Abstract WMP61: RNA Expression Signature to Diagnosis Stroke Etiology by Atrial Fibrillation versus Large Artery Atherosclerosis Cause: A BASE Clinical Trial Analysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Glen Jickling ◽  
Frank Sharp ◽  
Edward Jauch ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Symptom Onset ◽  
Training Data ◽  
Rna Expression ◽  
Large Artery ◽  
Sample Collection ◽  
Hospital Data ◽  
Stroke Patients ◽  
Stroke Etiology

Background: Identifying atrial fibrillation in embolic stroke of ischemic stroke populations would be of significant clinical utility. Using the Biomarkers of Acute Stroke Etiology (BASE) trial (NCT02014896) dataset, our goal was to determine if blood gene expression signatures accurately differentiated patients with atrial fibrillation from large artery stroke patients. Methods: The BASE trial enrolled suspected stroke patients presenting to 20 hospitals within 24 hrs of symptom onset. Final gold standard diagnosis and stroke etiology were determined by an adjudication committee using all hospital data but blinded to RNA test results. Whole blood, obtained in PAXgene tubes, was frozen at -20C within 72 hrs and analyzed at a core lab (Ischemia Care, LLC, Dayton, OH) using Affymetrix HTA micro arrays. Approximately 38,000 genes on the HTA microarray were filtered to eliminate genes with low expression or high CV (> 10%) when run on replicate samples leaving 9,513 potential signature genes. A two-way random forest classifier was built through cross validation of the training data resulting in a 23 gene diagnostic signature. Results: There were 58 patients enrolled between 18 and 24 hours of symptom onset, with NIHSS>5, 27 (47%) with atrial fibrillation cause of stroke and 31 (53%) with large artery stroke; 64% were male, and median (IQR) age was 69.7 (62.8, 81.0). Median (IQR) time from symptoms to sample collection was 1323.5 (1208.8, 1381.3) minutes. Coexistent pathology at presentation was high blood pressure 49 (84%), hyperlipidemia 28 (48%), diabetes 9 (16%), and coronary artery disease 15 (26%). The panel was able to distinguish atrial fibrillation from large vessel stroke with a C-statistic 0.92 (0.55-1.0, 95% CI), sensitivity 0.90 (0.51-1.0, 95% CI) and specificity of 0.85. Conclusion: RNA expression differentiates strokes due to atrial fibrillation from large artery stroke and may have therapeutic and outcome implications in ischemic stroke populations.

Abstract 50: RNA Expression for Diagnosis of Stroke Etiology Differentiating Large Artery and Cardioembolic Stroke: Analytical Validation of Testing From the BASE Clinical Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Edward C Jauch ◽  
Keyword(s):  
Acute Stroke ◽  
Symptom Onset ◽  
Training Data ◽  
Cardioembolic Stroke ◽  
Blood Collection ◽  
Rna Expression ◽  
Large Artery ◽  
Hospital Data ◽  
Stroke Patients ◽  
Stroke Etiology

Background: An accurate test to differentiate large artery stroke (LAS) patients from those with cardioembolic stroke (CES) would be of significant clinical utility. Using the Biomarkers of Acute Stroke Etiology (BASE) trial (NCT02014896) dataset, our purpose was to utilize blood gene expression signatures for accurately differentiating LAS from CES acute stroke etiologies. Methods: The BASE trial enrolled suspected stroke patients presenting to 20 hospitals within 24 hrs of symptom onset. Final gold standard diagnosis and stroke etiology were determined by an adjudication committee using all hospital data but blinded to RNA test results. Whole blood, obtained in PAX tubes, was frozen at -20C within 72 hrs and analyzed at a core lab (Ischemia Care, Dayton, OH) using Affymetrix HTA microarrays. Genes on the HTA microarray were filtered to eliminate genes with low expression or high CV (> 10%) when run on replicate samples leaving 9,513 potential signature genes. A two-way random forest classifier was built through cross validation of the training data resulting in a 45 gene diagnostic signature. Results: This is a planned interim cohort study of the 1700 patients enrolled in the BASE trial that does not include lacunar strokes, TIA, or stroke mimics. Overall, 222 patients were enrolled with NIHSS>5, 70 (32%) with LAS and 152 (68%) with CES; 59% were male, and median (IQR) age was 70.7 yrs (62.0, 80.2). Median (IQR) time from symptom onset to blood collection was 1200 (448, 1568) minutes. Coexistent pathology at presentation included atrial fibrillation 90 (48%), hypertension 153 (82%), hyperlipidemia 87 (47%), diabetes 60 (32%), and coronary artery disease 70 (37%). Patients were randomly divided into training (148), early symptom onset (<18hrs) validation (39) and a late symptom onset (>18 hrs) validation (35). The diagnostic gene signature results in the early validation cohort distinguished LAS from CES; C-statistic 0.78 (0.50-1.0, 95% CI), sensitivity 0.90 (0.55-1.0, 95% CI) and specificity of 0.70 (0.43-1.0, 95% CI). Conclusion: Early RNA expression differentiates large artery stroke patients from those with cardioembolic stroke, and may have therapeutic and secondary prevention implications.

