bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12422: Does a Jump in the Atrioventricular Conduction Curve Really Indicate a Switch From Fast Pathway to Slow Pathway Conduction?
Authors: Zhang Youhua
Published: December 2023

Introduction:
A jump in the atrioventricular (AV) conduction curve (aka, a discontinuous curve) remains the current clinical criterion for diagnosing dual pathway AV nodal electrophysiology. However, it has never been proven that a jump in the AV conduction curve indicating a transition from fast pathway (FP) to slow pathway (SP) conduction, as it has been assumed.

Hypothesis:
A jump in the AV conduction curve may not reflect the transition from FP to SP conduction, as assumed it does by the current clinical criterion.

Methods:
Eighty-one experimental records from rabbit AV nodal preparations containing the following data were analyzed. 1. had at least one AV conduction curve, and 2. had intracellular action potential recordings from AV nodal fibers and/or recording of His electrogram alternans (a validated new index of dual pathway conduction).

Results:
There were 11 (13%) of 81 preparations showing a jump in the AV conduction curve. In these preparations, the transition from FP to SP conduction was smooth. The jumps always occurred after the FP to SP transition at a much shorter prematurity (Figure). On average, the FP-SP transition occurred at prematurity of 196±39ms versus the jump at 117±9ms (P<0.001). Complex intranodal/nodal-atrial reentries were detected after the FP to SP transition. The jumps were always associated with and most likely caused by the intranodal/nodal-atrial reentry and its subsequent conduction to the His bundle, rather than a direct conduction by the premature beat itself.

Conclusions:
The transition from FP to SP conduction does not produce a jump in the AV conduction curve. A jump in the AV conduction curve is likely caused by induction of intranodal/nodal-atrial reentry by the premature beat and the subsequent conduction of the reentrant beat to the His bundle, rather than a direct conduction by the premature beat itself. Thus, a jump in the AV conduction curve as the current clinical criterion of dual pathway conduction should be invalidated.
Abstract 12427: Prescribing Patterns of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Agonists in Patients With Type 2 Diabetes at Cardiology, Endocrinology and Primary Care Visits in a Community Health System
Authors: Dixon Dave L , Robinson Amanda , Salgado Teresa , Carbone Salvatore , Wagner Tyler , Hyder Haroon , Kirschner Bryan , Musselman Kerri , Sabo Roy
Published: December 2023

Introduction:
Both SGLT2i and GLP-1 RA are cardio- and kidney-protective, yet their uptake in clinical practice has been poor. Prescribing patterns of these drug classes at cardiology, endocrinology, and primary care visits are not well understood.

Research Questions:
What proportion of patients with T2DM and ASCVD, HF, or CKD were prescribed an SGLT2i or GLP-1 RA, and which medical visits were these agents prescribed?

Aim:
To determine the prescribing rates of SGLT2i and GLP-1 RA at cardiology, endocrinology, and primary care visits.

Methods:
A cross-sectional study using EHR data from Bon Secours Mercy Health clinics across Virginia (2019, 2020, 2021) included patients ≥18 yo with T2DM and either ASCVD, HF, or CKD, and ≥1 outpatient visit. Adults with T1DM, ESRD, pregnancy, or on hospice or palliative care were excluded. Visit-level prescribing rates were compared overall and for each subgroup between cardiology, endocrinology, and primary care visits using generalized linear mixed modeling with a random practice-level effect. A positive prescription was considered a prescription for either medication for the overall analysis and a prescription of the preferred drug class according to comorbidities for each subgroup. The potential dependence between repeated measurements was estimated using a compound symmetric correlation structure.

Results:
The 22,060 included patients had a mean age of 68 years, 50% female, 41.3% black, 80% ASCVD, 24% CKD, and 27% HF. Overall, prescriptions for either drug class occurred in 17% of the population. Endocrinology visits had the highest prescription rates per visit overall and for each subgroup, while cardiology visits had the lowest prescription rate overall and for each subgroup (Table 1).

Conclusion:
Overall prescribing rates for SGLT2i and GLP-1 RA were low among adults with T2DM and ASCVD, HF, or CKD. Cardiology visits had the lowest prescription rates (0.3%) versus endocrinology (7.9%) and primary care visits (2.5%).
Abstract 12433: miR 187a-3p Prevents Septic-Induced Myocardial Dysfunction by Targeting the Inflammatory Cytokines TNFa and IL-6
Authors: Ektesabi Amin M , Tsoporis James N , Vaswani Chirag , Izhar Shehla , Desjardins Jean-Francois , Parker Thomas , Leong-Poi Howard , dos Santos Claudia
Published: December 2023

Introduction:
Patients with severe, sepsis can develop acute heart failure characterized by left ventricular dilatation and decreased contractility. Inflammatory mediators, including TNFα, IL-6 and IL-1β contribute to the activation of inflammation and ventricular remodeling. Therapeutic interventions for sepsis are lacking. Previously, we demonstrated that miR187-3p, a regulator of TNFα is dysregulated in the septic heart, in a pre-clinical model of sepsis.

Hypothesis:
We hypothesize that administering miR187-3p mimic would reduce inflammatory cytokine production and improve cardiac function and mortality rate.

Methods:
Polymicrobial sepsis was induced in mice via cecal ligation and perforation (CLP) surgery, mice undergoing sham surgery served as controls. MiR187-3p mimic, miRNA negative control, or saline were administered IV 6 hrs post-CLP. At 48 hrs post-CLP, following echocardiographic and hemodynamic assessments, the mice were sacrificed, and the hearts collected for biochemical, and molecular analysis. To complement the experimental findings, autopsy human hearts and circulatory blood samples from septic patients and healthy controls were collected and the expression of miR187a-3p and inflammatory cytokines were analyzed.

