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BACKGROUND: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA).METHODS: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220.FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]).INTERPRETATION: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow.FUNDING: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.

BackgroundThe relationship between the interventionist’s experience and outcomes of endovascular thrombectomy (EVT) for acute ischemic stroke of the anterior circulation, is unclear.ObjectiveTo assess the effect of the interventionist’s level of experience on clinical, imaging, and workflow outcomes. Secondly, to determine which of the three experience definitions is most strongly associated with these outcome measures.MethodsWe analysed data from 2700 patients, included in the MR CLEAN Registry. We defined interventionist’s experience as the number of procedures performed in the year preceding the intervention (EXPfreq), total number of procedures performed (EXPno), and years of experience (EXPyears). Our outcomes were the baseline-adjusted National Institutes of Health Stroke Scale (NIHSS) score at 24–48 hours post-EVT, recanalization (extended Thrombolysis in Cerebral Infarction (eTICI) score ≥2B), and procedural duration. We used multilevel regression models with interventionists as random intercept. For EXPfreq and EXPno results were expressed per 10 procedures.ResultsIncreased EXPfreq was associated with lower 24–48 hour NIHSS scores (adjusted (a)β:−0.46, 95% CI −0.70 to −0.21). EXPno and EXPyears were not associated with short-term neurological outcomes. Increased EXPfreq and EXPno were both associated with recanalization (aOR=1.20, 95% CI 1.11 to 1.31 and aOR=1.08, 95% CI 1.04 to 1.12, respectively), and increased EXPfreq, EXPno, and EXPyears were all associated with shorter procedure times (aβ:−3.08, 95% CI−4.32 to −1.84; aβ:−1.34, 95% CI−1.84 to −0.85; and aβ:−0.79, 95% CI−1.45 to −0.13, respectively).ConclusionsHigher levels of interventionist’s experience are associated with better outcomes after EVT, in particular when experience is defined as the number of patients treated in the preceding year. Every 20 procedures more per year is associated with approximately one NIHSS score point decrease, an increased probability for recanalization (aOR=1.44), and a 6-minute shorter procedure time.

Background Insight into outcome variation between hospitals could help to improve quality of care. We aimed to assess the validity of early outcomes as quality indicators for acute ischemic stroke care for patients treated with endovascular therapy (EVT). Methods and Results We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, a large multicenter prospective cohort study including 3279 patients with acute ischemic stroke undergoing EVT. Random effect linear and proportional odds regression were used to analyze the effect of case mix on between‐hospital differences in 2 early outcomes: the National Institutes of Health Stroke Scale (NIHSS) score at 24 to 48 hours and the expanded thrombolysis in cerebral infarction score. Between‐hospital variation in outcomes was assessed using the variance of random hospital effects (tau 2 ). In addition, we estimated the correlation between hospitals' EVT‐patient volume and (case‐mix–adjusted) outcomes. Both early outcomes and case‐mix characteristics varied significantly across hospitals. Between‐hospital variation in the expanded thrombolysis in cerebral infarction score was not influenced by case‐mix adjustment (tau 2 =0.17 in both models). In contrast, for the NIHSS score at 24 to 48 hours, case‐mix adjustment led to a decrease in variation between hospitals (tau 2 decreases from 0.19 to 0.17). Hospitals' EVT‐patient volume was strongly correlated with higher expanded thrombolysis in cerebral infarction scores ( r =0.48) and weakly with lower NIHSS score at 24 to 48 hours ( r =0.15). Conclusions Between‐hospital variation in NIHSS score at 24 to 48 hours is significantly influenced by case‐mix but not by patient volume. In contrast, between‐hospital variation in expanded thrombolysis in cerebral infarction score is strongly influenced by EVT‐patient volume but not by case‐mix. Both outcomes may be suitable for comparing hospitals on quality of care, provided that adequate adjustment for case‐mix is applied for NIHSS score.

Background: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment. Methods: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes. Results: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71–0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16–0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24–0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50–0.89]; P =0.005; adjusted cOR, 0.74 [95% CI, 0.55–1.0]; P =0.04). Conclusions: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.

Background and Purpose: The benefit of endovascular treatment (EVT) for posterior circulation stroke (PCS) remains uncertain, and little is known on treatment outcomes in clinical practice. This study evaluates outcomes of a large PCS cohort treated with EVT in clinical practice. Simultaneous to this observational study, several intervention centers participated in the BASICS trial (Basilar Artery International Cooperation Study), which tested the efficacy of EVT for basilar artery occlusion in a randomized setting. We additionally compared characteristics and outcomes of patients treated outside BASICS in trial centers to those from nontrial centers. Methods: We included patients with PCS from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry: a prospective, multicenter, observational study of patients who underwent EVT in the Netherlands between 2014 and 2018. Primary outcome was a score of 0 to 3 on the modified Rankin Scale at 90 days. Secondary outcomes included reperfusion status and symptomatic intracranial hemorrhage. For outcome comparison between patients treated in trial versus nontrial centers, we used ordinal logistic regression analysis. Results: We included 264 patients of whom 135 (51%) had received intravenous thrombolysis. The basilar artery was most often involved (77%). Favorable outcome (modified Rankin Scale score 0–3) was observed in 115/252 (46%) patients, and 109/252 (43%) patients died. Successful reperfusion was achieved in 178/238 (75%), and symptomatic intracranial hemorrhage occurred in 9/264 (3%). The 154 nontrial patients receiving EVT in BASICS trial centers had similar characteristics and outcomes as the 110 patients treated in nontrial centers (modified Rankin Scale adjusted cOR: 0.77 [95% CI, 0.5–1.2]). Conclusions: Our study shows that high rates of favorable clinical outcome and successful reperfusion can be achieved with EVT for PCS, despite high mortality. Characteristics and outcomes of patients treated in trial versus nontrial centers were similar indicating that our cohort is representative of clinical practice in the Netherlands. Randomized studies using modern treatment approaches are needed for further insight in the benefit of EVT for PCS.

