bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4135846: Cardiovascular Effectiveness of Glucagon-like Peptide-1 Receptor Agonists and Empagliflozin Combination Therapy in Adults with Type 2 Diabetes
Authors: Htoo Phyo , Paik Julie , Tesfaye Helen , Schneeweiss Sebastian , Glynn Robert , Shay Christina , Schmedt Niklas , Koeneman Lisette , Wexler Deborah , Patorno Elisabetta
Published: November 2024

Introduction/Background:
Both empagliflozin and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated cardiovascular (CV) benefits in clinical trials. However, few trials examined the combination of both therapies and evidence is scarce on whether the addition of empagliflozin to GLP-1RA has further CV benefits.

Aim/Goal:
We evaluated the risk of CV outcomes in patients with type 2 diabetes (T2D) initiating baseline GLP-1RA therapy that added empagliflozin compared to those that added sulfonylureas (SU).

Methods:
Using Medicare, Optum, and Marketscan data (2014-22), we identified patients with T2D aged ≥18 years initiating GLP-1RA that subsequently added either empagliflozin or SU. Follow-up began on the date of additional therapy and continued until discontinuation of either drug, a gap in insurance coverage, death, or study end. After propensity score standardized mortality ratio weighting adjusting for 98 covariates, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years evaluating a composite of myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), or all-cause death in the overall population and in patients with history of CV disease.

Results:
We identified 27,962 patients initiating GLP-1RA + empagliflozin vs 25,137 patients initiating GLP-1RA + SU. After weighting, relative to patients initiating GLP-1RA + SU, those initiating GLP-1RA + empagliflozin had lower risks of MI-stroke [HR 0.70 (0.55, 0.90); RD: -4.3 (-6.6, -2.0)], HHF in the primary hospital discharge position [HR: 0.59 (0.43, 0.81); RD: -3.9 (-5.8, -2.1)]; HHF in any discharge positions [HR: 0.84 (0.72, 0.98); RD: -7.6 (-11.6, -3.6)], and all-cause death [HR: 0.83 (0.62, 1.11); RD: -1.3 (-3.2, 0.56)]. Findings were similar but with larger RDs in patients with baseline CV disease (
Table
).

Conclusion:
In US clinical practice, patients with T2D initiating GLP-1RA that added empagliflozin had lower risks of MI-stroke, HHF, and death compared to adding SU, which suggests an additive CV benefit when combining GLP-1RA and empagliflozin therapies.
Abstract 4135852: Safety and Post-operative Complications of Endovascular Versus Surgical Versus Follow-up and Medical Treatment for Patients with Vertebrobasilar Artery Stenosis: Propensity Score Weighting and a Machine Learning Driven Analysis
Authors: Shaheen Ahmed , Saha Ram , Shaheen Nour
Published: November 2024

Background:
Vertebrobasilar artery stenosis (VBAS) can cause posterior circulation strokes (PCS). Optimal management is controversial, with options including medical therapy (MT), endovascular stenting (ES), and surgical revascularization (SR). This study compares outcomes of these treatments and evaluates the correlation between clinical features and medical history with 30-day outcome.

Methods:
Patients with VBAS were identified from the 2017-2018 National Inpatient Sample (NIS). Propensity scores adjusted for baseline differences. Outcomes included mortality, neurological complications (NC), discharge destination (DD), length of stay (LOS), total charges (TC), and procedural complications (PC). Predictive ability of clinical variables was assessed using logistic regression (LR) and machine learning techniques (MLT).

Results:
Of 1,343 patients, 1,061 (79.0%) received NI, 234 (17.4%) underwent ES, and 24 (1.8%) had SR. Mean age was 69.45 years, with 64.1% male. Demographics: 69.8% White, 14.9% Black, 10.0% Hispanic, and 5.3% other races. Hypertension (HTN, 85.4%) and diabetes (DM, 18.9%) were prevalent. After propensity weighting, ES was associated with higher odds of mortality, surgical/medical complications (SMC), and device/graft complications (DGC) compared to NI. SR showed a non-significant trend toward higher non-home discharges (NHD). ES and SR groups had higher resource utilization with longer LOS and greater TC. Clinical variables alone were weak predictors, with AUC values ranging from 0.454 to 0.71 across different outcomes and models.

Conclusion:
ES of VBAS was associated with higher mortality and complication rates compared to MT alone, with inconsistent benefits for NC. SR also carried elevated risks without clear advantages over MT. These results support that current clinical independent variables from the NIS are weak predictors. This highlights the limitation of the database in relying solely on clinical and medical history, and suggests that future use of radiological and anatomical features can improve predictions of outcomes and determination of subgroups that can benefit from certain treatment. More studies should be conducted, including post hoc analyses based on radiological and anatomical features, to better inform treatment decisions and determine subgroups that can benefit from intervention or surgery. These findings suggest a need for judicious patient selection and reinforce the role of optimal MT.
Abstract 4135985: Association of Plasma Cystatin-C with Cancer Risk in Individuals with and without Cardiovascular and Chronic Kidney Disease: An Atherosclerosis Risk in Communities (ARIC) Study
Authors: Elsayed Omar , Wang Xiaoling , Weintraub Neal , Harris Ryan , Datta Biplab , Coughlin Steven , Joshu Corinne , Coresh Josef , Platz Elizabeth , Guha Avirup
Published: November 2024

Background:
While previous studies suggested a relationship between circulating Cystatin-C (Cys-C), a cysteine protease inhibitor involved in regulating tissue inflammation and a renal filtration marker, and both cancer and CVD, they often lacked long-term follow-up or did not account for the impact of CVD on the relationship between Cys-C and cancer.