Results:
Administration of miR-187-3p mimic to septic mice 6 hrs post-CLP increased survival, improved echo-derived indices of cardiac function (left ventricular ejection fraction, fractional shortening), increased bacterial clearance and reduced inflammation when compared to septic mice receiving a scrambled control miR. In septic mice, miR-187-3p expression decreased in both the circulation and heart tissue. In addition to TNFα, bioinformatic analysis, confirmed by luciferase assays, identified IL-6 as a specific target of miR187-3p in cardiac myocytes. In septic patients, the expression of miR-187-3p and target inflammatory cytokines decreased in plasma and autopsied hearts.

Conclusions:
Delivery of miR-187-3p improves outcomes in sepsis-induced myocardial dysfunction. Thus, miR-187-3p serves as a potential biomarker and therapeutic target for prevention and prognostic reflection in sepsis-induced myocardial dysfunction.
Abstract 12449: Association of Left Atrial Function With Mitral Regurgitation Progression: Atherosclerosis Risk in Communities Study
Authors: Zhang Chunxiao , Wang Wendy , Inciardi Riccardo , Ji Yuekai , Shelbaya Khaled , EATON ANNE , Alonso Alvaro , Soliman Elsayed Z , Solomon Scott , Shah Amil M , Chen Lin Y
Published: December 2023

Background:
Left atrial (LA) enlargement and atrial fibrillation (AF) are associated with functional mitral regurgitation (MR). It is unknown whether lower (worse) LA function is associated with MR progression, independent of LA size, in individuals without AF.

Hypothesis:
We hypothesized that lower LA function was associated with higher odds of MR progression.

Aims:
To evaluate the association of echocardiographic-based LA function with MR progression in the Atherosclerosis Risk in Communities (ARIC) Study, a community-based cohort.

Methods:
We included 2,444 ARIC participants (mean age, 73.8 ± 4.4 years, 42% male, 21% Black) who underwent 2D-echocardiogram at visits 5 (2011-2013) and 7 (2018-2019) and excluded those with AF, heart failure, and heart valve surgery at visit 5. Based on American College of Cardiology/American Heart Association guidelines, MR was graded as stages A-D. MR progression was defined as new onset of MR at visit 7, any increase in MR stage, or mitral valve surgery for MR between visit 5 and 7. LA function was measured using strain analysis and included reservoir, conduit, and contractile strain. Logistic regression models were used for the analysis.

Results:
After mean follow up of 6.5 ± 2.4 years, MR progression occurred in 504 (21%) participants. As shown in the table, lower reservoir strain was associated with higher odds of MR progression (OR [95% CI] per SD decrement, 1.16 [1.003, 1.34]) after adjusting for demographics, clinical risk factors, LA size and LV mass and function. LA conduit and contractile strain were not significantly associated with MR progression.

Conclusion:
Lower LA function is associated with higher odds of MR progression, independent of LA size, in individuals without AF. More research is needed to clarify the mechanism to identify novel prevention strategies for MR progression.
Abstract 12450: Mystifying Masquerade: Renal Cell Carcinoma Associated Arteriovenous Fistula Presenting as High-Output Heart Failure
Authors: Jasti Jaswanth Rao , Sivaprakasam Thabuna , Saad Shaukat Muhammad Hamza , Lamfers Randall , Jonsson Orvar
Published: December 2023

Case Presentation:
59 year-old woman with CKD stage 3b and hypertension presented with 3 months of progressive dyspnea, abdominal distension, bilateral lower extremity edema, and a 60-pound weight gain. Physical exam noted diffuse anasarca, with stable hemodynamics on room air. EKG revealed low voltage leads and chest X-ray demonstrated an enlarged cardiac silhouette. CT abdomen was remarkable for significant ascites, body wall edema, and a suspicious large right renal mass. Diagnostic paracentesis indicated cardiac ascites. Echocardiogram showed preserved ejection fraction, moderate pericardial effusion and an enlarged right side of the heart. Right heart catheterization confirmed high-output heart failure (HOHF). A suspected renal mass-related arteriovenous fistula (AVF) was confirmed through inferior vena caval and renal venogram blood gas sampling, indicating arteriovenous shunting within the renal mass. Hepatic venogram excluded portal hypertension. MRI abdomen confirmed a large necrotic right renal mass consistent with renal cell carcinoma (RCC). Symptoms significantly improved after nephrectomy, with aggressive diuresis, and therapeutic paracenteses leading to an 80-pound weight loss. Postoperative echocardiography illustrated decrease in pericardial effusion and right ventricular size. Cardiac MRI and stress test were unremarkable prior to planned immunotherapy for stage III RCC.

Discussion:
AVF and HOHF associated with malignancy are unusual presentations. RCC is the most prevalent underlying malignancy linked with AVF and is hypothesized to be a result of hypervascularity caused by a VHL gene mutation. The most often utilized imaging modalities for detecting a tumor-related AVF are contrast enhanced CT or MRI. When imaging is inconclusive, a venogram with blood gas sample, as observed in our case, may be considered to establish an RCC-associated AVF.
Abstract 12453: Racial Disparities in Long-Term Survival Among Patients With Moderate and More Severe Tricuspid Regurgitation
Authors: Olgun Kucuk Hilal , Lara-Breitinger Kyla , Scott Christopher , Alabdaljabar Mohamad S , Anand Vidhu , Brewer LaPrincess C , Pislaru Cristina , Shapiro Brian P , Chaliki Hari P , Nkomo Vuyisile T , Eleid Mackram F , Pellikka Patricia A , Pislaru Sorin V
Published: December 2023

Introduction:
Tricuspid regurgitation is a common echocardiographic finding leading to excess morbidity and mortality in adult population.

Hypothesis:
Racial and ethnic disparities have been observed in various cardiovascular disorders’ prevalence and natural course, including valvular lesions. However, little is known about the epidemiology and clinical correlations of TR among non-Hispanic Black adults.

