bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15439: Association of Vigorous Physical Activity With Cardiovascular Disease and Mortality in 136,766 Adults From High-Income, Middle-Income and Low-Income Countries: The Prospective Urban Rural Epidemiological (PURE) Study
Authors: Lear Scott , LI SIDONG , Rangarajan Sumathy , Yusuf Salim
Published: December 2023

Background:
It’s recommended adults get 150-300 minutes of moderate physical activity (MPA) and/or 75-150 minutes of vigorous physical activity (VPA) per week. Some studies have found high VPA to be protective and others found it to be harmful. These studies have been conducted in high-income countries using recreational VPA as the exposure of interest.

Purpose: To evaluate the effects of VPA with all-cause mortality, and cardiovascular disease (CVD) in countries at different economic levels.

Methods:
Participants aged 35-70 years were recruited from 21 countries at various stages of economic development. Physical activity (total, walking, MPA, VPA, as well as recreational vs. non-recreational PA) was assessed using the International Physical Activity Questionnaire. Primary clinical outcomes were the composite of mortality plus major CVD (CVD mortality, myocardial infarction, stroke, or heart failure) and mortality. A total of 136,766 participants without baseline CVD, cancer, and HIV were analyzed. Models were adjusted for age, sex, urban/rural residency, country income level, education, household wealth index, smoking, baseline chronic diseases, physical impairments, MPA, walking and centre as a random effect.

Results:
During the median follow-up of 11.5 (8.6-12.4) years, there were 9846 deaths and 7900 major CVD events. The median min/wk (IQR) for total PA, walking, MPA and VPA were 690 (250-1530), 40 (0-420), 330 (75-860), 0 (0-0). The mean VPA was 103±390 min/wk. Compared to no VPA, 150-299 minutes per week of VPA was associated with reduced risk for the composite outcome and mortality, HR = 0.82 (0.73,0.92) and 0.74 (0.64,0.86), respectively. When VPA was stratified into either recreational or non-recreational VPA, recreational VPA displayed a U-shape relationship, such that higher levels were associated with less benefit. Increasing non-recreational VPA continued to confer reduced risk even above 3000 min/wk. At any amount of moderate PA, higher VPA was associated with reduced risk for the composite outcome and mortality.

Conclusion:
Higher levels of VPA were associated with reduced risk for mortality and major CVD events up to more than 40 times the minimum recommended amount. At no point did VPA confer an increased risk.
Abstract 15451: Regulations of Nrf2 by Nf-κB in Ischemic Heart Failure
Authors: Navar Evelyn , Thai Phung , Diloretto Daphne , Sirish Padmini , Zhang Xiao-Dong , Chiamvimonvat Nipavan , Knowlton Anne A
Published: December 2023

Introduction:
Oxidative stress is an important pathophysiological factor in the development and progression of ischemic heart failure (IHF). Nuclear factor E2-related factor 2 (Nrf2) is a major regulator of the protective antioxidant response and has been found to decrease by 50% in IHF. However, the mechanism of Nrf2 downregulation remains incompletely understood. NF-kB is a critical transcription factor that influences many cellular processes and is activated in IHF with increased reactive oxygen species (ROS). We hypothesize that activation of NF-kB may underlie the decreased Nrf2 activity in IHF.

Methods and Results:
To induce IHF, we performed left anterior descending coronary artery (LAD) ligation surgery in Sprague Dawley rats and FVB/NJ mice. We found a significant reduction in cardiac function after LAD surgery in ischemia/reperfusion (I/R) mice relative to sham-operated mice using echocardiography. Tissue sample analyses reveal a crucial role of NF-kB activation in the regulation of Nrf2 in IHF. Additionally, after 2 weeks of I/R, we found that rats treated with Nrf2 overexpressed lentivirus demonstrated greater pressure development than rats with vehicle treatment. Using rat cardiac myoblast cells (H9C2) and western blot analysis, we tested the expression of cytosolic and nuclear Nrf2 and p65 (a component of NF-kB) following time- and dose-dependent treatments of H2O2. We found that p65 activation inhibited Nrf2 activity, while inhibitions of p65 nuclear translocation prevented the decrease in Nrf2 nuclear activities. We then generated a knockout of p65 in H9C2 cells and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using CRISPR-Cas9 technology to test NF-κB regulation on the Nrf2 activities, which further strengthened our previous findings.

Conclusions:
Taken together, our data support the critical role of NF-kB activation in the regulation of Nrf2 in IHF, providing new insights into possible molecular targets for the treatment of IHF through the regulation of the protective antioxidant response.
Abstract 15452: Using a Commercial Virtual Health Platform to Effectively Treat Obesity and Improve Cardiometabolic Risk Factors at Scale
Authors: Boyd Kim , medeiros kaelen L , Ryan Donna , Kenyon Isabelle
Published: December 2023

Introduction:
Obesity is a critical risk factor for cardiometabolic disease, yet effective treatment has not been available at scale for the >200 million Americans who meet criteria for obesity treatment. To improve access to evidence-based treatment, we established a virtual metabolic health company to provide medically supervised obesity treatment at scale.

Research Questions: This real-world evaluation examines the impact of a virtual health program on weight and related cardiometabolic markers as well as self-reported assessment of key health behaviors in food, exercise, sleep, and emotional health.

Methods:
Data were analyzed for individuals who completed at least 12 months in the core program. Obesity treatment involved GLP-1 receptor agonist medications combined with a proprietary intensive lifestyle intervention delivered with virtual coaching. Weights were submitted via cellular connected scale. Waist circumference, metabolic labs, and patient questionnaires were also analyzed at baseline and 12 months.

