Flat-panel Detector Perfusion Imaging and Conventional Multidetector Perfusion Imaging in Patients with Acute Ischemic Stroke : A Comparative Study.

PURPOSE: Flat-panel detector computed tomography (FDCT) is increasingly used in (neuro)interventional angiography suites. This study aimed to compare FDCT perfusion (FDCTP) with conventional multidetector computed tomography perfusion (MDCTP) in patients with acute ischemic stroke. METHODS: In this study, 19 patients with large vessel occlusion in the anterior circulation who had undergone mechanical thrombectomy, baseline MDCTP and pre-interventional FDCTP were included. Hypoperfused tissue volumes were manually segmented on time to maximum (Tmax) and time to peak (TTP) maps based on the maximum visible extent. Absolute and relative thresholds were applied to the maximum visible extent on Tmax and relative cerebral blood flow (rCBF) maps to delineate penumbra volumes and volumes with a high likelihood of irreversible infarcted tissue ("core"). Standard comparative metrics were used to evaluate the performance of FDCTP. RESULTS: Strong correlations and robust agreement were found between manually segmented volumes on MDCTP and FDCTP Tmax maps (r = 0.85, 95% CI 0.65-0.94, p < 0.001; ICC = 0.85, 95% CI 0.69-0.94) and TTP maps (r = 0.91, 95% CI 0.78-0.97, p < 0.001; ICC = 0.90, 95% CI 0.78-0.96); however, direct quantitative comparisons using thresholding showed lower correlations and weaker agreement (MDCTP versus FDCTP Tmax 6 s: r = 0.35, 95% CI -0.13-0.69, p = 0.15; ICC = 0.32, 95% CI 0.07-0.75). Normalization techniques improved results for Tmax maps (r = 0.78, 95% CI 0.50-0.91, p < 0.001; ICC = 0.77, 95% CI 0.55-0.91). Bland-Altman analyses indicated a slight systematic underestimation of FDCTP Tmax maximum visible extent volumes and slight overestimation of FDCTP TTP maximum visible extent volumes compared to MDCTP. CONCLUSION: FDCTP and MDCTP provide qualitatively comparable volumetric results on Tmax and TTP maps; however, direct quantitative measurements of infarct core and hypoperfused tissue volumes showed lower correlations and agreement.

Connecting the DOTs: a novel imaging sign on flat-panel detector CT indicating distal vessel occlusions after thrombectomy.

BACKGROUND: Immediate non-contrast post-interventional flat-panel detector CT (FPDCT) has been suggested as an imaging tool to assess complications after endovascular therapy (EVT). We systematically investigated a new imaging finding of focal hyperdensities correlating with remaining distal vessel occlusion after EVT. METHODS: A single-center retrospective analysis was conducted for all acute ischemic stroke patients admitted between July 2020 and December 2022 who underwent EVT and immediate post-interventional FPDCT. A blinded core lab performed reperfusion grading on post-interventional digital subtraction angiography (DSA) images and evaluated focal hyperdensities on FPDCT (here called the distal occlusion tracker (DOT) sign). DOT sign was defined as a tubular or punctiform, vessel confined, hyperdense signal within the initial occlusion target territory. We assessed sensitivity and specificity of the DOT sign when compared with DSA findings. RESULTS: The median age of the cohort (n=215) was 74 years (IQR 63-82) and 58.6% were male. The DOT sign was positive in half of the cohort (51%, 110/215). The DOT sign had high specificity (85%, 95% CI 72% to 93%), but only moderate sensitivity (63%, 95% CI 55% to 70%) for detection of residual vessel occlusions. In comparison to the core lab, operators overestimated complete reperfusion in a quarter of the entire cohort (25%, 53/215). In more than half of these cases (53%, 28/53) there was a positive DOT sign, which could have mitigated this overestimation. CONCLUSION: The DOT sign appears to be a frequent finding on immediate post-interventional FPDCT. It correlates strongly with incomplete reperfusion and indicates residual distal vessel occlusions. In the future, it may be used to complement grading of reperfusion success and may help mitigating overestimation of reperfusion in the acute setting.