Methods:
To examine risk factors and clinical outcomes in non-Hispanic Black adults with moderate or more severe TR, 685 patients (7%) self-identified as non-Hispanic Black and 9127 (93%) self-identified as non-Hispanic White with a first echocardiographic report of moderate or more severe TR between 2005-2016 were studied.

Results:
Non-Hispanic Black patients had more severe TR when compared to white patients (25% vs. 20%, p<0.001). After adjusting for age and sex, non-Hispanic Black patients had significantly higher 10-year all-cause mortality (HR=1.34 (1.18, 1.52), p<0.001). Black race remained a risk factor for all-cause mortality even after adjustment for comorbidities like CHF, COPD, DM, CKD, hypertension, and ischemic heart disease (HR=1.23 (1.08, 1.40), p=0.002).

Conclusions:
Significant racial disparities exist in demographic, clinical and echocardiographic characteristics between non-Hispanic Black and White patients with moderate or more severe TR. Black race is a potential disease modifier leading to excess mortality.
Abstract 12470: Sacubitril/Valsartan in Patients With Heart Failure and Deterioration of Kidney Function to Estimated Glomerular Filtration Rate Less Than 30ml/min/1.73m
2
: Insights From PARAGON-HF and PARADIGM-HF
Authors: Chatur Safia , Vaduganathan Muthiah , Claggett Brian L , McCausland Finnian , Desai Akshay S , Beldhuis Iris , Rouleau Jean L , Zile Michael R , Packer Milton , Pfeffer Marc A , Lefkowitz Martin P , McMurray John J , Solomon Scott D
Published: December 2023

Background:
Sacubitril/valsartan is a foundational therapy for patients with heart failure (HF). Although current US FDA labeling does not identify threshold kidney function below which initiation or continuation of sacubitril/valsartan is precluded, guidelines generally identify eGFR<30mL/min/1.73m
2
as a contraindication to therapy.

Methods:
The RCTs PARAGON-HF and PARADIGM-HF assessed sacubitril/valsartan versus valsartan or enalapril in patients with HF. Patients with eGFR <30 (PARADIGM) or <25 mL/min/1.73 m
2
(PARAGON) at randomization were excluded. Discontinuation below this eGFR during follow-up was not mandated. We examined the effects of sacubitril/valsartan on efficacy and safety in patients experiencing progression of CKD to eGFR<30mL/min/1.73m
2
in follow-up.

Results:
Among 4,746 patients in PARAGON-HF and 8,346 patients in PARADIGM-HF (with eGFR>30ml/min/1.73m
2
at randomization), 613 (12.9%) and 691 (8.3%), respectively, had an eGFR<30mL/min/1.73m
2
at least once in follow-up. Patients with CKD progression had higher rates of study drug discontinuation and hyperkalemia (>5.5 mmol/L); however, rates remained similar between treatment groups. Patients with deterioration in kidney function to eGFR<30ml/min/1.73m
2
were at a higher risk of the primary composite outcome in both PARAGON-HF (RR 2.08; 95% CI: 1.72-2.52) and PARADIGM-HF (HR 2.32; 95% CI: 1.94-2.76). The incidence of the primary composite outcome was lower in patients treated with sacubitril/valsartan irrespective of deterioration in kidney function to eGFR<30mL/min/1.73m
2
in both PARAGON-HF (P
int
=0.74) and PARADIGM-HF (P
int
=0.50);
Figure 1
.

Conclusion:
HF patients with progression of CKD to eGFR<30ml/min/1.73m
2
experience high risk of CV outcomes and continuation of sacubitril/valsartan was associated with persistent benefit. These data support potential continuation of sacubitril/valsartan, even among patients experiencing progression to advanced CKD.
Abstract 12476: QT Prolongation Predicts All-Cause Mortality Above and Beyond a Validated Risk Score
Authors: Adabag Selcuk , Gravely Amy , Kattel Sharma , Buelt-Gebhardt Melissa , Westanmo Anders
Published: December 2023

Introduction:
QT prolongation is a risk factor for life-threatening arrhythmias and sudden cardiac death. In large cohorts, QT interval was associated with all-cause mortality after adjusting for cardiovascular risk factors, but these analyses may contain residual confounding. Whether the QT interval provides prognostic information above and beyond a validated mortality risk score is unknown.

Hypothesis:
QT interval on ECG will independently predict mortality after adjustment for the Care Assessment Needs (CAN) score, which was validated to predict mortality nationwide at the Veterans Administration (VA) (c-index 0.86).

Methods:
Patients receiving primary care at the Minneapolis VA from 2012 to 2016, with at least one ECG were included in this retrospective cohort study. QT intervals were corrected for heart rate (QTc) using the Bazett’s formula. CAN score, calculated within 1-week of the ECG, was obtained from the VA Corporate Data Warehouse.

Results:
Of the 36,240 patients, 1526 (4.2%) had QTc ≥ 500 ms, 3249 (9.0%) had QTc 470-500 ms, and 31,465 (86.8%) had QTc < 470 ms. A total of 2,189 (6.0%) patients died at 1-year follow-up and 7898 (21.8%) died at 5-year follow-up. Mortality was higher in patients with longer QTc (Table 1). Compared to those with QTc < 470 ms, CAN-adjusted odds of 1-year and 5-year mortality were significantly higher in those with longer QTc (Table 2). C-index for CAN score predicting 1-year and 5-year mortality (0.829 and 0.826, respectively) improved marginally after adding QTc data (0.834 and 0.832, respectively; p <0.0001 for both).

Conclusions:
QT prolongation predicts all-cause mortality independently of a validated mortality risk prediction score.
Abstract 12487: Healthcare Access and Cardiovascular Risk Factor Management in Low-Income Working-Age Adults After the COVID-19 Pandemic
Authors: Marinacci Lucas X , Zheng ZhaoNian , Bartlett Victoria , Wadhera Rishi K
Published: December 2023

Background:
Low-income working age adults disproportionately experienced disruptions in care and deepening financial hardship at the onset of the COVID-19 pandemic. Little is known about how health care access and cardiovascular (CV) risk factor management changed as the pandemic went on, and if these patterns differed by state Medicaid expansion status.

