Stroke Research Articles

Consent-Related Outcomes in the Alteplase Compared to Tenecteplase Trial.

In recent years, researchers have sought to address the challenges of obtaining informed consent for participation in acute stroke trials. We studied outcomes related to the use of deferral of consent in the phase 3 Alteplase Compared to Tenecteplase (AcT) trial. As part of our protocol, we captured methods of consent, participant withdrawals, door-to-randomization times, and door-to-needle times. Participants at 3 sites were invited to complete a survey of attitudes regarding consent for AcT and for acute stroke trials generally. The AcT trial enrolled 1,600 participants from 22 centers across Canada of whom 1,537 were enrolled through deferral of consent (96.0%) and 63 (4.0%) were enrolled by prospective verbal consent followed by written informed consent. Of those enrolled by deferral of consent, 95% (1,454/1,537) consented to ongoing participation. Door-to-randomization times were similar regardless of method of consent, with an overall median of 30 minutes (interquartile range [IQR] 22-42): 29 minutes (IQR 22-42) in the deferral of consent group vs 32 minutes (IQR 25-44) in the prospective consent group (p = 0.1602). Survey respondents overwhelming agreed or strongly agreed with the use of deferral of consent in AcT (86%) and in any acute stroke trial (76%). Deferral of consent was broadly acceptable to participants in the AcT trial as demonstrated by low rates of withdrawal and by survey results. Door-to-randomization times using deferral of consent in AcT were short, although a system of prospective verbal consent used at 1 center took only slightly longer. These results support the importance of innovation around consent for acute stroke trials.

Management of people after stroke in 383 Victorian general practices, 2014-2018: analysis of linked stroke registry and general practice data.

To evaluate the management in Victorian general practice of people who have been hospitalised with stroke or transient ischaemic attacks (TIA). Retrospective observational study; analysis of linked Australian Stroke Clinical Registry (AuSCR) and general practice data. 383 general practices in the Eastern Melbourne, South Eastern Melbourne, and Gippsland primary health networks (Victoria), 1 January 2014 - 31 December 2018. Adults who had been hospitalised with acute stroke or TIA and had at least two encounters with the same general practice during the observation period (7-18 months after the acute event). Assessment of cardiometabolic risk factors (blood pressure, serum lipids, blood glucose, urinary protein); prescribing of guideline-recommended prevention medications (blood pressure-, lipid-, or glucose-lowering, antithrombotic agents); attainment of guideline targets for cardiometabolic risk factors at final assessment during observation period. During 2014-2018, 3376 eligible AuSCR registrants (1465 women, 43.4%) had at least two encounters with one of the 383 general practices during the observation period; median age at stroke onset was 73.9 (interquartile range, 64.4-81.9) years, 737 events were TIAs (21.8%). Blood pressure was assessed in 2718 patients (80.5%), serum lipids in 1830 (54.2%), blood glucose in 1708 (50.6%). Prevention medications were prescribed for 2949 patients (87.4%), including lipid-lowering (2427, 71.9%) and blood pressure-lowering agents (2363, 70.0%). Blood glucose targets had been achieved by 1346 of 1708 patients assessed for this risk factor (78.8%), blood pressure targets by 1935 of 2717 (71.2%), and serum lipid targets by 765 of 1830 (41.8%). The incidence of having risk factors assessed was lower among patients aged 60 years or younger (incidence rate ratio [IRR], 0.97; 95% confidence interval [CI], 0.92-1.03) and those over 80 years of age (IRR, 0.92; 95% CI 0.88-0.97) than for those aged 61-80 years, and for women (IRR, 0.91; 95% CI, 0.87-0.95) and people with dementia (IRR, 0.89; 95% CI, 0.81-0.98). The likelihood of having classes of prevention medication prescribed was lower for patients aged 60 years or younger (IRR, 0.92; 95% CI, 0.88-0.97) and those over 80 years of age (IRR, 0.96; 95% CI, 0.92-0.997) than for patients aged 61-80 years, and for women (IRR, 0.95; 95% CI, 0.91-0.98) and people with dementia (IRR, 0.88; 95% CI, 0.78-0.98). The general practice management of people who have been hospitalised with stroke or TIA could be improved. Effective monitoring of cardiometabolic risk factors will enable general practitioners to optimise care for people who need careful attention to prevent adverse secondary events.

Efficacy and Safety of Sovateltide in Patients with Acute Cerebral Ischaemic Stroke: A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Phase III Clinical Trial.

