bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13061: Association of Right Ventricular - Pulmonary Arterial Coupling and Progression of Tricuspid Regurgitation in Patients With Non-Valvular Atrial Fibrillation
Authors: Kim Dae-Young , Ryu Sung Kee , Jang Ji-Hun , Shin Sung-Hee
Published: December 2023

Introduction:
Tricuspid regurgitation (TR) severity in patients with atrial fibrillation (AF) is associated with poor prognosis. Recently, right ventricular-pulmonary arterial (RV-PA) coupling has been shown to be related to clinical outcomes in TR patients. However, data on the relationship of RV-PA coupling to the progression of significant TR is limited.

Hypothesis:
This study aimed to investigate whether RV-PA coupling affects the progression of significant TR in patients with non-valvular AF.

Methods:
A total of 300 consecutive AF patients with insignificant TR were included among 371 patients with AF who underwent follow-up echocardiography. Insignificant TR was defined as TR less than a mild degree. We excluded other significant valvular diseases, regional wall motion abnormality, LVEF <50%, the cardiac implantable electronic device, cardiac surgery, and poor echo image for RV analysis. RV-PA coupling was assessed by the ratio of RV global longitudinal strain (GLS) using speckle tracking echocardiography to pulmonary artery systolic pressure (PASP).

Results:
During a mean 4.7±2.5 years of follow-up, 31 (10.3%) patients (mean age 67.5±11.7 years, 37.0% female) have progressed to significant TR as more than moderate degree. The patients who progressed to significant TR were older, more likely to be female, and had a higher prevalence of ischemic stroke, higher PASP, larger RV size, lower right atrial (RA) strain, lower RVGLS, and lower RVGLS/PASP than patients without TR progression. RV-PA coupling reflected by RVGLS/PASP was independently related to the progression of TR after adjusting for age, gender, and history of stroke (p<0.001). It remained significant for predicting TR progression even after further adjustment for PASP, RA strain, or RV strain (Figure).

Conclusions:
RV-PA coupling was associated with the progression of TR in patients with non-valvular AF, which might suggest that it can be a helpful parameter in monitoring this population.
Abstract 13087: TRPM7 Kinase Regulates Inflammation in Hypomagnesemia-Induced Cardiac Diastolic Dysfunction
Authors: Liu Man , Liu Hong , Kang Gyeoung-Jin , Guo Yugene , Ali Salman , Dudley Samuel C
Published: December 2023

Introduction:
Hypomagnesemia (HypoMg) is commonly observed in heart failure and associated with inflammation. We have reported that inflammation contributes to mitochondrial oxidative stress and causes cardiac diastolic dysfunction (DD) in diabetic mice and that Mg supplementation shows therapeutic benefits. Meanwhile, diet-induced HypoMg alone can lead to DD. Transient receptor potential melastatin 7 (TRPM7), a Mg transporter with a kinase domain, regulates Mg homeostasis in different types of cells.

Object:
We aim to assess the role of TRPM7 in HypoMg-associated inflammation and DD.

Methods:
Wild type (WT) C57BL/6J and transgenic kinase dead TRPM7
K1646R
mice (with a global homozygous K1646R mutation in the kinase domain) were fed with a normal (2 g/kg Mg) or a HypoMg diet (15-30 mg/kg Mg) for 6 weeks. Echocardiography was performed to monitor E/e’ (an DD indicator when increased). Hearts were collected for protein levels of TRPM7, inflammatory markers IL-1β and NLRP3, and total protein oxidation. Isolated cardiac macrophages (Mϕs) were used for phenotyping by flow cytometry. Raw264.7 cells (a Mϕ cell line) and RL-14 cells (a cardiomyocyte cell line) were treated with a normal (0.81 mM Mg) or a HypoMg medium (0.04 mM Mg) for 48 h. TRPM7 protein and IL-1β collected from the culture media or from cell lysates were tested.

Results:
In the WT-HypoMg mouse group, E/e’, protein levels of TRPM7, IL-1β and NLRP3, and total protein oxidation were all significantly elevated, which were not observed in the TRPM7
K1646R
-HypoMg group. Cardiac Mϕs phenotype showed increased recruited pro-inflammatory Mϕs and decreased resident pro-resolving Mϕs, while the former was prevented by TRPM7
K1646R
. TRPM7 protein levels in Raw264.7 and RL-14 cells were also significantly increased by HypoMg treatment, as well as Mϕ-secreted IL-1β (2.7±0.6 pg/mL vs. undetectable in control, P=0.012) and IL-1β in RL-14 cell lysates (2.6±0.2-fold of control, P=0.006).

Conclusions:
TRPM7 kinase function is upregulated under HypoMg in both Mϕs and cardiomyocytes. It contributes to inflammatory Mϕ activation, elevated IL-1β production, increased oxidative stress, and cardiac DD, suggesting inflammation as a potential mediator of HypoMg-induced DD.
Abstract 13088: The Psychometric Properties of the Advance Care Planning Engagement Survey in Cardiovascular Diseases
Authors: Heo Seongkum , An Minjeong , KIM SUN HWA , Kang JungHee , Yang jisun , Kim JinShil , Cho KyungAh
Published: December 2023

Background:
Patients with cardiovascular diseases (CVDs) have high mortality rates, and the progress is uncertain. Advance care planning (ACP) can help these patients and their caregivers prepare for expected or unexpected end-of-life situations effectively. However, the implementation of ACP is suboptimal in this population, resulting in unnecessary suffering of patients and their caregivers and increased health costs. Different versions of the Advance Care Planning Engagement Survey (ACPES) have been used to assess ACP engagement. However, the comprehensive psychometric properties of the ACPES-9 have not been tested in South Korea.