Methods:
We identified adults aged 18-64 using the CDC’s Behavioral Risk Factor Surveillance System. Low-income adults were defined as those with incomes <138% of the federal poverty level (FPL), and high-income adults >400% FPL. We fit logistic regression models to compare changes in measures of health care access and CV risk factor management in 2021 to a pre-pandemic baseline (2019), adjusted for age and sex. We included an interaction term for income level and year, to evaluate whether there was a differential change between low- and high-income adults. We also evaluated changes among low-income adults in Medicaid expansion vs. non-expansion states.

Results:
As shown in the
Table
, health insurance coverage, access to personal health care provider, and ability to afford care all improved in 2021 compared to pre-pandemic baseline (2019), although gains were more pronounced for high-income vs low-income groups. In contrast, the proportion of adults with a check-up in the past 12 months, or who received recommended cardiovascular risk factor screening, worsened in both low- and high-income groups. Among the low-income group, those in Medicaid expansion states experienced greater increases in insurance coverage than those in non-expansion states (OR 1.53 [1.40,1.68] vs 1.27 [1.11,1.46], p = 0.0283).

Conclusion:
In this national study, low- and high-income working-age adults experienced decreases in outpatient check-ups and CV risk factor screening in 2021 compared with pre-pandemic baseline. Public health initiatives are needed to improve screening for CV risk factor as the US emerges from the pandemic.
Abstract 12492: Relation of Medical and Social Determinants of Health to Use of Guideline-Directed Medical Therapy for Heart Failure With Reduced Ejection Fraction in the All of Us Research Program
Authors: Do Trinh K , Grace Kyrillos , Gong Yufan , Devineni Divya , Lombardo Dawn , Wong Nathan D , Lee Andy
Published: December 2023

Background:
HFrEF is associated with significant morbidity and mortality. The standard of care is guideline-directed medical therapy (GDMT) consisting of evidence-based pharmacological interventions which have demonstrated improved outcomes in HFrEF. However, paltry adherence to GDMT remains an ongoing challenge. We examined in US adults the relationship between social determinants of health (SDOH), demographics, and risk factors on GDMT adherence for HFrEF.

Methods:
The NIH All of Us Research Program started in May 2018 with the goal of enrolling over 1 million US residents. Over 315,000 participants have shared electronic health records, physical measurements, surveys, and lab results. Demographics, risk factors, and SDOH measures were captured for HFrEF in US adults 18 years or older. Patients with HFrEF who were on quadruple therapy (ACE-inhibitor/angiotensin receptor/combination angiotensin receptor-neprilysin inhibitor, beta-blocker, SGLT2 inhibitor, mineralocorticoid antagonist) were compared to those on fewer. Multiple logistic regression analyses were conducted to examine the association between risk factors/SDOH measures and medical therapy optimization.

Results:
In the All of Us data, 6049 patients were identified with HFrEF. Of those patients, 5838 (97%) patients were on less than 4 GDMT, while 210 (3%) patients were on quadruple therapy. Multiple logistics regression showed participants with ASCVD, and diabetes had higher odds (95% CI) of being on quadruple therapy, 2.19 [1.28, 3.99] and 9.07 [4.88, 18.84], respectively, while hypertension had lower odds (0.64 [0.43, 0.95]). Race, income, education, and health insurance types did not predict medical therapy optimization.

Conclusion:
Various cardiovascular conditions were associated with higher odds of being on quadruple therapy. However, sociodemographic factors did not show a correlation of predicting the odds of achieving maximal medical therapy.
Abstract 12494: Role of Ceramide in Estrogen-Induced Oxidative Stress in Endothelial Cells From Individuals Assigned Male at Birth
Authors: Zirgibel Zachary , SenthilKumar Gopika , Lindemer Brian J , Bordas-Murphy Henry , Jaramillo-Torres Maria , Freed Julie K
Published: December 2023

Compared to cis-males and females, risk for cardiovascular disease (CVD) is elevated in trans-females undergoing estrogen-containing gender affirming therapy. We have previously shown that continuous estrogen treatment of arterioles from healthy adults assigned male at birth promotes microvascular endothelial dysfunction, however the mechanism through which estrogen contributes to endothelial damage remains unknown. Estrogen increases expression of neutral sphingomyelinase (NSmase), an enzyme responsible for the production of ceramides. Ceramides are bioactive sphingolipids that can increase cellular levels of hydrogen peroxide (H
2
O
2
). Together, we hypothesize that estrogen increases endothelial levels of oxidative stress through NSmase-mediated ceramide formation. Primary male human umbilical vein endothelial cells (HUVECs; pooled from n=3) were seeded in 8-well microscopy plates prior to treatments. Peroxy yellow 1 (PY1) was used to measure changes in endothelial H
2
O
2
. Wells were imaged at 20x and analyzed using ImageJ. Difference between %change in fluorescence ±standard error (SE) is reported, and significance is determined using One-Way ANOVA. Treatment with 17β-estradiol (E2; 100nM, 48hrs) increased endothelial H
2
O
2
production (control, n=6 vs E2, n=7; 13.9±6.3, p=0.038), an effect diminished in the presence of the NSmase inhibitor GW4869 (GW4869, 4μM, 48hrs; control, n=6 vs E2+GW4869, n=7; 1.7±6.3, p=0.78). Signal specificity for H
2
O
2
was confirmed with PEG-catalase treatment (500U/ml, 48hrs; control, n=6 vs E2+catalase, n=3; 2.3±7.9, p=0.77). Together, these results suggest that estrogen increases oxidative stress in endothelial cells isolated from individuals assigned male at birth which can be prevented through inhibition of the ceramide-forming enzyme NSmase. This work offers mechanistic insight into how estrogen containing gender affirming therapy may potentially contribute to endothelial damage and increase CVD risk in trans-females.
Abstract 126: Does a Difference in Bystander Cardiopulmonary Resuscitation Initiation and Continuation Exist Due to Patient Sex After Accounting for the Bystander-Patient Relationship?
Authors: Aldridge Emogene S , Ball Stephen , Bray Janet , Perera Nirukshi , Whiteside Austin , Finn Judith C
Published: December 2023

Introduction/Background:
Differences in bystander cardiopulmonary resuscitation (B-CPR) provision based on the patient’s sex have been reported extensively, with equivocal results.