Value of Immediate Flat Panel Perfusion Imaging after Endovascular Therapy (AFTERMATH): A Proof of Concept Study.

BACKGROUND AND PURPOSE: Potential utility of flat panel CT perfusion imaging (FPCT-PI) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCT-PI obtained directly post-MT could provide additional potentially relevant information on tissue reperfusion status. MATERIALS AND METHODS: This was a single-center analysis of all patients with consecutive acute stroke admitted between June 2019 and March 2021 who underwent MT and postinterventional FPCT-PI (n = 26). A core lab blinded to technical details and clinical data performed TICI grading on postinterventional DSA images and qualitatively assessed reperfusion on time-sensitive FPCT-PI maps. According to agreement between DSA and FPCT-PI, all patients were classified into 4 groups: hypoperfusion findings perfectly matched by location (group 1), hypoperfusion findings mismatched by location (group 2), complete reperfusion on DSA with hypoperfusion on FPCT-PI (group 3), and hypoperfusion on DSA with complete reperfusion on FPCT-PI (group 4). RESULTS: Detection of hypoperfusion (present/absent) concurred in 21/26 patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 patients (group 1), while in 5 patients there was a mismatch by location (group 2). Of the remaining 5 patients with disagreement regarding the presence or absence of hypoperfusion, 3 were classified into group 3 and 2 into group 4. FPCT-PI findings could have avoided TICI overestimation in all false-positive operator-rated TICI 3 cases (10/26). CONCLUSIONS: FPCT-PI may provide additional clinically relevant information in a considerable proportion of patients undergoing MT. Hence, FPCT-PI may complement the evaluation of reperfusion efficacy and potentially inform decision-making in the angiography suite.

Long-Term Effect of Mechanical Thrombectomy in Stroke Patients According to Advanced Imaging Characteristics.

PURPOSE: Data on long-term effect of mechanical thrombectomy (MT) in patients with large ischemic cores (≥ 70 ml) are scarce. Our study aimed to assess the long-term outcomes in MT-patients according to baseline advanced imaging parameters. METHODS: We performed a single-centre retrospective cohort study of stroke patients receiving MT between January 1, 2010 and December 31, 2018. We assessed baseline imaging to determine core and mismatch volumes and hypoperfusion intensity ratio (with low ratio reflecting good collateral status) using RAPID automated post-processing software. Main outcomes were cross-sectional long-term mortality, functional outcome and quality of life by May 2020. Analysis were stratified by the final reperfusion status. RESULTS: In total 519 patients were included of whom 288 (55.5%) have deceased at follow-up (median follow-up time 28 months, interquartile range 1-55). Successful reperfusion was associated with lower long-term mortality in patients with ischemic core volumes ≥ 70 ml (adjusted hazard ratio (aHR) 0.20; 95% confidence interval (95% CI) 0.10-0.44) and ≥ 100 ml (aHR 0.26; 95% CI 0.08-0.87). The effect of successful reperfusion on long-term mortality was significant only in the presence of relevant mismatch (aHR 0.17; 95% CI 0.01-0.44). Increasing reperfusion grade was associated with a higher rate of favorable outcomes (mRS 0-3) also in patients with ischemic core volume ≥ 70 ml (aOR 3.58, 95% CI 1.64-7.83). CONCLUSION: Our study demonstrated a sustainable benefit of better reperfusion status in patients with large ischemic core volumes. Our results suggest that patient deselection based on large ischemic cores alone is not advisable.

No-reflow phenomenon in stroke patients: A systematic literature review and meta-analysis of clinical data.