Aim:
To test the reliability and validity of the ACPES-9 in patients with CVDs.

Hypothesis:
The reliability of the ACPES-9 is supported by Cronbach’s alpha ≥ .70, and the validity is supported by meeting the cut points of good model fit indices (chi-square test: not significant, CFI ≥ .95, TLI ≥ .95, SRMR < .05, and RMSEA < .07) with factor loadings > .40 in confirmatory factor analysis (CFA) and significant associations of ACP engagement with registration of advance directive (AD) and the intention.

Methods:
In this cross-sectional study, data on ACP engagement (ACPES-9) and registration of ADs and the intention and sociodemographic characteristics (sample characteristics questionnaire) were collected from 4 hospitals or public health centers (N = 105, mean age: 66.3) between February and March, 2023. Cronbach’s alpha was used to test the reliability. Confirmatory factor analysis and independent t-tests were used to test the validity.

Results:
Cronbach’s alphas for the total scale and self-efficacy and readiness dimensions were .93, .82, and .97, respectively. In CFA with two factors, all indices of model fit were acceptable: chi-square test = 21.76, p = .151; CFI = .995; TLI = .989; SRMR = .024; RMSEA = .059). All factor loadings were > .65. Patients who registered AD (35.3 vs. 24.3, p < .001) or had the intention (28.9 vs. 20.6, p < .001) had higher scores of the ACPES-9 than their counterparts, respectively.

Conclusions:
The findings demonstrate that the ACPES-9 was a reliable and valid instrument by supporting the hypothesis. Healthcare providers can use this instrument to assess and manage ACP engagement in patients with CVDs.
Abstract 13089: Plasma Proteomics and Risk of Incident Ischemic Stroke: Meta-Analysis of the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS)
Authors: Wang Wendy , Kalani Rizwan , Zhang Michael J , Pankow Jim S , Lakshminarayan Kamakshi , Alonso Alvaro , Lutsey Pamela L , Longstreth W T , Ballantyne Christie M , Matsushita Kuni , Tin Adrienne , Johansen Michelle C , Gottesman Rebecca F , Coresh Josef , Pan Wei , Walker Keenan , Heckbert Susan R , Chen Lin Y
Published: December 2023

Background:
Proteomic profiling can screen large numbers of proteins to discover novel biomarkers related to ischemic stroke. However, prior studies have used a targeted approach or assessed a limited number of proteins (<1300). Using data from the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), we examined the prospective association between 4954 plasma protein targets and incident ischemic stroke.

Methods:
Participants free of prevalent stroke at the time of proteomic profiling were included. Proteomics data were obtained from the 1990-92 exam in ARIC and the 1992-93 exam in CHS. Plasma proteins were quantified using the aptamer-based SOMAScan platform. Ischemic stroke events were ascertained and adjudicated through 2019 in ARIC and June 30, 2015 in CHS. Cox proportional hazards models adjusting for demographics, ischemic stroke risk factors, and estimated glomerular filtration rate were used. ARIC and CHS results were combined using fixed-effects meta-analysis. A Bonferroni-corrected p<1.01e-5 was considered significant.

Results:
Median follow-up time in ARIC and CHS were 25 and 12 years, respectively. Among 10,856 ARIC participants (mean age 57 years, 56% female, 23% Black), 890 had an incident ischemic stroke. Among 3,283 CHS participants (mean age 74 years, 62% female, 18% Black), 507 had an incident ischemic stroke. In the meta-analysis, 44 proteins were significantly associated with incident ischemic stroke, of which 32 have not been previously reported (
Figure
). Of the 32, amyloid-like protein and kit ligand were the most strongly associated with ischemic stroke; each SD increment in log
2
(amyloid-like protein) and log
2
(kit ligand) were associated with 20% and 19% lower risk of ischemic stroke.

Conclusion:
In a meta-analysis of two community-based cohorts, we identified 32 novel protein associations with incident ischemic stroke. Further research is needed to determine causal associations.
Abstract 13107: Addressing Sudden Cardiac Arrest: An Analysis of the Efficacy and Implementation of Automated External Defibrillators in New Jersey Schools
Authors: Schneier Ezra , Blecherman Mira , Nyirenda Themba , kipel george
Published: December 2023

Introduction:
Out of hospital sudden cardiac arrest is a major health concern with a low survival rate. Proper Automated External Defibrillator use has been shown to decrease mortality associated with OHCA. In 2014, New Jersey passed Janet’s Law to mandate automated external defibrillator access in all public and private schools. Our project surveyed NJ schools to evaluate the implementation of AEDs and to analyze their usage and outcomes.

Hypothesis:
Schools that were adherent to AED placement and training as outlined in Janet’s Law will likely have more positive outcomes from sudden cardiac arrests on school properties than schools that do not.

Methods:
An observational, cross sectional study was conducted via an online form (Redcap 12.4.2) sent to New Jersey public school nurses. Data was collected from February to June 2023 and analyzed using SAS version 9.4.

Results:
301 (99.7%) responses reported having automated external defibrillators. 85.3% of schools provided AED staff training. 42 schools (14.4%) utilized an AED in a cardiac emergency, most often occurring to students in classrooms. An AED was administered by school employees 95.8% of the time. In 80.5% of cases, the patient was resuscitated on scene with no long term neurological complications. 87.2% of schools have an emergency response plan.

