bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18520: Impaired Ubiquitin-Proteasome Function in Right Ventricular Myocardium Correlates to Postoperative Outcomes in Tetralogy of Fallot
Authors: Edwards Jonathan J , Yang Yifan , Uy Genevieve , Rajagopal Hari , Friedberg Mark K , Arany Zoltan , Reddy Sushma , Mercer-Rosa Laura M
Published: December 2023

Introduction:
At the time of initial repair, patients with Tetralogy of Fallot (TOF) undergo a sudden shift from a pressure to volume loaded right ventricle (RV). It is difficult to predict how TOF RVs will respond to this hemodynamic transition. Identifying mechanisms and targets may enable interventions to improve outcomes.

Hypothesis:
RV myocardial gene expression profiles at the time of TOF repair correlate to pre- and early postoperative clinical outcomes.

Methods:
RNAseq was performed from RV myocardium resected at the time of initial TOF repair (n=44). Gene expression profiling was performed using a weighted gene correlation network analysis (WGCNA) against pre- and post-op clinical variables. Mouse pulmonary artery band (PAB, n=9) stratified by degree of RV dilation was used to correlate pathways.

Results:
WGCNA identified a gene module that was associated with younger age at repair and worse TOF postop outcomes (prolonged milrinone, decreased right atrial and right ventricular strain) without a concomitant association with preop oxygen saturation. Biological process gene-set enrichment analysis using the 2023 Gene Ontology library revealed enrichment of regulators for ubiquitination, cell cycle/mitosis, DNA repair, microtubule polymerization, and Rho/GTPase. PAB mouse RV demonstrated a RV-dilation severity-dependent increase in bound ubiquitin (R
2
=0.61, p=0.01) and loss of free ubiquitin (R
2
=0.72, p=0.004; Figure).

Conclusions:
WGCNA reveals a RV myocardial gene expression profile that is associated with preoperative characteristics and early postoperative outcomes, and which is enriched for ubiquitination regulators. The PAB mouse recapitulates a severity-dependent increase in bound ubiquitin and loss of free ubiquitin which is consistent with literature suggesting proteostatic dysfunction and accumulation of misfolded proteins in RVF. Targeting proteostatic disruption prior to TOF repair may improve postoperative outcomes.
Abstract 18533: Exploring the Rising Incidence of Myocarditis and Other Cardiovascular Adverse Events of Nivolumab and Ipilimumab: Analysis of FDA Adverse Event Reporting System Database
Authors: Khanal Resha , Oli Sharad , Rajak Kripa , Halder Anupam , Hufdhi Raied , BHANDARI BINITA , Oli Shital , Alraies M Chadi C
Published: December 2023

Introduction:
Nivolumab and Ipilimumab are human monoclonal antibodies that target cell surface PD1 and anti-CTLA-4 receptors respectively. Nivolumab and ipilimumab combination is used for metastatic small cell lung carcinoma, advanced renal cell carcinoma and metastatic melanoma. The pre-approval CHECKMATE trials have underestimated the occurrence of cardiovascular adverse events (AEs). In contradiction, post-marketing studies have demonstrated a higher incidence of cardiac AEs, particularly myocarditis.Therefore, it is important to establish a post-marketing safety profile of these medications.

Methods:
We investigated the cardiovascular AEs of nivolumab and ipilimumab using U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Healthcare professionals (HCPs) reported 79.73% and 80.92% of AEs until March 2023 for nivolumab and ipilimumab respectively. We conducted further subgroup analysis of cardiovascular AEs in male, females as well as in three age groups: 18-64, 65-85 and >85 years.

Results:
Amongst the cardiovascular AEs reported by HCPs, myocarditis was reported in 905 (1.55 %) in nivolumab vs 445 (1.72%) in ipilimumab group. There were higher reports of other cardiovascular AEs including heart failure (1.15% vs 0.74%), pericarditis/pericardial effusion (1.19% vs 0.6% ), myocardial infarction (0.18% vs 0.71%), cardiomyopathy (0.36% vs 0.29%), cardiac arrest (0.41% vs 0.53%) and cardiac death (0.01% vs 0.02%) in nivolumab vs ipilimumab. On sub-group analysis, we observed higher incidence of myocarditis in females (1.54% vs 1.6%) males (1.73% vs. 1.84%) and in patient with age 18-65 years (1.17% vs 1.15%) in both nivolumab vs ipilimumab group as compared to previous studies.

Conclusions:
The reported events of myocarditis were significantly higher in FAERS reporting as compared to the CHECKMATE trials (<1%) in both nivolumab and ipilimumab groups. Clinicians need to be vigilant in detecting immune-mediated myocarditis, as it often manifests with nonspecific symptoms, with early onset and rapid progression. Given the growing utilization of these medications, it is imperative to conduct additional randomized controlled trials to gain a better understanding of their cardiovascular safety profile.
Abstract 18559: Sex Differences In Acute Myocardial Infarction Related Cardiogenic Shock Across Different Levels Of Care
Authors: Datta Sajal , Sharma Apurva , Roslin Kylie , Smoller Rebecca , ahmad sana , Mokhtari Moein , Stevens Gerin R , Maybaum Simon , Alvarez Villela Miguel
Published: December 2023

Background
Previous registry data have suggested important sex-based differences in management and clinical outcomes for patients with acute myocardial infarction related cardiogenic shock (AMI-CS).

Methods:
We classified 11 hospitals in a metropolitan health network as different levels of care (LOC) for CS based on their highest mechanical circulatory support (MCS) capability; L1: Durable LVAD, L1A: ECMO, L2: Impella. We identified all patients ≥ 18 years of age treated for AMI-CS (ICD-10 diagnosis codes) from 2016 to 2022. Sex differences in management and hospital outcomes are reported. Descriptive statistics and logistic regression were performed using PRISM version 9.

