bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4134531: BST2 induces vascular smooth muscle cell plasticity and phenotype switching during cancer progression
Authors: Bell Caitlin , Baylis Richard , Ma Wei Feng , Miller Clint , Leeper Nicholas
Published: November 2024

Rationale:
Smooth muscle cell (SMC) plasticity and phenotypic switching play prominent roles in the pathogenesis of multiple diseases like atherosclerosis and pulmonary hypertension, but their role in tumorigenesis is unknown.

Objective:
To investigate SMC diversity and plasticity in tumor angiogenesis and its underlying molecular drivers.

Methods and Results:
Here we use SMC-specific lineage-tracing mouse models and single cell RNA sequencing (scRNA-seq) to observe the phenotypic diversity of SMCs participating in tumor vascularization. We find that around 10% of SMCs adopt a phenotype which includes features traditionally associated with macrophage-like cells, suggesting they may contribute to the immune profile of the tumor microenvironment (TME). These cells are transcriptionally similar to ‘resolution phase’ M2b macrophages, which have been described to have a role in inflammation resolution. Signaling from bone marrow stromal antigen 2 (BST2) on the surface of tumor cells to PIRA2 on SMC promotes this phenotypic transition, leading to a SMC phenotype that is more proliferative, migratory, and phagocytic. Knockdown of BST2 in the tumor significantly decreases the transition towards a macrophage-like phenotype, and the cells that were able to transition had a comparatively higher inflammatory signal typically associated with anti-tumor effect.

Conclusions:
As BST2 is known to be a poor prognostic marker in multiple cancers where it is associated with an M2 macrophage-skewed TME, these studies suggest that phenotypically switched SMCs may have a previously unidentified role in this immunosuppressive milieu. The novel concept of SMC contribution to the immune landscape suggests manipulation of SMC phenotypic switching as an approach to altering cancer pathogenesis. Further translational work is needed to understand how this phenotypic switch could influence response to anti-cancer agents and if targeted inhibition of SMC plasticity would be therapeutically beneficial.
Abstract 4134551:
Outstanding Research Award in Pediatric Cardiology:
Cardiomyopathy-Associated Pathogenic Variants in Pediatric Myocarditis: A Study from the Pediatric Cardiomyopathy Registry
Authors: Kamsheh Alicia , Ware Stephanie , Bhatnagar Surbhi , Martin Lisa , LEE Teresa , Towbin Jeffrey , Kantor Paul , Colan Steven , Canter Charles , Lipshultz Steven
Published: November 2024

Background:
Recent studies have demonstrated that patients with myocarditis (MC) may have a higher burden of cardiomyopathy (CM)-associated gene variants than the general population. However, data in children is limited. The Pediatric Cardiomyopathy Registry (PCMR), a large multi-center registry of children with CM, includes patients with dilated CM (DCM) secondary to myocarditis (MC).

Hypothesis:
We hypothesized patients with DCM secondary to MC in the PCMR have a higher burden of CM-associated gene variants than healthy controls, and clinical genetic testing in this population is rare.

Aims:
We aimed to: (1) calculate the prevalence of pathogenic (P) or likely pathogenic (LP) CM-associated variants in patients with DCM secondary to MC and compare to the prevalence in heart-healthy controls and (2) report the rate of clinical genetic testing in this population.

Methods:
The PCMR was queried to identify patients with DCM secondary to MC who underwent exome sequencing as part of a prior prospective study at 14 sites in North America. Controls from the Indiana University Biobank were matched 4:1 with cases based on genomic similarity. A curated gene list was comprised of 46 genes associated with CM. A second gene list included 102 genes associated with CM or MC in the ClinVar database. The prevalence of variants was compared using Chi-Square or Fisher’s exact tests.

Results:
A total of 32 patients were identified with DCM secondary to MC. Median enrollment age was 1.5 years (IQR 0.4-10.3) and 53% were female. There was no family history in 88%. The prevalence of P/LP variants from the curated list was 34.4% in cases compared to 4.7% in controls (p<0.001). The prevalence of P/LP variants from the ClinVar list was 31.3% in cases compared to 6.3% in controls (p<0.001). Variants were identified in 8 genes: ABCC9, ANKRD1, MYH6, MYH7, MYPN, PLN, TPM1 and TTN. No P/LP variants were found in desmosomal genes. The prevalence of variants was higher but not significantly different in older children compared to infants (45.0% vs 16.6%, p=0.1). The prevalence of variants in MC was similar to previously reported rates in all causes of DCM (34.4% vs 28.8%, p=0.5). Only 22% of cases received clinical genetic testing.

Conclusion:
Approximately 1 in 3 children with DCM secondary to MC carry a CM-associated P/LP variant, which is significantly higher than the prevalence in healthy controls. Given the high prevalence, routine genetic testing should be considered in this population.
Abstract 4134619: A Novel Missense Mutation in TNNT2 Gene in a Lebanese Pedigree With Ebstein Anomaly And Wolf-Parkinson-White Syndrome: A Case Report
Authors: Atasi Montaser , Dankar Razan , Barakat Salim , Wehbi Jad , Refaat Marwan
Published: November 2024

Background:
Ebstein anomaly (EA) is a rare congenital heart defect occurring in 1.2 to 5 in 100,000 live births, characterized by a downward displacement of the tricuspid valve, thin-walled right ventricle, and tricuspid valve regurgitation. It can present variably from asymptomatic cases to severe symptoms like arrhythmias and right-sided heart failure. EA is often associated with other anomalies such as interatrial communication and mitral valve prolapse. The condition can lead to accessory atrioventricular pathways, frequently resulting in Wolff-Parkinson-White syndrome (WPW), which involves abnormal heart electrical activity and increases the risk of sudden cardiac death. While the genetic basis of EA is not fully understood, it appears to involve multiple genes like FLNA and NKX2-5, MYH6, MYH7 suggesting a complex polygenic inheritance pattern. TNNT2 is known to be associated with Cardiomyopathy but has not been previously associated with EA and WPW.