Abstract TMP100: Biology of Stroke: Role of ELL2, GLIPR1, MAPKAPK3 Genes in Identifying Atrial Fibrillation Cause of Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Glen Jickling ◽  
Frank Sharp ◽  
Edward Jauch ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Training Data ◽  
Blood Collection ◽  
Large Artery ◽  
Hospital Data ◽  
Stroke Patients ◽  
Stroke Etiology ◽  
Signature Genes ◽  
Diagnostic Signature ◽  
Artery Disease

Background: An accurate test to identify atrial fibrillation in ischemic stroke populations would be of significant clinical utility. Using the Biomarkers of Acute Stroke Etiology (BASE) trial (NCT02014896) dataset, our goal was to utilize a database of genes appearing in literature determine if gene expression accurately differentiate patients with atrial fibrillation from those with large artery stroke. Methods: BASE enrolled suspected stroke patients presenting to 20 hospitals within 24 hrs of symptom onset. Final gold standard diagnosis and stroke etiology were determined by an adjudication committee using all hospital data but blinded to RNA test results. Whole blood, obtained in PAXgene tubes, was frozen at -20C within 72 hrs and analyzed at a core lab (Ischemia Care, LLC, Dayton, OH) using Affymetrix HTA micro arrays. Genes were filtered to those appearing in stroke literature resulting in 543 potential signature genes. A two-way random forest classifier was built through cross validation of the training data resulting in a 3 gene diagnostic signature with robust performance conserved across literature consisting of ELL2, GLIPR1, MAPKAPK3 genes. Results: Overall, 99 patients were enrolled with NIHSS>5, 68 (69%) with atrial fibrillation cause of stroke and 31 (31%) with large artery stroke; (48%) were male, and median (IQR) age was 74.4 (66.1,81.7). Median (IQR) time from symptoms to blood collection was 420 (322, 472) minutes. Coexistent pathology at presentation included high blood pressure 84 (85%), hyperlipidemia 45 (45%), diabetes 31 (31%), and coronary artery disease 38 (38%). Three genes were able to differentiate atrial fibrillation from large vessel stroke; C-statistic 0.86 (0.52-1.0, 95% CI), sensitivity 0.93 (0.56-1.0, 95% CI) and specificity of 0.58 (0.35-0.81, 95% CI ). Conclusion: RNA expression of ELL2, GLIPR1, MAPKAPK3 genes differentiates atrial fibrillation stroke patients from those with large artery stroke, and may have therapeutic and outcome implications.

