bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11917: Reduced Left Atrial Strain Can Predict Higher Risk of Long-Term Major Adverse Cardiovascular Events Post-Myocardial Infarction: A Meta-Analysis
Authors: Sachdeva Sonali , Desai Rupak , Khandait Harshwardhan , SAEED TAHA , Gupta Sneha , Shireen Kanamgode Shihla , Bajaj Siddharth , NANDWANA VARSHA , Hussain Zeeshan Gulam , Vyas Ankit
Published: April 2024

Background:
Risk stratification after acute myocardial infarction (AMI) is essential to plan management and reduce mortality. Deformation imaging of the left atrium (LA) has tremendous prognostic importance following AMI. LA dilation and larger LA volumes are associated with poor patient outcomes post-MI. LA strain is a more sensitive indicator that can be used to assess major adverse cardiovascular events (MACE) in post-MI patients, however, pooled data exploring its use in predicting long-term outcomes remain limited.

Methods:
A systematic literature search of PUBMED, Google Scholar, and SCOPUS databases was performed to identify studies reporting the association of MACE and LA strain. Data on the odds ratio (OR) with 95% confidence interval (CI) were collected and pooled to compute the pooled odds ratio using random-effects models. Heterogeneity was assessed using the I
2
test. I
2>
75% was considered a moderate inter-study variation. P<0.05 was considered statistically significant.

Results:
A total of 6 studies were included with 2931 AMI patients. Baseline characteristics of included studies are shown in
Table 1
. The median follow-up in the studies ranged from 6 months to 4 years. Meta-analysis of included studies using random-effects models showed that reduced LA strain was predictive of long-term adverse cardiovascular events following MI (Pooled Odds ratio: 0.93 (0.90-0.96, p=<0.001, I
2
=48%)
(Figure 1)
.

Conclusion:
Reduced LA strain is associated with higher major adverse cardiovascular events in post-myocardial infarction patients and can be used in addition to LVEF to evaluate MACE.
Abstract 11924: Guiding Strategies in Tricuspid Edge-to-Edge Intervention
Authors: Ruf Tobias F , Ben Ali Walid , Gerdes Patrick , da Rocha e Silva Jaqueline G , Kreidel Felix , Tamm Alexander , Geyer Martin , Muenzel Thomas , von Bardeleben Ralph Stephan
Published: April 2024

Introduction:
Echocardiographical guiding gains further importance as transcatheter interventions for heart valve diseases advance. In transcatheter edge-to-edge repair for tricuspid regurgitation (TEER-TR), the use of transesophageal echocardiography (TEE) employing biplane imaging with views perpendicular to the inflow-outflow-view is suggested. However, robust data on echocardiographical guiding in this setting is lacking, as well as on the role of fluoroscopy settings.

Hypothesis:
The aim of the study was to evaluate different guiding-approaches and fluoroscopy settings in TEER-TR procedures.

Methods:
We retrospectively assessed the effect of different echocardiographical guiding strategies and fluoroscopy angulations on immediate TR reduction (ΔTR), and device time in the TEER-TR interventions. Echocardiographical guiding was rated using a new quality scoring system, MACES
3
.

Results:
From July 2016 to December 2019 a total of 190 cases of TEER-TR procedures were conducted. In all but 2, the procedure was successfully completed. Device deployment was achieved using transesophageal imaging in 65 cases (n[mid-esophageal]=47, (midE); n[deep-esophageal]=18, (deepE)), while live-MPR was employed 4 times. The transgastric en-face view (TG) constituted the grasping view 119 times (Fig. 1). The best imaging quality with the highest MACES
3
scores were observed in deepE and TG. MACES
3
scores significantly influenced the acute outcome. In cases of secondary TR, the use of TG was superior to other imaging in achieving a ΔTR of ≥ 2 grades. Both the use of TG and special fluoroscopy alignment significantly reduced the device time.

Conclusions:
TEER-TR can be effectively guided using different echocardiographic strategies. To strive for the best imaging quality clearly increases procedural success. Using the TG approach offers benefits in immediate procedural result and device time, with the latter further reduced using fluoroscopic alignment.
Abstract 11945: A Paradox of Medical Cost and Outcomes: A Comparison of Acute Heart Failure Outcomes in the United States vs. Japan
Authors: Bates Benjamin , Enzan Nobuyuki , Tohyama Takeshi , Gandhi Poonam , Matsushima Shouji , Tsutsui Hiroyuki , Ide Tomomi , Setoguchi Soko
Published: April 2024

Background:
Despite advances in therapy, the burden of heart failure (HF) has not declined in the US. Comparing HF between nations may provide hypothesis generating research to improve outcomes and decrease costs. We directly compared characteristics, management, cost, and outcomes of acute HF hospitalization in the US vs. Japan.

Methods:
We identified acute HF patients (age >65) in US Medicare Part A, B, and D data and Japanese Registry Of Acute Decompensated Heart Failure (JROADHF), a retrospective, multicenter registry in 2013. We described patient characteristics, length of stay (LOS), cost paid, post-discharge follow-up (f/u), CV medications, death, and CV readmission.

Results:
We identified 11,193 Japanese and 120,289 US patients hospitalized for acute HF. While similar in age and gender, US patients were more likely to have multiple comorbidities (Table). Japanese patients had a 3-fold longer median LOS, a 3-fold lower median per-day hospital cost paid, more than 10-fold likely to receive cardiac rehab, and were more likely to receive CV medications. While inpatient mortality was higher in Japan (8.6% vs 3.2%), overall mortality after HF admission and CV readmission was 1.5-2-fold higher in US patients (Figure). US patients had higher physician f/u within 14 days but overall f/u rate was higher in Japan.

