bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143964: Combined electrocardiography artificial intelligence and echocardiography model to characterize precapillary versus postcapillary pulmonary hypertension in end stage chronic kidney disease.
Authors: Scalia Isabel , FARINA JUAN , Pereyra Milagros , Baba Nima , Mahmoud Ahmed K. , Abbas Mohammed Tiseer , Kamel Moaz , Awad Kamal , Sell-Dottin Kristen , Alsidawi Said , Barry Timothy , Scott Robert , Ayoub Chadi , Mour Girish , Arsanjani Reza
Published: November 2024

Introduction:
Pulmonary hypertension (PHTN) is common in patients with chronic kidney disease (CKD), however categorization as precapillary or postcapillary is challenging due to the need for invasive right heart catheterization (RHC). Studies have validated transthoracic echocardiography (TTE) to characterize PHTN and ECG-artificial intelligence (AI) to predict diastolic dysfunction risk. The utility of these noninvasive tools in patients with CKD is unknown.

Methods:
Retrospective analysis of patients with end stage CKD who underwent RHC between 2011 and 2021. Patients with PHTN (pulmonary artery pressure >20mmHg on RHC) were categorized as having precapillary (pulmonary capillary wedge pressure, PCWP, ≤15mmHg and pulmonary vascular resistance, PVR, >2WU) or postcapillary PHTN (PCWP >15mmHg and PVR ≤2WU for isolated postcapillary or PVR >2WU for combined). TTE and ECG within 3 months of RHC were obtained. TTE measurements were used to calculate ePLAR (echocardiographic pulmonary to left atrial ratio); tricuspid regurgitant peak velocity (TRV
max
) divided by mitral E/e’. ECGs were analyzed with an AI risk tool for diastolic dysfunction (score 0-3, increasing with increasing risk). Receiver operating curves (ROC) evaluated the performance of these tests.

Results:
60 patients were included; 16 (27%) with precapillary and 44 (73%) with postcapillary PHTN. ROC analysis found good accuracy for both ECG-AI diastolic dysfunction risk score to predict precapillary PHTN with AUC 0.724 (sensitivity=60% and specificity=88% for an ECG score value ≤1) and ePLAR with AUC 0.715 (sensitivity=75% and specificity=70% for ePLAR >0.17m/sec). Highest accuracy for detection of precapillary PHTN was reached by combination of ePLAR and ECG-AI tool, with AUC 0.756 (sensitivity=73%, accuracy of 86% for a value ≤1.17).

Conclusions:
ECG-AI generated diastolic risk score of 0-1 (low risk) and high ePLAR showed good accuracy in characterizing precapillary PHTN in patients with end stage CKD. The combination of these noninvasive tools further increased the diagnostic accuracy, reflecting its potential utility in classification of patients with CKD and PHTN, a crucial determinant of the ideal therapeutic plan in kidney transplant candidates.
Abstract 4143974: hiPSCs Derived Cardiomyocyte Spheroid Transplantation Induces Proliferation of Pig Myocytes by Mediating YAP Signaling
Authors: Wei Yuhua , Walcott Gregory , NGUYEN THANH , Geng Xiaoxiao , Guragain Bijay , Zhang Hanyu , Green Akazha , Rosa-Garrido Manuel , Rogers Jack , Garry Daniel , Ye Lei , Zhang Jianyi
Published: November 2024

Background:
Our previous study showed that cardiomyocytes (CMs) differentiated from hiPSCs with cyclin-D2 overexpression (
CCND2-OE
hiPSC-CMs) induced the proliferation to repopulate > 50% of the scar in immunodeficient mouse hearts. To reduce the immunogenicity of
CCND2-OE
hiPSCs, we knocked out the HLA classes -I and -II (
KO/OE
hiPSCs) and assessed the therapeutic efficacy and mechanism of
KO/OE
hiPSCs-derived CMs (
KO/OE
hiPSC-CMs) for myocardial infarction (MI) treatment.

Methods:
KO/OE
hiPSC-CM or wild-type hiPSC-CM (
WT
hiPSC-CM) spheroids were differentiated in shaking flasks, purified, characterized, and injected into pig hearts post ischemia/reperfusion (I/R), while controls received medium injection only. Cardiac function was evaluated using cardiac magnetic resonance imaging (cMRI). CM proliferation was assessed through immunostaining and single-nucleus RNA sequencing (snRNAseq).