Results:
In our cohort (n=1,956), women were a minority in L1 (30%) and L1A (31%) and L2 (41%) and were older with decreasing LOC, L1: 72y. (61-81), L1A: 74y. (64-82) and L2: 81y. (72-88), p<0.01 for trend.Across LOC, left heart catheterization (LHC) and percutaneous coronary interventions (PCI) were used similarly in women and men, while coronary artery bypass grafting (CABG) in surgical centers (L1 and L1A) and MCS in PCI centers (except L1A) were used more frequently in men (Figure). After adjustment for LOC and other relevant covariates, female sex (aOR: 1.35, 95%CI: 1.09-1.67; p=0.007), age (aOR: 1.04, 95%CI: 1.03-1.05, p<0.001) and admission cardiac arrest (aOR: 5.36, 95%CI: 3.63-8.54, p<0.001) were associated with higher hospital mortality.

Conclusion:
In a metropolitan health system, despite similar rates of LHC and PCI across different LOC, women with AMI-CS received less CABG and MCS than men and had higher adjusted hospital mortality.
Abstract 18568: Machine Learning Model for the Prediction of Early Discharge of Patient Underwent Transcatheter Aortic Valve Replacement Using Electronic Medical Record
Authors: Li Xiang , Ren Hui , Sun Yee-Ping , Scirica Benjamin , Li Quanzheng
Published: December 2023

Introduction:
With the increasing experience in TAVR, early discharge (within 24 to 72 h) has become a goal to accelerate patient recovery. Several studies suggest the possibility of safe, early discharges. But there is little consensus and considerable variation in early discharge protocols. Optimizing patient selection for early discharge can avoid prolonged hospital stays and save substantial costs without sacrificing patient safety.

Hypothesis:
The decision for early discharge after TAVR can be modeled and predicted by a machine learning model based on EMR data.

Methods:
Detailed demography, laboratory, medications, and comorbidities data from the EMR of all 1075 TAVR patients at Brigham and Women's Hospital from 2017-22 were included in a Random Forest machine learning model to make a binary prediction of whether the patient will be discharged within 36 hours after the procedure. We performed a 10-fold cross-validation experiment using the proposed model on the 1075-patient data. Receiver-operating characteristics (ROC) evaluated the prediction accuracy and uncertainty of the model, and clinical outcomes of patients with early discharge were evaluated by 6-month readmissions.

Results:
The mean age was 81± 9 years; 57% were male. The median length of stay was 51.3 hours. A total of 481 (44.7%) were discharged within 36 hours. Only 12 patients in this cohort were admitted with 24 hours. The average area under the ROC curve (AUC) of the 10-fold cross-validation was 0.83 (SD 0.04). (Figure) A total of 76 (7.1%) patients were readmitted due to cardiovascular reasons within 6 months, including 16/481 (3.3%) early-discharge patients vs. 60/594 (10.1%) non-early discharge patients (p<0.001).

Conclusions:
Our model accurately predicts early (36 hours) discharge after TAVR, indicating the feasibility of utilizing machine learning to develop an EMR-based patient risk stratification and early discharge protocol.
Abstract 18574: Association Between Left Ventricular Diastolic Function and Right Ventricular Morphology and Function Assessed With Automated 3D Software Analysis
Authors: Romero Pabon Ardel J , Lo Kevin B , Alzubi Jafar , Port Zachary A , Morris Sarah , Clift Bridget , Friend Evan , Pressman Gregg S
Published: December 2023

Background:
Left ventricular (LV) diastolic dysfunction (DD) is a hallmark of heart failure with preserved ejection fraction (HFpEF). Right ventricular (RV) function is a strong and independent prognostic factor in this population, but its correlation with LV DD has not yet been explored. 3D echocardiography allows for accessible, accurate, reproducible analyses of RV function. Our study aims to assess the association between LV diastolic function and RV function (measured via automated 3D echocardiography software)

Hypothesis:
The RV enlarges and its systolic function decreases, in a graded fashion, with increasing degrees of LV DD

Methods:
We conducted a prospective, single-center, cross-sectional cohort study in patients with clinically indicated echocardiography and 3D RV assessment. We excluded patients with non-WHO group 2 pulmonary hypertension, non-sinus rhythm during echocardiogram, and those with a LVEF <40%. We conducted an interim analysis of the first 187 patients. Patients were stratified according to DD grading, and different RV parameters were compared using ANOVA

Results:
187 patients underwent interim analysis, 65% were women. Mean age 60±17 years, 64% African-American, 16% Hispanic, 12% Caucasian. Mean BMI 29±6 kg/m
2
. Mean LVEF and LV GLS were 57±10% and -17.7±3.6, respectively. A graded worsening in RV systolic function and morphology were noted in patients with DD. Patients with grade II/ III DD had worse RV EDV (146±42 mL), RV FAC (32±9%), TAPSE (19±5 mm), and RVEF (40±9%), than patients without DD (RV EDV 114±36 mL, p=0.0011; RV FAC 39±7.4%, p<0.001; TAPSE 21±5 mm, p<0.001; and RVEF 47±8%, p<0.001), and grade I DD

Conclusion:
Our results suggest that there is a graded worsening in the RV function and morphology as LV diastolic function worsens in patients with preserved EF. This denotes the importance of widespread, accurate, and reproducible RV assessment during standard echocardiography
Abstract 18584: Predictive Accuracy Of The Pooled Cohort Equations For Estimating Atherosclerotic Cardiovascular Disease Risk Among Women Exposed To Potentially Cardiotoxic Breast Cancer Therapies
Authors: Patterson Vanessa P , Anderson Heather , Saba Laura , Kondapalli Lavanya
Published: December 2023

Introduction:
Risk estimation is a critical component in clinical decision making for preventive cardiovascular care. Suboptimal identification and management of cardiovascular disease (CVD) risk, may contribute to excess CVD morbidity and mortality among breast cancer (BC) patients and survivors. This study aimed to assess the performance of the Pooled Cohort Equations (PCEs) in predicting atherosclerotic cardiovascular disease (ASCVD) events among a real-world population of adult women treated for BC.

