bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4128250: Healthier Lifestyle is Associated with Better Arterial Health in People without Prevalent Cardiovascular Disease
Authors: Ruda Maria , Zhang Lu , Jha Mawra , Dong Zhiyong , Prescott Brenton , Xanthakis Vanessa , Benjamin Emelia , Vasan Ramachandran , Mitchell Gary , Tsao Connie
Published: November 2024

Background:
Higher arterial stiffness contributes to atherogenesis and arterial calcification, resulting in cardiovascular morbidity and mortality.

Research Question:
The relations of lifestyle, measured by the AHA Life’s Essential 8 (LE8), with arterial health (AH) and CVD outcomes are incompletely understood.

Aims:
To examine the association of LE8 with AH and extent to which carotid-femoral pulse wave velocity (PWV) mediates the association of LE8 with outcomes in a sample free of CVD.

Methods:
In 3 Framingham Heart Study cohorts, we studied the relations of LE8 (total score and components) with AH, assessed by arterial stiffness (PWV, by tonometry) and coronary calcification score (CAC, by computed tomography) using multivariable-adjusted linear regression (p<0.01 considered significant after Bonferroni correction). We evaluated the extent to which PWV mediates the association of LE8 with outcomes using Cox proportional hazards regression models (p<0.05 considered significant).

Results:
We studied 5222 participants, aged 50±15 years, 56% women. Characteristics of the sample are presented in
Table
. Higher LE8 score (better cardiovascular health) was associated with more favorable AH measures (PWV inverse transformed, standardized; CAC log(CAC+1); all β±SE, x10
-3
): β
PWV
=-14.4±0.7, β
CAC=
-51.9±7.8, both p<0.01). Of the LE8 components, BMI (β
PWV
=-1.53±0.31), BP (β
PWV
=-9.74±0.36), fasting glucose (β
PWV
=2.03±0.45), lipids (β
PWV
=-1.54±0.31, β
CAC
=-16.14±3.30) and smoking (β
CAC
=-17.9±2.8) were the greater contributors to AH (all p<0.01). PWV mediated modest degrees of the associations between LE8 and CHD, HF, CVD, and CVD mortality [
Figure
].

Conclusions:
In people without prevalent CVD, healthier lifestyle was associated with better AH. Arterial stiffness mediates the association between lifestyle measures and CHD, HF, CVD, and CVD-mortality. Our results support studying lifestyle interventions to improve arterial health and their benefits for CVD outcomes.
Abstract 4128606: Detailed Measurements of Surgical Mitral Valves: Implications for Transcatheter Mitral Valve-in-Valve Interventions
Authors: Kassab Joseph , Mohammed Nour , Lababede Nour , El Hajjar Abdel Hadi , West Karl , Unai Shinya , Kapadia Samir , Harb Serge
Published: November 2024

Background:
With the increasing prevalence of transcatheter mitral valve-in-valve interventions (V-in-V), a detailed understanding of the surgical valves (SV) is of paramount importance. Left ventricular outflow tract obstruction (LVOTO) is a feared complication and is typically caused by the anterior displacement of the LVOT-facing surgical leaflet, which, along with the surgical post at that level, forms a fixed obstruction. Traditionally, the risk is estimated using computed tomography software by simulating a valve that extends to the surgical post height of the implanted SV. However, this does not account for the actual leaflet length and post width at the level of the leaflet tip, which could differ significantly from the surgical post height but accurately estimate LVOTO risk.

Methods:
We conducted detailed measurements of three different sizes of two commonly used surgical mitral valves: the Biocor EPIC (
Abbott
) in sizes 27 mm, 31 mm, and 33 mm, and the Mosaic (
Medtronic
) in sizes 25 mm, 31 mm, and 33 mm. Using a digital caliper and height gauge, we measured several key parameters for each valve, including leaflet height, post height, leaflet width, post width at the level of the leaflet tip, maximal post width, and valve inner diameter.

Results:
The results, presented in Table 1, show significant differences in leaflet height and post widths across manufacturers and sizes. Leaflet height was consistently shorter than post height in both
Abbott
and
Medtronic
valves, with this discrepancy more pronounced in larger valves and
Medtronic
valves. The post width at the leaflet tip also varied considerably.

Conclusions:
Given the substantial differences between leaflet and post heights—with the leaflet typically much shorter—an accurate assessment of LVOTO risk should account for both the leaflet height and the width of the post at that level to avoid overestimating the risk of LVOTO.
Abstract 4129223: Large Language Modeling-Enabled Analysis of Atrial Fibrillation Topics and Sentiments on Social Media
Authors: Parsa Shyon , Somani Sulaiman , Hernandez-Boussard Tina , Rodriguez Fatima
Published: November 2024

Purpose:
We utilized large language modeling (LLM) and automated topic modeling techniques to describe public perceptions regarding AF on Reddit, a social media platform.

Methods:
In this qualitative study, we curated all AF-related discussions on Reddit from 2006 to 2023 by searching for all posts and comments containing AF-related terms (“atrial fibrillation”, “afib”, and “atrial flutter”). Discussions were embedded using a state-of-the-art embedding model (BAAI/bge-base-en-v1.5). Embeddings are reduced in dimensionality using Uniform Manifold Approximation and Project and clustered using K-Means Clustering to find topics and groups. Topic and group labels are enhanced using large language models (Llama2 and GPT4, respectively).

Results:
We identified a total of 86,323 discussions related to AF from 38,183 unique users between April 14, 2006 and November 20, 2023. Discussions around wearables and ablations increased over time, while discussions around anticoagulation had periodic spikes. The topic modeling pipeline automatically identified 64 topics and 9 groups (Figure 1). Groups emphasized the following themes: lifestyle factors and triggers associated with AF (groups 1, 5, 7); patient experiences with management strategies including anticoagulation, rate control, pharmacological rhythm control, and ablation (groups 2, 4, 5); experiences with wearable devices (group 8); psychological burden of living with AF (group 6); and online advertisements for AF-related medications (groups 3, 9).