Results:
The cohort includes 2,643 patients who completed at least 12 months. Average weight loss at 12, 15, and 18 months was 15.58% (n=2,397), 15.97% (n=1,319), and 15.82% (n=569). Improvement was observed for all collected metabolic markers: waist circumference, AST/ALT, lipids, HbA1c, insulin, hs-CRP. Specifically for cardiovascular labs, 12 month endpoints showed improvement in HDL in 51% (n= 1180), in LDL for 61% (n=1174), in hs-CRP for 81% (n=956). Of n=303 with abnormal A1c at baseline, 72.9% achieve A1c <5.7%. Average reduction in waist circumference was 5.95 inches (n=1,507). Positive changes were also seen for patient-reported outcomes.

Discussion:
Given limited access to effective obesity treatment as a pathway to better cardiometabolic disease management, novel approaches must be developed. Results from 2,643 enrollees in a virtual metabolic health program demonstrate clinically significant and sustained weight loss through 18 months, with improvement in associated key cardiometabolic risk markers, health behaviors, and patient-reported outcomes. This commercial program demonstrates promising results in cardiometabolic risk improvement through medically managed weight loss delivered virtually.
Abstract 15455: Unraveling the Mechanism of Ischemia in Pediatric Patients With R-AAOCA: Fixed and Dynamic Obstruction
Authors: Eilers Lindsay , Doan Tam , Gowda Srinath , Qureshi Athar , Sachdeva Shagun , Binsalamah Ziyad , Reaves-O’Neal Dana , Molossi Silvana M
Published: December 2023

Introduction:
Although rare, anomalous aortic origin of the right coronary artery (R-AAOCA) is associated with exercise-related sudden cardiac death and dynamic obstruction to coronary flow in the intramural segment has been proposed as the ischemia mechanism. We aim to describe fixed and dynamic obstruction mechanism of ischemia in select group of R-AAOCA patients undergoing invasive transcatheter stress FFR and iFR.

Hypothesis:
Ischemia in R-AAOCA involves a 2-tier mechanism involving both fixed and dynamic obstruction.

Methods:
Single institution retrospective study of R-AAOCA patients undergoing cardiac catheterization due to ischemic symptoms and negative perfusion defects on dobutamine stress CMRI. Coronary angiography was performed in all patients. Instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) were performed at baseline and under pharmacologic stress with adenosine (aFFR)/dobutamine (diFR) when the coronary ostium was engaged in a stable manner. Significant fixed obstruction was considered if aFFR<0.80 and dynamic if diFR <0.85.

Results:
A total of 14/446 (3%) R-AAOCA patients were included. In 10 patients, a Verrata pressure guide wire (Volcano, San Diego, CA) was able to be advanced to perform iFR and FFR. Fixed RCA obstruction was demonstrated in 4/10 patients (40%) and 2 of these (2/10, 20%) also had dynamic RCA obstruction (Table). All 4 patients were referred to surgery: 3 completed, 1 pending. In 4/14 (28%) patients, iFR and FFR were not performed due to inability to engage the RCA ostium, all of which found to be hypoplastic (1-1.5 mm) and slit-like at surgery. There were no procedural complications.

Conclusions:
In a small cohort of R-AAOCA patients, mechanisms for myocardial ischemia during stress suggest dynamic and fixed components. Our preliminary results provide important insight for risk stratification. Long-term follow-up will be important to validate the performance of iFR/FFR in R-AAOCA
Abstract 15466: Social Determinants of Health Vulnerabilities Among Patients With Substance Use Disorder and Infective Endocarditis
Authors: Mansoor Hend , Bae Jungjun , Anthony Nicholas , Harris Daniel , Delcher Chris
Published: December 2023

Introduction:
Data indicate that the incidence of infective endocarditis (IE) is rising among patients with substance use disorder (SUD) and is linked with increased mortality. However, the social determinants of health (SDOH) vulnerabilities associated with IE in this population has not been well characterized.

Aims:
To examine the SDOH associated with IE among patients with SUD.

Methods:
Using our electronic medical records, we identified patients with concurrent diagnosis of IE and SUD from 2017 until May 2023. Socio-demographics and SDOH including unstable housing (identified using diagnosis codes, residential address test, and natural language processing of clinical notes documenting homelessness and shelter referrals) were identified. A multivariable regression model was conducted to identity independent risk factors associated with IE among patients with SUD.

Results:
Among 26,918 patients admitted with an SUD encounter, 1,422 (5.3%) had an IE encounter. Patients with IE were younger (37 vs 43 years, P<0.001), mostly white (96% vs 87.7%, P<0.001), Medicaid enrollees (84.2% vs 58.6%, P<0.001), and had less than high school education (10.6% vs 8.1%, P=0.005). They were more likely to reside in rural areas (58.1% vs 44.8%) and have unstable housing (28.6% vs 16.3%). Patients with IE had higher prevalence of smoking (83.5% vs 67.3%) as well as cardiac, dental, mental and other health conditions. Certain socio-demographics and SDOH were independently associated with IE on multivariable regression (Figure).

Conclusions:
Patients with SUD and IE have distinct socio-demographics and SDOH characteristics. Incorporating these factors into future risk prediction tools could better help identifying SUD patients who are at risk to implement targeted techniques which have been proven to lower the risk of infection.
Abstract 15476: Advanced Assessment of Regional Differences in Myocardial Perfusion by Spectral CT in Patients With Acute Myocarditis
Authors: Herrera Flores Cristian , Sánchez-Puente Antonio , de Molina Claudia , Vicente-Palacios Víctor , Perez-Sánchez Pablo , López-Jiménez Rosa Ana , Hernández-Martos Ángel , Rodriguez-Diego Sara , Nieto García Leticia , Rincon Luis M , Sánchez Javier , Wiemker Rafael , Sanchez Pedro L , Pérez del Villar Candelas
Published: December 2023

Introduction:
Spectral CT (SCT) is a valuable tool for assessing coronary anatomy and myocardial damage. Iodine distribution maps (IDM) obtained by SCT serve as surrogates for first-pass myocardial perfusion, exhibiting reduced iodine uptake in ischemic areas and increased uptake in hyperemic areas due to inflammatory injury. Hypothesis: We aimed to determine if SCT data analysis can detect regional differences in first-pass myocardial perfusion reflecting inflammatory injury in acute myocarditis (AM) patients.

