bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12942: The D801N Variant in
ATP1A3
-Encoded Na/K-atpase Alpha 3 Shortens the Cardiac Myocyte Action Potential and Increases Risk for Calcium Mediated Arrhythmias
Authors: BIDZIMOU MINU , ZHANG ZHUSHAN , Ezekian Jordan E , Clifford Alex , Le Ninh Dao An , Moya-Mendez Mary E , Zheng Scott , Perelli Robin , Sun Bo , Hunanyan Arsen , Breglio Andrew , Helfer Abbigail , Bers Donald M , Bursac Nenad , Mikati Mohamad , Landstrom Andrew P
Published: December 2023

Background:
Alternating hemiplegia of childhood (AHC) is a rare
de novo
syndrome that manifests with episodic hemiplegia, seizures, dystonia, and, notably, sudden unexplained death. Gene positive patients carry a pathogenic variant in the
ATP1A3
-encoded Na/K ATPase alpha 3 isoform (ATP1A3), and the variant D801N is the most common pathogenic variant. Our group recently found that AHC patients with ATP1A3-D801N missense have short QTc and are at risk of ventricular fibrillation.

Hypothesis:
We hypothesized that the D801N variant results in reduced ATPase function leading to Ca
2+
overload resulting in shortened repolarization time and increased arrhythmogenic risk.

Methods:
We differentiated iPSCs into cardiomyocytes from an AHC patient hosting the ATP1A3-D801N variant (iPSC-CM
D801N
), and an ostensibly healthy individual (iPSC-CM
WT
). Patch clamp was conducted to determine APD90, and the ratio of cells with delayed after depolarization events (DADs). iPSC-CM
WT
were perfused with 10
-7
M ouabain, an ATP1A3 inhibitor, and APD90 and DADs were measured. SR store ([Ca
2+
]
SR
) was measured with Cal-520 dye under 10 mM caffeine. Resting [Ca
2+
]
i
was measured with Fura-2 dye, and Na/Ca exchanger (NCX) peak current was measured as Ni
2+
sensitive current in a stepwise voltage-clamp protocol.

Results:
iPSC-CM
D801N
APD90 was shorter 40% than iPSC-CM
WT
. IPSC-CM
WT
treated with ouabain had 17% shorter APD90 than vehicle. iPSC-CM
D801N
had DADs (3/11 cells) when iPSC-CM
WT
(0/24) did not, and 6/12 ouabain treated iPSC-CM
WT
had DADs vs vehicle treated (0/18). Post caffeine, iPSC-CM
D801N
had higher [Ca
2+
]
SR
than iPSC-CM
WT
. Finally, iPSC-CM
D801N
had higher resting [Ca
2+
]
i
than iPSC-CM
WT
and iPSC-CM
D801N
had higher peak NCX current density at +80mV but no difference at RMP.

Conclusions:
Our results show that both iPSC-CM
D801N
and ouabain-treated iPSC-CM
WT
, have a shorter APD compared to WT controls and exhibit DADs. This is associated with higher NCX-mediated influx of Ca
2+
and increased intracellular Ca
2+
. Our findings highlight the emerging role of ATP1A3-D801N in creating a myocardium vulnerable to arrhythmias.
Abstract 12985: Trends and Disparities in Cardiovascular Death in Sarcoidosis: A Population-Based Retrospective Study in the United States From 1999 to 2020
Authors: Tan Min Choon , Mirza Noreen , Yeo Yong Hao , San Boon Jian , Tan Jian Liang , Lee Justin , Mazzarelli Joanne , Russo Andrea M
Published: December 2023

Background:
Sarcoidosis is a multisystem inflammatory disease that could result in debilitating cardiac manifestations. Despites, data on the cardiovascular deaths (CVDs) among patients with sarcoidosis are limited.

Objective:
This study sought to determine the longitudinal trends in mortality attributed to CVDs with comorbid sarcoidosis by age, sex, and race in the United States.

Methods:
We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database and performed serial cross-sectional analyses of national death certificate data for CVDs with comorbid sarcoidosis among patients aged 25 and above. Diseases of the circulatory system (ICD-10 I00-I99) were listed as the underlying cause of death, and sarcoidosis (ICD-10 D86) as contributing cause of death. We calculated age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and determined the trends over time by estimating the annual percent change using the Joinpoint Regression Program.

Results:
In the 22-year study period, 5,630 CVDs with comorbid sarcoidosis in the United States were identified between 1999 and 2020. The AAMRs from CVDs with comorbid sarcoidosis increased from 1.03 (95% CI, 0.88-1.17) in 1999 to 1.38 (95% CI, 1.24-1.52) in 2020. Overall, women recorded a higher AAMRs compared to men (1.25 [95% CI, 1.21-1.30] vs. 1.10 [95% CI, 1.06-1.15]). Black individuals had higher AAMRs than White individuals (5.17 [95% CI, 4.97-5.37] vs. 0.68 [95% CI, 0.66-0.71]). A higher percentage of CVDs with comorbid sarcoidosis was seen in the age groups of 55-64 in men (24.68%) and 65-74 in women (22.62%).

Conclusion:
The CVDs in sarcoidosis have increased over the last two decades, with disparities seen in women and Black individuals. Most CVDs with comorbid sarcoidosis occurred at a younger age compared to general population. This highlights the importance of early screening for cardiovascular diseases in sarcoidosis individuals.
Abstract 12995: South Asian Representation in Cardiovascular Disease Randomized Controlled Trials
Authors: Uppal Nishant , Patel Aniruddh , Bhatt Deepak , Natarajan Pradeep
Published: December 2023

Introduction:
South Asian individuals are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared to individuals of European descent. Although US practice guidelines uniquely recognize South Asian ancestry as a risk-enhancing factor for ASCVD, the degree to which South Asian individuals are included in clinical trials is unknown. We sought to evaluate South Asian representation in major cardiovascular disease (CVD) randomized controlled trials (RCTs) reported in major medical journals.