Methods:
We included participants from the Atherosclerosis Risk in Communities (ARIC) study followed from visit 2 (1990-1992) through 2015. Plasma Cys-C level was measured by SomaScan. Other renal filtration markers beta-2 microglobulin (B2M) and beta-trace protein (BTP) were used to compare their cancer association with Cys-C. Incident cancer was ascertained by state cancer registry linkage supplemented with medical records. After adjusting for age, sex, race, and study center, adjusted hazard ratios (aHR) of total and site-specific cancers were estimated using Cox proportional hazards regression stratified by baseline chronic kidney disease (CKD) and CVD status.

Results:
Among 10,869 individuals (median age of 56.9 years, 55% female, 25% Black, 74% White), 3352 incident cancers were ascertained over a median follow-up of 22.9 years. Among 9585 individuals with no history of CKD or CVD, higher Cys-C was significantly associated with a higher risk of total (aHR 1.22, 95%CI 1.02-1.46), bladder, lung, colorectal, and hematologic malignancies. Among 1,050 individuals with CVD, but not CKD, Cys-C level was not associated with total cancer (aHR 1.22, 95%CI 0.74-2.01), but was significantly inversely associated with colorectal (aHR 0.19, 95%CI 0.05-0.76) and positively associated with post-menopausal breast (aHR 4.52, 95%CI 1.05-19.40) cancer risk. In individuals with CKD but not CVD, Cys-C was negatively associated with bladder (HR 0.08, 95%CI 0.0-0.77) and lung (0.23, 95%CI 0.06-0.82) cancers. Lastly, those with both CKD and CVD showed higher hematopoietic and lymphatic cancer with higher Cys-C (HR 4.68, 95%CI 1.32-16.60). Similar patterns were observed for B2M and BTP proteins.

Conclusions:
Our study highlights the intricate relationship between various renal filtration markers and cancer risk. It suggests that they may play a significant role in cancer development among the general population and CVD patients but not CKD patients. Further research should explore the biological mechanism underlying these associations with even more CKD cases to refine risk estimates.

Funding: NHLBI, NCI, NPCR
Abstract 4136025: Establishing normal values for central systolic blood pressure and augmentation index in healthy young people
Authors: Hersant Jeanne , Breslin Monique , Kodithuwakku Vimarsha , Boutouyrie Pierre , Urbina Elaine , Bruno Rosa , Climie Rachel
Published: November 2024

Background:
The process of cardiovascular disease (CVD), a leading cause of death worldwide, commences in childhood. Increasing evidence indicates that early exposure to CVD risk factors in childhood is associated with impaired arterial distensibility and other vascular alterations, suggesting that vascular ageing biomarkers, that capture the deterioration in vascular structure and function, can be used to identify children at risk. However, the identification of early vascular alterations in the young is hampered by the lack of a recognized, vascular biomarker that can be used in clinical practice. The Youth Vascular Consortium, an international collaborative open resource has been established to answer these gaps by analysing different biomarkers, including central systolic blood pressure (cSBP) and augmentation index (AIx). These two non-invasive measures are related to CVD and end-organ damage, however, their assessment in clinical practice is limited by the lack of established normal values.

Aims:
We aimed to establish cSBP and AIx normal values in a young, healthy, international population.

Methods:
The Consortium collected data on 36,973 participants from 24 countries. We included 14,476 and 5,047 subjects respectively for the cSBP and AIx populations. Subjects were free of any CVD or cardiovascular risk factors. Data were collected from participants aged from 1 to 40 years. Normal values of cSBP and AIx were calculated as percentiles stratified by age and sex. Percentiles curves were generated using generalised additive models.

Results:
The cSBP percentile curves increase with the same trend for both males and females until age 13 years. Over this age, males experience greater cSBP than females. This is in contrast to AIx, which decreases with the same trend in both sexes until 15 years of age, after which females experience increased AIx.

Conclusion:
Normal values of cSBP and AIx in healthy young are now available according to age and sex with a wide geographical representation. Incorporating these values into clinical practice for young could facilitate their utilization as targets for the introduction and monitoring of interventions.
Abstract 4136033: High-Dose Folic acid Supplementation in Acute Myocardial Infarction - A systematic review
Authors: Hashim Hashim Talib , Alhatemi Ahmed Qasim Mohammed , Ahmed Shahzaib , Khan Mudassir Ahmad , Iqbal Uzair , Hafeez Muhammed Hassan , Al-Obaidi Ahmed Dheyaa , Saab Omar
Published: November 2024

Background:
Folic acid, a B vitamin, is essential for DNA synthesis and repair, and its role in reducing homocysteine levels has been linked to cardiovascular health. Elevated homocysteine is a risk factor for cardiovascular diseases, including acute myocardial infarction (MI) and coronary artery disease (CAD). Despite evidence suggesting that folic acid supplementation may lower homocysteine levels, its clinical benefits in reducing cardiovascular events remain unclear.

Methods:
A comprehensive literature search was conducted in PubMed/Medline, Google Scholar, and Cochrane Library databases for studies published from 2000 to 2024 using MeSH terms related to “folic acid,” “B vitamin,” “acute myocardial infarction,” “cardiac arrest,” “heart attack,” and “coronary heart disease.” Only randomized controlled trials (RCTs) and observational studies in English involving adult patients with acute MI or CAD were included. Exclusion criteria were applied to poor-quality studies, irrelevant outcomes, overlapping populations, and non-English texts. Data on study characteristics and patient demographics were extracted, and study quality was assessed using the RoB2 tool. Outcomes were pooled using RevMan 5.3.4 software.