Methods:
We retrospectively searched for acute myocarditis patients admitted to our center who also underwent SCT angiography to rule out CAD. Spectral images (40 keV monoenergetic images and IDM) from a dual-layer CT scanner (Philips Spectral CT 7500) were analyzed using a perfusion tool developed by Philips Research. LV myocardium was segmented following the AHA-17 model, and CT number (HU) and iodine density values (mg/ml) were quantified. Data were normalized using blood pool values. Healthy controls were included for comparison and differences were assessed with a one-way ANOVA.

Results:
Six patients with myocarditis (median age: 57 [IQR 30-65]; table 1) and 3 controls (median age: 50 [IQR: 47.5-59.5]) were analyzed. Myocarditis patients (figure 1) showed higher normalized median iodine density values (ratio 0.13 vs. 0.11, p<0.001) and similar differences in 40 keV monoenergetic images (ratio 0.16 vs. 0.13, p=0.005).

Conclusions:
Spectral CT data analysis can detect first-pass myocardial perfusion differences in acute myocarditis patients, likely reflecting hyperemia. Further research is needed to evaluate the clinical benefits of SCT in this context.
Abstract 15482: Trends in Cardiovascular Health Among Older Adults With and Without Cardiovascular Diseases: National Health and Nutrition Examination Survey (NHANES), 2013-2018
Authors: Walker James , Won Daniel , Patel Ravi , Ning Hongyan , Lloyd-Jones Donald M
Published: December 2023

Introduction:
American Heart Association’s (AHA) Life’s Essential 8 (LE8) is a framework for quantifying cardiovascular health (CVH). Prior studies have focused on individuals without clinical cardiovascular disease (CVD). We sought to examine recent trends in LE8 scores among older adults with prevalent CVD.

Methods:
We included non-institutionalized older US adults (ages 65+) from NHANES (2013-18). Overall LE8 scores (range 0-100; higher = better CVH) were calculated for all participants with or without CVD, using methods recommended by the AHA. CVD diagnoses were self-reported, including coronary heart disease (CHD), stroke, heart failure (HF), hypertension (HTN), angina, and myocardial infarction (MI). Percent change in LE8 scores from 2013-18 was calculated for each diagnosis group, and a linear regression tested for significance of changes within groups.

Results:
The 3,050 participants represented 37,908,305 adults (54.7% women; mean age 72.6 y); 3.4% self-identified as Asian, 7.2% Black, 3.9% Mexican, 3.3% Other Hispanic, 2.4% Multi-racial, and 79.9% Non-Hispanic White. Overall LE8 scores tended to stay stable or decline between 2013-14 and 2017-18 for individuals with and without CVD (Figure 1). Significant decreases in mean LE8 scores occurred in those with HTN, with a 4.1% decline from 2013-18 (from 59.6 [95% CI: 58.4-60.8] to 57.1 [55.9-58.4]), stroke, with a 11.5% decline (from 60.6 [56.0-65.2] to 53.6 [50.7-56.5]), and HF, with a 15.2% decline (from 60.9 [57.2-64.6] to 51.6 [48.0-55.2]).

Conclusions:
Recent LE8 scores remained stable or declined for older US adults even before the pandemic. In particular, individuals with HTN, stroke, and HF had significant declines in LE8 scores. Since LE8 metrics include behavioral and physiologic metrics associated with CVD risk, these data indicate concerning trends and primary and secondary prevention opportunities in older US adults, who are at highest risk for incident and recurrent CVD events.
Abstract 15484: Heart Transplantation in a Light-Chain Amyloidosis Patient at Mayo Stage IIIa After Anti-Plasma Cell Chemotherapy With Complete Remission
Authors: Bi Keying , Wan Ke , Xu Yuanwei , Wang JIE , Li Weihao , Chen Yucheng
Published: December 2023

A 42-year-old female patient was admitted for lower limb edema. Laboratory tests showed nephrotic proteinuria (2.76g/24h). Serum-free λ light chains were 84.9 mg/L, with a κ/λ ratio of 0.12. Bone marrow examination detected 6% immature clonal plasma cells. Amyloid deposition was identified in a renal biopsy. Cardiac magnetic resonance (CMR) revealed normal left ventricular ejection fraction (LVEF), left ventricular circumferential late gadolinium enhancement (LGE), and elevated myocardial T1 value (1459ms) and extracellular volume (47.4%). She was diagnosed with AL amyloidosis and classed as IIIa by the Mayo Stage 2004. A hematologic complete response (CR) was achieved and sustained after treatment with sequencing cyclophosphamide, bortezomib, dexamethasone (CyBorD) and daratumumab regimen. The follow-up CMRs were underwent at 6, 12, and 18 months after starting chemotherapy, which monitored cardiac changes in reponse to CR. Unfortunately, there was no alleviation of cardiac involvement. CMR re-examination (at 42 months) revealed severe cardiac function impairment (LVEF 28%), and dramatically increased extracellular volume (66.2%). Then, she underwent heart transplantation (HTx) evaluated by the heart transplantation multidisciplinary team. Three months later, she was doing well, CMR demonstrated stable cardiac allograft function. Repeated endomyocardial biopsies showed no amyloid deposits. This case illustrates that cardiac amyloid deposition might be a dynamic process in AL amyloidosis and highlights the value of CMR in long-term monitoring and identifying the patients reached CR who need HTx.
Abstract 15558: Blood Pressure Responses During Exercise Were Associated With Average Home Blood Pressure and Home Blood Pressure Variability: The Electronic Framingham Heart Study
Authors: Wang Xuzhi , Zhang Yuankai , Pathiravasan Chathurangi H , Spartano Nicole L , Benjamin Emelia J , McManus David D , Lewis Gregory , Larson Martin , Ramachandran Vasan S , Murabito Joanne , Liu Chunyu , Nayor Matthew G
Published: December 2023

Introduction:
Abnormal blood pressure (BP) responses during exercise are associated with incident hypertension and cardiovascular disease, but how exercise BP responses relate to average home BP and home BP variability (BPV) over one-year follow-up is unknown.

