Anat Horev

Higher volume endovascular stroke centers have faster times to treatment, higher reperfusion rates and higher rates of good clinical outcomes

Background and purpose Technological advances have helped to improve the efficiency of treating patients with large vessel occlusion in acute ischemic stroke. Unfortunately, the sequence of events prior to reperfusion may lead to significant treatment delays. This study sought to determine if high-volume (HV) centers were efficient at delivery of endovascular treatment approaches. Methods A retrospective review was performed of nine centers to assess a series of time points from obtaining a CT scan to the end of the endovascular procedure. Demographic, radiographic and angiographic variables were assessed by multivariate analysis to determine if HV centers were more efficient at delivery of care. Results A total of 442 consecutive patients of mean age 66±14 years and median NIH Stroke Scale score of 18 were studied. HV centers were more likely to treat patients after intravenous administration of tissue plasminogen activator and those transferred from outside hospitals. After adjusting for appropriate variables, HV centers had significantly lower times from CT acquisition to groin puncture (OR 0.991, 95% CI 0.989 to 0.997, p=0.001) and total procedure times (OR 0.991, 95% CI 0.986 to 0.996, p=0.001). Additionally, patients treated at HV centers were more likely to have a good clinical outcome (OR 1.86, 95% CI 1.11 to 3.10, p<0.018) and successful reperfusion (OR 1.82, 95% CI 1.16 to 2.86, p<0.008). Conclusions Significant delays occur in treating patients with endovascular therapy in acute ischemic stroke, offering opportunities for improvements in systems of care. Ongoing prospective clinical trials can help to assess if HV centers are achieving better clinical outcomes and higher reperfusion rates.

Advanced modality imaging evaluation in acute ischemic stroke may lead to delayed endovascular reperfusion therapy without improvement in clinical outcomes

Purpose Advanced neuroimaging techniques may improve patient selection for endovascular stroke treatment but may also delay time to reperfusion. We studied the effect of advanced modality imaging with CT perfusion (CTP) or MRI compared with non-contrast CT (NCT) in a multicenter cohort. Materials and methods This is a retrospective study of 10 stroke centers who select patients for endovascular treatment using institutional protocols. Approval was obtained from each institutions review board as only de-identified information was used. We collected demographic and radiographic data, selected time intervals, and outcome data. ANOVA was used to compare the groups (NCT vs CTP vs MRI). Binary logistic regression analysis was performed to determine factors associated with a good clinical outcome. Results 556 patients were analyzed. Mean age was 66±15 years and median National Institutes of Health Stroke Scale score was 18 (IQR 14–22). NCT was used in 286 (51%) patients, CTP in 190 (34%) patients, and MRI in 80 (14%) patients. NCT patients had significantly lower median times to groin puncture (61 min, IQR (40–117)) compared with CTP (114 min, IQR (81–152)) or MRI (124 min, IQR (87–165)). There were no differences in clinical outcomes, hemorrhage rates, or final infarct volumes among the groups. Conclusions The current retrospective study shows that multimodal imaging may be associated with delays in treatment without reducing hemorrhage rates or improving clinical outcomes. This exploratory analysis suggests that prospective randomised studies are warranted to support the hypothesis that advanced modality imaging is superior to NCT in improving clinical outcomes.

Primary manual aspiration thrombectomy (MAT) for acute ischemic stroke: safety, feasibility and outcomes in 112 consecutive patients

Aim To describe procedural aspects and clinical outcomes in a consecutive series of patients in whom manual aspiration thrombectomy (MAT) was performed as the first treatment modality with other techniques used only in case MAT did not yield recanalization. Methods A retrospective review of a prospectively acquired acute stroke intervention database was performed. Primary MAT was carried out with a preference for the largest catheter considered to be trackable into the target occlusive lesion. The catheter was wedged into the thrombus followed by manual aspiration with a 20 ml syringe. Results 112 consecutive patients were evaluated. The median age was 66 years and the median NIH Stroke Scale score was 17. Occlusion locations included the M1 (62%), M2 (8%), internal carotid artery terminus (19%) and the vertebrobasilar artery (11%). Patients with anterior occlusions had tandem extracranial/intracranial occlusive lesions in 18.7% Median time from symptom onset to groin puncture was 267 min, and from groin puncture to recanalization was 70 min. Successful recanalization (defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3) with primary MAT was 59% with a median of two passes. 41% of patients required the use of adjunctive therapy yielding an overall recanalization rate of TICI 2b/3 (86%) and TICI 3 (30.6%). Parenchymal hematoma of any type (PH1/PH2) was seen in 9.8% of patients, with symptomatic hemorrhage in 6%. Favorable outcomes (90-day modified Rankin Scale ≤2) were 46%. Mortality at 3 months was 31%. Primary MAT was associated with faster procedural times (mean 63 vs 97 min, p<0.0001) but not with higher rates of favorable outcomes. Conclusions Primary MAT is an alternative endovascular recanalization technique with reasonable first pass efficacy that will likely improve with technology and experience.

