Virtual International Stroke Trials Archive Research Articles

Initial blood pressure and adverse cardiac events following acute ischaemic stroke: An individual patient data pooled analysis from the VISTA database.

Adverse cardiac events following ischaemic stroke (stroke-heart syndrome, SHS) pose a clinical challenge. We investigated the association between initial blood pressure at stroke presentation and the risk of SHS. We utilised data from the Virtual International Stroke Trials Archive (VISTA). We defined SHS as the incidence of cardiac complications within 30 days post-ischaemic stroke. These presentations included acute coronary syndrome encompassing myocardial injury, heart failure/left ventricular dysfunction, atrial fibrillation/flutter, other arrhythmia/electrocardiogram abnormalities, and cardiorespiratory arrest. Using Cox proportional hazards models, we assessed the risk trajectories for developing SHS and its presentations associated with initial blood pressure. We also explored the risk trajectories for 90-day mortality related to initial blood pressure. From 16,095 patients with acute ischaemic stroke, 14,965 (mean age 69 ± 12 years; 55% male) were analysed. Of these, 1774 (11.8%) developed SHS. The risk of SHS and initial blood pressure showed a U-shaped relationship. The lowest blood pressures (⩽130 mmHg systolic and ⩽55 mmHg diastolic) were associated with the highest risks (adjusted hazard ratio [95%confidence interval]: 1.40 [1.21-1.63]; p < 0.001, 1.71 [1.39-2.10]; p < 0.001, respectively, compared to referential blood pressure range).Cardiorespiratory arrest posed the greatest risk at higher blood pressure levels (2.34 [1.16-4.73]; p = 0.017 for systolic blood pressure >190 mmHg), whereas other presentations exhibited the highest risk at lower pressures. The 90-day mortality risk also followed a U-shaped distribution, with greater risks observed at high blood pressure thresholds. There is a U-shaped relationship between initial blood pressure at ischaemic stroke presentation and the risk of subsequent SHS.

The incidence and outcome of patients with early cardiovascular complications following intracerebral haemorrhage: An individual patient data pooled analysis from the VISTA database

Abstract Background Early cardiovascular (CV) complications in patients following intracerebral haemorrhage (ICH) is poorly understood. Such incident CV complications could be part of the so-called stroke-heart-syndrome occurring following ICH (SHS-ICH). We investigated the incidence and outcomes of patients with SHS-ICH. Methods Data were sought from the Virtual International Stroke Trials Archive (VISTA), an international repository of clinical trials data. We reviewed relevant adverse events and identified patients based on the incidence of cardiovascular complications within 30 days of post-ICH or ischaemic stroke (acute coronary syndrome [ACS] including acute myocardial injury, heart failure [HF]/left ventricular [LV] dysfunction, atrial fibrillation [AF]/atrial flutter [AFL], other arrhythmia/ ECG abnormalities, and cardio-respiratory arrest [CRA]). We conducted propensity score matching (PSM) to compare the incidence and outcomes of patients with SHS following ICH (SHS-ICH) with patients with SHS following acute ischaemic stroke (AIS). Poor outcome was defined as modified Rankin Scale, mRS ≥2, at 90 days. Results We pooled data from 12,438 participants recruited in acute stroke trials (mean age 68±12 years; 56% male), of which 1,171 (9.4%) were patients with ICH. Of the ICH patients, 150 patients (12.8%) had SHS-ICH. Following PSM, a total of 2,342 patients (1,171 for each of the ICH and AIS cohorts) were analysed. The incidence of SHS was not significantly different in the ICH and AIS cohorts (Table 1). The incidence of AF was significantly lower in patients with ICH compared to patients with AIS (1.5% vs. 4.5%, p&amp;lt;0.0001), despite comparable incidences of other arrhythmia/ECG abnormalities (9% vs. 9%, p=0.9). Multivariate-adjusted analysis found that SHS-ICH was associated with poor outcomes (Table 2, odds ratio, OR 1.08 [95%CI: 1.03-1.16], p=0.04, compared to ICH patients without SHS). Conclusions Stroke-heart syndrome is common and serves as a crucial prognostic marker in patient with ICH, with outcomes similar to SHS patients related to AIS. The development of SHS-ICH was associated with poorer outcomes compared to ICH patients without SHS.