Objective:
We investigated whether exercise BP was associated with average home BP and home BPV, after accounting for resting BP, in the electronic Framingham Heart Study (eFHS). We hypothesized that higher exercise BP predicts higher average home BP and home BPV over one-year follow-up.

Methods:
At a FHS research exam (2016-2019), participants underwent maximum incremental ramp cycle ergometry cardiopulmonary exercise testing (CPET) with BP measured every two minutes. Participants enrolled in the eFHS were provided with a digital BP cuff to measure home BP weekly for up to one year. Linear regression models were used to examine associations of exercise BP with average home systolic BP (SBP) and week-to-week average real variability (ARV) of home SBP over one-year follow-up, adjusting for covariates. ARV, which considers both the dispersion and order of BP readings, was quantified as the average of the absolute differences between consecutive BP readings. We used p<0.05 for significance.

Results:
The study sample included 806 participants (mean age 53 years, 58% women, 46% hypertension, median number of home BP returns 22, average home SBP 122 mmHg). Adjusting for resting SBP and other covariates, higher exercise SBP (as measured by peak SBP, SBP at 75 Watts, and SBP/workload slope) was associated with higher average home SBP (
Figure 1A
). Higher SBP/workload slope was associated with elevated ARV of home SBP in men (
Figure 1B
).

Conclusion:
Higher exercise SBP responses are associated with higher average digital home-based SBP and home-based SBP variability over one-year follow-up after accounting for resting SBP.
Abstract 15566: Dissecting the Genetic Architecture of Intracranial Aneurysms
Authors: Adkar Shaunak , lynch julie , Bamezai Sharika , Sorondo Sabina , Choi Ryan , Cabot John , Levin Michael , Damrauer Scott M , Pyarajan Saiju , Tsao Philip S , Skirboll Stephen , Leeper Nick J , Klarin Derek
Published: December 2023

Introduction:
The genetic risk of intracranial aneurysm (IA) development has been ascribed largely to smoking and hypertension. The contribution of IA risk loci to aberrant gene programs within cerebrovascular cell types remains unclear.

Hypothesis:
We hypothesized that candidate causal genes at IA susceptibility loci are enriched within extracellular matrix producing cell types.

Methods:
We identified participants enrolled in the Million Veterans Program (MVP) with and without IA. Thirty-two million genotyped and imputed variants were tested for association with IA using mixed effect regression modeling, controlling for age, sex, and population structure prior to external replication and meta-analysis. Candidate causal genes were prioritized through expression quantitative trait loci colocalization and transcriptome wide association studies. We constructed a cerebrovascular single nucleus RNA sequencing (snRNA-seq) dataset and integrated IA summary statistics to compute a ‘disease relevance score’ per nucleus using the scDRS pipeline. Cell type level analysis was used to assess association of cerebrovascular cell types with IA.

Results:
We identified 3165 participants (2280 European, 627 African, and 258 Hispanic ancestry) with and 592927 without IA in the MVP. After replication and meta-analysis with data from an additional 12273 cases and 591046 controls, we identified 22 loci (5 novel) associated with IA. We prioritized 16 candidate causal genes. Gene expression analysis of snRNA-seq genes revealed enrichment of several candidate genes, including
EDNRA
and
PLCE1
within smooth muscle cells (SMCs) and pericytes. Integration of summary statistics and snRNA-seq data revealed significant association of matrix-producing pericytes and smooth muscle cell populations with IA.

Conclusion:
Here, we identify novel loci associated with IA and found enrichment of candidate causal genes in pericytes and SMCs. Integration of summary statistics with cerebrovascular snRNA-seq reveals association of cell-types involved in matrix production, suggesting an intrinsic deficit in matrix production and vascular integrity that may drive IA pathogenesis independent of systemic hypertension.
Abstract 15568: Myocardial Strain Assessment for Comprehensive Risk Prediction in Patients Following Acute Myocardial Infarction
Authors: Lange Torben , Gertz Roman , Schulz Alexander , Backhaus Soeren J , Evertz Ruben , Kowallick Johannes T , Hasenfuss Gerd , Desch Steffen , Desch Steffen , Thiele Holger , Stiermaier Thomas , Eitel Ingo , Schuster Andreas
Published: December 2023

Background:
Cardiovascular magnetic resonance-feature tracking (CMR-FT) derived strain analyses provide incremental prognosticbenefit in patients following acute myocardial infarction (AMI). This study aimed to evaluate and re-validate previously reportedprognostic implications of comprehensive strain analyses in a large independent cohort of patients with ST-elevation myocardialinfarction (STEMI).

Methods:
Overall, 566 STEMI patients of the CONDITIONING-LIPSIA trial including pre-/postconditioning treatment and/orconventional percutaneous coronary intervention underwent CMR imaging in median 3 days after primary percutaneous coronaryintervention. CMR-based left atrial (LA) reservoir (Es), conduit (Ee) and boosterpump (Ea) strain as well as left ventricular (LV)global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain analyses were carried out. Previously identified cut-offvalues were revalidated for risk stratification. Major adverse cardiac events (MACE) comprising death, reinfarction and newcongestive heart failure were assessed within 12 months after the index event.

