Time Of Ischemic Stroke Research Articles

Race disparities in atrial fibrillation detection using implantable loop recorder for cryptogenic stroke

Abstract Background Cryptogenic stroke represents about 25–30% of all ischemic strokes. Continuous electrocardiographic monitoring using implantable loop recorder (ILR) can detect asymptomatic and undiagnosed atrial fibrillation (AF). Purpose To assess patient-specific factors in ILR implantation and AF detection in patients with cryptogenic strokes. Methods We retrospectively reviewed 379 patients with cryptogenic stroke indicated for ILR implantation, from January 2017 to June 2021 at our university hospital. We evaluated patient demographic and clinical characteristics to assess the risk factors associated with higher incidence of AF detection, using logistic regression models. Results Of the 379 ILRs implanted, 60.4% were males with 71.2% Caucasian, mean age 67.6 years, and mean BMI 28.5. The mean CHADSVASC score of 3.9 at the time of ischemic stroke. These patients had prior diagnosis of diabetes mellitus (27.4%), hypertension (65.7%), chronic kidney disease (19.5%), coronary artery disease (20%) and congestive heart failure (2%). Of the entire cohort, AF was diagnosed in 16% of patients with 14 months mean follow up. There were more females diagnosed with AF on ILR (20% v. 18.7%, p>0.05). Caucasians were more likely to have AF detected compared to non-Caucasians (OR 2.3, 95% CI, p<0.02). There were 52 patients with mobile cardiac outpatient telemetry (MCOT) before having ILR implantation. AF was not detected on MCOT, but 15% were diagnosed with AF with ILR monitoring. In univariate analysis, increasing age is strongly associated with the detection of AF (p=0.03). Conclusions There continues to exist race disparities in ILR implantation and eventual AF detection, leading to further socioeconomic health disparities. ILR should be considered especially in elderly with cryptogenic stroke given the higher incidence of AF detection. Funding Acknowledgement Type of funding sources: None.

Formalised assessment of systemic thrombogenicity in patients with Polycythemia vera suffered an ischemic stroke

Introduction. Thrombosis diagnosis and prevention in patients with Polycythemia vera (PV) suffered an ischemic stroke (IS) are still open. The aim was to find the reasons for systemic thrombogenicity and to compare the applicability of the main scales assessing thrombosis risk in patients with PV suffered IS.Materials and methods. We followed up 127 people (42-75 y.o.), of which 68 were patients with PV suffered IS (group I) and 59 non-PV-patients with ischemic stroke (group II). Clinical study included common blood analysis, rheological properties of erythrocytes, coagulation and endothelial parameters, cytokines, inflammation markers, angiogenesis markers, and testing for the V617F mutation in the JAK2 gene. The follow up included common and neurological examinations as well, and the assesment of thrombosis risk factors with both Caprini scale and CHA2DS2-VASc scale. All patients were examined twice as in the acute period of IS as well as in 16-18 months.Results. Between the groups no significant differences were found for the NIHSS average score and for Bartel index as well.The Caprini score belonged to the “very high risk” (score > 6) in both groups in the acute period of IS. At the same time, the score “8-10 points” prevailed in group II (68%) whereas the score “11-12 points” prevailed in group I.In the acute time of IS the CHA2DS2-VASc score revealed 12% of patients from both groups who had a score of “3-4 points” (moderate risk of thrombosis).In group I thrombotic complications rate correlated significantly with the JAK2V617F gene allelicloading (r = 0.236; p < 0.05), and the development of recurrence cerebrovascular disorders correlated significantly with Caprini score (r = 0.241; p < 0.05), but not with CHA2DS2-VASc score.Aiming to predict thrombotic complications in PV-patients the threshold (cut off) points were established for those markers as factor VIII, factor VII, red blood cell deformability, thrombin activated fibrinolysis inhibitor (TAFI), red blood cell count, white blood cell count, t-PA, VEGF-A, p-thrombomodulin, and ADAMTS-13.This pattern of parameters showed the odds ratio of thrombotic complications 10.3 (95% CI 7.6-13.8) in PV-patients in thelong-term period.At the end of the follow up the Caprini score showed a trend towards a decreasing in total while the CHA2DS2-VASc score remained virtually unchanged.Conclusion. We assume the accurate assessment of thrombotic risk in patients with Polycythemia vera suffered an ischemic stroke requires a proposed pattern of parameters including the test for JAK2V617F allelicloading and the calculation of Caprini score but not CHA2DS2-VASc score. Final results may provoke to change standard antithrombotic therapy in those patients towards its intensification due to pathogenetic featues of cancer-associated thrombosis.