Conclusion:
Despite longer LOS with lower hospital costs, Japanese HF patients had high inpatient cardiac rehab participation, more CV medications, higher f/u rate with a physician, and better survival. Further studies may assess potential interventions (e.g. inpatient cardiac rehab, prevention of premature discharge) to improve outcomes in US HF patients.
Abstract 11959: Left Atrial Size and Function in Children and Young Adults With Obstructive vs. Nonobstructive Hypertrophic Cardiomyopathy
Authors: Gearhart Addison , El-Assad Iqbal , Gauvreau Kimberlee , Colan Steven D , Chen Ming H
Published: April 2024

Introduction:
Left atrial (LA) strain has been recently used to improve assessment of left atrial (LA) function. In adults with hypertrophic cardiomyopathy (HCM), increased LA size and decreased LA strain are associated with LVOT obstruction (LVOTO) and higher risk for adverse cardiovascular outcomes. Scant data exists on the association of LA strain and size in children with HCM, comparing those with and without obstruction.

Methods:
For this pilot study, all patients from an existing pediatric BCH stress echo HCM registry who had adequate echocardiographic images to assess both LA size and strain were consecutively enrolled and retrospectively reviewed. Post-processing LA size and strain (reservoir and conduit) were performed with use of Tomtec/Philips LV strain. Children with HCM were divided into 2 groups: those with resting LVOT gradients <30 mm Hg (no obstruction) versus ≥30 mm Hg (obstruction). LA size, strain and diastolic indices were compared for those with and without obstruction.

Results:
A total of 48 children (63% male, median age 13 yrs, range 6-23yrs) with HCM and analyzable images from the registry formed the cohort. Patient demographics, LA size and strain, and diastolic indices are summarized in Table 1. HCM children with LVOTO had larger LA size (apical 4-chamber (A4C) cross sectional area: p<0.001), lower LA conduit and reservoir strain (p<0.05 for all), and increased diastolic dysfunction (p<0.05 for all).

Conclusions:
Despite their younger age, children with obstructive HCM had larger LA size, lower LA reservoir and conduit strain, and increased diastolic dysfunction compared to children with nonobstructive HCM. Larger studies are needed with longer follow-up time to assess association of LA strain with cardiac events in children.
Abstract 11981: Prognostic Value of Liver Stiffness Measurement in Patients Undergoing Left-Sided Valvular Surgery
Authors: Yu Si-Yeung , Li Hang Long , Tse Yi Kei Stephanie , Ren Qingwen , Wu Meizhen , LI Kwan Yu , Wong Pui-Fai , Lam Lok Yee Jane , Yu Shuk Yin , Yiu Kai Hang
Published: April 2024

Introduction:
Hepatic fibrosis is a recognised extracardiac manifestation of advanced heart diseases. The assessment of cardiac hepatopathies with non-invasive tools such as FibroScan(®) has shown promising prognostic value in patients undergoing right-sided valvular surgery. While an increased level of liver stiffness has been observed in patients with left-sided heart failure (HF), the prognostic value of liver stiffness measurement (LSM) remains unknown in patients undergoing left-sided valvular surgeries.

Methods:
Pre-operative LSM were taken from 239 patients undergoing left-sided valvular surgery prospectively between February 2013 and March 2021 using FibroScan(®). Patients were followed up for adverse outcomes, including mortality or HF requiring hospitalisation. Clinical parameters were collected and patients’ EuroSCORE II were calculated. The prognostic value of LSM for mortality was determined by Cox proportional-hazards regression adjusted for EuroSCORE II; whereas the Fine-and-Gray method was used to assess the prognostic value for (HF) for taking mortality into account as a competing risk. Any incremental value to EuroSCORE II was assessed by continuous net reclassification (cNRI) and integrated discrimination improvement (IDI) indicies.

Results:
Over a median follow-up of 4.1 years, 20 patients died and 28 were hospitalized for HF. LSM was an independent predictor of mortality (hazard ratio [HR]=1.07, 95%CI 1.04-1.10) and provided incremental prognostic value when added to EuroSCORE II (cNRI=0.17, 95%CI 0.02-0.34; IDI=0.39, 95%CI 0.14-0.66). LSM was predictive of subsequent HF (subdistribution HR=1.04, 95% CI 1.01-1.06) whereas EuroSCORE II was not.

Conclusion:
Pre-operative LSM negatively affects long term outcomes in patients undergoing left-sided valvular surgery.
Abstract 11985: Association of GlycA and Progression of Coronary Artery Calcification: The Multi-Ethnic Study of Atherosclerosis
Authors: Manubolu Venkat Sanjay , Duprez Daniel A , Jacobs David R , Otvos James D , Szklo Moyses , Budoff Matthew
Published: April 2024

Background:
GlycA, a composite biomarker of systemic inflammation, predicts cardiovascular morbidity and mortality. Despite growing evidence regarding the association of GlycA and CVD, there are no data about the association of GlycA with coronary artery calcium (CAC), a marker of subclinical atherosclerosis.

Objective:
To investigate the relationship between GlycA levels and progression of CAC.

Methods:
MESA is a multiethnic cohort study of 6814 men and women aged 45-84 years, free of clinical CVD at baseline. Serum level of GlycA was measured by nuclear magnetic resonance (NMR) spectroscopy at baseline. CAC score was assessed by CT at baseline and follow up using either a cardiac gated electron beam CT scanner or 4-16 detector CT systems. Progression of CAC from baseline was defined as average yearly change in Agatston score >= 3 for CAC 0 to 100 and >=10% for CAC >100. Mean follow up period was 9.6±0.6 years. Multivariate regression analysis was performed adjusting for atherosclerotic risk factors.

Results:
Cross-sectional mean GlycA level, stratified by race/ethnicity, was higher in those with CAC > 0 compared to no CAC across all race/ethnicity groups and in both men and women (Fig1A). In regression analysis, the progression of annualized CAC was associated with higher baseline GlycA levels (Fig1B). Analysis was stratified due to interaction between GlycA and BMI (Fig2). In multivariable adjusted models, a one unit increase in GlycA was related to 0.23% higher average annual CAC change in normal BMI (p=0.002). In those who were excess weight (BMI >25) one unit increase in GlycA was associated with a 0.04% yearly average CAC change, after adjusting for covariates(p=0.07).