Results:
Both atrial and ventricular strain values were significantly reduced in patients with MACE (p<0.01 for all). PredeterminedLA and LV strain cut-offs enabled accurate risk assessment. All LA and LV strain values were associated with MACE on univariableregression modeling (p<0.001 for all) with LA Es emerging as independent predictor of MACE on multivariable regression modeling(HR 0.92, p=0.033). Furthermore, LA Es provided an incremental prognostic value above LVEF (c-index increase from 0.7 to 0.74,p=0.03).

Conclusion:
External validation of CMR-FT-derived LA and LV strain evaluations confirmed the prognostic value of cardiacdeformation assessment in STEMI patients. Within the current study especially LA strain parameters enabled further riskstratification and prognostic assessment over and above clinically established risk parameters.
Abstract 15591: Well-Being of Interventional Cardiologists: Sex Differences
Authors: Alexandrou Michaella , Simsek Bahadir , Rempakos Athanasios , Kostantinis Spyridon , Karacsonyi Judit , Rangan Bavana V , Mastrodemos Olga , Kirtane Ajay J , Bortnick Anna E , Jneid Hani , Azzalini Lorenzo , Milkas Anastasios , Alaswad Khaldoon , Linzer Mark , Egred Mohaned , Mutlu Deniz , Al-ogaili Ahmed , Rao Sunil V , Allana Salman S , Sandoval Yader , Brilakis Emmanouil S
Published: December 2023

Background:
Sex differences in the well-being of interventional cardiologists have received limited study.

Methods:
We conducted an international, anonymous, online survey exploring the sex variations in the well-being of interventional cardiologists.

Results:
Of 1,251 survey participants 121 (9.7%) were women. Women were more likely to be under 50 (82.6% vs 73.1%, p=0.031) and single (25.6% vs 7.9%, p<0.001) and were more commonly practicing at academic institutions or hospitals with academic affiliation (69.2% vs 59.3%, p=0.046). There was no difference in overall burnout between women and men (68.7% vs 63.4%, p=0.353). On a scale of 0-10, men reported more often that too much paperwork (6.9±2.5 vs 6.2±2.7, p=0.013) and government regulations (4.8±3.1 vs 3.6±2.8, p<0.001) are contributors to burnout. Women reported less often getting well along with colleagues (7.0±2.9 vs 7.5±2.1, p=0.047) and more often felt lonely during the last year (5.5±3.1 vs 4.3±3.2, p=0.001). Men reported that they more commonly choose exercise as a coping mechanism for burnout (4.8±3.2 vs 3.8±3.1, p=0.005), while women more often choose talking with family/friends (6.8±2.5 vs 5.8±2.8, p=0.003). Women prioritize additional paid time off (7.5±2.5 vs 6.9±2.7, p=0.041) as the most preferable wellness-related action and asked more often for respect/recognition from administration, opportunities for professional growth and mentorship opportunities.

Conclusions:
This survey indicates sex differences in contributors and coping mechanisms to burnout. Our data suggest that communication with administration and career development opportunities could be explored as remediable factors for burnout among all interventional cardiologists; and might be especially valuable in women.
Abstract 15622: Impella Use in Patients With Cardiogenic Shock is Associated With the Highest Inpatient Mortality in Comparison to Lowest Mortality Seen With the Use of Intraaortic Balloon Pump Using Large Nationwide Inpatient Sample (NIS) Database
Authors: Movahed Mohammad Reza , Talle Armin , Hashemzadeh Mehrtash
Published: December 2023

Introduction:
Impella and intra-aortic balloon pumps (IABP) are commonly used in patients with cardiogenic shock. However, the effect on mortality in this population has not been well established.

Hypothesis:
To evaluate the effect of Impella or IABP on mortality in patients with cardiogenic shock.

Methods:
We utilized the very large Nationwide Inpatient Sample (NIS) database to evaluate any association between the use of IABP or Impella on mortality in adults with cardiogenic shocks using uni- and multivariate analysis adjusting for comorbid conditions.

Results:
ICD-10 codes for Impella, IABP, and cardiogenic shock for available years 2016-2020 were utilized. A total of 844,020 patients had a cardiogenic shock. 101,870 (mean age 65.2) were treated with IABP and 39,645 (mean age 64.4) with an Impella. Total inpatient mortality without any device was 34.2% vs only 25.1% with IABP but was highest 40.7% with Impella. Using multivariate analysis adjusting for age, gender, race, three-vessel intervention, left main myocardial infarction, cardiomyopathy, systolic heart failure, acute ST-elevation myocardial infarction, peripheral vascular disease, chronic renal disease, diabetes, and smoking, Impella utilization remained associated with the highest mortality (OR: 1.56, CI 1.48-1.64, p<0.001) whereas IABP remained associated with the lowest mortality (OR: 0.69, CI 0.66-0.72, p<0.001).

Conclusions:
Using the largest database of its kind revealed that the use of Impella was associated with much higher mortality compared to no use as opposed to utilization of IABP showing the lowest mortality in patients with cardiogenic shock.
Abstract 15626: Novel Function Annotation Tool Revealed Obesity-Induced Inflammation is Exacerbated by miR-150 Regulated B Cell Receptor Signaling
Authors: Matz Alyssa J , Qu Lili , Karlinsey Keaton , Li Ivy , Vella Anthony T , Aguiar Derek , Zhou Beiyan
Published: December 2023

B cells exacerbate obesity-induced metabolic dysfunction and become the second most abundant immune lineage in obese adipose tissue. However, high-resolution strategies to interrogate cellular dynamics driving B cell responses under chronic obesity stress are lacking, stifling innovative B cell-targeted therapies against obesity-induced health risk. Our previous work established the potent role of miR-150 in adipose tissue B cells’ (ATB) pro-inflammatory responses under obesity. This project aims to elucidate the mechanism of miR-150 regulated ATB actions that bolster obesity-induced inflammation.