Sovateltide (Tycamzzi™), an endothelin-B (ET-B) receptor agonist, increases cerebral blood flow, has anti-apoptotic activity, and promotes neural repair following cerebral ischaemic stroke. The objectives of this study were to evaluate the efficacy and safety of sovateltide in adult participants with acute cerebral ischaemic stroke. This was a randomised, double-blind, placebo-controlled, multicentre, Phase III clinical trial of sovateltide in participants with cerebral ischaemic stroke receiving standard of care (SOC) in India. Patients aged 18-78 years presenting up to 24 h after the onset of symptoms with radiologic confirmation of ischaemic stroke and a National Institutes of Health Stroke Scale score (NIHSS) of ≥ 6were enrolled. Patients with recurrent stroke, receiving endovascular therapy, or with intracranial haemorrhage were excluded. The study drug (saline or sovateltide [0.3 µg/kg] was administered intravenously in three doses at 3 ± 1 h intervals on Days 1, 3, and 6, and follow-up was 90 days). The Multivariate Imputation by Chained Equations (MICE) was used to impute the missing assessments on the endpoints. An unpaired t-test, two-way analysis of variance with Tukey's multiple comparison test, and the Chi-square test were used for the statistical analysis. The objective was to determine at Day 90 (1) the number of patients with a modified Rankin Scale score (mRS) 0-2, and (2) the number of patients with an NIHSS 0-5 at 90 days. Patients were randomised with 80 patients in the sovateltide and 78 in the control group. Patients received the investigational drug at about 18 h of stroke onset in both control and sovateltide groups. The median NIHSS at randomisation was 10.00 (95% CI 9.99-11.65) in the control group and 9.00 (95% CI 9.11-10.46) in the sovateltide group. Seventy patients completed the 90-day follow-up in the control group and 67 in the sovateltide group. The proportion of intention-to-treat (ITT) patients with mRS 0-2 score at Day 90 post-randomisation was 22.67% higher (odds ratio [OR] 2.75, 95% CI 1.37-5.57); similarly, the proportion of patients with NIHSS score of 0-5 at Day 90 was 17.05% more (OR 2.67, 95% CI 1.27-5.90) in the sovateltide group than in the control group. An improvement of ≥ 2 points on the mRS was observed in 51.28% and 72.50% of patients in the control and sovateltide groups, respectively (OR 2.50, 95% CI 1.29-4.81). Seven of 78 patients (8.97%) in the control group and 7 of 80 (8.75%) in the sovateltide group developed intracranial haemorrhage (ICH). The adverse events were not related to sovateltide. The sovateltide group had a greater number of cerebral ischaemic stroke patients with lower mRS and NIHSS scores at 90 days post-treatment than the control group. This trial supported the regulatory approval of sovateltide in India, but a multinational RESPECT-ETB trial will be conducted for US approval. Clinical Trials Registry, India (CTRI/2019/09/021373) and the United States National Library of Medicine, ClinicalTrials.gov (NCT04047563).

Transradial versus transfemoral access for mechanical thrombectomy: A single institution experience.

There has been debate in the literature regarding the adoption of a "radial-first" approach for mechanical thrombectomy (MT) in acute ischemic stroke (AIS). Conflicting reports suggest that transradial access (TRA) may allow for shorter times to reperfusion while others conclude that long-term functional outcomes may favor transfemoral access (TFA). Here, we report a single-institution experience with the adoption of TRA as the primary route for acute stroke intervention. We retrospectively reviewed a single-institution database of patients undergoing MT for AIS from March 2020 to April 2023. This time period was selected to capture the change in clinical practice at our institution from TFA to TRA. Primary and secondary outcomes included technical success, procedural complications, and long-term functional outcomes. Patients were stratified into two cohorts from initial access. Cohorts were compared utilizing inferential statistics. A total of 192 consecutive cases were identified, with 80 in the TFA cohort and 112 in the TRA cohort. There was no difference in outcomes with respect to time from puncture to recanalization, rates of successful recanalization (TICI ≥ 2b), number of passes, rates of symptomatic intracranial hemorrhage (sICH), modified Rankin scale (mRS) at discharge and 90 days, and 90-day mortality (p ≥ 0.05, all). The TRA had a higher rate of access conversion (p < 0.001), while the TFA cohort had a higher rate of access site complications (p < 0.05).

Cerebral Infarct Growth: Pathophysiology, Pragmatic Assessment, and Clinical Implications.

Cerebral ischemic injury occurs when blood flow drops below a critical level, resulting in an energy failure. The progressive transformation of hypoperfused viable tissue, the ischemic penumbra, into infarction is a mechanism shared by patients with ischemic stroke if timely reperfusion is not achieved. Yet, the pace at which this transformation occurs, known as the infarct growth rate (IGR), exhibits remarkable heterogeneity among patients, brain regions, and over time, reflecting differences in compensatory collateral flow and ischemic tolerance. We review (1) the pathophysiology of infarct growth, (2) the advantages and pitfalls of different approaches of IGR measurement, (3) research gaps for future studies, and (4) the clinical implications of stroke progressor phenotypes. The estimated average IGR in patients with acute large vessel occlusion stroke is 5.4 mL/h although there is wide variability based on ischemic stroke subtype, occlusion location, presence of collaterals, and patient baseline status. The IGR can be calculated using various pragmatic strategies, mostly either quantifying the extension of the infarct at a particular time and dividing this measure by the time that elapsed from symptom onset to imaging assessment or by using collateral blood flow status as a radiological surrogate marker. The IGR defines a spectrum of clinical stroke phenotypes, often dichotomized into fast and slow progressors. An IGR ≥10 mL/h and the perfusion metric hypoperfusion intensity ratio ≥0.5 are commonly used definitions of fast progressors. A nuanced understanding of the IGR and stroke progressor phenotypes could have clinical implications, including informing prognostication, acute decision-making in peripheral-to-comprehensive transfer patients eligible for thrombectomy, and selection for adjuvant neuroprotective agents.