Methods:
Using electronic medical record data collected between Jan. 1, 2011 and Jan. 31, 2023, this external validation study retrospectively identified a cohort of BC women, age 40-79, without history of ASCVD in the one year prior to initiation of a potentially cardiotoxic BC therapy. For all cohort members with cholesterol and blood pressure measurements recorded within one year prior to the index cancer therapy exposure (n=1,239), a 5-year ASCVD risk estimate was calculated. Predictive accuracy of the risk estimate was assessed using a Poisson model-based framework for calibration, including evaluation of calibration-in-the-large, the calibration slope, and calibration plots. To account for potential biases related to informative censoring, calibration was assessed among an inverse probability of censoring weighted (IPCW) pseudopopulation with stabilized and unstabilized weights, and a complete case cohort (n=306).

Results:
Among the IPCW pseudopopulation, calibration-in-the-large, expressed as a standardized incidence ratio, was 1.85 (95% CI: 1.73, 1.98), indicating that, on average, women in this subpopulation experience a significantly higher number of ASCVD events than expected from baseline PCE risk estimates. The calibration slope, estimated at 0.55 (95% CI: 0.45, 0.66), and evaluation of calibration plots, further indicate particularly poor performance of the PCEs at low and high levels of estimated risk. Findings were consistent across the assessed populations.

Conclusions:
When calculated prior to initiation of a potentially cardiotoxic BC therapy, the PCEs significantly underestimate 5-year ASCVD risk for BC women, indicating this commonly used ASCVD risk estimate is poorly calibrated for this subpopulation.
Abstract 18602: A Rare Case of Ehrlichiosis Induced Myocarditis
Authors: Watson Christopher , Sanchez Josue , Atalla Jasmyn , Modi Ritu
Published: December 2023

Description of Case:
A 64-year-old female presented with progressively worsening shortness of breath, headaches, weakness, intermittent confusion, and persistent fevers. Laboratory work-up revealed leukopenia, thrombocytopenia, elevated transaminases, negative viral panel, and elevated CRP. Chest CT revealed ground glass opacities and bilateral interlobular thickening. TTE obtained was normal. She was started on empiric meningitis treatment. She was transferred to the ICU after becoming more hypoxic and hypotensive. Further history revealed recent tick exposure while visiting the eastern North Carolina woods. Doxycycline was started for suspected tick-borne disease on day 2 of her ICU stay. LP was non-revealing. Her course was complicated by development of inferolateral ST segment elevation on EKG. Initial troponin I level was 155.66 ng/mL peaking at 209.24 ng/mL (reference range <= 0.03 ng/mL). Cardiac catheterization revealed no epicardial coronary disease. Repeat TTE showed a decreased LVEF at 25-30% and global hypokinesis. Cardiac MRI revealed evidence of an inflammatory myocardial process, myocardial edema and epicardial fibrosis. The patient had a positive Erhlichia chaffensis IgG antibody titer and Ehrlichia chaffensis DNA polymerase chain reaction was positive. She demonstrated improvement with continuation of doxycycline. Heart failure guideline directed medical therapy was initiated prior to her discharge.

Discussion:
Ehrlichia infections occur primarily in areas of south and central United States. Transient flu-like symptoms are the most typical manifestations, but more severe complications can occur such as meningoencephalitis, respiratory failure, coagulopathy, myocarditis and death. There are only a few documented cases of myocarditis due to Ehrlichia infections. If not recognized early, myocarditis can be a serious and fatal complication of ehrlichiosis, even in immunocompetent patients. A high level of suspicion for this should be kept in the differential for patients with cardiac manifestations presenting from endemic areas, especially during warmer seasons. Doxycycline therapy should be started promptly for clinical suspicion of Ehrlichia infection.
Abstract 18610: Focal Pericoronary Adipose Tissue Evaluated by Electron Density Numbers on Non-Contrast Spectral Computed Tomography Was Associated With Coronary Arterial Plaques: A Site-by-Site Analysis
Authors: Funabashi Nobusada , Shukuya Atsushi , Asano Hiroki , Kawamura Akio , Mizuno Naoko
Published: December 2023

Introduction:
Inflammation in pericoronary adipose tissue (PCAT) around the coronary arterial wall causes coronary arterial sclerosis. Many studies evaluated the relationship between total PCAT volume and coronary arterial sclerosis on a patient-by-patient basis. Hypothesis: Inflammation in PCAT may occur focally in coronary arterial system to which coronary arterial plaques localize. Using novel spectral CT, based on electron density number (EDN) as a new parameter, the focal characteristics of PCAT were evaluated.

Methods:
17 patients (10 males, mean age 70 years) underwent cardiac spectral CT (7500, Philips, Tokyo, Japan). From non-contrast data, EDNs of PCAT were determined at a 1) right side site and 2) left anterior side site of a proximal portion of right coronary arteries (RCA), 3) anterior side site of the left main coronary arteries, 4) left side site of a proximal portion of the left circumflex artery, and left side site of a distal portion of the RCA (five sites each patient). We also evaluated coronary arterial plaques on enhanced CT images at five corresponding sites for which EDNs were determined.