Risk of death in patients with early cardiovascular complications following ischaemic stroke: an individual patient data pooled analysis from the VISTA database

Abstract Background Early cardiovascular complications may occur in patients following ischaemic stroke (stroke-heart-syndrome, SHS). We investigated the risk of death in patients with SHS, and across the SHS manifestations. Methods Data were sought from the Virtual International Stroke Trials Archive (VISTA), an international repository of clinical trials data. We reviewed relevant adverse events and classified patients into two cohorts based on the incidence of cardiovascular complications within 30 days post-stroke (acute coronary syndrome [ACS] including acute myocardial injury, heart failure [HF]/left ventricular [LV] dysfunction, atrial fibrillation [AF]/atrial flutter [AFL], other arrhythmia/ ECG abnormalities, and cardio-respiratory arrest [CRA]), i.e. those with SHS and those with stroke-only (without SHS). Using Cox proportional hazards model, we evaluated the 90-day risk of death trajectories associated with SHS. We also compared the 90-day risk of death across SHS manifestations excluding CRA, using multivariate analysis. Results Among 15,054 patients with ischaemic stroke (mean age 72±11 years; 55% male), 1,787 (11.8%; 95% confidence interval [CI]: 11.3-12.3, Table 1) developed SHS, with incidence peaked at day 3 post-stroke (interquartile range: 2-5). Other arrhythmia/ECG abnormalities were the most prevalent (6.5%; 95%CI: 6.1-6.9), followed by AF/AFL, HF/LV dysfunction, ACS/acute myocardial injury, and CRA. Patients who developed SHS between 10-30 days post-stroke had significantly higher risks of death compared to those with SHS within the first 0-3 days (adjusted hazard ratio [HR]: 2.13 [1.57-2.89]). In the multivariate-adjusted analysis which includes 13 background factors such as age and sex, SHS manifested as ACS/acute myocardial injury and HF/LV dysfunction were associated with highest risk of death within 90-day post-stroke (adjusted hazard ratio [HR] [95% CI], HR 2.13 (1.08-4.18) and HR 2.28 (1.42-3.66), respectively, Figure 1). Conclusions Stroke-heart syndrome is associated with high risk of death, with greater risk observed with the delayed SHS onset. Among the SHS manifestations, ACS/acute myocardial injury and HF/LV dysfunction were associated with the highest risk of death post-stroke.Figure 1

Stroke-heart syndrome and early mortality in patients with acute ischaemic stroke using hierarchical cluster analysis: An individual patient data pooled analysis from the VISTA database.

The patient clinical phenotypes at particularly high risk for early cardiac complications after a recent acute ischaemic stroke (AIS), that is, stroke-heart syndrome (SHS), remain poorly defined. We utilised hierarchical cluster analysis to identify specific phenotypic profiles associated with this risk. We gathered data on patients with AIS from the Virtual International Stroke Trials Archive, a global repository of clinical trial data. We examined cardiac complications within 30 days post-stroke, including acute coronary syndrome, heart failure, arrhythmias and cardiorespiratory arrest. We employed hierarchical cluster analysis to define distinct phenotypic risk profiles. The incidence/risk of SHS and 90-day mortality were compared across these profiles. We included 12,482 patients (mean age 69 ± 12 years; 55% male), yielding five phenotypes: Profile 1 ('elderly and AF'), Profile 2 ('young and smoker'), Profile 3 ('young'), Profile 4 ('cardiac comorbidities') and Profile 5 ('hypertension with atherosclerotic comorbidities'). Profiles 4 and 1 exhibited the highest risk for SHS (adjusted HR (95% CI): 2.01 (1.70-2.38) and 1.26 (1.05-1.51), respectively, compared to Profile 3), while Profiles 5 and 2 showed moderate risk and Profile 3 had the lowest risk. Although Profiles 1 and 4 were at the highest risk for most SHS presentations, Profile 5 had the highest risk for cardiorespiratory arrest (adjusted HR (95% CI): 2.99 (1.22-7.34)). The 90-day mortality risk was stratified by phenotype, with the highest risk observed in Profiles 5, and 4. Hierarchical cluster analysis effectively identified phenotypes with the highest risk of SHS and early mortality in patients with AIS.

High Resting Heart Rate Is Associated with Cardiovascular Death in Patients with Stroke, Independent of Sex

Introduction: High resting heart rate (HRHR) is a surrogate marker of increased sympathetic outflow. In acute stroke patients, HRHR is more commonly observed in women than in men. We analyzed whether HRHR (>86 bpm) adds incremental prognostic value for stroke outcomes in women. Methods: We analyzed data of 6,024 patients (2,568 women, mean age 68.98 years) with acute ischemic stroke from the Virtual International Stroke Trials Archive (VISTA). Results: Patients with HRHR were more often female (45.3 vs. 41.8%, p = 0.017), younger (66.0 ± 13.2 vs. 67.8 ± 12.6 years, p < 0.001), had higher baseline systolic blood pressure and more often diabetes. The primary composite endpoint of recurrent ischemic stroke, transient ischemic attack, myocardial infarction, or cardiovascular death within 90 days occurred more often in patients with HRHR (19.3 vs. 14.6%, p < 0.001). HRHR was associated with worse functional outcome at 90 days as assessed by modified Rankin Scale (mRS90: 3.03 ± 1.98 vs. 2.82 ± 1.94, p = 0.001). As exclusion of deceased patients (mRS90 of 6) resulted in a loss of association of HRHR with mRS90, it can be assumed that HRHR is mainly associated with poststroke vascular mortality, but not disability. Female sex was not associated with the primary endpoint but with adverse functional outcome measured by mRS90. Conclusion: HRHR was associated with adverse events and mortality after stroke. Despite a higher prevalence of HRHR in women, they did not reach the primary endpoint more often. However, women had a worse functional outcome (mRS) 3 months after stroke, independent of HRHR.