Real-Life Incident Atrial Fibrillation in Outpatients with Coronary Artery Disease.

Background: The risk, correlates, and consequences of incident atrial fibrillation (AF) in patients with chronic coronary artery disease (CAD) are largely unknown. Methods and results: We analyzed incident AF during a 3-year follow-up in 5031 CAD outpatients included in the prospective multicenter CARDIONOR registry and with no history of AF at baseline. Incident AF occurred in 266 patients (3-year cumulative incidence: 4.7% (95% confidence interval (CI): 4.1 to 5.3)). Incident AF was diagnosed during cardiology outpatient visits in 177 (66.5%) patients, 87 of whom were asymptomatic. Of note, 46 (17.3%) patients were diagnosed at time of hospitalization for heart failure, and a few patients (n = 5) at the time of ischemic stroke. Five variables were independently associated with incident AF: older age (p < 0.0001), heart failure (p = 0.003), lower left ventricle ejection fraction (p = 0.008), history of hypertension (p = 0.010), and diabetes mellitus (p = 0.033). Anticoagulant therapy was used in 245 (92%) patients and was associated with an antiplatelet drug in half (n = 122). Incident AF was a powerful predictor of all-cause (adjusted hazard ratio: 2.04; 95% CI: 1.47 to 2.83; p < 0.0001) and cardiovascular mortality (adjusted hazard ratio: 2.88; 95% CI: 1.88 to 4.43; p < 0.0001). Conclusions: In CAD outpatients, real-life incident AF occurs at a stable rate of 1.6% annually and is frequently diagnosed in asymptomatic patients during cardiology outpatient visits. Anticoagulation is used in most cases, often combined with antiplatelet therapy. Incident AF is associated with increased mortality.

Left Atrial Dilation and Risk of One-Year Readmission after Embolic Stroke of Undetermined Source

Background: Structural left atrial and ventricular abnormalities on the electrocardiogram (ECG) and transthoracic echocardiogram (TTE) at the time of ischemic stroke have been associated with morbidity and mortality. Yet, the prognostic impact of the same in embolic stroke of undetermined source (ESUS), a relevant subtype of ischemic stroke with a unique pathophysiology, has not been well studied to date. Our aim was to assess the predictive impact of left atrio-ventricular ECG and TTE abnormalities on one-year hospital readmission after ESUS from an ongoing single center prospective stroke registry in the U.S. Methods: We identified 369 ESUS patients who had at least 1 year of complete follow-up between 2013 and 2018. We examined the association of abnormal left atrio-ventricular findings on ECG and TTE, as well as basic demographic and clinical characteristics, measured at index admission with time to 1-year hospital readmission using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regression. Results: Recurrent ischemic stroke and cardiovascular causes constituted 60% of all readmissions. Patients with left atrial dilation on TTE were more likely to readmitted within 1 year (HR 1.51; 95% CI, 1.04–2.21). Bundle branch block, pathologic Q-wave, and troponin elevation curves diverged, but were not significantly associated with readmission (log-rank p=0.34, p=0.08, p=0.42, respectively). Conclusions: Following ESUS, left atrial dilation on TTE was associated with 1-year overall hospital readmission, of which cardiovascular and cerebrovascular ischemic events, and heart failure were a notable proportion. Our data support ongoing studies of atrial cardiopathy in ESUS patients.

Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation

Background and purposeUnderstanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. MethodsThe Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. ResultsOf the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were women. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10–2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06–3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. ConclusionSmall stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes.

The correlation of serum long non-coding RNA ANRIL with risk factors, functional outcome, and prognosis in atrial fibrillation patients with ischemic stroke.