Results:
For a total of 85 sites among 17 patients using enhanced CT, 31 sites had no plaques (group 1), 14 sites had only non-calcified plaques (group 2), 20 sites had only calcified plaques (group 3), 16 sites had mixed plaques (group 4), and four sites had stent implantations (group 5). The mean of EDNS (%EDW) for 81 sites, excluding four sites with a stent implantation, were 93.5, 93.3, 93.2, and 93.8 in groups 1-4, respectively (P=NS). For a total of 81 sites, excluding four implantation sites, we evaluated the relationship between age and EDNs in groups 1-4. Positive correlations were observed in group 1 (R= 0.40), and 3 (R= 0.40), however negative correlation was observed in group 2 (R= -0.22) and 3 (R= -0.22) between age and EDNs. No significant differences in EDNs were noted between males and females (P=NS).

Conclusions:
This is the first study in which focal PCAT was evaluated by EDNs and the relationship to coronary arterial plaques determined by site-by-site analysis. This new CT parameter may evaluate the status of PCAT and be a predictor of the future occurrence of coronary arterial plaques, which are related to PCAT inflammation even on non-contrast CT alone.
Abstract 18612: Stem Cell-Derived Extracellular Matrix as a Treatment for Cardiac Remodeling in Post-MI Hearts: A Pilot Study
Authors: Broadwin Mark , Xu Cynthia , Harris Dwight , St Angelo Katerina , Sellke Frank W , Morgan Jeffrey , Abid Ruhul
Published: December 2023

Introduction:
Post-myocardial infarction (post-MI) cardiac remodeling and decline in cardiac function remains a vexing problem. Tissue engineered extracellular matrix (ECM) has been used in the past but was restricted by the manufactured structure and mechanical limitations. Here, we use a novel ECM substrate generated by self-assembled cells seeded into spherical molds, that are devoid of the hierarchical structure of ECM fabrication, as a treatment for post-MI cardiac remodeling.

Hypothesis:
Intramyocardial (IM) injection of ECM particles will result in improved cardiac function and reduced infarct size in post-MI hearts.

Methods:
Human bone marrow mesenchymal stem cells were cultured and ECM particles were isolated, seeded into micro molds, purified, and characterized. ECM particles were suspended at a concentration of 63,400 particles per mL to create an injectable solution. WT mice underwent left anterior descending (LAD) artery ligation followed by IM injection of 10uL of saline control (n=3) or ECM solution (n=7) to the infarcted area (Figure 1A). Mice then underwent post-operative day 3 (POD 3) and POD 7 echocardiogram to determine changes in cardiac function.

Results:
There was a trend in improving ejection fraction (EF) in ECM injection group compared to control injection in post-MI at POD 3 while no difference was seen at POD 7 (Figure 1B). No difference in fractional shortening (FS) was observed at POD 3 or POD7 (Figure 1C). Echos at POD 14, POD 21, and POD 28 and additional animals will be added to increase study power.

Conclusion:
IM injection of ECM trends towards mitigating decline in EF at POD3 and does not affect FS in post-MI hearts. These results are likely underpowered (n=3 versus n=7) and may be a portent of significant myocardial protection post-MI. Our ongoing studies (n=10 per group) investigating the mechanisms by which ECM injections assuage ischemic insult to the myocardium may represent a future strategy for clinical therapy.
Abstract 18631: Mechanistic Insight on the Protective Role of Microbiome-Derived Butyrate in Pulmonary Hypertension
Authors: Pulgarin Andres , Alabdallat Mohamad , Methe Barbara , Morris Alison , Al Ghouleh Imad
Published: December 2023

Introduction:
Endothelial cell (EC) dysfunction is increasingly recognized as a precipitating event in Pulmonary hypertension (PH), a progressive, severe disease characterized by high blood pressure in the pulmonary circulation and excessive pulmonary vascular remodeling and inflammation. Microbiome-derived metabolites are altered in PH but their role in this disease remains poorly understood. Butyrate, a microbiome-derived short-chain fatty acid (SCFA) with biological activity, has been associated with benefit in cardiovascular diseases such as atherosclerosis. We aimed to test whether and how butyrate plays a protective role in PH.

Results:
PH-related inflammatory cytokine IL1β (10 ng/ml) increased expression of mesenchymal markers fibronectin, N-cadherin and transgelin (SM22) in human pulmonary arterial EC (HPAEC), consistent with induction of endothelial-to-mesenchymal transdifferentiation (EndMT). Butyrate (given as sodium butyrate, NaB; 2mM) attenuated this IL1β -induced upregulation (p<0.01, p<0.001, p<0.001 for each gene, respectively). Likewise, butyrate inhibited IL1β-induced upregulation of b-catenin (p<0.001), an important mediator of EndoMT. We previously showed that butyrate reversed IL1 β-induced downregulation of the PDZ protein EBP50, which we showed as a critical modulator of EndMT. In vivo, butyrate (NaB, 150mM) reversed PH phenotypes in wildtype mice (WT) following hypoxia exposure. In contrast, this reversal was attenuated in EBP50 heterozygous mice (Het, 50% EBP50 expression vs. WT) under hypoxia supplemented with butyrate. Similarly, butyrate reduced the number of circulating monocytes in hypoxia exposed WT but not Het mice.