Purpose: To determine whether spectral detector CT (SDCT) with a plain non-enhanced monochromatic CT, a water-weighted image after iodine removal, an iodine map, and Mono energetic images changes the diagnosis and classification of intracranial hemorrhage based on single energy CT after endovascular treatment (EVT) for ischemic stroke. Methods: Two readers evaluated single energy and SD CT data collected from 63 patients within one week after EVT. They diagnosed ICH or contrast staining, and graded ICH according to the Heidelberg and Safe Implementation of Thrombolysis in Stroke–Monitoring Study (SITS-MOST) classification. Differences in diagnosis between single energy and SD CT were tested with Pearson's chi-squared test. Diagnostic values of single energy CT were calculated. Interrater agreement was based on Cohen’s Kappa. Results: When spectral data were added to single energy CT, the diagnosis of ICH changed in 8 CT scans (13%): in 4, the diagnosis of ICH was rejected and in 4, initially undetected ICH was diagnosed. In an additional 3 patients, the ICH grade was modified. CT alone had 88% sensitivity, 87% specificity, 88% positive diagnostic value, 87% negative diagnostic value, and 87% overall accuracy for ICH compared to SDCT. Interreader agreement on the presence of ICH was 0.84 (95% CI 0.51–0.86) for spectral CT and 0.84 (95% CI 0.73–0.97) for single energy CT. Conclusion: SD CT after endovascular treatment contributes to the distinction between intracranial hemorrhage and contrast staining.

Supplemental Digital Content is available in the text., Background and Purpose: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice. Methods: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic. Results: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low (

Background: Symptomatic intracranial hemorrhage (sICH) is a serious complication after endovascular treatment for ischemic stroke. We aimed to identify determinants of its occurrence and location. Methods: We retrospectively analyzed data from the Dutch MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and MR CLEAN registry. We included adult patients with a large vessel occlusion in the anterior circulation who underwent endovascular treatment within 6.5 hours of stroke onset. We used univariable and multivariable logistic regression analyses to identify determinants of overall sICH occurrence, sICH within infarcted brain tissue, and sICH outside infarcted brain tissue. Results: SICH occurred in 203 (6%) of 3313 included patients and was located within infarcted brain tissue in 50 (25%), outside infarcted brain tissue in 23 (11%), and both within and outside infarcted brain tissue in 116 (57%) patients. In 14 patients (7%), data on location were missing. Prior antiplatelet use, baseline systolic blood pressure, baseline plasma glucose levels, post-endovascular treatment modified treatment in cerebral ischemia score, and duration of procedure were associated with all outcome parameters. In addition, determinants of sICH within infarcted brain tissue included history of myocardial infarction (adjusted odds ratio, 1.65 [95% CI, 1.06–2.56]) and poor collateral score (adjusted odds ratio, 1.42 [95% CI, 1.02–1.95]), whereas determinants of sICH outside infarcted brain tissue included level of occlusion on computed tomography angiography (internal carotid artery or internal carotid artery terminus compared with M1: adjusted odds ratio, 1.79 [95% CI, 1.16–2.78]). Conclusions: Several factors, some potentially modifiable, are associated with sICH occurrence. Further studies should investigate whether modification of baseline systolic blood pressure or plasma glucose level could reduce the risk of sICH. In addition, determinants differ per location of sICH, supporting the hypothesis of varying underlying mechanisms. Registration: URL: https://www.isrctn.com/ ; Unique identifier: ISRCTN10888758.

Background: In patients with large vessel occlusion stroke of the anterior circulation, underlying cause is a determinant of outcome. Whether this is the case for posterior circulation large vessel occlusion stroke has yet to be determined. We aimed to report on cause in patients with posterior circulation stroke treated with endovascular thrombectomy and to analyze the association with functional outcome. Methods: We used data of patients with posterior circulation stroke included in the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) registry, a prospective multicenter observational study, between 2014 and 2018. Stroke cause was categorized into large artery atherosclerosis (LAA), cardioembolism, arterial dissection, embolic stroke of undetermined source (ESUS), other determined cause, or undetermined cause. For primary analysis on the association between cause and outcome, we used multivariable ordinal logistic regression analysis to estimate the adjusted common odds ratio for a shift towards a better functional outcome on the modified Rankin Scale at 90 days with LAA as a reference group. Secondary outcomes included favorable functional outcome (modified Rankin Scale score 0–3), National Institutes of Health Stroke Scale score at 24 to 48 hours, reperfusion on digital subtraction angiography, and stroke progression. Results: Of 264 patients with posterior circulation stroke, 84 (32%) had LAA, 48 (18%) cardioembolism, 31 (12%) dissection, and 14 (5%) ESUS. Patients with a dissection were younger (48 [interquartile range, 43–60] years) and had a lower National Institutes of Health Stroke Scale at baseline (12 [interquartile range, 6–31]) than patients with other cause. Functional outcome was better for patients with cardioembolism and ESUS compared to LAA (modified Rankin Scale adjusted common odds ratio, 2.4 [95% CI, 1.1–5.2], respectively adjusted common odds ratio, 3.1 [95% CI, 1.0–9.3]). Patients with a dissection had a lower chance of successful reperfusion compared with LAA (adjusted odds ratio, 0.20 [95% CI, 0.06–0.70]). Conclusions: Unlike the anterior circulation, most frequent cause in our posterior large vessel occlusion stroke cohort is LAA followed by cardioembolism, dissection, and ESUS. Patients with cardioembolism and ESUS have a better prognosis for functional outcome after endovascular thrombectomy than patients with LAA.

Background: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. Methods: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). Results: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P P P Conclusions: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.