Results:
Fourteen studies on all-cause mortality showed a risk ratio (RR) of 0.99 [95% CI: 0.94-1.04], indicating no significant difference between folic acid and control groups. Eight studies on cardiovascular mortality yielded a RR of 0.90 [95% CI: 0.82-0.99], suggesting a significant reduction in cardiovascular deaths with folic acid supplementation. Analyses of sudden death, coronary artery bypass graft (CABG) events, revascularization procedures, stroke, and recurrent MI found no significant associations with folic acid supplementation.

Conclusions:
High-dose folic acid supplementation appears to reduce cardiovascular mortality in post-MI patients but shows no significant impact on other clinical outcomes. This meta-analysis’s limitations include potential publication bias, heterogeneity among included studies, and variability in folic acid dosages and treatment durations. Furthermore, the lack of comprehensive homocysteine level data constrained the analysis. Future large-scale RCTs are needed to fully ascertain the therapeutic potential of folic acid supplementation in secondary prevention of cardiovascular events.
Abstract 4136116: Metformin Therapy for Reperfusion Injury Consolidates Cardioprotection in the High-Risk Elderly Heart
Authors: Rouhi Nadiyeh , Wang Hao , Nguyen Jennie , Slotabec Lily , Seale Blaise , Wen Changhong , Filho Fernanda , Adenawoola Michael , Chen Qun , LESNEFSKY EDWARD , Li Ji
Published: November 2024

Introduction:
Metformin (MET), a first-line diabetes therapy, exhibits cardioprotective effects during acute ischemia and reperfusion (I/R). Cardiac injury is enhanced in the aging heart in murine and humans. Acute, high dose MET treatment at the onset of reperfusion (R) markedly reduced infarct size (MI) in the high risk aged heart via modulation of mitochondrial complex I. However, the effect of subsequent chronic, standard dose MET to consolidate and possibly enhance cardioprotection and survival following I/R in the aged heart remains unknown.

Hypothesis:
Administration of chronic standard dose of MET will ameliorate mortality and morbidity following MI through rescuing an impaired adaptive metabolic remodeling.

Methods:
Aged (22-24 month) C57BL6/J mice were subjected to sham operations or 45 min of ischemia by LAD ligation followed by R. All mice received acute, high dose MET (2 mM, i.v.) at the onset of R followed by randomization to chronic MET (300 mg/kg/day) in drinking water versus vehicle (VEH) administered for 14 days. Cardiac function was determined by echocardiography weekly. IonOptix Myocyte Calcium and Contractility System measured the contractile functions and transient calcium signaling of isolated cardiomyocytes.

Results:
The Kaplan-Meier survival analysis showed that chronic MET treatment following acute treatment at the onset of R significantly reduced mortality compared to VEH group. Although chronic MET treatment did not further reduce MI size, echo and histology showed that chronic MET preserved diastolic function, prevented left ventricular hypertrophy and reduced collagen deposition following I/R in aging. Moreover, isolated cardiomyocytes from MET treated hearts showed improvements in contractile function, transit calcium signaling, and the coupling between contractility and calcium levels as compared to the cardiomyocytes from VEH group hearts. Immunoblotting results showed that Sens2/AMPK metabolic signaling was significantly upregulated by chronic MET post-MI, indicating the metabolic homeostasis modulated by MET is a critical factor involved in the beneficial effects of chronic MET on limiting I/R-induced myocardial damage that leads to deleterious remodeling in aging.

Conclusions:
The mortality and morbidity of MI in the high risk aged heart is attenuated with acute, high dose of MET treatment followed by chronic standard dose MET treatment to consolidate protection via rescuing the impaired adaptive metabolic response in aging.
Abstract 4136145: All-cause and Cause-specific Mortality Disparities in the District of Columbia: Temporal Trends from 2000 to 2020
Authors: Hashemian Maryam , Conners Katherine , Powell-Wiley Tiffany , Rafi Rebeka , Henriquez Santos Gretell , Shearer Joe , Joo Jungnam , Shiels Meredith , Roger Veronique
Published: November 2024

Background:
A report evaluating all-cause mortality in 30 major U.S. cities documented that inequality between Black and White populations in Washington, D.C. was the greatest. However, little is known about disparities in cause-specific mortality over time or by racial groups.

Aims:
Evaluate trends in all-cause and cause-specific mortality in D.C. from 2000 to 2020 by race, and concurrently examine trends in cardiovascular (CV) risk factors.

Methods:
Using the CDC WONDER database, we calculated age-adjusted mortality rates per 100,000 persons (2000-2020) for Non-Hispanic Black and Non-Hispanic White populations in D.C. and corresponding rate ratios. Average Annual Percentage Change (AAPC) was examined with joinpoint regression. We examined the prevalence of risk factors (obesity, hypertension, diabetes, smoking, and hypercholesterolemia) using the Behavioral Risk Factor Surveillance System (2000-2020).

Results:
Among 102,710 deaths that occurred in D.C. (80% Black), cardiovascular diseases (CVD, 32%) and cancer (22%) accounted for over half of the deaths. All-cause mortality declined between 2000-2012 (AAPC: -2.9%, 95% CI: -5.6, 1.0) but stagnated between 2012-2018 (AAPC:-1.1%, 95% CI: -4.6, 0.9) and increased after 2018 (AAPC: 7.7%, 95% CI: 0.6, 11.9). CVD mortality declined between 2000-2011 and plateaued thereafter among Black individuals, contrasting with a monotonous decline (AAPC: -4.7%, 95% CI: -5.3, -4.0) among White individuals, resulting in a magnification of the disparities. Cancer mortality decreased over time for both White and Black individuals (AAPC: -3.4%, 95% CI: -3.9, -2.9 vs. AAPC: -1.8%, 95% CI: -2.1, -1.4, respectively), with a greater magnitude in White individuals. Risk factors were more prevalent among Black individuals over the period.