Case:
In this report, we present findings from a lebanese family with EA, comprising 2 affected individuals. Whole exome sequencing in the affected individuals identified a pathogenic variant in the TNNT2 gene at coding strain position 260 (a missense mutation: C to T), resulting in the substitution of Proline with Leucine at position 87 in affected individuals (Figure 1). No variants were detected in any other candidate gene examined. Individuals I:1 and II:2 were found to be normal, with no EA findings on echocardiography.

Methods:
Whole exome sequencing in the patients involved collecting blood samples after obtaining consent. These samples were sent to Centogene lab, where genomic DNA is enzymatically fragmented. The regions of interest are then enriched using DNA capture probes, facilitating detailed genetic analysis.

Results:
The whole exome sequencing identified a heterozygous missense mutation in both the father and his daughter. This nonsynonymous variant is located on chromosome 1 (GRCh37) in the TNNT2 gene region. The specific variant, NM_001276345.1:c.260C>T p.(Pro87Leu), was found in both individuals.

Conclusion:
In conclusion, the genetic basis of EA is rather complex and remains poorly understood. It is established that mutations in the TNNT2 gene are linked to several cardiomyopathies, none of them overlap with the described phenotype of our patients. In this report, we therefore confirm the potential role of TNNT2 gene mutation in the genetic basis of familial EA with WPW.
Abstract 4134744: Trends and Disparities in Mortality Among Patients with Hypertensive Heart Disease and Congestive Heart Failure in the United States from 1999 to 2020
Authors: Goyal Aman , Saeed Humza , Maheshwari Surabhi , . Abdullah , Jain Hritvik , Shamim Urooj , Bansal Kamna
Published: November 2024

Background:
Hypertensive heart disease (HHD) poses a growing public health concern. Global data reveal a concerning rise in HHD prevalence, deaths, and disability-adjusted life years (DALYs) between 1990 and 2019. The Framingham Study highlights that hypertension is linked to approximately one-quarter of heart failure cases. This association is even stronger among older adults, in whom hypertension is responsible for up to 68% of heart failure cases.

Methods:
This study analyzed death certificates within the CDC WONDER database for patients in the United States from 1999 to 2020. We identified deaths among individuals aged 25 years and older caused by HHD and CHF using the International Classification of Diseases, Tenth Revision (ICD-10) code I11.0. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, race/ethnicity, and urbanization status.

Results:
Between 1999 and 2020, a total of 302,270 deaths were reported in patients due to HHD with CHF. Overall, AAMR increased from 37.3 to 134.9 per 1,000,000 population between 1999 and 2020, with a significant decrease from 1999 to 2004 (APC: -7.91; 95% CI: -20.16 to -1.04), followed by a significant increase from 2004 to 2007 (APC: 42.47; 95% CI: 21.27 to 55.62), a slight decrease from 2007 to 2014 (APC: -0.9; 95% CI: -9.38 to 2.39), and finally a steep increase from 2014 to 2020 (APC: 14.22; 95% CI: 10.87 to 20.84). Gender-based analysis revealed that men had slightly higher AAMRs than women (Men: 63.1; 95% CI: 62.8 to 63.5 vs. Women: 60.7; 95% CI: 60.5 to 61). Moreover, AAMRs were highest among non-Hispanic African Americans (109.6; 95% CI: 108.6 to 110.6), followed by non-Hispanic American Indian or Alaska Natives (66.6; 95% CI: 63.1 to 70.1), non-Hispanic Whites (58.5; 95% CI: 58.2 to 58.7), Hispanics (53.7; 95% CI: 52.9 to 54.5), and non-Hispanic Asian or Pacific Islanders (39; 95% CI: 38–39.9). In addition, non-metropolitan areas had higher AAMRs than metropolitan areas (non-metropolitan: 65.7; 95% CI: 65.2 to 66.3 vs. metropolitan: 62.1; 95% CI: 61.8 to 62.3) (Figure 1).

Conclusions:
Despite an initial decline, mortality from combined HHD and CHF has risen significantly since 1999. Notably, mortality was most pronounced among men, non-Hispanic African Americans, and individuals residing in non-metropolitan areas.
Abstract 4134778: Myocardial Recovery and Survival after Weaning of Left Ventricular Assist Device Therapy in Patients with Toxic and non-Toxic Cardiomyopathy, A Canadian Experience
Authors: Lalancette Jean-Simon , Belzile David , Cinq-Mars Alexandre , Dubois-Senechal Sacha-Michelle , Lemay Sylvain , Rimac Goran , Turgeon Pierre Yves , Morin Joelle , Bourgault Christine , Leblanc Marie-Helene , Dupuis Celine , Charbonneau Eric , Laflamme Maxime , bernier mathieu , Beaulieu-Shearer Alexander , Senechal Mario
Published: November 2024

Left ventricular assist devices (LVAD) are increasingly used in refractory heart failure, mainly as a bridge to transplant or as destination therapy. LVAD unloading of the left ventricle (LV) can also promote myocardial recovery leading to improvement of the LV systolic function, allowing LVAD explantation. However, parameters associated with LVAD weaning and long-term outcomes are not well documented. The aim of this study was to assess the clinical and echocardiographic characteristics of weaned patients and to evaluate their event-free survival post-explantation.

We conducted a single-center retrospective study recruiting patients who underwent a second or third generation LVAD implantation at a Canadian cardiology center between November 2009 and October 2021.

