistencia al t-PA limitando los beneficios de la trombólisis, por otra, pueden favorecer los procesos de sangrado en las transformaciones hemorrágicas. Objetivos El objetivo de este estudio es determinar el impacto de los niveles pre-tratamiento de inhibidores de la fibrinolisis (Inhibidor del Activador del Plasminógeno (PAI-1), lipoproteína(a), Inhibidor de la Fibrinolisis Activado por Trombina (TAFI) y homocisteína) sobre recanalización arterial, transformación hemorrágica sintomática (SICH) y evolución clínica. Métodos Estudiamos pacientes consecutivos con un ictus por oclusión de la arteria cerebral media tratados con t-PA. Se obtuvieron muestras de sangre justo antes de la administración de t-PA para la determinación de las moléculas inhibidoras de la fibrinolisis. Se determinó la recanalización arterial mediante monitorización continua por Doppler Transcraneal. Una tomografía computarizada craneal a las 24 horas o inmediatamente después de observar un empeoramiento clínico permitió descartar la presencia de una transformación hemorrágica sintomática. El estado neurológico se determinó mediante la escala NIHSS y la discapacidad a largo plazo mediante la escala modificada de Rankin (mRS) al tercer mes. Resultados Estudiamos 77 pacientes (40% mujeres, edad media 75 años). Al ingreso la mediana en la escala NIHSS fue de 17 (rango, 7 a 22) y el tiempo medio de tratamiento desde el inicio de los síntomas fue de 160 minutos. En aquellos pacientes que presentaron una recanalización arterial después de la infusión de t-PA se observaron niveles basales de PAI-1 inferiores que en los que peristió la oclusión (27.8 ng/ml Vs 38.8 ng/ml; p=0.047). Igualmente, aquellos pacientes que presentaron una mejoría clínica espectacular (decremento > 10 puntos en la escala NIHSS) a las 12 horas mostraron niveles significativamente más bajos de PAI-1 (24.6 ng/ml Vs 36.1 ng/ml; p=0.012) así como aquellos con una independencia funcional (mRS≤2) al tercer mes (24.4 ng/ml Vs 34.3 ng/ml; p=0.03). Se observó además una tendencia a presentar niveles más bajos de lipoproteina(a) en aquellos pacientes que recanalizaron tras una hora, mientras que no se observó ninguna relación entre TAFI o Homocisteína y recanalización. El modelo de regresión logística mostró que el único predictor independiente de resistencia a la trombólisis era presentar niveles basales de PAI-1>34 ng/ml (OR 12.8; 95%CI 1.7-97.2; p=0.014) Seis pacientes (7.9%) presentaron una SICH. Los análisis de las variables clínicas y radiológicas no mostraron relación con el desarrollo de SICH. Al analizar los datos de laboratorio se observó que los pacientes con SICH presentaron niveles basales de PAI-1 más bajos (21.7+/-3.5 ng/mL versus 31.8+/-12.1 ng/mL; p180% (OR, 12.9; CI, 1.41 to 118.8; P=0.02) y PAI-1 180% al ingreso era capaz de predecir SICH con una sensibilidad de 75% , una especificidad de 97.6% (P 10 points in NIHSS) at 12 hours exhibited significantly lower PAI-1 levels (24.6 ng/ml Vs 36.1 ng/ml; p=0.012) as did those functionally independent (mRS≤2) at third month (24.4 ng/ml Vs 34.3 ng/ml; p=0.03). We observed a trend towards lower lipoprotein(a) in patients who achieved recanalization at 1 hour, whereas no relation was found between TAFI or homocysteine levels and recanalization. After a regression model was applied the only independent predictor of thrombolysis resistance was baseline PAI-1>34 ng/ml (OR 12.8; 95%CI 1.7-97.2; p=0.014) Six patients (7.9%) presented with a SICH. In analyses based on clinical and radiological variables, no relation could be found with SICH. When laboratory data were analyzed, patients who experienced SICH showed lower baseline PAI-1 (21.7+/-3.5 ng/mL versus 31.8+/-12.1 ng/mL; P180% (OR, 12.9; CI, 1.41 to 118.8; P=0.02) and PAI-1 180% had a sensibility of 75% and a specificity of 97.6% (P<0.01) predicting SICH, with a positive predictive value of 75% and negative predictive value of 97.6%. Conclusion High PAI-1 levels interfere with tPA-induced recanalization in stroke, predicting a higher susceptibility towards clot-lysis resistance and poor outcome. On the other hand, very low PAI-1 and high TAFI levels predict SICH after tPA therapy. In the future, rapid determination of these biomarkers could be used to improve thrombolysis safety and efficacy