BACKGROUND: The no-reflow phenomenon refers to the absence of microvascular reperfusion despite macrovascular reperfusion. AIM: The aim of this analysis was to summarize the available clinical evidence on no-reflow in patients with acute ischemic stroke. METHODS: A systematic literature review and a meta-analysis of clinical data on definition, rates, and impact of the no-reflow phenomenon after reperfusion therapy was carried out. A predefined research strategy was formulated according to the Population, Intervention, Comparison, and Outcome (PICO) model and was used to screen for articles in PubMed, MEDLINE, and Embase up to 8 September 2022. Whenever possible, quantitative data were summarized using a random-effects model. RESULTS: Thirteen studies with a total of 719 patients were included in the final analysis. Most studies (n = 10/13) used variations of the Thrombolysis in Cerebral Infarction scale to evaluate macrovascular reperfusion, whereas microvascular reperfusion and no-reflow were mostly assessed on perfusion maps (n = 9/13). In one-third of stroke patients with successful macrovascular reperfusion (29%, 95% confidence interval (CI), 21-37%), the no-reflow phenomenon was observed. Pooled analysis showed that no-reflow was consistently associated with reduced rates of functional independence (odds ratio (OR), 0.21, 95% CI, 0.15-0.31). CONCLUSION: The definition of no-reflow varied substantially across studies, but it appears to be a common phenomenon. Some of the no-reflow cases may simply represent remaining vessel occlusions, and it remains unclear whether no-reflow is an epiphenomenon of the infarcted parenchyma or causes infarction. Future studies should focus on standardizing the definition of no-reflow with more consistent definitions of successful macrovascular reperfusion and experimental set-ups that could detect the causality of the observed findings.

Susceptibility vessel sign, a predictor of long-term outcome in patients with stroke treated with mechanical thrombectomy.

BACKGROUND: The absence of the susceptibility vessel sign (SVS) in patients treated with mechanical thrombectomy (MT) is associated with poor radiological and clinical outcomes after 3 months. Underlying conditions, such as cancer, are assumed to influence SVS status and could potentially impact the long-term outcome. We aimed to assess SVS status as an independent predictor of long-term outcomes in MT-treated patients. METHODS: SVS status was retrospectively determined in consecutive MT-treated patients at a comprehensive stroke center between 2010 and 2018. Predictors of long-term mortality and poor functional outcome (modified Rankin Scale (mRS) ≥3) up to 8 years were identified using multivariable Cox and logistic regression, respectively. RESULTS: Of the 558 patients included, SVS was absent in 13% (n=71) and present in 87% (n=487) on baseline imaging. Patients without SVS were more likely to have active cancer (P=0.003) and diabetes mellitus (P<0.001) at the time of stroke. The median long-term follow-up time was 1058 days (IQR 533-1671 days). After adjustment for active cancer and diabetes mellitus, among others, the absence of SVS was associated with long-term mortality (adjusted HR (aHR) 2.11, 95% CI 1.35 to 3.29) and poor functional outcome in the long term (adjusted OR (aOR) 2.90, 95% CI 1.29 to 6.55). CONCLUSION: MT-treated patients without SVS have higher long-term mortality rates and poorer long-term functional outcome. It appears that this association cannot be explained by comorbidities alone, and further studies are warranted.

Prediction of delayed reperfusion in patients with incomplete reperfusion following thrombectomy.

BACKGROUND: The clinical course of patients with incomplete reperfusion after thrombectomy, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) score of 2a-2c, is heterogeneous. Patients showing delayed reperfusion (DR) have good clinical outcomes, almost comparable to patients with ad-hoc TICI3 reperfusion. We aimed to develop and internally validate a model that predicts DR occurrence in order to inform physicians about the likelihood of a benign natural disease progression. PATIENTS AND METHODS: Single-center registry analysis including all consecutive, study-eligible patients admitted between 02/2015 and 12/2021. Preliminary variable selection for the prediction of DR was performed using bootstrapped stepwise backward logistic regression. Interval validation was performed with bootstrapping and the final model was developed using a random forests classification algorithm. Model performance metrics are reported with discrimination, calibration, and clinical decision curves. Primary outcome was concordance statistics as a measure of goodness of fit for the occurrence of DR. RESULTS: A total of 477 patients (48.8% female, mean age 74 years) were included, of whom 279 (58.5%) showed DR on 24 follow-up. The model's discriminative ability for predicting DR was adequate (C-statistics 0.79 [95% CI: 0.72-0.85]). Variables with strongest association with DR were: atrial fibrillation (aOR 2.06 [95% CI: 1.23-3.49]), Intervention-To-Follow-Up time (aOR 1.06 [95% CI: 1.03-1.10]), eTICI score (aOR 3.49 [95% CI: 2.64-4.73]), and collateral status (aOR 1.33 [95% CI: 1.06-1.68]). At a risk threshold of R = 30%, use of the prediction model could potentially reduce the number of additional attempts in one out of four patients who will have spontaneous DR, without missing any patients who do not show spontaneous DR on follow-up. CONCLUSIONS: The model presented here shows fair predictive accuracy for estimating chances of DR after incomplete thrombectomy. This may inform treating physicians on the chances of a favorable natural disease progression if no further reperfusion attempts are made.