BackgroundThis study aimed to evaluate the predictive value of long non‐coding RNA (lncRNA) antisense non‐coding RNA in the INK4 locus (ANRIL) for atrial fibrillation (AF) patients with ischemic stroke and investigate its correlation with risk factors, functional outcome, and prognosis.MethodsA total of 386 consecutive AF patients were recruited. AF patients were followed up for 24‐48 months by outpatient follow‐up, telephone follow‐up, and medical record. The time of ischemic stroke in patients with AF was recorded, and follow‐up was continued for 6 months. LncRNA ANRIL expression from serum was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR).ResultsCompared with the AF with ischemic stroke group (14.3 ± 2.3), patients in the AF without ischemic stroke group (11.9 ± 1.8) had significantly lower serum lncRNA ANRIL levels (P < .05). The sensitivity and specificity of lncRNA ANRIL for identifying AF with ischemic stroke were 76.6% and 81.4%, respectively. Spearman correlation analysis results shown that lncRNA ANRIL was significantly correlated with the NIHSS score (r Spearman = .490, P < .001) and the mRS score (r Spearman = .466, P < .001). Compared with the lncRNA ANRIL high‐expression group, the recurrence‐free survival (RFS) of the lncRNA ANRIL low‐expression group was significantly higher (χ2 = 11.009, log‐rank P < .001). Cox proportional regression model analysis indicated that the serum lncRNA ANRIL level (P = .004), NIHSS score (P = .001), infarct volume (P = .035), and smoking (P < .001) were the risk factors for AF with ischemic stroke.ConclusionSerum lncRNA ANRIL exerts a good predictive value for AF with ischemic stroke, and its increased expression is correlated with worse RFS for patients.

Ischemic Stroke and Intracranial Hemorrhages during Percutaneous Left Ventricular Assist Device Cardiac Support

Mechanical circulatory support systems for cardiogenic shock and heart failure are associated with ischemic strokes and intracranial hemorrhages. Impella is a percutaneously placed, ventricular assist device for short-term cardiac support. We aimed to study the prevalence of acute neurologic complications during short-term support with Impella. We reviewed prospectively collected data of 79 consecutive persons implanted with Impella at a single, tertiary center between October 2010 to July 2018. Acute neurological events (ANE) were defined as ischemic strokes or intracranial hemorrhages, including intracerebral hemorrhage, subdural hematomas and subarachnoid hemorrhages. Among those with ANE, specific causes of ischemic and hemorrhagic events were collected and discussed. Of 79 persons with Impella with median 8 days of support (range 1-33 days), 6 (7.5%) developed ANE at a median of 5 days from implant (range 1-8 days). There were 3 ischemic strokes, 2 intracerebral hemorrhages, and 1subdural hematoma. Hemorrhagic events were attributed to anticoagulant use and thrombocytopenia at the time of the events. Two ischemic strokes were attributed to inadequate anticoagulation with one case of pump thrombosis diagnosed at time of ischemic stroke. Only 2 of the 6 patients survived the acute cardiogenic shock period to achieve heart transplantation. In-hospital ischemic strokes and intracranial hemorrhages are common during the short-term cardiac support period with Impella. Antithrombotic intensity, duration of device support time, and thrombocytopenia might contribute to the incidence of these events.

Abstract TP215: Machine Learning Analysis of Gene Expression Data and Predictive Stroke Outcomes in Acute Ischemic Stroke