Conclusions:
Our AI-enabled topic modeling analysis revealed public perceptions about AF including triggers, experiences with different management strategies, impact of wearables, and psychological burden of the diagnosis, which may help guide potential strategies for improving shared decision making around the AF patient journey.
Abstract 4129273: Severe Mitral Regurgitation from Impella-associated Mitral Chordae Rupture with Successful Transcatheter Edge-to-edge Repair
Authors: Wangmang Felix , Takahashi Tatsunori , Desai Pooja , Bansal Priya , Skaf Sabah , Nakamura Mamoo
Published: November 2024

Background:
Limited data exists describing Impella-related mechanical mitral valve complications. Diagnosis and management can be challenging due to potential underestimation of mitral regurgitation severity from Impella and acute clinical deterioration upon removal. We present a case of successful mitral transcatheter edge-to-edge repair (TEER) for acute severe MR secondary to Impella-related mitral chordae rupture resulting in acute pulmonary edema post-Impella removal.

Case Summary:
A 37-year-old male smoker presented with chest pain complicated by cardiac arrest due to ventricular fibrillation. Spontaneous circulation could not be restored, requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Coronary angiography revealed total occlusion of the proximal left anterior descending artery, which was successfully stented. Transfemoral Impella CP was placed for left ventricular venting under fluoroscopy (Panel A) with TTE showing no complications. In the intensive care unit, the Impella was advanced under TTE guidance; its tip was found to be positioned deep at the base of the posteromedial pupillary muscle without suction alarms or ventricular arrhythmias on the following day (Panel B). Several days later, TTE revealed new eccentric MR with hyperdynamic left ventricular motion (Panel C). The patient remained hemodynamically stable after VA-ECMO decannulation with Impella at P4. Following Impella removal, he developed repeated flash pulmonary edema despite aggressive fluid removal attributed to acute severe MR secondary to a flail P3 leaflet with ruptured chordae tendineae confirmed by transesophageal echocardiography (Panel D). Given the patient's poor surgical candidacy with a STS score of 13.2%, the team proceeded with mitral TEER, successfully reducing MR severity from severe to mild with a single NT Mitraclip
®
across the medial commissure (Panel E). His post-operative cardiac course was uneventful without recurrence of pulmonary edema.

Discussion:
Irreversible mechanical damage to the mitral valve apparatus caused by Impella placement and repositioning is a rare, potentially fatal complication requiring emergent intervention. Mitral TEER can be a viable salvage option for poor surgical candidates.
Abstract 4129945: Risk of stroke for AMI treated with temporary mechanical circulatory support: ten-year data from National Inpatient Sample
Authors: Zhang Mingyou
Published: November 2024

Objectives:
The aim of this study was to assess the risk of stroke for temporary mechanical circulatory support (tMCS) device treated acute myocardial infarction (AMI).

Background:
Data are limited regarding risk of stroke for temporary mechanical circulatory support (tMCS) device treated acute myocardial infarction (AMI).

Methods:
The national inpatient sample database was analyzed to identify adults who were hospitalized for AMI between 2012 and 2021, hospitalizations were grouped based on the temporary mechanical circulatory support device.

Study design:
In the final cohort, there are 8,272,163 (96.0%) weighted hospitalizations treated without tMCS, 265,870 (3.1%) with Intra-Aortic Balloon Pump (IABP) alone, 59,240 (0.7%) with Impella alone, and 16,225 (0.2%) with Extracorporeal Membrane Oxygenation (ECMO) used during the hospitalization.

Results:
The overall stroke rates for patients who treated without tMCS, IABP alone, Impella alone, and ECMO group were 3.41%, 3.46%, 4.51%, and 13.34% respectively. Specifically, the rates of ischemic stroke for these groups were 2.95%, 3.12%, 3.96% and 10.11% respectively. The rates for hemorrhagic stroke were 0.68%, 0.55%, 0.81%, and 4.90% for the same groups. In the stepwise forward Cox regression analysis, the adjusted OR (aOR) of ECMO use for overall stroke was 3.04 (95%CI [2.66-3.48]), followed by Impella only use with an aOR of 1.79 (95%CI [1.61-2.00]), and atrial fibrillation (aOR 1.34, 95%CI [1.31-1.38]). The subgroup analysis revealed that hospitalization with age younger than 50 years old, those without hypertension, and those presented with ST-elevation myocardial infarction are at particularly high risk of stroke for ECMO treated AMI.

Conclusion:
This ten years AMI hospitalizations analysis revealed that ECMO and Impella treatment associated with increased risk of both ischemic and hemorrhagic stroke. Particularly for those younger than 50, those without hypertension, and those presented with ST-elevation myocardial infarction. However, treatment with IABP alone does not increase the risk of stroke.
Abstract 4129965: Efficacy of Sodium Glucose Cotransporter 2 Inhibitors In Patients With Acute Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials
Authors: Ahmed Mushood , Jain Hritvik , Javaid Hira , Ahsan Areeba , Ramphul Kamleshun , Ahmad Adeel , Shahid Farhan , Basit Jawad , Ahmed Raheel
Published: November 2024

Background:
Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with or without type 2 diabetes and heart failure (HF). However, studies have shown conflicting evidence regarding their efficacy in patients following acute myocardial infarction (MI). We conducted a systematic review and meta-analysis to synthesize the available evidence regarding the effectiveness of SGLT2 inhibitors in MI.