Cerebral vascular shunting and oxygen metabolism in sickle cell disease.

Patients with sickle cell disease (SCD) are at elevated risk of silent cerebral infarcts and strokes; however, they frequently lack established stroke risk factors (e.g., macrovascular arterial steno-occlusion) and as such the mechanisms underlying such events are incompletely characterized. This study evaluated cerebral metabolism with respect to imaging markers of vascular shunting in 143 SCD participants, including 73 pediatric (6-17 years) and 70 adult (18-40 years) participants. Participants completed clinical and cerebral imaging assessments using 3-Tesla brain MRI to quantify cerebral hemo-metabolic measures. Vascular shunting was assessed in each patient using a previously published ordinal venous hyperintensity score (VHS=0, 1, or 2) on cerebral blood flow-weighted MRI. Relationships between age group (pediatric versus adults) and hemo-metabolic measures for varying VHS were investigated using two-way ANOVA. Participants with VHS=2, indicative of the most rapid arterio-venous transit, had significantly reduced blood oxygen content (CaO2=10.90±1.69 ml O2/100ml blood), oxygen extraction fraction (OEF=33.52±5.54%), and cerebral metabolic rate of oxygen consumption (CMRO2=2.91±0.69 ml O2/100g tissue/min) compared to their counterparts with VHS=0 (CaO2=12.42±1.58 ml O2/100ml blood; OEF=39.03±3.80%; CMRO2=3.77±0.84 ml O2/100g tissue/min) or VHS=1 (CaO2=11.86±1.73 ml O2/100ml blood; OEF=36.37±5.11%; CMRO2=3.59±0.78 ml O2/100g tissue/min). Both pediatric and adult SCD patients presenting with greater imaging evidence of vascular shunting had mildly reduced OEF and CMRO2. These findings highlight that imaging markers of vascular shunting are associated with significant, albeit mild, evidence of reduced OEF and CMRO2 in patients with SCD.

Factors affecting emergency medical dispatchers decision making in stroke calls - a qualitative study.

Emergency Medical Communication Centers (EMCC) have a key role in the prehospital chain-of-stroke-survival by recognizing stroke patients and reducing prehospital delay. However, studies on EMCC stroke recognition report both substantial undertriage and overtriage. Since mis-triage at the EMCC challenges the whole chain-of-stroke-survival, by occupying limited resources for non-stroke patients or failing to recognize the true stroke patients, there is a need to achieve a more comprehensive understanding of the dispatchers' routines and experiences. The aim of this study was to explore factors affecting EMCC dispatcher's decision-making in stroke calls. A qualitative exploratory study, based on individual semi-structured interviews of 15 medical dispatchers from EMCC Oslo, Norway. Interviews were conducted during August and October 2022 and analyzed using the principles of thematic analysis. We identified four themes: [1] Pronounced stroke symptoms are easy to identify [2]. Non-specific neurological symptoms raise suspicion of acute stroke but are difficult to differentiate from other medical conditions [3]. Consistent use of the Criteria Based Dispatch (CBD) protocol may increase EMCC overtriage [4]. Contextual conditions at EMCC can affect dispatchers' decision-making process and the ability for experiential learning. Medical dispatchers at the EMCC perceive vague and non-specific stroke symptoms, such as dizziness, confusion or altered behaviour, challenging to differentiate from symptoms of other less time-critical medical conditions. They also perceive the current CBD protocol in use as less supportive in assessing such symptoms. High workload and strict EMCC response time interval requirements hinder the gathering of essential patient information and the ability to seek guidance in cases of doubt, potentially exacerbating both EMCC undertriage and overtriage. The absence of feedback loops and other strategies for experiential learning in the EMCC hampers the medical dispatcher's ability to evaluate their own assessments and improve dispatch accuracy.

Hippocampal exosomes from stroke aggravate post-stroke depression by regulating the expression of proBDNF and p75NTR and altering spine density.