Abstract WP255: Can Normal Electrocardiogram Rule Out Newly Diagnosed Atrial Fibrillation in Ischemic Stroke Patients

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Joshua Santucci ◽  
Takashi Shimoyama ◽  
Ken Uchino
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cryptogenic Stroke ◽  
Cardiac Monitoring ◽  
Large Artery ◽  
Newly Diagnosed ◽  
Stroke Patients ◽  
Stroke Subtype ◽  
History Of

Introduction: Electrocardiogram (ECG) findings of premature atrial contraction and prolonged PR interval are associated with risk of onset atrial fibrillation (AF) in cryptogenic stroke. We sought to see if normal ECG and AF incidence is incompletely understood. Methods: From a prospective single-hospital stroke registry from 2018, we identified ischemic stroke patients who had ECG done on admission for review. We excluded patients with AF on admission ECG, history of AF, and implanted device with cardiac monitoring capability. Normal ECG was interpreted based on the standardized reporting guidelines for ECG studies evaluating risk stratification of emergency department patients. Stroke subtype was diagnosed according to the TOAST classification: large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolism, others/undetermined and embolic stoke of undetermined source (ESUS) criteria. We compared the incidence of newly diagnosed AF during hospitalization and from outpatient cardiac event monitoring between normal and abnormal ECG. Results: Of the 558 consecutive acute ischemic stroke patients, we excluded 135 with AF on admission ECG or history of AF and 9 with implanted devices. Of the remaining 414 patients that were included in the study, ESUS (31.2%) was the most frequent stroke subtype, followed by LAA (30.0%), SVO (14.0%), others/undetermined (15.7%), and cardioembolism (9.2%). Normal ECG was observed in 125 patients (30.2%). Cardioembolic subtype was less frequent in the normal versus abnormal ECG group (1.6% vs. 12.5%, p<0.001). New AF was detected in 17/414 patients (4.1%) during hospitalization. Of these 17 patients, none had normal ECG (0/125) and all had abnormal ECG (17/289, 5.9%) (p=0.002). After discharge, of 111 patients undergoing 4-week outpatient cardiac monitoring, new AF was detected in 16 (14.4%). Of these 16 patients, only 1 had a normal ECG (1/35, 2.9%) while 15 had abnormal ECG (15/76, 19.7%) (p=0.02). Conclusions: Normal ECG at admission for acute ischemic stroke is associated with low likelihood of detection of new atrial fibrillation in either the inpatient or outpatient setting.

scholarly journals The Conditions Under Which Piracetam Is Used and the Factors That Can Improve National Institute of Health Stroke Scale Score in Ischemic Stroke Patients and the Importance of Previously Unnoticed Factors From a Hospital-Based Observational Study in Taiwan

2019 ◽  
Vol 8 (1) ◽  
pp. 122 ◽  
Author(s):  
Shu-Yi Chen ◽  
Jai-Wen Liu ◽  
Yu-Hsun Wang ◽  
Jing-Yang Huang ◽  
Shiuan-Chih Chen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Subgroup Analysis ◽  
Clinical Characteristics ◽  
Current Smoker ◽  
Normal Weight ◽  
Large Artery ◽  
Stroke Patients ◽  
Related Factors ◽  
Registration Data

This study aimed to explore the associations of piracetam use and the clinical characteristics of NIHSS (National Institute of Health Stroke Scale) changes—the importance of which, as prognosis related factors, was previously unnoticed—and analyze the associations of piracetem with NIHSS changes by stratifying clinical characteristics. This observational retrospective study was conducted by enrolling patients based on 2483 stroke registration data cohorts from a 1200-bed regional Tungs’ Taichung MetroHarbor Hospital, located in central Taiwan from 1 January 1 2011 to 31 December 2015. Patients were excluded if they had intravenous a thrombolytic agent within 3 hours of symptoms onset (n = 49), incomplete or erroneous NIHSS scores (n = 953), or transient ischemia stroke (n = 130). Logistic regression model was applied for associating piracetam treatment and clinical characteristics with NIHSS score changes between admission and discharge, and subgroup analysis to assess the conditions under which piracetam can be used. Multivariate analysis revealed NIHSS scores improvement in atrial fibrillation, large-artery atherosclerosis, underweight, current smoker, ex-smoker, and piracetam. Subgroup analysis showed piracetam is beneficial in the following: age ≥75 years olds, males, those of normal weight, those who are obese, ex-smokers, those with hypertension, dyslipidemia, those without diabetes mellitus, nor atrial fibrillation. The selection of the conditions under which piracetam treatment should be given, and clinical characteristics, is important for NIHSS improvement of ischemic stroke patients in Taiwan.