Background and Purpose: Whereas a clear benefit of endovascular treatment for anterior circulation stroke has been established, randomized trials assessing the posterior circulation have failed to show efficacy. Previous studies in anterior circulation stroke suggest that advanced thrombectomy devices were of great importance in achieving clinical benefit. Little is known about the effect of thrombectomy techniques on outcomes in posterior circulation stroke. In this study, we compare first-line strategy of direct aspiration to stent retriever thrombectomy for posterior circulation stroke. Methods: We analyzed data of patients with a posterior circulation stroke who were included in the Multicentre Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry between March 2014 and December 2018, a prospective, nationwide study, in which data were collected from consecutive patients who underwent endovascular treatment for ischemic stroke in the Netherlands. We compared patients who underwent first-line aspiration versus stent retriever thrombectomy. Primary outcome was functional outcome according to the modified Rankin Scale. Secondary outcomes were reperfusion grade, complication rate, and procedure duration. Associations between thrombectomy technique and outcome measures were estimated with multivariable ordinal logistic regression analyses. Results: Overall, 71 of 205 patients (35%) were treated with aspiration, and 134 (65%) with stent retriever thrombectomy. Patients in the aspiration group had a lower pc-ASPECTS on baseline computed tomography, and general anesthesia was more often applied in this group. First-line aspiration was associated with better functional outcome compared with stent retriever thrombectomy (adjusted common odds ratio for a 1-point improvement on the modified Rankin Scale 1.94 [95% CI, 1.03–3.65]). Successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2B) was achieved more often with aspiration (87% versus 73%, P =0.03). Symptomatic hemorrhage rates were comparable (3% versus 4%). Procedure times were shorter in the aspiration group (49 versus 69 minutes P Conclusions: In this retrospective nonrandomized cohort study, our findings suggest that first-line aspiration is associated with a shorter procedure time, better reperfusion, and better clinical outcome than stent retriever thrombectomy in patients with ischemic stroke based on large vessel occlusion in the posterior circulation.

Background Time to reperfusion in patients with ischemic stroke is strongly associated with functional outcome and may differ between hospitals and between patients within hospitals. Improvement in time to reperfusion can be guided by between‐hospital and within‐hospital comparisons and requires insight in specific targets for improvement. We aimed to quantify the variation in door‐to‐reperfusion time between and within Dutch intervention hospitals and to assess the contribution of different time intervals to this variation. Methods and Results We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry. The door‐to‐reperfusion time was subdivided into time intervals, separately for direct patients (door‐to‐computed tomography, computed tomography‐to‐computed tomography angiography [CTA], CTA‐to‐groin, and groin‐to‐reperfusion times) and for transferred patients (door‐to‐groin and groin‐to‐reperfusion times). We used linear mixed models to distinguish the variation in door‐to‐reperfusion time between hospitals and between patients. The proportional change in variance was used to estimate the amount of variance explained by each time interval. We included 2855 patients of 17 hospitals providing endovascular treatment. Of these patients, 44% arrived directly at an endovascular treatment hospital. The between‐hospital variation in door‐to‐reperfusion time was 9%, and the within‐hospital variation was 91%. The contribution of case‐mix variables on the variation in door‐to‐reperfusion time was marginal (2%–7%). Of the between‐hospital variation, CTA‐to‐groin time explained 83%, whereas groin‐to‐reperfusion time explained 15%. Within‐hospital variation was mostly explained by CTA‐to‐groin time (33%) and groin‐to‐reperfusion time (42%). Similar results were found for transferred patients. Conclusions Door‐to‐reperfusion time varies between, but even more within, hospitals providing endovascular treatment for ischemic stroke. Quality of stroke care improvements should not only be guided by between‐hospital comparisons, but also aim to reduce variation between patients within a hospital, and should specifically focus on CTA‐to‐groin time and groin‐to‐reperfusion time.

Objectives Over 2500 percutaneous transhepatic cholangiography and biliary drainage (PTCD) procedures are yearly performed in the Netherlands. Most interventions are performed for treatment of biliary obstruction following unsuccessful endoscopic biliary cannulation. Our aim was to evaluate complication rates and risk factors for complications in PTCD patients after failed ERCP. Methods We performed an observational study collecting data from a cohort that was subjected to PTCD during a 5-year period in one academic and four teaching hospitals. Primary objective was the development of infectious (sepsis, cholangitis, abscess, or cholecystitis) and non-infectious complications (bile leakage, severe hemorrhage, etc.) and mortality within 30 days of the procedure. Subsequently, risk factors for complications and mortality were analyzed with a multilevel logistic regression analysis. Results A total of 331 patients underwent PTCD of whom 205 (61.9%) developed PTCD-related complications. Of the 224 patients without a pre-existent infection, 91 (40.6%) developed infectious complications, i.e., cholangitis in 26.3%, sepsis in 24.6%, abscess formation in 2.7%, and cholecystitis in 1.3%. Non-infectious complications developed in 114 of 331 patients (34.4%). 30-day mortality was 17.2% (N = 57). Risk factors for infectious complications included internal drainage and drain obstruction, while multiple re-interventions were a risk factor for non-infectious complications. Conclusion Both infectious and non-infectious complications are frequent after PTCD, most often due to biliary drain obstruction.

Alteplase with EVT versus EVT Alone for Stroke Trials involving Asian patients with acute stroke have suggested that endovascular treatment alone is not inferior to the usual practice of thrombolysis before endovascular treatment. This trial involving European patients did not show noninferiority or superiority of endovascular treatment alone.Background The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. Methods We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. Results The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). Conclusions In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, .)

Outcome of endovascular treatment in acute ischemic stroke patients depends on collateral circulation to provide blood supply to the ischemic territory. We evaluated the performance of a commercially available algorithm for assessing the collateral score (CS) in acute ischemic stroke patients.Retrospectively, baseline CTA scans (≤ 3-mm slice thickness) with an intracranial carotid artery (ICA), middle cerebral artery segment M1 or M2 occlusion, from the MR CLEAN Registry (n = 1627) were evaluated. All CTA scans were evaluated for visual CS (0-3) by eight expert radiologists (reference standard). A Web-based AI algorithm quantified the collateral circulation (0-100%) for correctly detected occlusion sides. Agreement between visual CS and categorized automated CS (0: 0%, 1:0- ≤ 50%, 2:50-100%, 3: 100%) was assessed. Area under the curve (AUC) values for classifying patients in having good (CS: 2-3) versus poor (CS: 0-1) collaterals and for predicting functional independence (90-day modified Rankin Scale 0-2) were computed. Influence of CTA acquisition timing after contrast material administration was reported.In the analyzed scans (n = 1024), 59% agreement was found between visual CS and automated CS. An AUC of 0.87 (95% CI: 0.85-0.90) was found for discriminating good versus poor CS. Timing of CTA acquisition did not influence discriminatory performance. AUC for predicting functional independence was 0.66 (95% CI 0.62-0.69) for automated CS, similar to visual CS 0.64 (95% CI 0.61-0.68).The automated CS performs similar to radiologists in determining a good versus poor collateral score and predicting functional independence in acute ischemic stroke patients with a large vessel occlusion.• Software for automated quantification of intracerebral collateral circulation on computed tomography angiography performs similar to expert radiologists in determining a good versus poor collateral score. • Software for automated quantification of intracerebral collateral circulation on computed tomography angiography performs similar to expert radiologists in predicting functional independence in acute ischemic stroke patients with a large vessel occlusion. • The timing of computed tomography angiography acquisition after contrast material administration did not influence the performance of automated quantification of the collateral status.