Research question:
Do differences in B-CPR according to the patient’s sex exist after adjusting for the bystander-patient relationship?

Aim:
To explore sex differences in B-CPR initiation and continuation for out-of-hospital cardiac arrest (OHCA) patients while accounting for the bystander-patient relationship.

Methods:
We analysed consecutive paramedic-confirmed OHCA emergency calls, from 1 January to 30 April 2021, in Western Australia. Calls included were non-traumatic, non- emergency medical service (EMS)-witnessed OHCA, where the bystander was with the patient and CPR was not already in progress. Calls were reviewed in full, and patient and bystander characteristics were coded. Bystander relationship was categorised as either related to the patient or unrelated. We performed a logistic regression of B-CPR initiation by sex, adjusting for patient age (<65 and ≥65) and location (private and public), and bystander-patient relationship.

Results:
Of the 295 calls included, 203 (69%) of the patients were male, and 164 (56%) were over 65 years of age. Two thirds of the bystanders (65%) were related to the patient. The majority of OHCAs were in private locations (84%). Bystander CPR was initiated in 205 (69%) calls, 69% (139 out of 201) in male patients and 70% (66 out of 94) in female patients (p=0.85). There was no difference in CPR initiation between male and female patients, unadjusted (odds ratio, OR=0.95, 95% confidence interval, 95% CI = 0.56-1.62), or when adjusted for bystander-patient relationship, location, and patient age (OR=0.92, 95% CI=0.53-1.59). Of those who started CPR (205), 175 (85%) bystanders continued performing CPR till EMS arrived. Male OHCA patients were less likely to have CPR continue to EMS arrival than female OHCA patients (OR=0.46, 95% CI=0.16-1.29).

Conclusion:
There was no effect of patient sex on bystander CPR, both before and after accounting for bystander-patient relationship. Bystanders were more likely to continue performing CPR on female OHCA patients.
Abstract 12639: Comparison of Very High-Power Short-Duration, High-Power Short-Duration, and Low-Power Long-Duration Radiofrequency Ablation for Atrial Fibrillation: A Systematic Review and Network Meta-Analysis
Authors: Junarta Joey , Rodriguez Sebastian , Ullah Waqas , Siddiqui Muhammad , Riley Joshua M , Patel Anjani , Dikdan Sean J , Fradin James J , Rosen Jake , Frisch Daniel J
Published: December 2023

Introduction:
The optimal power and duration settings for radiofrequency (RF) atrial fibrillation (AF) ablation is unclear. We compared low-power long-duration (LPLD), high-power short-duration (HPSD), and very HPSD (vHPSD) settings for AF ablation.

Hypothesis:
Ablation utilizing HPSD and vHPSD are expected to have shorter procedural times than LPLD and may have improved arrhythmic outcomes.

Aims:
To compare LPLD, HPSD, and vHPSD ablation by network meta-analysis

Methods:
This network meta-analysis (NMA) was structured according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Observational and randomized studies were included. Eligible studies compared outcomes in AF patients who underwent first-time RF ablation with the following settings: vHPSD (70-90 Watts for 3-10 seconds), HPSD (45-60 W, 5-10 s), or LPLD (20-40 W, 20-60 s).

Results:
Thirty-six studies comprising 10375 patients were included (33% female). Frequentist NMA showed LPLD tended towards a lower odds of freedom from arrhythmia (FFA) vs. HPSD (OR 0.93, 95% CI 0.86-1.00). There was no difference in FFA between vHPSD vs. HPSD. Splitwise interval estimates showed a lower odds of FFA in LPLD vs. vHPSD on direct (OR 0.78, 95% CI 0.65-0.93) and network estimates (OR 0.85, 95% CI 0.73-0.98). Frequentist NMA showed less total procedural (TP) time with HPSD vs. LPLD (generic variance 1.06, 95% CI 0.83-1.29) and no difference between HPSD vs. vHPSD.

Conclusion:
This NMA shows improved procedural times in HPSD and vHPSD vs. LPLD. Although HPSD tended towards improved odds of FFA compared to LPLD, the result was not statistically significant. The odds of FFA in LPLD was lower vs. vHPSD on direct and network estimates on splitwise interval analysis. Randomized clinical trials are needed to validate HPSD and vHPSD settings.
Abstract 12653: Plasma LTBP-2 is Associated With Myocardial LTBP-2 and Poor Prognosis in Dilated Cardiomyopathy
Authors: Nishiura Kazuto , Yokokawa Tetsuro , Misaka Tomofumi , Ichimura Shohei , Tomita Yusuke , Miura Shunsuke , Shimizu Takeshi , Sato Takamasa , Kaneshiro Takashi , Oikawa Masayoshi , Yoshihisa Akiomi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: December 2023

Introduction:
Cardiac extracellular matrix proteins provide structural support to the heart function and are associated with fibrosis in dilated cardiomyopathy (DCM). Latent transforming growth factor beta-binding protein 2 (LTBP-2) is a type of extracellular matrix protein, but the significance of LTBP-2 in patients with dilated cardiomyopathy is still unclear.