Method:
We employed single-cell techniques to decipher obesity-perturbed signaling networks in B cell-specific miR-150 gain/loss of function mouse models 
in vivo
and 
ex vivo
. We utilized our novel B cell function annotation tool, B-RAY, to quantify B cell cytokine production, antibody secretion, and antigen presentation from single-cell RNA-Seq. These strengths permitted several key findings:

Result:
A) miR-150 overexpression in mature B cells alone improved systemic glucose tolerance in obesity, despite similar body adiposity. In line, miR-150 knock-out worsened glucose tolerance. B) In obese adipose tissue, B cells were skewed towards higher cytokine production and antigen presentation and away from antibody secretion compared to lean tissue. Importantly, ATBs in obesity displayed increased activity of miR-150 direct targets, Myb, Etf1, and Elk1, and reduced expression of miR-150. C) ATBs in obesity were enriched in B cell receptor (BCR) signaling and downstream cascades. miR-150 overexpression B cells exhibited reduced BCR-mediated Syk phosphorylation and calcium influx, while miR-150 knock-out yielded enhanced responses.

Conclusion:
These results support the hypothesis that miR-150 regulation of ATBs limits chronic inflammation in obese adipose tissue via modulating BCR signaling to prevent excessive B cell cytokine production and antigen presentation. Future work will investigate ATB actions and BCR activation in miR-150 gain/loss of function mice across time in diet-induced obesity. Collectively, this work will elucidate an important immunoregulatory network bolstering obesity-induced inflammation and health risk.
Abstract 15634: Primary Prevention Defibrillator Use in a Safety-Net Setting
Authors: Durstenfeld Matthew S , Thakkar Anjali , Jeon Diane , Short Robert , Ma Yifei , Dewland Thomas A , lee byron , Davis Jonathan D , Hsue Priscilla Y
Published: December 2023

Introduction:
Disparities in use of implantable cardioverter-defibrillators (ICD) for primary prevention have been documented; however, whether ICDs may be underutilized within a safety-net healthcare system has not been studied.

Methods:
Using an electronic health record cohort of all patients with heart failure (HF) who received care within the public safety-net system in San Francisco from 2001-2018 linked to device implantation records from two health systems, we identified all patients with ICD implantation (adjudicated with manual chart review) and primary prevention ICD-eligible with no indication for secondary prevention ICD, EF<35% on 2 echocardiograms at least 90 days apart, HF hospitalization (to increase specificity for symptomatic HF), and prescribed beta blocker and ACEi/ARB. For exploratory survival analysis, eligibility and follow up started at the second echocardiogram.

Results:
Out of 14,230 patients with HF, at least 384 patients were potentially eligible for primary prevention ICD, but only 9 (2.3%) had an ICD implanted (2 CRT-D, 7 ICD). Of these 6 were nonischemic, and 3 had revascularized ischemic cardiomyopathy. Those who received ICD were younger (47 years vs 55 years; p=0.05), with lower rates of substance use (Table). Among 4 patients who died after ICD, median survival after device placement was 2.8 years (range 0.73 to 7.3); among 5 still alive, median follow up is 6.2 years (range 5.5 to 7.0). In an exploratory analysis, survival did not greatly differ by ICD placement (logrank p=0.53; age-adjusted HR 1.55; 95%CI 0.57-4.24).

Conclusion:
Among individuals receiving care at a safety-net system in San Francisco, even acknowledging that not all barriers to ICD placement are measured, very few guideline-eligible patients received primary prevention ICD. Additional studies are needed to identify patient-level and systems-level barriers to referral and implantation specific to a diverse, publicly insured patient population.
Abstract 15691: Permanent Pacemaker Implantation After Aortic Valve Surgery for Infective Endocarditis Was Associated With an Increased Risk of Heart Failure
Authors: Bearpark Lisa O , Dismorr Michael , Franco-Cereceda Anders , Sartipy Ulrik , Glaser Natalie
Published: December 2023

Background
Surgery for infective endocarditis (IE) is associated with a high risk of receiving a new permanent pacemaker. The clinical impact of permanent pacemaker implantation in these patients is unknown.
Research question
Does permanent pacemaker implantation after aortic valve surgery for IE affect long-term clinical outcomes?
Aims
To analyze the risk of mortality, heart failure hospitalization, and prosthetic valve endocarditis in patients who received a permanent pacemaker within 30 days of aortic valve surgery for IE.

Methods:
In this nationwide, population-based, observational cohort study based on the SWEDEHEART register, we included all patients who underwent primary aortic valve replacement for IE in Sweden from 1997 to 2022. Patients with a preoperative cardiac implantable electronic device were excluded. The primary outcome was all-cause mortality. Secondary outcomes were heart failure hospitalization and prosthetic valve endocarditis. Follow-up was complete. Inverse probability of treatment weighting was used to account for intergroup differences and flexible parametric models were used to estimate cause-specific hazards and cumulative incidences.

Results:
Among 2110 patients, 131 patients (6%) received a new permanent pacemaker, and 1979 patients (94%) did not. The mean age was 59 years, and 433 patients (21%) were female. During a mean follow-up time of 8.5 years (maximum 26 years), 873 patients (41%) died. The cumulative incidence of all-cause mortality and heart failure hospitalization at 20 years was 66% (95% CI 46%-79%) versus 61% (95% CI 58%-64%) and 45% (95% CI 33%-58%) versus 32% (95% CI 29%-34%) in the pacemaker versus the non-pacemaker group, respectively. After adjustment, there was no difference in the risk of mortality (HR 1.14, 95% CI: 0.82-1.59) or reinfection (HR 1.00, 95% CI 0.63-1.59), but the risk of heart failure was increased in the pacemaker group (HR 1.67, 95% CI: 1.11-2.52).