Evaluation of time-resolved whole brain flat panel detector perfusion imaging using RAPID ANGIO in patients with acute stroke: comparison with CT perfusion imaging.

BACKGROUND: In contrast to conventional CT perfusion (CTP) imaging, flat panel detector CT perfusion (FD-CTP) imaging can be acquired directly in the angiosuite. OBJECTIVE: To evaluate time-resolved whole brain FD-CTP imaging and assess clinically important qualitative and quantitative perfusion parameters in correlation with previously acquired conventional CTP using the new RAPID for ANGIO software. METHODS: We included patients with internal carotid artery occlusions and M1 or M2 occlusions from six centers. All patients underwent mechanical thrombectomy (MT) with preinterventional conventional CTP and FD-CTP imaging. Quantitative performance was determined by comparing volumes of infarct core, penumbral tissue, and mismatch. Eligibility for MT according to the perfusion imaging criteria of DEFUSE 3 was determined for each case from both conventional CTP and FD-CTP imaging. RESULTS: A total of 20 patients were included in the final analysis. Conventional relative cerebral blood flow (rCBF) <30% and FD-CTP rCBF <45% showed good correlation (R2=0.84). Comparisons of conventional CTP Tmax >6 s versus FD-CTP Tmax >6 s and CTP mismatch versus FD-CTP mismatch showed more variability (R2=0.57, and R2=0.33, respectively). Based on FD-CTP, 16/20 (80%) patients met the inclusion criteria for MT according to the DEFUSE 3 perfusion criteria, in contrast to 18/20 (90%) patients based on conventional CTP. The vessel occlusion could be correctly extrapolated from the hypoperfusion in 18/20 cases (90%). CONCLUSIONS: In our multicenter study, time-resolved whole brain FD-CTP was technically feasible, and qualitative and quantitative perfusion results correlated with those obtained with conventional CTP.

Association of Intravenous Thrombolysis with Delayed Reperfusion After Incomplete Mechanical Thrombectomy.

PURPOSE: Treatment of distal vessel occlusions causing incomplete reperfusion after mechanical thrombectomy (MT) is debated. We hypothesized that pretreatment with intravenous thrombolysis (IVT) may facilitate delayed reperfusion (DR) of residual vessel occlusions causing incomplete reperfusion after MT. METHODS: Retrospective analysis of patients with incomplete reperfusion after MT, defined as extended thrombolysis in cerebral infarction (eTICI) 2a-2c, and available perfusion follow-up imaging at 24 ± 12 h after MT. DR was defined as absence of any perfusion deficit on time-sensitive perfusion maps, indicating the absence of any residual occlusion. The association of IVT with the occurrence of DR was evaluated using a logistic regression analysis adjusted for confounders. Sensitivity analyses based on IVT timing (time between IVT start and the occurrence incomplete reperfusion following MT) were performed. RESULTS: In 368 included patients (median age 73.7 years, 51.1% female), DR occurred in 225 (61.1%). Atrial fibrillation, higher eTICI grade, better collateral status and longer intervention-to-follow-up time were all associated with DR. IVT did not show an association with the occurrence of DR (aOR 0.80, 95% CI 0.44-1.46, even in time-sensitive strata, aOR 2.28 [95% CI 0.65-9.23] and aOR 1.53 [95% CI 0.52-4.73] for IVT to incomplete reperfusion following MT timing <80 and <100 min, respectively). CONCLUSION: A DR occurred in 60% of patients with incomplete MT at ~24 h and did not seem to occur more often in patients receiving pretreatment IVT. Further research on potential associations of IVT and DR after MT is required.

Importance of Delayed Reperfusions in Patients With Incomplete Thrombectomy.