Methods:
A systematic literature search was conducted using PubMed/MEDLINE, the Cochrane Library, and Embase databases to identify randomized controlled trials (RCTs) that compared clinical outcomes of SGLT2 inhibitors with placebo following MI. We conducted the statistical analysis using RevMan, version 5.4, and pooled risk ratios (RRs) along the corresponding 95% confidence interval (CI) for all outcomes. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.

Results:
Five RCTs reporting data for 11,211 patients were included in our study. Our pooled analysis showed that SGLT2 inhibitors significantly reduced the risk of hospitalizations for heart failure (HHF) (RR = 0.76, 95% CI: 0.61-0.88,
p
= 0.001; high certainty). In terms of absolute effects, this translated to 12 fewer HHF per 1,000 patients who received SGLT2 inhibitors compared with the placebo (absolute risk difference 12 (95% CI 17 to 5) fewer per 1000 patients) in patients with MI. However, the risk of all-cause mortality (RR = 1.05, 95% CI: 0.78-1.41,
p
= 0.76; high certainty), cardiovascular (CV) mortality (RR = 1.04, 95% CI = 0.84-1.29,
p
= 0.73; high certainty), and all-cause hospitalizations (RR = 1.06, 95% CI: 0.96-1.17,
p
= 0.25; high certainty) remained comparable across the two groups.

Conclusion:
SGLT2 inhibitors reduce HHF without affecting all-cause mortality, CV mortality, and all-cause hospitalizations. However, further evidence is required to reach a definitive conclusion.
Abstract 4130929: The Effect of Weight loss and Weight Maintenance on Branch Chain Amino Acid Levels
Authors: Swift Damon , McGee Joshua , Matarese Laura , Houmard Joseph , Carels Robert , Pories Walter
Published: November 2024

Introduction:
Elevated branch chain amino acid levels (BCAA) have been associated with cardiovascular disease (CVD) and type-2 diabetes. While weight loss has been shown to improve BCAA levels, few studies have evaluated the impact of weight loss and weight maintenance with the OPTIFAST® weight loss program and supervised exercise training.

Methods:
The present study is a secondary analysis of the PREVAIL-P study. During the weight loss phase, overweight and obese adults (N=30) completed a 10-week OPTIFAST® program with supervised aerobic exercise training with the goal of achieving clinically significant weight loss (≥7%). Participants who met the weight loss goal were randomized to levels of aerobic training consistent with physical activity recommendations (PA-REC) (~550 MET minutes per week) or weight maintenance recommendations (WM-REC) (~970 MET minutes per week) for 18 additional weeks. Valine, leucine, isoleucine and total BCAA levels were measured using nuclear magnetic resonance (NMR) at baseline, after the weight loss phase (10 weeks) and at follow-up (28 Weeks) (LabCorp, Raleigh, NC).

Results:
Following the weight loss phase, participants had a significant mean reduction in weight (-8.8 kg, p<0.001), total BCAA (-37.4 μmol/L, p<0.001), valine (-15.2 μmol/L, p=0.012), leucine (-20.0 μmol/L, p<0.001), but not isoleucine (-4.1 μmol/L, p=0.214) levels. Improvements in BCAA levels were associated with changes in HDL levels (r=-0.39, p=0.03) and approached significance for visceral fat (r=0.34, p=0.07). Furthermore, changes in BCAA metabolites were not associated with weight, glucose metabolism or other lipid variables for the weight loss phase (p>0.05). In a subset of participants (N=14) who completed the weight maintenance phase (due to COVID pandemic), there were no group differences in the change in total BCAA, valine, leucine between the PA-REC and the WM-REC groups (all ps >0.05). Changes in total BCAA levels (baseline to 28 weeks) were associated with higher mean aerobic exercise training intensity during the intervention (r=-0.64, p=0.013).

Conclusion:
Weight loss using the OPTIFAST® weight loss program diet combined with aerobic exercise improved BCAA levels, which is associated with decreased CVD risk. Lower BCAA levels during weight maintenance may be influenced by higher exercise intensity exercise. Future studies should evaluate the impact of lifestyle interventions on BCAA levels during long-term weight maintenance.
Abstract 4131100: Effect of metabolic surgery on cardiovascular outcomes in people with obesity and pre-existing cardiovascular disease: A systematic review and meta-analysis
Authors: Qazi Shurjeel , Ali Hassan , Ansari Huzaifa , Qazii Sana , Dawood Muhammad Hamza , Batool Ruqiat , Shaikh Muhammad Ahmed , Ahmed Syed Zaeem , Aisha Eliza , Siddiqi Tariq Jamal , Hall Michael
Published: November 2024

Background:
Previous literature shows that metabolic surgery effectively decreases the risk of cardiovascular disease (CVD) events in patients with obesity. The use of metabolic surgery has, however, been limited in people with obesity and pre-existing CVD due to concerns of poor post-operative cardiovascular outcomes. This study aims to determine the effectiveness and safety of metabolic surgery in patients with pre-existing CVD.

Methods:
A search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from their inception till May 2024. The study was conducted adhering to the PRISMA guidelines. Outcomes of interest were risk of all-cause mortality, major adverse cardiovascular events (MACE), risk of myocardial infarction (MI), and cerebrovascular events in patients with and without prior CVD undergoing bariatric surgery. Data was pooled as generic inverse variance using a random effects model, and presented as hazard ratios (HR) with their 95% confidence intervals (CI).