Conclusion:
Participants with higher baseline GlycA levels have CAC >0 as compared to lower baseline GlycA levels. The annualized progression of CAC is also higher in participants with baseline elevated GlycA levels. This association was statistically significant in participants with normal BMI.
Abstract 11987: Bariatric Surgery Reduces the Incidence of Heart Failure in Patients With Obesity
Authors: Kostanjsek Luke , Ardissino Maddalena , Moussa Osama , Collins Peter , Purkayastha Sanjay
Published: April 2024

Introduction:
Obesity, and the related metabolic syndrome, is one of the largest public health challenges facing medical systems across the globe. A growing body of evidence supports using bariatric surgery in patients with obesity for weight loss and prevention of cardiovascular disease. However, relatively little research has considered whether bariatric surgery reduces the risk of heart failure. This propensity-score matched UK-wide retrospective study aims to answer that question.

Hypothesis:
We hypothesised that bariatric surgery would reduce the incidence of heart failure in patients with obesity, as compared to non-surgical management.

Methods:
Using the Clinical Practice Research Datalink, a study cohort containing 3,052 patients who had received bariatric surgery were matched by propensity score to 3,052 controls. The primary endpoint was development of any heart failure. The secondary endpoints were all-cause mortality, development of heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) specifically, and hospitalisations due to heart failure. These endpoints were assessed using a Cox proportional hazards model.

Results:
The mean follow-up duration was 7.50 years. Patients who received bariatric surgery had a significantly lower incidence of new heart failure (hazard ratio 0.45, 95% confidence interval 0.28-0.73, p=0.0011) and all-cause mortality (hazard ratio 0.56, 95% confidence interval 0.38-0.83, p=0.0036). There was no significant difference in the rates of HFrEF or HFpEF individually, though these analyses were notably underpowered.

Conclusions:
In conclusion, this UK retrospective study provides evidence of lower rates of heart failure and all-cause mortality in patients who have bariatric surgery when compared to propensity-score matched controls. Future efforts to understand the mechanism behind this reduction and explore the lifetime benefits in high risk cohorts are paramount.
Abstract 11992: Rat Engineered Heart Tissue is a Novel in vitro Model to Evaluate Cardiomyocyte Proliferation and Fibroblast Activation After Injury
Authors: Ciucci Giulio , Collia Dario , Cimmino Giovanni , Golino Paolo , Pedrizzetti Gianni , Sinagra Gianfranco , Loffredo Francesco
Published: April 2024

Introduction:
Adult mammals, including humans, fail to regenerate the majority of the lost cardiomyocytes (CMs) that are replaced with scar tissue after injury. This lack of regenerative response is due to the loss of proliferative capacity of adult CMs which in mice occurs 7 days after birth. An in vitro model that recapitulates these changes has not been developed yet.

Hypothesis:
Using rat engineered heart tissues (rEHT) we have developed a custom-made cryoinjury system to test the hypothesis that maturation of CMs in EHTs regulates the proliferative response of CMs after injury.

Methods:
rEHT were generated using neonatal rat heart cells. A discrete lesion was produced on the mid-section of mature (day 18) and immature (day 6) EHTs using a custom-made system based on liquid nitrogen and a 23G needle and medium was supplemented with EdU for 48h.

Results:
Cryoinjury in mature EHTs produces a localized injury, preserving their residual contractile activity that does not recover over time. We observed a significant increase of EdU
+
CMs post injury (6.3 ± 1.9% vs. 10.1 ± 1.6 %) without significant changes in Ki67
+
and pH3
+
CMs suggesting that cryoinjury in mature rEHTs induces DNA synthesis but not CM proliferation. Injury in mature EHTs induced also significant proliferation and activation of fibroblasts with collagen deposition. Interestingly, cryoinjury performed in immature EHTs stimulated a significant proliferative response in CMs.

Discussion:
Similar to adult rodents, we show that cryoinjury induces DNA synthesis in CMs without proliferative response and contractile recovery. On the other hand, cryoinjury in immature EHTs leads to CMs proliferation. Moreover, mature EHT fibroblast response to injury retraces the activation progression of cardiac fibroblast after infarction characterized by proliferation, increase of activation markers, increase of collagen deposition suggesting EHTs as a novel model to investigate the biology of cardiac regeneration upon injury.
Abstract 12366: Intracoronary Delivery of E06 Antibody Directed to Oxidized Phospholipids Decreases Infarct Size in a Porcine Model of Ischemia/Reperfusion Injury
Authors: Stamenkovic Aleksandra , Pierce Grant N. N , Witztum Joseph L , Tsimikas Sotirios , Ravandi Amir
Published: April 2024

Introduction:
Myocardial ischemia/reperfusion injury (IRI) results in additional myocardial cell loss post reperfusion. Oxidized phosphocholine(PC)-containing phospholipids (OxPL) have been shown to result in cardiomyocyte cell death during IRI. E06 is a natural murine monoclonal IgM antibody which binds to the PC headgroup of OxPL. Transgenic mice expressing a single-chain Fv E06 fragment have recently been shown to have smaller infarct sizes post myocardial IRI. The objective of this study was to determine if directly infused E06 IgM reduced IRI in a porcine model of reperfusion injury that more closely reflects human physiology.

Methods:
Male pigs, 45 to 50 kg, were randomized equally to IRI in two groups: 1) control with saline coronary infusion (n=7). 2) IgM E06 coronary infusion over 1 hour (n=7). The left anterior descending (LAD) artery was occluded distal to the second diagonal branch for 60 minutes using an angioplasty balloon. Following balloon deflation, saline or IgM E06 was infused over 60 min through a microcatheter. Following 120 min of total reperfusion, the area at risk (AAR) and infarct size (IS) were determined by triphenyltetrazolium chloride staining technique (TTC), and myocardial salvage index determined.

