Predictors of Infarct Growth in Patients with Large Vessel Occlusion Treated with Endovascular Therapy.
ABSTRACT: Introduction:Endovascular therapy (EVT) is now evidence based in anterior circulation stroke caused by large vessel occlusion. Outcome is related to infarct size, but data on predictors of infarct growth is limited. We analyzed our cohort of EVT treated patients primarily selected by magnetic resonance imaging (MRI) to examine predictors of infarct growth and the association between infarct size and outcome. Methods:We identified 342 patients with anterior circulation stroke from 2004 to 2014 in our prospectively collected EVT database. Baseline infarct size was available for 281 (measured by MRI) while final infarct size was available for 312 patients. Functional outcome was defined by modified Rankin Score (mRS) after 90?days and good outcome was defined as mRS 0-2. Predictors of infarct growth were examined by regression analysis. Results:Successful reperfusion [odds ratio (OR) 0.17, 95% confidence interval (CI) (0.09-0.33)] was the strongest predictor of reduction of infarct growth. Receiving intravenous thrombolysis and a short time span from symptom onset to scanning also reduced infarct growth. Occlusion of the internal carotid artery (ICA) intracranially predicted infarct growth (OR?=?7.29, 95% CI: 2.36-22.53). EVT under general anesthesia and having a NIHSS between 10 and 15 were also associated with infarct growth. Discussion:Failure of reperfusion resulted in an average infarct growth of approximately 50?ml. Lack of reperfusion generally results in a poor outcome likely due to infarct growth. Occlusion of the intracranial ICA and EVT under general anesthesia predicted infarct growth, while successful reperfusion, getting intraveneous thrombolysis, and a short time span from onset to scan protected against growth. A median infarct size of 52?ml best discriminates between a good and a bad outcome.
Project description:<h4>Background</h4>Endovascular therapy (EVT) with stent retrievers in addition to i.v. thrombolysis (IVT) has proven effective in acute stroke patients with middle cerebral artery (MCA, M1 segment) and distal internal carotid artery (ICA) occlusion. Limited data exist concerning acute cervical ICA occlusion, either alone or in combination with intracranial ICA occlusion (tandem occlusion). Therefore we analyzed outcome and treatment effects in stroke associated with cervical ICA occlusion, with specific focus on the impact of intracranial ICA or M1 patency.<h4>Methods</h4>Seventy-eight patients with cervical ICA occlusion from our local stroke unit registry were analyzed retrospectively. Thrombolysis in Cerebral Infarction (TICI) classification, infarct size, modified Rankin scale (mRS), symptomatic intracerebral hemorrhage (ICH), and death were assessed as outcome parameters.<h4>Results</h4>Forty-three patients had isolated cervical ICA occlusion whereas 35 patients presented with extra-/intracranial tandem occlusion. Patients underwent IVT alone (n = 23), combined IVT/EVT (n = 28) or no treatment (n = 27). Treated and untreated patients with tandem occlusion had a worse outcome after 90 days compared to isolated cervical occlusion (OR for moderate outcome 0.29, 0.27-0.88, p = 0.01). Additional EVT improved outcome in patients with tandem occlusion (OR for moderate outcome: 15.43, 1.60-148.90, p = 0.008) but not isolated cervical occlusion (OR 1.33, 0.38-11.60, NS).<h4>Conclusions</h4>In contrast to tandem occlusion, stroke outcome in patients with isolated cervical ICA occlusion was generally more benign and not improved by combined IVT/EVT compared to IVT alone. Intracranial vessel patency may be critical for treatment decision in acute cervical ICA occlusion.