Results:
We included four studies in our analysis (n = 5,244). Our pooled analysis shows that metabolic surgery leads to significant reduction in risk of all-cause mortality (HR = 0.51, 95% CI: [0.42, 0.61]; p<0.01). We also observed a significant risk reduction of 43% in MACE with metabolic surgery (HR = 0.57, 95% CI: [0.5, 0.64]; p<0.01). Metabolic surgery was not associated with a significant reduction in the risk of MI (HR = 0.53, 95% CI: [0.24, 1.18]; p = 0.12, I
2
= 83%). Similarly, a non-significant decrease in risk of cerebrovascular events was observed with metabolic surgery (HR = 0.89, 95% CI: [0.65, 1.22]; p = 0.48)

Conclusion:
Metabolic surgery is associated with decreased risk of all-cause mortality and MACE in patients with obesity and established CVD. These results are thought to be mediated through reduction in risk factors such as obesity, but also by reducing inflammatory mediators and having other beneficial effects on cardiac structure and left ventricular workload.
Abstract 4131128: Cardiomyocyte-specific Deletion of
Creg1
Impairs Autophagy and Leads to Age-dependent Dilated Cardiomyopathy
Authors: Qi Yanmei , Joo Yechaan , Pepe Russell , Tejeda Glenn , Hayes Kevin , Yang NaYoung , Chao Joshua , Rahimi Saum , Lee Leonard , Li Shaohua
Published: November 2024

CREG1 is a small glycoprotein predominantly localized in the endolysosomal system. In mouse heart, CREG1 expression increases with age. We previously observed cardiac hypertrophy and ventricular non-compaction in a small percentage of constitutive
Creg1
knockout mice during the neonatal stage. To elucidate the physiological function of CREG1 in the heart, we generated cardiomyocyte-specific
Creg1
knockout (cm
Creg1
KO) and knock-in (cm
CREG1
KI) mice by crossing

Creg1
fl/fl

and Rosa

hCREG1/hCREG1

with Myh6-Cre mice, respectively. By 6 months of age, the cm
Creg1
KO mice developed severe myocardial interstitial fibrosis. Echocardiography at 10 months revealed markedly dilated left ventricles and significantly reduced ejection fractions. All the cm
Creg1
KO mice succumbed to heart failure between 10-12 months, while

Creg1
fl/fl

control littermates exhibited no obvious cardiac abnormalities. Necropsy of deceased cm
Creg1
KO mice showed increased heart-to-body weight ratios, enlarged cardiac chambers, and left atrial thromboses. Electron microscopy revealed sparse and elongated myofibers, scant and bizarre-shaped mitochondria, empty cytoplasm, and increased interstitial collagen accumulation. The cm
CREG1
KI mice exhibited better endurance to nutritional deprivation than Rosa

hCREG1/hCREG1

littermate controls. In sharp contrast to cm
Creg1
KO hearts, cm
CREG1
KI and Rosa

hCREG1/hCREG1

control hearts displayed very mild fibrosis at 8 months, suggesting that CREG1 overexpression may confer cardioprotective effects. In cultured cardiomyocytes, CREG1 colocalizes with the autophagosome marker LC3B following serum deprivation. Immunofluorescence microscopy demonstrated a marked reduction of LC3B puncta in cm
Creg1
KO hearts. Analysis of autophagic flux using CAG-RFP-EGFP-LC3 transgenic mice and immunoblotting indicated that the absence of CREG1 impairs both autophagosome formation and degradation, whereas knock-in of
CREG1
enhances these autophagic processes. These findings suggest that CREG1 promotes autophagy and protects the heart from age-dependent dilated cardiomyopathy.
Abstract 4131445: The Effects of Percutaneous Pulmonary Valve Implantation (PPVI) or Stenting on RV Diastolic Relaxation
Authors: Uike Kiyoshi , Mroczek Dariusz , Karunanithi Zarmiga , Lam Christopher , Benson Lee , Chaturvedi Rajiv
Published: November 2024

Introductions:
Pulmonary regurgitation is a diastolic phenomenon but little is known of the impact of RV-PA conduit interventions on RV diastolic function. We measured the acute effects of PPVI or stent implantation on RV diastolic relaxation with high-fidelity pressure catheters.

Methods:
Right and left heart pressure measurements with Millar Mikro-Cath pressure catheters in children undergoing RV-PA conduit intervention, who had also had an MRI. The relaxation time constant (RV-tau) was calculated as the time constant of the monoexponential pressure decay in the interval between the pressure at dP/dt
min
(P
0
) to when the pressure fell to 10% of P
0
.

Result:
The age for PPVI (n=29) or stent (n=21) implantations were (mean ± sd): 14 ± 2.8 and 11.8 ± 4.2 years, respectively. RV-tau decreased 33% in the PPVI group and increased 11% in the Stent group (Table 1). The absolute value of RV dP/dt
min
decreased 9% in the Stent but not the PPVI group. The absolute value of LV dP/dt
min
increased 12% in the PPVI but not the Stent group. There was a small increase in peak VO
2
at the last follow-up (median 1.04 years, range 0.15-4.69 years) in the PPVI but not the Stent group compared to baseline (from 27.1 to 31.6 ml/kg/min, p = 0.01). The Δpeak VO
2
correlated with ΔRV-tau (r = 0.75, p = 0.01, n = 10) but not with ΔRV-PA gradient or pre pulmonary regurgitation fraction.

Conclusions:
PPVI results in faster RV diastolic relaxation. This may contribute to post-procedure enhanced exercise capacity more than either RV pressure and volume unloading alone.
Abstract 4131488: Artificial Intelligence-Enhanced Electrocardiogram for the Diagnosis of Cardiac Amyloidosis: A Systemic Review and Meta-analysis
Authors: Khan Laibah , Noor Isma , Siddique Amber , Shakil Saad , Keen Mahnoor , Zafar Bayan , Farooqi Maheera , Essam Nabeeha , Khan Muhammad Sami , Siddiqi Tariq Jamal , Hall Michael
Published: November 2024

Background:
Diagnosis of cardiac amyloidosis (CA) is often delayed due to variability in clinical presentation. The electrocardiogram (ECG) is one of the most common and widely available tools for assessing cardiovascular diseases. Artificial intelligence (AI) models analyzing ECG have recently been developed to detect CA, but their pooled accuracy is yet to be evaluated.