Results:
All animals survived post reperfusion and no differences were present in hemodynamics at the baseline and 2 h post reperfusion between groups. A 51.3% reduction in infarct size was noted in animals receiving intracoronary E06 compared to controls (IS/AAR 21.7% ± 3.4 vs 42.3% ± 3.7 p<0.0005). IS/LV size (7.7 ± 3.2 vs 11.9 ± 1.2 p<0.004) and myocardial salvage index (82.6% vs 57.6% in controls) were significantly improved in animals receiving E06 compared to controls.

Conclusion:
Intracoronary delivery of E06 antibody at the time of reperfusion leads to a significant reduction in infarct size, suggesting that generation of OxPL during reperfusion leads to cardiomyocyte cell death. Translation of this approach using humanized anti-OxPL antibodies may allow a novel approach to treat myocardial IRI in humans.
Abstract 12392: Rethinking Re-Hospitalization in Heart Failure Care Transitions: Heterogeneity in Utilization Typologies
Authors: Wei Sijia , McConnell Eleanor S , Pan Wei , Corazzini Kirsten N , Granger Bradi B
Published: April 2024

Introduction:
Re-hospitalization for patients with heart failure (HF) is a persistent challenge. Person-oriented analysis may highlight heterogeneities and inform strategies to avert acute-care utilization.

Purpose:
To evaluate how outpatient utilization and sociodemographic, health behavior, and clinical factors are associated with high acute-care utilization using trajectory modeling.

Methods:
This retrospective cohort study used group-based trajectory modeling to identify latent groups of emergency department (ED), inpatient, and outpatient utilization one year before and after the initial HF hospitalization in adults (n= 1269) who had the index hospitalization between January 2016 and December 2018. Factors associated with high acute-care utilization were assessed by multinomial logistic regression.

Results:
People with medium or high outpatient utilization (44.9%) versus those with low outpatient utilization (37.7%) were associated with higher acute-care utilization after controlling for other significant factors such as insurance and comorbidities. Patients had six distinct typologies of acute-care utilization (Figure 1). Four typologies (14.3%) with higher acute-care utilization (ED or inpatient or both) accounted for 52% and 33.0% of the total ED and inpatient encounters. However, the association between outpatient and higher acute-care utilization was not significant among people with fluctuating outpatient utilization (17.4%).

Conclusions:
A person-oriented approach characterizing heterogeneity in acute-care utilization complements the hospital-focused 30-day readmission metric by revealing patients’ unique changes in utilization over time. High-frequency outpatient care may indicate fragmented care. Developing tailored interventions in the outpatient setting to address the small subgroup of patients with consistently high ED or inpatient utilization may improve re-hospitalization for patients with HF.
Abstract 12396: Association of Lipid Profiles With Presence of Aortic Stenosis in Older Adults: Atherosclerosis Risk in Communities Study
Authors: Agha Ali M , Al Rifai Mahmoud , Deshotels Matthew , Sun Wensheng , Hoogeveen Ron C , Ballantyne Christie M , Virani Salim S , Shah Amil M , Selvin Elizabeth , Matsushita Kunihiro , nambi vijay
Published: April 2024

Introduction:
Many risk factors for atherosclerosis are also risk factors for aortic stenosis. We sought to determine if novel and traditional lipid parameters are associated with aortic stenosis in a population-based study.

Methods:
We conducted a prospective analysis of participants without aortic stenosis at visit 4 (1996-98) of the ARIC Study. We used logistic regression to assess the association between lipoprotein (a) [Lp(a)], remnant-like particle cholesterol (RLP-C), low-density lipoprotein triglycerides (LDL-TG), small dense low-density lipoprotein-cholesterol (sdLDLc), non-high-density lipoprotein-cholesterol (non-HDLc), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) and incident aortic stenosis (defined as peak aortic valve velocity ≥2.0 m/s) on transthoracic echocardiogram (TTE) performed during visits 5 (2011-13) and 7 (2018-19).

Results:
Our study population included 11,587 individuals (mean age (SD): 76 (5) years, 56% women, 23% Black). 49% and 24.8% had TTE performed at visits 5 and 7 and the presence of aortic stenosis was 5% and 8%, respectively. In adjusted models, LDL-TG, RLP-C, sdLDLc, non-HDLc, TG, and LDLc at visit 4 were associated with aortic stenosis at visit 5. Lp(a) at visit 4 was predictive of aortic stenosis at visit 7 (table).

Conclusions:
Among persons who survived to old age, novel lipid parameters (including Lp(a), LDL-TG, RLP-C, and sdLDLc) in mid-life were associated with aortic stenosis in late-life. Further studies should determine if lipid-lowering therapies can prevent the development of aortic stenosis.
Abstract 12416: Modeling Diabetic Endothelial Cell Dysfunction With Induced Pluripotent Stem Cells
Authors: Kovacs Beatrix , Gorashi Rayyan , Jiang Bin
Published: April 2024

Introduction:
Diabetes is one of the major risk factors for cardiovascular diseases (CVDs), which is mediated by vascular endothelial dysfunction. Currently, there is no in vitro disease model of endothelial cell (EC) dysfunction in diabetic patients, which hinders mechanistic understanding and therapeutic discovery. The goal of this study is to develop a comprehensive model of diabetic EC dysfunction using patient-derived induced pluripotent stem cells (iPSCs) and recapitulating the diabetic microenvironment.

