bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13829: Assessing the Recovery From COVID-19-Related Disruptions to Cardiovascular-Related Screening Services by Race and Ethnicity
Authors: Alba Christopher , Zheng ZhaoNian , Wadhera Rishi K
Published: November 2023

Introduction:
The COVID-19 pandemic significantly disrupted routine clinical care in 2020. We aimed to assess recovery from COVID-19’s impacts on health care utilization, affordability, and cardiovascular risk factor screening in 2021, both overall and by race and ethnicity.

Methods:
We used 2019 and 2021 National Health Interview Survey data-a nationally-representative, cross-sectional household interview survey of US adults (
>
18 years old). Outcomes included measures of health care access, affordability, and cardiovascular risk factor screening. Logistic regression models compared outcomes in 2021 (second year of pandemic) to 2019 (pre-pandemic baseline), adjusting for age and sex. An interaction term for race/ethnicity and year assessed for differential change across racial/ethnic groups.

Results:
The weighted population size was 250.9 and 253.1 million adults in 2019 and 2021. In 2021, wellness visits significantly decreased for all racial/ethnic groups compared with 2019, a decline most pronounced for Asian adults. Medical financial concerns decreased for White, Black, and Hispanic adults. Blood pressure, cholesterol, and diabetes screening significantly decreased for all groups in 2021 vs. 2019, with the largest declines among Asian adults (see Table 1 and Figure 1 for all results).

Conclusions:
In this national study of US adults, there were significantly fewer wellness visits and lower rates of cardiovascular risk factor screening in 2021 compared to pre-pandemic levels, overall and across all racial and ethnic groups. These results suggest that policy efforts are needed to improve access and cardiovascular screening as the US emerges from the pandemic.
Abstract 13830: Pheochromocytoma in a Patient With Tetralogy of Fallot and Chromosome 17p12 Duplication
Authors: Aggarwal Muskaan , Wang Roy X , Colello Stephanie S , Saef Joshua M , Vaikunth Sumeet
Published: November 2023

Description of Case:
A 22-year-old male with Tetralogy of Fallot (TOF) status post transannular patch repair, hypothyroidism, and known partial duplication of chromosome 17p12 concerning for Charcot-Marie-Tooth disease (CMT), presented to his cardiologist with exertional angina and dyspnea, difficulty gaining weight, and diaphoresis. Cardiac MRI demonstrated moderate to severe pulmonic regurgitation with regurgitation fraction of 35% and RV end-diastolic volume index of 150 cc/m
2
. He was referred for pulmonic valve replacement surgery. While awaiting surgical evaluation, he presented to an ER with new hypertension with blood pressure to 240/140 and tachycardia to 107. A CT scan demonstrated a 4.3 x 5.0 x 4.4 cm mass in the right adrenal gland. On admission he was started on phenoxybenzamine and carvedilol. Workup revealed elevated catecholamines and metanephrines (
Table
). He underwent surgical adrenalectomy without complications. Immunohistochemical staining was consistent with pheochromocytoma. Post-procedurally, he was normotensive off medications. He was seen in clinic three weeks after surgery with significant improvement in symptoms.

Discussion:
We report on a novel genetic association of chromosome 17p12 duplication and pheochromocytoma. The region transcribes peripheral myelin protein-22, which has associations with CMT. Overlap has been demonstrated in other CMT-associated mutations and pheochromocytoma syndromes (e.g. kinesin family member 1B). In congenital heart disease, risk for pheochromocytoma is felt to be driven by hypoxia causing catecholamine secretion, adrenal hyperplasia, and eventual neoplasia. Further study is needed to characterize genetic associations between pheochromocytoma, neuropathy, and congenital heart disease. This patient’s presentation is a lesson in maintaining a high index of suspicion for pheochromocytoma in congenital heart disease, especially with associated genetic syndromes.
Abstract 13840: Safety Outcomes From a First-in-Human Study of a Novel Investigational Monoclonal Antibody, REGN5381, an Agonist to the Natriuretic Peptide Receptor 1
Authors: Kithcart Aaron P , Dunn Michael E , de Hoon Jan , Botermans Wouter , Karnik Satyajit , Burczynski Michael E , Zheng Wenjun , Rankin Andrew J , Herman Gary , Olenchock Benjamin
Published: November 2023

Introduction:
Natriuretic peptides (NPs) regulate vascular volume and tone via the membrane-bound guanylate cyclase, natriuretic peptide receptor 1 (NPR1). Activation of this pathway is known to lower systemic and venous blood pressure (BP) and effect natriuresis and diuresis. Previous recombinant NP infusions for heart failure were limited by their duration of effects. REGN5381, a novel investigational NPR1 agonist monoclonal antibody, showed sustained hemodynamic effects in animal models. Here, we report safety and pharmacodynamic (PD) outcomes from a phase 1, first-in-human study of REGN5381.

Hypothesis:
REGN5381 is sufficienty well tolerated in healthy humans to warrant continued clinical investigation.

Aim:
To assess the safety, tolerability, and REGN5381 PD in normotensive humans.

Methods:
This double-blind, single-ascending dose study (NCT04506645), randomized healthy adults aged 18-55 years (6:2) to receive a single intravenous dose of REGN5381 or placebo. Participants received a fixed-sodium and fluid diet and remained 4 days in the clinic for non-invasive hemodynamics monitoring and safety assessment.

Results:
A total of 48 participants were enrolled; 12 were randomized to placebo and 6 to each of 6 REGN5381 dose levels (total n=36). Eight (66.7%) participants in the placebo and 24 (66.7%) in the total REGN5381 group reported ≥1 treatment-emergent adverse event (TEAE), with no obvious relationship to dose level. Four (33.3%) participants in the placebo and 15 (41.7%) in the total REGN5381 group reported ≥1 study drug related TEAE, with no obvious relationship to dose level. Common TEAEs (experienced by >10% of participants in the total group) were postural dizziness (placebo: 2 [16.7]%; total REGN5381: 6 [16.7]%) and headache (placebo: 5 [41.7%]; total REGN5381: 4 [11.1%]). Pyuria and orthostatic hypotension were reported in 4 (11.1%) participants in the total group, but none in the placebo group. No serious or severe TEAEs or deaths were reported in any dose groups. Participants treated with the highest dose saw a 7-11 mmHg reduction of systolic BP that was sustained over 72 hours (the full duration of inpatient monitoring).