Aim:
To meta-analyze the accuracy of AI-enhanced ECG in diagnosing CA.

Methods:
We searched the Scopus, MEDLINE, and Cochrane CENTRAL databases up until April 2024 for studies assessing AI-enhanced ECG diagnosis of CA. Studies reporting findings from derivation and validation cohorts were included. Studies combining other diagnostic modalities such as echocardiography were excluded. The outcome of interest was the area under the receiver operating characteristic curve (AUC) for overall CA and subtypes transthyretin amyloidosis (ATTR) and light chain amyloidosis (AL). Analysis was done using RevMan 5.4.1 general inverse variance random effects model, pooling data for AUC and 95% confidence intervals (CI).

Results:
5 studies comprising 7 cohorts met the eligibility criteria. The total derivation and validation cohorts were 8,639 and 3,843 respectively. The AUC were 0.89 (95% CI, 0.86-0.91) for cardiac amyloidosis, 0.90 (95% CI, 0.86-0.95) for ATTR amyloidosis and 0.80 (95% CI, 0.80-0.93) for AL amyloidosis. The forest plots can be found in the Figure 1.

Conclusion:
AI-enhanced ECG models effectively detect CA and may provide a useful tool for the early detection and intervention of this disease.
Abstract 4131622: Opportunistic Screening of Chronic Liver Disease With Deep Learning Enhanced Echocardiography
Authors: Sahashi Yuki , Vukadinovic Milos , Amrollahi Fatemeh , Trivedi Hirsh , Rhee Justin , Chen Jonathan , Cheng Susan , Ouyang David , Kwan Alan
Published: November 2024

Introduction:
Chronic liver disease affects more than 1.5 billion adults worldwide, but the majority of cases are asymptomatic and undiagnosed. Echocardiography is broadly performed and visualizes the liver; however, this information is not diagnostically leveraged.

Hypothesis and Aims:
We hypothesized that a deep-learning algorithm can detect chronic liver diseases using subcostal echocardiography images that contains hepatic tissue. To develop and evaluate a deep learning algorithm on subcostal echocardiography videos to enable opportunistic screening for chronic liver disease.

Methods:
We identified adult patients who received echocardiography and abdominal imaging (either abdominal ultrasound or abdominal magnetic resonance imaging) with ≤30 days between tests. A convolutional neural network pipeline was developed to predict the presence of cirrhosis or steatotic liver disease (SLD) using echocardiogram images. The model performance was evaluated in a held-out test dataset, dataset in which diagnosis was made by magnetic resonance imaging, and external dataset.

Results:
A total of 2,083,932 echocardiography videos (51,608 studies) from Cedars-Sinai Medical Center (CSMC) were used to develop EchoNet-Liver, an automated pipeline that identifies high quality subcostal images from echocardiogram studies and detects presence of cirrhosis or SLD. In a total of 11,419 quality-controlled subcostal videos from 4,849 patients, a chronic liver disease detection model was able to detect the presence of cirrhosis with an AUC of 0.837 (0.789 - 0.880) and SLD with an AUC of 0.799 (0.758 - 0.837). In a separate test cohort with paired abdominal MRIs, cirrhosis was detected with an AUC of 0.726 (0.659-0.790) compared to MR elastography and SLD was detected with an AUC of 0.704 (0.689-0.718). In the external test cohort of 66 patients (n = 130 videos), the model detected cirrhosis with an AUC of 0.830 (0.738 - 0.909) and SLD with an AUC of 0.768 (0.652 – 0.875).

Conclusions:
Deep learning assessment of clinically indicated echocardiography enables opportunistic screening of SLD and cirrhosis. Application of this algorithm may identify patients who may benefit from further diagnostic testing and treatment for hepatic disease.
Abstract 4131737: Atherosclerotic Cardiovascular Disease Risk Management in a Primary Care Residency Clinic
Authors: Manalo Kathryn , Tieliwaerdi Xiarepati , Jackson Megan , Arrigo Alexis , Mascara Mariah , Maharjan Srijana , Gadani Mrudula
Published: November 2024

The 2018 AHA/ACC Multisociety Guideline on the Management of Blood Cholesterol recommends to target an LDL-C <70mg/dL in very high risk ASCVD patients. If the patient is on maximally tolerated statin therapy and LDL-C remained >70mg/dL, addition of ezetimibe was recommended. If LDL continued to be elevated, the addition of PCSK9 inhibitor was discussed. In 2019, the European Atherosclerosis Society recommended lowering the target LDL-C goal to <55mg/dL in patients with very high ASCVD risk. This is based on prior studies demonstrating dose-dependent reduction in ASCVD with LDL-C reduction. The purpose of this study is to identify individuals at very high ASCVD risk and determine if they are on optimal medical therapy to achieve LDL <55mg/dL with the intention to improve atheroscloertic cardiovascular risk management in primary care residency clinics.

A review of electronic medical records from a primary care residency clinic was performed. Patients with hyperlipidemia and prior ASCVD event were identified. Additional data including lipid panel and current medical management were collected. Patients were stratified into very high risk and not very high risk groups according to AHA classification and analyzed.