BACKGROUND: There is paucity of data regarding the effects of delayed reperfusion (DR) on clinical outcomes in patients with incomplete reperfusion following mechanical thrombectomy. We hypothesized that DR has a strong association with clinical outcome in patients with incomplete reperfusion after mechanical thrombectomy (expanded Thrombolysis in Cerebral Infarction, 2a-2c). METHODS: Single-institution's stroke registry retrospective analysis of patients admitted from February 2015 to December 2020. DR was defined as the absence of any perfusion delay on ≈24-hour contrast-enhanced follow-up perfusion imaging, whereas persistent perfusion deficit denotes a perfusion delay corresponding to the catheter angiographic deficit directly after the intervention. The association of perfusion outcome (DR versus persistent perfusion deficit) with the occurrence of new infarcts and 90-day functional independence (modified Rankin Scale score 0-2) was evaluated using logistic regression analyses. Comparison of predictive accuracy was evaluated by calculating area under the curve for models with and without perfusion outcome. RESULTS: In 566 patients (mean age 74, 49.6% female), new infarcts in the incomplete reperfusion areas were less common in DR versus persistent perfusion deficit patients (small punctiform: 17.1% versus 25%, large confluent: 7.9% versus 63.2%; P=0.001). After adjustment for confounders, DR was a strong predictor of functional independence (adjusted odds ratio, 2.37 [95% CI 1.34-4.23]). There was a significant improvement in predictive accuracy of functional independence when perfusion outcome was added to expanded Thrombolysis in Cerebral Infarction alone (area under the curve 0.57 versus 0.62, P=0.01). CONCLUSIONS: Occurrence of DR is closely associated with tissue outcome and functional independence. DR may be an independent prognostic parameter, suggesting it as a potential outcome surrogate for medical rescue therapies.

Bridging intravenous thrombolysis in patients with atrial fibrillation.

Background and purpose: 40% of acute ischemic stroke patients treated by mechanical thrombectomy (MT) have a clinical history of atrial fibrillation (AF). The safety of bridging intravenous thrombolysis (IVT) (MT + IVT) is currently being discussed. We aimed to analyze the interaction between oral anticoagulation (OAC) status or AF with bridging IVT, regarding the occurrence of symptomatic intracranial hemorrhage (sICH) and functional outcome. Materials and Methods: Multicentric observational cohort study (BEYOND-SWIFT registry) of consecutive patients undergoing MT between 2010 and 2018 (n = 2,941). Multinomial regression models were adjusted for prespecified baseline and plausible pathophysiological covariates identified on a univariate analysis to assess the association of AF and OAC status with sICH and good outcomes (90-day modified Rankin Scale score 0-2). Results: In the total cohort (median age 74, 50.6% women), 1,347 (45.8%) patients had AF. Higher admission National Institutes of Health Stroke Scale (NIHSS) score (aOR 1.04 [95% 1.02-1.06], per point of increase) and prior medication with Vitamin K antagonists (VKA) (aOR 2.19 [95% 1.27-3.66]) were associated with sICH. Neither AF itself (aOR 0.71 [95% 0.41-1.24]) nor bridging IVT (aOR 1.08 [0.67-1.75]) were significantly associated with increased sICH. Receiving bridging IVT (aOR 1.61 [95% 1.24-2.11]) was associated with good 90-day outcome, with no interaction between AF and IVT (p = 0.92). Conclusion: Bridging IVT appears to be a reasonable clinical option in selected patients with AF. Given the increased sICH risk in patients with VKA, subgroup analysis of the randomized controlled trials should analyze whether patients with VKA might benefit from withholding bridging IVT. Registration: clinicaltrials.gov; Unique identifier: NCT03496064.

Association of diabetes mellitus and admission glucose levels with outcome after endovascular therapy in acute ischaemic stroke in anterior circulation.