Objective:
To elucidate the significance of LTBP-2 in dilated cardiomyopathy.

Methods:
Plasma LTBP-2 levels were measured by Enzyme-linked immunosorbent assay in 131 DCM patients who underwent endomyocardial biopsy and 44 controls who had no history of cardiac diseases. Immunohistochemistry for LTBP-2, LTBP-1 (another LTBP family member), and Elastica-Masson staining were performed in endomyocardial biopsy specimens. DCM patients were followed up for cardiac death or ventricular assist device (VAD) implantation.

Results:
DCM patients had elevated plasma LTBP-2 levels compared to controls (104 vs. 57 ng/mL, P < 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen (R = 0.311, P < 0.001). Myocardial LTBP-2-positive fraction was positively correlated with myocardial LTBP-1-positive fraction (R = 0.444, P = 0.014) and fibrosis fraction estimated by Elastica-Masson staining (R = 0.387, P < 0.001). In the Kaplan-Meier analysis, the high plasma LTBP-2 concentration group and the high myocardial LTBP-2-positive fraction group had more cardiac deaths or VAD implantations than low groups (P = 0.008 and P < 0.001, respectively). Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with cardiac death or VAD implantation.

Conclusion:
Plasma LTBP-2 reflects myocardial LTBP-2 and can be a biomarker to predict adverse outcomes in DCM patients.
Abstract 12661: Area Deprivation Index, Symptoms, and Biomarkers Among Black and African Americans Living With Heart Failure
Authors: Herring Christopher H , Davis Erica , Higgins Melinda K , Morris Alanna , Dunbar Sandra B , Butts Brittany
Published: December 2023

Introduction:
Heart failure (HF) is a complex chronic condition that disproportionally affects Black adults. Social determinants of health, such as the lived environment and socioeconomic status, contribute to higher incidence and poorer outcomes, including higher stress and poorer sleep in this population. This study aims to examine the relationship between neighborhood socioeconomic disadvantage with symptoms, and inflammatory and cardiometabolic markers in Black adults living with HF.

Methods:
A secondary analysis of a pilot study that enrolled self-identified Black adults living with HF was performed (N=41, 57 ± 11 years of age, 66% women). Neighborhood socioeconomic disadvantage was measured by Area Deprivation Index (ADI) national and state rankings generated from the Neighborhood Atlas; higher scores reflect higher neighborhood disadvantage. Questionnaires included Perceived Stress Scale (PSS) and PROMIS Sleep Disturbance. Inflammatory and cardiometabolic biomarkers were measured via immunoassay. Spearman correlation analyses were performed.

Results:
Mean ADI scores were 61.23 ± 21.1 (national) and 5.7 ± 2.4 (state). National and State ADI scores were positively associated with both PSS (ρ=.584, p<.001; ρ=.551, p<.001) and PROMIS Sleep Disturbance (ρ=.486, p=.04; ρ =.551, p=<.001), respectively. Additionally, National and State ADI scores were positively associated with inflammatory cytokines IL-4 (ρ=.345, p=.031; ρ=.371, p=.020) and IL-18 (ρ=.408, p=.009; ρ=.392, p=.012). National and State ADI scores were also related to cardiometabolic biomarkers VCAM-1 (ρ=.360, p=.022; ρ=.363, p=.021) and C1QNTF1 (ρ=.483, p=.002; ρ=.447, p=.004). No significant association was found between ADI scores and demographics.

Discussion:
These findings suggest higher ADI scores are associated with higher perceived stress, sleep disturbance, and inflammatory and cardiometabolic biomarkers among Black adults living with HF. These results highlight the potential role neighborhood socioeconomic status contributes to adverse health outcomes in this population.Further research is warranted to identify mechanisms contributing to these relationships and to develop approaches to reduce the impact of health disparities in HF.
Abstract 12703: Hydroxychloroquine Induced Cardiomyopathy: A Case Report and Suggestions for Screening
Authors: Hamza Izhan , Ellauzi Rama , Malik Hamza , Mushtaq Mahammed , Safdar Zaid
Published: December 2023

Introduction:
Hydroxychloroquine (HCQ) is a commonly used drug for autoimmune diseases. However, it can in rare instances result in life-threatening cardiac consequences. We present a case of HCQ-induced cardiomyopathy in a 61-year-old female.

Case presentation:
A 61-year-old female with a 15-year history of SLE (Systemic Lupus Erythematosus) presented with new onset heart failure and atrial fibrillation. The patient reported slowly progressive dyspnea on exertion for the last 6 months with worsening bilateral lower extremity swelling. A TTE revealed a moderately dilated left ventricle with an ejection fraction of 20%, with biatrial enlargement. An admission EKG showed new-onset atrial fibrillation. Subsequently, left and right heart catheterization showed normal coronaries, elevated filling pressures with equalization of the wedge, and right atrial pressure suggestive of a restrictive etiology. cMRI was deferred as the patient had multiple abdominal pellets from a prior gunshot wound. An endomyocardial biopsy was obtained which revealed myocardial vacuolization and lipofuscin deposition consistent with HCQ-induced cardiomyopathy. HCQ was discontinued and the patient was discharged on Guideline-directed medical therapy with repeat TTE showing an improved ejection fraction of 40% without the persistence of any symptoms.