A total of 98 patients underwent LVAD implantation during this period. All patients were on guideline-directed medical therapy (GDMT). Fourteen patients (14%) had significant LV recovery and were explanted/decommissioned after a median support time of 309 days (range 55-595 days). Toxic cardiomyopathy, defined as abuse of amphetamines (n=2), energy drinks (n=2) or multiple substances (n=6), was the most likely diagnosis in 10 of the weaned patients (71%). The LVEF was significantly higher and the left ventricular end-diastolic diameter (LVEDD) was significantly lower in weaned patients compared to unweaned patients after 3 months of support. Myocardial recovery manifested as pump thrombosis in 4 of the weaned patients (29%). Prior to explantation, 12 patients had a decrease in GDMT doses to minimize post explantation vasoplegia. After explantation, median follow-up time was 40 months (range 8-109 months) and the majority of patients were anticoagulated for 3 months. At last follow up, the LVEF was 44±6% and no patient had a LVEF below 35%. All patients were NYHA I or II and no death, heart transplant, or mechanical support initiation occurred.

LVAD therapy can induce LV reverse remodeling leading to myocardial recovery in a significant proportion of patients, especially young patients with toxic and non-ischemic cardiomyopathies. Early reverse remodeling with decreasing LVEDD and improving LVEF at 3 months following implantation is associated with successful weaning. Pump thrombosis seems to be associated with LV reverse remodeling and weaning of mechanical support in certain patients. Weaned patients maintain satisfactory LVEF recovery after explantation and have good long-term event-free survival.
Abstract 4134824: Evaluation of ChatGPT-4.0 and Google Bard ‘s Capabilities in Clinical Decision Support in Cardiac Electrophysiology
Authors: Tieliwaerdi Xiarepati , Samra Gursharan , Mutabi Erasmus , Saleh Saleh , Liu Emerson
Published: November 2024

Background:
ChatGPT-4.0 and Bard have shown clinical decision support (CDS) potential in general medicine, but their role in EP is unknown. This study aims to evaluate ChatGPT and Bard’s CDS potential by assessing their accuracy in multiple-choice questions (MCQs), guideline recommendations (GRs) and treatment (Tx) suggestions.

Methods:
Two chatbots were tested with 15 clinical vignettes (CVs) and 47 case-related MCQs from Heart Rhythm Case Reports, focusing on ablation, arrhythmia and CIEDs management. CVs included narrative diagnostic images results. 3 tasks were performed: 1) Generating GRs, rated 0 for incorrect or correct but irrelevant to the primary problem, 0.5 for correct for the primary problem, 1 for case-specific (CS) if relevant to both the primary problem and concomitant conditions (e.g. afib with HF); 2) Suggesting Tx steps, scored 0 for incorrect, 0.5 for correct and 1 for CS. Tx was deemed correct if referenced in the case or guidelines, and CS if used in the case. For Tx responses not CS, a prompt was provided before reassessment. The prompt included one similar CV and its Tx from PubMed case reports. 3) Answering MCQs, rated 1 for correct and 0 for incorrect. Welch's T-test was used for analysis.

Results:
Bard outperformed ChatGPT in generating CS-GRs (P = 0.01). However, there was no significant difference in CS-Tx suggestions with a prompt (P value = 0.12, Figure 1C) or without a prompt (P value = 0.59, Figure 1A). When prompted for non-CS-Tx responses, ChatGPT significantly improved from 0.66 to 0.93 (P value = 0.02), suggesting an enhanced ability to provide CS-Tx plans post-prompt. In contrast, Bard showed no notable improvement (0.73 vs. 0.76, P value = 0.79, Figure 1B). Both chatbots demonstrated similar MCQ accuracy, with scores below 70%, indicating EP training gaps or the need for prompts to activate existing knowledge.

Conclusion:
This study showed Bard's superiority in generating GRs and ChatGPT's remarkable improvement in suggesting Tx when external knowledge is provided, revealing their CDS potential in specialized fields.
Abstract 4134873: Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk - A Systematic Review and Meta Analysis
Authors: Raja Sandesh , Raja Adarsh , Asghar Muhammad Sohaib , Shafique Muhammad Ashir , Saqlain Mustafa Muhammmad , Alim Ur Rahman Hafsah , Ahmed Muhammad , Fahim Muhammad Ahmed Ali , Azeem Bazil , Salman Madiha
Published: November 2024

Background:
Hypertriglyceridemia, a common lipid disorder linked to increased risks of cardiovascular diseases and metabolic syndrome, remains a global health challenge. Traditional treatments, though widely used, often have limited efficacy and adverse effects. Olezarsen, a novel antisense oligonucleotide, targets apolipoprotein C-III and shows promise in significantly reducing triglyceride levels.

Aim:
To conduct a meta-analysis comparing Olezarsen with placebo in patients with hypertriglyceridemia.

Methods:
We performed an extensive literature search of PubMed, EMBASE, and Cochrane Library databases up to May 2024 to identify studies comparing Olezarsen and placebo in patients with hypertriglyceridemia, irrespective of comorbid cardiovascular disease. Effect estimates were pooled using a random-effects model and reported as risk ratios (RR) for dichotomous outcomes and standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs) for each.

Results:
Three randomized controlled trials (RCTs) with a total of 334 participants were included. Olezarsen significantly reduced triglyceride levels at 6 months (SMD: -1.69; 95% CI -2.22 to -1.17; P < 0.00001;
Figure
) and 12 months (SMD: -1.64; 95% CI -2.22 to -1.07; P < 0.00001;
Figure
). VLDL levels also decreased at 6 months (SMD: -1.95; 95% CI -2.38 to -1.51; P < 0.00001) and 12 months (SMD: -0.83; 95% CI -1.13 to -0.53; P < 0.00001). Lipid profile improvements included reductions in total cholesterol, non-HDL cholesterol, and apoB levels, with increases in HDL cholesterol and apoA-1. Adverse events were comparable between Olezarsen and placebo, although serious adverse events were significantly higher in the Olezarsen group (RR: 2.55; 95% CI 1.17 to 5.58; p = 0.02).