Conclusion:
In D.C., the mortality rate is higher in Black vs. White populations, and disparities are increasing over time. While CVD and cancer mortality rates declined overall, profound disparities remain. CVD risk factors are more common in Black populations, with persisting disparities. There is an urgent need for CVD prevention and management, tailored to Black populations in D.C.
Abstract 4136203: Risk of Mortality and Heart Failure with Myosin Inhibition Among Hypertrophic Cardiomyopathy Patients
Authors: Patel Nirav , Shetty Naman , Gaonkar Mokshad , Divekar Girija , Vekariya Nehal , Peng Li , Arora Garima , Arora Pankaj
Published: November 2024

Background:
While prior studies have established that mavacamten therapy in symptomatic obstructive hypertrophic cardiomyopathy (oHCM) leads to significant clinical and functional improvement, long-term data on the effect of mavacamten on mortality and heart failure with reduced ejection fraction (HFrEF) in these patients is lacking.

Methods:
In this retrospective cohort study utilizing electronic health record data from the TriNetX Network, we aimed to assess the association of mavacamten therapy with mortality and HFrEF compared to medical management among patients with oHCM between 04/2022 and 04/2024. The hazard ratio (HR) and 95% confidence interval (CI) for the study outcomes were estimated by comparing propensity-score matched groups.

Results:
Among 47,601 adults (45.4% females; mean age: 63.5±16.6 years), 701 and 46,900 patients were included in the mavacamten and medical management groups, respectively. (
Table
) In the propensity-matched analysis, mavacamten was associated with a lower risk of mortality (HR=0.40;95%CI:0.21-0.73,p=0.002), but a similar risk of incident HFrEF (HR=1.03;95%CI:0.56-1.88,p=0.93) compared with medical management. (
Figure
)

Conclusions:
The current study is among the first to report improved survival with mavacamten therapy among patients with oHCM utilizing real-world data. The similar risk of HFrEF between the mavacamten and medical management cohorts highlighted in this study indicates the efficacy of the Risk Evaluation and Mitigation Strategy (REMS) program in maintaining patient safety and offsetting any potential excess risk of HFrEF.
Abstract 4136234: Increased Reactive Oxygen Species using [18F]ROStrace PET and Dihydroethidium Staining in Myocardial Infarction Reperfusion injury
Authors: Awad Marina , Swago Sophia , Camillo Chiara , Thompson Elizabeth , Bhattaru Abhijit , Moon Brianna , Ferrari Giovanni , Castillero Estibaliz , Gallagher Evan , McManus Meagan , Ferrari Victor , Gorman Robert , Tschabrunn Cory , Mach Robert , KARP JOEL , Bravo Paco , Witschey Walter
Published: November 2024

Introduction:
Patients with reperfusion injury following myocardial infarction (MI) are at a higher risk of heart failure. Reactive oxygen species (ROS) activity can further damage cardiomyocytes and compromise heart function. Imaging methods are needed to assess ROS
in vivo
to investigate targeted adjunctive therapies. Our group developed a novel ROS-activated PET radiotracer [18F]ROStrace to fill this gap. In this study, we measured [18F]ROStrace fractional uptake rate (FUR) and for the first time compared it with histologic assessment of infarct and myocardium specimens. We hypothesized that [18F]ROStrace FUR was increased in the infarct and that [18F]ROStrace FUR was supported by [18F]ROStrace analogue dihydroethidium (DHE) staining.

Methods:
MI was induced in five swine, followed by reperfusion after 90 minutes.
In vivo
LGE CMR imaging and [18F]ROStrace and [82]Rb PET were performed at ~3-4 days after infarction. A terminal procedure was then performed. DHE and 4′,6-diamidino-2-phenylindole (DAPI) staining was done. Two swine received injections of DHE in the right and left coronary arteries to assess ROS. ROS activity was determined from [18F]ROStrace by computing the [82]Rb myocardial blood flow (MBF) corrected FUR. The linear relationship between infarct and MVO size, and MBF-corrected [18F]ROStrace FUR were calculated using the Pearson’s r.

Results:
There was a strong and positive correlation between infarct and MVO size (r=0.9, p=0.04). The MBF-corrected ROStrace FUR at baseline was 0.07±0.06 ml/g, infarct was 0.15 ± 0.05 ml/g, and remote was 0.09 ± 0.05 ml/g. We observed a significant difference between ROS in the infarct and remote region (p=0.01), which is also seen in the increased DHE staining in the infarct. We also observed increased DAPI staining in the infarct region compared to free wall due to the presence of inflammatory cells, thus increasing the number of nuclei.

Conclusion:
[18F]ROStrace is increased in the infarct during the subacute period post-MI compared to healthy and remote myocardium and supported by histological assessment. This work may lead to the use of
in vivo
[18F]ROStrace PET to support development of therapeutic strategies targeting ROS to reduce MI.
Abstract 4136334: Treatment Satisfaction With an “Inclisiran First” Implementation Strategy Versus Usual Care in Patients With Atherosclerotic Cardiovascular Disease
Authors: East Cara , Koren Michael , Rodriguez Fatima , Ali Yousuf , Sarwat Samiha , Kleeman Kelly , Abbas Cheryl , Toth Peter
Published: November 2024

Background:
Despite the availability of effective lipid-lowering therapies (LLTs), most patients (pts) with ASCVD do not meet guideline-recommended LDL-C goals. In VICTORION-INITIATE (NCT04929249), an “inclisiran first” (IF) strategy of adding inclisiran immediately on failure to achieve LDL-C <70 mg/dL, despite maximally tolerated statin therapy, in pts with ASCVD led to significantly higher LDL-C goal attainment vs usual care (UC) at Day 330.

Objective:
To evaluate change from baseline to Day 330 in pt-reported treatment satisfaction with an IF implementation strategy vs UC in pts with ASCVD enrolled in VICTORION-INITIATE.