Discussion:
Myocardial toxicity associated with HCQ remains a difficult diagnosis, particularly due to the multiplicity of clinical presentations, echocardiographic and EKG features. The onset of cardiomyopathy in these patients is seen after exposure to a high cumulative dose. Presently there are no guidelines regarding the need for cardiac surveillance in patients using HCQ, unlike the need for Ophthalmic exams. Therefore, it is paramount that patients exposed to high cumulative doses of HCQ be screened in a cost-effective way. Especially since a delayed diagnosis is associated with a poorer prognosis.
Abstract 12704: Racial, Ethnic, and Socioeconomic Disparities in Incidence and Survival for Pediatric Out-of-Hospital Cardiac Arrest in the United States: A Report From the Cardiac Arrest Registry to Enhance Survival (CARES)
Authors: Gathers Cody-Aaron , Naim Maryam , Griffis Heather , McNally Bryan F , Al-Araji Rabab , Berg Robert A , chung sarita , Nadkarni Vinay M , Rossano Joseph
Published: December 2023

Introduction:
Racial, ethnic, and socioeconomic disparities in pediatric out-of-hospital cardiac arrest (OHCA) exist; however, pediatric OHCA incidence and survival outcomes among race, ethnicity, and socioeconomic status (SES) are unknown. We evaluated the incidence and outcomes of pediatric OHCA among race, ethnicity, and SES, hypothesizing that Black and Hispanic children, and children from a lower SES, would have higher incidence rates and lower survival compared to White children.

Methods:
We conducted a retrospective cohort study using the Cardiac Arrest Registry to Enhance Survival database, analyzing nontraumatic OHCAs in children<18 years old between 2015 and 2019. A previously validated SES risk score, incorporating race, ethnicity, household income, high school graduation rates, and unemployment rates, was developed on a scale from 0-4, with 4 indicating the highest-risk neighborhood.

Results:
Among 6945 OHCAs, 33% occurred in Black children, 11% in Hispanic children, 31% in White children, and 41% in the highest-risk neighborhood. Black children had the highest OHCA incidence (15.5 per 100,000 children) compared to White children (3.8 per 100,000 children) and Hispanic children (3.3 per 100,000 children) (p<0.001). OHCA incidence was higher in high-risk neighborhoods (11.6 per 100,000) compared to low-risk neighborhoods (4.3 per 100,000) (p<0.001). In multivariable analysis, Black children had lower odds of survival to hospital discharge (aOR 0.74, CI 0.59-0.92) and neurologically favorable survival (aOR 0.64, CI 0.50-0.82) compared to White children. Hispanic children did not have significantly worse survival outcomes compared to White children. Children from the lowest-risk neighborhoods had higher odds of survival to hospital discharge (aOR 1.45, CI 1.12-1.87) and neurologically favorable survival (aOR 1.65, CI 1.24-2.20) compared to children from the highest-risk neighborhoods.

Conclusions:
Significant racial, ethnic, and socioeconomic disparities exist in pediatric OHCA. Black children have over four times the incidence of OHCA compared to White and Hispanic children and significantly worse survival outcomes. Children from low-risk neighborhoods have significantly better survival outcomes.
Abstract 12705: Identification and Characterization of Solbinsiran, a GalNAc Conjugated siRNA Targeting Angiopoietin-Like 3
Authors: Dudek Hank , Abrams Marc , Saxena Utsav , Turanov Anton , Brown Bob , Ruotolo Giacomo , Michael Laura
Published: December 2023

Introduction:
While statins play an important role in reducing LDL-C levels and the risk of ASCVD events, residual risk from apolipoprotein B (apoB)-containing lipoprotein particles persists among patients with or at high risk of ASCVD.

Hypothesis:
Blocking ANGPTL3 activity or preventing its expression is a therapeutic approach to reduce apoB-containing lipoprotein particles. Solbinsiran (LY3561774), a novel Dicer-substrate small interfering RNA oligonucleotide, was designed to reduce the levels of ANGPTL3 protein expression.

Methods:
Nucleotide base sequences of a library of anti-ANGPTL3 siRNAs were selected using an
in silico
RNAi prediction algorithm on
ANGPTL3
mRNA sequences conserved in humans and cynomolgus monkeys. Through a large-scale
in vitro
screen of the anti-ANGPTL3 library in human cells, the candidate solbinsiran sequence was identified as an efficacious siRNA. Solbinsiran
in vivo
efficacy was measured by RT-qPCR of liver from CD-1 female mice overexpressing human
ANGPTL3
. The degree and durability of
ANGPTL3
mRNA knockdown and circulating protein level reduction by solbinsiran was evaluated in cynomolgus monkeys administered single dose subcutaneous injections of either PBS or 3 mg/kg solbinsiran. Blood samples to measure ANGPTL3 protein were collected on Study Days -8, -5, and 0, and weekly after dosing until Day 113. Ultrasound-guided core needle liver biopsies were collected on Study Days 5, 28, 56, 84, and 113. Total RNA derived from the liver biopsy samples to measure
ANGPTL3
mRNA was subjected to RT-qPCR analysis.

Results:
When given a single dose at 1 mg/kg subcutaneously, solbinsiran reduced human
ANGPTL3
mRNA by 65% in hepatocytes as compared to vehicle-treated mice. A single dose of solbinsiran reduced liver
ANGPTL3
mRNA expression by up to 72.9% (p<0.0001) and serum ANGPTL3 protein expression by 68.6% (p<0.001). Solbinsiran also displayed a long duration of activity, as indicated by a greater than 50% mRNA knockdown remaining 12 weeks after a single dose.

Conclusions:
These data supported the advancement of solbinsiran to Phase 1 clinical testing in participants with mixed dyslipidemia (ClinicalTrials.gov Identifier: NCT04644809).
Abstract 12734: A Sex-Stratified Analysis of Social Determinants of Health and Adverse Cardiovascular Outcomes in Atrial Fibrillation
Authors: Zhou Yusheng , Houle Jonathan , Proietti Marco , Raparelli Valeria , Norris Colleen M , Abrahamowicz Michal , Lip Gregory , Boriani Giuseppe , Pilote Louise
Published: December 2023

Introduction:
Atrial fibrillation (AF) is associated with a heightened risk of adverse cardiovascular outcomes. Current prediction models often overlook potential sex differences, as well as the combined influence of gendered social determinants of health (SDOH) with traditional cardiovascular risk factors. The objective of this study is to compare the associations between social determinants and adverse outcomes in models stratified by sex.