Cerebral Small Vessel Disease and Infarct Growth in Acute Ischemic Stroke Treated with Intravenous Thrombolysis.

We investigated relations between cerebral small vessel disease (cSVD) markers and evolution of the ischemic tissue from ischemic core to final infarct in people with acute ischemic stroke treated with intravenous thrombolysis. Data from the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) were used. Any pre-existing lacunar infarcts and white matter hyperintensities (WMH) were assessed on magnetic resonance (MR) before thrombolytic therapy. Acute ischemic core and final infarct volume were then assessed by two independent radiologists. The relationship among baseline markers of cSVD, acute ischemic core volume, final infarct volume, infarct growth (IG = final infarct - ischemic core), and infarct growth ratio (IGR = final infarct/ischemic core) was then assessed using linear and ordinal regression adjusted for age, sex, onset-to-treatment time, and stroke severity. We included 165 patients, mean (± SD) age 69.5 (± 15.7) years, 74 (45%) males, mean (± SD) ischemic core volume 25.48 (± 42.22) ml, final infarct volume 52.06 (± 72.88) ml, IG 26.58 (± 51.02) ml, IGR 8.23 (± 38.12). Seventy (42%) patients had large vessel occlusion, 20 (12%) acute small subcortical infarct. WMHs were present in 131 (79%) and lacunar infarcts in 61 (37%) patients. Final infarct volumes were 53.8ml and 45.2ml (WMHs/no WMHs), p = 0.139, and 24.6ml and 25.9ml (lacunar infarcts/no lacunar infarcts), p = 0.842. In linear and ordinal regression analyses, presence of lacunar infarcts was associated with smaller IG (β = - 0.17; p = 0.024; cOR = 0.52; 95%CI = 0.28-0.96, respectively) and WMHs were associated with smaller IGR (β = - 0.30; p = 0.004; cOR = 0.27; 95%CI = 0.11-0.69, respectively). In people with acute ischemic stroke treated with intravenous thrombolysis, cSVD features were associated with smaller growth of the acute ischemic area, suggesting less salvageable tissue at time of reperfusion therapy.

Bayesian modeling framework for optimizing pre-hospital stroke triage decisions

Ischemic stroke is responsible for significant morbidity and mortality in the United States and worldwide. Stroke treatment optimization requires emergency medical personnel to make rapid triage decisions concerning destination hospitals that may differ in their ability to provide highly time-sensitive pharmaceutical and surgical interventions. These decisions are particularly crucial in rural areas, where transport decisions can have a large impact on treatment times – often involving a trade-off between delay in pharmaceutical therapy or a delay in endovascular thrombectomy. In this work, we explore a Bayesian modeling framework to address this decision-making process, showing how these techniques may be used to fully account for diagnostic and therapeutic uncertainty. We demonstrate how these techniques can contextualize triage decision at a fine-grained spatial scale. We further show the application of this modeling approach in the US State of Iowa, using data from the Virtual International Stroke Trials Archive (VISTA), and describe potential next steps for improved triage. ABBREVIATION LVO: large vessel occlusion; non-LVO, non-large vessel occlusion; IVT: intravenous tissue plasminogen activator; EVT: endovascular thrombectomy; CSC: comprehensive stroke centers; PSC: primary stroke centers; DS: drip and ship; MS, mothership; EMS: Emergency Medical Service; BGLM: Bayesian Generalized Linear Model; BGAM: Bayesian Generalized Additive Model; BART: Bayesian Additive Regression Trees; VISTA: Virtual International Stroke Trials Archive; NIHSS: National Institute of Health Stroke Severity Scale; ASPECTS: Alberta Stroke Programme Early CT Score; mRS, modified Rankin score; ROCAUC: Area under the receiver operating characteristic curve; ELPD: Expected Log pointwise Predictive Density; SE: Standard Error; ICA: Internal Carotid Artery; M1: Middle Cerebral Artery segment 1; M2: Middle Cerebral Artery segment 2; TIA: Transient Ischemic Attack; Cr-I: Credible Intervals; LKW: Last Known Well

Abstract TMP95: Context Matters: Geographic Decision-Making Could Improve Prehospital Stroke Triage