Background and Purpose: The ability to predict ischemic stroke outcomes in the first day of admission could be vital for patient counseling, rehabilitation, and care planning. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) collects blood samples distal and proximal to the intracranial thrombus during mechanical thrombectomy. These samples are a novel resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and patient demographics that are predictive of stroke outcomes (infarct and/or edema volume) in acute ischemic stroke patients. Methods: The BACTRAC study is a non-probability, convenience sampling of subjects (≥ 18 year olds) treated with mechanical thrombectomy for emergent large vessel occlusion. We evaluated relative concentrations of mRNA for gene expression in 84 inflammatory molecules in static blood distal and proximal to the intracranial thrombus from adults who underwent thrombectomy. We employed a machine learning method, Random Forest, utilizing the first set of enrolled subjects, to predict which inflammatory genes and patient demographics were important features for infarct and edema volumes. Results: We analyzed the first 28 subjects (age = 66 ± 15.48, 11 males) in the BACTRAC registry. Results from machine learning analyses demonstrate that the genes CCR4, IFNA2, IL9, CXCL3, Age, DM, IL7, CCL4, BMI, IL5, CCR3, TNF, and IL27 predict infarct volume. The genes IFNA2, IL5, CCL11, IL17C, CCR4, IL9, IL7, CCR3, IL27, DM, and CSF2 predict edema volume. There is an intersection of genes CCR4, IFNA2, IL9, IL7, IL5, CCR3 to both infarct and edema volumes. Overall, these genes depicts a microenvironment for chemoattraction and proliferation of autoimmune cells, particularly Th2 cells and neutrophils. Conclusions: Machine learning algorithms can be employed to develop predictive biomarker signatures for stroke outcomes in ischemic stroke patients, particularly in regard to identifying acute gene expression changes that occur during stroke.

Expression of Cytokines and Chemokines as Predictors of Stroke Outcomes in Acute Ischemic Stroke.

Introduction: Ischemic stroke remains one of the most debilitating diseases and is the fifth leading cause of death in the US. The ability to predict stroke outcomes within the acute period of stroke would be essential for care planning and rehabilitation. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) study collects arterial blood immediately distal and proximal to the intracranial thrombus at the time of mechanical thrombectomy. These blood samples are an innovative resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and important immune factors during mechanical thrombectomy for emergent large vessel occlusion (ELVO) and which patient demographics were predictors for stroke outcomes (infarct and/or edema volume) in acute ischemic stroke patients.Methods: The BACTRAC study is a non-probability sampling of male and female subjects (≥18 year old) treated with mechanical thrombectomy for ELVO. We evaluated 28 subjects (66 ± 15.48 years) relative concentrations of mRNA for gene expression in 84 inflammatory molecules in arterial blood distal and proximal to the intracranial thrombus who underwent thrombectomy. We used the machine learning method, Random Forest to predict which inflammatory genes and patient demographics were important features for infarct and edema volumes. To validate the overlapping genes with outcomes, we perform ordinary least squares regression analysis.Results: Machine learning analyses demonstrated that the genes and subject factors CCR4, IFNA2, IL-9, CXCL3, Age, T2DM, IL-7, CCL4, BMI, IL-5, CCR3, TNFα, and IL-27 predicted infarct volume. The genes and subject factor IFNA2, IL-5, CCL11, IL-17C, CCR4, IL-9, IL-7, CCR3, IL-27, T2DM, and CSF2 predicted edema volume. The overlap of genes CCR4, IFNA2, IL-9, IL-7, IL-5, CCR3, and IL-27 with T2DM predicted both infarct and edema volumes. These genes relate to a microenvironment for chemoattraction and proliferation of autoimmune cells, particularly Th2 cells and neutrophils.Conclusions: Machine learning algorithms can be employed to develop prognostic predictive biomarkers for stroke outcomes in ischemic stroke patients, particularly in regard to identifying acute gene expression changes that occur during stroke.

Fibrinolytic parameters under ischemic stroke with diabetes mellitus combination

Abstract Background: Fibrinolysis and thrombosis alterations include important parts of stroke pathophysiology. At the same time fibrinolytic system disorders are a common feature of patients with metabolic syndrome and diabetes. So it may increase the possibility of developing atherosclerotic lesions and occlusive intravascular thrombi. The present study investigated the influence of type 2 diabetes mellitus presence on the indicators of fibrinolytic parameters (plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA) content, streptokinase-activated plasminogen and α2-antiplasmin activities, euglobulin clot lysis time (ECLT) and Hageman-factor-dependent fibrinolysis time) under ischemic stroke (IS). Materials and methods: Participants were 87 subjects with IS, 22 of them had diabetes mellitus. Blood samples besides for aforementioned parameters were analyzed for glucose and glycosylated haemoglobin content. Results: The research established increase of plasma PAI-1 and tPA levels, ECLT, Hageman-factor-dependent fibrinolysis time in IS and IS with diabetes mellitus patient groups in comparison with the control. PAI-1 concentration in plasma was positively correlated with both lysis time tests but tPA content was negative correlated with glucose level and PAI-1 for only IS patients. But there was a high negative correlation between tPA and ECLT as well as Hageman-factor-dependent fibrinolysis time for both investigated IS forms. Conclusions: The results showed important differences in the characteristics of the fibrinolytic mechanism in IS patients compared with healthy population. The major differences were elevated PAI-1 and t-PA contents and prolonged ECLT in IS patients but no significant differences in these parameters were observed between the patients with IS and IS with diabetes.