A total of 1,727 patients were found to have hyperlipidemia and a prior ASCVD event. The not very high risk group had an average age of 51 years with 54% (n=40) females and 45.9% (n=34) males. The very high risk group contained 95.7% (n=1,653) patients. The average age in the very high risk group was 68 years with 53.2% (n=879) of patients being female and 46.8% (n=774) being males. Of those patients, 73.6% (n=1,216) had an LDL ≥ 55 mg/dL. In these patients, 563 were on high intensity statin, 163 on moderate intensity statin and 15 on low intensity statin. There were 475 patients not on any statin. Of those on statin therapy, 66 were on ezetimibe alone and 10 were on both ezetimibe and PCSK9 inhibitors.

Over 95% of patients with a prior ASCVD event were identified as being very high risk. Our data demonstrates that 3 in 4 patients were not on optimal medical therapy based on a stricter LDL goal. There was poor escalation of medical therapy as not all patients were on high intensity statin and only 10% of patients were on ezetimibe while even fewer patients were on additional PCSK9 inhibitor therapy. This study highlights the importance of risk stratification and vigilance in optimizing medical therapy.
Abstract 4131775: Effectiveness of Lipid-lowering therapy with Bempedoic Acid plus Ezetimibe in a Real-world Cohort
Authors: Nelson James , Bloedon Leanne , Lewandowski David , Bonafede Machaon , Sarnes Evelyn
Published: November 2024

Introduction:
Bempedoic acid and the combination with ezetimibe (BA+EZE) have demonstrated low-density lipoprotein cholesterol (LDL-C) lowering in clinical trials of adults with primary hyperlipidemia at high risk for or with cardiovascular disease. The impact of BA+EZE on LDL-C outcomes in a real-world cohort has not been studied.

Aim:
To evaluate the effectiveness of BA+EZE on LDL-C reduction and goal achievement using real-world data.

Methods:
This was a retrospective cohort study using deidentified electronic health records and linked claims data. Adult patients were included if they had a pharmacy claim for BA+EZE from March 1, 2020 to March 15, 2024 (date of first pharmacy claim =
index date
), had ≥1 baseline LDL-C lab result on or within 6 months prior to the index date, and ≥2 LDL-C lab results post-index, including 1 lab result 12 months post-index (±60 days). Patients with documented use of ezetimibe on or within 6 weeks prior to index were excluded. For all patients with available valid lab results, LDL-C was determined at baseline (the value closest to but not after the index date), 3 months (±30 days), 6 months (±60 days) and 12 months (±60 days).

Results:
A total of 615 BA+EZE patients were identified (mean age 62±11 years, 52% women). At baseline, 64% had evidence of statin use in the prior 12 months and the mean LDL-C was 131±52 mg/dl. Figure 1 shows the change in the proportion of patients achieving LDL-C control at index, 3-, 6-, and 12-months post-index. The proportion of patients achieving LDL-C <100 mg/dL more than doubled from index (30%) to 3 months (67%), and was sustained through 12 months (55%). At 12 months, there were fewer patients with LDL-C ≥130 mg/dL (24% vs 47% at index). The mean LDL-C reduction was 28% at 3 months (to 94±47 mg/dL), 27% at 6 months (96±44 mg/dL), and 22% at 12 months (102±47 mg/dL) (p<0.0001 for all vs index).

Conclusion:
Patients who initiated BA+EZE showed early and sustained improvements in LDL-C. Future research should consider the impact of time on therapy and adherence on LDL-C control.
Abstract 4132120: Down syndrome-trisomy-mediated gene, Dscr-1, protects against lifestyle-related vascular diseases
Authors: Minami Takashi
Published: November 2024

Epidemiological studies indicate that individuals with Down syndrome (DS) have an increased risk of leukemia and neuronal diseases but a significantly reduced incidence of most solid tumors and advanced vascular dysfunction. This suggests that one or a combination of trisomy genes on human chromosome 21 (HSA21) or murine chromosome 16 (
Mmu16
) may be responsible for protecting against vasculopathy. Our previous research has shown that the
Down syndrome critical region (Dscr)-1
gene, located on HSA21 or
Mmu16
, encodes a feedback modulator of calcineurin-NFAT signaling in endothelial cells (ECs). Null mutation or overexpression of Dscr-1 has been found to increase or prevent septic mortality, angiogenesis, liver steatosis, and susceptibility of tumor metastasizing to the lung, respectively, demonstrating its significant role in these processes.

In a unique approach, we crossed DS model mice with
ApoE
-null mice and fed them a high-fat diet (HFD) for 12 weeks to survey the effects of DS-related genes on atherosclerosis. The results were striking, with HFD-mediated increased LDL and triglyceride levels in
ApoE
-null mice significantly reduced in the combined DS plus
ApoE
-null mice. This innovative method allowed us to observe a remarkable (~35%) reduction in ApoE-null mediated atheroma formation in the DS model. This finding was also replicated in EC-specific DSCR-1 transgenic (DSCR-1
ECTg
) mice.

Furthermore, to test the effect of HSA21, we have collected DS patient-derived trisomy and disomy iPS cells and executed them for the chromatin conformation capture analysis and the
in vitro
ECs differentiation experiments. DS-derived trisomy iPS cells already changed the whole chromatin structure, typically within the X chromosome. Moreover, the trisomy iPS-derived ECs revealed less proliferation compared to the disomy. RNA-seqs indicated trisomy iPS derived ECs dramatically (21-fold) increased
DSCR-1
, but some HSA21 genes, Alzheimer’s related
App
and
Bace2
, e.g., were inversely reduced the expression.

Our comprehensive studies not only shed new light on the mechanisms of atherosclerosis in vascular pathology but also offer potential therapeutic strategies. The discovery of the
Dscr-1
gene on the DS chromosome, which could be a powerful tool in combating lifestyle-related vascular diseases, underscores the significance of our research.
Abstract 4134079: Neighborhood-Level Indices of Social Disadvantage and Cardiovascular-Kidney-Metabolic Health
Authors: Krishnan Vaishnavi , Huang Xiaoning , McGowan Cyanna , Shah Nilay , Kershaw Kiarri , Freedman Alexa , Miller Gregory , Lloyd-Jones Donald , Khan Sadiya
Published: November 2024

Background:
Several area-level indices exist that integrate a variety of social drivers of health. However, whether certain indices better capture neighborhood-level variability in cardiovascular-kidney-metabolic (CKM) outcomes is not well known.