Introduction: Emergency medical services (EMS) play a key role in stroke outcomes, as triage decisions made under diagnostic uncertainty impact availability of time sensitive treatments. Quantifying both time varying effects and uncertainty allows for optimized algorithms to improve destination decisions for stroke patients. We developed a Bayesian model of neurological outcomes and an algorithm for hospital triage based on clinical trials data. Methods: We used data from Virtual International Stroke Trials Archive (VISTA), RACECAT, and FAST-MAG. To model prehospital diagnosis, we included patients with any stroke-like illness (ischemic/hemorrhagic stroke, and mimics). Primary outcome was 90-day modified Rankin scale (mRS). Due to variability in reported measures from each trial, model-based Bayesian imputation was used. Our model accepts time-from symptoms, location, and capability of all local hospitals as inputs. Results: We included 9048 participants with 8600 (95%) ischemic strokes, 1801 (20%) had large vessel occlusion, and 4064 (45%) had a 90-day mRS of 0-2 (good neurologic outcome). We evaluated the impact of our algorithm using 1,320 stroke events from RACECAT. The estimated median absolute difference in chance of good mRS score between bypass and non local hospital bypass was 2.3% (ranging from 0 to 7.4%) among 1,320 stroke events in the RACECAT data set; covariate-adjusted patient scenarios predicted a preference for local hospital bypass of -2.9% to 7.4%. Destination maps for Catalonia show important patterns of bypass optimality. Conclusion: We found that no uniform destination selection approach is likely to be optimal under all circumstances. This finding is important, because it suggests that a personalized approach considering diagnostic uncertainty, patient characteristics, and geospatial factors could outperform simpler approaches. Predicted time-to-treatment targets may be insufficient for appropriate system optimization.

Validation of general pain scores from multidomain assessment tools in stroke

PurposeWe describe how well general pain reported in multidomain assessment tools correlated with pain-specific assessment tools; associations between general pain, activities of daily living and independence after stroke.Materials and methodsAnalyses of individual participant data (IPD) from the Virtual International Stroke Trials Archive (VISTA) described correlation coefficients examining (i) direct comparisons of assessments from pain-specific and multidomain assessment tools that included pain, (ii) indirect comparisons of pain assessments with the Barthel Index (BI) and modified Rankin Scale (mRS), and (iii) whether pain identification could be enhanced by accounting for reported usual activities, self-care, mobility and anxiety/depression; factors associated with pain.ResultsEuropean Quality of Life 3- and 5-Level (EQ-5D-3L and EQ-5D-5L), RAND 36 Item Health Survey 1.0 (SF-36) or the 0–10 Numeric Pain Rating Scale (NPRS) were available from 10/94 studies (IPD = 10,002). The 0–10 NPRS was the only available pain-specific assessment tool and was a reference for comparison with other tools. Pearson correlation coefficients between the 0–10 NPRS and (A) the EQ-5D-3L and (B) EQ5D-5 L were r = 0.572 (n = 436) and r = 0.305 (n = 1,134), respectively. mRS was better aligned with pain by EQ-5D-3L (n = 8,966; r = 0.340) than by SF-36 (n = 623; r = 0.318). BI aligned better with pain by SF-36 (n = 623; r = −0.320). Creating a composite score using the EQ-5D 3 L and 5 L comprising pain, mobility, usual-activities, self-care and anxiety/depression did not improve correlation with the 0–10 NPRS.DiscussionThe EQ-5D-3L pain domain aligned better than the EQ-5D-5L with the 0–10 NPRS and may inform general pain description where resources and assessment burden hinder use of additional, pain-specific assessments.

Effect of alteplase, benzodiazepines and beta-blocker on post-stroke pneumonia: Exploration of VISTA-Acute.

Post-stroke pneumonia is a frequent complication of stroke and is associated with high mortality. Investigators have described its associations with beta-blocker. However, there has been no evaluation of the role of recombinant tissue plasminogen activator (RTPA). We postulate that RTPA may modify the effect of stroke on pneumonia by reducing stroke disability. We explore this using data from neuroprotection trials in Virtual International Stroke Trials Archive (VISTA)-Acute. We evaluated the impact of RTPA and other medications in random forest model. Random forest is a type of supervised ensemble tree-based machine learning method. We used the standard approach for performing random forest and partitioned the data into training (70%) and validation (30%) sets. This action enabled to the model developed on training data to be evaluated in the validation data. We borrowed idea from Coalition Game Theory on fair distribution of marginal profit (Shapley value) to determine proportional contribution of a covariate to the model. Consistent with other analysis using the VISTA-Acute data, the diagnosis of post-stroke pneumonia was based on reports of serious adverse events. The overall frequency of pneumonia was 10.9% (614/5652). It was present in 11.5% of the RTPA (270/2358) and 10.4% (344/3295) of the no RTPA groups. There was significant (p<0.05) imbalance in covariates (age, baseline National Institutes of Health Stroke Scale (NIHSS), diabetes, and sex). The AUC for training data was 0.70 (95% CI 0.65-0.76), validation data was 0.67 (95% CI 0.62-0.73). The Shapley value shows that baseline NIHSS (≥10) and age (≥80) made the largest contribution to the model of pneumonia while absence of benzodiazepine may protect against pneumonia. RTPA and beta-blocker had very low effect on frequency of pneumonia. In this cohort pneumonia was strongly associated with stroke severity and age whereas RTPA had a much lower effect. An intriguing finding is a possible association between benzodiazepine and pneumonia but this requires further evaluation.