Results:
KO/OE
hiPSC-CM spheroids secreted abundant follistatin compared to
WT
hiPSC-CM spheroids (30.3±4.13 vs 16.6±1.43 ng/mL, p=0.0056). Follistatin, which interacts with HIPPO/YAP pathway, stimulated
WT
hiPSC-CM proliferation and increased cell number by 28.3% over 16 days
in vitro
and promoted adult mice CM proliferation after MI
in vivo
. cMRI assessments indicated better cardiac function and scar sizes in
KO/OE
hiPSC-CM spheroid treated pig hearts compared to medium or
WT
hiPSC-CM spheroid treated pigs. Although the injected cells were only identified at 1 week, cell-cycle activity was significantly higher in the CMs of
KO/OE
hiPSC-CM spheroid treated pig hearts compared to the other two groups. A cluster of cycling CMs, enriched for five genes associated with cell proliferation according to snRNAseq data, was more prevalent in the
KO/OE
hiPSC-CM spheroid (3.65%) compared to the medium (0.89%) or
WT
hiPSC-CM spheroid treated (1.33%) hearts at 1 week. Pathways linked to cardiac regeneration—MAPK, HIPPO/YAP, and TGFB—were significantly upregulated in pig CMs treated with
KO/OE
hiPSC-CM spheroids. Furthermore, YAP protein levels and nuclear localization in CMs were higher in the
KO/OE
hiPSC-CM spheroid treated pig hearts compared to controls. Thus, follistatin secreted by implanted
KO/OE
hiPSC-CM spheroids appear to target the HIPPO/YAP pathway to promote pig CM proliferation.

Conclusions:
KO/OE
hiPSC-CM spheroids significantly improved cardiac function and reduced infarct size in pig hearts after I/R by secreting follistatin which promoted pig CM proliferation through YAP signaling.
Abstract 4143983: Benefits and Risks Associated with Mineralocorticoid Receptor Antagonists in Tafamidis-treated Transthyretin Amyloid Cardiomyopathy: A Real-World Analysis
Authors: Chi Kuan Yu , Borkowski Pawel , Osabutey Anita , Varrias Dimitrios , Song Junmin , Chang Yu , Madan Shivank , Patel Snehal
Published: November 2024

Background:
There is currently no data on the use of mineralocorticoid receptor antagonists (MRA) in tafamidis-treated transthyretin amyloid cardiomyopathy (ATTR-CM).

Research Question:
Does the addition of MRA provide extra benefits in ATTR-CM patients treated with tafamidis?

Aim:
To assess the benefits and risks associated with MRA in tafamidis-treated ATTR-CM through a new-user design propensity-score matching (PSM) analysis.

Methods:
We conducted a retrospective, PSM cohort study using the TriNetX Global database. We included adult ATTR-CM patients who had their first tafamidis prescription within 1 year after the identification of amyloidosis between January 1, 2018, and May 1, 2023. MRA users and non-users were subsequently identified, with the former defined as those having both tafamidis and spironolactone/eplerenone, and the latter having tafamidis without MRA. Patients with prior MRA use before their first tafamidis prescription were excluded. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause mortality, heart failure (HF) hospitalization, or cardiac arrest/ventricular tachycardia/fibrillation. Secondary endpoints were individual MACE. The safety endpoint was a composite of acute kidney injury (AKI) or hyperkalemia. Incident gastrointestinal bleeding and pneumonia were set as falsification endpoints. We compare study endpoints occurring within two years of tafamidis initiation between MRA users and non-users.

Results:
Among 2,174 tafamidis-treated ATTR-CM patients, 471 MRA users were matched to 471 non-users with similar age (76.7 vs. 76.7), sex (female, 16.8% vs. 17.4%), and mean ejection fraction (50.1% vs. 49.9%). Amyloid staging markers and important medications were also balanced
(Figure)
. MRA use was not associated with a significant reduction in MACE (HR, 0.90; 95% CI, 0.64 to 1.27)
(Figure)
. Conversely, it was associated with a significant increase in AKI or hyperkalemia (HR, 1.69; 95% CI, 1.13 to 2.54)
(Figure)
. The two falsification endpoints were comparable between the two groups
(Figure)
.