Conclusions:
Our data highlights the impact of proper AED utilization to positively influence out of hospital sudden cardiac arrest outcomes in pediatric populations. Despite Janet’s law being an unfunded mandate, we found near complete compliance among New Jersey schools. The majority of reported sudden cardiac arrests occurred in a classroom setting, necessitating available resources throughout school facilities. In these events, the percentage of positive patient outcomes in our study was significantly higher than the national average with excellent neurological recovery. This discovery may be a product of excellent response rates by trained staff as mandated in Janet’s law. Our findings highlight the need for awareness, training, and accessibility regarding AEDs.
Abstract 13149: Sociodemographic Factors and Prevalence in Physical Inactivity: Analysis of Rural and Non-Rural Counties in the United States, 2004-2019
Authors: Tabatabaei Yeganeh Hanieh Sadat , Lahr Brian , Mielke Michelle , Vella Adrian , Bailey Kent , Dugani Sagar
Published: December 2023

Introduction:
US rural areas have a disproportionate burden of CVD and hypertension. Physical inactivity is a major risk factor, with 25% prevalence in US adults. However, rural disparities in physical inactivity are incompletely described. The aim was to evaluate differences in prevalence of physical inactivity based on county-level rurality.

Methods:
We used CDC county-level data for adults aged ≥20 years, 2004–2019, available for 97.6% of US counties (n=3148/3226). CDC defined physical inactivity as self-reported lack of leisure time physical activity in the month preceding the survey. Rurality was based on six categories ordered from least rural (large central metro) to most rural (noncore). We used weighted least squares regression to compare prevalence by rurality level, adjusting for 13 county-level sociodemographic factors; results reported as prevalence ratios (95% CI) with partial
F
-tests and
P
-values.

Results:
In age and sex ratio adjusted analysis (model 1), we observed a gradient in the prevalence of physical inactivity across levels of rurality, with significantly higher rates in small metro (1.03 [1.00–1.06]), micropolitan (1.05 [1.02–1.07]), and noncore (1.05 [1.02–1.08]) compared with large central metro counties (
F
-statistic=7.5;
P
<.001). With further adjustment for other sociodemographic factors (model 2), the relative differences were negated in noncore counties (0.99 [0.97-1.02]), attenuated in intermediate counties, and accentuated in large fringe metro counties (1.06 [1.04-1.08]) (
F
-statistic=14.3;
P
<.001). Further adjustment for obesity (model 3) largely attenuated the association of rurality with physical inactivity, resulting in no significant differences relative to large central metro counties (
F
-statistic=4.8;
P
<.001).

Conclusions:
County-level rurality was associated with prevalence of physical inactivity. These disparities were largely accounted for by obesity, which may be targeted for intervention.
Abstract 13155: Safety and Efficacy of Anti-Hypertensive Medications in Patients With Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Alqadi Mohammad , Al-Sadawi Mohammed , Aslam Faisal , Rahman Tahmid , Kim Paul , Mann Noelle
Published: December 2023

Introduction:
Hypertension (HTN) is a co-morbidity that is commonly associated with heart failure (HF) with preserved ejection fraction (HFpEF). This meta-analysis aims to evaluate the association of anti-hypertensive medications (AHM) therapy with cardiovascular (CV) outcomes in patients with HFpEF.

Hypothesis:
Treatment of HTN in HFpEF patients is associated with improved CV outcomes.

Methods:
Performed a database search (OVID Medline, Web of Science, and Embase) for studies reporting the association of AHM with CV outcomes in patients with HFpEF. The primary endpoint was all-cause mortality. Secondary endpoints include CV mortality, worsening HF, CV hospitalization, and major adverse CV events (MACE).

Results:
A total of 15 studies with 17507 HFpEF participants (8732 treated with medical therapy vs 8775 treated with placebo) met inclusion criteria. Use of AHM was not associated with lower all-cause mortality or CV mortality compared to treatment with placebo (OR 1.01, 95% CI 0.80-1.27; p=0.95, OR 0.97, 95% CI 0.86-1.08; p=0.53). Use of AHM was associated with a statistically significant lower risk of MACE and CV hospitalization (OR 0.90, 95% CI 0.83-0.97; p<0.01, OR 0.89, 95% CI 0.81-0.97; p<0=0.04). Subgroup analysis demonstrated this to be primarily driven by studies with mixed HFpEF patients with or without HTN, not HFpEF patients with HTN. There was a non-significant trend toward lower risk of worsening HF in patients treated with AHM, and was driven by HFpEF patients with or without HTN, not HFpEF patients with HTN (OR 0.87, 95% CI 0.78-0.97; p=0.02 versus OR 0.57, 95% CI 0.18-1.86; p=0.35).

Conclusion:
While treatment with anti-hypertensives was not associated with lower risk of all-cause mortality, their use may be associated with reduced risk of adverse CV outcomes in patients with HFpEF regardless of whether they have HTN. Further studies are needed to clarify this association and determine the effect based on specific classes of medications.
Abstract 13260: Large Scale Plasma Proteomics Identifies MMP-12 as a Novel Biomarker of Aortic Stenosis Progression
Authors: Shelbaya Khaled , Lamberson Victoria , Yang Yimin , Dorbala Pranav , Buckley Leo , Claggett Brian , Skali Hicham , Dufresne Line , Thanassoulis George , Yang Ta-Yu , Engert Jamie C , Floyd James S , Austin Thomas , Bortnick Anna E , Kizer Jorge R , Costade Freitas Renata Caroline C , Singh Sasha A , Aikawa Elena , Ballantyne Christie M , Hoogeveen Ron C , Yu Bing , Coresh Josef , Matsushita Kuni , Shah Amil M
Published: December 2023

Background:
Aortic stenosis (AS) is associated with significant morbidity and mortality and is increasing in prevalence. Limited data exist regarding circulating biomarkers of AS risk.