Conclusions:
Collectively our results demonstrate that butyrate attenuates PH potentially via protecting against pulmonary vascular endothelial reprogramming and myeloid cell induction, through a mechanism that involves EBP50. These findings support the possible therapeutic benefits of butyrate in PH and shed mechanistic insight on the underlying cellular pathways propagating butyrate protection.
Abstract 18638: Myocardial Infarction Induces Dysfunction of Endothelial Colony Forming Cells With Independence of Common Cardiovascular Comorbidities
Authors: Jimenez Trinidad Francisco Rafael , Arrieta Ruiz Marta , Solanes Nuria , Llonch Bertran Blanca , Vea Angela , Roque Merce , Freixas Xavier , Ortega-Paz Luis G. , Rodriguez Arias Juan Jose , Brugaletta Salvatore , Sabate Manel , Dantas Ana Paula V , Tura Olga , Rigol Montserrat
Published: December 2023

Introduction:
Endothelial Colony Forming Cells (ECFCs) present a dysfunctional and senescent phenotype in ischemic heart disease. However, the effect of myocardial infarction (MI), independently of common cardiovascular comorbidities (CCVC), on ECFCs functionality has not been evaluated up to date.

Hypothesis:
MI induces dysfunction of ECFCs with independence of CCVC

Methods:
To determine the potential effect of MI on ECFCs, human ECFCs (hECFCs) were isolated from peripheral blood from healthy volunteers (n=6), patients immediately after MI (n=6) (AMI-hECFCs) and patients 6 months after MI (n=6) (CMI-hECFCs). To determine the effect of MI on ECFCs impairment, isolated from the effect of common cardiovascular comorbidities that are found in patients, 6 healthy pigs were subjected to 90 minutes of myocardial ischemia by coronary balloon occlusion followed by reperfusion. Porcine ECFCs (pECFCs) (n=6) were isolated from blood samples before the MI and 1 month after the procedure (CMI-pECFCs) (n=6). For all groups, the following parameters were determined: days until colonies appearance, morphometry, percentage of senescent cells, and migratory, proliferatory and angiogenic capacities.

Results:
Both CMI-hECFCs and CMI-pECFCs showed a delayed time until colonies appearance (p-ANOVA=0,0117 and p-ANOVA=0,0159 respectively) but no differences were found in AMI-hECFCs. AMI- and CMI-hECFCs showed changes in their area and shape, but only shape changes were observed in CMI-pECFCs. In terms of senescence, both AMI- and CMI-hECFCs, but not CMI-pECFCs, presented an increment of senescence (p-ANOVA= 0,0011). In terms of functionality, AMI- and CMI-hECFCs and CMI-pECFCs showed a significant reduction of angiogenesis and proliferation, and only CMI-hECFCs showed an impaired migratory capacity.

Conclusions:
MI Induces dysfunction of ECFCs with independence of CCVC
Abstract 18650: Differences in Hypertension Prevalence, Awareness, and Treatment Between Sexual Minority and Heterosexual Adults in the All of Us Research Program
Authors: Pepe Vincent , Nguyen Vince , Doan Danny , Sharma Yashika , Caceres Billy A
Published: December 2023

Introduction:
Hypertension accounts for approximately half of cardiovascular disease morbidity and mortality globally. There is growing evidence that younger sexual minority (e.g., gay and bisexual) men and bisexual women report a higher prevalence of hypertension than their heterosexual counterparts. However, there is limited evidence on differences in hypertension prevalence, awareness, and treatment among sexual minority middle-aged and older adults. Therefore, we sought to examine differences in hypertension prevalence, awareness and treatment between sexual minority and heterosexual middle-aged and older adults.

Hypothesis:
Compared to heterosexual adults, sexual minority participants will: 1) have a higher prevalence of hypertension, 2) be less likely to be aware of their hypertension, and 3) be less likely to obtain hypertension treatment.

Methods:
We analyzed questionnaire, physical examination, and diagnostic data from the All of Us Research Program. We used sex-stratified multivariate logistic regression models to examine sexual identity differences in objective hypertension (i.e., a systolic blood pressure ≥ 130 and/or a diastolic blood pressure ≥ 80), hypertension awareness, and hypertension treatment among adults.

Results:
The sample included 53,582 participants with a mean age of 56.3 years (±16.4); 66% were female and 78% were non-Hispanic White. Among men who met objective criteria for hypertension, bisexual men were less likely to report they were unaware they had hypertension compared to heterosexual men (AOR = 0.67, 95% CI = 0.52-0.88). There were no differences in hypertension prevalence or hypertension treatment between sexual minority and heterosexual adults.

Conclusions:
This is the first study to use data from the All of Us Research Program to examine disparities in hypertension prevalence, treatment, and awareness among sexual minority middle-aged and older adults. We found few differences between sexual minority and heterosexual participants, which contradicts prior work that has largely focused on younger adults. Findings suggest that researchers should investigate factors that contribute to the narrowing of hypertension disparities among sexual minority adults as they age.
Abstract 18656: Characterization of Pulmonary Vein Reconnection in Repeat Procedures After After Initial Cryoballoon Ablation Identified With High Density Mapping
Authors: Katrapati Praneeth , Bai Rong , Su Wilber
Published: December 2023

Introduction:
Catheter ablation of atrial fibrillation using the cryoballoon has become an alternate strategy to radiofrequency for pulmonary vein isolation (PVI). Both techniques, however, can result in pulmonary vein reconnection and the need for recurrent ablations.