Conclusions:
In ATTR-CM patients treated with tafamidis, MRA was not associated with a significant reduction in MACE but with an increased risk of AKI or hyperkalemia.
Abstract 4143988: Activation of TRPA1 with allyl isothiocyanate prevents age-related cardiac diastolic dysfunction
Authors: Qian Chunqi , Fernandez Zachary , Wang Donna , Ma Shuangtao
Published: November 2024

While its role in aging processes in mammals is largely unknown, activation of transient receptor potential ankyrin 1 (TRPA1), a sensor for noxious cold and oxidative stress , has been shown to decelerate aging and promote longevity in invertebrate animal models. Our previous study demonstrated that knockout of the Trpa1 gene accelerated age-related cardiac fibrosis and dysfunction in mice. The present study aimed to investigate whether activation of TRPA1 with its selective agonist allyl isothiocyanate (AITC) prevents age-related cardiac remodeling and dysfunction. Male and female 78-week-old aging C57BL/6J mice were randomized to receive either control diet or diet containing AITC (15 mg/Kg) for 26 weeks, and 12-week-old C57BL/6J mice were used as young controls. Transthoracic echocardiography was performed at the end of the experiment and showed that 104-week-old male and female aged mice that received control diet for 26 weeks developed restrictive-like diastolic dysfunction with significantly increased E/A ratio (2.41±0.84 vs. 1.22±0.03,
P
<0.01) and isovolumetric relaxation time (IVRT, 15.17±1.31ms vs. 10.32±1.81ms,
P
<0.01) compared to 12-week-old young mice. Remarkably, aged mice on AITC diet showed significantly improved diastolic function with decreased E/A ratio (1.60±0.24 vs. 2.41±0.84,
P
<0.01) and IVRT (11.75±2.09ms vs. 15.17±1.31ms,
P
<0.05) compared to aged mice on control diet. In contrast, the left ventricular end-diastolic and end-systolic wall thickness, internal diameter, and volume as well as left ventricular ejection fraction (young mice: 66.30±4.47% vs. aged mice on control diet: 59.49±11.27% vs. aged mice on AITC diet: 65.19±8.32%,
P
>0.05) were not significantly different among the three groups. Pathologic analyses demonstrated that aged mice on control diet developed increased cardiac collagen I, collagen III, and transthyretin deposition compared to young mice, which were significantly improved in aged mice on AITC diet. Taken together, these results show that aged mice developed restrictive-like cardiomyopathy with remarkable diastolic but not systolic dysfunction, and that chronic activation of TRPA1 with oral AITC prevented age-related cardiac fibrosis, transthyretin deposition, and diastolic dysfunction. These results indicate that TRPA1 may serve as a therapeutic target for age-related heart failure with preserved ejection fraction.
Abstract 4143994: Unraveling the Genetic Overlaps in Heart Failure Subtypes: A Systems Biology Approach
Authors: Pavicic Venegas Mirko Vierislav , Sullivan Kyle , Gopal Jay , Vlot Hendrika , Lane Matthew , Rahafrooz Maryam , Elbers Danne , Gagnon David , Hui Qin , Liu Chang , Sun Yan , Joseph Jacob , Jacobson Daniel
Published: November 2024

Background:
Heart failure (HF), a progressive condition with a complex etiopathology causes significant morbidity, mortality, and reduced quality of life. HF affects 64 million people worldwide and imposes a global healthcare burden exceeding $346 billion annually. Currently, HF is classified into two major clinical subtypes based on cardiac contractility: HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Given the complex pathophysiology of HF, we utilized systems biology tools applied to gene-level results from genome-wide association studies (GWAS) of HF, HFrEF, and HFpEF to identify underlying molecular pathways underlying these phenotypes.

Methods:
We utilized the union of three SNP-to-gene mapping methods: SNP-nearest gene, MAGMA, and H-MAGMA which uses Hi-C datasets from cardiovascular, lung, and liver tissues. Additionally, we built a gene-gene multiplex network from protein-protein interactions, transcription factor-target relationships, and predictive expression networks created with explainable-Artificial Intelligence (AI) algorithms from cardiac/metabolic layers, aorta, atrial appendage, left ventricle, coronary artery, whole blood plus lymphocytes, lung, and liver. The multiplex network was then used by the systems biology tools Gene set Refinement through Interacting Networks (GRIN) to refine the genes assigned from SNPs, while Multiplex Embedding of Networks For Team-Based Omics Research (MENTOR) grouped genes into functional clusters using hierarchical clustering of network embeddings.

Results:
Multiple SNP-to-gene assignment methods identified 51 genes for HF, 6 for HFpEF, and 109 for HFrEF. GRIN retained 42 connected genes for HF, 4 genes for HFpEF, and 78 genes for HFrEF. Ultimately, 119 unique genes were identified in total, with 86 of them being retained by GRIN. MENTOR clustering identified key biological processes affected by these genes including cytoskeletal function, extracellular matrix composition, inflammatory cytokine activity, and post-transcriptional modification of mRNA.