Post-stroke depression (PSD) affects millions of patients who suffer cerebral stroke. However, the molecular mechanisms and pathophysiology are poorly understood. Previous studies have shown that exosomes have been proven to be involved in neuropsychiatric disorders such as stroke and post-stroke depression in neurotransmitter release, neuronal remodeling, and neuron angiogenesis. Here we extracted and purified hippocampal exosomes from stroke mouse model to investigate mechanisms of hippocampal exocytosis in PSD assessed by using behavioral tests and biochemical methods. Aiming at the effect of hippocampal exosomes from stroke on the development of PSD, behavioral test was compared including sugar water preference experiment, open fields, forced swimming test, to explore it in depth. Further, the expression of depression-related protein (proBDNF and p75NTR) and synapse-associated proteins (Synaptotagmin and PSD95) was evaluated by Western blotting, RT-qPCR or immunofluorescence staining. Density of dendritic protrusions of neurons was assessed by Golgi staining to measure changes in spine density after the treatment of hippocampal exosomes from stroke. Our results revealed that injection of exosomes from stroke models significantly aggravated depressive-like behaviors, increase of depression-related protein (proBDNF and p75NTR) expression and deficiency of synapse-associated proteins (Synaptotagmin and PSD95) expression, and the decreased number of spin density. Our findings together suggest that hippocampal exosomes from stroke cause exacerbation of depressive-like behavior in mice, possibly resulting from the regulation of neurogenesis by its depression-associated proteins (proBDNF and p75NTR). Therefore, hippocampal exosomes from stroke are promising targets for the diagnosis and treatment of PSD.

Characteristics of cerebellar cognitive affective syndrome in patients with acute cerebellar stroke and its impact on outcome

Purpose To evaluate the cerebellar cognitive affective syndrome scale (CCAS-S) in patients with acute cerebellar stroke (ACS) and examine its relationship with the discharge destination. Methods Patients with first-time ACS admitted to our hospital between April 2021 and April 2023 were included. The CCAS-S, Mini-Mental State Examination (MMSE), and Scale for the Assessment and Rating of Ataxia (SARA) were evaluated 1 week after stroke onset, and Functional Independence Measure (FIM)/Barthel Index (BI) at discharge, duration of hospitalization, and discharge destination were evaluated. The Mann–Whitney U test was used to compare CCAS-S and variables. Results Thirteen consecutive patients with ACS and age-matched comparison groups were included. The MMSE was within the normal range in all patients; however, patients with stroke had a lower total CCAS-S score (median 72, IQR 66–80) and a higher number of failed tests (median 4, IQR 3–5) than comparison. Significant deficits were observed in semantic fluency (p = 0.008), category switching (p = 0001), and similarity (p = 009). Definite CCAS were diagnosed 10 patients, respectively. Patients discharged home showed better SARA and FIM/BI but similar CCAS-S compared to those discharged to rehabilitation hospitals. Conclusion In patients with ACS, it is the impairment of motor function, not CCAS, that affects discharge destination.

Electroencephalography based delirium screening in acute supratentorial stroke.

Up to 25% of patients suffering from an acute stroke are diagnosed with delirium during the hospital stay, with older age increasing the risk. Generalized slowing in the electroencephalogram (EEG) supports the diagnosis of delirium. We examined the potential of single-channel EEG (DeltaScan®) as an easy-to-use device on intensive care units for detecting delirium. Our aim was to investigate characteristics of bihemispheric EEG recordings and single-channel EEG in patients suffering from strokes with and without delirium and to analyze the diagnostic accuracy of EEG-based diagnoses. Within the first five days after stroke onset, patients received single-channel EEG DeltaScan® and a routine 21-channel EEG. The DeltaScan® analyzes right sided fronto-parietal EEG using a proprietary algorithm focusing on polymorphic delta activity (PDA). In routine EEG the power spectral density (PSD) in predefined frequency bands was analyzed based on 2-minute eyes-closed resting state segments. EEG-analyses were conducted in MNE (v1.3.1) in Python (3.10) and RStudio (v4.2.1). In 9 of 53 patients (52-90 years) delirium was diagnosed according to DSM-V criteria. Sensitivity of DeltaScan® was 44% (95% CI = 15.3-77.3%), while specificity was 71% (95% CI = 57-83%). We found patients with right hemispheric stroke having a higher probability to be false positive in DeltaScan® (p = 0.01). The 21-channel EEG based power analysis revealed significant differences in frontal delta and theta power between patients with and without delirium (p < 0.05). When EEG is used in clinical practice to support a delirium diagnosis in stroke patients, bihemispheric recordings are likely preferable over unilateral recordings. Slowing in the delta- or theta-frequency spectrum over the site of stroke may lead to false-positive results in single channel EEG based delirium scoring.

Imaging, biomarkers, and vascular cognitive impairment in China: Rationale and design for the VICA study.

Vascular cognitive impairment (VCI) is highly heterogeneous, with unclear pathogenesis. Individuals with vascular risk factors (VRF), cerebral small vessel disease (CSVD), and stroke are all at risk of developing VCI. To address the growing challenges posed by VCI, the "Vascular, Imaging and Cognition Association of China" (VICA) was established. VICA aims to recruit 10,000 participants, including 2000 with VRF, 3000 with CSVD, and 5000 stroke patients, to form a nationwide multicenter cohort. The study integrates clinical, neuroimaging, and multi-omics data to better understand VCI heterogeneity, improve disease prediction, and ensure timely diagnosis. VICA has screened 2045 eligible VRF participants from six communities in Wuhan, Shanghai, and Taizhou, along with 602 CSVD and 1269 stroke patients from 135 hospitals nationwide. Baseline enrollment and follow-up work are still ongoing. Establishing a high-quality longitudinal cohort is crucial for understanding VCI pathogenesis and developing novel markers for early screening and diagnosis. Establish a large-scale prospective longitudinal cohort comprising 10,000 participants, focusing on the high-risk population of vascular cognitive impairment (VCI) in China. Establish a nationwide three-tier medical network, make full use of resources, and achieve extensive enrollment of patients with cerebral small vessel disease and stroke patients. Utilize multimodal imaging and biomarkers to lay the foundation for constructing more-precise risk models. Introduce eye movement and gait analysis as new methods for assessing cognitive function. Use positron emission tomography to further investigate the interaction between vascular factors and neurodegeneration.