Hypothesis:
South Asian individuals are under-represented relative to the global South Asian population in CVD RCTs.

Methods:
We extracted citations of CVD RCTs reported from 2018 to 2022. Studies were identified as RCTs based on reported randomization of participants and the publication of post-randomization data. We determined self-reported representation rates for South Asian individuals across all studies and further stratified representation rates by clinical trial phase, type of intervention under investigation, and country of origin. Post-randomization participant representation rates were estimated for South Asian individuals and compared to other self-reported racial/ethnic groups.

Results:
588,329 participants were enrolled across 128 included trials. Conditions studied included CVA (17.97%), HF (12.50%), CAD (11.72%), HTN (7.81%), ASCVD screening/prevention (7.81%), and others. 2,753 of all CVD RCT participants were South Asian individuals, corresponding to a representation rate of 0.47%. No South Asian individuals had available post-randomization data, whereas post-randomization data were reported for 164,035 white individuals, 20,459 Black individuals, and 6,040 Hispanic individuals.

Conclusions:
Although South Asian individuals comprise nearly a quarter of the global population and have well-documented excess CVD risk, they represent a small minority of CVD trial participants. No RCTs reported South Asian participant-level data, which limits the generalizability of study findings to South Asians.
Abstract 130: Sex Differences in Survival Outcomes of OHCA Patients With Adjustment of In-Hospital Managements With Sex Disparities
Authors: Ahn Sejoong , Kim Woosik , Kim Hyunju , Jin Bo-Yeong , Lee Sukyo , Sung Jin Kim , Cho Hanjin , Moon Sungwoo , Park Sung Joon , cho youngduck , Park Jong-Hak
Published: December 2023

Introduction:
Recently, our group reported that sex differences in in-hospital management such as coronary angiography, and percutaneous coronary intervention exist. Therefore, this study aimed to determine sex differences in survival outcomes of out-of-hospital cardiac arrest (OHCA) after adjusting prehospital and in-hospital variables.

Methods:
This is a retrospective observational study using prospective multicenter registry, Korean Cardiac Arrest Research Consortium. Adult OHCA patients between October 2015 and December 2021 were included. Primary outcome was survival to discharge. Multivariable logistic regression analyses were performed after adjusting prehospital and in-hospital variables.

Results:
Total 10879 adult OHCA patients were analyzed. Survival to discharge and good neurologic outcomes at discharge were lower in women than men (9.4% vs. 16.6%, p<0.001 and 5.6% vs. 11.8%, p<0.001, respectively). After adjustment of prehospital and in-hospital variables (coronary angiography, percutaneous coronary intervention, targeted temperature management and extracorporeal membrane oxygenation), women were more likely to survive to discharge and have good neurologic outcome than men (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.02-1.43, p=0.033 and aOR 1.48, 95% CI 1.18-1.85, p<0.001, respectively). The sex difference in survival to discharge pronounced in age from 45 to 74, and the sex difference in good neurologic outcome pronounced in age from 45 to 84.

Conclusion:
After adjusting prehospital and in-hospital variables, women with OHCA were more likely to survive to discharge and have good neurologic outcome than men.
Abstract 13020: Trend and Disparities in Cardiovascular Death in Amyloidosis: A Population-Based Retrospective Study in the United States From 1999 to 2020
Authors: Tan Min Choon , Yeo Yong Hao , San Boon Jian , Arsanjani Reza , Rosenthal Julie , Lee Kwan S
Published: December 2023

Background:
Despite advancements in the management of cardiac amyloidosis, the contemporary estimates of the cardiovascular deaths (CVDs) in amyloidosis are not well-established.

Objective:
This study sought to assess the longitudinal trends of CVDs with comorbid amyloidosis and analyze the disparities in mortality in terms of race, gender, and geographical location.

Methods:
We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database and performed serial cross-sectional analyses of national death certificate data for cardiovascular mortality with comorbid amyloidosis among patients aged 25 and above. Diseases of the circulatory system (ICD-10 I00-I99) were listed as the underlying cause of death, and amyloidosis (ICD-10 E85) as contributing cause of death. We calculated age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and determined the trends over time by estimating the annual percent change using the Joinpoint Regression Program.

Results:
In the 22-year study period, 4,145 CVDs with comorbid amyloidosis in the United States were identified between 1999 and 2020. The AAMRs increased significantly from 0.69 per 1,000,000 individuals in 1999 to 2.13 per 1,000,000 individuals in 2020 (p< 0.05), with an annual percent increase of +3.92. The AAMRs for the span of 22 years were higher in males than females (1.66 vs. 0.75, p<0.05). When stratified by race, African American populations had the highest cumulative AAMR (2.34) compared to other racial groups. In terms of urbanization, the AAMR was significantly higher in the urban regions compared to the rural areas (1.15 vs. 0.91, p<0.05).

Conclusion:
The AAMRs from CVDs with comorbid amyloidosis have increased significantly over the past two decades, with significant disparities in male and African American individuals. This emphasises the need of further research in the development of effective treatments for amyloid heart disease.
Abstract 13041: Effects of Parity on Arterial Stiffness Persists Into Old Age, Independent of Chronological Ageing
Authors: Thangaraja Keerthana , Basker Gayathri , Gao Fei , Tan Ru S , Lee Gina S , Cheng Charmaine , Teo Loon Yee , Ewe See H , Li Ling-Jun , Koh Angela S
Published: December 2023

Introduction:
Persistent effects of reproductive factors on vascular ageing, over chronological ageing, as examined through objective measurements of arterial stiffness, are rarely studied.

Hypothesis:
We hypothesized that the effects of parity and maternal age at first birth (AFB) on vascular ageing will persist over time independent of chronological ageing, in older Asian women.