Conclusion:
A single dose of REGN5381 is generally well-tolerated and provides sustained hemodynamic effects.
Abstract 13847: Biomarker-Based Phenomapping in Chronic Stable HFpEF and Exercise Capacity: An Analysis of the RELAX Trial
Authors: Segar Matthew W , Raiker Nisha , Subramanian Vinayak , Geffin Ryan , Patel Kershaw , Pandey Ambarish
Published: November 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a heterogenous disease associated with low exercise capacity.

Hypothesis:
Unsupervised clustering of biomarker data can identify subgroups of individuals with HFpEF and differences in exercise capacity.

Methods:
The study included participants with chronic, stable HFpEF from the RELAX trial with available serum biomarker data. We used unsupervised hierarchical clustering analysis of 9 serum biomarkers to derive phenogroups of participants with HFpEF. Adjusted linear regression was used to assess the association between cluster membership with peak oxygen consumption (VO2), maximum exercise watts, and VO2 anaerobic threshold.

Results:
Among 211 participants in the RELAX trial, 3 phenogroups were identified based on the gain in within-inertia. No significant differences were observed in age, sex, or race across phenogroups. Phenogroup 1 (n=136) participants had the lowest burden of CV (cardiovascular) risk factors, including diabetes, anemia, and kidney disease as well as the lowest overall biomarkers levels (
Fig.
A
). Phenogroup 2 (n=61) consisted of participants who were older with a higher burden of CV risk factors and fibrosis biomarkers, including galectin-3, collagen-I, and troponin-I levels. Phenogroup 3 (n=14) participants were younger with high burden of CV risk factors and inflammatory biomarkers including aldosterone, CRP, and uric acid. Compared with phenogroup 1, phenogroup 2 and 3 had significantly lower peak VO2, adjusted for traditional CV risk factors [estimate (95% CI): -1.99 (-2.83, -1.16) and -2.31 (-3.66, -0.95), respectively]
(Fig. B
). Additionally, phenogroup 3 vs. 1 had lower exercise watts and VO2 anaerobic threshold.

Conclusion:
Using serum biomarkers, we identified 3 unique phenogroups of patients with chronic, stable HFpEF and significant differences in CV risk factor burden and exercise capacity.
Abstract 13848: Time to Coronary Angiography in Patients With NSTE-ACS is Longer in Women as Compared to Men
Authors: Suba Sukardi , Carey Mary G , Pelter Michele M
Published: November 2023

Introduction:
Timely invasive coronary angiography (ICA) to restore myocardial blood flow in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) improves prognosis and reduces morbidity and mortality. NSTE-ACS practice guidelines recommend ICA <2 hours [hrs] (very high-risk) or <24 hrs (high-risk). Troponin is useful for guiding timing of ICA. However, there is little evidence comparing time to troponin and ICA in women
vs.
men, which could uncover important treatment differences. Therefore, the purpose of this study was to examine time to ICA and first troponin in women vs. men in a cohort of hospitalized NTSE-ACS patients.

Methods:
Secondary data analysis in 121 patients with NSTE-ACS; women (
n
=41, 34%) vs. men (
n
=80, 66%), who underwent ICA and had a troponin test. Variables of interest were obtained from the electronic health record.

Results:
Compared to men, women were older (67±12 vs. 62±11 years,
p
=0.039), had a higher proportion of diabetes (44% vs. 19%,
p
=0.006), and were non-smokers (61% vs. 31%,
p
=0.013). Time, in
minutes
, to first troponin did not differ between women vs. men (81.53±261.04 vs
.
33.49±107.20,
p
=0.167), when including one outlier (one woman). Excluding this outlier, it remained non-significant (44.43±127.66 vs. 33.49±107.20,
p
=0.167). Overall, the time to ICA, in
hours
, was longer in women than men (24.01±27.64 vs. 13.83±12.89,
p=
0.007). The first troponin was positive in 26 women (67%) and 53 men (69%),
p
=0.98; however, time to ICA, in
hours
, was longer in women vs. men (21.55±20.26 vs. 12.56±11.41,
p=
0.014).

Conclusions:
In patients with confirmed NSTE-ACS, time from admission to ICA was nearly twice as long in women as compared to men. One explanation could be symptoms differences and should be explored further. Time from admission to first troponin was not statistically different (with and without oulier [one women]). Despite an equivalent rate of the first troponin being positive, time to ICA was on average 9 hours longer in women vs. men. Future studies in a larger cohort(s) using contemporary data are needed to explore possible reasons for ICA delay (symptoms and clinical characteristics) to confirm if similar trends persists and whether short- and long-term outcomes are different by sex.
Abstract 13855: Epigenetic Aging Markers Mediate the Association of Life’s Essential Eight With Cardiovascular Disease and All-Cause Mortality
Authors: Carbonneau Madeleine , Li Yi , Liu Chunyu , Huan Tianxiao , Joehanes Roby , Murabito Joanne , Heard-Costa Nancy , Ma Jiantao , Levy Daniel
Published: November 2023

Background:
The American Heart Association recommended Life’s Essential 8 (LE8) as a simple cardiovascular health (CVH) metric. While optimal LE8 scores are associated with greater CVH and longevity, the mechanisms underlying these associations are unclear.

Objective:
To characterize the associations between LE8, epigenetic age scores, CVD, and all-cause mortality.