Effects of Social Determinants of Health on Acute Stroke Care Among Patients With Acute Ischemic Stroke: A Retrospective Cohort Study.

Social determinants of health (SDOH) are important contributors to poor stroke-related outcomes. While some have suggested that this association is driven by the increased incidence of stroke observed with poor SDOH, others have raised concerns regarding disparities in acute stroke care. This study aimed to determine the association between SDOH and the administration of thrombolytic therapy and mechanical thrombectomy among patients with acute ischemic stroke. A retrospective cohort analysis was conducted using Texas Emergency Department Public Use Data (2016-2019), including adult patients diagnosed with acute ischemic stroke. The risk ratios (RRs) of administering thrombolysis and thrombectomy based on variables representing SDOH and a collective measure (Social Vulnerability Index [SVI]) were computed using mixed-effects Poisson regression models accounting for the nested nature of patients in hospitals and neighborhoods. The Charlson comorbidity score was considered as a covariate. Of the 139,852 patients with ischemic stroke (female, 51.7%; White, 67.2%; Black, 16.6%; Hispanic, 25.1%), 16,831 (12.3%) received thrombolytic therapy and 5,951 (4.3%) received mechanical thrombectomy. Age older than 65 years (RR 0.578 [0.537-0.621]) vs 18-45 years, Black (RR 0.801 [0.761-0.844]) vs White, Hispanic (RR 0.936 [0.895-0.98]) vs non-Hispanic, Medicare/Medicaid/Veterans Affairs (VA) (RR 0.917 [0.882-0.954]) or uninsured (RR 0.883 [0.833-0.935]) vs private insurance, and rural (RR 0.782 [0.723-0.845]) vs urban dwelling were less likely to be associated with thrombolysis. Patients in the highest quintile based on the SVI were less likely to receive thrombolysis than those in the lowest quintile (RR 0.926 [0.867-0.989]). Patients were less likely to receive thrombectomy if they were 65 years and older (RR 0.787 [0.691-0.895]), belonged to the Black race (RR 0.745 [0.679-0.818]) or Hispanic ethnicity (RR 0.919 [0.851-0.992]), had Medicare/Medicaid/VA insurance (RR 0.909 [0.851-0.971]), or were from a rural area (RR 0.909 [0.851-0.971]). Similarly, SVI decreased the likelihood of undergoing mechanical thrombectomy (RR 0.842 [0.747-0.95]). Despite many improvements in stroke management, SDOH continue to be a significant driver of treatment access for acute ischemic stroke. While our findings are limited to Texas, our results should raise awareness and promote more studies regarding the effects of these SDOH at the national and international levels.

Abstract 4135712: Mortality and Cardiovascular Complications Associated with Weight Loss Drugs among Breast Cancer Females Under Cardiotoxic Therapies: A Real-World Populational Study in the United States

Background: Obesity is an adverse prognostic factor for breast cancer (BC). While liraglutide and semaglutide, derived from antidiabetic glucagon-like peptide-1 receptor agonists (GLP1RA), are established weight loss drugs known for their cardiovascular safety in the general obese population, their safety in BC patients undergoing cardiotoxic antineoplastic therapies remains less understood. Objective: To investigate the mortality and cardiovascular outcomes related to GLP1RA used for weight loss among the highly susceptible BC females. Methods: This retrospective cohort study was based on the TrinetX network, comprising real-time health records from over 60 US healthcare organizations. The study population included obese females (≥18 years old) who received at least three prescriptions of either exclusive GLP1RA (liraglutide or semaglutide) or non-GLP1RA weight loss drugs (phentermine, bupropion-naltrexone, orlistat) upon BC diagnosis between 01/01/2015 and 01/01/2022. The index date was the initiation of systemic anti-cancer treatment, including chemotherapy (anthracycline, taxane, or cyclophosphamide), and/or anti-HER2 agents (trastuzumab, pertuzumab, or lapatinib). We used 1:1 propensity score-matching (PSM) to balance demographics, BMI, comorbidities, concurrent medications for cardiovascular diseases and metabolic disorders, BC receptor status and prior treatment, and levels of serum cholesterol (LDL, HDL) and hemoglobin A1c. Cox regression models were applied to compute hazard ratios (HR) and 95% confidence intervals (CIs). Follow-up continued until 05/24/2024, or until adverse cardiovascular events or death occurred. Results: Among 380 PSM-balanced pairs, the GLP1RA group (mean age: 57.6±11) showed significantly lower risks of all-cause mortality (HR 0.593, 95% CI 0.457-0.77), acute heart failure (HR 0.496, 95% CI 0.286-0.859), angina pectoris (HR 0.566, 95% CI 0.343-0.936), and acute stroke (HR 0.661, 95% CI 0.46-0.951) than the non-GLP1RA group (mean age: 57.5±12). Otherwise, no significant difference was shown in acute myocardial infarction (HR 0.787, 95% CI 0.495-1.251), pulmonary hypertension (HR 0.777, 95% CI 0.55-1.099), or arrhythmias (HR 0.829, 95% CI 0.566-1.215). Conclusion: Compared to non-GLP1RA weight loss agents, GLP1RA offers better survival and cardiovascular protection for BC patients undergoing cardiotoxic therapies. Future studies are warranted to validate the safety of these weight loss drugs during the BC treatment continuum.