Prospectively collected lifestyle and health information as risk factors for white matter hyperintensity volume in stroke patients.

Most studies of white matter hyperintensity volume (WMHV) in stroke patients lack reliable information on antecedent exposure to vascular risk factors. By leveraging prospective cohort data, we explored associations between lifestyle and health factors assessed 1year prior to stroke and WMHV in individuals who experienced an ischemic stroke. This analysis was nested within two large prospective studies of initially healthy individuals. Information on lifestyle factors and health conditions was collected prior to the stroke event through annual or biannual questionnaires. For individuals who experienced their first confirmed ischemic stroke and had available magnetic resonance imaging, we measured WMHV using a validated semiautomated method. Linear regression was used to explore associations between lifestyle factors and health conditions and log-transformed WMHV. We measured WMHV in 345 participants with a first ischemic stroke event (mean age = 74.4years; 24.9% male). After multivariate adjustment, history of diabetes was associated with decreased WMHV (p value = 0.06) while history of transient ischemic attack (p value = 0.09) and hypertension (p value = 0.07) were associated with increased WMHV. Most lifestyle factors and health conditions measured 1year prior to stroke were not associated with WMHV measured at the time of ischemic stroke. Future studies could examine whether long term exposure to these factors impacts diffuse microvascular ischemic brain injury among stroke patients.

Long-Term Risk of Hip Fracture After Ischemic Stroke.

Data are lacking on the long-term risk of hip fracture among patients with ischemic stroke. A better understanding of the contemporary incidence of hip fracture after ischemic stroke could benefit patient care by promoting strategies to prevent this disabling complication in stroke survivors. We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients ≥66 years of age who were hospitalized with acute ischemic stroke, defined through a validated diagnostic code algorithm. We excluded patients who had a prior or concurrent hip fracture diagnosis at the time of ischemic stroke. The primary outcome was hip fracture requiring hospitalization. Survival statistics were used to calculate crude incidence rates, and the Kaplan-Meier method was used to calculate cumulative rates. Among the 1 772 550 beneficiaries in our sample, 60 099 were diagnosed with an acute ischemic stroke without prior or concomitant hip fracture. During 4.5 (±2.2) years of follow-up, the incidence of hip fracture was 1.6 (95% confidence interval [CI]: 1.5-1.6) per 100 person-years in patients with acute ischemic stroke versus 0.6 (95% CI: 0.6-0.6) per 100 person-years in patients without acute ischemic stroke. The cumulative 5-year rate of hip fracture was 7.6% (95% CI: 7.2%-8.0%) among patients with acute ischemic stroke versus 2.8% (95% CI: 2.8%-2.9%) among the remaining Medicare beneficiaries. We found that among elderly Medicare beneficiaries with acute ischemic stroke, nearly 1 in 12 developed a hip fracture over the next 5 years.