Supplemental Digital Content is available in the text., Background: Cerebral white matter lesions (WMLs) have been associated with a greater risk of poor functional outcome after ischemic stroke. We assessed the relations between WML burden and radiological and clinical outcomes in patients treated with endovascular treatment in routine practice. Methods: We analyzed data from the MR CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischaemic Stroke in the Netherlands)—a prospective, multicenter, observational cohort study of patients treated with endovascular treatment in the Netherlands. WMLs were graded on baseline noncontrast computed tomography using a visual grading scale. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included early neurological recovery, successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b), futile recanalization (modified Rankin Scale score ≥3 despite successful reperfusion), and occurrence of symptomatic intracranial hemorrhage. We used multivariable logistic regression models to assess associations between WML severity and outcomes, taking the absence of WML on noncontrast computed tomography as the reference category. Results: Of 3180 patients included in the MR CLEAN Registry between March 2014 and November 2017, WMLs were graded for 3046 patients and categorized as none (n=1855; 61%), mild (n=608; 20%), or moderate to severe (n=588; 19%). Favorable outcome (modified Rankin Scale score, 0–2) was achieved in 838 patients (49%) without WML, 192 patients (34%) with mild WML, and 130 patients (24%) with moderate-to-severe WML. Increasing WML grades were associated with a shift toward poorer functional outcome in a dose-dependent manner (adjusted common odds ratio, 1.34 [95% CI, 1.13–1.60] for mild WML and 1.67 [95% CI, 1.39–2.01] for moderate-to-severe WML; Ptrend

BackgroundRandomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen well. However, outcomes after EVT in these late window patients without perfusion imaging are largely unknown. We assessed their characteristics and outcomes in routine clinical practice.MethodsThe Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, multicentre study in the Netherlands, included patients with an anterior circulation occlusion who underwent EVT between 2014 and 2017. CT perfusion was no standard imaging modality. We used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age, prestroke modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, Alberta Stroke Programme Early CT Score (ASPECTS), collateral status, location of occlusion and treatment with intravenous thrombolysis. Outcomes included 3-month mRS score, functional independence (defined as mRS 0–2), and death.ResultsOf 3264 patients who underwent EVT, 106 (3.2%) were treated beyond 6.5 hours (median 8.5, IQR 6.9–10.6), of whom 93 (87.7%) had unknown time of stroke onset. CT perfusion was not performed in 87/106 (80.2%) late window patients. Late window patients were younger (mean 67 vs 70 years, pConclusionsWithout the use of CT perfusion selection criteria, EVT in the 6.5–24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/CT angiography characteristics. randomised controlled trials with lenient inclusion criteria are needed to identify more patients who can benefit from EVT in the late window.

To determine whether spectral detector CT (SDCT) with a plain non-enhanced monochromatic CT, a water-weighted image after iodine removal, an iodine map, and Mono energetic images changes the diagnosis and classification of intracranial hemorrhage based on single energy CT after endovascular treatment (EVT) for ischemic stroke.Two readers evaluated single energy and SD CT data collected from 63 patients within one week after EVT. They diagnosed ICH or contrast staining, and graded ICH according to the Heidelberg and Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) classification. Differences in diagnosis between single energy and SD CT were tested with Pearson's chi-squared test. Diagnostic values of single energy CT were calculated. Interrater agreement was based on Cohen's Kappa.When spectral data were added to single energy CT, the diagnosis of ICH changed in 8 CT scans (13%): in 4, the diagnosis of ICH was rejected and in 4, initially undetected ICH was diagnosed. In an additional 3 patients, the ICH grade was modified. CT alone had 88% sensitivity, 87% specificity, 88% positive diagnostic value, 87% negative diagnostic value, and 87% overall accuracy for ICH compared to SDCT. Interreader agreement on the presence of ICH was 0.84 (95% CI 0.51-0.86) for spectral CT and 0.84 (95% CI 0.73-0.97) for single energy CT.SD CT after endovascular treatment contributes to the distinction between intracranial hemorrhage and contrast staining.

Background and Purpose: Thrombectomy with stent retriever and direct aspiration are equally effective in the endovascular treatment of anterior circulation acute ischemic stroke. We report efficacy and safety of initial treatment technique per occlusion segment. Methods: For this study, we analyzed data from the MR CLEAN Registry, a prospective, observational study in all centers that perform endovascular therapy in the Netherlands. We used ordinal logistic regression analysis to compare clinical and technical results of first line direct aspiration treatment with that of stent retriever thrombectomy stratified for occlusion segment. Primary outcome measure was functional outcome at 3 months. Secondary outcome measures included reperfusion grade expressed as the extended Thrombolysis in Cerebral Infarction score, periprocedural complication risk, time to reperfusion, and mortality. Results: Of the 2282 included patients, 1658 (73%) were initially treated with stent retriever and 624 (27%) with aspiration. Four hundred sixty-two patients had an occlusion of the intracranial part of the carotid artery, 1349 of the proximal middle cerebral artery, and 471 of the distal parts of the middle cerebral artery. There was no difference in functional outcome between aspiration and stent retriever thrombectomy (odds ratio, 1.0 [95% CI, 0.9–1.2]) in any of the occlusion segments ( P value for interaction=0.2). Reperfusion rate was higher in the aspiration group (odds ratio, 1.4 [95% CI, 1.1–1.6]) and did not differ between occlusion segments ( P value for interaction=0.6). Procedure times were shorter in the aspiration group (minutes 50 versus 65 minutes; P Conclusions: In unselected patients with anterior circulation infarcts, we observed equal functional outcome of aspiration and stent retriever thrombectomy in all occlusion segments. When aspiration was the first line treatment modality, reperfusion rates were higher and procedure times shorter in all occlusion segments.