Objective:
To study the incidence and specific location of pulmonary vein reconnection in patients with prior cryoballoon ablation for atrial fibrillation

Methods:
Retrospective analysis of patients that underwent radiofrequency ablation following a single initial cryoballoon PVI ablation was performed. Twenty patients were studied, all of whom underwent repeat ablation using radiofrequency with a mapping system (Rhythmia, Boston Scientific). A gap was defined as entrance conduction from the LA into the PV as suggested by the activation map.

Results:
Patients had an average of a 20 month period of normal sinus rhythm after initial ablation. A total of 48 gaps were identified in 18/20 patients (2.4 gaps per patient). The most common site of PV-LA conduction reconnection was at the superior pulmonary veins, specifically on the anterior portions. 60% (12/20) of patients had noted reconnection sites at the left superior pulmonary vein. All but one of these patients had gaps on the anterior surface of the vein. 75% (15/20) of patients were identified as having reconnection sites at the right superior pulmonary vein. All of these patients had gaps on the anterior surface of the vein. Less commonly, the left and right inferior veins each had 40% (8/20) patients with reconnection at these areas, with no consistent surface as the main site of reconnection. Further, 85% (17/20) patients had procedural ablation beyond only pulmonary vein re-isolation, owing primarily to the occurrence of atypical atrial flutters or atrial tachycardias that were seen during the repeat procedure itself

Conclusion:
Cryoballoon ablation is a successful technique for PVI in AF patients. However, reconnection of these sites is possible. Our analysis shows that the most common sites are at the anterior surface of the superior pulmonary veins. This could portend a potential drawback to be cognizant of during these initial procedures. Further analysis with a larger patient population will be necessary
Abstract 18657: Diagnostic Yield of Whole Genome Sequencing in Congenital Heart Disease: Data From the UK 100,000 Genomes Project
Authors: Baross Stephanie L , Williams Simon G , Hentges Kathryn E , Keavney Bernard D
Published: December 2023

Congenital heart disease (CHD) is the most common birth defect affecting around 1% global live births. The aetiology of CHD is poorly understood: while a number genetic loci have already been identified, the majority of cases remain unexplained. Many CHD cases occur with additional abnormalities, or as part of a defined syndrome (eg. Noonan or CHARGE syndromes). The 100,000 Genomes Project conducted whole genome sequencing for patients with a range of rare diseases and cancers in partnership with the UK National Health Service. We analysed clinical and genetic data from the project in 2638 participants with CHD, including both primary CHD cases and secondary cases who have CHD as part of a syndromic presentation but were recruited under other disease categories. Both cohorts are primarily composed of patients with CHD accompanied by additional extra-cardiac abnormalities without a prior diagnosis of a defined syndrome. We found that families recruited as primary CHD cases were significantly less likely to have been classed as “solved cases” (indicating a pathogenic variant has been identified) than phenotypically similar secondary CHD cases (5.4% primary, 16.2% secondary; p = 6.78х
-11
). This is primarily due to differences in the gene lists used in analysis, with the majority of diagnoses in both groups due to genes not included in the CHD gene panel (83% primary and 97% secondary cases). Expanding standard CHD screening to include a wider range of syndromic CHD genes is likely to increase the diagnostic yield for the primary CHD cohort by more than two-fold. Copy number variants (CNVs) also contribute to CHD, especially in cases with additional abnormalities. CHD cases have a significantly higher burden of both deletions (p = 1.00х10
-5
) and duplications (p = 0.009) than an ethnically-matched control cohort. However, only 7 of 2638 participants have CNVs in known CHD-causative regions such as the 22q11.2 or Williams-Beuren syndrome regions indicating novel CNVs are likely to contribute to a significant number of cases. Wider screening of syndromic CHD genes and novel copy number variants is likely significantly increase the diagnostic yield for CHD both within the 100,000 Genomes Project and in healthcare settings, and potentially yield novel CHD-associated loci.
Abstract 18693: Effect of Mechanical Unloading on Cardiogenic Shock Severity in Venoarterial Extracorporeal Membrane Oxygenation Patients
Authors: ahmad sana , Varrias Dimitrios , Smoller Rebecca , Bayat Mokhtari Moein , Floyd Kayla , Roslin Kylie , Kansara Tikal , Stevens Gerin R , Maybaum Simon , Alvarez Villela Miguel
Published: December 2023

Introduction:
Mechanical unloading (MU) with Intra-aortic balloon pump (IABP) or Impella is commonly used to prevent left ventricular (LV) distension in VA-ECMO patients, but its impact on shock severity is not well described.

Methods:
Patients treated with VA-ECMO in our hospital between 2016-2022 for cardiogenic shock (CS) due to LV failure not related to cardiac surgery were included if no MU was used or it was instituted within 24h of ECMO cannulation. Patients were grouped according to MU: ECMO alone, ECMO + IABP or ECMO + Impella. Linear mixed effects models adjusting for age, sex, hypertension, acute myocardial infarction (AMI) etiology of shock and pre-ECMO cardiac arrest (CA) were used to assess the impact of MU on hemodynamic and perfusion markers. R version 4 was used for analysis.

Results:
Among 68 patients included, 18 received ECMO alone, 17 ECMO + IABP, and 33 ECMO + Impella. Age and CA were similar across groups. The Impella group had a higher proportion of men and patients with AMI. Pulmonary artery diastolic pressure was unchanged in all groups. Compared to ECMO alone, MU did not enhance lactate clearance (interaction: IABP p=0.7, Impella p=0.22), but it did improve the vasopressor-inotropic score (IABP p=0.03, Impella p=0.01), serum creatinine (IABP p=0.03, Impella p=0.04), and alanine transaminase (IABP only p=0.02). Survival to decannulation was similar in patients with ECMO alone (50%), Impella (64%) and IABP (65%) (p=0.68).