RCT versus real-world cohorts: Differences in patient characteristics drive associations with outcome after EVT.

The selection of patients with large-vessel occlusion (LVO) stroke for endovascular treatment (EVT) depends on patient characteristics and procedural metrics. The relation of these variables to functional outcome after EVT has been assessed in numerous datasets from both randomized controlled trials (RCT) and real-world registries, but whether differences in their case mix modulate outcome prediction is unknown. We leveraged data from individual patients with anterior LVO stroke treated with EVT from completed RCTs from the Virtual International Stroke Trials Archive (N = 479) and from the German Stroke Registry (N = 4079). Cohorts were compared regarding (i) patient characteristics and procedural pre-EVT metrics, (ii) these variables' relation to functional outcome, and (iii) the performance of derived outcome prediction models. Relation to outcome (functional dependence defined by a modified Rankin Scale score of 3-6 at 90 days) was analyzed by logistic regression models and a machine learning algorithm. Ten out of 11 analyzed baseline variables differed between the RCT and real-world cohort: RCT patients were younger, had higher admission NIHSS scores, and received thrombolysis more often (all p < 0.0001). Largest differences at the level of individual outcome predictors were observed for age (RCT: adjusted odds ratio (aOR), 1.29 (95% CI, 1.10-1.53) vs real-world aOR, 1.65 (95% CI, 1.54-1.78) per 10-year increments, p < 0.001). Treatment with intravenous thrombolysis was not significantly associated with functional outcome in the RCT cohort (aOR, 1.64 (95 % CI, 0.91-3.00)), but in the real-world cohort (aOR, 0.81 (95% CI, 0.69-0.96); p for cohort heterogeneity = 0.056). Outcome prediction was more accurate when constructing and testing the model using real-world data compared to construction with RCT data and testing on real-world data (area under the curve, 0.82 (95% CI, 0.79-0.85) vs 0.79 (95% CI, 0.77-0.80), p = 0.004). RCT and real-world cohorts considerably differ in patient characteristics, individual outcome predictor strength, and overall outcome prediction model performance.

Stroke Outcome Related to Initial Volume Status and Diuretic Use.

Background We hypothesized that stroke outcome is related to multiple baseline hydration-related factors including volume contracted state (VCS) and diuretic use. Methods and Results We analyzed a prospective cohort of subjects with ischemic stroke <24 hours of onset enrolled in acute treatment trials within VISTA (Virtual International Stroke Trials Archive). A VCS was defined based on blood urea nitrogen-to-creatinine ratio. The primary end point was modified Rankin Scale score at 90 days. Primary analysis used generalized ordinal logistic regression over the mRS range, adjusted for Totaled Health Risks in Vascular Events score, onset-to-enrollment time, and thrombolytic use. Of 5971 eligible patients with stroke, 42% were taking diuretics at the time of hospitalization, and 44% were in a VCS. Patients in a VCS were older, had more vascular risk factors, were more likely taking diuretics, and had more severe strokes. Diuretic use was associated with both reduced chance of achieving a good functional outcome (odds ratio [OR], 0.57 [95% CI, 0.52-0.63]) and increased mortality at 90 days (OR, 2.30 [95% CI, 2.04-2.61]). VCS was associated with greater mortality 90 days after stroke (OR, 1.53 [95% CI, 1.33-1.76]). There was no evidence of effect modification among the 3 exposures of VCS, diuretic use, or hypokalemia in relation to outcome. Conclusions A VCS at the time of hospitalization was associated with more severe stroke and odds of death but not associated with worse functional outcome when accounting for relevant characteristics. Diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.

Validation and comparison of multiple risk scores for prediction of symptomatic intracerebral hemorrhage after intravenous thrombolysis in VISTA.