Project description:Importance:Reperfusion is a key factor for clinical outcome in patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) for large-vessel intracranial occlusion. However, data are scarce on the association between the time from onset and reperfusion results. Objective:To analyze the rate of reperfusion after EVT started at different intervals after symptom onset in patients with AIS. Design, Setting, and Participants:We conducted a meta-analysis of individual patient data from 7 randomized trials of the Highly Effective Reperfusion Using Multiple Endovascular Devices (HERMES) group. This is a multicenter cohort study of the intervention arm of randomized clinical trials included in the HERMES group. Patients with anterior circulation AIS who underwent EVT for M1/M2 or intracranial carotid artery occlusion were included. Each trial enrolled patients according to its specific inclusion and exclusion criteria. Data on patients eligible but not enrolled (eg, refusals or exclusions) were not available. All analyses were performed by the HERMES biostatistical core laboratory using the pooled database. Data were analyzed between December 2010 and April 2015. Main Outcomes and Measures:Successful reperfusion was defined as a modified thrombolysis in cerebral infarction score of 2b/3 at the end of the EVT procedure adjusted for age, occlusion location, pretreatment intravenous thrombolysis, and clot burden score and was analyzed in relation to different intervals (onset, emergency department arrival, imaging, and puncture) using mixed-methods logistic regression. Results:Among the 728 included patients, with a mean (SD) age of 65.4 (13.5) years and of whom 345 were female (47.4%), decreases in rates of successful reperfusion defined as a thrombolysis in cerebral infarction score of 2b/3 were observed with increasing time from admission or first imaging to groin puncture. The magnitude of effect was a 22% relative reduction (odds ratio, 0.78; 95% CI, 0.64-0.95) per additional hour between admission and puncture and a 26% relative reduction (odds ratio, 0.74; 95% CI, 0.59-0.93) per additional hour between imaging and puncture. Conclusions and Relevance:Because the probability of reperfusion declined significantly with time between hospital arrival and groin puncture, we provide additional arguments for minimizing the intervals after symptom onset in anterior circulation acute ischemic stroke.
Project description:PURPOSE:Clinically successful endovascular therapy (EVT) in ischemic stroke requires reliable noninvasive pretherapeutic selection criteria. We investigated the association of imaging parameters including CT angiographic collaterals and degree of reperfusion with clinical outcome after EVT. METHODS:In our database, we identified 93 patients with large vessel occlusion in the anterior circulation treated with EVT. Besides clinical data, we assessed the baseline Alberta Stroke Program Early CT score (ASPECTS) on noncontrast CT (NCCT) and CT angiography (CTA) source images, collaterals (CT-CS) and clot burden score (CBS) on CTA and the degree of reperfusion after EVT on angiography. Three readers, blinded to clinical information, evaluated the images in consensus. Data-driven multivariable ordinal regression analysis identified predictors of good outcome after 90 days as measured with the modified Rankin Scale. RESULTS:Successful angiographic reperfusion (OR 26.50; 95%-CI 9.33-83.61) and good collaterals (OR 9.69; 95%-CI 2.28-59.27) were independent predictors of favorable outcome along with female sex (OR 0.35; 95%-CI 0.14-0.85), younger age (OR 0.88; 95%-CI 0.83-0.92) and higher NCCT ASPECTS (OR 2.54; 95%-CI 1.01-6.63). Outcome was best in patients with good collaterals and successful reperfusion, but there was no statistical interaction between collaterals and reperfusion. CONCLUSIONS:CTA-collateral status was the strongest pretherapeutic predictor of favorable outcome in ischemic stroke patients treated with EVT. CTA-collaterals are thus well suited for patient selection in EVT. However, the independent effect of reperfusion on outcome tended to be stronger than that of CTA-collaterals.
Project description:INTRODUCTION:Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception. METHODS AND ANALYSIS:The Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24?hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0-2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design. ETHICS AND DISSEMINATION:Patients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations.
Project description:We aimed to evaluate the impact of underlying mechanism of basilar artery (BA) occlusion on the outcomes after endovascular therapy (EVT) for reperfusion and the outcome factors associated with each mechanism, and to identify radiologic parameters enabling to distinguish the underlying mechanism.From a registry database, 194 consecutive patients with acute BA occlusion who underwent EVT were analyzed. Stroke mechanism, classified into in situ atherosclerotic thrombosis (ISAT) and embolism, clot sign location profiles in pre-angiography magnetic resonance image (MRI), parameters of angiography and EVT, and reperfusion were assessed. Poor outcome was defined as a modified Rankin-Scale score at 90 days of 3-6.The mean age was 68.8±11.8 years (range 21-92 years) and seventy-eight (40.2%) were female patients. 102 (52.6%) patients were classified into an embolism mechanism and 92 (47.4%) into an ISAT mechanism. Overall, ISAT mechanism compared with embolism was significantly associated with poor outcomes (P = 0.002), along with the NIHSS scores, reperfusion status, and collateral status. In the embolism group, reperfusion (P = 0.001), NIHSS scores (P < 0.001), and onset-to-treatment time (P = 0.030) were significant outcome factors. However, in the ISAT group, baseline collateral status (P = 0.001) and NIHSS scores (P < 0.001) were significant outcome factors. A clot sign at the distal BA segment on pre-angiography MRI was strongly associated with embolism mechanism (P < 0.001).Stroke mechanism has a major influence on outcomes, and outcome predictors differ according to the underlying mechanism in acute BA occlusion with EVT. Clot sign profile on pre-angiography MRI might be useful to determine the underlying mechanism.