Background This case report demonstrates the value of IMPEDE-FX plugs in an embolization procedure of a false lumen of an infrarenal post-dissection aneurysm. Case presentation A 69-year-old patient was treated with mitral valve replacement, complicated by a Stanford type-A dissection. After 9 years he presented with an enlarging infrarenal post-dissection aneurysm. The false lumen was embolized using multiple IMPEDE-FX plugs as part of the treatment in addition to embolization of the inferior mesenteric artery and overstenting of the re-entry in the right iliac artery. At 15 months the CTA showed a fully thrombosed false lumen and remodeling of the true lumen. Conclusions The false lumen of an infrarenal post-dissection aneurysm can successfully be embolized using IMPEDE-FX embolization plugs as part of the treatment strategy. Prospective trials on patients with non-thrombosed false lumina are indicated.

Contains fulltext : 220823.pdf (Publisher’s version ) (Closed access) Before 2015, endovascular treatment (EVT) for acute ischemic stroke was considered a promising treatment option. Based on limited evidence, it was performed in several dedicated stroke centers worldwide on selected patients. Since 2015, EVT for patients with intracranial large vessel occlusion has quickly been implemented as standard treatment in many countries worldwide, supported by the revised international guidelines based on solid evidence from multiple clinical trials. We describe the development in use of EVT in the Netherlands before, during, and after the pivotal EVT trials. We used data from all patients who were treated with EVT in the Netherlands from January 2002 until December 2018. We undertook a time-series analysis to examine trends in the use of EVT using Poisson regression analysis. Incidence rate ratios per year with 95% CIs were obtained to demonstrate the impact and implementation after the publication of the EVT trial results. We made regional observation plots, adjusted for stroke incidence, to assess the availability and use of the treatment in the country. In the buildup to the MR CLEAN (Multicenter Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands), a slow increase of EVT patients was observed, with 0.2% of all ischemic stroke patients receiving EVT. Before the trial results were formally announced, a statistically significant increase in EVT-treated patients per year was observed (incidence rate ratio, 1.72 [95% CI, 1.46-2.04]), and after the trial publication, an immediate steep increase was seen, followed by a more gradual increase (incidence rate ratio, 2.14 [95% CI, 1.77-2.59]). In 2018, the percentage of ischemic stroke patients receiving EVT increased to 5.8%. A well-developed infrastructure, a pragmatic approach toward the use of EVT in clinical practice, in combination with a strict adherence by the regulatory authorities to national evidence-based guidelines has led to successful implementation of EVT in the Netherlands. Ongoing efforts are directed at further increasing the proportion of stroke patients with EVT in all regions of the country.

Introduction: Outcomes after endovascular treatment (EVT) for acute ischemic stroke are highly time dependent, but whether active reduction of time to treatment leads to better outcome has not been demonstrated. We compared data of the two subsequent MR CLEAN Registry cohorts, comprising all patients in the Netherlands who had EVT for acute ischemic stroke from 2014-2017, for a trend in time to treatment and its association with outcome. Methods: We compared workflow, successful reperfusion (eTICI 2B-3), NIHSS at 24h, functional outcome (mRS) at 90 days, occurrence of symptomatic intracranial hemorrhage (sICH) and mortality in patients with ischemic stroke and a proximal intracranial occlusion in the anterior circulation included in the second cohort of the Registry (June 2016-November 2017; n = 1779) to those in patients included in the first cohort (March 2014-June 2016; n = 1526) using logistic regression. Results: Baseline NIHSS was 16 in both cohorts. Times from onset-to-groin and onset-to-reperfusion were shorter in the second cohort than in the first (185 versus 210 minutes; p Discussion: Our data show that outcomes after EVT in routine clinical practice are improving, likely attributable to improved workflow and experience.

ObjectiveTo compare outcomes after endovascular treatment (EVT) for acute ischemic stroke with 3 different types of anesthetic management in clinical practice, as anesthetic management may influence functional outcome.MethodsData of patients with an anterior circulation occlusion, included in the Dutch nationwide, prospective Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry between March 2014 and June 2016, were analyzed. Patients were divided into 3 groups defined by anesthetic technique performed during EVT: local anesthesia only (LA), general anesthesia (GA), or conscious sedation (CS). Primary outcome was the modified Rankin Scale score at 90 days. To compare functional outcome between groups, we estimated a common odds ratio (OR) with ordinal logistic regression, adjusted for age, sex, prestroke modified Rankin Scale score, baseline NIH Stroke Scale score, collaterals, and time from onset to arrival at intervention center.ResultsA total of 1,376 patients were included. Performed anesthetic technique was LA in 821 (60%), GA in 381 (28%), and CS in 174 (13%) patients. Compared to LA, both GA and CS were associated with worse functional outcome on the modified Rankin Scale score at 90 days (GA cORadj 0.75; 95% confidence interval [CI] 0.58–0.97; CS cORadj 0.45; 95% CI 0.33–0.62). CS was associated with worse functional outcome than GA (cORadj 0.60; 95% CI 0.42–0.87).ConclusionsLA is associated with better functional outcome than systemic sedation in patients undergoing EVT for acute ischemic stroke. Whereas LA had a clear advantage over CS, this was less prominent compared to GA.Classification of evidenceThis study provides Class III evidence that for patients with acute ischemic stroke undergoing EVT, LA improves functional outcome compared to GA or CS.

BackgroundMechanical thrombectomy with stent retrievers has proved to be safe and effective in endovascular treatment of acute ischemic stroke. Direct aspiration has shown revascularization rates comparable to those of stent retrievers in the recent ASTER and COMPASS trials. However, the efficacy of aspiration in routine clinical practice has not yet been shown.ObjectiveTo show that aspiration has clinical and technical outcomes equal to those of stent retriever thrombectomy in daily clinical practice.MethodsWe analysed data of patients with a large vessel occlusion of the anterior circulation registered in the Dutch MR CLEAN Registry between March 2014 and June 2016. Primary outcome was functional outcome measured with the modified Rankin Scale (mRS) score. Secondary outcomes were reperfusion grade, periprocedural complication rate, and procedure duration. Association of treatment technique with functional outcome was estimated with univariable and multivariable ordinal logistic regression analysis and expressed as a common OR (cOR) for a shift towards better outcome on the mRS.ResultsAs first-line treatment, 207 of 1175 patients (17.6%) were treated with direct aspiration, and 968 (82.4%) by a stent retriever. We observed no differences in functional outcome (adjusted cOR=1.020 (95% CI 0.68 to 1.52)) and periprocedural complications. Successful reperfusion (extended Thrombolysis in Cerebral Infarction ≥2b) was similar. Duration of the procedure was shorter with aspiration (57 min (IQR 35–73) vs 70 min (IQR 47–95), pConclusionDirect aspiration shows clinical outcomes equal to those of stent retriever thrombectomy in our large multicenter real-life cohort. We found no difference in complication rates and shorter procedure times for aspiration.