Methods:
Among a community-based cohort of older Asian adults without cardiovascular disease, we prospectively studied demographics, parity, AFB, and cardiovascular risk factors, at baseline and 5-year examination timepoints. Arterial stiffness was measured through pulse wave velocity (PWV) using a cuff-based auscultatoric oscillometric pulse wave analysis machine.

Results:
170 women (baseline mean age 60.76±13.75 years) were included. Parity ranged from 0 to 8 (mean parity 2±1.3). AFB ranged from 18 to 44 (mean age 28±4.4) years. By regression, univariate determinants of 5-year PWV were parity (β=0.491, p=<.001), αFB (β=-0.107, p=.011), baseline age (β=3.884, p=<.001), body mass index (βμΙ) (β=0.147, p=.006), waist circumference (β=0.076, p=<.001), diabetes (β=1.681, p=<.004), hypertension (β=2.383, p=<.001), dyslipidemia (β=2.220, p=<.001), 5-year age (β=3.886, p=<.001),waist circumference (β=0.085, p=<.001), diabetes (β=1.723, p=.001), hypertension (β=2.485, p=<.001). Based on multivariate regression, parity (β=0.345, 95% CI 0.105, 0.586, p=.005), but not AFB, was independently associated with 5-year PWV, independent of age.

Conclusions:
Parity and AFB correlated with PWV, a marker of arterial stiffness, in old age in Asian women. Accounting for chronological ageing and clinical factors across 5 years, parity exerted a persistent independent effect on arterial stiffness in older women. Other biological factors surrounding parity in these women apart from traditional cardiovascular risk factors may explain these observations.
Abstract 13048: Outcomes of Transcatheter Edge-to-Edge Repair in Hypertrophic Cardiomyopathy: A Patient-Level Meta-Analysis
Authors: Mascarenhas Lorraine , Yang Gloria , Hubers Scott , Adabag Selcuk
Published: December 2023

Background:
Hypertrophic cardiomyopathy (HCM) is a genetic heart disease, commonly associated with left ventricular outflow tract (LVOT) obstruction and mitral regurgitation (MR). Septal myectomy and alcohol septal ablation are the current treatment options for LVOT obstruction and MR in symptomatic patients who are unresponsive to medical therapy. Recently, transcatheter edge-to-edge repair (TEER) of the mitral valve has been introduced as a new therapeutic alternative for these individuals, but there are insufficient outcome data.

Objective:
Perform a systematic review and patient-level meta-analysis of the studies reporting the outcomes of TEER in HCM.

Methods:
Original studies published in English in PubMed and Google scholar were included if ≥1 of the following pre- and post-TEER measures were reported: peak resting or provoked LVOT gradients, MR grade, or New York Heart Association (NYHA) class. Variables were presented as means with 95% confidence intervals. Paired t-test was used to compare variables pre- and post-TEER. A p-value <0.05 was statistically significant.

Results:
A total of 15 publications reporting the outcomes of 30 patients (mean age 74 years, 45% female, average follow-up of 10 months) were included. Compared to pre-TEER measures, there was a significant reduction in resting LVOT gradient (68.29 vs. 11.76 mmHg), provoked LVOT gradient (119.67 vs. 14.11 mmHg), MR grade (3.52 vs. 1.07), and NYHA class (3.14 vs. 1.38) post-TEER (all p<0.0001) (Figure). However, mean MV gradients increased post-TEER (2.00 vs. 3.55 mmHg, respectively, p=0.0018). There was 1 procedural complication noted in which a patient developed a severe mitral valve (MV) gradient of 10 mmHg after complete leaflet clip closure. This decreased to 6 mmHg when the clips were re-deployed partially open (30°).

Conclusion:
TEER can be an effective therapeutic option for improving LVOT gradient, MR severity, and NYHA class in patients with obstructive HCM.
Abstract 13057: The Role of Ischemic and Bleeding Scores in Patients With Acute Coronary Syndromes Submitted to Coronary Surgical Revascularization During the Same Hospitalization
Authors: Nicolau Jose C , Montero Ribera Jorge L , Bertolin Adriadne , Baracioli Luciano , Giraldez Roberto , Lima Felipe G , Andrade Maria , Castro Vintimilla Santiago , Salis Leonardo , Jatene Fabio , Freitas Fabiane , Dallan Luis Alberto Oliveira , Lisboa Luiz Augusto , Asdrubal Vilca Mejia Omar , Furtado Remo , Godoy Lucas C , farkouh michael
Published: December 2023

Introduction:
The role of bleeding and ischemic scores in ACS patients (pts) submitted to coronary artery bypass surgery (CABG) is poorly understood.

Hypothesis:
To analyze the role of ACUITY/HORIZONS bleeding score (BlS), TIMI ST-elevation myocardial infarction (TIMI-STEMI)/non-ST-elevation ACS (TIMI-ACS), and GRACE in CABG pts.

Methods:
From an administrative databank, we analyzed 999 ACS pts submitted to CABG in the same hospitalization (70.6% men, median age 64 years), from 1999 to 2022. From the whole population (pop.) 504 pts had all above scores available; the whole and sub-group pop. were similar in baseline characteristics, median score values and area under the ROC curves (AUC). Categorical variables were compared with chi-square test; continuous variables (non-Gaussian distribution) were compared with Mann-Whitney test. Multivariable logistic regression, with in-hospital mortality as dependent variable, was performed. The AUC ROC were compared with De Long test.

Results:
1) Association between risk scores and in-hospital mortality: The median (25
th
-75
th
) for pts dead or discharged alive were 19.00 (13.00-26.00) vs 14.00 (10.00-19.00), P<0.001; GRACE 166.00 132.00-202.00 vs. 115.00 96.00-133.00, P<0.001; TIMI STEMI (N=100) 7.00 (4.75-8.00) vs. 4.00 (3.00-5.50), P=0.004; TIMI-ACS (N=404) 4.00 (3-4.50) vs. 4.00 (3.00-4.00), P=0.119. 2) AUC (±SE) for ROC curves: BS 0.674 ± 0.044 P<0.001; GRACE 0.815 ± 0.037 P<0.001; TIMI STEMI 0.775 ± 0.077 P=0.004; TIMI-ACS 0.579 ± 0.046 P=0.131. The predictive value of GRACE score was superior to BlS P=0.015 and TIMI-ACS score P<0.001. 3) Adjusted models: only GRACE was associated with in-hospital mortality in all models; OR=1.032 P<0.001 for the whole pop.; OR=1.078, P=0.002, for STEMI; and OR=1.036, P<0.001for non-STEMI.