Conclusion:
Utilizing systems biology approaches, we were able to identify biologically connected genes and distinct molecular pathways underlying HF, HFrEF, and HFpEF.
Abstract 4144001: Association Between Diabetes Mellitus and Angina With Nonobstructive Coronary Arteries
Authors: Latif Nida , Cigarroa Natasha , Kostantinis Spyridon , Garcia Castro Gabriel , Kunnirickal Steffne , Odanovic Natalija , Shah Samit
Published: November 2024

Introduction:
Diabetes mellitus (DM) is a risk factor for coronary microvascular dysfunction (CMD) and endothelial dysfunction. These disorders and other syndromes of angina and nonobstructive coronary arteries (ANOCA) are increasingly recognized. However, the association between DM and non-CMD ANOCA endotypes, such as vasospastic angina (VA) and symptomatic myocardial bridging (MB), is not well defined. This study aims to report the findings of coronary function testing (CFT) in patients with DM and to determine the association between DM and specific ANOCA endotypes.

Methods:
We conducted a retrospective study of patients who underwent clinically indicated invasive coronary angiography and CFT with intracoronary acetylcholine provocation and bolus thermodilution between January 2018 and May 2024. Data regarding patient demographics, medical history, and physiological measurements—including coronary flow reserve (CFR), index of microcirculatory resistance (IMR), fractional flow reserve (FFR), resting full-cycle ratio (RFR), and post-procedure diagnosis—were obtained.

Results:
233 patients were included, 163 (70%) were female, with a mean age of 57 ± 11 years. Of the total cohort 52 patients (22.3%) had DM. Among patients with DM, 23 (44%) had CMD, 13 (25%) had VA, 6 (12%) had mixed CMD/VA, 11 (21%) had endothelial dysfunction, and 4 (7.7%) had other phenotypes such as elevated resting flow and MB. The median CFR was reduced in patients with DM compared to those without DM (2.6 vs. 3.45; p=0.001), and the median IMR was higher (28 vs. 19; p<0.001). No statistically significant differences were found in the median FFR (0.89 vs. 0.9; p=0.375) or median RFR (0.91 vs. 0.93; p=0.1). The risk of having any ANOCA diagnosis was comparable between patients with DM and those without DM (risk ratio = 1.03 [0.92, 1.15]; p=0.67), but patients with DM had a significantly increased risk of CMD compared to patients without DM (risk ratio = 1.82 [1.22, 2.71]; p=0.0052). No association was observed between DM and any other ANOCA endotypes.

Conclusion:
Our analysis revealed that DM is associated with lower CFR, higher IMR, and an increased risk of CMD. No association was found between DM and any other ANOCA endotype. These findings align with existing data using a contemporary, reproducible CFT protocol. Future studies will explore the clinical implications of these findings and evaluate the impact of glycemic control on outcomes in this patient population.
Abstract 4144008: MindMoves: Effect of Lifestyle Physical Activity and Cognitive Training Interventions on Blood Biomarkers in Older Women with Cardiovascular Disease
Authors: Halloway Shannon , Borgia Jeffrey , Shakya Shamatree , Schoeny Michael , Volgman Annabelle , Wilbur Joellen , Barnes Lisa , Vispute Sachin , Wilhelm Kaitlin , Auger Claire , Pressler Susan , Arvanitakis Zoe
Published: November 2024

Background:
Physical activity and cognitive training can improve cognitive health, including related neurotrophic biomarkers, with potential interactive effects. In older women with cardiovascular disease (CVD) who are at increased risk for poor cognitive health, we evaluated the efficacy of
MindMoves
, a 24-week multidomain physical activity and cognitive training intervention, on change in serum biomarkers, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), and growth differentiation factor 15 (GDF-15).

Methods:
This randomized controlled trial (NCT04556305) with a 2x2 factorial design tested independent and combined efficacies of
Mind
(tablet-based cognitive training) and
Move
(lifestyle physical activity) on change in serum biomarkers (BDNF, VEGF, IGF-1, GDF-15). Women (
n
= 253) aged 65 years and older with CVD were randomized to
Mind
,
Move
,
MindMoves
, or usual care. Women completed fasting venipunctures at baseline, 24, 48, and 72 weeks. We conducted multilevel linear growth models adjusting for age, education, and racial and ethnic background. To examine intervention effects on linear change in serum biomarkers over 72 weeks, we included main and interaction effects of
Mind
and
Move
.