Abstract 4119129: PREDICTING 30-DAY ALL-CAUSE READMISSION AFTER STROKE: THE APPLICATION OF MACHINE LEARNING TO LINKED REGISTRY DATA

Background: Thirty-day readmission following hospital discharge for stroke is an important quality measure for US hospitals. Current US prediction models for post stroke readmission based on electronic medical records from single healthcare systems or hospitals have modest discrimination (AUC range 0.64 - 0.74). Aim: To develop 30-day all-cause readmission prediction model using a machine learning (ML) based method trained on linked stroke registry and administrative claims data. Methods: Using probabilistic linking, we matched acute stroke (ICD-10 I61-I63) discharges from 31 hospitals participating in the Michigan Acute Stroke registry between 2016-2020 to multipayer administrative claims data provided by the Michigan Value Collaborative for Medicare and Blue Cross Blue Shield of Michigan commercial beneficiaries. Stroke registry data included patient demographics, clinical characteristics, past medical history, and treatments. Claims data was used to identify readmissions within 30 days of discharge. We used multivariable LASSO logistic regression- a simple ML technique to predict 30-day all-cause-readmission and evaluated the prediction accuracy using a hospital-split internal validation scheme to generate hospital-specific and pooled AUC estimates with 95% confidence intervals (Figure 1). Results: Of 19,382 linked stroke discharges, 2,724 (14.1%) were readmitted within 30-days. Readmitted patients were older, more likely to be male, black, and have higher stroke severity (NIHSS &gt;5). Registry hospitals were either primary (64%) or comprehensive (26%) stroke centers. Hospital-specific 30-day readmission ranged between 9.9%-23.1% ( P &lt;.001) with an average of 14.1% (95% CI:13.6%-14.5%) (Figure 2). Hospital specific AUC estimates ranged between 0.60-0.80 with a pooled AUC of 0.68 (95% CI:0.65-0.70) (Figure 2). Conclusions: ML prediction model fitted to linked registry data can be used to predict hospital-specific and statewide readmissions post stroke.

Abstract 4119428: Monosialoganglioside-containing nanoliposomes protect against acute and chronic ischemic stroke injury

Background: Stroke remains a leading cause of mortality and disability. The narrow temporal window and limited availability of, and eligibility for thrombolytic therapy or endovascular thrombectomy are major therapeutic limitations in treating stroke. Neuroprotective therapies that could be given early to replace or augment these existing therapies are needed to improve stroke outcomes. We showed that monosialoganglioside (GM1) containing nanoliposomes composed of phosphatidylcholine, cholesterol and GM1 (70/25/5% molar ratios, NLGM1) protect against hypoxic injury likely through Nrf2-dependent upregulation of antoxidant enzymes. Aims: To test if post-occlusion NLGM1 treatment could reduce 1) acute stroke injury following middle cerebral artery occlusion (MCAO) and 2) chronic injury following photothrombotic (PT) stroke injury. Methods: 20 week old C57BL/6 mice underwent MCAO for 60 minutes and then injected with saline or NLGM1 (1 or 2 mg IV) prior to reperfusion. Neurologic deficit score and brain infarct % area were measured the next day. Separately, mice underwent PT injury followed by injection of saline or NLGM1 (1 or 2 mg immediately and 2 hours post-injury) and cognitive/behavior tests done 1-90 days post injury. Results: Following MCAO, there was reduced neurologic impairment, infarct volume and brain edema with NLGM1 versus saline control (Fig. 1). Following PT injury, there was reduced neurologic, cognitive and motor impairment from Day 2-90 post-injury with NLGM1 versus saline control (Fig. 2). In both stroke models, there was no difference in efficacy between 1 and 2 mg NLGM1 doses. Conclusions: Treatment of mice with NLGM1 following MCAO or PT stroke injury resulted in improved structural (infarct size, edema) and functional (cognitive, behavior, motor) outcomes in the acute (MCAO) and chronic (PT) timeframes. NLGM1 is a potential novel therapeutic agent for stroke.