Methods:
Our model utilizes iPSC derived ECs from the following sources: healthy subjects and diabetic patients with underlying CVDs (n=3). To simulate in situ conditions of diabetes, we used the following treatment for 5 days: hyperglycemia (25 mM glucose); high urea (9 mM); and inflammatory stimulation with tumor necrosis factor alpha (TNF-α, 8 pg/ml). EC dysfunction was assessed through oxidative stress, inflammation, permeability, and thrombosis. Immunofluorescence identified localization for surface adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), endothelial selectin (E-sel), and platelet selectin (P-sel). Enzyme-linked immunosorbent assay (ELISA) quantitatively measured expression of these surface adhesion molecules.

Results:
Overall, the qualitative effect of the diabetic microenvironment resulted in increased expression of ICAM-1, E-sel, and P-sel. After TNF-α treatment, we observed a stronger increase in expression of P-sel in healthy subject-derived cells than diabetic patient-derived cells. This indicates a possible pre-conditioned tolerance of pro-inflammatory conditions. Ongoing experimentation will provide results for quantitative expression of ICAM-1, E-sel, and P-sel after treatment with the diabetic microenvironment.

Conclusion:
The development of a robust in vitro model of diabetic endothelial dysfunction, similar to the onset of type 2 diabetes, will allow for high-throughput testing of pharmacological agents to ultimately treat the disease’s effects within the vascular bed. The widespread implications of type 2 diabetes on the vascular bed further amplify the significance of this study in the development of pharmacological agents to treat the disease.
Abstract 12424: A Non-Invasive Proteomic Model Predicts Pulmonary Arterial Hypertension Survival
Authors: Griffiths Megan , Simpson Catherine , Yang Jun , Torres Guillermo , Vaidya Dhananjay , Nies Melanie , Brandal Stephanie , Damico Rachel L , Ivy Dunbar D , Austin Eric D , Pauciulo Michael , Lutz Katie , Benza Raymond L , Hirsch Russel , Yung Delphine , Berman Rosenzweig Erika S , Nichols Bill , Manlhiot Cedric , Everett Allen D
Published: April 2024

Background:
Pulmonary arterial hypertension (PH) is a progressive disease of the pulmonary vasculature. Risk assessment to guide treatment is fundamental to improved outcomes. Current risk models rely on invasive (cardiac cath) and subjective features, prompting need for a non-invasive risk assessment tool in PH.

Hypothesis:
A multi-marker protein model will accurately predict PH survival

Methods:
Using a custom multiplex ELISA (based on prior models), we measured proteins targeting pathobiologic pathways in PAH; NTproBNP (cardiac function), ST2 (cardiac fibrosis), IL-6 (inflammation), endostatin (angiogenesis), and HDGF (vascular growth). Subjects were enrolled from the PH Biobank (PAHB, N=2335, age>15) and a validation cohort from Johns Hopkins and Vanderbilt Universities (N=250, age>18). Unsupervised k-means clustering classified subjects by biomarkers. Transplant free survival by cluster were examined using Kaplan-Meier and Cox proportional hazard modeling. Risk by cluster was compared to current clinical models (REVEAL and ESC/ERS Risk) using Harrell’s C Index.

Results:
The algorithm generated 4 clusters with excellent risk discrimination in both cohorts (Figure 1). The HR for the severe group (vs lowest risk) in the PAHB was 10.1, (C Index 0.72), while in the validation the HR was 8.6 (C Index 0.74). Addition of genetic mutations, age, sex, and comorbidities did not improve model fit. When compared to the REVEAL and ERS/ESC scores (C Index 0.69 and 0.59 respectively), the proteomic model had better discrimination.

Conclusions:
This multimarker proteomic model non-invasively assessed PH severity and prognosis with improved accuracy compared to current clinical models. A simple blood test may enable frequent assessment of PH patients in a routine clinic setting to support therapeutic decision-making. In addition, this non-invasive model may provide a surrogate endpoint for future clinical trial designs (after prospective validation).
Abstract 12434: Long-Term Clinical Outcomes After Major versus Minor Bleeding in Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: Ishigami Kenjiro , Ogawa Hisashi , Ikeda Syuhei , DOI KOSUKE , Hamatani Yasuhiro , Ide Yuya , Fujino Akiko , ISHII MITSURU , Iguchi Moritake , Masunaga Nobutoyo , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: April 2024

Introduction:
Oral anticoagulants reduce the risk of ischemic stroke but may increase the risk of bleeding in atrial fibrillation (AF) patients. However, the clinical outcomes of patients after major or non-major bleeding are unknown.

Methods:
In the Fushimi AF Registry, follow-up data were available in 4,470 patients by the end of September 2020. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. We investigated the demographics and outcomes of AF patients who experienced major bleeding and clinically relevant non-major bleeding (CRNM) during follow-up period.

Results:
During the median follow-up period of 1,459 days, major bleeding and CRNM occurred in 350 (7.8%) and 719 patients (16.1%) as first bleeding event, respectively. Patients with major bleeding were older (major vs CRNM vs no-bleeding; 75.6 vs 73.9 vs 73.3, p=0.001), and more likely to have chronic kidney disease (44.6% vs 35.2% vs 35.1%, p=0.002), previous major bleeding (8.0% vs 3.5% vs 4.4%, p=0.006). Patients with major bleeding had higher CHADS
2
score (2.3 vs 2.0 vs 2.0, p<0.001), higher CHA
2
DS
2
-VASC score (3.7 vs 3.4 vs 3.3, p=0.001), and higher HAS-BLED score (2.0 vs 1.8 vs 1.7, p<0.001). On landmark analysis, all-cause mortality occurred in 137 patients after major bleeding (15.8 /100 person-years), 134 patients after CRNM (5.3 /100 person-years), and 803 patients without bleeding during follow-up period (5.2 /100 person-years) (hazard ratio [HR] 2.68, 95% confidence interval [CI] 2.24-3.22, p<0.0001 [major bleeding vs. no-bleeding]; HR 0.97, 95%CI 0.81-1.17, p=0.761 [CRNM vs. no-bleeding]). (Figure)

Conclusion:
AF patients after major bleeding had significantly higher incidence of all-cause mortality, but those after CRNM did not have significant incidence of all-cause mortality in a community-based AF cohort.
Abstract 12471: Bleeding Challenges in Pediatric Ventricular Assist Devices- A Study From the ACTION Registry
Authors: Bansal Neha , Shezad Muhammad , O'Connor Matthew J , Edelson Jonathan , Butto Arene , Auerbach Scott R , Conway Jennifer , Zafar Farhan , Rosenthal David N
Published: April 2024

Background:
Ventricular assist devices (VAD) are increasingly used in children with end-stage heart failure. Bleeding is a major complication of VAD, but most reports have focused on central nervous system (CNS) bleeding. Our objective was to determine the incidence & consequences of non-CNS bleeding in pediatric VADs.