Methods:
VICTORION-INITIATE, a Phase 3b, open-label, prospective trial, was conducted at 45 representative clinical sites across 20 US states. Pts randomized 1:1 (stratified by insurance status) received inclisiran 284 mg (300 mg inclisiran sodium) at Days 0, 90, and 270 plus UC or UC alone (lipid management directed by treating physicians). We evaluated change from baseline to Day 330 in pt-reported satisfaction with IF vs UC using the validated 11-question Treatment Satisfaction Questionnaire for Medication (TSQM)-II comprising 4 domains (effectiveness, side effects, convenience, and global satisfaction) scored from 0–100. As a post-hoc analysis of a pre-specified exploratory endpoint, we analyzed the difference in least-squares (LS) mean change in TSQM-II domain scores for IF vs UC using ANCOVA with baseline scores as a covariate.

Results:
We randomized 450 patients: median age 67 years, 30.9% female, 25.8% with a history of statin intolerance. From baseline to Day 330, difference in LS mean change (95% confidence interval) in TSQM-II scores for IF (n=139) vs UC (n=105) was significant (p<0.001) for effectiveness (10.4 [5.4, 15.5]), convenience (10.5 [5.8, 15.2]), and global satisfaction (12.1 [7.2, 16.9]). Statistical comparison was not applicable for the side effects domain at Day 330 due to the small sample size (IF: n=6, UC: n=7). On Day 330, mean scores for IF exceeded UC for each TSQM-II question (Figure).

Conclusions:
An IF implementation strategy resulted in significantly greater change from baseline to Day 330 across multiple domains of pt-reported treatment satisfaction vs UC.
Abstract 4136355: Investigating Changes in Hazardous and Harmful Drinking Among Young Adults Through Zoom Intervention
Authors: Lee Sangeun , Adomah Ruth , HALLI HAN HAGAR
Published: November 2024

Introduction/Background:
Hazardous drinking is a major adverse factor for young adults’ health. This study investigates the efficacy of an integrated contingency management and problem-solving Zoom intervention in addressing hazardous and harmful drinking among young adults.

Research Questions/Hypothesis:
Participants who receive the 8-session integrated Zoom CM-PST intervention will demonstrate a significant reduction in hazardous and harmful drinking behaviors compared to baseline measurements.

Goals/Aims:
The aims of this study were to evaluate the effectiveness of 8-session integrated Zoom contingency management and problem-solving Zoom intervention in reducing hazardous and harmful drinking reduction and abstinence.

Methods/Approach:
This pilot randomized controlled trial study employed a single-arm design with post-intervention and follow-up assessments at 12 weeks. The study targeted young adults aged 18-24 in Chicagoland who regularly consume alcohol at least once a week and have alcohol use disorder. Participants completed the Alcohol Use Disorders Identification Test (AUDIT), Drinking Motives Questionnaire-Revised (DMQ-R), and the 90-day Timeline Follow-back (TLFB) at baseline and 12 weeks after the intervention. The Zoom CM-PST intervention was administered to the participants, and a self-reported questionnaire was utilized to evaluate participants’ drinking use, severity, motivation, and hazardous drinking behavior at baseline and at the 12-week follow-up. A paired t-test, correlation, and multiple regressions were performed to investigate changes in hazardous and harmful drinking among 20 young adults aged 18-24.

Results:
A paired t-test showed that the participant’s level of alcohol use problem and social, coping, and enhancement motivation for alcohol use decreased from pre- to post-intervention. High drinking behaviors accounted for 40% at baseline, while 35% at post-intervention assessment. Over 12 weeks, 45% of participants demonstrated an improvement in hazardous drinking behaviors. Motivation at baseline was a significant factor affecting post-intervention alcohol use problems at 12 weeks.

Conclusions:
The results showed notable enhancements in alcohol use problem reduction and motivation for alcohol use at 12 weeks. The study provides useful insights into the effectiveness of web-based integrated contingency management and problem-solving Zoom interventions in mitigating hazardous and harmful drinking among young adults.
Abstract 4136509: Children in Foster Care with Heart Disease Have Greater Resource Utilization and Mortality
Authors: Martens Anna , Gauvreau Kimberlee , Smith Taylor , Laccavole Michael , Perez Jennifer , Cox Joanne , Antonelli Richard , Shah Snehal , Newburger Jane , Moynihan Katie
Published: November 2024

Background:
While children and youth in foster care (CYFC) have greater healthcare needs generally, data are lacking in heart disease. We characterize CYFC with heart disease, assess the impacts of being in foster care on outcomes, and examine validity of ICD-10 code Z62.21 for identification of CYFC in administrative data.

Methods:
In this single-center, retrospective cohort study of all cardiac surgical patients (<18yo) admitted 2017-2022, CYFC were identified using institutional Electronic Medical Records via natural language processing or ICD codes, with confirmation by chart review. Demographics, medical characteristics and outcomes of CYFC were compared to children not in foster care. Generalized linear models assessed associations with primary outcomes of mortality at current follow-up (logit link) and total hospital days (log link), controlling for clinical factors and length of follow-up. We separately added Child Opportunity Index (COI) and payer to models. This cohort was then studied in the administrative pediatric health information system (PHIS) dataset to calculate ICD code sensitivity and specificity.