Abstract 4134637: Impact of Glucagon-Like Peptide-1 Agonists on Cardiovascular Outcomes in Chronic Kidney Disease Stage 5: A Propensity Score-Matched Analysis

Background: Patients with chronic kidney disease stage 5 (CKD-5) face heightened risks of cardiovascular (CV) complications and mortality. Glucagon-like peptide-1 agonists (GLP-1a), primarily used in type 2 diabetes, are being investigated for potential CV benefits in this population. This study aims to evaluate the impact of GLP-1a treatment on CV outcomes and survival among CKD-5 patients. Methods: This retrospective cohort study utilized data of adult patients diagnosed with CKD-5 between January 2014 and August 2023 from the TriNetX global research network. A propensity score matching analysis of those treated with GLP-1a for at least six months versus those never exposed to GLP-1a therapy was conducted. Results: Our analysis showed significantly reduced odds for the composite primary outcome of acute myocardial infarction (AMI), stroke, and mortality (OR = 0.66, 95% CI: 0.57-0.78, p&lt;0.001), and other CV outcomes such as cardiac arrest, hypertensive crisis, and hypertensive urgency, among the GLP-1a cohort compared with the non-GLP-1a cohort. Kaplan-Meier survival analysis revealed a significantly higher five-year incidence-free probability for the composite primary outcome (63.5% vs. 50.5%, p&lt;0.001) and for other CV outcomes such as hypertensive events, AMI, cardiac arrest, and hemorrhagic stroke for the GLP-1a cohort. Conclusion: The study suggests that GLP-1a therapy in CKD 5 patients may confer certain CV benefits. Further investigations are warranted to elucidate the underlying mechanisms and confirm the therapeutic efficacy of GLP-1a in this patient population.

Abstract 4137781: Relationship between Race, Predelivery Cardiology Care and Cardiovascular Outcomes in Pre-eclampsia/Eclampsia among a Commercially Insured Population

Background: Inequities in Preeclampsia/Eclampsia (PrE/E) persist. It is unknown if the receipt of cardiology care relates to future risk of major adverse cardiovascular events (MACE) in Black and White patients with PrE/E. We sought to determine the cumulative incidence of MACE by race and whether predelivery cardiology care was associated with the hazard of MACE up to 1-year post-delivery for Black and White patients with PrE/E. Methods: Using Optum’s Clinformatics® Data Mart Database (CDM), we identified Black and White patients with PrE/E who had a delivery between 2008 to 2019. MACE was defined as the composite of heart failure, acute myocardial infarction, stroke, and death. Cumulative incidence functions were used to compare the incidence of MACE by race. Cox regression models were used to assess the hazard of MACE by cardiology care for Black and White patients. Results: Among 29,336 patients (83.4% White, 16.6% Black, mean age of 30.9 years) with PrE/E, 11.2% received cardiology care (10.9% White, 13.0% Black). Black patients had a higher incidence of MACE than White patients at 1-yr post-delivery (2.7% vs 1.4%). After adjusting for age and clinical comorbidities, receipt of cardiology care was associated with lower hazard of MACE for White patients (HR= 0.68, 95%CI: 0.50-0.92 p=0.013) but not Black patients (HR: 1.22, 95% CI: 0.82-1.81; p= 0.328). The interaction effect between race and cardiology care was statistically significant (p=0.013) Conclusions: Among a well-insured population of patients with PrE/E, Black patients had a higher cumulative incidence of MACE up to a year post-delivery. However, cardiology care significantly lowered the hazard of MACE for only White women. This observation does not suggest that cardiology care is detrimental to Black individuals but underscores the necessity to investigate why outcomes are disparate among these racial groups.

Abstract 4119303: The New Strait-Jacket Designed for Endovascular Therapy Reduces the First Reperfusion Time of Emergency Thrombectomy for Stroke

Introduction: Conscious sedation during cerebrovascular interventional surgery can shorten the time of vascular recanalization and bring significant benefits to patients, but patients are often difficult to cooperate, which affects the operation of interventional surgery. This study aims to develop a novel cerebral vascular intervention strait-jacket and explore its safety and effectiveness in emergency cerebral vascular intervention surgery. Methods: Using the convenient sampling method, patients with acute large artery occlusion stroke who underwent emergency mechanical thrombectomy in Zhongnan Hospital of Wuhan University from September 2018 to March 2021 were selected as the research objects. The control group was treated with conventional restraint belt, and the experimental group was treated with new cerebrovascular interventional surgery strait-jacket. The first reperfusion time, total operation time, modified Rankin score (mRS) at 30 days, intraoperative limb prolapse rate, average surgical cost, and safety indicators were compared between the two groups. The t test, Mann-Whitney U test or Fisher exact test were used for comparison between groups according to the data type. A p&lt;0.05 indicated statistical significance. Results: The new type of cerebrovascular interventional surgical strait-jacket developed in this study are shown in Figure 1, which have been patented and transformed into products. A total of 140 patients were included for mechanical thrombectomy, randomly divided into an experimental group (n=69) and a control group (n=71). Using the new strait-jacket significantly shortened the first reperfusion time (43.5±13.7 vs 50.7±15.7, P=0.039) and the total operation time (81.1±12.6 vs 93.2±21.1, P=0.027). There was a significant decrease in limb dislodgement rate (0% vs 35.2%, P&lt;0.001) and a noticeable reduction in average surgical cost (76315±12400 vs 81462±14142 P=0.040) by using the strait-jacket. In terms of safety performance, using the strait-jacket significantly lower rates of skin redness than the control group (8.7% vs 42.3%, P&lt;0.001). Conclusion: The new type of cerebrovascular interventional surgical strait-jacket is safe, which can effectively shorten the operation time, reduce the rate of intraoperative limb prolapse and the average operation cost, and can bring good social benefits.