Methods:
We examined adverse events (AE) & outcomes of all patients implanted with a VAD at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers between 9/2018-5/2021. Major bleeding event (MBE) was defined as an episode of suspected bleeding resulting in death, reoperation, hospitalization or blood transfusion (>7days after implant). Variables were analyzed using chi square & Mann Whitney test and outcomes were assessed by Kaplan Meier (KM) survival curves.

Results:
A total of 407 patients were prospectively enrolled in the ACTION registry, of which 82 (20.1%) had a MBE. The median duration of support was 72 days (range 6-1101). MBE was most common in paracorporeal continuous flow devices (42/82 devices, 51%). MBE was gastrointestinal in 30.3% & thoracic in 38.5%. Patients with MBE were more likely to have congenital heart disease (CHD) or previous cardiac operation & were less likely to have had VAD as a bridge to transplant (Table). Within 14 days post MBE, 31 subjects had another major AE (14 major infection, 13 another MBE, 2 stroke and 1 device malfunction). Unadjusted survival in patients with MBE was significantly worse than those without (p<0.001) (Figure).

Conclusion:
MBE after VAD implant was seen in 20% of pediatric VAD patients, a higher proportion of whom had CHD. MBE was associated with other major AEs post-VAD and also with worse survival.
Abstract 12478: Investigating the Shared Genetic Architecture Between Coronary Artery Disease and Major Depressive Disorder
Authors: Singh Kritika , Miller-Fleming Tyne M , Hodges Emily C , Davis Lea K
Published: April 2024

Coronary Artery Disease is a highly polygenic disorder and has increased comorbidity with Major Depressive Disorder (MDD). Our previous work demonstrated that the PRS for MDD was significantly associated with manifestations of CAD including ischemic heart disease (OR = 1.09, p=8.28x10-6) and coronary atherosclerosis (OR = 1.10, p=1.08x10-5) in a large hospital population. Furthermore, the association remained robust after adjusting for known CAD risk factors, suggesting that some proportion of genes that increase susceptibility to MDD act pleiotropically to increase CAD risk. Therefore, the aim of our study was to identify genes that increase risk for both CAD and MDD. We first performed an imputed TWAS using existing GWAS data on CAD from the CARDIoGRAMplusC4D consortium and UKBB and MDD from Psychiatric Genomics Consortium. TWAS uses the summary statistics from a GWAS and expression prediction models to infer the association between the genetically predicted expression of each gene and a phenotype of interest. We identified genes for which predicted expression was associated with increased risk of both MDD and CAD. We then further tested the relationship between those genes and quantitative biomarkers recorded in the Vanderbilt electronic health record (EHR). For this, we used Vanderbilt’s collection of de-identified biosamples (BioVU) which currently includes ~100k genotyped patient DNA samples linked with their EHRs. We used PredixVU, a gene-based association method to determine whether genes identified in the TWAS were associated with clinical biomarkers. We identified significant overlap in the genes associated with both MDD and CAD at an FDR of 0.01 (hypergeometric enrichment factor of 3.2; p = 0.002) and 0.05 (hypergeometric enrichment factor of 2.4; p = 8.35e-9). TMEM106B was significantly associated with both MDD and CAD after Bonferroni correction was applied. TMEM106B is involved in lysosomal activity and has been independently associated with both, CAD and MDD. The predicted expression of TMEM106B in the putamen is associated with decreased levels of hydroxyproline (OR = 0.830, P-Value = 7.5 e-5). For our future work, we aim to investigate the shared pathways of these genes across Asian, European and African ancestry using BioVU.
Abstract 12562: Prasugrel May Be Associated With All-Cause Mortality Benefit in Patients on Chronic Dialysis
Authors: Davis Clayton , Phadnis Milind , Dai Junqiang , Rasu Rafia , Mehta Jawahar L , Jain Nishank
Published: April 2024

Introduction:
Although prasugrel has been shown to be more effective over other P2Y12 inhibitors (P2Y12-I) in the general population, it remains unclear whether it is also superior in reducing all-cause death in patients on chronic dialysis (ESKD).

Methods:
This longitudinal analysis included Medicare patients with ESKD on P2Y12-I from the U.S. Renal Data System registry between 2011-2015. Patients were followed from receipt of new prescription until death or censoring. The primary outcome was all-cause death, and the secondary outcome was CV death, as ascertained from the registry. Survival analysis was performed after propensity matching.

Results:
Our analysis included 44,619 ESKD patients on P2Y12 inhibitors - 95% received clopidogrel (n= 42,523), 3% received prasugrel (n = 1,205), and 2% received ticagrelor (n = 891). During a median follow up of 1 year, there were 2,555 (30.7%), 1,370 (31.1%), and 404 (23.0%) deaths in the prasugrel-clopidogrel, the ticagrelor-clopidogrel, and the prasugrel-ticagrelor matched cohorts, respectively. Similarly, there were 1,266 (15.2%), 667 (15.1%) and 210 (11.9%) CV-deaths in the three cohorts respectively. Prasugrel vs. clopidogrel was associated with reduced risk for death (HR 0.80; 95% CI: 0.70, 0.90). Similar findings were noted when compared to ticagrelor (HR 0.75; 95% CI: 0.57, 0.98). Prasugrel was also associated with a borderline reduced risk for CV-death when compared with clopidogrel (HR 0.85; 95% CI: 0.72, 1.01) and ticagrelor (HR 0.80; 95% CI: 0.60, 1.07).