Abstract WP246: Long Term Risk of Hip Fracture After Ischemic Stroke

Introduction: The recent Insulin Resistance Intervention after Stroke trial found that pioglitazone decreased the risk of stroke and myocardial infarction in patients with insulin resistance and a recent cerebrovascular event. However, by 5 years, patients receiving pioglitazone had a significantly increased risk of bone fracture requiring surgery or hospitalization compared to patients who received placebo (5.1% versus 3.2%). Data is lacking on the long-term real-world risk of bone fracture among patients with ischemic stroke. Methods: We performed a retrospective cohort study using inpatient and outpatient claims data between 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries. We included patients who were ≥65 years old and hospitalized with ischemic stroke, defined by validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. We excluded patients who had a prior or concurrent hip fracture diagnosis at the time of ischemic stroke. The primary outcome was hip fracture requiring hospitalization. Survival statistics were used to calculate incidence rates and Kaplan-Meier statistics were used to calculate cumulative rates of hip fracture. Results: Among the 1,952,305 beneficiaries in our sample, 60,099 patients developed an ischemic stroke in the absence of a prior or concomitant hip fracture. During 4.5 (±2.2) years of follow-up, the incidence of hip fracture was 1.6 (95% CI, 1.5-1.6) per 100 person-years in the patients with ischemic stroke versus 0.6 (95% CI, 0.6-0.6) per 100 person-years in patients without ischemic stroke. The cumulative 5-year rate of hip fracture was 7.6% (95% CI, 7.2-8.0%) among patients with ischemic stroke compared to 2.8% (95% CI, 2.8-2.9%) among the remaining Medicare beneficiaries. Conclusions: We found that the 5-year cumulative risk of hip fracture in the overall population of Medicare beneficiaries with ischemic stroke was approximately 7.5%.

Abstract WP540: Acid Base and Electrolyte Alterations in Acute Large Vessel Occlusion Stroke

Background and Purpose: In the setting of mechanical thrombectomy for emergent large vessel occlusion (ELVO), we have developed a protocol to collect and evaluate blood immediately distal and proximal from the removed intracranial thrombus. These samples provide a unique resource in evaluating acute changes in acid/base and electrolyte concentrations at the time of ischemic stroke. The purpose of this study is to compare acid/base and electrolyte differences obtained proximal and distal to the occluded intracranial thrombus in acute ischemic stroke patients. Methods: We developed the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol: an IRB-approved tissue banking strategy for ELVO (clinicaltrials.gov NCT03153683). We compared arterial blood gases (ABG) of blood distal versus proximal to the thrombus during thrombectomy. Comparisons were evaluated by Paired Samples T-Tests (p &lt; 0.05). Results: We analyzed the first 46 subjects (age = 67 ± 14.23, 20 males) in the BACTRAC registry. Preliminary results demonstrate that, while pH is nonsignificant (p = 0.513), distal blood in relation to proximal blood showed significantly lower oxygen (p &lt; 0.001), carbon dioxide (p &lt; 0.001), bicarbonate (p &lt; 0.001), ionized calcium (p &lt; 0.001), and potassium (p &lt; 0.001). Sodium concentration was significantly higher (p &lt; 0.001) in distal blood. These results suggest alterations occurring intravascularly during ischemia. Conclusions: These preliminary findings provide a novel insight into the pathology of large vessel stroke in humans, particularly in regard to identifying acute changes in acid/base balance and electrolyte concentrations that occur during stroke.

Abstract WMP45: Gene Expression Levels in Acute Large Vessel Occlusion Stroke in Humans

Background and Purpose: The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) tissue bank collects blood proximal and distal to the intracranial thrombus during the process of mechanical thrombectomy in human stroke patients. These samples provide a unique resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to evaluate gene expression changes occurring within the thrombus and across the occlusion in the intravascular space in acute ischemic stroke patients. Methods: We developed the BACTRAC protocol: an IRB-approved tissue banking approach for ELVO (clinicaltrials.gov NCT03153683). We evaluated relative concentrations of gene expression in 84 inflammatory molecules in thrombi removed from adults who received thrombectomy for ischemic stroke, in static blood distal to thrombus, and in peripheral circulation. Results: We analyzed the first 46 subjects (age = 67 ± 14.23, 20 males) in the BACTRAC registry. Results from qPCR gene expression analyses demonstrate that 21 genes (CCL1, CCL11, CCL13, CCL17, CCL26, CCL8, CSF3, CX3CL1, CXCL1, CXCL9, IFNA2, IL13, IL17C, IL17F, IL1A, IL27, IL3, IL33, LTA, TNFSF11, and TNFSF13) had at least 25 mean fold change in the distal blood compared to the peripheral blood. Fourteen genes (AIMP1, CCL11, CCL13, CCL15, CCL16, CCL23, CCR2, CCR4, CCR8, CD40LG, CXCL10, IL10RA, IL15, and TNFSF13B) had at least 10 mean fold change in the thrombus compared to the peripheral blood. Overall, these genes are associated with chemo-attraction and cell proliferation of monocytes, neutrophils, and T cells. Conclusions: These findings provide a novel insight into the initial pathology of large vessel stroke in humans, particularly in regard to identifying acute gene expression changes that occur during stroke.