Conclusions:
In adults treated with VA-ECMO for CS unrelated to cardiac surgery, LV MU can lead to improvements in CS severity.
Abstract 18698: PCBP1 Regulates Alternative Splicing of Aars2 in Congenital Cardiomyopathy
Authors: Lu Yao Wei , Liang Zhuomin , Guo Haipeng , Fernandes Tiago , Espinoza-Lewis Ramon , Wang Tingting , Li Kathryn , Li Xue , Singh Gurinder B , Wang Yi , Cowan Douglas B , Mably John D , Philpott Caroline C , Chen Hong , Wang Da-Zhi
Published: December 2023

Rationale:
Alanyl-transfer RNA synthetase 2 (AARS2) is a nuclear encoded mitochondrial tRNA synthetase that is responsible for charging of tRNA-Ala with alanine during mitochondrial translation. Homozygous or compound heterozygous mutations in the Aars2 gene, including those affecting its alternative splicing, are linked to congenital cardiomyopathy in humans. However, the underlying molecular mechanism of how Aars2 regulates heart development remains unknown.

Hypothesis:
The alternative splicing of Aars2 and its function is essential for cardiac development.

Methods and Results:
We found that alternative splicing of the Aars2 transcript is mediated by poly(rC) binding protein 1 (PCBP1), an RNA binding protein, through direct interaction. Cardiomyocyte-specific deletion of Pcbp1 in mice resulted in defects in heart development that are reminiscent of human congenital cardiac defects, including noncompaction cardiomyopathy and a disruption of the cardiomyocyte maturation trajectory. Loss of Pcbp1 led to an aberrant alternative splicing and a premature termination of Aars2 in cardiomyocytes. Therefore, Pcbp1 is critical for the expression and function of Aars2. Additionally, Aars2 mutant mice with exon-16 skipping recapitulated heart developmental defects observed in Pcbp1 mutant mice. Mechanistically, we found dysregulated gene and protein expression of the oxidative phosphorylation pathway in both Pcbp1 and Aars2 mutant hearts; these data provide further evidence that the infantile hypertrophic cardiomyopathy associated with the disorder oxidative phosphorylation defect type 8 (COXPD8) is mediated by Aars2.

Conclusion:
Our study therefore identifies Pcbp1 and Aars2 as critical regulators of heart development and provides important molecular insights into the role of disruptions in metabolism on congenital heart defects.
Abstract 18700: Immune Checkpoint Inhibitor-Related Myocarditis and Overlapping Syndromes
Authors: Heffernan Shannon , Chen Yimin , Tehrani Babak , Ewer Steven , Hillerson Dustin , Rahko Peter S
Published: December 2023

Background:
Immune checkpoint inhibitor (ICI)-related myocarditis is a rare adverse effect of ICI's. When accompanied by overlapping myasthenia gravis, prognosis is worsened. While established guidelines aid in the treatment of ICI-associated adverse events, management of overlapping syndromes is complex and challenging.

Case description:
A 66-year-old man with metastatic renal cell carcinoma recently started on ipilimumab and nivolumab presented with dizziness and diplopia. He had high-grade atrioventricular (AV) block with junctional escape. He had elevated troponin, transaminases, and creatinine kinase. Coronary angiogram showed no evidence of obstructive coronary artery disease. A permanent pacemaker was placed. Cardiac MRI showed no specific features of myocarditis, though quality was limited by pacemaker artifact; left ventricular ejection fraction was 29%. MRI of the orbits showed no signs of extraocular myositis. Acetylcholine receptor (AChR) antibody and muscle-specific kinase (MuSK) antibody was negative. Given ongoing suspicion for ICI-associated adverse events, the patient underwent endomyocardial biopsy. This revealed lymphocytic myocarditis, confirming the diagnosis of ICI-related myocarditis. Despite improvement of troponin, transminases, and creatinine kinase, he developed progressive weakness, dysphagia, and respiratory failure, and died one month after initial presentation.

Discussion:
We highlight a case of ICI-related myocarditis presenting as high-grade AV block with concurrent hepatitis, myositis, and probable serologic-negative myasthenia gravis (MG). Overlapping syndromes are common in patients with exposure to ICI's, and are associated with significantly higher mortality. Although steroids are first-line for treating ICI-associated adverse events including myocarditis, they can initially lead to acute worsening of MG symptoms. While our patient had laboratory and biomarker improvement of his myocarditis, hepatitis, and myositis, he developed progressive weakness and respiratory failure. Our case highlights the complexity and challenges of managing ICI-related myocarditis and overlapping syndromes, including MG, and its poor prognosis despite prompt treatment.
Abstract 18703: No Time for Horseplay: A Case on a Traumatic Septal Defect
Authors: Siraj Talhah Z , Chib Anjula , Sharifi Sasha , Thang Sophia , Menon Vivek , Volansky Paul , JAGTAP DO MANDAR , Patel Mehul
Published: December 2023

Background:
A 74-year-old male with no past medical history presented to the clinic due to shortness of breath that had worsened over the past two weeks. He reports being “knocked over by a horse” about one month before and experienced chest pain immediately afterwards. A new holosystolic murmur was found prompting further evaluation. A walking test showed his oxygen saturation dropped from 98% to 81% on room air and was in respiratory distress. TTE revealed a large VSD of 1.5 cm with a left to right shunt, a dilated right ventricle measured at 4.9 cm, and severe pulmonary hypertension. Coronary angiography ruled out a prior myocardial infarction. RHC revealed an increase of oxygen saturation from the right atrium at 68.6% to 92% in the right ventricle. The patient was transferred to a facility where he underwent successful surgical VSD closure. He was discharged to rehab on post-operative day 8. He presented to the clinic one month later reporting resolution of his symptoms.