Results:
Participants were, on average, 72.4 years old at baseline (
range
= 65–90), primarily of non-Hispanic White (54%) and Black (38%) racial backgrounds, and 60% graduated college. A total of 86% (
n
= 218) of participants completed the 72-week data collection. Attrition was not a significant function of intervention condition or sociodemographics (all
p
’s > .05). There were no significant main effects of
Mind
or
Move
on linear change for any of the four serum biomarkers. However, there was a significant interaction effect (
Mind
*
Move
) on linear change over all four timepoints for GDF-15, whereby those in the control and combined conditions improved (decreased) relative to those in the
Mind
or
Move
conditions (
t
= -2.20,
p
= .028).

Conclusions:
In this cohort of older women with CVD, there were significant
Mind*Move
interactive effects on GDF-15, a biomarker that may be associated with risk of Alzheimer’s disease or other conditions related to neuroinflammation. However, there were no significant intervention effects for the other biomarkers. Future analyses should examine other biomarkers related to Alzheimer’s disease and inflammation that may provide more mechanistic insight.
Abstract 4144019: Early total cell-free DNA, but not donor fraction, predicts late events in heart transplantation
Authors: Zangwill Steven , Deshpande Shriprasad , Richmond Marc , Zhang Liyun , Simpson Pippa , Dasgupta Mahua , Tomita-Mitchell Aoy , Mitchell Michael
Published: November 2024

Introduction:
Donor fraction (DF) cell-free DNA (cfDNA) is an emerging tool for non-invasive rejection surveillance in heart transplantation (HTx). Little is known about the significance of DF and/or total cfDNA (TcfDNA) in the first month post HTx. We explored the relationship between early cfDNA results and later clinical events in adult and pediatric HTx recipients.

Aims:
1. Explore the relationship between early cfDNA levels and late events after HTx 2. Describe the decline in DF during the first month post HTx

Methods:
Retrospective data from the multicenter prospective blinded DTRT study (DNA-based transplant rejection test) was used. DF and TcfDNA results from samples drawn post HTx day 1 (<24h), day 4 (+/- 12h), day 7 (+/- 12h), day 14 (+/- 24h) and day 28 (+/- 7 days) were compared in subjects with or without events >35d to 1 year post HTx. Captured events include cardiac arrest, mechanical circulatory support or death. Exclusions included absent TcfDNA, multiorgan Tx, any PTLD, or other cancer in previous 2 yrs. Cell-free DNA values were compared across event groups and time windows using GEE (generalized estimating equation) with Max Likelihood Estimation.

Results:
190 subjects had 566 samples drawn < 35 days post HTx. Median age was 17.8 yrs with a range of 26 days - 73.4 yrs; 51.8% were pediatric. 16 subjects (8.4%) had events bridging or following day 35 post HTx; 23 with events prior to day 35 were included as non-event subjects. TcfDNA was significantly higher in event subjects on days 4, 7 and 28 post HTx. [Fig 1]. There was no difference in DF between event and non-event subjects. Median (IQR) DF at 14 days was 0.26% (0.20, 0.39) and 0.19% (0.13, 0.29) at 28 days.

Conclusions:
Elevated TcfDNA, even in the setting of normal DF, may be a useful early marker to identify patients at risk for later events in the first year post HTx. The majority of patients reach low DF levels by 28 days post HTx suggesting an opportunity to incorporate cfDNA earlier into rejection surveillance protocols.
Abstract 4144024: AI-Enabled Photoplethysmography Can Help Detect Elevated Blood Pressure And Predict Near-Term Incidence Of Hypertension
Authors: Di Achille Paolo , Su Hao-Wei , Ko Ho , Taylor James , Shreibati Jacqueline , Thompson Matthew , Poh Ming-Zher
Published: November 2024

Background:
Improving detection of individuals with undiagnosed hypertension (HTN) and those at risk of developing HTN are global priorities. Sensors within smartphone and consumer devices capable of photoplethysmography (PPG) may provide novel tools to support these efforts.

Aims:
Determine risk of baseline elevated blood pressure (BP) and incident HTN using a deep learning model (AI-PPG-BP) derived from PPG waveforms.