Methods:
LE8 scores were calculated for 5,669 participants in the Framingham Heart Study. Mixed proportional hazard models were used to evaluate the associations between LE8 score and CVD and all-cause mortality. We conducted mediation analyses to calculate the proportion of the association between LE8 score and CVD and all-cause mortality that is mediated by DNA methylation-based epigenetic age markers (GrimAge and PhenoAge). We performed stratified mediation analyses based on median-dichotomized polygenic risk score (PRS) of epigenetic age markers.

Results:
Higher LE8 scores, indicating better CVH, were associated with lower risk of CVD. One standard deviation (SD) increase in LE8 score was associated with a 35% decreased risk of CVD (95% CI: 27%, 41%,
p
=1.8E-15). One SD increase in LE8 was also associated with a 29% decreased risk of all-cause mortality (95% CI: 22%, 35%,
p
=7.0E-15). These associations were partly mediated by epigenetic age: the mean proportions of mediation by GrimAge and PhenoAge were 21% and 2% (
p
=0.23) for CVD and 67% and 6% for all-cause mortality, respectively. In our stratified analysis, potential mediation effects of GrimAge and PhenoAge were more profound in participants with a higher PRS. For GrimAge, the proportion of mediation for the association between LE8 and CVD was 39% (95% CI: 14%, 80%,
p
=8.8E-04) for participants in the upper half of higher GrimAge PRS whereas there was no significant mediation for those with low GrimAge PRS values. For the association between LE8 and all-cause mortality, the proportion of mediation by GrimAge was 81% (95% CI: 48%, 100%,
p
<2.0E-16) in participants with the highest GrimAge PRS and not significant for those with the lowest GrimAge PRS.

Conclusion:
LE8 shows a strong association with CVD and all-cause mortality. Our observations suggest that these associations are mediated in part by DNA methylation-related mechanisms.
Abstract 13865: Home Monitoring and Unanticipated Interstage Readmissions: Evaluating the Impact of Neighborhood Social Vulnerability
Authors: Shustak Rachel J , Faerber Jen , Stagg Alyson , Ravishankar Chitra , Mercer-Rosa Laura , Giglia Therese M , Gardner Monique M
Published: November 2023

Introduction:
Unanticipated interstage (IS) readmissions are common in infants with hypoplastic left heart syndrome (HLHS). Enrollment in our center’s Infant Single Ventricle Management and Monitoring Program (ISVMP) has been associated with increased readmission frequency. We examined the impact of neighborhood social vulnerability on the association of ISVMP with readmission frequency and cumulative readmission days. We hypothesized that greater social vulnerability was associated with greater risk for readmission.

Methods:
We performed a retrospective single-center cohort study comparing infants with HLHS enrolled in ISVMP (12/2010-12/2019) to historical controls (01/2007-11/2010). Outcomes were number of readmissions per IS days and cumulative IS readmission days. Neighborhood social vulnerability was measured by the Centers for Disease Control Social Vulnerability Index (SVI). High SVI signifies greater vulnerability. Negative binomial regression models were used to examine the association between ISVMP, SVI tertiles, and the outcomes. Models were adjusted for demographic, operative, and discharge characteristics.

Results:
We evaluated 328 infants with HLHS; 198 ISVMP infants and 128 historical controls. The association of ISVMP and IS readmissions strengthened as social vulnerability increased. ISVMP was not associated with IS readmissions in low SVI infants (IRR 1.55; 95% CI 0.94, 2.54). However, middle and high SVI infants enrolled in ISVMP were significantly more likely to be readmitted than their historical counterparts (middle SVI: IRR 1.67; 95% CI 1.01, 2.76; high SVI: IRR 2.14; 95% CI 1.33, 3.45). On stratified analysis, there was no relationship between SVI tertile and cumulative IS readmission days in the historical controls. However, in the ISVMP cohort, high SVI infants had 70% more cumulative readmission days compared to their middle SVI peers (IRR 1.69; 95% CI 1.11, 2.59).

Conclusions:
High social vulnerability infants with HLHS enrolled in ISVMP are at high risk for IS readmission compared to their historical, middle and low vulnerability peers. Future efforts should focus on understanding whether these findings are due to disparities in IS medical complexity, illness severity, or readmission criteria.
Abstract 13869: The Association Between
DYRK4
Hypomethylation in Peripheral Blood and Coronary Heart Disease: A Case-Control Study
Authors: Yang Rongxi , jin jialie , song yakang , zhang ruotian , yang yining
Published: November 2023

Backgrounds:
Coronary heart disease (CHD) is a leading cause of morbidity and mortality worldwide, with myocardial infarction (MI) representing its most prevalent type. Previous studies have suggested an association between the dual-specificity tyrosine-regulated kinases (
DYRK)
gene family and various cardiovascular disease risks. However, the specific role of
DYRK4
in CHD, particularly in MI, remains unclear.

Objective:
We hereby investigated the association between blood-based
DYRK4
methylation and CHD, MI and non-MI related CHD.

Methods:
A total of 88 CHD cases (23 MI and 65 non-MI) were diagnosed by coronary angiography and clinical presentation at Chinese People's Liberation Army General Hospital from 2018 to 2019. 93 persons who participated in the annual health examination were randomly selected as controls. The
DYRK4
methylation, which contains three measurable CpG sites, was quantified by mass spectrometry of nucleic acid. Covariates-adjusted odds ratios (ORs) for -10% methylation was calculated by binary logistic regression, and receiver operating characteristic (ROC) curves were generated to evaluate the discriminatory power.

Results:
Decreased methylation of DYRK4_CpG_2 and DYRK4_CpG_3 in peripheral blood was significantly associated with increased CHD risk (OR: 1.49 and 1.20;
p
= 0.044 and 0.049). Notably, these two CpG sites were only significant in non-MI related CHD (OR: 1.71 and 1.33;
p
= 0.015 and 0.009) rather than MI (OR: 1.11 and 0.99;
p
= 0.759 and 0.968). The combination of DYRK4_CpG_2 and DYRK4_CpG_3 methylation levels could efficiently discriminate CHD, MI and non-MI related CHD patients from controls (area under curve (AUC) = 0.771, 0.795 and 0.784, respectively).