Results:
Of 4,431 cardiac surgical patients, 67 (1.5%) were in foster care. CYFC did not have significantly higher mortality (9% vs 5.8%), 30-day readmission or cardiac reoperation, number of complex chronic conditions (CCC), RACHS-2, or distance from center compared to non-CYFC. CYFC had lower COI (median 61 vs 72, p=0.016) and more Medicaid coverage (87% vs 40%, p<0.001). Length of stay after index surgery was similar; however, cumulative hospital days during the study were significantly higher for CYFC (median 22 [IQR 10,45] vs 12 [6,27], p<0.001). Adjusting for RACHS-2, CCC, age, readmission, reoperation, and follow-up duration, CYFC had higher odds of mortality (2.7 [95%CI 1.0,6.9] p=0.046) and more total hospital days (p=0.008). With COI or payer in the model, CYFC was not associated with mortality but remained an independent risk factor for more total hospital days. Only 16/67 (23.9%) of CYFC were coded with the Z62.21 in PHIS, yielding sensitivity of 21.9% (95%CI 13.1,33.1), and specificity of 100% (99.9,100).

Conclusion:
CYFC with heart disease have a relative social disadvantage, greater hospital resource utilization, and long-term mortality despite similar illness severity. Improved capture of foster care status in administrative data is needed to guide future studies and reduce health disparities for the vulnerable population of CYFC.
Abstract 4136518: All-cause mortality for Patients with Preserved Ejection Fraction Heart Failure stratified by B-blocker Therapy and Presence of Permanent Pacemaker.
Authors: Leavitt Jonas , Cunn Gregory , Coleman Kristie , ahmad sana , Bekiaridou Alexandra , Gasparis Christopher , Fishbein Joanna , Mountantonakis Stavros
Published: November 2024

Background:
Beta blockers (BB) and particularly high dose beta blockers might be beneficial for patients with heart failure with preserved ejection fraction (HFpEF), however their use is often limited by commonly coexisting sinus node dysfunction. It is unclear whether the presence of permanent pacemakers (PPM) allows for adequate therapy with BB which in turn confers a mortality benefit.

Objective:
We sought to evaluate differences in BB treatment between HFpEF patents with and without PPM and evaluate their effect on outpatient mortality.

Methods:
We identified patients admitted to 1 of 13 Northwell hospitals receiving intravenous diuretics in response to elevated BNP and included in our analysis only those with left ventricular ejection fraction >45%. Status on BB therapy and presence of PPM was assessed at discharge. The vital status of our cohort was identified for the length of the observation period.

Results:
Of 17,682 patients (42.8% female, 73.5 ± 15.7 years) admitted for HFpEF, 7,910 (44.7%) were discharged on BB, while PPM was present in 397 (2.3%). Treatment with BB was more common among patients with PPM (51.4% vs 48.6%, p=X￼). There were 1,316 deaths during a follow-up period of 2.4 ± 0.9 years post index admission. Mortality was highest among patients discharged on a BB without PPM and lowest among patients on both BB and PPM (log rank p=0.003)

Conclusion:
Additional studies are required to assess the complimentary role of pacing and BB therapy in patients with HFpEF.
Abstract 4136539: Management of Malignant SVC Syndrome and Acute SVC Thrombosis with Complex Endovascular Intervention
Authors: Fischer Karley , Reddy Ananya , Valencia Damian , Rehman Abdur
Published: November 2024

Superior vena cava (SVC) syndrome occurs when there is SVC occlusion or obstruction. SVC obstruction can cause an increase in venous return pressure up to 40 mm Hg, producing edema of the face, neck and chest wall. Blood flow can be diverted to the right atrium through collateral venous networks in cases of gradual SVC compression. The most common cause of SVC syndrome is malignancy, as seen in 70% of cases. Traditionally, treatment is with radiation therapy but advances have now allowed for an endovascular approach. We present a case of malignant SVC syndrome with a complex percutaneous treatment approach that provided palliation with near immediate symptom improvement.

A 64 year-old-female with history of cerebrovascular accident on Eliquis, right upper lobe squamous cell carcinoma of the lung in remission, and a mediastinal nodule under surveillance presented with facial and bilateral upper extremity edema. CT revealed bilateral pulmonary embolism and a large SVC thrombus causing impaired venous return. Invasive angiogram confirmed a 95% thrombotic tubular stenosis for which she underwent aspiration thrombectomy with alpha VAC F-18, then angioplasty with an Armada (Abbott) 10 x 40 mm compliant balloon and stenting with the Express (Boston Scientific) 10 x 37 mm stent. There was 0% residual stenosis and immediate clinical improvement. Oncological workup confirmed the right mediastinal mass to be a recurrence of squamous cell carcinoma.

SVC syndrome occurred due to mediastinal mass compression and a near occlusive SVC thrombus. Aspiration thrombectomy was effective in treating the SVC thrombosis and was performed alongside pulmonary embolism thrombectomy. The Armada balloon is intended for lesion dilation in the peripheral arteries, but was safely used here for venous dilation. The Express stent is intended for palliation of malignant biliary neoplasms but has versatility and was utilized here for malignant neoplasm surrounding the SVC. Peripheral endovascular stenting is an advantageous treatment option for malignant SVC syndrome given the challenges due to recurrence from mass effect. This provides additional support to maintain vessel patency and is a safe palliation option for improvement in quality of life.
Abstract 4136550: In-hospital cardiac arrest can be detected by Innovative smart healthcare syste
Authors: Huang Wei-Chun , Juang Wang-chuan , Chao Huang-Jeng , LIN Kun-Chang , Chen Wei-Hsin , HSU Chien-Wei , Liao Man-Ling , Huang Hsiao-Wen , HSU Shu-Shong
Published: November 2024

Background:
Predicting in-hospital cardiac arrest (IHCA) is crucial for preventing patient fatalities. However, it remains challenging due to the irregularities in time series data across various features. Previous studies relied on traditional medical scoring systems, but their accuracy was limited as the models were overly simplistic. Recent research using machine learning methods has shown improved results. In our work, we employ deep learning and time series approaches, which are considered the most powerful models for addressing complex problems in recent years.