Door‐to‐Puncture: A Practical Metric for Capturing and Enhancing System Processes Associated With Endovascular Stroke Care, Preliminary Results From the Rapid Reperfusion Registry

Background In 2011, the Brain Attack Coalition proposed door‐to‐treatment times of 2 hours as a benchmark for patients undergoing intra‐arterial therapy (IAT). We designed the Rapid Reperfusion Registry to capture the percentage of stroke patients who meet the target and its impact on outcomes. Methods and Results This is a retrospective analysis of anterior circulation patients treated with IAT within 9 hours of symptom onset. Data was collected from December 31, 2011 to December 31, 2012 at 2 centers and from July 1, 2012 to December 31, 2012 at 7 centers. Short “Door‐to‐Puncture” (D2P) time was hypothesized to be associated with good patient outcomes. A total of 478 patients with a mean age of 68±14 years and median National Institutes of Health Stroke Scale (NIHSS) of 18 (IQR 14 to 21) were analyzed. The median times for IAT delivery were 234 minutes (IQR 163 to 304) for “last known normal‐to‐groin puncture” time (LKN‐to‐GP) and 112 minutes (IQR 68 to 176) for D2P time. The overall good outcome rate was 39.7% for the entire cohort. In a multivariable model adjusting for age, NIHSS, hypertension, diabetes, reperfusion status, and symptomatic hemorrhage, both short LKN‐to‐GP (OR 0.996; 95% CI [0.993 to 0.998]; P<0.001) and short D2P times (OR 0.993, 95% CI [0.990 to 0.996]; P<0.001) were associated with good outcomes. Only 52% of all patients in the registry achieved the targeted D2P time of 2 hours. Conclusions The time interval of D2P presents a clinically relevant time frame by which system processes can be targeted to streamline the delivery of IAT care nationally. At present, there is much opportunity to enhance outcomes through reducing D2P.

Streamlining door to recanalization processes in endovascular stroke therapy

Background In acute stroke due to large vessel occlusion, faster reperfusion leads to better outcomes. We analyzed the effect of optimization steps aimed to reduce treatment delays at our center. Methods Consecutive patients with ischemic stroke treated with endovascular therapy were prospectively analyzed. We divided the patients into pre-optimization (20 April 2012 to 8 October 2013) and post-optimization (9 October 2013 to 29 July 2014) periods. The main interventions included: (1) continuous feedback; (2) standardized immediate emergency department attending to stroke attending communication with interventional team activation for all potential interventions; (3) pre-notification by the emergency medical service; (4) minimizing additional diagnostic testing; (5) direct transport to the CT scanner; (6) transport directly from the CT scanner to the angiography suite. The main metric used to measure improvement was door to groin puncture time (D2P). Results We included a total of 286 patients (178 pre-optimization, 108 post-optimization). There were no significant differences between major baseline characteristics between the groups with the exception of higher median CT Alberta Stroke Program Early CT Score in the pre-optimization group (p=0.01). Median D2P improved from 105 min pre-optimization to 67 min post-optimization (p=0.0002). Rates of good clinical outcomes (modified Rankin Scale 0–2 at 3 months) were similar in both groups, with a trend toward a better outcome in the post-optimization group in a subgroup analysis of patients with anterior circulation occlusion who received intravenous tissue plasminogen activator. Conclusions This pilot study demonstrates that D2P times can be significantly reduced with a standardized multidisciplinary approach. There was no significant difference in the rate of 3-month good outcome, which is most likely due to the small sample size and confounding baseline patient characteristics.