Methods:
Using the UK Biobank dataset, participants aged 40-74 without previously known HTN or cardiovascular disease were split into train (N=58,216), tune (N=31,671), and test (N=44,684) sets based on location of the data collection site. We trained a 1D convolutional neural network incorporating age, sex, weight and height to estimate BP from PPG waveforms (obtained from a 10-15 second recording with an infra-red sensor). Performance of model-predicted BP (AI-PPG-BP) in detecting elevated BP at baseline was compared to a logistic regression model using risk factors of age, sex, BMI, parental HTN, and smoking status (RF-BP). Additionally, we developed a Cox proportional hazards model to predict 4-year incident HTN (AI-PPG-HTN), using AI-PPG-BP as well as the risk factors. Model performance for incident HTN was compared to a Cox model using risk factors alone (RF-HTN), as well as the Framingham HTN risk score.

Results:
In the test set, AI-PPG-BP detected elevated baseline SBP/DBP of >140/90 (n=15,696, 35.1%) and >160/110 mmHg (n=3,546, 7.9%) with AUROCs of 0.818 [95%CI: 0.814-0.822] and 0.867 [0.861-0.872], respectively, outperforming RF-BP (AUROC 0.696 [0.691-0.700] and 0.706 [0.698-0.714]). AI-PPG-BP stratified cumulative incidence of HTN, and was significantly associated with risk of incident HTN (HR per SD: 1.48 [1.41-1.54], p<0.001) after adjusting for risk factors. The c-statistic for AI-PPG-HTN (0.733 [0.725, 0.741]) outperformed RF-HTN (0.711 [0.703, 0.721]); and was non-inferior to the Framingham HTN risk score (0.736 [0.728, 0.745]; prespecified non-inferiority margin 0.010, p<0.01).

Conclusion:
A deep learning model, AI-PPG-BP, may be able to serve as a useful pre-screener by helping to detect elevated BP and stratifying risk of near-term, incident HTN using finger PPG.
Abstract 4144032: Decadal Trends in Heart Failure Prevalence (2013-2023) Among Women of Childbearing Age with Prior Adverse Pregnancy Outcomes: Insights from a Population-Based Study
Authors: Awoyemi Toluwalase , Jaamour Dania , Anuforo Anderson , Odo Chinenye , Tolu-Akinnawo Oluwaremilekun
Published: November 2024

Background:
Heart failure (HF) represents a critical public health concern, especially among women of childbearing age, where its prevalence has been steadily increasing over recent years. Women with prior adverse pregnancy outcomes, such as hypertensive disorders of pregnancy, gestational diabetes mellitus, or preterm birth, face an elevated risk of developing heart failure later in life.

Methods:
This study investigated heart failure prevalence and trends over the period 2013 to 2023, leveraging data from 64 healthcare organizations within the TriNetX global health research network within the US Collaborative Network. The cohort consisted of 979,178 females aged 15-60 who had maternal care-related encounters and were diagnosed with specific conditions indicative of adverse pregnancy outcomes. These conditions included hypertensive disorders of pregnancy, gestational diabetes mellitus, placenta previa, intrauterine growth restriction, or macrosomia. Prevalence rates were calculated annually and stratified by age and race. The analysis encompassed January 1, 2013, to December 31, 2023, with a one-day lookback period.

Results:
Across the decade from 2013 to 2023, there was a notable surge in heart failure prevalence, escalating from 0.39% to 1.26%, corresponding to an average annual increase of approximately 12.38%. When examining racial disparities, Asians exhibited the lowest prevalence rates, initiating at 0.236% in 2013 and ascending to 0.673% in 2023, with an average annual increase of roughly 10.1%. Of note, the Black or African American cohort manifested the highest prevalence rates in both 2013 (0.708%) and 2023 (2.35%), with an average annual increase of approximately 12.77%. Within the 45-49 years age group, prevalence surged from 1.69% to 2.57%, signifying an average annual rise of about 4.36%, highlighting the escalating burden of heart failure among middle-aged adults.

Conclusions:
This study illuminates a concerning surge in heart failure prevalence over the past decade, revealing alarming rises across age and racial demographics. Particularly noteworthy is the heightened impact on younger individuals and certain minority groups, notably Black or African American patients.
Abstract 4144040: Porcine Coronary Plaque Morphology And Composition Closely Resemble Different Stages of Human Atherosclerosis
Authors: Li Mingqiao , Delafontaine Patrice , Sukhanov Sergiy
Published: November 2024

Background:
Coronary heart disease (CHD) remains the primary cause of mortality and morbidity in the USA. Although rodents are widely used to explore mechanisms, they have major biological differences with humans. Pigs develop CHD similar to humans, and pigs are the FDA-preferred species for testing anti-atherosclerotic drugs. Pigs with familial hypercholesterolemia (FH pigs) are known to develop advanced atheromas containing thin fibrous caps, and large necrotic cores. However, little is known about the porcine plaque phenotype and whether pigs develop a full range of coronary plaques similar to humans.