Method/Research Design:
The cohort study took place in a hospital in Taiwan from January 2016 to August 2022, involving 252,000 patients in general wards. Input data encompassed basic information, vital signs, Glasgow Coma Scale scores, medication, etc., to predict IHCA occurrences within 24 hours. Given the immediacy of IHCA events, we utilized left alignment to handle time series. Evaluation metrics included the area under the receiver operating characteristic curve (AUROC).

Results:
We compared three types of settings. The first was based on scoring systems, where the national early warning system (NEWS) achieved an AUROC of 0.756, and the modified early warning score (MEWS) reached 0.653. In the next setting, based on the data summary within a given time interval, the machine learning models XGBoost and deep learning model TabNet achieved AUROCs of 0.863 and 0.839, respectively. This indicates that machine learning outperforms traditional medical methods. The final setting involved time series analysis, where XGBoost and the Gate Recurrent Unit (GRU) network achieved 0.848 and 0.904, respectively, surpassing all previous settings.

Conclusion:
Our study demonstrates that learning-based methods outperform rule-based methods in predicting IHCA events. Machine learning algorithms offer more possibilities and have the potential to address complex problems effectively. Moreover, considering time series data rather than summarizing within fixed intervals preserves information and leads to better scores. Leveraging the time series deep learning method, GRU shows promising potential in significantly reducing the risk of IHCA events.
Abstract 4136677: High Visceral-to-Subcutaneous Fat Ratio is Correlated with Increased Cardiovascular Events in Patients with Low Waist Circumference Suspected of Coronary Artery Disease
Authors: Miyagi Takuya , Otagiri Kyuhachi , Okawa Keishiro , Oyama Yushi , Sakai Takahiro , Kitabayashi Hiroshi
Published: November 2024

Introduction:
Waist circumference (WC) has been recognized as an appropriate index of obesity and is closely associated with the amount of abdominal fat. Although abdominal fat distribution (AFD), which is represented by the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) area (V/S ratio), is possibly related to an increased risk of cardiovascular disease (CVD), few studies have explored the relationship between AFD and CVD outcomes. This study aimed to assess the influence of AFD based on the V/S ratio and physique categorized by WC on long-term clinical results in patients with suspected coronary artery disease (CAD).

Methods:
We evaluated 931 consecutive patients (mean age, 67 years; 42.4% women) with suspected CAD who underwent computed tomography (CT) angiography. The patients also underwent plain abdominal CT to assess and measure VAT and SAT areas; V/S ratio was calculated to assess AFD. The patients were divided into four groups based on the median V/S ratio (0.624) and reference values of WC for metabolic syndrome in Japan (85 cm for men, 90 cm for women). We assessed the relationship between the V/S ratio and long-term clinical outcomes in each WC group. The main outcome was major adverse cardiac events (MACEs, including cardiac death, any coronary revascularization, acute coronary syndrome, and emergency hospitalization due to cardiac cause).

Results:
Over a median follow-up of 1869 days, although the incidence of any cardiovascular event was not related to the V/S ratio among patients with high WC, a higher incidence of MACE and cardiac death was noted among patients with low WC in the high V/S ratio group than in the low V/S ratio group. Furthermore, Kaplan–Meier analysis revealed a significantly lower MACE-free survival rate among patients with low WC in the high V/S ratio group than in the low V/S ratio group, despite of no differences being noted among high WC patients in both the V/S ratio groups (Figure).

Conclusion:
Only in patients with low WC, a high V/S ratio was linked to increased risks of MACE. Thus, high V/S ratio may be an essential risk factor for CVD, specifically in patients with low WC. However, AFD did not influence CVD prognosis in patients with high WC.
Abstract 4136692: Spatial Transcriptomics Identifies Novel Clinical Markers to Classify the Etiology of Rare and Aggressive Cardiac Sarcomas
Authors: Zhang Liwei , Yuan Dan , Dong Meng , Cai Ying , Jin Su-Han , Frey Benjamin , Gaipl Udo , Sun Pin , Martinez-Jimenez Celia , Wang Jinjing , Ma Hu , Zhou Jian-Guo
Published: November 2024

Background:
Cardiac sarcomas, such as leiomyosarcoma (LMS), synovial sarcoma (SS), and undifferentiated pleomorphic sarcoma (UPS), lack sufficient diagnostic markers for early diagnosis and tailored therapeutic interventions. Understanding their molecular signatures with spatial-temporal resolution compared to normal heart tissue is crucial.

Hypothesis:
Spatial transcriptomics will reveal a comprehensive set of novel clinical markers, including changes in cellular composition, stemness, and metabolic profiles unique for each cardiac sarcoma subtypes.

Aims:
Identify novel molecular markers for the accurate diagnosis of cardiac sarcoma subtypes.

Methods:
Using 10X Visium spatial transcriptomics, we analyzed three cardiac sarcoma subtypes (LMS, SS, UPS) and compared them with normal heart tissue. Differential expression analysis identified novel target genes suitable for clinical disease stratification. Subsequently, machine learning models reveal an unbiased transcriptomic profile to distinguish normal from sarcoma tissues. Finally, immunohistochemistry analysis validated the differential marker gene expression.