Conclusion:
Our study suggests that hypomethylation of DYRK4_CpG_2, DYRK4_CpG_3 in blood is associated with CHD, and
DYRK4
methylation model may provide a new strategy for detection of CHD, especially non-MI related CHD.
Abstract 15606: Effectiveness and Safety of the Dual Epicardial & Endocardial Procedure (DEEP) Approach for Treatment of Subjects With Persistent or Long Standing Persistent Atrial Fibrillation (PersAF/LSPAF) With Radiofrequency Ablation
Authors: Ellenbogen Kenneth , Khoynezhad Ali , de Asmundis Carlo , KASIRAJAN Vigneshwar , koneru Jayanthi , Johnkoski John , Rist Kevin , Mumtaz Mubashir , Link Michael , de Groot Joris R , Driessen Antoine , Lee Mark , Hoff Steven , Bello David , Dunnington Gansevoort , Eisenberg Susan , Vloka Margot , Taylor Benedict , Jones Stephen , Philpott Jonathan , Beaver Thomas , Miles William , khan junaid , Kang Steven , Gandhi Gaurang , Okum Eric , Badhwar Nitesh , Baykaner Tina , Lee Anson M , Vesco Paul A , Smith J Michael , Gaynor Sydney , Frazier Ken , La Meir Mark
Published: November 2023

Background:
A collaborative approach between Electrophysiologists (EP) and Cardiothoracic Surgeons (CTS) to effectively target pulmonary veins (PVs) and substrate beyond PVs may improve outcomes for persistent and longstanding persistent AF (PersAF/LSPerAF).

Hypothesis:
A minimally invasive hybrid approach of bilateral thoracoscopic epicardial ablation and left atrial appendage exclusion (LAAE) with endocardial mapping/ablation (Hybrid approach) is safe and effective to treat advanced AF patients who have failed medical therapy.
Aim:
DEEP (NCT02393885) aims to establish safety and effectiveness of a Bipolar Radiofrequency (RF) System in a Hybrid approach to treat PersAF/LSPerAF.

Methods:
DEEP is a prospective, international, single arm trial at 17 sites. Key eligibility: adults with drug refractory PersAF/LSPerAF, left atrial diameter (LAD) ≤5.5cm, failed class I/III AAD, and ≤2 previous failed endocardial catheter ablations (CA). Epicardial surgical ablation included PV isolation, roof and floor lines (posterior LA box), left superior PV to LAA lesion, ganglionic plexi and Ligament of Marshall ablation and LAAE. CA followed 91-121 D post epicardial procedure. After 90 D blanking and 90 D AAD optimization periods, 24-hr rhythm monitoring and ECG were performed 6 and 12 M post CA with symptom driven monitoring between. Primary effectiveness was defined as freedom from atrial arrhythmia (>30 sec) absent new/increased dose of previously failed AAD through 12 M. Safety was device/procedure-related SAEs within 30 D of epicardial ablation and 7 D of CA in all who received anesthesia.

Results:
Ninety patients were enrolled in 2015-2020, 83.3% PersAF, 16.7% LSPerAF, mean age 63.4±7.74 yrs, 83.3% male, mean BMI 29.9, CHAD2DS2-VASc median 2.0 (1.0, 3.0), 48% failed CA, median AF duration 3.8 yrs, mean LAD 4.5cm. Primary effectiveness 70.6% (60/85; 95% CI 60.9%, 80.3%, p=0.0232) and freedom from AF through 12 M 78.8% (p=0.0002). The adverse event rate was 6.7% (6/90); equal in epi- and endocardial cohort. Both primary endpoints met prespecified success criteria.

Conclusion:
A collaborative approach between EP and CTS to Hybrid ablation is effective for PersAF/LSerPAF when benefit-risk is deemed favorable, given limited alternative treatments.
Abstract 15609: ParSE-seq: A Calibrated Multiplexed Assay for Clinical Interpretation of Putative Splice-Altering Variants
Authors: Oneill Matthew J , Yang Tao , Laudeman Julie , Calandranis Maria , Glazer Andrew , Roden Dan M
Published: November 2023

Background:
Up to 10% of disease-associated variants are predicted to affect RNA-splicing. Interpreting the clinical significance of putative splice-altering variants outside the 2-base pair canonical splice sites remains difficult without functional studies.
Goal:
To develop a calibrated, high-throughput assay to adjudicate variant effects on RNA splicing.

Methods:
We established Parallel Splice Effect Sequencing (ParSE-seq), a multiplexed minigene assay, to test variant effects on RNA splicing quantified by high-throughput sequencing. We used the tool SpliceAI to prioritize exonic and intronic candidate splice variants, and ClinVar to select curated benign and pathogenic controls in
SCN5A
, which encodes the major voltage-gated cardiac sodium channel. We transfected 271 barcoded minigene constructs into HEK cells or induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), and calibrated to the American College of Medical Genetics and Genomics scheme. Variants were interpreted using the calibrated functional data, and experimental data correlated to SpliceAI predictions. We studied selected variants by automated patch clamp (APC) in HEK cells and by assessing splicing and channel function directly in CRISPR-edited iPSC-CMs.

Results:
ParSE-seq revealed the splicing effect of 245
SCN5A
variants in iPSC-CMs. The assay had concordant scores for 43/45 benign and pathogenic control variants, achieving both PS3- and BS3-strong levels of evidence after calibration. 41/114 exonic variants and 30/66 intronic variants with determinate scores disrupted splicing. 9 of 42 Variants of Uncertain Significance were reclassified, and 30 of 34 variants with conflicting interpretations were reinterpreted using the functional data. Predictions from SpliceAI performed well on experimental data (AUC = 0.96). We identified 3 clinically relevant splice-altering missense variants that had normal function when tested with a cDNA-based APC assay. A splice-altering intronic variant, c.1891-5C>G also disrupted splicing and sodium channel electrophysiology when introduced into iPSC-CMs by CRISPR-editing.