Aims:
To quantify the distribution of porcine coronary plaque types, assess plaque morphology and cellular composition to obtain insights into mechanisms of atherosclerosis in a large animal model and to facilitate development of new therapies.

Methods:
Right coronary and left anterior descending arteries were dissected from FH pig hearts (n=9), each artery split into 6 fragments and a total of 108 vascular fragments were used to obtain cross-sections. The sections were stained with Trichrome to quantify intima/media thickness ratio (IMT), medial and necrotic core areas. The sections were also used for immunohistochemistry with cell marker antibodies (to measure % plaque smooth muscle cells (SMC), macrophages (MF), and endothelial cells (EC)). Cell apoptosis was assessed by TUNEL assay.

Results:
All vascular fragments were classified into 4 groups based on IMT (from A to D). Increase in IMT significantly correlated with elevation in total vessel area (A: 3.8mm
2
to D: 7.2mm
2
), increase in necrotic core area (B: 13.8% to D: 30.7%), elevation in plaque MF (A: 16.7% to D: 22.5%), increase in plaque cell apoptosis (A: 5.2% to D: 17.4% apoptotic cells) and with thinning of vascular media (A:1.3mm
2
to D: 0.74mm
2
), decrease in number of plaque SMC (A: 62.5% to D:17.9%) and plaque EC (A:3.21% to D:1.48%). We assigned each porcine plaque group to the corresponding type of human plaque: A, human type III, early lesions, 28% of all coronary plaques; B, type III/IV, fibrous plaque, 43%; C, type V, fibroatheroma, 16%; D, type VI, complicated lesions, 13%.

Conclusions:
Like humans, pigs develop plaques that range from early lesions to advanced atheromas resembling type III-type VI lesions. These findings provide a rationale to use FH pigs to test the effect of novel anti-atherosclerotic drugs on the full range of coronary plaques mimicking human settings.
Abstract 4144041: AI-Based ECG Denoising Improves Smartwatch ECG Interpretation
Authors: Liao Shun , Di Achille Paolo , Vakharia Tanay , Faranesh Tony , Shreibati Jacqueline , Poh Ming-Zher
Published: November 2024

Background/Aim:
Smartwatch ECGs (SW-ECG) have emerged as a noninvasive solution to assess abnormal heart rhythms such as atrial fibrillation (AF). However, SW-ECGs recorded in free-living settings are often noisy and yield Inconclusive results from automated AF detection algorithms. We developed a deep learning model to denoise single-lead ECGs and reduce the number of inconclusive tracings that require manual overread.

Methods:
Using the MIMIC-III waveform database (N=2,988 patients, 10.1% AF), we created pairs of clean (high signal quality index based on dynamic beat template matching) 30-sec, single-lead ECGs and their noisy counterparts by injecting various combinations of noise including baseline wander, electrode motion and synthetic noise of different colors. The noisy ECGs served as the input to a 1D U-Net that was trained to reconstruct the corresponding clean ECG (AI-ECG-Denoise). We evaluated the performance of an offline automated ECG classifier before and after applying AI-ECG-Denoise on a held-out test set from MIMIC-III (N=34 patients, 52.9% AF) comprising 1,000 single-lead ECGs that we injected with noise at different signal-to-noise ratios (SNRs), and an external test set of 701 free-living SW-ECGs from 115 healthy consented study subjects using a prototype watch.

Results:
In the MIMIC-III test set, AI-ECG-Denoise significantly reduced the number of Inconclusive ECG results across noisy ECGs with SNRs ranging from -10 to 30 dB with no significant difference in sensitivity and specificity for AF down to an SNR of 3 dB. In the external wrist-worn test set, AI-ECG-Denoise significantly reduced the number of Inconclusive free-living SW-ECG Interpretations (p<0.001) by 33.3% [95% CI: 25.1, 39.9], recategorizing the majority as Normal, with no significant difference in specificity per McNemar’s test (99.2% [98.4, 99.8] before and 98.8% [97.8, 99.6] after denoising).