Introduction: We aimed to investigate the outcome of endovascular treatment (EVT) for acute ischemic stroke in patients with low Alberta Stroke Program Early CT Score (ASPECTS). Methods: This study reports on MR CLEAN Registry patients with available baseline ASPECTS (N=1423). ASPECTS was trichotomized in 0-4, 5, and 6-10 in order to create low ASPECTS groups of similar size. Primary outcome was modified Rankin Scale score (mRS) at 90 days. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. Benefit of reperfusion (defined as extended thrombolysis in cerebral infarction [eTICI] score 2B-3) was assessed by multivariable ordinal logistic regression analysis, including an interaction term of reperfusion and ASPECTS, and it was expressed as an adjusted common odds ratio (acOR). A comparison with the MR CLEAN trial control arm was made to assess benefit of EVT. Results: Higher trichotomized ASPECTS was associated with improved mRS (acOR 1.4, 95%CI 1.2-1.7). For ASPECTS 0-4 (n=93) successful reperfusion was not associated with improved mRS (acOR 1.4, 95%CI 0.6-2.9). ASPECTS 5 (n=63) and ASPECTS 6-10 subgroups (n=1267) however, did show significant benefit of reperfusion (acOR 3.9, 95%CI 1.3-11.8; acOR 2.7, 95%CI 2.2-3.3, respectively)(Fig1). Interaction between trichotomized ASPECTS and reperfusion was not significant ( p =0.13). Comparison with the MR CLEAN trial control group showed that trichotomized ASPECTS did not modify the effect of EVT ( p =0.14). Patients with lower trichotomized ASPECTS had a higher risk of mortality (aOR 0.9, 95%CI 0.9-1.0), but not of sICH (aOR 1.0, 95%CI 0.9-1.1). Conclusion: ASPECTS does not modify effect of reperfusion or EVT on functional outcome after acute ischemic stroke. Patients with ASPECTS 5 or higher seem to benefit from successful reperfusion.

Supplemental Digital Content is available in the text., Background and Purpose— It is unclear whether endovascular treatment (EVT) is beneficial for patients with acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery. We aimed to compare functional outcomes, technical aspects, and complications of EVT between patients with acute ischemic stroke because of M2 and M1 occlusions in clinical practice. Furthermore, outcome and complications after EVT in dominant and nondominant caliber M2 division occlusions were studied. Methods— Data were obtained from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) which is an ongoing observational study in 16 Dutch centers performing EVT in the Netherlands. Functional outcome was measured with the modified Rankin Scale score at 90 days. Neurological recovery (delta National Institutes of Health Stroke Scale), successful reperfusion rates (extended Thrombolysis in Cerebral Infarction ≥2B), and safety outcomes were also investigated. Associations between occlusion location and outcome were analyzed with ordinal logistic regression models, with adjustment for other prognostic factors. Results— In total, 244 (24%) patients with an M2 and 759 (76%) patients with an M1 occlusion who underwent EVT were analyzed. Functional outcomes were not significantly different between patients with M2 versus M1 occlusions (adjusted common odds ratio, 1.24; 95% CI, 0.87–1.73). Occurrence of symptomatic intracerebral hemorrhage was also similar for M2 and M1 occlusions (6.6% versus 5.9%; P=0.84). Further analysis about dominance of an M2 branch was performed in 175 (72%) patients. Neurological recovery was comparable (mean delta National Institutes of Health Stroke Scale, −2±10 for dominant M2, −5±5 for nondominant M2, and −4±9 [P=0.24] for M1 occlusions). Furthermore, the effect of reperfusion status on functional outcome was comparable between occlusion divisions (common odds ratio, 1.27; 95% CI, 1.06–1.53 for dominant M2; common odds ratio, 1.32; 95% CI, 0.93–1.87 for nondominant M2; and common odds ratio, 1.35; 95% CI, 1.24–1.46 for M1 occlusions). Conclusions— Outcomes and complication rates after EVT were similar in patients with M2 and M1 occlusions. Although based on observational data and a limited sample size, a similar association of reperfusion status with functional outcome for all subgroups provides no evidence that patients with either a dominant or a nondominant M2 occlusion should be routinely excluded from EVT.

Objective The objective of this study was to demonstrate the 3-year outcome of the covered endovascular reconstruction of the aortic bifurcation (CERAB) technique for the treatment of extensive aortoiliac occlusive disease (AIOD). Methods Between February 2009 and July 2016, all patients treated with the CERAB technique for AIOD were identified in the local databases of two centers and analyzed. Demographics and lesion characteristics were scored. Follow-up consisted of clinical assessment, duplex ultrasound, and ankle-brachial indices. Patency rates and clinically driven target lesion revascularization were calculated by Kaplan-Meier analysis. Results Of 130 patients (69 male and 61 female) treated, 68% were diagnosed with intermittent claudication and 32% suffered from critical limb ischemia. The majority (89%) were TransAtlantic Inter-Society Consensus II D lesions, and the remaining were B and C lesions (both 5%). Median follow-up was 24 months (range, 0-67 months). The technical success rate was 97%, and 67% of cases were performed completely percutaneously. The ankle-brachial index improved significantly from 0.65 ± 0.22 preoperatively to 0.88 ± 0.15 after the procedure. The 30-day minor and major complication rate was 33% and 7%. The median hospital stay was 2 days (range, 1-76 days). At 1 year and 3 years of follow-up, 94% and 96% of the patients clinically improved at least one Rutherford category (2% and 0% unchanged, 4% and 4% worsened). Limb salvage rate was 98% at 1 year and 97% at 3 years of follow-up. Primary, primary assisted, and secondary patency was 86%, 91%, and 97% at 1 year; 84%, 89%, and 97% at 2 years; and 82%, 87%, and 97% at 3 years. Freedom from clinically driven target lesion revascularization was 87% at 1-year follow-up and 86% at both 2-year and 3-year follow-up. Conclusions The CERAB technique is a safe and feasible technique for the treatment of extensive AIOD with good 3-year results regarding patency and clinical improvement.