Conclusions:
ParSE-seq is an efficient, calibrated, high-throughput assay to facilitate splice-altering variant interpretation.
Abstract 15612: EDG-7500, a Novel Cardiac Sarcomere Regulator That Preserves Intrinsic Myosin-Motor Function, Improves Cardiac Function and Reserve in a Minipig Model of Hypertrophic Cardiomyopathy
Authors: Del Rio Carlos L , Rupert Cassady , Tolley Jessica , Duvall Mike , Emter Craig , DiNatale Emy , Hawryluk Natalie , RUSSELL ALAN , Semigran marc , Evanchik Marc
Published: November 2023

Introduction:
Hypertrophic Cardiomyopathy (HCM) is a myocardial disease characterized by LV hypertrophy, hyperdynamic contraction, and diastolic dysfunction that results in impaired exercise capacity. In HCM, excess acto-myosin crossbridge formation during diastole increases myocardial stiffness leading to hindered ventricular filling and limited cardiac reserve. EDG-7500, a novel sarcomere regulator that slows the rate of contraction but does not directly inhibit the myosin motor head, may offer salutary effects in HCM with minimal reduction in systolic performance. Here, this hypothesis was tested in the setting of the pathological HCM beta-myosin heavy chain (MYH7) R403Q mutation.

Methods:
In vitro, force dynamics were evaluated in human IPSC-derived engineered heart tissues (EHT) with the MYH7 R403Q mutation compared to isogenic controls (WT). The biomechanical effects of EDG-7500 were evaluated in permeabilized fibers from tissues isolated from minipigs carrying the MYH7 R403Q mutation. The in vivo cardiac responses to EDG-7500 were studied via echocardiography and invasive hemodynamics in the R403Q minipigs. In a subset of pigs, β-adrenergic receptor (β-AR) dependent cardiac output reserve was studied.

Results:
R403Q mutant EHT preserved peak force (PF) relative to WT but impaired relaxation kinetics (RT90: +19±4 ms, 171±4 vs. 152±2 ms in WT, P<0.05). EDG-7500 (0.3uM) accelerated relaxation kinetics in R403Q EHTs (RT90: -8±3ms, 180±4 to 172±2 ms, P<0.05) without affecting PF. RT90 improvement occurred at 6-fold lower concentrations than systolic inhibition (PF IC20: 1.95 ± 0.70 μM). In vivo, EDG-7500 improved early LV filling, accelerating e’ (6.9 ± 0.8 to 8.6 ± 0.6 cm/s, P < 0.05) and decreased atrial volume (-22%, P < 0.05) while enhancing β-AR dependent cardiac output recruitment; in R403Q pigs, EDG-7500 plus dobutamine led to higher cardiac outputs relative to only dobutamine (3.1±0.3 vs. 2.6±0.3 L/min, P<0.05).

Conclusions:
EDG-7500, a novel cardiac sarcomere regulator, improved diastolic function in EHT and animals with the HCM-pathogenic MYH7 R403Q mutation, improving β-AR dependent cardiac output reserve. This novel profile could be valuable for the treatment of patients with HCM and diseases of diastolic dysfunction.
Abstract 15616: Decline in Temporal Trends of Medicare Physician Reimbursement for Cardiovascular Procedures
Authors: Bansal Kannu , Rawlley Bharat , Desai Nihar R , Yeh Robert W , Kolte Dhaval S
Published: November 2023

Introduction:
Utilization of cardiac procedures are common among Medicare beneficiaries and projected to increase over time. Temporal trends of physician fee reimbursement for CV procedures have not been studied.

Methods:
Cross-sectional study was conducted for national payment amounts that were extracted from Centers for Medicare & Medicaid Services (CMS) Physician Fee Schedule Look-Up Tool using Current Procedural Terminology (CPT) codes. Study time period ranged from 2013 through 2023. CPT codes were analyzed for coronary (percutaneous coronary intervention, coronary artery bypass graft), valvular (surgical aortic, mitral, tricuspid repair/replacement), and structural (transcatheter aortic valve replacement, mitral transcatheter edge-to-edge repair, left atrial appendage occlusion) procedures. All prices were adjusted for inflation to January 2023 US dollars. Primary outcomes were unadjusted and adjusted mean percentage changes (annual and total over 10-year period) and compound annual growth rates for each CV procedure.

Results:
From 2013 to 2023, mean total unadjusted percentage changes ranged from -0.54% to -21.78%; which decreased further after adjusting for inflation, ranging from -21.07% to -39.83%. The decline was seen in all studied CV procedures. Annual rates (mean and compound) were -3% for most procedures after adjusting for inflation.

Conclusions:
Our findings suggest a declining trend in physician reimbursement for CV procedures by Medicare, which may adversely influence access to procedures, affect commercial insurance pricing/coverage, and inform trainees and practicing CV physicians of current financial situation. Emphasis needs to be placed on value-based payment model for sustainable and efficient CV care.
Abstract 15617: Association Between Growth Differentiation Factor-15 and Outcomes Among Patients With Heart Failure: A Systematic Literature Review
Authors: Javaheri Ali , Kosiborod Mikhail N , Ozcan Mualla , Moubarak Lauren , Smoyer Karen E , Rossulek Michelle I , Revkin James H , Groarke John D , Tarasenko Lisa C
Published: November 2023

Background:
Growth differentiation factor-15 (GDF-15) is upregulated during myocardial injury and stress, and is an emerging biomarker of adverse outcomes in patients with heart failure (HF). Although systematic literature reviews (SLRs) of GDF-15 and HF have been conducted, few assessed outcomes other than mortality.
Aim:
This SLR examined the association of GDF-15 levels with a broad range of outcomes in patients with HF.

Methods:
Following PRISMA guidelines, Embase and Medline were searched to identify articles published 1/1/2014–8/23/2022 reporting outcomes associated with GDF-15 in adults with HF. Both cross-sectional (assessed at the same time as GDF-15) and longitudinal outcomes were included.