Prediction models/scores may help to identify patients at high risk of symptomatic intracerebral hemorrhage (sICH) after intravenous thrombolysis. We aimed to validate and compare the performance of different prediction models for sICH after thrombolysis using direct model estimation in the Virtual International Stroke Trials Archive (VISTA). We searched PubMed for potentially eligible prediction models from inception to 1 June 2019. Simple and practical models/scores were validated in VISTA. The primary outcome was sICH based on two criteria (National Institute of Neurological Diseases and Stroke, NINDS; Safe Implementation of Thrombolysis in Stroke-Monitoring Study, SITS-MOST) and the secondary outcome was parenchymal hematoma (PH). The discrimination performance of each model was evaluated using area under the curve (AUC) and calibration was evaluated by Hosmer-Lemeshow goodness-of-fit tests. We found 13 prediction models and five models (HAT, MSS, SPAN-100, GRASPS and THRIVE) were finally validated in VISTA. A total of 1884 participants were eligible for our study, of whom the proportion with sICH was 4.6% (87/1884) per NINDS and 3.9% (73/1884) per SITS-MOST, and with PH was 11.3% (213/1884). MSS and GRASPS had the greatest predictive ability for sICH (NINDS criteria: MSS AUC 0.7, 95% CI 0.63-0.77, p < 0.001; GRASPS AUC 0.69, 95% CI 0.63-0.76, p < 0.001; SITS-MOST criteria: MSS, AUC 0.76, 95% CI 0.68-0.85, p < 0.001; GRASPS, AUC 0.79, 95% CI 0.71-0.87, p < 0.001). Similar results were found for PH (MSS AUC 0.68, 95% CI 0.64-0.73, p = 0.017; GRASPS AUC 0.68, 95% CI 0.63-0.72, p = 0.017). The calibration of each model was almost good. MSS and GRASPS had good discrimination and calibration for sICH and PH after thrombolysis as assessed in VISTA. These two models could be used in clinical practice and clinical trials to identity individuals with high risk of sICH.

Outcome prediction in large vessel occlusion ischemic stroke with or without endovascular stroke treatment: THRIVE-EVT.

The THRIVE score and the THRIVE-c calculation are validated ischemic stroke outcome prediction tools based on patient variables that are readily available at initial presentation. Randomized controlled trials (RCTs) have demonstrated the benefit of endovascular treatment (EVT) for many patients with large vessel occlusion (LVO), and pooled data from these trials allow for adaptation of the THRIVE-c calculation for use in shared clinical decision making regarding EVT. To extend THRIVE-c for use in the context of EVT, we extracted data from the Virtual International Stroke Trials Archive (VISTA) from 7 RCTs of EVT. Models were built in a randomly selected development cohort using logistic regression that included the predictors from THRIVE-c: age, NIH Stroke Scale (NIHSS) score, presence of hypertension, diabetes mellitus, and/or atrial fibrillation, as well as randomization to EVT and, where available, the Alberta Stroke Program Early CT Score (ASPECTS). Good outcome was achieved in 366/787 (46.5%) of subjects randomized to EVT and in 236/795 (29.7%) of subjects randomized to control (P < 0.001), and the improvement in outcome with EVT was seen across age, NIHSS, and THRIVE-c good outcome prediction. Models to predict outcome using THRIVE elements (age, NIHSS, and comorbidities) together with EVT, with or without ASPECTS, had similar performance by ROC analysis in the development and validation cohorts (THRIVE-EVT ROC area under the curve (AUC) = 0.716 in development, 0.727 in validation, P = 0.30; THRIVE-EVT + ASPECTS ROC AUC = 0.718 in development, 0.735 in validation, P = 0.12). THRIVE-EVT may be used alongside the original THRIVE-c calculation to improve outcome probability estimation for patients with acute ischemic stroke, including patients with or without LVO, and to model the potential improvement in outcomes with EVT for an individual patient based on variables that are available at initial presentation. Online calculators for THRIVE-c estimation are available at www.thrivescore.org and www.mdcalc.com/thrive-score-for-stroke-outcome.

Machine learning prediction of symptomatic intracerebral hemorrhage after stroke thrombolysis: a cross-cultural validation in Caucasian and Han Chinese cohort.

Background:Previous studies found that Asians seemed to have higher risk of HT after thrombolysis than Caucasians due to its race differences in genetic polymorphism. Whether the model developed by Caucasians could predict risk of symptomatic intracerebral hemorrhage (sICH) in Asians was unknown.Objectives:To develop a machine learning–based model for predicting sICH after stroke thrombolysis in Caucasians and externally validate it in an independent Han Chinese cohort.Design:The derivation Caucasian sample included 1738 ischemic stroke (IS) patients from the Virtual International Stroke Trials Archive (VISTA) data set, and the external validation Han Chinese cohort included 296 IS patients who were treated with intravenous thrombolysis.Methods:Twenty-eight variables were collected across both samples. According to their properties, we classified them into six distinct clusters (ie, demographic variables, medical history, previous medication, baseline blood biomarkers, neuroimaging markers on initial CT scan and clinical characteristics). A support vector machine (SVM) model, which consisted of data processing, model training, testing and a 10-fold cross-validation, was developed to predict the risk of sICH after stroke thrombolysis. The receiving operating characteristic (ROC) was used to assess the prediction performance of the SVM model. A domain contribution analysis was then performed to test which cluster had the highest influence on the performance of the model.Results:In total, 85 (4.9%) patients developed sICH in the Caucasians, and 29 (9.8%) patients developed sICH in the Han Chinese cohort. Eight features including age, NIHSS score, SBP (systolic blood pressure), DBP (diastolic blood pressure), ALP (alkaline phosphatase), ALT (alanine transaminase), glucose, and creatine level were included in the final model, all of which were from demographic, clinical characteristics, and blood biomarkers clusters, respectively. The SVM model showed a good predictive performance in both Caucasians (AUC = 0.87) and Han Chinese patients (AUC = 0.74). Domain contribution analysis showed that inclusion/exclusion of clinical characteristic cluster (NIHSS score, SBP, and DBP), had the highest influence on the performance of predicting sICH in both Caucasian and Han Chinese cohorts.Conclusion:The established SVM model is feasible for predicting the risk of sICH after thrombolysis quickly and efficiently in both Caucasian and Han Chinese cohort.