Conclusions:
In ACS pts submitted to CABG, BlS, GRACE and TIMI STEMI scores were associated with in-hospital mortality. GRACE score showed the highest discrimination for predicting death.
Abstract 13063: Gut Microbiota-Derived Metabolites and Cardiometabolic Traits: Findings From a Monozygotic Twin Study
Authors: Miao Guanhong , Wu Christopher , Strachan Eric , Fowler Emily , Bacus Tamara , Zhao Jinying
Published: December 2023

Introduction:
Microbial metabolites are small chemical compounds produced by gut microbiota when it breaks down food, chemicals, or other environmental exposures. These metabolites serve as signaling molecules between the host and gut microbiota and regulate numerous aspects of host physiology, immunity, and metabolism.

Hypothesis:
Gut dysbiosis is associated with cardiometabolic disorders via alterations in microbial metabolites.

Aims:
To identify gut-microbiota-derived metabolites associated with cardiometabolic traits.

Methods:
Using hydrophilic interaction liquid chromatography (HILIC), we measured the relative abundances of 62 food and gut-microbiota-derived metabolites in plasma sample of 46 complete monozygotic twin pairs (34 female-female pairs, 12 male-male pairs, mean age 36.2) enrolled in the Mood and Methylation Study (MMS), an observational study designed to identify biomarkers associated with depressive symptoms using a twin design. Information for cardiometabolic traits, including body mass index, waist circumference, blood glucose, HbA1c, insulin, triglycerides, total cholesterol, HDL and LDL, was collected using standard questionnaires or laboratory methods. The association of each metabolite with cardiometabolic trait was examined by a linear mixed-effects model, adjusting for age, sex, smoking, drinking, and depressive symptoms. The co-twin correlation was accounted for by including twin pair as a random effect in the model.

Results:
After correction for multiple testing by false discovery rate (FDR<0.05), 15 microbial metabolites were significantly associated with one or more cardiometabolic traits. Of these, 7 glycerophospholipids (e.g., PC(32:1), PC(34:4), PE(38:6)) and 2 sphingomyelins (i.e., SM(d36:1), SM(d36:2)) were positively, whereas betaine, creatinine, urea, pipecolic acid, N1, N12-diacetylspermine, and 3-chloro-L-tyrosine were negatively associated with LDL, triglycerides, total cholesterol, and HbA1c.

Conclusions:
Our results revealed novel microbial metabolites associated with cardiometabolic traits and support their potentially important role in mediating the interactions between gut microbiota and host pathophysiology.
Abstract 13066: Ten-Year Atherosclerotic Cardiovascular Risk Trajectory Among Women Veterans Diagnosed With Breast, Colorectal, Lung and Thyroid Cancer
Authors: Whyne Erum Z , Shults Erika M , Choi Sung-Hee , Dowell Jonathan E , Conzen Suzanne , Jeon-Slaughter Haekyung
Published: December 2023

Introduction:
Despite recognized sex-difference in cardio-oncology, women are understudied due to lack of large and diverse data. The study examined atherosclerotic cardiovascular disease (ASCVD) risk in women veterans with breast, colorectal, lung, and thyroid cancer using Veterans Affairs (VA) national Electronic Health Records (EHR) data.

Hypothesis:
Elevated ASCVD risk in women with breast, colorectal, lung and thyroid cancer after cancer diagnosis due to accumulated cardiotoxicity induced from cancer therapy.

Methods:
We retrospectively followed 78,556 women veterans aged 30-79 from 2007 to 2017. We used AHA/ACC ASCVD risk score and VA women CVD risk score to measure ASCVD risk over the study period. Both scores included age, systolic blood pressure (treated/untreated), total cholesterol and HDL-C, smoking status, diabetes, and major depression. The study selected the top four most common cancers among women veterans. Discontinuity regression models were used to estimate trajectories of ASCVD risk at both pre and post cancer periods.

Results:
Both pre- and post-cancer ASCVD risk in women with breast, colorectal, and lung cancer was significantly elevated compared to the no cancer group, while women with thyroid cancer had lower ASCVD risk during the pre-cancer diagnosis. All women veterans with cancer except colorectal cancer showed premature aging in ASCVD risk after cancer diagnosis (Figure 1).

Conclusions:
Women cancer survivors are at increased risk of ASCVD not only post-cancer, but also long before their cancer diagnosis. ASCVD risk monitoring and management in women may serve as shared risk reduction and cancer prevention along with heightened cancer screening.
Abstract 13123: Sex-Based Disparity in Referral for Catheter Ablation for Atrial Fibrillation at a Single Integrated Health System
Authors: Gangadharan Arati A , Muhammad Lutfiyya N , Song Jing , Passman Rod S
Published: December 2023

Introduction:
Catheter ablation for atrial fibrillation (AFCA) is indicated for patients with symptomatic AF and has proven to reduce AF burden and improve quality of life. Older studies have shown that women are less likely to undergo ablation compared to men despite having more AF-related symptoms. We investigated whether an association exists between referral patterns and this sex-based disparity in the modern era of AFCA.