Results:
We identify several novel clinical markers, such as IGKC, PCOLCE, NET1, TLE2, MDFI, BGN, TNNC1, and CNN3, that classify normal heart tissue from sarcoma subtypes. Machine learning models and immunostaining analysis confirm the transcriptomic signature in each sarcoma subtype. Pathway enrichment analysis show LMS enriched in antigen processing and B cell-mediated immunity, SS in protein folding and response to incorrect proteins, and UPS in axon development and Wnt signaling regulation. Trajectory Reconstruction Analysis indicate higher stemness scores in all sarcomas, with SS highest, followed by UPS and LMS. Additional cell cycling analysis show LMS cells in G2M phase, SS in G1, and UPS in S phase. SS express a high number of cancer stem markers (EZH2, BMI1, KDM5B, LGR5, HIF1A), while UPS express KDM5B and CTNNB1, and LMS show fewer stem-related marker genes (EZH2, BMI1, KDM5B, CTNNB1). Both SS and LMS express CD44. Glucose and oxidative pathways are also differentially regulated in each sarcoma subtype.

Conclusion:
Spatial transcriptomics uncovers distinct clinical markers, stemness characteristics, and metabolic activity profiles in cardiac sarcomas, offering insights for fast, accurate and improved diagnostics and therapeutics.
Abstract 4136716: Frailty and Malnutrition Predict Mortality in Older Adults with Atherosclerotic Cardiovascular Disease
Authors: Mangalesh Sridhar , Fishman Emily , Ambrosini Alexander , Faridi Kamil , Nanna Michael
Published: November 2024

Background:
Frailty and malnutrition are related geriatric syndromes but it remains unknown if both provide independent prognostic information in older adults with atherosclerotic cardiovascular disease (ASCVD).

Aims:
We compared the prognostic value of combined frailty and malnutrition assessment with either parameter alone in predicting all-cause mortality.

Methods:
We analyzed 719 older adults (>70 years old) with prevalent ASCVD from visit-6 of the Atherosclerosis Risk in Communities Study. ASCVD was defined as prevalent coronary heart disease, stroke, or history of MI at visit-6. Malnutrition was assessed using the geriatric nutritional risk index (score <98), and physical frailty was determined using the Fried frailty phenotype. Participants were categorized as high-risk if both frail and malnourished, intermediate-risk if frail or malnourished, and low-risk if neither. Cox regression and model performance metrics were used to assess frailty, malnutrition, and their combination, both alone and in conjunction with a base model.

Results:
The mean age of the cohort was 80.5±4.5 years and 39.4% were women. A total of 67.2% had frailty, 13.4% had malnutrition and 11.1% had both. Median follow-up was 580 days with 61 mortality events. Compared to low-risk adults, intermediate-risk (2.3 [1.04-5.0], p=0.039) and high-risk (OR 3.1 [95% CI 1.1-8.5], p=0.027) adults had significantly higher adjusted risk of mortality (Figure). In contrast, frailty or malnutrition alone were not statistically significant predictors after multivariable adjustment. Addition of the combined risk to the base model led to a modest increase in the c-index compared to the malnutrition model (0.668 vs. 0.647) but not the frailty model (0.668 vs 0.667). There was no significant improvement in reclassification or integrated discrimination index, but the combined model had superior goodness-of-fit than the frailty and malnutrition models, as demonstrated by a difference >|2.0| in the Akaike information criterion (-3.4&-13.5 respectively).

Conclusion:
Frailty and malnutrition are highly overlapping syndromes. Incorporation of readily available nutritional risk measures to traditional frailty assessment may improve risk prediction in older adults with ASCVD.
Abstract 4136727: The role of immune mechanism in Immune Checkpoint Inhibitor-Associated Myocarditis: seeking key genes
Authors: Zhang Junyi , Qu Shenglin , Zhou Yafeng
Published: November 2024

Background:
Immune checkpoint inhibitors (ICIs) are extensively employed in cancer treatment; however, the development of ICI-associated myocarditis (ICI-MC) introduces a severe and potentially fatal complication with elusive pathophysiological mechanisms. This study aimed to pinpoint pivotal immune-related genes in ICI-MC and unveil potential therapeutic targets using bioinformatics.

Methods:
Utilizing the GSE180045 dataset (comprising three groups: Group A - ICI patients without immune adverse events, Group B - ICI patients with non-myocarditis immune adverse events, Group C - ICI patients with myocarditis), we scrutinized differentially expressed genes (DEGs) between ICI-MC samples (Group C) and non-myocarditis controls (Group A&B). These DEGs were cross-referenced with 1796 immune-related genes (IRGs) from the immPort database to derive IR-DEGs. We conducted functional enrichment analyses (GO, KEGG, GSEA), constructed a PPI network, and identified hub genes. Validation was performed using the GSE4172 dataset, and optimal feature genes (OFGs) were identified from the overlap of hub genes and validation DEGs. Predictions of target miRNAs were made, and a ceRNA network was constructed. Target drugs for hub genes were forecasted using the cMAP database.

Results:
We pinpointed 58 DEGs between ICI-MC and controls, leading to the identification of 32 IR-DEGs after intersecting with 1796 IRGs. Functional analyses revealed enrichment in cell lysis, CD8+ T cell receptor, natural killer cell-mediated cytotoxicity, and RAGE signaling. Up-regulated hub genes (IL7R, PRF1, GNLY, CD3G, NKG7, GZMH, GZMB, KLRB1, KLRK1, CD247) were highlighted. In the validation dataset, 407 DEGs were uncovered, resulting in the identification of 3 OFGs (KLRB1, NKG7, GZMH). Predicted target miRNAs, lincRNAs, and circRNAs formed a comprehensive ceRNA network. The top 10 drugs with elevated connectivity scores included acetohydroxamic-acid, suggesting caution in ICI treatment.

Conclusion:
NKG7, GZMH, and KLRB1 emerged as pivotal immune-related genes in ICI-MC. Biological enrichments encompassed cell lysis, CD8+ T cell receptor pathway, natural killer cell-mediated cytotoxicity, RAGE signaling, and proinflammatory pathways. The ceRNA network shed light on critical molecules, emphasizing the need to avoid drugs like acetohydroxamic-acid in ICI treatment.