Feasibility, complications, morbidity, and mortality results at 6 months for aneurysm treatment with the Flow Re-Direction Endoluminal Device: report of SAFE study

International audienceBACKGROUND AND PURPOSE:Flow diverters are increasingly used for the treatment of intracranial aneurysms. Evaluation of the first devices available for clinical use showed high efficacy of this treatment although safety results were worse compared with coiling or balloon-assisted coiling. The Safety and Efficacy Analysis of FRED Embolic Device in Aneurysm Treatment (SAFE) trial is a single-arm, multicenter, prospective study conducted to precisely analyze the safety and efficacy of the FRED and FRED Jr devices.METHODS:Unruptured and recanalized aneurysms located in the anterior circulation treated with FRED and FRED Jr were prospectively included. Adverse events were independently evaluated by a Clinical Event Committee with a vascular neurosurgeon and an interventional neuroradiologist. Primary safety outcome measures were morbidity and mortality rates at 6 months after treatment.RESULTS:A total of 103 patients/aneurysms were included in 13 interventional neuroradiology (INR) centers. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral artery or anterior communicating artery in nine (8.7%), and middle cerebral artery in eight (7.8%). Aneurysms were small (<10 mm) in 71 patients (68.9%). Treatment was successfully performed in 98/103 patients (95.1%). Thromboembolic (TE) complications occurred in 5/103 patients (4.9%), intraoperative rupture in 2/103 patients (1.9%), delayed aneurysm rupture in 1/103 patient (1.0%), and delayed hematoma occurred in 1/103 patient (1.0%). Six-months' mortality and morbidity rates were 1/102 (1.0%) and 2/102 (2.0%), respectively.CONCLUSIONS:Aneurysm treatment with the FRED device is safe with low mortality (1.0%) and morbidity (2.0%)

SAFE study (Safety and efficacy Analysis of FRED Embolic device in aneurysm treatment): 1-year clinical and anatomical results

International audienceFlow diversion is an innovative and increasingly used endovascular treatment for intracranial aneurysms. Its initial evaluation with the first devices available showed good efficacy of this treatment with variable safety results. The Flow Direction Endoluminal Device (FRED) has a specific design and was evaluated in a single-arm, multicenter, prospective, Good Clinical Practice study: SAFE (Safety and efficacy Analysis of FRED Embolic device in aneurysm treatment). This analysis reports clinical results at 1 year and anatomical results at 6 months and 1 year.METHODS:Patients with unruptured and recanalized aneurysms located in the anterior circulation treated with FRED and FRED Jr were prospectively included. A Clinical Event Committee and a Core Laboratory independently evaluated clinical outcome and anatomical results.RESULTS:Thirteen interventional neuroradiology centers included 103 patients/aneurysms. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral or anterior communicating artery in 9 (8.7%), and middle cerebral artery in 8 (7.8%). Most aneurysms were small (<10 mm) in 71 patients (68.9%). Cumulative 1-year mortality and morbidity rates were 2/103 (1.9%) and 3/103 (2.9%), respectively, one death being related to cancer. At 1 year, anatomical results were: complete occlusion in 66/90 patients (73.3%), neck remnant in 7/90 patients (7.8%), and aneurysm remnant in 17/90 patients (18.9%).CONCLUSIONS:SAFE study analysis at 1 year confirms the excellent safety profile of the FRED device for aneurysm treatment, with low morbidity and mortality rates (2.9% and 1.9%, respectively) and demonstrates its efficacy (adequate occlusion in 73/90 (81.1%)).CLINICAL TRIAL REGISTRATION:Unique identifier: NCT02921698; Results

Transvenous Curative Embolization of Cerebral Arteriovenous Malformations: A Prospective Cohort Study

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Aspirin versus aggressive antiplatelet therapy for acute carotid stenting plus thrombectomy in tandem occlusions: ETIS Registry results