Conclusion:
Olezarsen demonstrates significant efficacy in reducing triglyceride and VLDL levels while improving overall lipid profiles in hypertriglyceridemia patients. Despite higher rates of serious adverse events, its overall safety profile remains acceptable.
Abstract 4134926: Association of Eicosanoid Metabolites with Body Mass Index
Authors: Chitsazan Mandana , Parekh Juhi , Lau Emily , Alotaibi Mona , Yu Bing , Allen Norrina , Allison Matthew , Jain Mohit , Cheng Susan , Ho Jennifer
Published: November 2024

Introduction:
The specific molecular pathways from obesity to inflammation to cardiovascular disease remain unclear. Eicosanoids are a unique class of bioactive lipids that govern the upstream initiation of pro- and anti-inflammatory activity.

Objective:
We leveraged a novel lipidomic platform to quantify > 800 eicosanoid metabolites and examined their association with body mass index (BMI).

Methods:
We studied Multi-Ethnic Study of Atherosclerosis (MESA) participants with available samples for eicosanoid analysis. Eicosanoids and related metabolites were assessed using a directed, non-targeted mass spectrometry-based platform. We examined the cross-sectional association of eicosanoid metabolites with BMI using multivariable linear regression models. Analyses were considered significant at FDR q-value <0.01.

Results:
A total of 5101 individuals (age 63 ± 10 years; 53% women, 60% non-Whites) were included. The mean BMI was 28.3 ± 5.1 kg/m2. Of 811 eicosanoids analyzed, 255 showed a significant association with BMI (see Figure for putative metabolite identities; FDR q-value <0.01 for all). Derivatives of docosahexaenoic acid (DHA; 19,20 DiHDPA, β = - 0.206, standard error [SE] = 0.013) and eicosatetraenoic acid (11(S) HEPE, β = - 0.180, SE = 0.014) were associated with lower BMI. Linoleic acid derivatives (12,13 diHOME, an exercise-induced lipokine) had a similar association. Conversely, derivatives of linoleic acid (13-oxoODE, β = 0.241, SE = 0.01) and arachidonic acid (11-HETE, β = 0.236, SE = 0.017) were associated with higher BMI. Other derivatives of linoleic acid (15 (S) HETrE) and prostaglandin (11b PGF2α) were also associated with higher BMI.

Conclusions:
We found that specific eicosanoid metabolites, including DHA and linoleic acid derivatives with known anti-inflammatory, atheroprotective, and beneficial metabolic effects (e.g., 19,20 DiHDPA; 12,13 diHOME), were associated with lower BMI. By contrast, specific arachidonic acid and prostaglandin derivatives with known pro-inflammatory and adverse CV effects (e.g. oxylipin 11-HETE; PGF2α; 13-oxoODE) were associated with higher BMI. These findings further the understanding of specific inflammatory pathways underlying the development of obesity-related CVD.
Abstract 4134945: Biomechanical Impact of Crossing Neochords In Mitral Valve Repair Using Ex Vivo Mitral Valve Prolapse Models
Authors: Zhu Yuanjia , Huynh Chris , Wu Catherine , Park Matthew , Elde Stefan , Yajima Shin , Kim Joon Bum , Woo Y Joseph
Published: November 2024

Background:
Neochord repair is a common technique to mitigate mitral regurgitation (MR). Certain techniques, such as the loop technique, purposefully anchor all neochords to one papillary muscle head, generating crossed configurations. The objective was to evaluate the impact of crossing neochord on mitral valve (MV) biomechanics using ex vivo mitral valve prolapse (MVP) models.

Methods:
Twenty-four healthy porcine MVs were explanted. The valves were randomly assigned to generate A2 or P2 MVP models by transecting A2 or P2 primary and secondary native chords. For each model, the valves were further randomly assigned to neochord repair by crossing the medial-lateral plane or the anterior-posterior plane. Fiber Bragg grating force sensors were mounted to measure chordal forces. Data were collected using an ex vivo heart simulator for baseline, MVP, and neochord repair in the native and the crossed configuration. Statistical analysis was performed using repeated measures analysis of variance with post-hoc correction.

Results:
In the P2 MVP model, AP crossed configuration was effective in reducing MR (p=.003) compared with the native configuration (p=.004), but the medial-laterally (ML) crossed configuration was not effective in reducing MR (p=.07) compared with the native configuration (p=.05). In the A2 MVP model, anterior-posteriorly crossed configuration was associated with increased average neochordal force compared with the native configuration (0.16±0.06N vs. 0.09±0.07N, p=.05). The ML crossed configuration was also associated with increased average neochordal force compared with the native configuration (0.05±0.03N vs.0.03±0.03N, p=.03). Peak native secondary chordal forces were increased in the ML crossed configuration compared with the native configuration (0.76±0.45N vs. 0.61±0.38N, p=.05). No differences between the crossed and native configurations were observed in the P2 MVP model.

Conclusions:
Differences exist in P2 MVP model hemodynamics and A2 MVP model chordal forces when neochords were crossed compared with the native configurations. These findings may provide important biomechanics insight regarding neochord implantation techniques and repair durability.
Abstract 4134947: Explainable Machine Learning to Predict Heart Failure Outcomes Using Exercise and Clinical Data
Authors: Karanam Varsha , Magoon Matthew , Arunkumar Neha , Pattock Andrew , Dardas Todd , Boyle Patrick , Buber Yonatan , Leone David
Published: November 2024

Background:
Heart failure (HF) hospitalizations are associated with disease burden and cardiovascular mortality. International guidelines highlight cardiopulmonary testing (CPET) for risk stratification and prognosis in HF. Identifying individuals at risk could direct interventions to prevent admissions. This study uses explainable machine learning (XML) tools to identify CPET and clinical variables predictive of HF hospitalizations.