Project description:Reperfusion therapies are the mainstay of acute ischemic stroke (AIS) treatments and overall improve functional outcome. Among the established complications of intravenous (IV) tissue-type plasminogen activator (tPA), intracranial hemorrhage (ICH) is by far the most feared and has been extensively described by seminal works over the last two decades. Indeed, IV tPA is associated with increased odds of any ICH and symptomatic ICH responsible for increased mortality rate during the first week after an AIS. Despite these results, IV tPA has been found beneficial in several pioneering randomized trials and improves functional outcome at 3 months. Endovascular therapy (EVT) combined with IV tPA for AIS patients consecutive to an anterior circulation large-vessel occlusion does not increase ICH occurrence. Of note, EVT following IV tPA leads to significantly higher rates of early reperfusion than with IV tPA alone, with no difference in ICH, which challenges the paradigm of reperfusion as a major prognostic factor for ICH complications. However, several blood biomarkers (glycemia, platelet and neutrophil count), clinical factors (age, AIS severity, blood pressure management, diabetes mellitus), and neuroradiological factors (cerebral microbleeds, infarct size) have been identified as risk factors for ICH after reperfusion therapy. In the years to come, the ultimate goal will be to further improve either reperfusion rates and functional outcome, while reducing hemorrhagic complications. To this end, various approaches being investigated are discussed in this review, such as blood-pressure control after reperfusion or the use of new antiplatelet agents as an adjunct to IV tPA and exhibit reduced hemorrhagic potential during the early phase of AIS.
Project description:Background: High systolic blood pressure (BP) is associated with an increased risk of intracranial hemorrhage (ICH) in patients undergoing reperfusion therapy. However, there are no data from randomized trials to guide BP management after reperfusion following endovascular therapy (EVT) for patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO). The objective is to evaluate if BP control with a target of 100-129 mmHg systolic BP ("tight" SBP control) can reduce ICH as compared to 130-185 mmHg ("usual" SBP control) in AIS participants after reperfusion by EVT. Methods: The BP TARGET trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial. AIS participants with LVO experiencing successful reperfusion are randomly assigned, in a 1:1 ratio, to have a "tight" SBP control (100-129 mmHg) or a conservative SBP control (130-185 mmHg) during the following 24-36 h. The primary outcome is the rate of ICH (either symptomatic or asymptomatic) on follow-up CT scan at 24-36 h. Secondary outcomes include the rate of the symptomatic ICH, the overall distribution of the modified Rankin Scale (mRS) at 90 days, favorable outcome (90-day mRs 0-2), infarct volume at follow-up CT scan at 24-36 h, change in National Institute of Health Stroke Scale at 24 h, and all-cause mortality at 90 days. Conclusion: This is the first randomized trial directly comparing the efficacy of different SBP targets after EVT reperfusion. This prospective trial aims to determine whether a "tight" SBP control after EVT reperfusion can reduce the risk of ICH.
Project description:BACKGROUND:Futile reperfusion (poor functional status despite successful reperfusion) was observed in up to 67% of patients enrolled in recent endovascular treatment (EVT) clinical trials. We investigated the impact of baseline stroke severity on both futile reperfusion and therapeutic benefit of successful EVT. METHODS:Using a prospective multicenter stroke registry, we identified consecutive ischemic stroke patients with anterior circulation large artery occlusion, who were reperfused successfully by EVT (Thrombolysis in Cerebral Infarction grade 2b-3). The rate of futile reperfusion was assessed across the initial National Institutes of Health Stroke Scale (NIHSS) scores. The frequency of poor outcomes (modified Rankin scale [mRS] 3-6) according to NIHSS scores was compared between patients revascularized successfully by EVT and those who did not receive EVT, after standardizing for age. RESULTS:Among 21,591 patients with ischemic stroke, 972 (4.5%) received EVT within 12?h of onset, including 440 who met study eligibility criteria. Futile reperfusion was observed in 226 of the 440 study-eligible patients (51.4%) and was associated with stroke severity: 20.9% in NIHSS scores ?5, 34.6% in 6-10, 58.9% in 11-20, and 63.8% in >?20 (p?<?0.001). Nonetheless, the therapeutic benefit of EVT also increased with increasing stroke severity (p for interaction <?0.001): 0.1% in NIHSS ?5, 18.6% in 6-10, 28.7% in 11-20, and 34.3% in >?20. CONCLUSIONS:EVT is more beneficial with increasing stroke severity, although futile reperfusion also increases with higher stroke severity.