Aims:
We sought to examine the associations of census tract-level indices of social disadvantage with CKM outcomes.

Methods:
Exposures for the analysis included seven indices of social disadvantage (ADI, COI, EJI, NDI, SDI, SREI, SVI) based on census tract-level data from the 2010-2019 American Community Survey (ACS) and census tract-level median household income from the 2015-2019 ACS data. Outcomes included the census tract-level prevalence of CKM outcomes (obesity, hypertension, diabetes, hyperlipidemia, chronic kidney disease, coronary heart disease [CHD], and stroke) from the 2019 Behavioral Risk Factor Surveillance System. All indices and median income were standardized, and we used linear regression to examine the associations between each census tract-level social measure and CKM outcomes, adjusted for population size and median age. Next, we calculated the △r
2
in adjusted models for the association of median income with each CKM outcome when each index was added.

Results:
Among 65,476 US census tracts, median (IQR) population size was 4068 (2969, 5374), age was 39 years (35, 44), and household income was $58,870 (44276, 79802). Median income as well as each index was significantly associated with census tract-level prevalence of each CKM outcome assessed (p < 0.05). The r
2
(Panel A) and △r
2
values (Panel B) varied for each of the social measures and CKM outcomes, with higher r
2
values when each index was individually added to median income compared with income alone. For example, for CHD, the r
2
ranged between 0.39 to 0.67 and △r
2
ranged from 0.01 to 0.10.

Conclusions:
Neighborhood-level measures of social disadvantage are differentially associated with CKM outcomes, with a large proportion of the variability explained by median income. Identifying the advantages and disadvantages of each index and comparison with median income can inform the prioritization of measures for specific outcomes.
Abstract 4134417: Cardiotoxicity Conundrum: Distinguishing Immune Checkpoint Inhibitor Myocarditis from Fluorouracil Cardiotoxicity in Concurrent Therapy
Authors: Hu Vivian , Naidu Ishan , Singh Nausheen , Akinmolayemi Oludamilola , SAHNI GAGAN
Published: November 2024

Case Description:
The patient is a 37-year-old male with metastatic gastroesophageal junction adenocarcinoma presenting with chest pain and dyspnea two days after initiation of leucovorin, fluorouracil, oxaliplatin (FOLFOX), and nivolumab therapy. He was tachycardic and hypotensive with elevated cardiac biomarkers and globally reduced left ventricular systolic function. Suspecting immune checkpoint inhibitor (ICI) myocarditis versus fluorouracil (5-FU) cardiotoxicity, he was treated simultaneously for both.

After starting high-dose steroids and before uridine triacetate, he had improved symptoms, cardiac function, biomarkers, and invasive hemodynamics. Though his endomyocardial biopsy did not show inflammatory cell infiltrates, his CMR demonstrated increased T1 and T2 relaxation times consistent with myocarditis. Testing revealed normal dihydropyrimidine dehydrogenase (DPD) activity. He completed uridine triacetate and was discharged on a steroid taper. At follow-up, he remained clinically stable, tolerating oxaliplatin and docetaxel (FLOT) initiation and nivolumab rechallenge without 5-FU.

Discussion:
This case is challenging as the presentation does not conclusively identify a causative agent. The patient’s symptom severity suggests ICI myocarditis, while the early onset points to 5-FU cardiotoxicity. His quick recovery of cardiac function after medication cessation suggests 5-FU-associated Takotsubo cardiomyopathy. His improvement after steroids raises concern for an adverse immunologic response as in ICI myocarditis or idiosyncratic reactions to oxaliplatin with 5-FU.

This patient received ICI therapy and chemotherapy, increasing his risk for cardiac immune-related adverse events. His protracted 5-FU infusion increased his risk for 5-FU cardiotoxicity, but his normal DPD activity mitigates this risk. Although his biopsy was negative, it cannot exclude ICI myocarditis. By the IC-OS 2021 consensus, he meets the criteria for ICI myocarditis presenting 48 hours after nivolumab exposure with cardiogenic shock, elevated cardiac biomarkers, decline in cardiac function, and CMR with elevated T1 and T2 relaxation times. Yet, his biomarkers remained normal with nivolumab rechallenge, arguing against ICI myocarditis and suggesting 5-FU as the culprit.

Early recognition and differentiation of the culprit in concurrent therapies impact management and future treatment options. Rechallenge carries risk and requires interdisciplinary collaboration to ensure patient safety.
Abstract 4134426: Targeting the TRIM29-PERK signaling axis for treating viral myocarditis
Authors: Lu Wenting , Wang Junying , Li Shangqing , Yin Ellen , Zhang Zhiqiang , Xing Junji
Published: November 2024

Introduction:
Viral myocarditis is an inflammatory disease of the myocardium that significantly contributes to sudden death in children and young adults. The COVID-19 pandemic underscores the critical need to understand the pathogenesis and develop effective treatment strategies for viral myocarditis.