Hypothesis:
XML analysis of CPET parameters and clinical factors can yield accurate, patient-specific prediction of HF admission within one year.

Methods:
A retrospective single center review of 178 CPETs in patients referred for HF was completed. Clinical data within one year of CPET trained a boosted machine learning model (XGBoost). SHAP (Shapley Additive Explanations) explainability analysis emphasized key features for model predictions.

Results:
44 (24.7%) patients with CPET were admitted for HF within one year. The model predicted this outcome with an area under the receiver operating characteristic curve (AUC) of 0.772. SHAP analysis (Figure 1) selected factors for decision making: pulmonary artery systolic pressure (PASP) via cardiac catheterization or echocardiogram; oxygen consumption at the ventilatory threshold (VO
2
at VT); O
2
pulse at rest; ventilatory efficiency (VE/VCO
2
slope); minute ventilation per oxygen consumption at maximal exercise (VE/VO
2
max) during CPET; left ventricle end diastolic volume by echocardiogram; and sodium-glucose cotransporter-2 inhibitor usage. Peak VO2, predicted VO2, predicted O2 pulse, and VE/VCO2 slope were significant, consistent with past studies (Table 1).

Conclusion:
Our XML analysis emphasizes PASP (partially related to high left ventricular filling pressures) and VO
2
(at ventilatory threshold) as predictive for HF hospitalization within one year of CPET testing. Studies to prospectively evaluate these highlighted factors are needed to continue exploring predictive capabilities to tailor interventions.
Abstract 4134990: Body Fat Quantitation Predicts Progressive Cardiac Dysfunction with Age: Sex-Dependent Variations And Clinical Outcomes
Authors: Jiang Haowen , WONG JIE JUN , Tan Glades , Teo Loon Yee , Ewe See Hooi , Tan Ru , Gao Fei , Koh Angela
Published: November 2024

Background:
Among older adults whose body mass index (BMI) readings may be spuriously reduced due to loss of skeletal muscle, BMI alone may lack specificity for body fat quantitation. In addition, sex-based hormones differentially influence body fat composition between the sexes with aging. To evaluate the cardiometabolic effect of body fat on older adults, we hypothesize that sex would exert differential effects on baseline and progression of cardiac dysfunction in older adults.

Methods:
Community older adults without cardiovascular disease (CVD) underwent prospective transthoracic echocardiography with simultaneous body fat quantitation (body fat mass (BFM), percentage body fat (PBF), and waist-hip ratio (WHR) by bioimpedance, at baseline and five-year intervals. Mitral early diastolic inflow velocity to early diastolic annular tissue velocity (E/e') and early to late diastolic inflow velocity (E/A) ratios were recorded. Multivariable regression models were adjusted for significant clinical variables. Adverse clinical outcomes were defined as mortality or hospitalization during follow-up.

Results:
Baseline and interval annotation of 409 older adults (mean age 61±12.7 years, 52% females) demonstrated deteriorations in E/A ratios of -0.1 ± 0.3 and E/e' ratios of 1.8 ± 2.8, over a mean duration of 4.9 ± 0.4 years. Baseline BFM (β -0.01, p<0.001; β 0.023, p=0.352) and PBF (β -0.008, p=0.002; β -0.007, p=0.759) predicted interval changes in E/A but not E/e' respectively independent of covariates (Table 1). In sex-specific analyses, higher baseline PBF was associated with deteriorations in E/A (β 0.010, p=0.028) among women and E/e' among men (β -0.069, p=0.020). Increases in PBF over time were particularly associated with reductions in E/A among women (β -0.005, p=0.047) independent of higher baseline PBF, in addition to significant interactions between sex and PBF in predicting changes in E/A. (Figure 1). Higher baseline WHR predicted adverse clinical outcomes [w1] among women (HR 1.09, 95%CI 1.03-1.16, p=0.005).

Conclusion:
Baseline and longitudinal increases in fat quantity defined a trajectory of deteriorations in cardiac function among older adults, and prognosticated poorer future outcomes, particularly among women with central adiposity as represented by WHR. Refining CVD risk based upon quantitative sex-specific fat targets for older adults may be a strategy in the future.
Abstract 4135025: Inflammation-related 5-hydroxymethylation signatures as markers for clinical presentations of coronary artery disease
Authors: Xu Jing , Chen Hangyu , Lin Jian , Yang Yue-Jin
Published: November 2024

Background:
Coronary angiography, an invasive method, remains the gold standard technique for coronary artery disease (CAD) diagnosis in clinical practice. However, due to its invasive nature, it cannot be used for mass population screening. There is an urgent need in the clinical to identify new liquid biopsy molecular markers for screening patients with CAD.

Methods:
We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 724 CAD patients. To investigate the correlation between 5hmC modifications and CAD, we separated patients into training and validation cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict CAD patients in the validation cohort. Furthermore, we incorporated an external cohort comprising 167 samples to validate the reliability of our model.

Results:
We found that the differentially hydroxymethylated genes (DhMGs) in people with the normal coronary artery (NCA), nonfatal stable CAD (sCAD), non-ST-elevation myocardial infarction (NSTEMI), as well as ST-elevation myocardial infarction (STEMI) enriched in neutrophil-mediated inflammatory response pathways, and inflammation-related DhMGs can reflect the progression of atherosclerotic plaque. Furthermore, we used machine learning algorithms to develop a predictive model for predicting the occurrence of myocardial infarction (MI) based on 19 inflammatory markers, and the predictive model could effectively predict MI (NSTEMI and STEMI) (AUC = 0.913). Simultaneously, our model has demonstrated strong performance in external validation.