International audienceBackground: Patients treated with acute carotid stenting (CAS) may have higher odds of a favorable outcome than those treated without CAS during thrombectomy in tandem occlusions. Antiplatelet therapy is associated with CAS to avoid stent thrombosis, which occurs in around 20% of patients and negatively impacts outcomes. In this study we compared two antiplatelet strategies in tandem occlusion strokes treated with CAS and intracranial thrombectomy in clinical practice.Methods: The Endovascular Treatment in Ischemic Stroke Registry is an ongoing prospective observational study involving 21 comprehensive stroke centers performing thrombectomy in France. We analyzed patients with atherosclerotic tandem occlusions treated with acute CAS and intracranial thrombectomy who received at least one antiplatelet agent. Aggressive antiplatelet therapy included oral or intravenous glycoprotein (GP) IIb/IIIa or P2Y12 inhibitors. The primary outcome was cervical carotid artery patency at day 1 imaging follow-up.Results: Among the 187 included patients, 124 (66.3%) received aspirin alone and 63 (33.7%) received aggressive antiplatelet therapy. There was no significant difference regarding safety outcomes, especially in symptomatic intracerebral hemorrhage, parenchymal hematoma, and procedural complications. There was a significantly higher rate of carotid stent patency at day 1 in the aggressive antiplatelet therapy group (81.7% vs 97.1%, aOR 17.49, 95% CI 1.10 to 277.2, p=0.042). Odds of favorable functional outcome (90-day modified Rankin Scale score 0-2) were similar between the groups (OR 3.04, 95% CI 0.64 to 14.25, p=0.158).Conclusions: In tandem occlusions treated with CAS plus thrombectomy, an aggressive antiplatelet regimen was associated with an increased rate of carotid stent patency at day 1 without safety concerns. Randomized trials are warranted to confirm these findings

Carotid artery direct access for mechanical thrombectomy: the Carotid Artery Puncture Evaluation (CARE) study.

BACKGROUND In acute ischemic stroke due to anterior large vessel occlusion (AIS-LVO), accessing the target occluded vessel for mechanical thrombectomy (MT) is sometimes impossible through the femoral approach. We aimed to evaluate the safety and efficacy of direct carotid artery puncture (DCP) for MT in patients with failed alternative vascular access. METHODS We retrospectively analyzed data from 45 stroke centers in France, Switzerland and Germany through two research networks from January 2015 to July 2019. We collected physician-centered data on DCP practices and baseline characteristics, procedural variables and clinical outcome after DCP. Uni- and multivariable models were conducted to assess risk factors for complications. RESULTS From January 2015 to July 2019, 28 149 MT were performed, of which 108 (0.39%) resulted in DCP due to unsuccessful vascular access. After DCP, 77 patients (71.3%) had successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b) and 28 (25.9%) were independent (modified Rankin Scale (mRS) score 0-2) at 3 months. 20 complications (18.5%) attributed to DCP occurred, all of them during or within 1 hour of the procedure. Complications led to extension of the intubation time in the intensive care unit in 7 patients (6.4%) and resulted in death in 3 (2.8%). The absence of use of a hemostatic closure device was associated with a higher complication risk (OR 3.04, 95% CI 1.03 to 8.97; p=0043). CONCLUSION In this large multicentric study, DCP was scantly performed for vascular access to perform MT (0.39%) in patients with AIS-LVO and had a high rate of complications (18.5%). Our results provide arguments for not closing the cervical access by manual compression after MT

Endovascular reperfusion of M2 occlusions in acute ischemic stroke reduced disability and mortality: ETIS Registry results

International audienceBackground: The predictors of successful reperfusion and the effect of reperfusion after endovascular treatment (EVT) for M2 occlusions have not been well studied. We aimed to identify predictors of successful reperfusion and the effect of reperfusion on outcomes of EVT for M2 occlusions in current practice.Methods: Patients with acute ischemic stroke due to isolated M2 occlusions who were enrolled in the prospective multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France between January 2015 and March 2020 were included. The primary outcome was a favorable outcome, defined as modified Rankin Scale (mRS) score of 0-2 at 90 days. Successful reperfusion was defined as an improvement of ≥1 points in the modified Thrombolysis In Cerebral Infarction score between the first and the last intracranial angiogram.Results: A total of 458 patients were included (median National Institutes of Health Stroke Scale (NIHSS) score 14; 61.4% received prior intravenous thrombolysis). Compared with the non-reperfused patients, reperfused patients had an increased rate of excellent outcome (OR 2.3, 95% CI 0.98 to 5.36; p=0.053), favorable outcome (OR 2.79, 95% CI 1.31 to 5.93; p=0.007), and reduced 90-day mortality (OR 0.39, 95% CI 0.19 to 0.79; p&lt;0.01). Admission NIHSS score was the only predictor of successful reperfusion. First-line strategy was not a predictor of successful reperfusion or favorable outcome, but the use of a stent retriever, alone or with an aspiration catheter, was associated with higher rates of procedural complications and 90-day mortality.Conclusions: Successful reperfusion of M2 occlusions reduced disability and mortality. However, safety is a concern, especially if the procedure failed