Conclusion:
Our findings suggest a benefit in reduction of all-cause death, possibly by reducing CV-death with use of prasugrel over other P2Y12-I in patients on chronic dialysis. Since these results could be limited due to residual confounding, future trials should investigate whether prasugrel is superior to other P2Y12-Is in reducing all-cause death and CV-death among patients on chronic dialysis.
Abstract 12574: Syndromic Neonates With Symptomatic Tetralogy of Fallot Have Lower Early Mortality With Staged Repair Compared to Primary Repair
Authors: Lee Teresa M , Glatz Andrew C , Petit Christopher J , Goldstein Bryan H , Qureshi Athar M , Nicholson George , Law Mark A , Meadows Jeffrey , Zampi Jeffrey , Romano Jennifer , Mascio Christopher , Shahanavaz Shabana , Beshish Asaad , Maskatia Shiraz A , Batlivala Sarosh P , Pettus Joelle , Kelleman Michael , McCracken Courtney , Chung Wendy
Published: April 2024

Introduction:
Neonates with symptomatic tetralogy of Fallot (sTOF) require early intervention with staged repair (SR) or primary repair (PR). As sTOF is commonly associated with genetic syndromes, we examined outcomes of SR vs. PR for syndromic sTOF neonates.

Hypothesis:
We hypothesized that syndromic neonates with sTOF who underwent SR will have lower early mortality compared to PR.

Methods:
Syndromic neonates with sTOF who underwent initial intervention (initial palliation followed by later SR, or PR) from 2005-2017 were reviewed. The primary outcome was death. Secondary outcomes included complications, and hospital and intensive care unit (ICU) lengths of stay (LOS). Unadjusted and propensity score adjusted outcomes were compared.

Results:
The 176 syndromic sTOF neonates consisted mostly of DiGeorge (35%), trisomy 21 (16%), and VACTERL (10%). There were 110 and 66 neonates in the SR and PR groups, respectively. DiGeorge syndrome, pulmonary atresia, prematurity, and pre-procedural ventilation were more common in the SR group. The adjusted overall hazard of death was similar between groups, but early mortality favored SR (Figure). Procedural complications were lower in the SR group at the index procedure, but SR is associated with longer cumulative hospital and ICU LOS (Table).

Conclusions:
In syndromic neonates with sTOF, there was an early survival benefit to SR compared to PR, although there was no overall survival difference. The cumulative cost of the SR strategy was longer hospital and ICU LOS. These findings do not suggest a single superior management strategy in the syndromic sTOF population.
Abstract 12595: Fragmented QRS With Benign Early Repolarization Pattern is a Strong Predictor of Adverse Events in Patients With Suspected Acute Coronary Syndrome
Authors: Ahmad Abdullah , Faramand Ziad , Mahmoud Ahmad , Gregg Richard , Al-Zaiti Salah S
Published: April 2024

Introduction:
Early repolarization pattern (ERP) and fragmented QRS (fQRS) are well studied ECG markers of risk in various clinical populations. Emerging evidence suggests that coexistence of these patterns constitutes a synergistic substrate for arrhythmogenic events. Examining the prognostic value of these patterns would have immediate clinical applications for the triage of high-risk patients, including those with suspected acute coronary syndrome (ACS).

Methods:
This was a prospective study that enrolled chest pain patients transported via ambulance to UPMC hospitals. ERP was manually over-read by a blinded physician according to published guidelines. fQRS was automatically calculated as QRS loop notching on 3-D vectorcardiogram using manufacturer software. Patients were classified to four groups: 1) no ERP or fQRS; 2) ERP only; 3) fQRS only; and 4) both fQRS/ERP. Study outcome was major adverse cardiac events (MACE) within 30 days of admission, defined as: ACS, death, coronary revascularization, cardiac arrest, ventricular dysrhythmia, cardiogenic shock, and acute heart failure. Two independent reviewers adjudicated outcomes from the charts.

Results:
After excluding those with wide QRS (>110ms), this analysis included 1392 out of 1650 patients on whom ECG interpretation was available (Age 57 ± 16; 48% females, 41% Black, 20% with adjudicated 30-day MACE). The prevalence of patients with no ERP/fQRS, ERP-only, fQRS-only, and both fQRS/ERP were 13%, 22%, 24%, and 41% respectively. In univariate analysis, those with fQRS-only (OR: 1.74; [95% CI, 1.03-2.94], p=0.038), and fQRS/ERP (OR: 2.14; [95% CI, 1.32-3.48], p=0.002) were associated with MACE compared to no ERP or fQRS as reference group. In final multivariate model, controlling for demographic and clinical data, fQRS/ERP remained a strong predictor of MACE (OR: 2.27; [95% CI, 1.34-3.87], p=0.002).

Conclusions:
Coexistence of fQRS/ERP on presenting ECG provides a strong predictor for 30-day MACE in suspected ACS, independent of patient characteristics These qualitative patterns can be easily visualized by clinicians during ECG interpretation, enhancing their potential application. The incremental role of these patterns in established tools (e.g., TIMI) is yet to be determined.
Abstract 12609: Contemporary Trends of Outcomes in Left Ventricular Assist Device: Insight From Nationwide Readmission Database
Authors: Kalra Ankur , Majmundar Monil , Kumar Ashish , Doshi Rajkumar , Shariff Mariam , Il’Giovine Zachary J , Randhawa Varinder , Tang Wai Hong W , Starling Randall , Estep Jerry
Published: April 2024

Hypothesis:
We aimed to analyze trends of 30-day readmission and find high-risk patients associated with increased risk of mortality, resource utilization, and readmission after primary left ventricular assist device (LVAD) implantation.