Air Pollution and Ischemic Stroke Among Young Adults

Background and Purpose— Studies have demonstrated consistent associations between cardiovascular illness and particulate matter (PM) <10 and <2.5 &mgr;m in diameter, but stroke received less attention. We hypothesized that air pollution, an inflammation progenitor, can be associated with stroke incidence in young patients in whom the usual risk factors for stroke are less prevalent. We aimed to evaluate the association between stroke incidence and exposure to PM <10 and <2.5 &mgr;m, in a desert area characterized by a wide range of PM. Methods— We included all members of the largest health maintenance organization in Israel, who were admitted to a local hospital with stroke between 2005 and 2012. Exposure assessment was based on a hybrid model incorporating daily satellite remote sensing data at 1-km spatial resolution. We performed case-crossover analysis, stratified by personal characteristics and distance from main roads. Results— We identified 4837 stroke cases (89.4% ischemic stroke). Interquartile range of PM <10 and <2.5 &mgr;m was 36.3 to 54.7 and 16.7 to 23.3 &mgr;g/m3, respectively. The subjects’ average age was 70 years; 53.4% were males. Associations between ischemic stroke and increases of interquartile range average concentrations of particulate matter <10 or <2.5 &mgr;m at the day of the event were observed among subjects <55 years (odds ratio [95% confidence interval], 1.11 [1.02–1.20] and 1.10 [1.00–1.21]). Stronger associations were observed in subjects living within 75 m from a main road (1.22 [1.03–1.43] and 1.26 [1.04–1.51]). Conclusions— We observed higher risk for ischemic stroke associated with PM among young adults. This finding can be explained by the inflammatory mechanism, linking air pollution and stroke.

Outcomes after endovascular treatment for anterior circulation stroke presenting as wake-up strokes are not different than those with witnessed onset beyond 8 hours

Objective Previous studies have suggested that patients with wake-up stroke (WUS) may have superior outcomes compared with patients with a witnessed late time of onset after revascularization. We sought to test this hypothesis in patients with anterior circulation large vessel occlusion stroke (ACLVOS) treated with endovascular therapy beyond 8 h from time last seen well (TLSW). Methods A single center retrospective review of a prospectively acquired database of consecutive patients was performed to identify patients presenting beyond 8 h of TLSW with radiographic evidence of ACLVOS, small core, and large penumbra who subsequently underwent endovascular treatment. Results We identified 206 patients. Patients were divided into two groups: (1) patients with WUS (38%, n=78) and (2) patients with witnessed onset beyond 8 h (62%, n=128). The groups were similar in age, baseline National Institutes of Health Stroke Scale score, TLSW to reperfusion, baseline infarct volume, and rate of successful recanalization. Rates of good outcome (modified Rankin Scale score of 0–2 at 90 days, 43% vs 50%, p=0.3), parenchymal hematoma (9% vs 5.5%, p=0.3), and final infarct volume (75.2 vs 61.4 mL, p=0.6) were comparable. Multivariate analysis identified age (OR=0.95, 95% CI 0.91 to 0.99, p<0.042), successful recanalization (OR 6.0, 95% CI 1.5 to 23.5, p=0.009), and final infarct volume (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) but not mode of presentation as predictors of favorable outcomes. Conclusions Rates of good outcomes, parenchymal hematoma, and final infarct volumes following endovascular treatment may not be different in patients with WUS compared with patients with witnessed onset of symptoms beyond 8 h.

Posttreatment Variables Improve Outcome Prediction after Intra-Arterial Therapy for Acute Ischemic Stroke

Background: There are multiple clinical and radiographic factors that influence outcomes after endovascular reperfusion therapy (ERT) in acute ischemic stroke (AIS). We sought to derive and validate an outcome prediction score for AIS patients undergoing ERT based on readily available pretreatment and posttreatment factors. Methods: The derivation cohort included 511 patients with anterior circulation AIS treated with ERT at 10 centers between September 2009 and July 2011. The prospective validation cohort included 223 patients with anterior circulation AIS treated in the North American Solitaire Acute Stroke registry. Multivariable logistic regression identified predictors of good outcome (modified Rankin score ≤2 at 3 months) in the derivation cohort; model β coefficients were used to assign points and calculate a risk score. Discrimination was tested using C statistics with 95% confidence intervals (CIs) in the derivation and validation cohorts. Calibration was assessed using the Hosmer-Lemeshow test and plots of observed to expected outcomes. We assessed the net reclassification improvement for the derived score compared to the Totaled Health Risks in Vascular Events (THRIVE) score. Subgroup analysis in patients with pretreatment Alberta Stroke Program Early CT Score (ASPECTS) and posttreatment final infarct volume measurements was also performed to identify whether these radiographic predictors improved the model compared to simpler models. Results: Good outcome was noted in 186 (36.4%) and 100 patients (44.8%) in the derivation and validation cohorts, respectively. Combining readily available pretreatment and posttreatment variables, we created a score (acronym: SNARL) based on the following parameters: symptomatic hemorrhage [2 points: none, hemorrhagic infarction (HI)1-2 or parenchymal hematoma (PH) type 1; 0 points: PH2], baseline National Institutes of Health Stroke Scale score (3 points: 0-10; 1 point: 11-20; 0 points: >20), age (2 points: <60 years; 1 point: 60-79 years; 0 points: >79 years), reperfusion (3 points: Thrombolysis In Cerebral Ischemia score 2b or 3) and location of clot (1 point: M2; 0 points: M1 or internal carotid artery). The SNARL score demonstrated good discrimination in the derivation (C statistic 0.79, 95% CI 0.75-0.83) and validation cohorts (C statistic 0.74, 95% CI 0.68-0.81) and was superior to the THRIVE score (derivation cohort: C statistic 0.65, 95% CI 0.60-0.70; validation cohort: C-statistic 0.59, 95% CI 0.52-0.67; p < 0.01 in both cohorts) but was inferior to a score that included age, ASPECTS, reperfusion status and final infarct volume (C statistic 0.86, 95% CI 0.82-0.91; p = 0.04). Compared with the THRIVE score, the SNARL score resulted in a net reclassification improvement of 34.8%. Conclusions: Among AIS patients treated with ERT, pretreatment scores such as the THRIVE score provide only fair prognostic information. Inclusion of posttreatment variables such as reperfusion and symptomatic hemorrhage greatly influences outcome and results in improved outcome prediction.