Methods and Results:
A retrospective cohort study was conducted of outpatients with newly diagnosed AF between 2011 and 2020 using an EMR database at Northwestern Medicine. Of 5,445 patients analyzed, 2,108 were women (mean [standard deviation, SD] age 70 [13], 19.2% non-Hispanic Black) and 3,337 were men (mean [SD] age 66 [13], 11.7% non-Hispanic Black). Other characteristics including insurance status, comorbidities, and prior treatment of AF were also compared by sex. Logistic regression models adjusted for these factors were constructed to determine associations between sex and a set of binary dependent variables including referrals to and visits with general cardiology and electrophysiology (EP) as well as performance of AFCA. In adjusted models, among internal medicine and primary care patients, there were no significant differences in odds of referral to or visits with general cardiology or EP between men and women. Additionally, there was no significant difference in odds to undergo AFCA between men and women once seen by EP (Figure).

Conclusions:
Our study demonstrates no significant difference with respect to sex in referral patterns or performance of AFCA. Further work must be done to investigate whether these results are generalizable to other health systems regarding performance of AFCA as addressing these differences, when present, could prove essential in dismantling sex-based disparities in AF treatment.
Abstract 13184: Relationships Between Food Insecurity and Dietary Quality in Persons With Cardiovascular Disease in NHANES (National Health and Nutrition Examination Survey), 2009-2020
Authors: Godden Monica M , Bell Janice F , Porter Tequila , Bidwell Julie T
Published: December 2023

Background:
Most guidelines recommend a nutrient-rich, heart-healthy diet for management of cardiovascular disease (CVD). Following dietary guidelines may be challenging for individuals experiencing food insecurity, but there is limited knowledge on how food insecurity relates to diet quality in persons with CVD.

Hypothesis:
We hypothesized that for persons with CVD (hypertension, heart disease, angina, MI, heart failure, or stroke), higher levels of food insecurity would be associated with lower levels of dietary quality.

Methods:
This was a cross-sectional analysis of 5 cycles of data (2009-2020) from the nationally representative National Health and Nutrition Examination Survey (NHANES). Participants aged > 19 with self-reported CVD were included. Food insecurity was measured using the 10-item Food Security Scale. Dietary intake was measured using 24-hour dietary recall from which individual nutrients were derived. Key nutrients examined as indicators of diet quality included sodium, potassium, polyunsaturated and monounsaturated fats, fiber, and total sugars. Relationships between food insecurity and diet quality were quantified using multivariable linear regression models, incorporating NHANES sample weights and controlling for common sociodemographic confounders.

Results:
The sample consisted of 17,102 persons (weighted study
N
= 311,708,767). Half were female (55.48%); most were non-Hispanic White (68.74%) and in middle (45-64 years, 44.82%) or late adulthood (≥65 years, 32.29%). Nearly a quarter (23.9%) were food insecure. With the exception of sodium intake (sodium, mg, β=-156, p=0.02), higher levels of food insecurity were significantly associated with poorer diet quality (potassium, mg: β=-157, p<0.004; polyunsaturated fats, gm: β=-1.81, p<0.003; monounsaturated fats, gm: β= -2.19, p=0.003, fiber, mg: β= -1.08, p=0.003, total sugars, gm: β=13.15; p<0.010).

Conclusions:
In persons with CVD, higher levels of food insecurity were significantly associated with lower diet quality in key nutrients essential for a heart-healthy diet. This study underscores the importance of considering social determinants of health to support patient and family success in following heart-healthy guidelines.
Abstract 13185: Getting at the Heart of Allergies: A Case Series on Kounis Syndrome
Authors: Dragan Anamaria , Toleva Olga , Cutchins Alexis , Mehta Puja K
Published: December 2023

Kounis Syndrome (KS) is a complex medical condition where acute coronary syndrome coincides with allergic reactions. KS presents a unique clinical challenge due to its varied presentation and simultaneous management of an allergic response and a cardiac event. This study aims to further our understanding of this underreported condition to improve outcomes in patients. We demonstrated the intricacies of KS by examining two case studies. In Case 1, a 51-year-old male suffered a myocardial infarction after a wasp sting. Workup revealed elevated tryptase levels and mastocytosis on bone marrow biopsy concerning for mast cell activation syndrome. In Case 2, a 48-year-old female was diagnosed with vasospastic angina exacerbated by exposure to various allergens and associated with elevated histamine levels. Both patients underwent coronary angiography which demonstrated no obstructive coronary artery disease. Functional coronary angiography with acetylcholine provocation confirmed a predisposition for coronary vasospasm. Both patients were treated with anti-anginals and antihistamines. A literature review was performed to describe the pathophysiology, diagnosis, and treatment of KS. The underlying pathophysiology includes mast cell degranulation, where the release of inflammatory mediators like histamine and tryptase provokes coronary vasospasm, plaque rupture, and thrombus formation. With prompt recognition and appropriate management, the prognosis of KS is favorable. A greater understanding of KS can support clinicians in delivering quality care for patients. Our cases demonstrate the importance of maintaining a high index of suspicion in patients exhibiting an acute allergic reaction with concurrent evidence of cardiac ischemia. While the current literature provides some management guidance, additional research is required to improve our mechanistic understanding, diagnostic criteria, and therapeutic strategies.
Abstract 13228: Finerenone Inhibits the Progression of Cardiac Hypertrophy in the HFpEF Mouse Model
Authors: morikawa kei , Arima Yuichiro , Tsujita Kenichi
Published: December 2023

Background:
The efficacy of mineralocorticoid receptor antagonists (MRA) for heart failure with preserved ejection fraction (HFpEF) has not been established, but there are some reports of MRA being effective for early HFpEF.Furthermore, the FIGARO-DKD trial has demonstrated that finerenone, a nonsteroidal MRA, improves cardiovascular outcomes in patients with type 2 diabetes mellitus.The pathogenesis of HFpEF has yet to be fully elucidated, and further investigation is required to validate the mechanistic role of MRAs based on the distinct pathogenesis of HFpEF.