Carotid artery direct access for mechanical thrombectomy: the Carotid Artery Puncture Evaluation (CARE) study

Background In acute ischemic stroke due to anterior large vessel occlusion (AIS-LVO), accessing the target occluded vessel for mechanical thrombectomy (MT) is sometimes impossible through the femoral approach. We aimed to evaluate the safety and efficacy of direct carotid artery puncture (DCP) for MT in patients with failed alternative vascular access. Methods We retrospectively analyzed data from 45 stroke centers in France, Switzerland and Germany through two research networks from January 2015 to July 2019. We collected physician-centered data on DCP practices and baseline characteristics, procedural variables and clinical outcome after DCP. Uni- and multivariable models were conducted to assess risk factors for complications. Results From January 2015 to July 2019, 28 149 MT were performed, of which 108 (0.39%) resulted in DCP due to unsuccessful vascular access. After DCP, 77 patients (71.3%) had successful reperfusion (modified Thrombolysis In Cerebral Infarction (mTICI) score >= 2b) and 28 (25.9%) were independent (modified Rankin Scale (mRS) score 0-2) at 3 months. 20 complications (18.5%) attributed to DCP occurred, all of them during or within 1 hour of the procedure. Complications led to extension of the intubation time in the intensive care unit in 7 patients (6.4%) and resulted in death in 3 (2.8%). The absence of use of a hemostatic closure device was associated with a higher complication risk (OR 3.04, 95% CI 1.03 to 8.97; p=0043). Conclusion In this large multicentric study, DCP was scantly performed for vascular access to perform MT (0.39%) in patients with AIS-LVO and had a high rate of complications (18.5%). Our results provide arguments for not closing the cervical access by manual compression after MT

Collateral status reperfusion and outcomes after endovascular therapy: insight from the Endovascular Treatment in Ischemic Stroke (ETIS) Registry

International audienceBackground Studies have suggested that collateral status modifies the effect of successful reperfusion on functional outcome after endovascular therapy (EVT). We aimed to assess the association between collateral status and EVT outcomes and to investigate whether collateral status modified the effect of successful reperfusion on EVT outcomes. Methods We used data from the ongoing, prospective, multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry. Collaterals were graded according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) guidelines. Patients were divided into two groups based on angiographic collateral status: poor (grade 0–2) versus good (grade 3–4) collaterals. Results Among 2020 patients included in the study, 959 (47%) had good collaterals. Good collaterals were associated with favorable outcome (90-day modified Rankin Scale (mRS) 0–2) (OR 1.5, 95% CI 1.19 to 1.88). Probability of good outcome decreased with increased time from onset to reperfusion in both good and poor collateral groups. Successful reperfusion was associated with higher odds of favorable outcome in good collaterals (OR 6.01, 95% CI 3.27 to 11.04) and poor collaterals (OR 5.65, 95% CI 3.32 to 9.63) with no significant interaction. Similarly, successful reperfusion was associated with higher odds of excellent outcome (90-day mRS 0–1) and lower odds of mortality in both groups with no significant interaction. The benefit of successful reperfusion decreased with time from onset in both groups, but the curve was steeper in the poor collateral group. Conclusions Collateral status predicted functional outcome after EVT. However, collateral status on the pretreatment angiogram did not decrease the clinical benefit of successful reperfusion