Abstract 4119116: Percutaneous Aspiration of Mitral Valve Endocarditis using the AngioVac Device

Case Description: A 68-year-old man with end-stage renal disease on dialysis, peripheral vascular disease with metatarsal amputations, atrial fibrillation and type 1 diabetes was admitted for foot osteomyelitis secondary to MSSA bacteremia. Transesophageal echocardiogram revealed mobile mitral valve vegetations up to 1.8cm on the atrial aspect of the posterior mitral valve leaflet which prolapsed through the mitral valve during diastole. Ejection fraction was 60% and there was trivial-mild mitral regurgitation without valvular destruction or peri-annular extension into the mitral annulus. MRI brain showed bilateral cerebral and cerebellar hemispheric infarcts, consistent with acute embolic stroke. He was at high risk for both recurrent embolism and operative mortality (STS risk score 51%) due to his comorbidities and risk of hemorrhagic conversion of stroke. After shared decision making, percutaneous aspiration of the mitral vegetation was performed with AngioVac (Fig). Cerebral embolism protection devices were deployed prior to AngioVac evacuation of the mass. There was no residual mitral regurgitation and only a small vegetation strand remained (Fig). Surgical pathology confirmed MSSA endocarditis. Blood cultures remained negative, and the patient did not suffer from recurrent embolic events. The patient underwent revision metatarsal amputation and was discharged with a 6-week course of IV cefazolin. Discussion: Infective endocarditis with high embolic risk is life-threatening and challenging to treat in patients with high surgical risk. We illustrate a case of percutaneous vegetation aspiration using the AngioVac device in our patient who suffered from embolic strokes due to MSSA mitral valve endocarditis. Meta-analyses have shown clinically successful debulking in 90% of cases, with 82% of patients able to clear bacteremia with AngioVac. Although most commonly used in right-sided lesions, percutaneous debulking of left-sided endocarditis with AngioVac and cerebral protection can be considered as a treatment strategy in select patients with prohibitive surgical risk.

Abstract 4135434: Effect of early nutritional guidance for patients with acute myocardial infarction: A single center retrospective cohort study

Introduction/Background: Acute myocardial infarction (AMI) stands as a major global cause of mortality. Various intervention strategies, such as pre-hospital care, reperfusion therapies, pharmacological interventions, dietary modifications, and exercise therapies, have been researched to improve patient prognosis. Research Question: There remains a lack of evidence regarding the impact of early nutritionist-led dietary guidance on the prognosis of AMI patients. Aim: This study aimed to elucidate whether nutritional guidance by nutritionists who have national qualifications would improve the mortality and the primary composite endpoint (including acute decompensated heart failure, stroke, and acute coronary syndrome) of patients following an acute myocardial infarction. Methods/Approach: A retrospective cohort study enrolling 409 AMI patients who underwent emergency percutaneous coronary interventions between September 1, 2015, and October 31, 2023. Nutritionists guided 223 patients (54.5%) during hospitalization in this study. The nutritional guidance used in our study was also based on the definition of adequate caloric intake of 25–30 kcal per ideal body weight (kg). Under an appropriate total energy intake, a fat energy ratio of 20–25% and a carbohydrate energy ratio of 50–60% are recommended, with protein and lipid restrictions depending on the disease state. Results/Data: During a median follow-up of 39 months, 24 cases of all-cause mortality (5.9%) and 6 cases of cardiovascular mortality (1.5%) were recorded. Kaplan–Meier curves demonstrated significantly higher incidence rates of death and primary composite endpoints among patients without nutritional guidance during hospitalization. The multivariate Cox regression model revealed early nutritional guidance as a significant predictor for long-term mortality but not for primary composite endpoints. Furthermore, undernourished patients, defined as those with a geriatric nutritional risk index of 98 or less, showed a similar prognosis to those with good nutritional status after receiving nutritional guidance, indicating that nutritional guidance improves prognosis. Conclusion: Nutritionist-led dietary guidance for patients with AMI can potentially improve total mortality and is expected to be more effective in undernourished patients. Further research is warranted to explore the physiological impacts of improved diets resulting from such guidance and their effects on enhancing prognosis.