Methods:
Among Atherosclerosis Risk in Communities study participants with available proteomics (Somascan v4) at study Visit 5 (2011-13; n=4,899; age 76 ± 5 years, 57% women), we used multivariable linear regression to evaluate the association of 4,877 plasma proteins with peak aortic valve (AV) velocity and AV dimensionless index. We then tested their association, when assessed at study Visit 3 (1993-95; n=11,430; age 60 ± 6, 54% women), with incident AV-related hospitalization post-Visit 3 (median follow-up 22, IQR 14 - 25 years) using multivariable Cox PH regression models. For the resulting candidate proteins, we assessed the association of Visit 5 protein levels with change in AV peak velocity over 6 years from Visit 5 to 7 (2018-19; n=2,314) and with quantitative AV calcification by cardiac CT at Visit 7 (n=1,804); associations with incident adjudicated AS in the Cardiovascular Health Study (CHS; n=3,413); and differences in AV tissue expression in normal, fibrotic, and calcific segments of explanted stenotic human AVs (n=3).

Results:
We identified 52 plasma proteins with consistent associations with AV peak velocity, AV dimensionless index, and incident AV hospitalization. Of these 52 proteins, MMP12 was also associated with magnitude of increase in AV peak velocity between Visits 5 and 7 (Figure), and with magnitude of AV calcification by CT at Visit 7 (adjusted OR 1.25 [95% CI 1.19-1.32], p=1.7x10
-17
). Higher MMP12 was also associated with incident moderate or severe AS in CHS, an independent cohort. MMP12 expression was greater in calcific compared to fibrotic or normal AV tissue segments.

Conclusions:
Plasma MM12 is a potential novel circulating biomarker of AS risk.
Abstract 13284: New Elastic Fiber Formation by Non-Smooth Muscle Lineage Cells During the Progression of Aortic Dissections
Authors: Sawada Hisashi , Ito Sohei , Lu Hong S , Daugherty Alan
Published: December 2023

Introduction:
Aortic dissection (AD) is a life-threatening vascular disease displaying the disruption of the extracellular matrix (ECM). Elastic fibers are a major component of ECM and confer structural integrity to the aortic wall. Normally, elastic fibers are minimally synthesized in adulthood. However, it remains unknown whether and how elastic fibers are synthesized following ADs.

Methods and Results:
AD was induced by administration of β-aminopropionitrile (BAPN, 0.5% wt/vol) to male C57BL/6J mice at 4 weeks of age. Thoracic aortas were collected after 4 or 12 weeks of BAPN administration. False lumen formation with fresh hematomas was observed at 4 weeks of BAPN administration, indicating development of acute ADs. The false lumen developed striking remodeling at 12 weeks, suggesting progression to the chronic phase. RT-qPCR revealed that mRNA abundance of tropoelastin, a precursor of elastic fibers, was increased significantly at the chronic phase of ADs, but not at the acute phase. Tropoelastin mRNA was observed primarily in the vascular wall of the false lumen, as evidenced by in situ hybridization. Of interest, elastic fibers were formed in the wall of the false lumen in chronic ADs. These data suggest that elastic fibers were newly synthesized during the progression of ADs. Immunostaining revealed that the walls of true and false lumens of chronic ADs were mainly composed of cells expressing both αSMA (encoding by
Acta2
) and MYH11, common markers for smooth muscle cells (SMCs). However, in a lineage tracing study, the walls of the false lumen of chronic ADs were negative for the
Acta2
lineage, suggesting that cells in the wall of the false lumen were derived from a non-SMC lineage but acquired SMC properties during AD progression. Bulk RNA sequencing identified the increased abundance of 2,799 genes in chronic ADs and 102 transcription factors were predicted to regulate these genes. Among them, JunB was the most abundant molecule that can be aligned in the promotor region of tropoelastin. Of note, JunB was expressed adjacent to both αSMA-positive cells and new elastic fibers in the dissected aortas.

Conclusion:
ADs exhibit vascular remodeling with newly elastic fiber formation by non-SMC lineage cells during the disease progression.
Abstract 13302: Associations of Allostatic Load With Brain Macro-Morphology, Subclinical Cerebrovascular Disease, and Microstructural Integrity of White Matter Pathways: The Boston Puerto Rican Health Study
Authors: Chen Fan , Koo Bang-Bon , Scott Tammy , Guan Yi , Bigornia Sherman , Bhadelia Rafeeque , Tucker Katherine L
Published: December 2023

Introduction:
Allostatic load (AL), a measure of overall body wear and tear, has been associated with structural and functional alterations of the brain, but the evidence remains scarce. We aimed to evaluate the prospective associations of AL with brain MRI measures in the Boston Puerto Rican Health Study (BPRHS).

Research Questions:
Whether AL is associated with 1) brain macro-morphology: brain age and volumes, 2) subclinical cerebrovascular disease: white matter hyperintensity (WMH) and brain infarcts, and 3) microstructural integrity of white matter (WM) pathways in Puerto Rican adults.

Methods:
Adults from the BPRHS cohort who provided blood and urine samples at baseline, 2-y, and 6-y visits and underwent MRI scans at 13-y visit were included in analyses (n=226). AL was evaluated as a composite score (0-11) of 11 physiological parameters in five body systems. An overall AL score was calculated by averaging the scores of the baseline, 2-y, and 6-y visits, with higher scores indicating greater dysregulation. We evaluated brain age and volumes using T1-weighted MRI, WMH and brain infarcts using T2-weighted MRI, and microstructural integrity of WM pathways using diffusion tensor imaging. Multivariable logistic regression models were used to examine the associations between AL and brain infarcts, and linear regression models were used for other MRI outcomes.