Serum Troponin Level in Acute Ischemic Stroke Identifies Patients with Visceral Infarcts

Background and Purpose: Patients with ischemic stroke of cardioembolic origin are at risk of visceral (renal or splenic) infarction. We hypothesized that serum troponin level at time of ischemic stroke would be associated with presence of visceral infarction. Methods: Data were abstracted from a single center prospective stroke database over 18 months and included all patients with ischemic stroke who underwent contrast-enhanced computerized tomography (CT) of the abdomen and pelvis for clinical purposes within 1 year of stroke. The primary predictor was troponin concentration ≥.1ng/mL. The primary outcome was visceral infarct (renal and/or splenic) on CT abdomen and pelvis. Univariate and multivariable logistic regression models were used to estimate the odds ratio and 95% confidence intervals (OR, 95% CI) for the association of troponin with visceral infarction. Results: Of 1233 patients with ischemic stroke, 259 patients had a qualifying visceral CT. Serum troponin level on admission was measured in 237 of 259 patients (93.3%) and 41 of 237 (17.3%) had positive troponin. There were 25 patients with visceral infarcts: 16 renal, 7 splenic, and 2 both. In univariate models, patients with a positive troponin level (versus negative) were more likely to have visceral infarcts (39.1% [9/23] versus 15.0% [32/214], P = .008) and this association persisted in multivariable models (adjusted OR 3.83; 95% CI 1.42-10.31, P = .006). Conclusions: In ischemic stroke patients, elevated serum troponin levels may help identify patients with visceral infarcts. This suggests that troponin in the acute stroke setting is a biomarker of embolic risk. Larger studies with systematic visceral imaging are needed to confirm our findings.

Duration of Heightened Ischemic Stroke Risk After Acute Myocardial Infarction.

BackgroundThe duration of heightened stroke risk after acute myocardial infarction (MI) remains uncertain.Methods and ResultsWe performed a retrospective cohort study using claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Both acute MI and ischemic stroke were ascertained using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM), diagnosis codes. To exclude periprocedural strokes from percutaneous coronary intervention, we did not count strokes occurring during an acute MI hospitalization. Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or September 30, 2015. We fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. We used the corresponding survival probabilities to compute the hazard ratio in each 4‐week interval after discharge. Confidence intervals were computed using the nonparametric bootstrap method. Among 1 746 476 eligible beneficiaries, 46 182 were hospitalized for acute MI and 80 466 for ischemic stroke. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (hazard ratio: 2.7; 95% confidence interval, 2.3–3.2), remained elevated during weeks 5 to 8 (hazard ratio: 2.0; 95% confidence interval, 1.6–2.4) and weeks 9 to 12 (hazard ratio: 1.6; 95% confidence interval, 1.3–2.0), and was no longer significantly elevated afterward.ConclusionsAcute MI is associated with an elevated risk of ischemic stroke that appears to extend beyond the 1‐month window that is currently considered the at‐risk period.

Abstract TMP58: Is Lactate Dehydrogenase Level a Biomarker of Ischemic Stroke in Ventricular Assist Device?