Validation of a cloud-based tele-stroke system reliability in determining national institutes of health stroke scale scores for acute ischemic stroke screening in the emergency department

Remote diagnosis; Tele-strokeDiagnóstico remoto; Tele-ictusDiagnòstic remot; Tele-ictusBackground and purpose: The National Institutes of Health Stroke Scale (NIHSS) is the most recommended tool for objectively quantifying the impairment caused by a suspected stroke. Nevertheless, it is mainly used by trained neurologists in the emergency department (ED). To bring forward the NIHSS to the pre-hospital setting, a smartphone-based Telestroke system was developed. It captures the full NIHSS by video, transmits it off-line, and enables assessment by a distant stroke physician. We aimed to compare the reliability of an NIHSS score determined by a neurologist from afar, using the platform with a standard NIHSS assessment performed in the emergency departments. Methods: A multi-center prospective study was conducted in two centers (Vall d'Hebron, Barcelona, and Rambam, Israel). Patients admitted to the ED with suspected stroke had a neurological exam based on the NIHSS, while being recorded by the system. A skilled neurologist rated the NIHSS according to the videos offline. The results were compared with the NIHSS score given by a neurologist at the bedside. Results: A total of 95 patients with suspected stroke were included. The overall intraclass correlation coefficient was 0.936 (0.99 in VdH and 0.84 in Rambam), indicating excellent and good reliability, respectively. Conclusion: Remote stroke assessment based on the NIHSS, using videos segments collected by a dedicated platform, installed on a standard smartphone, is a reliable measurement as compared with the bedside evaluation.The authors declare that this study received funding from CVAID Company. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication

Benchmarking the Extent and Speed of Reperfusion: First Pass TICI 2c-3 Is a Preferred Endovascular Reperfusion Endpoint

Isquèmia cerebral; Trombectomia mecànica; ReperfusióIsquemia cerebral; Trombectomía mecánica; ReperfusiónBrain ischaemia; Mechanical thrombectomy; ReperfusionBackground and Purpose: End-of-procedure substantial reperfusion [modified Treatment in Cerebral Ischemia (mTICI) 2b-3], the leading endpoint for thrombectomy studies, has several limitations including a ceiling effect, with recent achieved rates of ~90%. We aimed to identify a more optimal definition of angiographic success along two dimensions: (1) the extent of tissue reperfusion, and (2) the speed of revascularization. Methods: Core-lab adjudicated TICI scores for the first three passes of EmboTrap and the final all-procedures result were analyzed in the ARISE II multicenter study. The clinical impact of extent of reperfusion and speed of reperfusion (first-pass vs. later-pass) were evaluated. Clinical outcomes included 90-day functional independence [modified Rankin Scale (mRS) 0–2], 90-day freedom-from-disability (mRS 0–1), and dramatic early improvement [24-h National Institutes of Health Stroke Scale (NIHSS) improvement ≥ 8 points]. Results: Among 161 ARISE II subjects with ICA or MCA M1 occlusions, reperfusion results at procedure end showed substantial reperfusion in 149 (92.5%), excellent reperfusion in 121 (75.2%), and complete reperfusion in 79 (49.1%). Reperfusion rates on first pass were substantial in 81 (50.3%), excellent reperfusion in 62 (38.5%), and complete reperfusion in 44 (27.3%). First-pass excellent reperfusion (first-pass TICI 2c-3) had the greatest nominal predictive value for 90-day mRS 0–2 (sensitivity 58.5%, specificity 68.6%). There was a progressive worsening of outcomes with each additional pass required to achieve TICI 2c-3. Conclusions: First-pass excellent reperfusion (TICI 2c-3), reflecting rapid achievement of extensive reperfusion, is the technical revascularization endpoint that best predicted functional independence in this international multicenter trial and is an attractive candidate for a lead angiographic endpoint for future trials.Cerenovus sponsored the ARISE II study, and provided support for open access to this article

Health economic impact of first-pass success among patients with acute ischemic stroke treated with mechanical thrombectomy: a United States and European perspective