Methods:
As an HFpEF mouse model, we used the 15 weeks combined stress model of obesity and hypertension. (Schiattarella et al., Nature 2019). High fat diet ingestion and 0.5 g / L of Nω-nitro-L-arginine methyl ester drinking were loaded. As a drug administration experiment, with combined stress for 10 weeks, placebo or 10 mg/kg/day finerenone was administered for the last two weeks. After loading, body weight, blood pressure, heart weight, myocardial cross-sectional area, and mitochondrial protein acetylation were evaluated.

Results:
Histological analysis revealed the enlargement of cardiomyocyte cross-sectional areas in the combined stress group. In addition, we found mitochondrial protein acetylation level, adjusted by ubiquinol-cytochrome c reductase, rieske iron-sulfur polypeptide 1 (UQCRFS1) was also enhanced in the combined stress model. Subsequently, finerenone administration did not show remarkable reduction of blood pressure compared to the placebo group. However, echocardiography showed that the finerenone group reduced left ventricular diastolic septal wall thickness. And histological analysis revealed reduction of cardiomyocyte CSAs in the finerenone group. Mitochondrial protein hyperacetylation tended to be reduced with the finerenone group, but the difference was not significant.

Conclusion:
In the HFpEF murine model, finerenone improved cardiac hypertrophy independent of blood pressure. In addition, mitochondrial protein hyperacetylation, which involves mitochondrial dysfunction, was also alleviated by finerenone administration. Our findings indicate that the cardioprotective effects of finerenone may also affect mitochondrial function.
Abstract 13229: Coiled-Coil Domain-Containing Protein 80 Protects Against Aortic Dissection by Maintaining the Contractile Smooth Muscle Cell Phenotype
Authors: Shen Linghong , Xiao Qingqing , Yang Xiaoxiao , Cai Bin , Li Yi , Huang Xiying , Xu Ke , Zhang Weifeng , Wang Xiaolei , Wang Xia
Published: December 2023

Background:
Aortic dissection (AD) is a life-threatening medical emergency characterized by adverse vascular remodeling. Effective prevention and treatment options are lacking for AD. Coiled-coil domain-containing protein 80 (CCDC80) plays an essential role in regulating vascular remodeling. In the present study, we aimed to define the role of CCDC80 in the formation and development of AD.

Methods:
The expression and subcellular localization of CCDC80 were determined in human and mouse AD. CCDC80 knockout mice (CCDC80
–/–
) and vascular smooth muscle cell (VSMC)-specific CCDC80 knockout mice (CCDC80
fl/fl
SM22α Cre
+
) were treated with angiotensin II (Ang II) or Ang II combined with β-aminopropionitrile monofumarate (BAPN) to induce AD models. RNA-Seq analysis combined with immunoprecipitation and blockage of the JAK2/STAT3 signaling pathway in CCDC80
–/–
mice were used to evaluate the effect of CCDC80 deficiency on this pathway.

Results:
CCDC80 was downregulated in VSMCs in human and mouse AD. CCDC80
–
/
–
mice challenged with Ang II and BAPN developed AD with higher frequency and severity compared with their littermate controls (66.7% vs. 100%, p < 0.05). Remarkably, compared with littermate controls treated with Ang II, CCDC80
–/–
mice (8.3% vs. 87.5%, p < 0.05) and CCDC80
fl/fl
SM22α Cre
+
mice (12.5% vs. 80%, p < 0.05) frequently developed AD with severe elastin fragmentation and collagen deposition. CCDC80 interacted with JAK2; CCDC80 deficiency could promote VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. The JAK2/STAT3 pathway-specific inhibitor ameliorated adverse vascular remodeling and reduced AD formation (90% vs. 55%, p < 0.05) in CCDC80 knockout mice.

Conclusion:
CCDC80 deficiency exacerbates the progression of AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. Our findings suggest that CCDC80 is a potential target for the prevention and treatment of AD.
Abstract 13233: Disparities in Speed of Diagnosis of Hypertrophic Cardiomyopathy in the United States
Authors: Masri Ahmad , Stevens Warren , Buessing Marric , Zuk Eric , Lam Jenny , Zhang Yuanhui , Maksabedian Hernandez Ervant J , Seabury Seth A
Published: December 2023

Background:
Hypertrophic cardiomyopathy (HCM) is a cardiac disease that can be genetic in cause. Early diagnosis, risk stratification, and pharmacological management can reduce the disease burden, yet several studies have highlighted disparities in early diagnosis by gender and race.

Goals:
This study compares age, severity at diagnosis, and time-to-diagnosis, by gender, race, and county-level poverty rate in a nationally representative population of over 65-year-olds.

Methods:
We used Medicare claims data from 2016-2020 to construct a sample who had at least two HCM claims and continuous enrollment for at least 2 years prior to their first HCM claim. We measured age and severity of heart disease at diagnosis, as well as time from the first observed indication of heart disease to HCM diagnosis.

Results:
We identified 48,857 patients with an HCM diagnosis in the study period, of which 60% were women and 81% were Non-Hispanic White. Comparing relative rates, Black and Hispanic patients at the time of HCM diagnosis had a 16% higher prior rate of heart failure (HF), and a 11% higher rate of prior major adverse cardiovascular events (MACE). In addition, in Black HCM patients, the share of atrial and non-atrial arrhythmias that were clinically diagnosed before HCM diagnosis was 28% lower than among White patients (p<0.001). Importantly our multi-attribute approach highlighted the composite roles of race and county-level poverty: at the time of HCM diagnosis, Black men in the poorest quartile of counties had a 26% higher rate of HF, 22% higher rate of MACE and a 53% lower rate of clinically diagnosed arrhythmia (all p<0.001) than White men in the wealthiest quartile of counties. Additionally, the median time from the first indication of heart disease until the diagnosis of HCM in Black and Hispanic patients from the poorest quartile of counties was 347 days longer than for Non-Hispanic White patients from the wealthiest quartile of counties (p<0.001).