Introduction: Lactate dehydrogenase (LDH) is used as a biomarker of pump thrombosis in patients with left ventricular assist device (LVAD). The relationship of LDH level to ischemic stroke remains unclear. We aimed to explore the relationship of LDH as a marker for LVAD-associated ischemic stroke. Methods: We reviewed consecutive patients with ischemic stroke in a prospectively collected data of LVAD patients in a single, tertiary center from October 2004 to December 2016. LDH values from various time points were collected: at the time of stroke, and 1, 3, and 6-month (± 2 weeks) prior as controls. The clinical reference used for LDH’s normal range was 110 - 200 U/L. Pump thrombosis was diagnosed by isolated power elevations, LDH rise, evidence of hemolysis, and new heart failure symptoms as defined by the International Society for Heart and Lung Transplantation. The LDH levels were compared using Rank Sum test. Results: Of 477 persons with LVAD, 61 (12.7%) developed ischemic stroke within a median of 143.5 days (Interquartile range [IQR] 10.5 - 410.2) from implantation to stroke event. Nineteen of 61 patients were diagnosed with pump thrombosis at the time of ischemic stroke. The LDH was significantly higher at the time of ischemic stroke with a median level of 500 [IQR 279 - 958] than at 6 months prior to stroke (median 294 [IQR 247 - 380], p= 0.001) or at 3 months prior to stroke (median 316 [IQR 270 - 420], p = 0.01), but not compared to those at 1 month prior to stroke (406 [IQR 228 -749], p= 0.28) (Figure). Conclusion: Elevated LDH may not only be indicative of pump thrombosis but may start to rise before stroke occurrence and might serve as a risk marker for ischemic stroke.

Pilot study of volume contracted state and hospital outcome after stroke

An increasing body of research suggests that acute stroke patients who are dehydrated may have worsened functional outcomes. We sought to explore the relationship between a volume contracted state (VCS) at the time of ischemic stroke and hospital outcomes as compared with euvolemic patients. We enrolled a consecutive series of ischemic stroke patients from a single academic stroke center within 12 hours from stroke onset. VCS was defined via surrogate markers (blood urea nitrogen/creatinine ratio >15 and urine specific gravity >1.010). The primary outcome was change in NIH Stroke Scale (NIHSS) score from admission to discharge. Multivariable analyses included adjustment for demographics and infarct size. Over an 11-month study period, 168 patients were eligible for inclusion. Of the126 with complete laboratory and MRI data, 44% were in a VCS at the time of admission. Demographics were similar in both the VCS and euvolemic groups, as were baseline NIHSS scores (6.7 vs 7.3; p = 0.63) and infarct volumes (12 vs 16 mL; p = 0.48). However, 42% of patients in a VCS demonstrated early clinical worsening, compared with 17% of the euvolemic group (p = 0.02). A VCS remained a significant predictor of worsening NIHSS in adjusted models (odds ratio 4.34; 95% confidence interval 1.75-10.76). Acute stroke patients in a VCS demonstrate worse short-term outcomes compared to euvolemic patients, independent of infarct size. Results suggest an opportunity to explore current hydration practices.

Abstract 172: Duration of Heightened Stroke Risk after Acute Myocardial Infarction

Introduction: The duration of heightened stroke risk after acute myocardial infarction (MI) remains uncertain. Methods: We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2015 from a nationally representative 5% sample of Medicare beneficiaries ≥66 years of age. Our exposure of acute MI and the outcome of ischemic stroke were ascertained using previously validated ICD-9- CM diagnosis codes. To exclude periprocedural strokes from percutaneous coronary intervention, we only included strokes occurring after discharge from acute MI hospitalization. Patients were censored at the time of ischemic stroke, death, end of Medicare coverage, or September 30, 2015. We fit Cox regression models separately for the groups with and without acute MI to examine its association with ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. We used the corresponding survival probabilities to compute the hazard ratio (HR) in each 4-week interval after discharge. Confidence intervals (CI) were computed using the nonparametric bootstrap method. Results: Among 1,746,476 beneficiaries, 46,182 were hospitalized for acute MI and 80,466 for ischemic stroke. Compared to patients without acute MI, patients with acute MI were older (mean age 79.0 vs 73.1 years) and had more stroke risk factors. After adjustment for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 4 weeks after discharge from the MI hospitalization (HR, 2.7; 95% CI, 2.3-3.2), remained substantially elevated during weeks 5-8 (HR, 2.0; 95% CI, 1.6-2.4) and weeks 9-12 (HR, 1.6; 95% CI, 1.3-2.0), and was no longer significantly elevated afterward (Figure). Conclusions: Acute MI is associated with a substantially elevated short-term risk of ischemic stroke which appears to extend beyond the 30-day period enshrined in current stroke etiological classification systems.