Economics; Stroke; ThrombectomyEconomia; Ictus; TrombectomiaEconomía; Ictus; TrombectomíaBackground First-pass effect (FPE), restoring complete or near complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) in a single pass, is an independent predictor for good functional outcomes in the endovascular treatment of acute ischemic stroke. The economic implications of achieving FPE have not been assessed. Objective To assess the economic impact of achieving complete or near complete reperfusion after the first pass. Methods Post hoc analyses were conducted using ARISE II study data. The target population consisted of patients in whom mTICI 2c–3 was achieved, stratified into two groups: (1) mTICI 2c–3 achieved after the first pass (FPE group) or (2) after multiple passes (non-FPE group). Baseline characteristics, clinical outcomes, and healthcare resource use were compared between groups. Costs from peer-reviewed literature were applied to assess cost consequences from the perspectives of the United States (USA), France, Germany, Italy, Spain, Sweden, and United Kingdom (UK). Results Among patients who achieved mTICI 2c–3 (n=172), FPE was achieved in 53% (n=91). A higher proportion of patients in the FPE group reached good functional outcomes (90-day modified Rankin Scale score 0–2 80.46% vs 61.04%, p<0.01). The patients in the FPE group had a shorter mean length of stay (6.10 vs 9.48 days, p<0.01) and required only a single stent retriever, whereas 35% of patients in the non-FPE group required at least one additional device. Driven by improvement in clinical outcomes, the FPE group had lower procedural/hospitalization-related (24–33% reduction) and annual care (11–27% reduction) costs across all countries. Conclusions FPE resulted in improved clinical outcomes, translating into lower healthcare resource use and lower estimated costs.This study was funded by Cerenovus, a subsidiary of Johnson and Johnson

Stroke etiologies in patients with COVID-19: the SVIN COVID-19 multinational registry

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Ictus; MortalitatCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Ictus; MortalidadCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Stroke; MortalityBackground and purpose Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology. Methods We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20–6/16/20). Results Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p</=0.05 for all comparisons). In a multivariable backward stepwise regression model estimating the odds of in-hospital mortality, cryptogenic stroke mechanism was associated with a fivefold greater odds in-hospital mortality than strokes due to any other mechanism (adjusted OR 5.16, 95%CI 1.41–18.87, p = 0.01). In that model, older age (aOR 2.05 per decade, 95%CI 1.35–3.11, p < 0.01) and higher baseline NIHSS (aOR 1.12, 95%CI 1.02–1.21, p = 0.01) were also independently predictive of mortality. Conclusions Our findings suggest that cryptogenic stroke among COVID-19 patients carries a significant risk of early mortality.MER-A was funded by The Instituto de Salud Carlos III (JR19/00020), Spain

Mechanical thrombectomy with a novel device: initial clinical experience with the ANA thrombectomy device

Mechanical thrombectomy; New device; StrokeTrombectomia mecànica; Nou dispositiu; IctusTrombectomía mecánica; Nuevo dispositivo; IctusIntroduction The ANA™ (Anaconda Biomed) thrombectomy system is a novel stroke thrombectomy device comprising a self-expanding funnel designed to reduce clot fragmentation by locally restricting flow while becoming as wide as the lodging artery. Once deployed, ANA allows distal aspiration in combination with a stentretriever (SR) to mobilize the clot into the funnel where it remains copped during extraction. We investigate safety and efficacy of ANA™ in a first-in-man study. Methods Prospective data was collected on 35 consecutive patients treated as first line with ANA™ at a single centre. Outcome measures included per-pass reperfusion scores, symptomatic intracerebral hemorrhage (sICH), NIHSS at day 5, and mRS at 90 days. Results Median NIHSS was 12(9−18). Sites of primary occlusion were: 5 ICA, 15 M1-MCA, 15 M2-MCA. Primary performance endpoint, mTICI 2b-3 within 3 passes without rescue therapy was achieved in 91.4% (n = 32) of patients; rate of complete recanalization (mTICI 2c-3) was 65.7%. First pass complete recanalization rate was 42.9%, and median number of ANA passes 1(IQR: 1−2). In 17.1% (n = 6) rescue treatment was used; median number of rescue passes was 2(1–7), leading to a final mTICI2b-3rate of 94.3% (n = 33). There were no device related serious adverse events, and rate of sICH was 5.7% (n = 2). At 5 days median NIHSS was 1 (IQR 1−6) and 90 days mRS 0−2 was achieved in 60% of patients. Conclusions In this initial clinical experience, the ANA™ device achieved a high rate of complete recanalization with a good safety profile and favourable 90 days clinical outcomes.The study was funded by Anaconda Biomed S.L