Project description:The contribution of lipids, including low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) and triglycerides (TG), to stroke outcomes is still debated. We sought to determine the impact of LDL-C concentrations on the outcome of patients with ischemic stroke in the anterior circulation who received treatment with endovascular thrombectomy (EVT). We performed a retrospective analysis of consecutive patients with acute ischemic stroke treated at a tertiary center between 2012 and 2016. Patients treated with EVT for large artery occlusion in the anterior circulation were selected. The primary endpoint was functional outcome at 3 months as measured with the modified Rankin Scale (mRS). Secondary outcome measures included hospital death and final infarct volume (FIV). Blood lipid levels were determined in a fasting state, 1 day after admission. We studied a total of 174 patients (44.8% men) with a median age of 74 years (interquartile range [IQR] 61-82) and median National Institutes of Health Stroke Scale at admission of 18 (14-22). Bridging therapy with intravenous tissue-plasminogen activator (t-PA) was administered in 122 (70.5%). The median LDL-C was 90 mg/dl (72-115). LDL-C demonstrated a U-type relationship with FIV (p = 0.036). Eighty-three (50.0%) patients had an mRS of 0-2 at 3 months. This favorable outcome was independently associated with younger age (OR 0.944, 95% CI 0.90-0.99, p = 0.012), thrombolysis in cerebral infarction 2b-3 reperfusion (OR 5.12, 95% CI 1.01-25.80, p = 0.015), smaller FIV (0.97 per cm3, 95% CI 0.97-0.99, p < 0.001), good leptomeningeal collaterals (OR 5.29, 95% CI 1.48-18.9, p = 0.011), and LDL-C more than 77 mg/dl (OR 0.179, 95% CI 0.04-0.74, p = 0.018). A higher LDL-C concentration early in the course of a stroke caused by large artery occlusion in the anterior circulation is independently associated with a favorable clinical outcome at 3 months. Further studies into the pathophysiological mechanisms underlying this observation are warranted.
Project description:BACKGROUND:Despite evidence of a quite large beneficial effect of endovascular treatment (EVT) for ischemic stroke caused by anterior circulation large vessel occlusion, many patients do not recover even after complete recanalization. To some extent, this may be attributable to incomplete microvascular reperfusion, which can possibly be improved by antiplatelet agents and heparin. It is unknown whether periprocedural antithrombotic medication in patients treated with EVT improves functional outcome. The aim of this study is to assess the effect of acetylsalicylic acid (ASA) and unfractionated heparin (UFH), alone, or in combination, given to patients with an ischemic stroke caused by an intracranial large vessel occlusion in the anterior circulation during EVT. METHODS:MR CLEAN-MED is a multicenter phase III trial with a prospective, 2?×?3 factorial randomized, open label, blinded end-point (PROBE) design, which aims to enroll 1500 patients. The trial is designed to evaluate the effect of intravenous ASA (300?mg), UFH (low or moderate dose), both or neither as adjunctive therapy to EVT. We enroll adult patients with a clinical diagnosis of stroke (NIHSS ??2) and with a confirmed intracranial large vessel occlusion in the anterior circulation on CTA or MRA, when EVT within 6?h from symptom onset is indicated and possible. The primary outcome is the score on the modified Rankin Scale (mRS) at 90?days. Treatment effect on the mRS will be estimated with ordinal logistic regression analysis, with adjustment for main prognostic variables. Secondary outcomes include stroke severity measured with the NIHSS at 24?h and at 5-7?days, follow-up infarct volume, symptomatic intracranial hemorrhage (sICH), and mortality. DISCUSSION:Clinical equipoise exists whether antithrombotic medication should be administered during EVT for a large vessel occlusion, as ASA and/or UFH may improve functional outcome, but might also lead to an increased risk of sICH. When one or both of the study treatments show the anticipated effect on outcome, we will be able to improve outcome of patients treated with EVT by 5%. This amounts to more than 50 patients annually in the Netherlands, more than 1800 in Europe, and more than 1300 in the USA. TRIAL REGISTRATION:ISRCT, ISRCTN76741621 . Dec 6, 2017.