Results:
Mean age at baseline was 54.6 ± 6.6 y, with 79.2% female. Higher AL was associated with higher brain age z scores (β = 0.129,
P
= 0.031) and lower volumes of total WM, cerebral WM (especially parietal and temporal lobes), cerebellum, and brain stem. Higher AL was also associated with higher grades of WMH (β = 0.207,
P
= 0.024) and higher odds of small vessel infarcts [OR (95% CI) = 3.50 (1.56-7.87),
P
= 0.002], but not large vessel infarcts [OR (95% CI) = 1.33 (0.73-2.40),
P
= 0.348]. Diffusion tensor imaging parameters showed that participants with higher AL had more microstructural deterioration patterns in major WM pathways.

Conclusions:
Higher AL score was associated with brain macro- and microstructural disruptions and a higher risk of subclinical cerebrovascular disease, suggesting that AL may be a potential indicator of the need for early intervention in preventing neuronal damage in older adults.
Abstract 13308: Characteristics of Participants Enrolled in a Randomized Controlled Trial Evaluating Vitamin D Normalization on Major Adverse Cardiovascular-Related Events: The Target-D Trial
Authors: May Heidi T , Le Viet T , Babcock Daniel , Wayman Libby , Maestas Heather , Anderson Jeffrey L , Horne Benjamin D , Bair Tami L , Knowlton Kirk U , Knight Stacey , Muhlestein Joseph B
Published: December 2023

Background:
Many observational studies have reported associations between low 25-hydroxyvitamin D (25[OH] vit D) levels and adverse cardiovascular (CV) outcomes. Recent randomized clinical trials have not found vitamin (vit) D
3
supplementation to reduce CV risk. However, these trials gave “blanket” doses regardless of 25[OH] vit D level, with none having "treated to target". We are performing the first study where subjects are prescribed vit D
3
supplementation based on individual 25[OH] vit D levels.

Methods:
The purpose of Target-D (NCT: 02996721) is to determine if achieving 25[OH] vit D levels >40 ng/mL among myocardial infarction (MI) patients will result in a reduction of adverse CV events. Subjects meeting study criteria from April 2017 to May 2023 were randomized to receive standard of care or clinical management of 25[OH] vit D levels. The treatment arm received targeted vit D
3
supplementation based on a dosing algorithm. Target-D is an event-driven trial that will conclude when 104 primary outcome events (composite of death, MI, heart failure hospitalization, and stroke) have occurred.

Results:
The study consort diagram is shown in Figure. Patient characteristics are shown in Table. Baseline 25[OH] vit D levels were 26.8±12.7 (median: 25) and were similar between arms (Table). Among those randomized to the treatment arm with a 25[OH] vit D levels
<
40, 58.5% of patients began vit D
3
dosing at 5000 IU.

Conclusions:
Average baseline 25[OH] vit D levels were deficient in Target-D participants. The discrepancy in findings between observational and randomized trials of vit D may be due to the inability of vit D
3
supplementation doses to achieve therapeutic 25[OH] vit D thresholds. Target-D will evaluate if it is the level of serum 25[OH] vit D achieved that provides CV benefit and not necessarily the vit D
3
supplementation dose that is received. It is anticipated that the number of events needed for this event-driven trial will be achieved by May 2024.
Abstract 13313: Risk of Atherosclerosis in Thoracic Aortic Disease: A Study of Multi-Modal Imaging Data From 40,479 UK Biobank Participants
Authors: Flores Alyssa M , Pirruccello James , Ellinor Patrick T , Lindsay Mark E
Published: December 2023

Background:
Despite some shared risk factors, aortic aneurysms and atherosclerosis manifest differently across the aorta. While atherosclerosis commonly co-exists with descending and abdominal aortic aneurysms, some observations suggested a decreased risk of atherosclerosis in patients with ascending aortic aneurysms. This has led to the suggestion that drivers of ascending aortic aneurysms may be anti-atherogenic.

Aim:
Using carotid intima-media thickness (cIMT) as a surrogate for atherosclerosis and deep learning-derived estimates of aortic diameter, this study examines whether ascending aortic aneurysms are protective against atherosclerosis in a longitudinal analysis of UK Biobank participants.

Methods:
Individuals who underwent both carotid ultrasound and cardiovascular MRI in the UK Biobank (N=40,479) were identified. We derived ascending and descending aortic measurements from a previously developed deep learning model that was trained to quantify dimensions in >4 million MRI images and extract diameter during ventricular systole. Measures of mean cIMT at 2 standardized angles for bilateral carotid arteries were utilized. The relationship between cIMT and aortic diameter was assessed using univariable and multivariable linear regression. β was calculated as μm change in cIMT per cm of aortic diameter.

Results:
In individuals with an aneurysmal ascending aorta (
>
4.5cm), there was no significant association between aortic diameter and cIMT after accounting for age, sex, height, and weight (adjusted β=-15.4, P=0.26). There was also no significant correlation between ascending aortic diameter at baseline and cIMT progression in follow-up (adjusted β=-2.5; P=0.48). In the entire cohort, larger ascending aortic size was nominally associated with greater cIMT (adjusted β=5.0; P=0.005). As expected, larger diameter in the descending thoracic aorta was associated with higher cIMT (adjusted β=23.9; P=1.9x10
-16
).

Conclusion:
Based on multi-modal imaging data from over 40K individuals, we find no evidence of an inverse relationship between ascending aortic aneurysmal disease and atherosclerosis.
Abstract 13317: Current Smoking Impedes Recovery in Cardiac Rehabilitation
Authors: Khadanga Sherrie , Savage Patrick , Yant Blair , Ades Phillip , Gaalema Diann
Published: December 2023

Purpose:
Current smoking is a powerful predictor of future morbidity and mortality and those who smoke are more likely to have higher risk clinical profiles and less likely to engage in secondary prevention. Little is known about how those who smoke benefit from secondary prevention following a cardiac event, such as cardiac rehabilitation (CR). The purpose of this study was to compare improvements in fitness among those who smoke vs those who do not during CR.