Conclusions:
This study shows evidence of disparities in diagnosis of older patients with HCM in the United States, particularly in terms of race and county-level poverty. New approaches are needed to address these disparities and improve access to care for patients in underserved and vulnerable communities.
Abstract 13253: Remotely-Controlled Cantilevered Cardiac Shim Coil (CSS) Corrects Cardiac MRI Magnetic-Field Inhomogeneities Due to Implanted Cardioverter Defibrillators (ICDs): Preclinical Validation
Authors: Hrovat Mirko , Wang Yifan , Gunderman Anthony , Halperin Henry R , Chen Yue , Schmidt Ehud J , Kolandaivelu Aravindan
Published: December 2023

Introduction:
1.4M people (US) have implanted ICDs, which reduce risk of sudden death due to ventricular arrhythmias. Cardiac MRI (cMR) is used in patients with ICDs to diagnose conditions that predispose to sudden death and to plan and guide ablation therapy. However, all ICDs contain a ferromagnetic transformer which imposes a large inhomogeneous (>100 parts-per-million, ppm) magnetic field in sections of the heart, creating large image voids that can mask pathology, such as myocardial scar. Wide-band Late Gad. Enhancement (LGE) imaging has improved evaluation of ICD patients, handling
<
25ppm artifacts, leaving unreadable voids in ~30% of patients. Hypothesis: ICD artifacts can be reduced with a remotely-displaced cardiac shim system (CSS), allowing clinical CMR imaging.

Methods:
The
CSS system
(Fig. 1A- C). A shim coil, placed in the bore, was designed to correct 75ppm fields at 15cm distances, using currents supplied from the MRI operator room (OpRm). The coil is immune to magnetic forces. A cantilevered beam holds the shim coil over the patient’s chest above the cardiac imaging coil allowing unrestricted imaging. MR-conditional motors, remotely-controlled from the OpRm, allow 2mm-resolution 3D shim-coil positioning.
Experiments
: swine (N=3) with chest-overlaid ICDs, emulating patients, were imaged. Magnetic-field maps were used to estimate shim-coil positioning, and current magnitude & polarity. Fine-tuning of location and current was performed during continuous 2D ECG-gated breath-held GRE/SSFP imaging. 2D/3D LGE cMR was subsequently acquired and evaluated.

Results:
CSS reduced field inhomogeneities due to implanted ICDs by 30ppm in 2D and 3D cMR sequences, correcting ICD-related image distortions in several heart regions (Fig. 1D, E).

Conclusion:
An externally-controlled shim-coil localization and drive system reduced artifacts without requiring entry into the scanner room, supporting efficient, higher quality cMR imaging of ICD patients.
Abstract 13276: Metabolic Pathways and Risk Biomarkers for Incident Heart Failure
Authors: Snow Sarah C , Kwee Lydia , Selvaraj Senthil , Rao Vishal , Patel Manesh R , Pagidipati Neha J , Shah Svati H
Published: December 2023

Introduction:
Metabolomic profiling provides important information about heart failure (HF) risk. Metabolites reporting on muscle fuel substrate including branched-chain amino acids (BCAAs) and ketones have been implicated in HF pathogenesis and as circulating biomarkers of risk. We sought to identify the role of these known metabolites and identify novel metabolites and related pathways associated with incident HF in a large population-based cohort.

Methods:
Metabolomic profiling has been performed in the UK Biobank cohort using the Nightingale NMR platform. Principal component analysis (PCA) was used for dimensionality reduction and to identify shared metabolic pathways. Cox proportional hazard models were used to test the association between each PCA factor, and of individual metabolites heavily loaded on significant factors, with time to incident HF.

Results:
Of n=118,021 participants with metabolomic profiling data, n=3,865 (3.3%) developed incident HF (mean [SD] follow-up: 12.5 [1.3] years). The 107 metabolite biomarkers clustered into 12 PCA factors (Table 1). Nine factors were associated with incident HF in adjusted models. Factor 5 (BCAAs, aromatic acids) was not associated with incident HF in adjusted models. However, higher levels of each individual BCAA were associated with decreased risk of incident HF, with valine as the most protective (HR 0.91 [CI 0.88-0.95], q = 3x10
-6
). Factors 2 (large HDL) and 6 (ketones) were associated with increased risk of incident HF, while factors 4 (small HDL) and 9 (omega-3 fatty acids) were associated with decreased risk of incident HF.

Conclusions:
In a large population-based cohort, we found that higher baseline levels of ketones and large HDL were associated with increased risk of incident HF, while higher levels of BCAAs, small HDL, and omega-3 fatty acids were associated with decreased risk of incident HF. These results highlight known and new metabolic pathways and related circulating biomarkers of HF risk.
Abstract 13286: Co-Morbidities Clustering According to Imaging Diagnostic Criteria in Cardiac Sarcoidosis
Authors: Khan Sakeeb , Tremblay John , Torosoff Mikhail
Published: December 2023

Background:
Cardiac sarcoidosis (CS) diagnostic guidelines updated in 2006 and in 2017 now include imaging findings of left ventricular (LV) dysfunction (LV EF < 50%) on cardiac MRI and echocardiography as major diagnostic criterion. Limited data is available with regards to co-morbidities clustering in sarcoidosis and CS according to the 2017 updated guideline diagnostic criteria.

Methods:
A case control, single tertiary medical center study included 558 sarcoidosis patients with documented extracardiac sarcoidosis and completed electrocardiogram and/or cardiac MRI imaging. CS 2006 and 2017 diagnostic criteria and co-morbidity data were extracted from electronic charts and were available for comparison in 540 patients.