Temporal Profile of Pneumonia After Stroke.

The occurrence of pneumonia after stroke is associated with a higher risk of poor outcome or death. We assessed the temporal profile of pneumonia after stroke and its association with poor outcome at several time points to identify the most optimal period for testing pneumonia prevention strategies. We analyzed individual patient data stored in the VISTA (Virtual International Stroke Trials Archive) from randomized acute stroke trials with an inclusion window up to 24 hours after stroke onset and assessed the occurrence of pneumonia in the first 90 days after stroke. Adjusted odds ratios and hazard ratios were calculated for the association between pneumonia and poor outcome and death by means of logistic and Cox proportional hazard regression, respectively, at different times of follow-up. Of 10 821 patients, 1017 (9.4%) had a total of 1076 pneumonias. Six hundred eighty-nine (64.0%) pneumonias occurred in the first week after stroke. The peak incidence was on the third day and the median time of onset was 4.0 days after stroke (interquartile range, 2-12). The presence of a pneumonia was associated with an increased risk of poor outcome (adjusted odds ratio, 4.8 [95% CI, 3.8-6.1]) or death (adjusted hazard ratio, 4.1 [95% CI, 3.7-4.6]). These associations were present throughout the 90 days of follow-up. Two out of 3 pneumonias in the first 3 months after stroke occur in the first week, with a peak incidence on the third day. The most optimal period to assess pneumonia prevention strategies is the first 4 days after stroke. However, pneumonia occurring later was also associated with poor functional outcome or death.

Acute Blood Pressure and Outcome After Intracerebral Hemorrhage: The VISTA-ICH Cohort

BackgroundRecent clinical trials suggest that it is safe to acutely lower systolic blood pressure (BP) to 140 mm Hg after ICH, but uncertainty remains regarding optimal management. We sought to better define the link between BP and outcome in ICH patients using data from the Virtual International Stroke Trials Archive (VISTA). MethodsWe performed a retrospective analysis of patients of the VISTA-ICH trials. We measured the strength of association between systolic and diastolic BP various components at different timepoints with unfavorable 3 month-outcome, defined as death or moderate-to-severe disability at 3 months (mRS of 4-6), after adjustment for known confounders. We also dichotomized BP values obtained at 24 h at different thresholds to better define an optimal treatment target. The association of BP with hematoma expansion (HE) was also analyzed. ResultsA total of 384 patients were included. Higher BP at 24 hours was associated with unfavorable outcome for systolic BP (OR 1.16, 95% C.I. 1.07–1.25), pulse pressure (OR 1.13, 95% C.I. 1.03–1.24), and diastolic BP (OR 1.11, 95% C.I. 1.01–1.23) per 10 mm Hg increment. The association between higher BP at 24 h and unfavorable outcome remained significant down to >140 mm Hg. Elevated systolic BP at 24 h was also associated with HE (OR 1.11, 95% C.I. 1.02–1.21 per 10 mm Hg increment). ConclusionElevated BP after ICH at 24 h is associated with poor outcome. Our results support the practice of targeting a systolic BP of 140 mm Hg.

Missing outcome data management in acute stroke trials testing iv thrombolytics. Is there risk of bias?

Missing outcome data may undermine interpretation of randomised clinical trials by weakening power and limiting apparent effect size. We assessed bias and inefficiency of two imputation methods commonly used in stroke trials evaluating the efficacy of iv thrombolysis. We searched the virtual international stroke trials archive (VISTA)-acute for ischaemic stroke patients with 90-day modified Rankin scale as an outcome, and known thrombolysis status. We excluded any with missing 30-day modified Rankin scale. We planned two analyses; first, we calculated odds ratios for outcome in thrombolysed versus not thrombolysed from imputed-only data, (a) among patients with missing modified Rankin scale 90 and (b) among matched patients with intact data (using propensity score methods and relevant covariates). Imputation approaches were last observation carried forward (LOCF) or multiple imputation. Outcome comparisons used dichotomisation and shift analysis. Thereafter, we calculated whole-population odds ratios using LOCF and multiple imputation (also through dichotomisation and shift analysis); first with the original 1.5% missing outcome data, and then artificially increasing the burden (5%; 10%; 20%; 30%). We considered 9657 patients from eight of the studies included in VISTA, 3034 (31%) thrombolysed. Missing data replacement by LOCF with analysis by dichotomisation gave the highest estimate of thrombolysis influence. Imputing while increasing the burden of missing data progressively raised the odds ratios estimates, though thresholds for overestimation were 10% for LOCF; 20% for multiple imputation.Discussion: Replacing missing outcome data tended to overestimate differences of thrombolysed versus non-thrombolysed patients, but had minimal impact below a 10% burden of missing data.Conclusion: In the specific context of acute stroke trials testing iv thrombolytics, replacing missing data by carrying forward the last observation tended to overestimate treatment odds ratios more than multiple imputation.