Methods:
Data were gathered on 2208 individuals entering the University of Vermont CR program from 1/1996-12/2021. Self-reported smoking status was collected at CR entry (current vs. formerly vs. never smoking). Cardiorespiratory fitness (CRF)(peak oxygen capacity [VO2peak]) was assessed via exercise tolerance test at entry to and exit from CR. Change in Peak VO2 was compared by smoking status univariately and in a multivariate model controlling for other potential contributing variables like age, sex, entry VO2, number and severity of exercise-limiting comorbidities, BMI, and number of CR sessions attended.

Results:
On average patients improved by 3.26 in their CRF during the course of CR. In univariate analyses improvement by smoking status was 2.29, 3.06, and 3.55 (current, former, never smoker respectively). The final multivariate model included smoking status, CRF at intake, comorbidities, age, BMI, and interactions between smoking status and age, and BMI and age. Least square means from this model were improvements of 1.95, 3.10, and 3.53 (current, former, never smoker respectively).

Conclusion:
These data suggest that those who are currently smoking improve less in fitness during CR than those who formerly or never smoked and that controlling for covariates highlights that the biggest difference in the effect of smoking is truly between the current smokers and the former/never smokers. Further research should be conducted to see if successful smoking cessation can improve fitness related gains during CR.
Abstract 13323: Impact of an Institutional Process Change Adopting End-Systolic Coronary CTA Acquisition on Patient Throughput and Image Quality
Authors: Hosadurg Nisha , Harrison Kara , Rodriguez Patricia , Patel Amit , Norton Patrick , Villines Todd C
Published: December 2023

Introduction:
Prospective ECG-triggered end-systolic coronary computed tomographic angiography (CCTA) acquisition is less prone to motion artifacts with arrhythmias and high heart rates, and with increasing utilization, has the potential to improve scan and CT laboratory efficiency by reducing the need for IV/oral beta-blockers (BB) prior to the scan.

Methods:
We implemented an institutional process change in CCTA performance effective January 2023, transitioning from prospective ECG-triggered mid-diastolic acquisitions supervised by a physician at the scanner to an algorithmic approach with prospective end-systolic acquisition (200-400 ms after R peak) without BB administration, all on 3
rd
-generation 192 slice dual-source scanners. We reviewed 100 consecutive CCTAs done pre- and post-process change in Jan 2022 and Jan 2023. Two experienced CCTA readers assessed segmental image quality by consensus using an 18-segment SCCT model on a 5-point Likert scale (1=non-interpretable; 2=poor; 3=satisfactory; 4=good; 5=excellent).

Results:
Post-process change, median overall patient appointment [94 (78 - 127) min vs. 69 (53 - 86) min;
P
< 0.001] and scan times [12 (10 - 16) min vs. 7 (6 - 9) min;
P
<.001] were significantly lower, and patient throughput doubled [2 (2 - 3)/day vs. 4 (3 - 6)/day;
P
=.024]. Median segmental image quality score decreased from excellent to good [5 (4 - 5) vs. 4 (4 - 5);
P
<.001], with a decrease in signal-noise ratio [23.5 (18 - 28.8) vs. 11.8 (8.7 - 14.7);
P
<.001], and no significant difference in poor or non-interpretable segments in the end-systolic cohort. More scans were repeated with end-systolic scans (10% vs. 18%), with no significant change in radiation dose (Table 1).

Conclusion:
Utilizing prospective ECG-triggered end-systolic acquisition avoided the use of BB, significantly reduced scan times, doubled patient throughput, at similar radiation doses, and maintained diagnostic performance with only a mild compromise in image quality.
Abstract 13327: Mechanistic Basis of Sinoatrial Node Pacemaker Failure in Atrial Cardiomyopathy
Authors: Marcoux Édouard , Mackasey Martin , Naud Patrice , Sirois Martin G , Quinn T. Alexander , Nattel Stanley
Published: December 2023

Introduction:
Sinoatrial node (SAN) dysfunction commonly occurs in atrial cardiomyopathy (ACM: “tachy-brady syndrome”), often requiring pacemaker implantation, but mechanisms are unknown. Atrial-selective myosin light chain-4 (MYL-4) mutations cause familial ACM with a high rate of early SAN dysfunction and pacemaker requirement. We studied rats engineered with a knock-in MYL-4 clinical E11K mutation and addressed mechanisms of SAN dysfunction.

Methods:
Atrial electrical properties were assessed with
in vivo
electrophysiology (EPS),
ex vivo
optical mapping, SAN single-cell voltage and current clamp, Ca
2+
-handling with Ca
2+
-sensitive dye microscopy. Gene expression was assessed by qPCR and fibrosis with Masson-Trichrome stain.

Results:
E11K rats showed progressive SAN recovery-time increases (Fig. A) and conduction-slowing (Fig. B). SAN cells showed slowed phase-4 depolarization (Fig. C) and reduced pacemaker “funny” current (I
f
) (Fig. D). Ca
2+
homeostasis was also affected, showing decreased Ca
2+
-transients (Fig. E). SAN also displayed remodeling with increased collagen deposition (Fig. F).