BACKGROUND AND PURPOSE: We aimed to assess the association of diabetes mellitus (DM) and admission hyperglycaemia (AH), respectively, and outcome in patients with acute ischaemic stroke with large vessel occlusion in the anterior circulation treated with endovascular therapy (EVT) in daily clinical practice. METHODS: Consecutive EVT patients admitted to our stroke centre between February 2015 and April 2020 were included in this observational cohort study. Patients with versus without DM and with versus without AH (glucose ≥ 7.8 mmol/L) were compared. RESULTS: We included 1020 patients (48.9% women, median age = 73.1 years); 282 (27.6%) had DM, and 226 (22.2%) had AH. Patients with versus without DM less often showed successful reperfusion (odds ratio [OR]adjusted  = 0.61, p = 0.023) and worse 3-month functional outcome (modified Rankin Scale [mRS] = 0-2: 31.3% vs. 48%, ORadjusted  = 0.59, p = 0.004; death: 38.9% vs. 24.1%, ORadjusted  = 1.75, p = 0.002; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.52, p = 0.005; death: ORadjusted  = 1.95, p = 0.005). If analysis was additionally adjusted for AH, only mRS shift was still significantly worse in patients with DM (padjusted  = 0.012). Patients with versus without AH showed similar successful reperfusion rates and worse 3-month functional outcome (mRS = 0-2: 28.3% vs. 50.4%, ORadjusted  = 0.52, p < 0.0001; death: 40.4% vs. 22.4%, ORadjusted  = 1.80, p = 0.001; mRS shift: padjusted  < 0.0001; if moderate/good collaterals and mismatch, mRS = 0-2: ORadjusted  = 0.38, p < 0.0001; death: ORadjusted  = 2.39, p < 0.0001). If analysis was additionally adjusted for DM, 3-month functional outcome remained significantly worse in patients with AH (mRS = 0-2: ORadjusted  = 0.58, p = 0.004; death: ORadjusted  = 1.57, p = 0.014; mRS shift: padjusted  = 0.004). DM independently predicted recurrent/progressive in-hospital ischaemic stroke (OR = 1.71, p = 0.043) together with admission National Institutes of Health Stroke Scale score (OR = 0.95, p = 0.005), and AH independently predicted in-hospital symptomatic intracranial haemorrhage (OR = 2.21, p = 0.001). The association of admission continuous glucose levels and most outcome variables was (inversely) J-shaped. CONCLUSIONS: Hyperglycaemia more than DM was associated with worse 3-month outcome in the patients studied, more likely so in the case of moderate/good collaterals and mismatch in admission imaging.

Heterogeneity of the Relative Benefits of TICI 2c/3 over TICI 2b50/2b67 : Are there Patients who are less Likely to Benefit?

PURPOSE: Incomplete reperfusion after mechanical thrombectomy (MT) is associated with a poor outcome. Rescue therapy would potentially benefit some patients with an expanded treatment in cerebral ischemia score (eTICI) 2b50/2b67 reperfusion but also harbors increased risks. The relative benefits of eTICI 2c/3 over eTICI 2b50/67 in clinically important subpopulations were analyzed. METHODS: Retrospective analysis of our institutional database for all patients with occlusion of the intracranial internal carotid artery (ICA) or the M1/M2 segment undergoing MT and final reperfusion of ≥eTICI 2b50 (903 patients). The heterogeneity in subgroups of different time metrics, age, National Institutes of Health Stroke Scale (NIHSS), number of retrieval attempts, Alberta Stroke Programme Early CT Score (ASPECTS) and site of occlusion using interaction terms (pi) was analyzed. RESULTS: The presence of eTICI 2c/3 was associated with better outcomes in most subgroups. Time metrics showed no interaction of eTICI 2c/3 over eTICI 2b50/2b67 and clinical outcomes (onset to reperfusion pi = 0.77, puncture to reperfusion pi = 0.65, onset to puncture pi = 0.63). An eTICI 2c/3 had less consistent association with mRS ≤2 in older patients (>82 years, pi = 0.038) and patients with either lower NIHSS (≤9) or very high NIHSS (>19, pi = 0.01). Regarding occlusion sites, the beneficial effect of eTICI 2c/3 was absent for occlusions in the M2 segments (aOR 0.73, 95% confidence interval [CI] 0.33-1.59, pi = 0.018). CONCLUSION: Beneficial effect of eTICI 2c/3 over eTICI 2b50/2b67 only decreased in older patients, M2-occlusions and patients with either low or very high NIHSS. Improving eTICI 2b50/2b67 to eTICI 2c/3 in those subgroups may be more often futile.