Methods:
Participants were sourced from the EURObservational Research Programme-Atrial Fibrillation (ESC-EHRA EORP-AF) General Long-Term Registry. Alongside CHA
2
DS
2
-VASc variables, SDOH factors, including education, living arrangements, gender inequality index (GII), and EQ-5D-5L questionnaire subscales, were evaluated. The primary outcome was a composite of major adverse cardiovascular events (MACE) and all-cause mortality. We evaluated the predictive performance of various models using C-statistics, including individual CHA2DS2-VASc components, SDOH only, and a combined model.

Results:
Among 11,096 patients (mean age: 69.2 years; 40.7% females) from 27 European countries, sex-stratified analyses indicated fewer SDOH associations with composite outcomes in females compared to males. For both females and males, higher self-reported health and regular exercise were associated with lower risk of composite outcomes. In the male model only, a higher education level, higher GII, reduced mobility, reduced self-care ability, alcohol use, and smoking were all associated with an increased risk of MACE and all-cause mortality (Figure 1). The combined model demonstrated modest superior predictive performance, while the improvement when combining CHA2DS2-VASc and SDOH components appears more pronounced in males compared to females.

Conclusions:
The study highlights the distinct impact of SDOH in AF, with males exhibiting a wider range of SDOH factors associated with outcomes.
Abstract 12756: The Interplay of Self-Care Maintenance, Social Support, Depressive Symptoms and Anxiety in Predicting Quality of Life in Patients With Heart Failure
Authors: Thapa Ashmita , Kang JungHee , Chung Misook L , Wu Jia Rong , Biddle Martha J , Moser Debra K
Published: December 2023

Introduction:
Depressive symptoms, anxiety, and inadequate social support are predictors of quality of life (QOL) in patients with heart failure (HF), but prediction of QOL is multifaceted and mechanisms underlying association are unknown. Essential to better HF outcomes, self-care maintenance (SCM) may moderate associations among these predictors. The interplay among depressive symptoms, anxiety, social support, and SCM and their influence on QOL remains uncertain.

Purpose:
To determine whether (1) depressive symptoms and anxiety mediate the association of social support with QOL, and (2) SCM moderates the relationship of social support with depressive symptoms, anxiety, and QOL.

Methods:
We included 167 patients (61 ± 12 years old, 65% male, 47% NYHA III/IV) with HF, who completed the Patient Health Questionnaire-9 to measure depressive symptoms, Brief Symptom Inventory for anxiety, Multidimensional Scale of Perceived Social Support for social support, Self-Care of Heart Failure Index for SCM, and Minnesota Living with Heart Failure Questionnaire for QOL. A moderated mediation model was performed using PROCESS macro.

Results:
We found an indirect association of social support with QOL, mediated by depressive symptoms and anxiety (Figure). The beneficial impact of social support on depressive symptoms and anxiety varied with SCM, suggesting a dose-response moderation effect, which is attenuated at lower SCM scores (Figure). The indices of moderated mediation via depressive symptoms and anxiety were -.007 (95%CI: -.150, -.002) and -.005 (95%CI: -.010, -.002), respectively. There was no direct nor moderated direct effect.

Conclusions:
There is a pivotal interplay of SCM, depressive symptoms, anxiety, social support, and QOL in HF. Findings suggest that improvement in depressive symptoms and anxiety may improve QOL in HF. Moreover, good SCM may enhance the positive effect of social support on depressive symptoms and anxiety.
Abstract 12762: Plasma Lipidomic Signature of Peripheral Artery Disease in Young and Middle-Aged American Indian Individuals: The Strong Heart Family Study
Authors: Chen Mingjing , Miao Guanhong , Roman Mary J , Devereux Richard B , Zhang Ying , Umans Jason G , Cole Shelley , Fiehn Oliver , Zhao Jinying
Published: December 2023

Introduction:
Dyslipidemia is an independent risk factor for peripheral artery disease (PAD). Ankle-brachial index (ABI) is a sensitive and cost-effective tool for screening and predicting PAD. The association between individual lipid species and the progression in subclinical PAD, assessed by change in ABI, remains to be determined, especially in understudied populations at high risk.

Hypothesis:
To identify individual molecular lipid species associated with PAD progression in American Indians, independent of traditional risk factors.

Methods:
Using an untargeted lipidomic method by liquid chromatography-mass spectrometry, we repeatedly measured 1,542 individual lipid species in 2,830 fasting plasma samples at two time points (2001-2003 and 2006-2009, mean 5 years apart) from 1,415 unique American Indians in the Strong Heart Family Study. Participants were free of prevalent PAD at both time points. ABI was measured in the right arm and bilateral (both left and right posterior tibial artery) using a handheld Doppler and was analyzed as a continuous variable. We first identified baseline lipid species associated with change in ABI by generalized estimating equation models, adjusting for baseline age, sex, BMI, smoking, eGFR, diabetes, hypertension, lipid-lowering medication and baseline ABI. We then examined the longitudinal association between change in lipid species and change in ABI, adjusting for same covariates plus baseline lipids.

Results:
Participants (63% female) were aged between 18-65 (mean 38) at baseline and 22-72 (mean 43) at follow-up. Higher baseline levels of 36 lipid species were positively (ORs: 1.01 - 3.60), whereas 16 lipid species were inversely (ORs: 0.26 - 0.98), associated with change in ABI. Longitudinal changes in 77 lipid species, largely glycerolipids, glycerophospholipids, and sphingolipids, were significantly associated with change in ABI during 5-year follow-up.

Conclusions:
Baseline plasma lipid species and their longitudinal changes over time are significantly associated with PAD progression beyond known risk factors. These findings shed light on the role of dyslipidemia in PAD among young and middle-aged American Indians who suffer high rates of obesity, diabetes and other cardiometabolic disorders.