APRIL: A double-blind, placebo-controlled, randomized, Phase Ib/IIa clinical study of ApTOLL for the treatment of acute ischemic stroke

Inflammation; Neuroprotection; StrokeInflamació; Neuroprotecció; IctusInflamación; Neuroprotección; IctusIn the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a <6h window from symptoms onset to ApTOLL/placebo administration. The trial is currently being conducted and is divided into two parts: Phase Ib and Phase IIa. In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo).The study is supported by grants from the Spanish Ministry of Science, Innovation and Universities (RTC-2017-6651-1 and RTC2019-006795-1). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication

Direct to angiography suite approaches for the triage of suspected acute stroke patients: a systematic review and meta-analysis

Mechanical thrombectomy; Stroke; TriageTrombectomia mecànica; Ictus; TriatgeTrombectomía mecánica; Ictus; TriajeBackground: Increasing evidence suggests improved time metrics leading to better clinical outcomes when stroke patients with suspected large vessel occlusion (LVO) are transferred directly to the angiography suite (DTAS) compared with cross-sectional imaging followed by transfer to the angiography suite. We performed a systematic review and meta-analysis on the efficacy and safety of DTAS approaches. Methods: We searched Embase, Medline, Scopus, and clinicaltrials.gov for studies comparing outcomes of DTAS and conventional triage. Eligible studies were assessed for risk of bias. We performed a random-effects meta-analysis on the differences of median door-to-groin and door-to-reperfusion times between intervention and control group. Secondary outcomes included good outcome at 90 days (modified Rankin Scale ⩽ 2) rate of symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. Results: Eight studies (one randomized, one cluster-randomized trial and six observational studies) with 1938 patients were included. Door-to-groin and door-to-reperfusion times in the intervention group were on median 29.0 min [95% confidence interval (CI): 14.3–43.6; p < 0.001] and 32.1 min (95% CI: 15.1–49.1; p < 0.001) shorter compared with controls. Prespecified subgroup analyses for transfer (n = 1753) and mothership patients (n = 185) showed similar reductions of the door-to-groin and door-to-reperfusion times in response to the intervention. The odds of good outcome did not differ significantly between both groups but were numerically higher in the intervention group (odds ratio: 1.38, 95% CI: 0.97–1.95; p = 0.07). There was no significant difference for mortality and sICH between the groups. Conclusion: DTAS approaches for the triage of suspected LVO patients led to a significant reduction in door-to-groin and door-to-reperfusion times but an effect on functional outcome was not detected. The subgroup analysis showed similar results for transfer and mothership patients

Outcome, efficacy and safety of endovascular thrombectomy in ischaemic stroke according to time to reperfusion: data from a multicentre registry

Endovascular; Mechanical thrombectomy; StrokeEndovascular; Trombectomia mecànica; Accident cerebrovascularEndovascular; Trombectomía mecánica; Accidente cerebrovascularBACKGROUND AND PURPOSE: In acute ischaemic stroke (AIS) of the anterior circulation (AC) treated with mechanical thrombectomy (MT), data point to a decline of treatment effect with increasing time from symptom onset to treatment. However, the magnitude of the decline will depend on the clinical setting and imaging selection used. The aims of this study were (1) to evaluate the clinical effect of time to reperfusion (TTR); and (2) to assess the safety and technical efficacy of MT according to strata of TTR. METHODS: Using the retrospective multicentre BEYOND-SWIFT registry data (ClinicalTrials.gov identifier: NCT03496064), we compared safety and efficacy of MT in 1461 patients between TTR strata of 0-180 min (n = 192), 180-360 min (n = 876) and >360 min (n = 393). Clinical effect of TTR was evaluated using multivariable logistic regression analyses adjusting for pre-specified confounders [adjusted odds ratios (aOR) and 95% confidence intervals (95% CI)]. Primary outcome was good functional outcome (modified Rankin Scale: mRS 0-2) at day 90. RESULTS: Every hour delay in TTR was a significant factor related to mRS 0-2 (aOR 0.933, 95% CI 0.887-0.981) with an estimated 1.5% decreased probability of good functional outcome per hour delay of reperfusion, and mRS 0-1 (aOR 0.929, 95% CI 0.877-0.985). Patients with late TTR had lower rates of successful and excellent reperfusion, higher complication rates and number of passes. CONCLUSIONS: TTR is an independent factor related to long-term functional outcome. With increasing TTR, interventional procedures become technically less effective. Efforts should be made to shorten TTR through optimized prehospital and in-hospital pathways