Background Clinical outcomes reported after treatment of infrapopliteal lesions with drug‐eluting stents (DESs) have been more favorable compared with percutaneous transluminal angioplasty with a bailout bare metal stent ( PTA ‐ BMS ) through midterm follow‐up in patients with critical limb ischemia. In the present study, long‐term results of treatment of infrapopliteal lesions with DESs are presented. Methods and Results Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA ‐ BMS or DESs with paclitaxel. Long‐term follow‐up consisted of annual assessments up to 5 years after treatment or until a clinical end point was reached. Clinical end points were major amputation (above ankle level), infrapopliteal surgical or endovascular reintervention, and death. Preserved primary patency (≤50% restenosis) of treated lesions was an additional morphological end point, assessed by duplex sonography. In total, 74 limbs (73 patients) were treated with DESs and 66 limbs (64 patients) were treated with PTA ‐ BMS . The estimated 5‐year major amputation rate was lower in the DES arm (19.3% versus 34.0% for PTA ‐ BMS ; P =0.091). The 5‐year rates of amputation‐ and event‐free survival (survival free from major amputation or reintervention) were significantly higher in the DES arm compared with PTA ‐BMS (31.8% versus 20.4%, P =0.043; and 26.2% versus 15.3%, P =0.041, respectively). Survival rates were comparable. The limited available morphological results showed higher preserved patency rates after DESs than after PTA ‐ BMS at 1, 3, and 4 years of follow‐up. Conclusions Both clinical and morphological long‐term results after treatment of infrapopliteal lesions in patients with critical limb ischemia are improved with DES compared with PTA ‐ BMS . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00471289.

Background & Purpose: Intra-arterial therapy (IAT) is being implemented worldwide as the main treatment option for acute ischemic stroke (AIS). We wondered whether effectiveness and safety results that have been reported in randomized clinical trials can be reproduced in everyday clinical practice. We will report results of the Dutch National post MR CLEAN IAT registry including work flow parameters, primary and secondary outcomes, as well as serious adverse events. Methods: The MR CLEAN Registry is a prospective registry of all patients undergoing IAT for AIS in the Netherlands, started after completion of the MR CLEAN trial in March 2014. Registration was required for reimbursement. A core set was defined, with inclusion criteria similar to those of the MR CLEAN trial, including a proven anterior circulation occlusion and treatment possible withing 6 hours from onset. The primary study outcome is the score on the modified Rankin Scale (mRS) at 90 days. The secondary clinical outcome is NIHSS after 24 to 48 hours. Secondary radiological outcomes include the mTICI score on DSA and final infarct volume and major bleeding on follow up NCCT. We used a propensity weighted and an unadjusted ordinal logistic regression model to compare outcomes in the MR CLEAN Registry core and total dataset with the treatment arm of MR CLEAN. Results: Between March 2014 and August 2016 the inclusion rate of the MR CLEAN Registry has been increasing steadily to an average of 79 (SD 22) per month for a cumulative inclusion of 1548 patients in July 2016 (Figure 1). Conclusions: The MR CLEAN registry data is now being analyzed. Results will be reported at the conference.

Supplemental Digital Content is available in the text., Background— Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions. Methods and Results— Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia–related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03). Conclusions— In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289.

Objective: The objective of this study was to assess the prognostic value of a high or immeasurable ankle-brachial index (ABI) at baseline for major amputation and amputation-free survival (AFS) in patients with critical limb ischemia (CLI). Methods: Data from two recent trials in patients with CLI and proven infrapopliteal arterial obstructive disease were pooled. Patients were allocated to the low (1.4)/immeasurable ABI subgroup. Major amputation and AFS rates were compared. Hazard ratios for major amputation and death were calculated. The net reclassification improvement of incorporating high/immeasurable ABI in the Project of Ex-Vivo vein graft Engineering via Transfection III (PREVENT III) prediction model was derived. Results: There were 146 patients (56.2%) who had a low ABI, 81 patients (31.2%) who had an intermediate ABI, and 33 patients (12.7%) who had a high/immeasurable ABI at baseline. Patients with high/immeasurable ABI showed higher 5-year major amputation (52.1%) and lower 5-year AFS (5.0%) rates than the intermediate (25.5% and 41.6%, respectively) and low ABI patients (23.5% and 46.9%, respectively; both P

Graft coronary artery disease (GCAD) limits allograft survival after cardiac transplantation. The objective of this study was to correlate GCAD with the level of immunosuppression in an established allogeneic rodent cardiac chronic rejection model to better understand the mechanisms of GCAD in this system.Donor PVG hearts were transplanted into the abdomen of ACI rats. Six recipient groups received either 10, 7.5 or 5 mg/kg/day of oral cyclosporine (CsA), for 90 (10 mg/90 d, 7.5 mg/90 d, 5 mg/90 d) or 10 days (10 mg/10 d, 7.5 mg/10 d, 5 mg/10 d; n = 10 all groups), and grafts procured on Day 90. GCAD was assessed by histology for percent luminal narrowing (%LN), percent affected vessels (%AV) and intima/media ratio (I/M ratio). Sections were stained for ED1-positive macrophages and MHC Class II-positive cells.The 10 mg/90 d treatment group showed significantly reduced GCAD compared with the 5mg/10d treatment group (%LN = 4.3 +/- 3.1% vs 39 +/- 11.9%, p0.05). The 7.5 mg/90 d group had a reduced %LN and I/M ratio compared with the 5 mg/10 d group (%LN = 8.0 +/- 3.5% vs 39 +/- 11.9%, p0.05; I/M ratio = 0.06 +/- 0.02 vs 0.41 +/- 0.14, p0.05). There was a trend toward reduction of GCAD with both increasing the dose of CsA as well as the duration of treatment. Continuous treatment with CsA reduced perivascular macrophage and MHC II cell infiltration. Macrophage infiltrates correlated strongly with GCAD (R(2)0.90, p0.01), and MHC II infiltrates showed a weak correlation, although not statistically significant (R(2)0.56, p = NS).This study further defines the effect of cyclosporine on GCAD in this cardiac transplantation model. In this system, higher dose and longer duration of treatment with CsA markedly reduces macrophage and MHC II infiltration, correlating with diminished GCAD. However, increasing dose and duration of CsA did not completely eliminate the development of GCAD. Non-immunologic factors could contribute to this occurrence.