Conclusions:
ACM resulting from E11K mutation induces multimodal electrical and structural remodeling of the SAN region, worsening with age. These observations provide new insights into mechanisms of the clinically important tachy-brady syndrome associated with ACM.
Abstract 13336: Myocardial Protection of Chitosan Cardiac Muscle Patch in Myocardial Infarcted Mice
Authors: Xiang Kun , Zhou Huatao , Tang Weijie , Tu Zhi , Zheng Zilong , Li Yichen , Yang Jinfu , Fan Chengming
Published: December 2023

Background:
Poor grafted rate of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) via direct injection into the myocardium limits the efficacy of cardiac repair after myocardial infarction (MI). Chitosan-based scaffolds has regarded as functional biomaterial for designing delivery systems in cardiac therapies. This study aimed to enhancing the potency of cardiac repair with the hiPSC-CMs loaded chitosan cardiac patch (hCCMP).

Methods:
The patches were fabricated with chitosan. Characterization of the chitosan patches was evaluated through the detection of swelling rate and porosity. Biocompatibility of the hiPSC-CMs loaded patches was analysed by scanning electron microscope (SEM) and CCK8 assay. The mice were randomly divided into 4 groups (n=10 for each). Animals underwent MI-inductive surgery followed by epicardium implantation of hCCMP or Empty-patch (without hiPSC-CMs); Sham and MI mice without further intervention were set as control. 4 weeks after MI, heart function was measured via echocardiography. Engraftment was evaluated with human cardiac troponin T staining. Infarction size, left ventricular anterior wall thickness, cardiac remodeling, angiogenesis, arterialization and apoptosis was detected via immunofluorescence in infarcted boder area.

Results:
SEM showed that the chitosan patch had regular pore size and good 3D structure; porosity was about (96.7±0.37)%. On day3, the patch swelling rate was about (715±64.55)%. SEM, CCK8 assay showed a normal cells growth in the chitosan patch. The hiPSC-CMs grafted well with chitosan patch delivery systems and was associated with significantly improvement in LV heart function, infarction size, LV anterior wall thickness, cardiac remodeling, angiogenesis and cardiomyocyte apoptosis 4 weeks after MI.

Conclusions:
The 3D chitosan cardiac patch with hiPSC-CMs loaded can enhance the potency of cardiac repair after MI and present a novel and promising therapic strategy.
Abstract 13351: Impact of a Second Incident Arrhythmia on Outcomes in Hospitalized COVID-19 Patients: Insights From the COVID-RHYTHM Registry
Authors: Ahmed Adnan , Bawa Danish , Charate Rishi , Russo Andrea M , Trivedi Jaimin , Wan Elaine Y , Mar Philip L , Kabra Rajesh , Gautam Sandeep , Stavrakis Stavros , Aksu Tolga , Saha Sandeep A , Liu Zhenguo , Dominic Paari , Asad Zain Ul Abideen U , Padmanabhan Deepak , Shenthar Jayaprakash , Al-Ahmad Amin , Natale Andrea , Lakkireddy Dhanunjaya , Gopinathannair Rakesh
Published: December 2023

Introduction:
Incident cardiac arrhythmias are common in hospitalized COVID-19 patients, but the impact of a second incident cardiac arrhythmia during hospitalization on clinical outcomes remain unclear.

Hypothesis:
The aim of this study was to assess the frequency and prognostic implications of a second incident arrhythmia in hospitalized COVID-19 patients over the pandemic course till vaccine availability.

Methods:
The multicenter COVID-RHYTHM Registry enrolled hospitalized COVID-19 patients from 3/8/2020 to 1/24/2021. Cardiac arrhythmia included documented atrial fibrillation (AF), atrial flutter (AFL), ventricular tachycardia (VT), severe sinus bradycardia (<40 bpm) or AV block. Outcomes were compared between patients with single vs. more than one incident arrhythmias adjusting for baseline variables.

Results:
Of 6299 hospitalized COVID-19 patients, 4398 had an had an incident cardiac arrhythmia during hospitalization, of which 822 (19%) had a second incident arrhythmia. Those with >1 incident arrhythmia had a higher baseline prevalence of heart failure, chronic kidney disease, coronary artery disease and sleep apnea (Table). Those with >1 incident arrhythmia had higher in-hospital mortality, need for ICU admission and need for rehab upon discharge. Length of stay was similar between the groups.

Conclusions:
In hospitalized COVID-19 patients with incident cardiac arrhythmias, a second incident arrhythmia during hospitalization was seen in 19%. Having >1 incident arrhythmia was associated with increased need for ICU admission and reduced survival.
Abstract 13370: Single-Cell RNA-seq Reveals Transcriptomic Modulation of Alzheimer’s Disease by Activated Protein C
Authors: Fatmi Mohammad K , Slotabec Lily , Wang Hao , Zhao Bi , Li Ji
Published: December 2023

Introduction:
Alzheimer’s Disease (AD) causes neuroinflammation characterized by degradation of neurological functions resulting in memory loss and confusion. Activated Protein C (APC), a plasma zymogen, has shown promising cytoprotection, anti-inflammation, and anti-apoptotic properties. ScRNA-seq allows for examining the underlying mechanisms by which APC therapy on AD at the cellular level.

Hypothesis:
APC treatment can ameliorate AD symptoms of 5xFAD transgenic mice. The scRNA Seq analysis could provide detailed responses of various cell populations to Alzheimer's disease pathogenesis and molecular aspects of APC therapy.

Methods:
Whole brain tissue were collected at 7 months, APC-treated 5xFAD mice received daily recombinant APC or saline injections. The 10x Genomics Next Gem kit was used to dissociate the tissue for sequencing. Bioinformatic analysis was performed using Seurat in R and an integrated dataset was used to compare multiple single-cell samples.