Results:
Sixty-three publications met eligibility criteria: 45 were observational studies and 18 post hoc analyses of randomized controlled trials. A total of 19 outcomes were identified. The most frequently reported longitudinal outcomes were mortality (n=32), composite endpoints (e.g., death ± hospitalization; n=28) and hospitalization (n=11). The most common cross-sectional outcome was biomarkers of kidney function (n=22). Of 27 studies assessing all-cause mortality, 24 conducted multivariable analyses (MVA), of which 22 (91.7%) reported a significant, independent association between higher baseline GDF-15 and all-cause death. Among the 26 studies reporting association between baseline GDF-15 and composite endpoints, 19 used MVA and 13/19 (68.4%) reported at least one significant association. Among 10 studies assessing hospitalization and baseline GDF-15, 8/10 (80%) reported outcomes using MVA, of which 50% found a significant association. Twenty studies assessed the cross-sectional association between baseline GDF-15 levels and measures of kidney function. Of these, 7 used MVA and reported statistically significant associations.

Conclusions:
The results of the SLR suggest that GDF-15 is an independent predictor of mortality and other adverse, nonfatal outcomes in patients with HF. Better understanding of the potential prognostic role of GDF-15 in HF could improve clinical risk prediction and identify patients with HF who may warrant additional treatment optimization/intensification.
Abstract 15619: Prevalence of Transthyretin Cardiac Amyloidosis in Elderly Subjects From the General Population: The Catch Study
Authors: Aimo Alberto , Castiglione Vincenzo , Barison Andrea , FABIANI IACOPO , Panichella Giorgia , Giorgetti Assuero , Genovesi Dario , Franzini Maria , Moscardini Stefano , Passino Claudio , Vergaro Giuseppe , Emdin Michele
Published: November 2023

Introduction:
The exact prevalence of transthyretin cardiac amyloidosis (ATTR-CA) in the general population has never been defined.

Methods:
We conducted a population screening in an area of Tuscany (Italy) where there is no cluster of variant ATTR. Six general practitioners proposed study participation to a total of 2,566 subjects aged ≥65 years, with 1,000 accepting. All subjects underwent first-line exams searching the following elements of suspicion of CA: high sensitivity-troponin T ≥14 ng/L, interventricular septal thickness ≥12 mm, any echocardiographic, ECG or clinical red flag. Individuals with any of these elements were referred to the search for a monoclonal protein and bone scintigraphy.

Results:
Step two exams (bone scintigraphy and search for a monoclonal protein) were proposed to 346 subjects, and 216 (62%) accepted. Three patients were ultimately diagnosed with ATTR-CA (a 79-year-old woman, an 85-year-old and a 74-year-old man), and the diagnosis was deemed likely in another patient (an 83-year-old woman with mild bone tracer uptake but intense uptake in the inferior wall, not willing to undergo endomyocardial biopsy). No patient had a monoclonal protein nor
TTR
gene mutations. All patients with ATTR-CA had left ventricular wall thickening and complained of dyspnea on moderate effort. The prevalence of ATTR-CA was 3 out of 870 (654 [Step two not proposed] + 216 [Step two performed]) = 0.34%, or 0.46% if considering also the fourth case.

Conclusions:
The prevalence of wild-type ATTR-CA in the elderly population is 0.34% (established diagnoses) or 0.46% (established or likely diagnoses).
Abstract 16090: Human Chart Abstraction Combined With Electronic Medical Record Programmed Queries Improves Identification of Patients With Cardiac Implanted Electronic Devices
Authors: Narowska Gabriela , Khanduja Shivalika , Horton Edward R , gangireddy chethan , Hamad Eman A , Pawlowski Colleen M , Behrens Kim , Whitman Glenn J , Whitman Isaac R
Published: November 2023

Background
The Society of Thoracic Surgery cardiac surgery database (STSD) is used for quality improvement and research. The STSD relies on human chart abstraction (STS-HA) to accurately identify cardiac patients with existing Cardiac Implanted Electronic Devices (CIED’s). Perioperative CIED management may impact surgical outcomes, yet the sensitivity of the STS-HA for CIED patients is unknown.

Methods
All 7 major STS cardiac surgeries performed at Johns Hopkins Hospital (JHH) and Temple University Hospital (TUH), between 7/2017 and 6/2022, were assessed for the presence of a CIED. CIED patients were identified using both STS-HA and a programmed EMR (Epic) reports (EMR-pro) relying on CPT codes, problem lists, structured data elements, and CIED interrogation reports. The presence of existing CIED in patients was confirmed by same-day chest imaging, which is not uniformly searchable using EMR-pro. McNemar’s chi square test was used to compare the sensitivity of STS-HA with EMR-pro to identify preoperative patients with existing CIED’s.

Results
Using the STSD, we identified 4770 surgical patients across both institutions during the study period (JHH n= 2627, TUH n=2143), of whom 167 patients had CIED’s (3.5%; JHH 77 (2.9%), TUH 90 (4.2%). Of these, STS-HA identified 144 (86.2% pooled sensitivity) as having existing CIED’s (JHH 69, 89.6%; TUH 75, 83.3%). EMR-pro identified 164 patients (98.2% pooled sensitivity; JHH 77, 100%; TUH 87, 96.7%). Each of the 3 TUH patients identified by STS-HA but not by the EMR-pro had CIED documentation in paper chart scans. The pooled sensitivity of EMR-pro was better than that of STS-HA in identification of CIED’s at the time of surgery (p<0.0001).