Background: Oxidative stress after ischemia and reperfusion leads to leukocyte activation, the production of injurious cytokines, and increased expression of inflammatory adhesion molecules. This initial event is one of the most important alloantigen-independent factors associated with graft coronary artery disease (GCAD). Cyclic adenosine monophosphate (cAMP) is an important second messenger that inhibits the expression of tumor necrosis factor α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1) in vitro. Its levels decrease during organ preservation. We hypothesized that augmenting allograft cAMP levels with the water-soluble adenylate cyclase activator, NKH477, could decrease ischemia–reperfusion injury and inhibit the progression of GCAD. Methods: PVG to ACI rat heterotopic cardiac allografts, treated with NKH477 solution or vehicle, were reperfused for 4 hours or 90 days after 60 minutes of ischemia. We analyzed grafts for intracellular adhesion molecule 1 (ICAM-1), VCAM-1, and ELAM-1 mRNA expression; TNF-α and interleukin-6 (IL-6) protein expression; and myeloperoxidase activity. We also performed immunohistochemical analysis for ICAM-1 and VCAM-1 protein expression. At post-operative Day 90, the progression of GCAD had increased morphometrically. Results: NKH477-treated grafts had significantly decreased levels of myeloperoxidase activity compared with controls. In this group, TNF-α, IL-6, and VCAM-1 protein expression was inhibited; however, ICAM-1 and ELAM-1 expression did not alter. We found no differences in the degree of development of GCAD between groups. Conclusion: Although augmented intracellular cAMP prevented acute reperfusion injury, it was insufficient to prevent the development of GCAD. Intracellular adhesion molecule 1 and ELAM-1, whose expression NKH477 does not inhibit, may play important roles in the development of GCAD.

The Percutaneous transluminal Angioplasty and Drug eluting stents for Infrapopliteal lesions in critical limb ischemia (PADI) trial is a prospective, multicenter, randomized, controlled, double-arm study investigating the safety and efficacy of primary paclitaxel-eluting stent implantation vs primary percutaneous transluminal angioplasty (PTA) in infrapopliteal lesions in critical limb ischemia (CLI). PTA with provisional “bailout” stent implantation is currently an accepted treatment for arterial obstructions in CLI, including those in below-the-knee arteries. A drawback compared to open bypass surgery is the relatively high restenosis rate. One proposed method to reduce restenosis is the use of drug-eluting stents (DES), as these have shown good results in the coronary bed. Primary DES implantation for focal obstructions in infrapopliteal arteries in CLI potentially reduces restenosis compared to PTA alone and may subsequently prolong effect of treatment, allowing for better wound healing, and preventing recurrence of symptoms. In this article, we report on rationale, design, and progress of the PADI trial, which investigates the safety and efficacy of a paclitaxel-eluting stent system compared to PTA with provisional bare metal stent implantation (Clinicaltrials.gov number NCT00471289).

We are planning a prospective study in 200 patients with an abdominal artery aneurysm (AAA). Non-invasive measurements will be performed including tonometry-based pulse wave analysis (PWA) and pulse wave velocity (PWV), echocardiography, and 24-hour blood pressure measurements. This study will provide insight in how PWV/PWA-parameters can help identify characteristics of prostheses used to treat AAA that best match native aortic characteristics and will lead to the best long-term outcome after aneurysm repair. Also the interaction between blood pressure (and control) and cardiac output will be evaluated. These results will form the basis for evidence-based practice for stent choice and lead to better outcomes after AAA treatment. First we will validate non-invasive against invasive central pressure in 20 patients treated with endovascular aneurysm repair (EVAR). This study will provide insight if arterial stiffness parameters change over time after treatment of AAA and the possible role of PWV/PWA for the surveillance after treatment. We expect to provide insight in the various determinants of the PWV/PWA-parameters pre- and post-repair of AAA evaluation also includes graft material, intraluminal thrombus, and inflammation. We will study whether the different PWV/PWA parameters predict outcome after AAA repair for different prostheses. Finally, this study will reveal whether parameters of cardiac output obtained by tonometry correspond with parameters obtained by echocardiography in AAA patients. If so, the PWV/PWA measurement can detect cardiologic problems at an early stage during follow-up. By early treatment, the development of heart failure can be delayed or even prevented. We look forward to input on our study-plan.

BACKGROUND: Bcl-2 has been shown to have antioxidant properties. Early oxidative stress is an important antigen-independent factor that contributes to the development of graft coronary artery disease (GCAD). We hypothesized that adenoviral up-regulation of bcl-2 would decrease early oxidative stress and inhibit GCAD after heart transplantation. METHODS: PVG rat hearts were treated with adenovirus carrying the human bcl-2 gene (AdvBcl-2) or null adenovirus (AdvNull) then transplanted into the abdomens of PVG recipients. After 4 days of reperfusion to allow adenoviral gene expression, grafts were retransplanted into ACI rat recipients and reperfused for 4 or 8 hours or 90 days (cyclosporine A 7.5 mg/kg on postoperative day [POD] 0-9). Production of tumor necrosis factor (TNF)-alpha after 4 hours and oxidized glutathione (GSSG) after 8 hours indicated development of oxidative stress. 90-day allografts were assessed for GCAD by way of computerized morphometry. RESULTS: Over-expression of bcl-2 at the time of allograft reperfusion was confirmed by Western blotting. Whereas AdvNull-treated hearts demonstrated elevated TNF-alpha levels after 4 hours and increased GSSG after 8 hours of reperfusion, AdvBcl-2-treated hearts were no different from nontransplanted hearts. AdvBcl-2 treatment also resulted in decreased luminal narrowing and intima-to-media ratio at POD 90. CONCLUSIONS: Bcl-2 over-expression interrupts the development of oxidative stress in reperfused rat-heart allografts. Early up-regulation of bcl-2 also decreases GCAD, indicating the importance of early oxidative stress and the role that bcl-2 may play in the long-term function of heart transplants.