Results:
Bioinformatic analysis of 5xFAD versus wild type (WT) C57BL/6J mouse brain revealed much of the sample consists of microglial cells. Interestingly, 5xFAD versus WT brains have notable decreases in astrocyte and neuron populations. Administration of recombinant APC rebounds these populations to comparable levels as WT while dramatically reduces the microglial population in 5xFAD versus WT brain. The largest proportion of oligodendrocytes are also recorded after APC treatment. Differential expression testing conveys transcriptomic regulation of known AD critical genes such as
Apoe
,
Ctsb
,
Trem2
, and
Tyrobp
by APC. Consequently, GO term enrichment uncovers inflammatory biological processes such as microglial activation to be downregulated by APC-treated 5xFAD. Additionally, recuperation of nervous system developmental processes was found in APC-treated 5xFAD mice.

Conclusions:
APC treatment drastically impacts the cellular pathophysiology of AD. Differential expression testing of APC treated 5xFAD versus WT mice revealed transcriptomic downregulation of AD implicated genes throughout multiple cell-types. Administration of APC significantly impacts AD implicated genes associated with AD pathogenesis through enrichment analysis.
Abstract 13403: Age-Related Echocardiographic Characteristics in Patients With Heart Failure With Preserved Ejection Fraction in PARAGON-HF
Authors: Wang Xiaowen , Skali Hicham , Cikes Maja , Vardeny Orly , Lam Carolyn S , Redfield Margaret M , Kosztin Annamaria , Omeara Eileen , Mullens Wilfried , McMurray John J , Shah Amil M , Solomon Scott , Hegde Sheila
Published: December 2023

Introduction:
Heart failure with preserved ejection fraction (HFpEF) may have different characteristics by age groups.

Aim
Compare clinical and echocardiographic characteristics in patients with HFpEF enrolled in the PARAGON-HF echocardiography substudy by age groups.

Methods:
Echocardiography was performed in 1097 patients in PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction), where patients with left ventricular ejection fraction (LVEF) >=45% were enrolled. Clinical and echocardiographic characteristics were compared in patients who were <65, 65-74, and >75 years of age.

Results:
Younger patients were more likely to be male, obese, have prior myocardial infarction (MI) and diabetes, but less likely to have atrial fibrillation (AF, Table 1). Older patients had smaller left ventricular (LV) dimension indices, more likely to have concentric hypertrophy or remodeling, higher LVEF and better global longitudinal strain, and more likely to have left atrial enlargement and echocardiographic evidence of higher LV filling pressure (Table 1). Echocardiographic measures of pulmonary pressure and right ventricular function were similar across age groups. After adjusting for sex, race, region, history of MI, diabetes, AF, and body mass index, every 10 years of increase in age was associated with 5.1 mL/m
2
decrease in LV end-diastolic volume index (95% confidence interval [CI] 3.9 - 6.5, p < 0.001), 0.4% increase in absolute global longitudinal strain (95% CI 0.1% - 0.7%, p = 0.017), and 1.07 increase in E/e’ septal ratio (95% CI 0.42 - 1.73, p = 0.001).

Conclusions:
Compared with younger patients, older patients with HFpEF were more likely to be female with AF, have better systolic function and higher LV filling pressure. These findings demonstrated the heterogeneity in cardiac structure and function in HFpEF by age and may have implications for treatment and future clinical trial recruitment.
Abstract 13425: Outcomes of Delayed vs Early Cardioversion in Patients With Paroxysmal Atrial Fibrillation: A Population-Based Study (2015-2020)
Authors: Mohamed Mohamed Salah , Hashem Anas , Khalouf Amani , Osama Muhammad , Pendela Venkata Satish , Rai Devesh , Aronow Wilbert S , Balmer-Swain Mallory
Published: December 2023

Introduction:
Data on clinical outcomes of Delayed Cardioversion (DCV) compared to Early Cardioversion (ECV) in patients with paroxysmal atrial fibrillation (PAF) remains limited.

Hypothesis:
Is there a difference in clinical outcomes between both procedures?

Methods:
We used the National Inpatient Sample database by utilizing ICD-10 codes to identify all hospitalizations with a diagnosis of PAF and cardioversion (CV) (2015-2020). The associations between the time of CV and outcomes were examined using multivariable logistic or generalized linear model regression. Propensity-score matched (PSM) analysis was utilized to determine adjusted odds ratio (aOR) of major clinical outcomes.

Results:
A total of 17,879 patients with PAF were included: 9,725 (54.4%) and 8,154 (45.6%) underwent ECV and DCV, respectively. Regarding inpatient mortality, there was no significant difference between both groups (aOR 0.81 [0.52-1.25], p=0.76). Considering cardiovascular outcomes, DCV was more associated with acute heart failure (AHF) (aOR 1.79 [1.67-1.92], p<0.01) with no significant difference in cardiac arrest (aOR 1.16 [0.73-1.84], p=0.38), cardiogenic shock (aOR 0.83 [0.59-1.17], p=0.97), need for permeant pacemaker (aOR 1.18 [0.91-1.54], p= 0.13), and arrhythmias (supraventricular and ventricular tachycardia) (aOR 0.97 [0.86-1.10], p=0.98) compared to ECV. As to neurological outcomes, there was no difference between both groups including transient ischemic attack (aOR 1.58 [0.82-3.04], p=0.12), ischemic stroke (aOR 1.06 (0.59-1.90), p=0.77), and hemorrhagic stroke (aOR 1.35 [0.36-5.07], p=0.45). Compared to ECV, DCV was associated with a higher median length of stay (4 days vs. 2 days, p<0.01) and cost of hospitalization ($33,410 vs. $21,738, p<0.01).

Conclusions:
Compared to ECV, DCV was associated with more AHF and resource utilization without significant differences in inpatient mortality and other major cardiovascular and neurological outcomes.