Introduction:
Limited data exist on the contemporary trends of readmission rates and patients at a higher risk of worse outcomes post-LVAD.

Methods:
This is a retrospective study of adults from the NRD who received primary durable LVAD implantation from 2010-2018. The main outcomes were 30-day readmission rates and their trends in patients with primary durable LVAD implantation from 2010-2018. This study also sought to identify the patients at the highest risk for readmission, in-hospital mortality, and resource utilization.

Results:
A total of 31,002 adults with primary durable LVAD implantation were included in the present analysis. Overall, 3808 (12.3%) died, and 27168 (87.6%) were discharged alive. Of those discharged alive, 8303 (30.6%) patients were readmitted within 30 days. The trend of 30-day all-cause readmission among LVAD implantation patients remained similar from 2010-2018 (p=0.809). The in-hospital mortality during index hospitalization significantly decreased (p=0.014), and the mean cost of index hospitalization increased (p=0.031) during the study period. The patients with post-LVAD in-hospital cardiac, vascular, and thromboembolic complications (i.e., high-risk patients) had the highest mortality, resource utilization, and readmission rates as compared with patients without major complications.

Conclusions:
This study found that the readmission rates associated with LVAD implantation did not change from 2010-2018 and identified high-risk patients who may benefit from closer monitoring after primary LVAD implantation.
Abstract 12612: Intrapersonal and Interpersonal Factors Influencing Physical Activity in Arab Americans: A Social-Ecological Approach
Authors: Nahari Ahmed M , Davis Leslie L , Wallace Debra , Pickett Stephanie , Davis Paul G , McCoy Thomas
Published: April 2024

Background:
Physical activity (PA) is an important determinant of health throughout the lifespan. Meeting PA guidelines improves health outcomes and prevents or slows the progression of many chronic health conditions. Yet, literature has shown that many Arab Americans do not meet the PA Guidelines. Little is known about determinants of PA in this population.

Objective:
Guided by the Social Ecological Model, we aimed to 1) describe PA and investigate the relationships between PA and sample characteristics, intrapersonal factors, and interpersonal factors and 2) examine to what extent these factors influence PA in Arab Americans.

Methods:
A cross-sectional, descriptive-correlational design using a self-administered questionnaire with 140 Arab Americans was used. Spearman's rho correlation was used to assess the associations between PA and sample characteristics, intrapersonal factors, and interpersonal factors. Three simultaneous gamma regression models were used to assess to what extent sample characteristics, intrapersonal, and interpersonal factors jointly influenced PA.

Results:
A majority (58.6%) of our participants reported a high level of PA. Findings revealed significant positive associations between PA and health status, religiosity, and PA self-efficacy (

r
s

= 0.21,
p
= 0.019;
r
s
= 0.19,
p
= 0.029;
r
s
= 0.28;
p
= 0.003, respectively). Multiple regression models revealed that being employed (Model 1 Exp(
b
) = 1.87,
p
= 0.030; Model 3 Exp(
b
) = 1.77,
p
= 0.043) and having chronic conditions (Model 1 Exp(
b
) = 1.88,
p
= 0.031; Model 2 Exp(
b
) = 1.96,
p
= 0.034; Model 3 Exp(
b
) = 1.91,
p
= 0.047) were associated with greater PA, when accounting for other sample characteristics, intrapersonal, and interpersonal factors.

Conclusion:
Clinicians need to recognize the importance of enhancing PA self-efficacy while considering presence of chronic health conditions and employment status when promoting PA in Arab Americans. Future research is needed to explore the relationship between religiosity and PA in this population.
Abstract 12624: Optimal Patient Selection for Simultaneous Heart-Kidney Transplant: A Modified Cost-Effectiveness Analysis
Authors: Wayda Brian , Cheng Xingxing S , Goldhaber-Fiebert Jeremy D , Khush Kiran K
Published: April 2024

Introduction:
Increasing rates of simultaneous heart-kidney (SHK) transplant in the United States exacerbate the shortage of deceased donor kidneys (DDK) for kidney-only transplant (KT-only) candidates. Current allocation policy imposes no constraints on eligibility for SHK, and how best to do so remains unknown.

Methods:
We apply a decision analytic model to evaluate options for heart transplant (HT) candidates with comorbid kidney dysfunction, comparing 1) upfront SHK transplant (using a DDK) and 2) a “Safety Net” strategy, in which HT-only is performed first and DDK transplant is performed six months later if native kidneys do not recover. We measure “cost” in expected number of DDKs allocated to HT recipients, effectiveness in quality-adjusted life years (QALYs), and cost-effectiveness in terms of QALYs gained per kidney. We evaluate each outcome for patients of varying “reversibility”, defined as their probability of native kidney recovery after HT-only. We identify those for whom SHK (compared to Safety Net) is efficient from a societal standpoint, producing more QALYs per kidney than each additional kidney used for KT-only.

Results:
For a candidate with 50% reversibility, SHK (compared to Safety Net) produces 0.54 - 0.77 more QALYs (varying by age) at a cost of 0.58 more kidneys used. SHK is inefficient in this scenario, producing fewer QALYs per DDK (0.92 - 1.31) than an additional DDK allocated for KT-only (2.2 QALYs per kidney, derived from published estimates). SHK confers more benefit and is more cost-effective with decreasing age and reversibility, and is preferred to Safety Net for patients with reversibility under 24 - 38%.

Conclusions:
A Safety Net strategy produces greater societal benefit than SHK for HT candidates with concurrent kidney dysfunction, excepting only those with a low probability of native kidney recovery. This finding favors implementation of a Safety Net provision and should inform the use of objective criteria to limit SHK eligibility.