Results:
The total study population was composed of 52.7% (281/540) females, aged 58.9+/-12.6 years old, with diabetes mellitus (DM) present in 29.6% (160/540), HTN in 51.7% (279/540), CAD in 13.3% (72/540), moderate to severe aortic, mitral, or tricuspid valvular disease in 14.8% (80/540), ESRD in 2.4% (13/540), and COPD or asthma in 21.9% (118/540). There was a significant clustering of co-morbidities according to the imaging CS diagnostic criteria. Patients meeting the 2017 CS imaging criteria were found to be older (61.4+/-11.3 vs 58.8+/-12.8 years old in patients not meeting criteria, p=0.085), predominantly male (69.2%, (54/78) vs. 44.4%, (205/462), p<0.001), and demonstrated significantly increased prevalence of DM (39.7%, (31/78) vs. 27.9%, (129/462), p=0.034), and valvular disease (33.3%, (26/78) vs. 11.7%, (54/462), respectively, p<0.001). However, there were no statistically significant difference in the prevalence of HTN (60.3%, (47/78) vs. 50.2%, (232/462), p=0.101), ESRD (3.9%, (3/76) vs. 2.2%, (10/456), p=0.361), and COPD or asthma (19.2%, (15/78) vs. 22.3%, (103/462), p=0.544) in patients meeting 2017 CS criteria compared to those that did not.

Conclusion:
CS patients meeting 2017 imaging diagnostic criteria were found to have statistically significant clustering of the following co-morbidities: male gender, DM, and valvular disease. These findings underscore importance of comprehensive care in CS patients and warrant caution in assigning LV abnormalities observed on imaging solely to CS etiology.
Abstract 13295: The Effects of Short-Term Exposure to Fine Particulate Matter and Ozone on Attending Outpatient Clinic Visit Appointments Among Patients With Depressive Symptoms
Authors: May Heidi T , Bride Daniel , Bair Tami L , Le Viet T , Knight Stacey , Anderson Jeffrey L , Knowlton Kirk U , Joy Elizabeth A , Horne Benjamin D
Published: December 2023

Background:
Air pollution is increasingly recognized as an environmental risk factor for mental health. However, data regarding the short-term influence on depressive symptoms are limited. It is known that depressed patients (pts) tend to be less adherent to prescribed medical regimens, including appointments. Therefore, we sought to determine how depression during times of increased particulate matter (PM
2.5
) and ozone during winter inversion (Nov-Mar) and wildfire seasons (June-Oct) affected pt behavior of attending clinic visit appointments.

Methods:
Pts (n=142,930) who completed a PHQ-9 as an outpatient between Mar 2003-Apr 2022 and resided on Utah’s Wasatch Front were studied. PHQ-9 results were used to classify depression by no depressive symptoms (<10) or any depressive symptoms (
>
10), with further stratification into severe (
>
20). A case-crossover design was used with odd ratios computed by Poisson regression.

Results:
A total of 43% (n=60,724) of pts had depressive symptoms, with 25% (n=15,278) being severe. Depressed pts were younger (37 vs. 45 yrs), female (62% vs. 56%), more often smoked (24% vs. 17%), and had fewer comorbidities. The likelihood of attending clinic visits was decreased when the moving average (mAvg) of PM
2.5
was increased in the 2 days and week prior among those with depression, particularly when severe (Figure a). Levels of PM
2.5
on lag day 0 did not affect visit attendance. Increases in ozone were associated with a decrease in clinic attendance (Figure b). Air pollution levels >7 to 28 days prior were not associated with clinic attendance.

Conclusion:
Short-term increases in air pollution, particularly in average PM
2.5
during inversion season, in the days and week prior were associated with a decrease in attending clinic visit appointments among depressed pts. These results could have healthcare delivery implications since people with depression were less likely to show up to non-emergent medical visits when the air has been polluted.
Abstract 13304: Intrinsic Morphology Influences the Natural History of Neo-Aortic Root Dilatation and Pathologic Neo-Aortic Regurgitation in Transposition of the Great Arteries
Authors: Sengupta Aditya , Gauvreau Kimberlee , Carreon Chrystalle K , Lee Ji M , Stephen P Sanders , Colan Steven D , Del Nido Pedro J , Mayer John E , Nathan Meena
Published: December 2023

Introduction:
Neo-aortic root dilatation and pathologic neo-aortic regurgitation (AR) can lead to significant late morbidity after the arterial switch operation (ASO) for dextro-transposition of the great arteries (dTGA).

Hypothesis:
The natural history of root dilatation in dTGA is influenced by intrinsic morphology.

Aims:
To i) delineate the natural history of root dilatation in repaired dTGA and ii) to histologically characterize the great arteries in unrepaired dTGA.

Methods:
A single-center review of patients who underwent the ASO from 07/1981-09/2022 was performed. Morphology was categorized as dTGA with intact ventricular septum (dTGA-IVS), dTGA with ventricular septal defect (dTGA-VSD), and double outlet right ventricle-TGA type (DORV-TGA). Echocardiographically-determined diameters and derived z-scores were measured at the annulus, sinus of Valsalva (SoV), and sinotubular junction (STJ) immediately before the ASO and throughout follow-up. Linear mixed-effects models assessed trends in dimensions over time. We also histologically examined the aortic and pulmonary roots of 10 cases of unrepaired dTGA from our Cardiac Registry.

Results:
Of 1359 patients meeting entry criteria, 593 (44%) had dTGA-IVS, 666 (49%) had dTGA-VSD, and 100 (7%) had DORV-TGA. At a median follow-up of 8.3 years (range 0.1-39.3 years), 129 (9.5%) patients had ≥moderate AR or required a neo-aortic valve or root reoperation (
Fig-A
). Overall growth of the root is shown in
Fig-B
. At baseline, there were no differences in annular, SoV, or STJ diameters between dTGA-IVS patients and dTGA-VSD or DORV-TGA patients. At 30 years, DORV-TGA patients had significantly larger diameters at the annulus (p<0.001), SoV (p=0.039), and STJ (p=0.041) relative to dTGA-IVS patients (
Fig-C
). Specimens of the aortic and pulmonary roots from a representative case of unrepaired dTGA are shown in
Fig-D
.

Conclusions:
Longitudinal surveillance of the neo-aortic root is warranted long after the ASO.