Conclusions:
We have identified a novel biomarker, the inflammation-associated 5hmC markers, which can reflect the clinical manifestations of CAD and can effectively predict the occurrence of MI.
Abstract 4135059: Enhanced Expression of iNOS is Associated with Aortic Valve Stenosis in Patients Undergoing Hemodialysis
Authors: Kashima Yumi , Matsumura Yoshiki , Kure Yusuke , Matsuo Masanori , Sakamoto Yuya , Nakagawa Masashi , Shimeno Kenji , Matsumoto Ryo , Abe Yukio , Naruko Takahiko
Published: November 2024

Background:
Patients undergoing hemodialysis (HD) have a greater prevalence of aortic valve calcification and aortic valve stenosis (AS). High prevalence and rapid progression of AS have been reported in patients undergoing HD. However, the precise mechanism of the relationship between HD treatment and rapid development of AS is still unknown.

Several findings suggest a pivotal role for oxidative stress in the progression and acceleration of atherosclerosis in patients undergoing HD. A considerable number of human diseases have an inflammatory component, and a key mediator of immune activation and inflammation is inducible nitric oxide synthase (iNOS). Overexpressed iNOS has been implicated in numerous pathogenetic processes, including coronary plaque destabilization. To elucidate the role of iNOS in the aortic valve of patients with AS, we studied its presence in aortic valve specimens from patients with AS undergoing HD.

Methods:
We enrolled 32 patients undergoing HD and 42 patients not undergoing HD who had severe AS and underwent AVR. Valve samples were analyzed immunohistochemically with antibodies against macrophages, microvessels, iNOS and 4-hydroxy-2-nonenal (4-HNE), an index of lipid peroxidation. Immunoreactivity was quantified with computer-aided polarimetry. Double immunostaining was also performed to identify cell types that stained positive for iNOS.

Results:
Quantitative analysis demonstrated that macrophage-, iNOS-, and 4-HNE-positive areas, as well as the number of microvessels, were significantly higher in patients with AS undergoing HD (macrophages,
P
<0.001; microvessels,
P
<0.05; 4-HNE,
P
<0.05; iNOS ,
P
<0.001). iNOS-positive areas were positively correlated with 4-HNE-positive areas (R=0.71,
P
<0.0001). Double immunostaining for both iNOS and macrophages identified iNOS-positive cells as macrophages.

Conclusions:
These findings indicate that accumulation of iNOS in macrophages may increase oxidative stress and contribute to the rapid progression of AS in patients undergoing HD.
Abstract 4135082: Small dense low-density lipoprotein cholesterol and risk of peripheral artery disease
Authors: Balling Mie , Nordestgaard Borge , Langsted Anne , Varbo Anette , KAMSTRUP PIA , Afzal Shoaib
Published: November 2024

Background:
High levels of small dense low-density lipoprotein (sdLDL) is a hallmark of dyslipidemia; however, studies on sdLDL cholesterol levels and risk of peripheral artery disease are sparse and results inconclusive.

Hypothesis:
We tested the hypothesis that higher levels of sdLDL cholesterol are associated with increased risk of peripheral artery disease in a primary prevention setting.

Methods:
We studied 31,036 individuals free of lipid-lowering therapy, ischemic stroke, and myocardial infarction at study entry in 2013-2017. All had fresh sample measurements of sdLDL cholesterol. During a median follow-up on 6.2 years, 155 were diagnosed with peripheral artery disease. The association was confirmed using ankle-brachial index (ABI) ≤ 0.9 as endpoint. Lastly, as comparison across different vascular beds risk estimates for myocardial infarction and ischemic stroke were calculated.

Results:
Higher levels of sdLDL cholesterol were associated with higher risk of peripheral artery disease and an ABI ≤ 0.9 illustrated by cubic splines multivariable adjusted for sex, systolic blood pressure, education, body mass index (BMI), diabetes, large buoyant LDL cholesterol, and age. Per 1 mmol/L (37 mg/dL) higher sdLDL cholesterol hazard ratio for peripheral artery disease was 2.01 (95% CI: 1.41-2.85) and odds ratio for an ABI ≤ 0.9 was 1.51 (95% CI: 1.07-2.14) in multivariable adjusted models. The cumulative incidence of peripheral artery disease was respectively 1.5%, 2.5%, and 3.5% for individuals having a sdLDL cholesterol in the 1
st
-50
th
, 51
st
-90
th
, and the 91
st
-100
th
percentiles at age 80. For the 91
st
-100
th
versus the 1
st
-50
th
percentile a hazard ratio on 2.51 (95% CI: 1.50-4.20) for peripheral artery disease, 2.18 (95% CI: 1.58-3.01) for myocardial infarction, and 1.85 (95% CI: 1.37-2.49) for ischemic stroke was found. Furthermore, the association of higher sdLDL cholesterol with increased risk of peripheral artery disease was robust in sensitivity analyses.

Conclusion:
Higher levels of sdLDL cholesterol were robustly associated with increased risk of peripheral artery disease in a primary prevention setting.
Abstract 4135142: Sex-Based Differences in In-Hospital Complications Among Older Patients With Prior Myocardial Infarction Undergoing Cardiac Resynchronization Therapy-Defibrillator Implantation; An Analysis of 13695 Procedures in the United States
Authors: Dhaliwal Jasninder , johal parampreet , Kumar Nomesh , Singla Rahul , Dhaliwal Kanwar Bir Singh , Verma Renuka , Ramphul Kamleshun , Sekhon Manraj , Rajotia Arush , Sakthivel Hemamalini
Published: November 2024

Introduction:
Cardiac Resynchronization Therapy-Defibrillator (CRT-D) use has increased over the past two decades. As this procedure often also involves patients with a prior history of myocardial infarction(MI), we aim to evaluate potential sex-based disparities in short-term complications among the elderly.

Methods:
Our sample consisted of patients ages >60 years with a prior history of myocardial infarction undergoing CRT-D. The data was extracted via the 2016-2021 National Inpatient Sample(NIS). Adjusted odds ratios(aOR) of in-hospital complications between Females and Males were estimated using multivariable regression analyses, taking into account potential confounders.