Abstract TMP87: Stroke Outcomes Related to Initial Volume Status, Diuretic Use, and Potassium Levels

Background and Purpose: The relationship between stroke outcome and initial presentation in a volume contracted state (VCS) has not been well established, and may intersect with concomitant diuretic use and serum potassium (K) levels. We hypothesized that stroke outcome is a function of multiple volume related factors. Methods: We analyzed a prospective cohort of subjects with ischemic stroke &lt;24 hours of onset, enrolled in acute treatment trials within the Virtual International Stroke Trials Archive. VCS was defined as a BUN-to-creatinine ratio&gt;20 and hypokalemia as &lt;3.5 mEq/L. The primary endpoint was modified Rankin Scale (mRS) at 90 days. Primary analysis employed generalized ordinal logistic regression over the full mRS range, with adjustment for THRIVE score, onset-to-enrollment time, and intravenous rtPA usage. Secondary analyses dichotomized the mRS. Results: Of 5971 eligible patients, 44% were in a VCS and 56% were euvolemic. Patients with VCS were older, had more vascular risk factors, more severe strokes, and were more likely taking diuretics. VCS was not significantly associated with mRS scores after adjustment (Table). Post hoc sensitivity analysis using BUN-to-creatinine ratio&gt;30 yielded similar results. Diuretic use was associated with worse outcomes (Table), mainly driven by non-K sparing diuretics, while K-sparing diuretics tended to have the opposite effect. Hypokalemia had discordant associations with mRS, depending on the analytic approach (Table). There was no evidence of effect modification among the three exposures of VCS, diuretic use, or hypokalemia in relation to outcome (all p&gt;0.30). Conclusions: A VCS at the time of hospitalization was associated with more severe stroke but not associated with worse functional outcome when accounting for key measurable baseline characteristics. However, diuretic use and low serum potassium at the time of stroke onset were associated with worse outcome and may be worthy of further investigation.

Liver Fibrosis Indices and Outcomes After Primary Intracerebral Hemorrhage.

Background and Purpose- Cirrhosis-clinically overt, advanced liver disease-is associated with an increased risk of hemorrhagic stroke and poor stroke outcomes. We sought to investigate whether subclinical liver disease, specifically liver fibrosis, is associated with clinical and radiological outcomes in patients with primary intracerebral hemorrhage. Methods- We performed a retrospective cohort study using data from the Virtual International Stroke Trials Archive-Intracerebral Hemorrhage. We included adult patients with primary intracerebral hemorrhage presenting within 6 hours of symptom onset. We calculated 3 validated fibrosis indices-Aspartate Aminotransferase-Platelet Ratio Index, Fibrosis-4 score, and Nonalcoholic Fatty Liver Disease Fibrosis Score-and modeled them as continuous exposure variables. Primary outcomes were admission hematoma volume and hematoma expansion. Secondary outcomes were mortality, and the composite of major disability or death, at 90 days. We used linear and logistic regression models adjusted for previously established risk factors. Results- Among 432 patients with intracerebral hemorrhage, the mean Aspartate Aminotransferase-Platelet Ratio Index, Fibrosis-4, and Nonalcoholic Fatty Liver Disease Fibrosis Score values on admission reflected intermediate probabilities of fibrosis, whereas standard hepatic assays and coagulation parameters were largely normal. After adjusting for potential confounders, Aspartate Aminotransferase-Platelet Ratio Index was associated with hematoma volume (β, 0.20 [95% CI, 0.04-0.36]), hematoma expansion (odds ratio, 1.6 [95% CI, 1.1-2.3]), and mortality (odds ratio, 1.8 [95% CI, 1.1-2.7]). Fibrosis-4 was also associated with hematoma volume (β, 0.27 [95% CI, 0.07-0.47]), hematoma expansion (odds ratio, 1.9 [95% CI, 1.2-3.0]), and mortality (odds ratio, 2.0 [95% CI, 1.1-3.6]). Nonalcoholic Fatty Liver Disease Fibrosis Score was not associated with any outcome. Indices were not associated with the composite of major disability or death. Conclusions- In patients with largely normal liver chemistries, 2 liver fibrosis indices were associated with admission hematoma volume, hematoma expansion, and mortality after intracerebral hemorrhage.