Conclusion
Permanent pacemaker implantation after aortic valve surgery for IE was associated with an increased risk of heart failure, but there was no difference in the risk of long-term mortality or prosthetic valve endocarditis. These results suggest that patients who receive a pacemaker after surgery for IE warrant careful observation.
Abstract 15714: Racial Disparities in Major Adverse Cardiac and Cerebrovascular Events Among Young Women (Aged 18-44) Admitted in Rural Settings: “A Comprehensive National Inpatient Analysis 2019”
Authors: Tera Chenna reddy , Vatsavayi Priyanka , Jitta Sahas Reddy , Maramreddy Supriya , Krishnamurthy Shobana , Tripuraneni Sridevi , Pasnoor Diksha Sanjana , Adla Jala Saisree Reddy , Reddy Medha , Dasari Utheja , Farooq Aisha , jammula kavya , Desai Rupak
Published: December 2023

Background:
Limited research has focused on the rising incidence of major adverse cardiac and cerebrovascular events (MACCE) among young women (aged 18-44) with at least one traditional cardiovascular disease risk factor (CVD), especially in rural hospital settings. We aimed to address this research gap by providing insights into the burden of CVD in this population.

Methods:
Using data from the National Inpatient Sample (2019), we identified young women (aged 18-44) with at least one cardiovascular risk factor admitted to rural hospitals. Baseline demographics, comorbidities, and outcomes were assessed, including MACCE and all-cause mortality. Multivariable logistic regression was performed, adjusting for age, race, income, and comorbidities.

Results:
Among 179,410 young women, MACCE occurred in 2,455 individuals (1.4%), with varying rates among racial groups: whites (1.2%), blacks (2.4%), Hispanics (1.3%), Asian or Pacific Islanders (API) (2%), Native Americans (NA) (1.6%), and others (1%). All-cause mortality was observed in 385 women (0.2%), with rates of 0.2% for whites and 0.4% for blacks. Blacks had twice the event rates of MACCE, and all-cause mortality compared to whites. Comorbidities and substance abuse were associated with MACCE (P<0.001). In higher-income households, multivariable analysis adjusted for confounders revealed significantly higher odds of MACCE in blacks (OR 1.23, 95% CI 0.11-14.08), API (OR 4.48, 95% CI 1.06-18.93), and NA (OR 10.22, 95% CI 1.03-101.50) compared to whites. In contrast, mortality rates were lower for Hispanics than whites (OR 0.24, 95% CI 0.02-3.80) (all p < 0.001) (Table 1).

Conclusion:
In higher-income households, greater odds of MACCE were noted among blacks, API, and NA compared to whites. Future research should focus on understanding factors contributing to these disparities and developing interventions to prioritize equitable healthcare access for rural women across diverse ethnic and income classes.
Abstract 15732: Chronic Mavacamten Treatment Has Opposing Effects on Contractility in Engineered Heart Tissue Models of Severe vs. Mild Hypertrophic Cardiomyopathy
Authors: De Lange Willem J , Gauchan Angeela , Nelson Natalie A , Farrell Emily T , Ralphe John C
Published: December 2023

Many hypertrophic cardiomyopathy (HCM) causing mutations result in myocardial hypercontractility by increasing the number of myosin crossbridges in the disordered relaxed (DRX) state, or by sensitizing the sarcomere to the effects of Ca
2+
. Mavacamten (Mava) recently became the first FDA-approved treatment of obstructive HCM that directly targets hypercontractility by reducing the number of DRX cross bridges. Mava improves outcomes in patients with obstructive HCM but has not been approved in children or adults without obstructive HCM. The efficacy of chronic Mava treatment at preventing phenotype development in asymptomatic HCM mutation carriers remains largely unexplored. We recently showed that ablation of cardiac myosin binding protein-C (cMyBP-C -/-) in engineered heart tissue (EHT) causes rapid phenotype development in a dish. Initial hypercontractility progresses to hypocontractility with impaired relaxation, mediated by Ca
2+
mishandling. Here we investigate whether chronic Mava administration prevents phenotype progression. cMyBP-C +/+, +/- and -/- EHT were treated with 100nM Mava starting on day 7 of EHT culture. Serial twitch force (TF) measurements were performed weekly for 5 weeks, using the Mantarray platform. At day 7, prior to Mava treatment, +/- and -/- produced significantly more TF than +/+ EHT (392 ± 9 μN vs. 390 ± 15 μN vs. 199 ± 13 μN). At day 14, Mava treatment reduced TF by 31% (p < 0.001) in +/+ EHT, 30% (p < 0.001) in +/- EHT and 12% (p = 0.115) in -/- EHT. After an additional 4 weeks, chronic Mava treatment reduced TF by 54% (p < 0.001) in +/+ EHT, 65% (p < 0.001) in +/- EHT but
increased
TF by 23% (p = 0.034) in -/- EHT.These data show that chronic Mava treatment prevents/slows maladaptive remodeling in -/- EHT, but depresses contractility in +/+ and +/- ECT, suggesting that chronic Mava treatment may be detrimental to patients with mild HCM. Our ongoing studies are assessing the effect of chronic Mava treatment on other EHT models of HCM and on Ca
2+
-handling.
Abstract 15734: Local Admixture Mapping of Metabolites in African Americans
Authors: Cruz Daniel E , Raffield Laura M , Deng Shuliang , Wilson James , Gerszten Robert E
Published: December 2023

Introduction:
There is increasing evidence that metabolite levels in African Americans (AA) are influenced by population differentiated genetic variation. We investigated how local genetic ancestry may be associated with levels of circulating plasma metabolites using metabolomic profiling in the Jackson Heart Study, an AA cohort, in an attempt to identify additional genetic determinants of metabolite levels.