Predictors of Good Outcome After Endovascular Therapy for Vertebrobasilar Occlusion Stroke

Background and Purpose— Endovascular therapy is increasingly used in acute ischemic stroke treatment and is now considered the gold standard approach for selected patient populations. Prior studies have demonstrated that eventual patient outcomes depend on both patient-specific factors and procedural considerations. However, these factors remain unclear for acute basilar artery occlusion stroke. We sought to determine prognostic factors of good outcome in acute posterior circulation large vessel occlusion strokes treated with endovascular therapy. Methods— We reviewed our prospectively collected endovascular databases at 2 US tertiary care academic institutions for patients with acute posterior circulation strokes from September 2005 to September 2015 who had 3-month modified Rankin Scale documented. Baseline characteristics, procedural data, and outcomes were evaluated. A good outcome was defined as a 90-day modified Rankin Scale score of 0 to 2. The association between clinical and procedural parameters and functional outcome was assessed. Results— A total of 214 patients qualified for the study. Smoking status, creatinine levels, baseline National Institutes of Health Stroke Scale score, anesthesia modality (conscious sedation versus general anesthesia), procedural length, and reperfusion status were significantly associated with good outcomes in the univariate analysis. Multivariate logistic regression indicated that only smoking (odds ratio=2.61; 95% confidence interval, 1.23–5.56; P=0.013), low baseline National Institutes of Health Stroke Scale score (odds ratio=1.09; 95% confidence interval, 1.04–1.13; P<0.0001), and successful reperfusion status (odds ratio=10.80; 95% confidence interval, 1.36–85.96; P=0.025) were associated with good outcome. Conclusions— In our retrospective case series, only smoking, low baseline National Institutes of Health Stroke Scale score, and successful reperfusion status were associated with good outcome in patients with posterior circulation stroke treated with endovascular therapy.

Direct Thrombectomy versus Bridging for Patients with Emergent Large-Vessel Occlusions

Background and Aims: Patients with emergent large-vessel occlusion (ELVO) that present earlier than 4 h from onset are usually treated with bridging systemic thrombolysis followed by endovascular thrombectomy (EVT). Whether direct EVT (dEVT) could improve the chances of favorable outcome remains unknown. Methods: Consecutively, prospectively enrolled patients with ELVO presenting within 4 h of onset were entered into a National Acute Stroke Registry of patients undergoing revascularization. Patients treated with bridging were compared to those treated with dEVT. Excellent outcome was defined as having a modified Rankin Scale score ≤1 at 90 days following stroke. Results: Out of 392 patients that underwent thrombectomy, 270 (68%) presented within 4 h and were included. Of those, 159 (59%) underwent bridging and 111 (41%) underwent dEVT. Atrial fibrillation and congestive heart failure were more common in the dEVT group (43 vs. 30%, p = 0.04 and 20 vs. 8%, p = 0.009, respectively), but other risk factors, demographics, stroke severity and subtypes as well as baseline vessel patency state and time metrics did not differ. Excellent target vessel recanalization defined as TICI 3 (thrombolysis in cerebral infarction score) was more common in the dEVT group (75 vs. 61%, p = 0.03), but in-hospital mortality, discharge destinations, short- and long-term excellent outcome rates did not differ. On multivariate regression analysis, treatment modality did not significantly modify the chances of excellent outcome at discharge (OR 0.7; 95% CI 0.3–1.5) or at 3 months (OR 0.78 95% CI 0.4–1.4). Conclusions: The chances of attaining excellent functional outcomes are similar in ELVO patients undergoing dEVT or bridging.