Discussion
The programmed EMR algorithm’s superior sensitivity to human abstraction in identifying cardiac surgical patients with existing CIED’s is an important enhancement in identifying this population. This improvement in sensitivity illustrates the power of EMR programmed reports to address the unreliability of human chart abstraction. Understanding the inherent limitations of the STS database and improving it are essential to the interpretation of past STSD based research and improving the reliability of STSD based studies performed in the future.
Abstract 16096: Systolic Blood Pressure, Preeclampsia, and Leiomyoma Genes - A Multivariable Mendelian Randomization and Mediation Analysis
Authors: Vaitinadin Nataraja Sarma , Shi Mingjian , Mosley Jonathan , Giri Ayush
Published: November 2023

Introduction:
Preeclampsia (PE) (sudden-onset hypertension (>20 weeks gestation) with proteinuria, maternal organ/uteroplacental dysfunction or angiogenic imbalance) affects ~4 million women annually, causing death of >70,000 women and 500,000 babies, and sequelae like heart failure.

Hypothesis:
We hypothesize that among the known genetic associations of PE is an independent risk factor (IRF).
Methods: Data
Publicly available European ancestry genome-wide association study (GWAS) summary statistics (SS) derived single nucleotide polymorphism (SNP) based genetic instruments (
P-
value≤5x10
-08
,
r
2
<0.001) for known associations of PE [body mass index (BMI, kg/m
2
) (339,224 subjects), high density lipoprotein (HDL, mg/dl) (188,577), blood pressure BP (mm Hg) - systolic (S) and diastolic (D) (458,577)] with SS for PE or eclampsia (7212 cases, 194266 controls) (outcome).
Analyses
1) univariate two-sample Mendelian randomization (MR) [inverse variance weighted method (IVWM) for results; MR-Egger, and weighted-median methods for sensitivity analyses]; 2) multivariable (MV) MR to identify IRF after MV adjustment, 3) quantify change in effect size of IRF after adjustment (results reported as odds of PE per 10 unit change in SBP/DBP/HDL, and per standard deviation (SD) change in BMI); and 4) FUMA based analysis of IRF SNPs to annotate uterine genes using GTEx v8.

Results:
In 1) IVWM analysis, SBP (OR= 2.23 [95% CI= 1.82, 2.72]), DBP (3.32 [2.46,4.48], HDL (0.22 [0.09,0.55]), and BMI (1.58 [1.34,1.86]) associated with the odds of a diagnosis of PE; 2) MVMR analysis, only SBP (1.82 [1.11, 3.00] remained significant, after adjustment for BMI, DBP, and HDL; 3) proportion-explained analysis, ~18% reduction in the OR of SBP, after adjustment for BMI, DBP, and HDL; and 4) in FUMA based analyses, out of 7 gene associations, the top 2 uterine genes for SBP SNPs were
ZNF859
, and
CDC25A
.

Conclusions:
Genetic predisposition to elevated SBP associated with increased odds of PE, independent of BMI, DBP, and HDL. Adjustment attenuated risk, suggesting shared genetic mechanisms. SBP is an independent risk factor for PE. SBP SNPs map to uterine
ZNF859
and
CDC25A,
known leiomyoma associated genes, suggesting a pleiotropic role in PE development.
Abstract 16906: Impact of ECPELLA Support on Mid-Term Survival and IABP-Shock II Score in Patients With Refractory Cardiogenic Shock Due to Acute Coronary Syndrome
Authors: Inamori Taiji , Unoki Takashi , Nakayama Tomoko , FUKUDA Toshiki , Toyofuku Takaaki , Matsura Junya , Konami Yutaka , Suzuyama Hiroto , Inoue Masayuki , Horio Eiji , Kodama Kazuhisa , Taguchi Eiji , Sawamura Tadashi , Sakamoto Tomohiro , Nakao Koichi , Koyama Jyunjiro
Published: November 2023

Introduction:
The prognosis remains extremely poor for acute coronary syndrome (ACS) with cardiogenic shock (CS) who required VA-ECMO. The IABP-SHOCK II score is a simple tool, and has demonstrated a high predictive ability for assessing the prognosis of patients with CS.

Objective:
To evaluate the impact of ECPELLA on intermediate-term survival compared to VA-ECMO with IABP support in patients with ACS and refractory CS and to assess the utility of the IABP-SHOCK II score in predicting outcomes for patients requiring VA-ECMO support.

Methods:
From January 2012 to December 2022, we enrolled 90 consecutive patients with ACS-CS who received VA-ECMO. Patents were divided into two groups; 44 patients received ECPELLA, and 46 patients received VA-ECMO with IABP. We assessed IABP-SHOCK II score and 180-day all-cause mortality.

Results:
There were no significant differences in age, rate of male sex, coronary risk factors, ST-elevated ACS, LMT lesion, extracorporeal cardiopulmonary resuscitation, and IABP-SHOCK II score between two groups. Kaplan-Meier analysis revealed that ECPELLA was associated with a significantly higher 180-day survival rate (p = 0.001). The patients were categorized into three groups based on the IABP-SHOCK II score: low (0-2), intermediate (3-4), and high (5-9). The IABP-SHOCK II risk score successfully stratified only the ECPELLA group into different risk categories for 30-day prognostic assessment.

Conclusions:
ECPELLA was associated with favorable mid-term survival compared to VA-ECMO with IABP support. Additionally, the IABP-SHOCK II score proved to be a useful tool for predicting mortality in patients treated with ECPELLA.
Abstract 16927: The Mother of All Pseudoaneurysms - A Rare Case
Authors: Chib Anjula , Menon Vivek , Ghaly Michael , Abu Rmilah Anan , Sharifi Sasha , Siraj Talhah , Thang Sophia , JAGTAP DO MANDAR , Pidikiti Nanni , Patel Mehul , PARKER AMY , Volansky Paul
Published: November 2023

Introduction:
Femoral artery pseudoaneurysms (FAP) are typically caused by percutaneous access during coronary and peripheral angiography. It occurs in 0.1 to 0.2% of diagnostic catheterization procedures and in 3.5% to 5.5% of interventional procedures. Cases of “Giant” femoral artery pseudoaneurysms have seldom documented in the past, however, our case is unique for two reasons:- Pseudoaneurysm presented 6 months after femoral arterial access, which is unusual.- This size of pseudo-aneurysm has yet to be documented.