Hypothesis:
Certain metabolites will be associated with local African genetic ancestry.

Methods:
We performed admixture mapping using local ancestry estimates (probabilities of whether an individual has 0, 1 or 2 alleles of African ancestry at each site in the genome from RFMix, based on similarity to 1000G reference panel) from TOPMed sequencing data for autosomal SNPs. Associations were then tested for 302 targeted metabolites measured using LC-MS. Each local ancestry regression model was adjusted for age, sex, and estimated global ancestry. We used a previously established significance threshold for local African ancestry analysis, p<2.1X10
-5
. We further adjusted findings for previously reported GWAS variants in conditional analysis.

Results:
There were 38 local admixture mapping signals for 32 metabolites. Fourteen metabolite signals survived conditional analysis and represent signals distinct from those identified in single variant GWAS. Metabolites of note include the branched chain amino acids, whose association with cardiometabolic disease has been shown to differ based on self-identified race.

Conclusions:
We present local admixture mapping results providing further evidence that population differentiated genetic variants influence circulating levels of plasma metabolites. For a large proportion of our findings, admixture associations were not attenuated by conditioning on previously reported SNPs from GWAS studies. These analyses suggest that admixture mapping may identify association signals that are missed by GWAS, and may help to elucidate population differences affecting key biologic pathways.
Abstract 15749: Long-Term Vascular Events in Pregnant Women With Congenital Heart Disease: The Magee Obstetric Maternal and Infant (MOMI) ACHD Substudy
Authors: Saraf Anita , Pastena Paola , Hindes Morgan , Berlacher Kathryn , Hoskoppal Arvind , Catov Janet M , Kalogeropoulos Andreas P
Published: December 2023

Introduction:
Data on long-term post-delivery risk for vascular events, including cerebrovascular and thromboembolic (TE) events, among women with adult congenital heart disease (ACHD), are limited.

Hypothesis:
Risk for vascular events remains elevated in the long-term after delivery in pregnant women with ACHD.

Methods:
Data from the University of Pittsburgh Medical Center clinical data warehouse were linked to all deliveries from 2004 to 2020 in pregnant women with ACHD (N=430) and without ACHD (N=876), who were included in the Magee Obstetric Maternal and Infant (MOMI) study. Women were matched at the delivery level for age, delivery year, and race. Ischemic and TE vascular events were captured until 8/31/2022. Cerebrovascular events were captured with codes I6X.X (ICD-10) and 43X.X (ICD-9); venous TE events with I82.X, I26.X, 453.X, and 415.X; arterial TE with I74.X, I75.X, 444.X, and 445.X; and acute coronary events with I20.X, I21.X, I24.X, 410.X, and 413.X. Kaplan-Meier (K-M) estimates were used for incidence and compared with Cox proportional hazards models.

Results:
Baseline characteristics and pregnancy outcomes are presented in
Table 1
. After a median of 5.1 (2.8, 8.8) years, women with ACHD experienced 24 cerebrovascular events (5-year K-M: 5.2%), compared to 8 events (5-year K-M: 0.3%) in controls (HR 7.00; 95%CI 3.14 - 15.6; P<0.001), and 8 venous TE (5-year K-M: 2.6%) vs. 11 (5-year K-M: 1.0%) events, (HR 1.69; 95%CI 0.68 - 4.18; P=0.26),
Fig. 1
. There were no arterial TE events. Only 1 woman (with ACHD) experienced an acute coronary event.

Conclusions:
Women with ACHD remain at elevated risk for cerebrovascular but not venous TE events in the long-term after delivery.
Abstract 15755: Associations Between Use of Assisted Reproductive Technology Intrauterine Insemination With Adverse Pregnancy Outcomes in U.S. Natality Data, 2016 - 2021
Authors: Avula Vennela , Boyer Theresa , Sun Kevin , Ndumele Chiadi E , Michos Erin D , Baker Valerie , Anderson Shannon , Vaught Arthur J , Hays Allison , Coresh Josef , Minhas Anum A
Published: December 2023

Background/Hypothesis:
Assisted reproductive technology (ART) and intrauterine insemination (IUI) may be associated with increased risk of adverse pregnancy outcomes (APOs) and contribute to future cardiovascular disease.

Aims:
To determine the joint association of ART/IUI and pre-pregnancy cardiometabolic factors with APOs in a national sample.

Methods:
We analyzed Natality Data from the National Vital Statistics System of the National Center for Health Statistics between 2016-2021. We used multivariable logistic regression to estimate the joint association of ART/IUI and pre-pregnancy cardiometabolic risk factors with APOs.

Results:
Among 21,625,155 deliveries, women who conceived with either ART (n=228,597) or IUI (n=136,630) were older, more likely White or Asian race, more educated, and less likely to smoke than those who conceived without fertility treatments. Compared to pregnancies conceived without fertility treatments and with no pre-pregnancy cardiometabolic risk factors, ART/IUI-conceived pregnancies were generally associated with increased risk of gestational diabetes, pregnancy induced hypertension, and eclampsia among both women with and without pre-pregnancy cardiometabolic risk factors (Table 1). Women who conceived with ART/IUI and had ≥ 2 cardiometabolic risk factors had the highest adjusted OR of gestational diabetes (2.45 [2.41, 2.67]), while those who conceived with ART/IUI and had pre-pregnancy diabetes had the highest adjusted OR of pregnancy induced hypertension (3.37 [3.00, 3.79]).

Conclusions:
Patients with pregnancies conceived by ART/IUI are at an increased risk of APOs, including gestational diabetes, pregnancy induced hypertension and eclampsia. The presence of pre-pregnancy cardiometabolic factors modestly increases this risk. Clinicians should consider targeted strategies to optimize the pre-pregnancy cardiometabolic health of women seeking infertility treatments.