Association of reperfusion success and emboli in new territories with long term mortality after mechanical thrombectomy.

BACKGROUND: The degree of reperfusion is the most important modifiable predictor of 3 month functional outcome and mortality in ischemic stroke patients treated with mechanical thrombectomy. Whether the beneficial effect of reperfusion also leads to a reduction in long term mortality is unknown. METHODS: Patients undergoing mechanical thrombectomy between January 2010 and December 2018 were included. The post-thrombectomy degree of reperfusion and emboli in new territories were core laboratory adjudicated. Reperfusion was evaluated according to the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Vital status was obtained from the Swiss population register. Adjusted hazard ratios (aHRs) using time split Cox regression models were calculated. Subgroup analyses were performed in patients with borderline indications. RESULTS: Our study included 1264 patients (median follow-up per patient 2.5 years). Patients with successful reperfusion had longer survival times, attributable to a lower hazard of death within 0-90 days and for >90 days to 2 years (aHR 0.34, 95% CI 0.26 to 0.46; aHR 0.37, 95% CI 0.22 to 0.62). This association was homogeneous across all predefined subgroups (p for interaction >0.05). Among patients with successful reperfusion, a significant difference in the hazard of death was observed between eTICI2b50 and eTICI3 (aHR 0.51, 95% CI 0.33 to 0.79). Emboli in new territories were present in 5% of patients, and were associated with increased mortality (aHR 2.3, 95% CI 1.11 to 4.86). CONCLUSION: Successful, and ideally complete, reperfusion without emboli in new territories is associated with a reduction in long term mortality in patients treated with mechanical thrombectomy, and this was evident across several subgroups.

Association of Time of Day When Endovascular Therapy for Stroke Starts and Functional Outcome.

OBJECTIVE: To investigate the association between EVT start time in acute ischemic stroke (AIS) and mid-term functional outcome. METHODS: This retrospective cohort study included all AIS cases treated with EVT from two stroke center registries from January 2012 to December 2018. The primary outcome was the score on the modified Rankin Scale (mRS) and the utility-weighted mRS (uw-mRS) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention at a given EVT start time would lead to lower scores on the mRS (shift analysis). RESULTS: One thousand five hundred fifty-eight cases were equally allotted into twelve EVT-start-time periods. The primary outcome favored EVT start times in the morning at 08:00-10:20 and 10:20-11:34 (common odds ratio (OR), 0.53; 95% confidence interval (CI), 0.38 to 0.75; P<0.001; OR, 0.62; 95% CI, 0.44 to 0.87; P=0.006, respectively), while it disfavored EVT start times at the end of the working day at 15:55-17:15 and 18:55-20:55 (OR, 1.47; 95% CI, 1.03 to 2.09; P=0.034; OR, 1.49; 95% CI, 1.03 to 2.15; P=0.033). Symptom onset-to-EVT start time was significantly higher and use of IV t-PA significantly lower between 10:20-11:34 (P<0.004 and P=0.012, respectively). CONSLUSION: EVT for AIS in the morning leads to better mid-term functional outcome, while EVT at the end of the work day leads to poorer mid-term functional outcome. Neither difference in baseline factors, standard workflow and technical efficacy metrics could be identified as potential mediators of this effect.

Safety and Efficacy of Intra-arterial Urokinase After Failed, Unsuccessful, or Incomplete Mechanical Thrombectomy in Anterior Circulation Large-Vessel Occlusion Stroke.