Case Description:
74-year-old male with history of diabetes mellitus type II and tobacco abuse presented with chest pain. He underwent cardiac catheterization via radial access, which confirmed severe multi-vessel disease with ejection fraction of 30%. Patient was started on goal-directed medical therapy with planned elective IABP-assisted coronary artery bypass grafting (CABG). On the day of surgery in anticipation of IABP, right femoral artery was accessed, however, intra-operative transesophageal echocardiography showed improvement of ejection fraction to 55%, which led to removal of the femoral sheath and application of a closure device. Six months later, patient presented with a large right groin mass. Computed tomography angiography confirmed a pseudoaneurysm anterior to the right common femoral artery, measuring 9.6 cm x 9.8 cm causing moderate stenosis of the superficial femoral artery. Peripheral arterial duplex ascertained the neck of pseudoaneurysm measuring 1.3 cm. Patient underwent emergent repair of the right femoral pseudoaneurysm, with thrombus removal. No further recurrence of pseudoaneurysm was noted.

Discussion:
Pseudoaneurysms may arise months after femoral arterial access. Any groin symptoms in patients who underwent percutaneous femoral arterial access warrant additional investigation. Further studies are needed to elucidate the factors that increase the risk of formation and rupture of pseudoaneurysms
Abstract 19124: Systemic Sclerosis Masquerading as Heart Failure
Authors: Prathivadhi-Bhayankaram Sruti , Mansour Shareef
Published: November 2023

Cardiac disease occurs in 80% of patients with systemic sclerosis (SS). Patients may present with various symptoms, including dyspnea, palpitations, chest pain, and heart failure. Of these, systolic heart failure has the rarest prevalence, estimated between 1-5% of patients. The mechanism behind myocardial damage is still unclear. Current literature supports a fibrotic process due to ischemic necrosis and reperfusion damage. There is a lack of representation of SS-related cardiac disease, but it is crucial to recognize it early for prompt intervention.

A 62-year-old male with a history of diastolic dysfunction presented with acute hypoxic respiratory failure. A transthoracic echocardiogram demonstrated a new severely reduced systolic function at 20%. Angiogram demonstrated non-obstructive coronary artery disease. Further autoimmune workup revealed a significantly elevated ANA and highly positive RNA polymerase III antibody. The patient underwent a cardiac magnetic resonance imaging (MRI) scan, which showed evidence of inflammation with diffuse myocardial fibrosis concerning an infiltrative process. Subsequent cardiac positron emission tomography (PET) showed increased uptake in the basal portions of the septum and anterior wall for myocarditis. Given his autoimmune workup results and imaging, the patient was subsequently diagnosed with rapidly progressive cutaneous systemic sclerosis and associated non-ischemic cardiomyopathy.

The patient was started on goal-directed medical therapy, including losartan, spironolactone, metoprolol, and empagliflozin. Additionally, he started on mycophenolate mofetil for immunosuppression. Roughly six months after discharge, his pulmonary function tests remain stable. His ejection fraction improved to 62%.

Roughly one-third of systemic sclerosis-related deaths are due to cardiac involvement. Yet, most patients are asymptomatic during the early stages, with a variable phenotype later in disease progression. We report a case of a patient who developed systemic sclerosis-related myocarditis with an initial presentation of acute systolic heart failure. His cardiac dysfunction recovered from optimal goal-directed therapy and immunosuppression.
Abstract 19133: Sodium Induced-RGMa Plays a Role in Salt-Sensitive Hypertension
Authors: Desta Selam , Pitzer Mutchler Ashley , Ertuglu Lale A , Saleem Mohammad , Ishimwe Jeanne , Sheng Quanhu , Kirabo Annet
Published: November 2023

Salt sensitivity of blood pressure, characterized by blood pressure fluctuations that mirror dietary sodium (Na
+
) intake, is an independent risk factor for cardiovascular morbidity and mortality in people with and without hypertension. We previously found that elevated Na
+
uptake via the amiloride-sensitive epithelial sodium channel (ENaC) in antigen-presenting cells leads to the upregulation of isoleuvoglandins and proinflammatory cytokines ultimately leading to T cell activation and salt-sensitive hypertension. In addition, we also showed that SMAD3 activation plays a role in inflammation and salt-sensitive hypertension. In previous studies, RGMa has been shown to be upstream of SMAD3. Furthermore, previous studies have also shown that knockdown of RGMa leads to reduced levels of TGFβ1-induced SMAD3 phosphorylation. The exact mechanism by which elevated extracellular Na
+
leads to increased blood pressure remains unknown. We hypothesized that RGMa complexes with TGFβ1R1 to promote SMAD3 phosphorylation ultimately contributing to inflammation in salt-sensitive hypertension. To test our hypothesis, we isolated monocytes from human participants (N =11) and treated them with either high (190 mMol/L) or normal (150 mMol/L) Na
+
in vitro
for 72 hours and subsequently performed bulk RNA sequencing. We found that TGFβ1R1 (8837 ± 780.9 vs. 9688 ± 942.5, p =0.350) and TGFβ1R2 (7012 ± 717.0 vs. 7176 ± 633.9, p = 0.059) were being similarly expressed between high or normal salt treatment. Interestingly, RGMa (2253 ± 441.0 vs. 516 ± 84.1, p <0.001) and TGFβ1 (5118 ± 353.9 vs. 9067 ± 826.4, p = 0.073) were significantly upregulated in human monocytes after high Na
+
treatment compared to normal salt. To further investigate, we performed an
in vivo
high Na
+
treatment by utilizing a rigorous salt-loading/depletion protocol on human participants (N = 9) and conducted single-cell transcriptomic analyses. We found a positive correlation between the changes in pulse pressure and RGMa (r = 0.5154, p = 0.1911). Our data suggest that RGMa mediates Na
+
-induced inflammation and salt-sensitive hypertension which may reveal a novel therapeutic target.