Results:
Out of 13695 CRT-D procedures among older patients (ages >60 years), 2880(21.0%) were Females, with 10815(79.0%) Males. The median age of all patients was 74.0 years(mean of 73.99 years). Females were at higher odds of experiencing cardiogenic shock (aOR 1.231, 95% CI 1.013-1.495, p=0.036), cardiac arrest(aOR 1.413, 95% CI 1.150-1.737, p=0.001), pericardial effusion(aOR 2.334, 95% CI 1.704-3.198,p=0.000), and pneumothorax(aOR 2.107, 95%CI 1.089-4.075, p=0.027) than Males. No differences were reported in events of acute kidney injury (AKI)(aOR 0.923,95%CI 0.832-1.024, p=0.132), acute ischemic stroke (AIS)(aOR 1.166, 95%CI 0.585-2.324,p=0.662), pleural effusion(aOR 0.827,95%CI 0.618-1.107, p=0.203), and sepsis(aOR 0.743,95%CI 0.506-1.092,p=0.130) between the two sexes. Furthermore, we found sex-based disparities in mortality as 1.6% of Females (vs. 1.0% of Males, aOR 1.729, 95% CI 1.161-2.576, p<0.01) did not survive their hospitalization.

Finally, our analysis noted that Males and Females did not have any differences in mean lengths of stay(LOS)(Males: 6.06 days vs. Females: 6.26 days, p=0.056).

Conclusion:
Our results confirm that among the elderly with a prior history of MI, Females are prone to a poor prognosis with multiple complications during CRT-D implantations, including pericardial effusion, cardiac arrest, cardiogenic shock, and all-cause mortality. It is vital to advocate for additional studies to understand the various factors predisposing females to these complications and bring forward adequate measures to prevent them.
Abstract 4135178: Short Term Outcomes Of Transcatheter Tricuspid Valve Interventions On Post-Procedural Length Of Hospital Stay, Readmissions For Heart Failure And Procedure Success If An Intracardiac Device Is Present: A Systematic Review And Meta-Analysis In A New Era Of Tricuspid Interventions
Authors: Kumanayaka Dilesha , Hernandez Perez Laura , Aiman Wajeeha , Abu ruman Yazeed , Chandra Aishwarya , Patel Palak , Patel Aharnish , Suleiman Addi
Published: November 2024

Background:
Tricuspid regurgitation (TR) is no longer considered forgotten. Transcatheter tricuspid valve repair/replacement (TVRR) has become widely accepted as gauged by clinical outcomes. FDA approved two tricuspid valve devices for the purpose of improving quality of life and not necessarily to improve TR severity. We aim to support evidence-based use of TVRR, by summarizing the latest evidence on the clinical effectiveness in terms of post-procedural length of hospital stay, readmissions for heart failure and procedure success if an Intracardiac device is present.

Methods:
We searched Pubmed, Embase and Cochrane databases and performed a meta-analysis of the included cohort studies using a fixed-effects model. Studies were excluded if they did not present an outcome in each intervention group or did not have enough information required for continuous data comparison. We performed a meta-analysis of hazard ratio (HR) for two outcomes and odds ratio (OR) for one outcome using the random effects model to remove inconsistency and compared the results with fixed effects model. The compared findings of both methods were similar. The variables used for analysis were number of events in exposure group and total amount of events. All data analyses were performed using MedCalc® Statistical Software version 22.023.

Results:
Of 161 potentially relevant studies, 8 retrospective studies with a total of 1,717 patients were included in the meta-analysis. Procedure (TVRR) success was associated with fewer readmissions for heart failure in all three studies included in the analysis of pooled HR (HR = 0.46, 95% confidence interval [CI]: 0.33 - 0.63, p<0.001). Procedure success was also associated with shorter length of hospitalization post-procedure in all three studies included in the analysis of pooled HR (HR = 0.48, 95% CI: 0.33 - 0.72, p<0.001). There was no significant association between procedure success and having an intra-cardiac device in all three studies included in the analysis of pooled OR (OR = 0.79, 95% CI: 0.56 - 1.12, p=0.18).

Conclusion:
Our meta-analysis showed that successful TVRR for high risk patients with severe TR is associated with significant positive outcomes on post-procedural length of hospital stay and readmissions for heart failure, regardless of presence of an intracardiac device. With emerging improvements in device technology and procedural performance, TVRR should be considered in severe and functional TR, to improve clinical prognosis.
Abstract 4135194: Safety and Efficacy of Mechanical Circulatory Support during VT ablation
Authors: Pelling Mary , Debakey Michael , Sajja Aparna , Bhatia Neal , Shah Anand
Published: November 2024

Introduction:
Ventricular arrythmias are prevalent in patients with advanced heart failure and associated with increased mortality. Outcomes of electrophysiology ablation on patients requiring mechanical circulatory support (MCS) are not well described. We aimed to analyze the safety and efficacy of ventricular tachycardia (VT) ablation in patients requiring MCS at the Emory system.

Methods:
Patients were identified via retrospective chart review from October 2022 through August 2023. Patients who underwent VT ablation with the support of Impella, left ventricular assist device (LVAD), intra-aortic balloon pump (IABP), and venoarterial extra-corpeal membrane oxygenation (VA ECMO), or any combination of these were included.