Methods:
To investigate the role of the novel E3 ligase TRIM29 in viral myocarditis, we used wild-type and TRIM29 knockout mice infected with coxsackievirus B3 (CVB3) and encephalomyocarditis virus (EMCV), to induce the myocarditis. Additionally, wild-type mice infected with CVB3 were treated with the protein kinase RNA-like endoplasmic reticulum kinase (PERK) inhibitor GSK2656157 or a DMSO control to evaluate potential therapeutic interventions. Mice survival and heart function were monitored using transthoracic echocardiography, and hearts were harvested for histological and immunohistochemical analysis. Techniques including real-time PCR, western blotting, co-immunoprecipitation, enzyme-linked immunoassay, flow cytometry, over-expression, and knockdown were employed to elucidate the pathogenic mechanisms by which TRIM29 regulates the endoplasmic reticulum stress response after viral infection.

Results:
We found that TRIM29 was highly induced by cardiotropic viruses, including CVB3 and EMCV, and promoted PERK-mediated endoplasmic reticulum (ER) stress, apoptosis, and reactive oxygen species (ROS) responses, which restricted viral replication in cardiomyocytes
in vitro
. TRIM29 deficiency protected mice from viral myocarditis by enhancing cardiac antiviral functions and reducing PERK-mediated inflammation and immunosuppressive cells
in vivo
. Mechanistically, TRIM29 interacted with PERK to catalyze the SUMOylation of PERK, maintaining its stability and thereby promoting PERK-mediated signaling pathways. Furthermore, we demonstrated that the PERK inhibitor GSK2656157 mitigated viral myocarditis by disrupting the TRIM29-PERK interaction, which improved cardiac function, enhanced cardiac antiviral responses, and reduced inflammation and immunosuppressive cells
in vivo
.

Conclusions:
Our findings provide the first evidence that the TRIM29-PERK signaling axis can be targeted for the treatment of viral myocarditis. This suggests that targeting the TRIM29-PERK axis could effectively mitigate viral myocarditis and associated cardiovascular diseases.
Abstract 4134460: Application of Principal Component Analysis to Heterogenous Fontan Registry Data to Identify Independent Contributing Factors to Decline
Authors: Ferrari Margaret , Schafer Michal , Hunter Kendall , Di Maria Michael
Published: November 2024

Introduction:
Single ventricle heart disease is a severe and life-threatening illness, and improvements in clinical outcomes of those with Fontan circulation have not yet yielded acceptable survival over the past two decades. Patients are at risk of developing a diverse variety of Fontan-associated comorbidities that may ultimately require heart transplant.

Goal:
Our study goal was to determine if principal component analysis (PCA), which determines unique directions of data variance, applied to data collected from a pediatric Fontan cohort can predict functional decline (N=140).

Methods:
Heterogeneous data broadly consisting of measures of cardiac and vascular function, exercise (VO
2max
), lymphatic biomarkers, and blood biomarkers were collected over 9 years at a single site as part of a prospectively applied clinical care pathway; in that time, 16 events occurred that are considered here in a composite adverse outcome measure. After standardization and PCA, principal components (PCs) representing >5% of total variance were thematically labeled based on their constituents and tested for association with the composite outcome.

Results:
Our main findings suggest that the 6
th
PC (PC6), representing 7.1% percent of the total variance in the set, is greatly influenced by albumin, alkaline phosphatase, total protein, BUN and BNP max and is a superior measure of proportional hazard compared to EF; it displayed the greatest accuracy for classifying Fontan patients as determined by AUC. In bivariate hazard analysis, we found that models combining systolic function (EF or PC5) and blood biomarkers (PC6) were most predictive, with the former having the greatest AIC, and the latter having the highest c-statistic.

Conclusion:
Our findings support the hypothesis that a broad, prospectively collected, multiorgan system model analyzed by way of unsupervised machine learning methods will improve prognosis of adverse outcomes in a Fontan cohort.
Abstract 4134630: Focal Delivery of Antiplatelet Therapy to Prevent Post-Stent Bleeding in High-Risk Patients
Authors: Mohammed Soheb Anwar , Amjad Muhammad Wahab , Romeo Jared , Harris Kathryn , Gawalt Ellen , Pacella John
Published: November 2024

Background:
Over 3 million percutaneous coronary interventions (PCI) are performed yearly to treat coronary artery stenosis. Stent thrombosis is a catastrophic complication associated with high morbidity and mortality, and its prevention requires the use of prolonged dual antiplatelet therapy (DAPT), which increases bleeding risk. Within the first 30 days after PCI, the mortality of DAPT-associated major bleeding is on par with recurrent myocardial infarction.

Research question:
No stent system that provides focal antiplatelet activity to prevent stent thrombosis exists, eliminating the need for systemic DAPT and subsequent bleeding risk.

Aim:
To address this unmet need, we have developed such a stent, termed “the ticagrelor coated stent” (TCS).

Methods:
Self-assembled monolayers (SAMs) of 12-aminododecylphosphonic acid (ADPA) were formed on cobalt-chromium stents. The amine tail group of ADPA was used to link the ticagrelor molecule through a Mitsunobu reaction and confirmed via infrared spectroscopy. Coating uniformity was validated via atomic force microscopy. In an ex-vivo porcine arterio-venous fistula model, the ticagrelor-coated stents (TCS) were placed in alternating series adjacent to uncoated bare metal stents (BMS). Similarly, TCS and everolimus-eluting stents were placed in the porcine left circumflex arteries for acute (7 days) and chronic (35 days) studies.

Results:
(
Figure 1
): Grossly, no thrombus was seen on the TCS compared to the BMS. Platelet and micro-thrombi adherence were significantly reduced on TCS. Notably, inflammation, measured by neutrophil and monocyte adherence, was also reduced by approximately 10-fold on the TCS vs the BMS. Angiography, optical coherence tomography (OCT), and histopathology results show the TCS widely patent without systemic DAPT.

Conclusion:
These findings show that TCS prevents stent thrombosis through focal anti-platelet action and may reduce the bleeding risk associated with prolonged use of systemic DAPT. Long-term safety and efficacy studies are underway.