Discussion:
This patient with no past cardiac history presented with progressive dyspnea that was later identified to be caused by a trauma he experienced one month prior. The incidence of traumatic VSDs is quite low. Most VSDs are congenital in nature however few are reported to be trauma related. Trauma so intense that could cause a rupture in the septal muscle is quite intriguing. Prompt work up with imaging modalities such as TTE is the best next step for any trauma-related symptoms. Shared decision making with the patient and a multidisciplinary team will help to decide on a percutaneous or surgical repair of the defect. This case demonstrated a systematic approach to a unique presentation of a typically congenital condition.
Abstract 18720: Association of Triglyceride-Glucose Index and Risk of Coronary Heart Disease, Congestive Heart Failure, Stroke and Hypertension Among Non-Diabetic Patients: NHANES Study 2001-2020
Authors: Sawaf Bisher , Swed Sarya , Bohsas Haidara , Alibrahim Hidar , Nasif Mohamad Nour , Haj Saleh Heba , Tashrifwala Fatema , Khair Eldien jabban Yazan , Al-Rassas Safwan H , Lakhani Sunita , Al Hennawi Hussam , Naguib Mervat , Battikh Naim , Mahmoud Mahmoud , Zaidi Abdul Rehman Zia , alghalyini Baraa , Hafez Wael
Published: December 2023

Introduction:
Not enough studies addressed the predictive value of the triglyceride glucose (TYG) index for developing cardiovascular diseases. This study highlights the association between TYG index and the risk of cardiovascular disease among non-diabetic patients.

Methods:
Our study used the National Health and Nutrition Examination Survey (NHANES) data. Data from 2001 to 2020 was involved, and the analysis was performed using a 4-year fasting weight (WTSAF4YR) per NHANES analysis criteria. We included non-diabetic participants aged 18 years or older. The Statistical Package for the Social Sciences (SPSS) v. 28 was used for the analysis. The sensitivity and specificity of the TyG index in predicting the endpoints of interest (coronary heart disease (CHD), Congestive Heart Failure (CHF), Heart attack (HA), Stroke, and Hypertension (HTN)) were calculated by receiver operating characteristic (ROC) analysis. We performed univariate and multivariate logistic regression to analyze the associated factors with the endpoints of our study.

Results:
Our study involved 10,937 non-diabetic individuals. The age was 48±18 years. Individuals with a TyG index of>8.96 had higher BMI, waist circumference, systolic/diastolic blood pressure, total cholesterol, LDL, and Apo-B levels (p<0.001). Overall, 360, 359, 385, 237, and 3254 patients had CHD, stroke, HA, CHF and HTN, respectively. We evaluated the predictor values of TyG index for CHF (AUC: 54.75%, 95% CI:0.542-0.614), stroke (AUC:52.32%,95%CI:0.529)-0.584), HA (AUC:55.67%, 95%CI:0.595-0.646), HTN (AUC: 55.59%, 95%CI:0.574-0.597), CHD (AUC: 50.31%,95%CI:0.592-0.646), and all of them were statistically significant(p-value<0.05).

Conclusions:
The value of the TyG index was a poor indicator for the studied cardiovascular diseases (congestive heart failure, stroke, heart attack, high blood pressure, and coronary heart disease).
Abstract 18727: Outcomes of Utilization of Transesophageal Echocardiogram (TEE) vs Intracardiac Echocardiogram (ICE) for Atrial Fibrillation Ablations in the Real-AF Registry
Authors: Minga Iva , Lee Kevin , Varley Allyson , Thorne Christopher , Osorio Jose , Singleton Matthew , DSouza Benjamin , Silverstein Joshua , Metzl Mark
Published: December 2023

Introduction:
Transesophageal (TEE) and intracardiac (ICE) echocardiogram are widely used strategies to rule out LAA thrombus prior to atrial fibrillation (AF) ablation. We compare the utilization of TEE and ICE, outcomes and complications of each strategy.

Methods:
The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal (PAF) and Persistent (PsAF) Atrial Fibrillation registry (Real-AF) is a multicenter prospective registry that is enrolling patients undergoing AF ablation at high-volume centers. We compared complications rates (Table 1) between TEE and ICE in patients with AF underdoing index ablation for AF in the REAL-AF registry. Patients who underwent both TEE and ICE were excluded from the analysis. Bleeding complication was defined as bleeding that occurs within the first 72 hours of the procedure requiring transfusion or resulting in >20% drop in hemoglobin. Vascular access complications included AV fistula or pseudo-aneurysm needing intervention.

Results:
A total of 1628 patients were included in the analysis.The mean age was 64.78 (SD=11.43) years, 45.7% were women, mean BMI was 30.36 (SD=6.71) and mean CHAD2DS2VASc score was 2.49 (SD=1.51). TEE was used in 911 patients (58.5%) and ICE was used in 717 (46.1%) ] prior to ablation. There were 0% strokes reported in the TEE group vs 0.1% in the ICE group (p = 0.095). Among other complications reported there was no statistical difference between the two groups (Table 1). There was no significant difference between the two groups on recurrence of arrhythmias at 12 months (HR: = 0.983, CI: 0.79,1.3 , p < 0.894)

Conclusion:
Both TEE and ICE are acceptable strategies for pre-ablation assessment of left atrium and LAA. There are no significant differences in stroke rates between the two groups. Other reported complications are also similar between the two groups. Choice of either TEE vs ICE depend on patient specific characteristics, hospital resources and operator preference.