Results:
A total of 7 patients of average age 56 ± 10 years, predominantly male (85.7%), with cardiomyopathy of mean EF 18.6% +/- 8.5 (ischemic 71.4%) underwent MCS supported VT ablation. One patient had 2 separate VT ablation procedures for refractory VT. Of these 8 procedures, 4 utilized a single type of MCS (2 impella, 2 LVAD) while 4 used a second type of MCS in combination with an Impella (2 impella RP, 1 VA ECMO, 1 IABP). Success at time of ablation was present in 75% of cases. Average time of outpatient follow up was 82 ± 31 days. At time of follow up, 50% of patients remained free of VT or with a single VT episode not requiring implantable cardioverter-defibrillator (ICD) shock. One patient had gone on to undergo successful heart transplantation. Procedural complications were noted in one patient, who suffered cardioembolic cerebrovascular accident (CVA) 2 days post-op. Transthoracic echo (TTE) 5 days post-op revealed LV mural thrombus as likely etiology of CVA.

Conclusion:
While there are no clear guidelines directing the use of MCS during VT ablation, our single academic institution experience suggests safety and feasibility of its use to support select, high risk cases.
Abstract 4135211: Children with the D801N Variant of the
ATP1A3-
Encoded Sodium-Potassium ATPase Alpha-3 Subunit Demonstrate Paradoxical QT Response to Bradycardia and Increased Ventricular Arrhythmia Risk
Authors: Srour Meredith , Bidzimou Minu-Tshyeto , Mitchell Saige , Muralidharan Padmapriya , Moya-Mendez Mary , Mikati Mohamad , Landstrom Andrew
Published: November 2024

Introduction:
Alternating hemiplegia of childhood (AHC) is a rare condition most frequently caused by mutations in
ATP1A3,
encoding for the alpha-3 subunit of Na
+
/K
+
-ATPase, and D801N is the most common variant. Individuals with ATP1A3-D801N have shorter corrected QT (QTc) than those with other variants and can experience ventricular arrhythmias following bradycardia; however, the mechanism of why this occurs is unknown.

Goals:
To analyze how QT and QTc change with heart rate in ATP1A3-D801N compared to healthy individuals.

Hypothesis:
Individuals with ATP1A3-D801N have increased shortening of QT and QTc at lower heart rate.

Methods:
In this retrospective observational study, patients seen for evaluation of AHC at Duke University Medical Center were categorized by genotype: ATP1A3-D801N, ATP1A3 non-D801N single nucleotide variant,
ATP1A3
loss-of-function variant, and genotype negative. A cohort of matched healthy children was also compiled. We collected average heart rate, QT, and QTc measurements over 5-minute intervals from Holter recordings using HScribe
TM
software and conducted manual blinded validation to ensure accuracy. We then used linear regression to investigate the relationship between heart rate, QT, and QTc.

Results:
The cohort consisted of 44 patients with
ATP1A3
-related phenotypes with 81 total Holter recordings (52.27% female; mean age at first Holter 8.04 years), compared to 36 healthy individuals with 57 total Holter recordings (52.78% female; mean age at first Holter 9.84 years). Patients with ATP1A3-D801N showed diminished prolongation of QT with decreasing heart rate, manifested as a reduced mean slope for heart rate vs QT compared to healthy (-0.85 ± 0.46 vs -1.52 ± 0.42, p<0.0001). This blunted QT response resulted in paradoxical shortening of QTc at lower heart rate, demonstrated by an increased mean slope for heart rate vs QTc compared to healthy (0.80 ± 0.51 vs 0.22 ± 0.43, p<0.0001). Further, patients with
ATP1A3-
related phenotypes and very short baseline QTc showed increased shortening of QT and QTc at lower heart rate compared to those with normal QTc (p=0.0025 and p=0.0013, respectively).

Conclusions:
Children with AHC and ATP1A3-D801N demonstrate a paradoxical shortening of QT and QTc with slowing of heart rate. The impaired prolongation of QT and resultant further shortening of QTc increase the risk of arrhythmia. We put this forward as a novel mechanism of sudden cardiac arrest in patients with
ATP1A3
mutations.
Abstract 4135212: An Overlap Between Takotsubo Cardiomyopathy and Hypertrophic Obstructive Cardiomyopathy Causing Dynamic Left Ventricular Outflow Tract Obstruction: A Unique Case Report
Authors: Sharif Muhammad Hammad , Latifi Ahmad Nawid , Naeem Nauman , baibhav bipul , Khaleeque Madeeha , Sanjeevi Aditya
Published: November 2024

Background:
Takotsubo cardiomyopathy (TC) can cause dynamic left ventricular outflow tract (LVOT) obstruction leading to cardiogenic shock. Due to differential wall-motion abnormalities, flow acceleration in the LVOT can lead to systolic anterior motion (SAM) of the mitral valve which worsens LVOT obstruction and leads to hemodynamic compromise. We present a case of overlap between TC and hypertrophic obstructive cardiomyopathy (HOCM) with worsening LVOT obstruction leading to cardiogenic shock.

Case:
A 76-year-old female presented with typical chest pain, nausea, and worsening shortness of breath. On examination, she was hypotensive and cold to touch. EKG showed T-wave inversions in lateral leads with elevated cardiac troponins. Coronary angiogram showed non-obstructive coronary artery disease, and right heart catheterization revealed elevated filling pressures. Transthoracic echocardiogram (TTE) showed septal hypertrophy and SAM of the mitral valve causing dynamic LVOT obstruction (Figure 1) and ejection fraction (EF) of 20%. TTE with contrast showed apical ballooning consistent with TC (Figure 2).

Decision Making:
Initially with diuresis, she became hypotensive so it was stopped and she received controlled intravenous fluids along with phenylephrine to reduce LVOT obstruction. Her blood pressure improved and she was started on low-dose metoprolol succinate along with ivabradine to reduce heart rate. She tolerated this therapy and hemodynamics stabilized.

Conclusion:
Cardiogenic shock can be a severe complication of TC. Early detection of LVOT obstruction in cardiogenic shock is important as traditional management strategies of increased inotropy and reduction of afterload can be fatal in these cases. The treatment strategy focuses on reducing the LVOT gradient and includes fluid administration to increase preload, beta-blockers to increase diastolic filling time, and vasopressors to raise afterload.