Recanalization Treatments for Pediatric Acute Ischemic Stroke in France

International audienceImportance: There is to date limited evidence that revascularization strategies are associated with improved functional outcome in children with acute ischemic stroke (AIS).Objectives To report clinical outcomes and provide estimates of revascularization strategy safety and efficacy profiles of intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) in children with AIS.Design, Setting, and Participants The KidClot multicenter nationwide cohort study retrospectively collected data of children (neonates excluded) with AIS and recanalization treatment between January 1, 2015, and May 31, 2018. Data analysis was performed from January 1, 2015, to May 31, 2019.Exposure: IVT and/or EVT.Main Outcomes and Measures Primary outcome was day 90 favorable outcome (modified Rankin Scale [mRs] 0-2, with 0 indicating no symptoms and 6 indicating death). Secondary end points included 1-year favorable outcome (mRs, 0-2), mortality, and symptomatic intracerebral hemorrhage. Other measures included the Pediatric National Institutes of Health Stroke Scale (pedNIHSS), with pedNIHSS 0 indicating no symptoms, 1 to 4 corresponding to a minor stroke, 5 to 15 corresponding to a mild stroke, greater than 15 to 20: severe stroke, and the adult Alberta Stroke Program Early CT Score (ASPECTS), which provides segmental assessment of the vascular territory, with 1 point deducted from the initial score of 10 for every region involved (from 10 [no lesion] to 0 [maximum lesions]).Results: Overall, 68 children were included in 30 centers (IVT [n = 44]; EVT [n = 40]; 44 boys [64.7%]; median [IQR] age, 11 [4-16] years; anterior circulation involvement, 57 [83.8%]). Median (IQR) pedNIHSS score at admission was 13 (7-19), higher in the EVT group at 16 (IQR, 10-20) vs 9 (6-17) in the IVT only group (P &lt; .01). Median time from stroke onset to imaging was higher in the EVT group at 3 hours and 7 minutes (IQR, 2 hours and 3 minutes to 6 hours and 24 minutes) vs 2 hours and 39 minutes (IQR, 1 hour and 51 minutes to 4 hours and 13 minutes) (P = .04). Median admission ASPECTS score was 8 (IQR, 6-9). The main stroke etiologies were cardioembolic (21 [30.9%]) and focal cerebral arteriopathy (17 [25.0%]). Median (IQR) time from stroke onset to IVT was 3 hours and 30 minutes (IQR, 2 hours and 33 minutes to 4 hours and 28 minutes). In the EVT group, the rate of postprocedure successful reperfusion (≥modified Treatment in Cerebral Infarction 2b) was 80.0% (32 of 40). Persistent proximal arterial stenosis was more frequent in focal cerebral arteriopathy (P &lt; .01). Death occurred in 3 patients (4.4%). Median pedNIHSS reduction at 24 hours was 4 (IQR, 0-9) points. Intracerebral hemorrhage occurred in 4 patients and symptomatic intracerebral hemorrhage occurred in 1 patient, all in the EVT group. The median mRS was 2 (IQR, 0-3) at day 90 and 1 (IQR, 0-2) at 1 year, which was not significantly different between EVT and IVT only groups, although different in initial severity.Conclusions and Relevance: The findings of this cohort study suggest that use of EVT and/or IVT is safe in children with AIS

Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm

International audienceIntracranial aneurysms (IAs) are acquired cerebrovascular abnormalities characterized by localized dilation and wall thinning in intracranial arteries, possibly leading to subarachnoid hemorrhage and severe outcome in case of rupture. Here, we identified one rare nonsense variant (c.1378A>T) in the last exon of ANGPTL6 (Angiopoietin-Like 6)—which encodes a circulating pro-angiogenic factor mainly secreted from the liver—shared by the four tested affected members of a large pedigree with multiple IA-affected case subjects. We showed a 50% reduction of ANGPTL6 serum concentration in individuals heterozygous for the c.1378A>T allele (p.Lys460Ter) compared to relatives homozygous for the normal allele, probably due to the non-secretion of the truncated protein produced by the c.1378A>T transcripts. Sequencing ANGPTL6 in a series of 94 additional index case subjects with familial IA identified three other rare coding variants in five case subjects. Overall, we detected a significant enrichment (p = 0.023) in rare coding variants within this gene among the 95 index case subjects with familial IA, compared to a reference population of 404 individuals with French ancestry. Among the 6 recruited families, 12 out of 13 (92%) individuals carrying IA also carry such variants in ANGPTL6, versus 15 out of 41 (37%) unaffected ones. We observed a higher rate of individuals with a history of high blood pressure among affected versus healthy individuals carrying ANGPTL6 variants, suggesting that ANGPTL6 could trigger cerebrovascular lesions when combined with other risk factors such as hypertension. Altogether, our results indicate that rare coding variants in ANGPTL6 are causally related to familial forms of IA