scholarly journals Safety and Efficacy of Tirofiban for Acute Ischemic Stroke Patients With Large Artery Atherosclerosis Stroke Etiology Undergoing Endovascular Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaochuan Huo ◽  
Raynald ◽  
Anxin Wang ◽  
Dapeng Mo ◽  
Feng Gao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Therapy ◽  
Large Artery ◽  
Stroke Patients ◽  
Anterior Circulation ◽  
Safety And Efficacy ◽  
Stroke Etiology ◽  
Significant Difference ◽  
Major Stroke

Objective: To investigate the safety and efficacy of tirofiban in acute ischemic stroke (AIS) patients with large artery atherosclerosis (LAA) stroke etiology receiving endovascular therapy (EVT).Methods: In this multi-center prospective study, patients who were considered to have an indication received a low dose intra-arterial bolus (0.25–1 mg) of tirofiban. The safety and efficacy outcomes at 90-day follow-ups included symptomatic intracranial hemorrhage (sICH), recanalization rate, functional outcome, and mortality.Results: Among the 649 AIS patients with LAA, those in the tirofiban group (n = 244) showed higher systolic blood pressure (BP) and NIHSS score on admission, puncture-to-recanalization time, lower frequency of intravenous thrombolysis and intra-arterial thrombolysis, higher frequency of antiplatelet, heparinization, mechanical stent retrieval, aspiration, balloon angioplasty, and more retrieval times compared with those in the non-tirofiban group (n = 405) (all P &lt; 0.05). Tirofiban was found to be associated with superior clinical outcomes in anterior circulation stroke and major stroke patients [adjusted odds ratio (OR) = 2.163, 95% confidence interval (CI) = 1.130–4.140, P = 0.02 and adjusted OR = 2.361, 95% CI = 1.326–4.202, P = 0.004, respectively] and a lower risk of mortality at 90-day follow-ups (adjusted OR = 0.159, 95% CI = 0.042–0.599, P = 0.007 and adjusted OR = 0.252, 95% CI = 0.103–0.621, P = 0.003, respectively). There was no significant difference in sICH between the two groups.Conclusions: Tirofiban in AIS patients with LAA undergoing EVT is safe and may benefit the functional outcomes in anterior circulation and major stroke patients and showed a trend for reduced mortality.

scholarly journals Acute reperfusion therapies for acute ischemic stroke patients with unknown time of symptom onset or in extended time windows: an individualized approach

2021 ◽  
Vol 14 ◽  
pp. 175628642110211
Author(s):  
Georgios Magoufis ◽  
Apostolos Safouris ◽  
Guy Raphaeli ◽  
Odysseas Kargiotis ◽  
Klearchos Psychogios ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Symptom Onset ◽  
Time Windows ◽  
Intravenous Thrombolysis ◽  
Inclusion Criteria ◽  
Stroke Patients ◽  
Treatment Algorithms ◽  
Late Presenters

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.

scholarly journals Resting Heart Rate and In-Hospital Mortality in Acute Ischemic Stroke Patients With and Without Atrial Fibrillation

2020 ◽  
Vol 84 (4) ◽  
pp. 656-661
Author(s):  
Qiao Han ◽  
Chunyuan Zhang ◽  
Shoujiang You ◽  
Danni Zheng ◽  
Chongke Zhong ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Rate ◽  
Ischemic Stroke ◽  
Hospital Mortality ◽  
Acute Ischemic Stroke ◽  
Resting Heart Rate ◽  
Stroke Patients

Blood biomarkers to detect new-onset atrial fibrillation and cardioembolism in ischemic stroke patients

Heart Rhythm ◽  
2021 ◽  
Author(s):  
Dorin Harpaz ◽  
Ram Bajpai ◽  
Geelyn J.L. Ng ◽  
Michael Soljak ◽  
Robert S. Marks ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Blood Biomarkers ◽  
Stroke Patients ◽  
Onset Atrial Fibrillation ◽  
New Onset
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