Importance: Achieving complete reperfusion is a key determinant of good outcome in patients treated with mechanical thrombectomy (MT). However, data on treatments geared toward improving reperfusion after incomplete MT are sparse. Objective: To determine whether administration of intra-arterial urokinase is safe and improves reperfusion after failed or incomplete MT. Design, Setting, and Participants: This observational cohort study included a consecutive sample of patients treated with second-generation MT from January 1, 2010, through August 4, 2017. Data were collected from the prospective registry of a tertiary care stroke center. Of 1274 patients screened, 69 refused to participate, and 993 met the observational studies inclusion criteria of a large vessel occlusion in the anterior circulation. Data were analyzed from September 1, 2017, through September 20, 2019. Intervention: One hundred patients received intra-arterial urokinase after failed or incomplete MT using manual microcatheter injections. Main Outcomes and Measures: Primary safety outcome was the occurrence of symptomatic intracranial hemorrhage (sICH) according to the Prolyse in Acute Cerebral Thromboembolism II criteria. Secondary end points included 90-day mortality and 90-day functional independence (defined as modified Rankin Scale score of ≤2). Efficacy was evaluated angiographically, applying the Thrombolysis in Cerebral Infarction (TICI) scale. Results: After exclusion of patients with posterior circulation strokes and those treated with intra-arterial thrombolytics only, 993 patients were included in the final analyses (median age, 74.6 [interquartile range, 62.6-82.2] years; 505 [50.9%] women). Additional intra-arterial urokinase was administered in 100 patients (10.1%). The most common reason for administering intra-arterial urokinase was incomplete reperfusion (TICI<3) after MT (53 [53.0%]). After adjusting for baseline characteristics underlying case selection, intra-arterial urokinase was not associated with an increased risk of sICH (adjusted odds ratio [aOR], 0.81; 95% CI, 0.31-2.13) or 90-day mortality (aOR, 0.78; 95% CI, 0.43-1.40). Among 53 cases of partial or near-complete reperfusion and treated with intra-arterial urokinase, 32 (60.4%) had early reperfusion improvement, and 18 of 53 (34.0%) had an improvement in TICI grade. Correspondingly, patients treated with intra-arterial urokinase had higher rates of functional independence after adjusting for the selection bias favoring a priori poor TICI grades in the intra-arterial urokinase group (aOR, 1.93; 95% CI, 1.11-3.37). Conclusions and Relevance: In selected patients, adjunctive treatment with intra-arterial urokinase during or after MT was safe and improved angiographic reperfusion. Systemic evaluation of this approach in a multicenter prospective registry or a randomized clinical trial seems warranted.

Clinical effect of successful reperfusion in patients presenting with NIHSS < 8: data from the BEYOND-SWIFT registry.

BACKGROUND AND PURPOSE: If patients presenting with large vessel occlusions (LVO) and mild symptoms should be treated with endvoascular treatment (EVT) remains unclear. Aims of this study were (1) assessing the safety and technical efficacy of EVT in patients with NIHSS < 8 as opposed to a comparison group of patients presenting with NIHSS ≥ 8 and (2) evaluation of the clinical effect of reperfusion in patients with NIHSS < 8. METHODS: Patients included into the retrospective multicenter BEYOND-SWIFT registry (NCT03496064) were analyzed. Clinical effect of achieving successful reperfusion (defined as modified Thrombolysis in Cerebral Infarction grade 2b/3) in patients presenting with NIHSS < 8 (N = 193) was evaluated using multivariable logistic regression analyses (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI). Primary outcome was excellent functional outcome (modified Rankin Scale, mRS 0-1) at day 90. Safety and efficacy of mechanical thrombectomy in patients with NIHSS < 8 was compared to patients presenting with NIHSS ≥ 8 (N = 1423). RESULTS: Among patients with NIHSS < 8 (N = 193, 77/193, 39.9% receiving pre-interventional IV-tPA), successful reperfusion was significantly related to mRS 0-1 (aOR 3.217, 95%-CI 1.174-8.816) and reduced the chances of non-hemorrhagic neurological worsening (aOR 0.194, 95%-CI 0.050-0.756) after adjusting for prespecified confounders. In interaction analyses, the relative merits of achieving successful reperfusion were mostly comparable between patients presenting with NIHSS < 8 and NIHSS ≥ 8 as evidenced by non-significantly different aOR. Interventional safety and efficacy metrics were similar between patients with NIHSS < 8 and NIHSS ≥ 8. CONCLUSIONS: Achieving successful reperfusion is beneficial in patients with persisting LVO presenting with NIHSS < 8 and reduces the risk of non-hemorrhagic neurological worsening.