Conclusion:
A deep learning model for ECG denoising decreased the number of Inconclusive results in the detection of AF from SW-ECGs. This could help reduce user anxiety and limit the overreading time spent by the physicians.
Abstract 4144048: Propensity Score-Matched Analysis of GLP-1 Agonists' Impact on Clinical Cardiovascular Outcomes in Patients with Concurrent Heart Failure and Atrial Fibrillation
Authors: Awoyemi Toluwalase , Anuforo Anderson , Alagbo Habib , Ogunmola Isaac , Gbekor Stephen , Awe Mishael , Daniel Emmanuel
Published: November 2024

Background:
Heart failure (HF) and paroxysmal atrial fibrillation (AF) are major causes of morbidity and mortality, each exacerbating the other and leading to poorer outcomes. Glucagon-like peptide-1 agonists (GLP-1a), primarily used for glycemic control in type 2 diabetes, may offer cardiovascular benefits in patients with concurrent HF and paroxysmal AF.

Objective:
This study aims to evaluate the impact of GLP-1a on clinical outcomes in patients with concurrent HF and paroxysmal AF.

Methods:
This retrospective study utilized data from 51,446 HFrEF patients across 91 global healthcare organizations between January 2014 and August 2023. Propensity score matching (PSM) analysis was used to compare cardiovascular outcomes such as all-cause mortality, the need for new antiarrhythmic medication, cardioversion, AF ablation, incidence of acute myocardial infarction (AMI), and cardiac arrest, between those treated with GLP-1a and those who were not.

Results:
Our analysis revealed that the GLP-1a group had significantly lower odds of requiring cardioversion (3.1% vs 5.0%, OR = 0.67, 95% CI: 0.45–0.99, p=0.041), AF ablation (1.7% vs 3.7%, OR = 0.51, 95% CI: 0.27–0.98, p=0.038), new antiarrhythmic drugs (12.0% vs 13.9%, OR = 0.81, 95% CI: 0.66–0.99, p=0.036), experiencing AMI (OR: 0.70, 95% CI: 0.50–0.98, p=0.035), experiencing cardiac arrest (OR: 0.54, 95% CI: 0.37–0.80, p=0.002), and all-cause mortality (OR: 0.59, 95% CI: 0.51–0.68, p<0.001) compared to the non-GLP-1a group. There were no significant differences between the groups in the need for pacemaker/ICD implantation, development of persistent or long-standing persistent AF, or the risk of ventricular fibrillation or flutter. Furthermore, Kaplan-Meier analysis showed a higher 5-year incidence-free probability of cardiac arrest (94.9% vs 90.5%), AMI (90.2% vs 87.2%, p=0.017), and a higher 5-year survival probability (62.3% vs 51.2%, p<0.001) in the GLP-1a group compared to the non-GLP-1a group

Conclusion:
GLP-1a treatment is associated with improved clinical cardiovascular outcomes, including reduced need for new antiarrhythmic drugs, AF ablation, cardioversion, lower incidence of AMI, cardiac arrest, and all-cause mortality in patients with concurrent HF and paroxysmal AF. These findings suggest potential therapeutic benefits of GLP-1a. Additional studies are recommended to validate these findings and investigate the underlying mechanisms.
Abstract 4144054: Circulating Senescence-Associated Secretory Phenotype (SASP) Proteins Are Associated with Risk of Late Life Heart Failure: the ARIC Study
Authors: Dehghan Arshama , Giugni Fernando , Lamberson Victoria , Yang Yimin , Boerwinkle Eric , Fornage Myriam , Giannarelli Chiara , Grams Morgan , Windham B Gwen , Mosley Thomas , Palta Priya , Yu Bing , Shah Amil
Published: November 2024

Introduction:
Emerging evidence suggests a role for cellular senescence in the pathogenesis of age-related cardiac dysfunction. Senescence-associated secretory phenotype (SASP) is a hallmark of senescent cells, but the extent to which circulating SASP protein levels associate with cardiac dysfunction is not known.

Objectives:
Determine associations of plasma SASP proteins with subclinical cardiac dysfunction and incident heart failure (HF).

Methods:
Among 4,484 HF-free participants in the community-based Atherosclerosis Risk in Communities study who attended the 5
th
study visit (2011-2013) and underwent protocol echocardiography, we measured 25 core SASP proteins (SomaScan aptamer-affinity assay). We assessed their associations with cardiac structure/function and incident adjudicated HF using multivariable linear and Cox proportional hazards models adjusted for demographics and clinical characteristics.

Results:
The mean age was 76±5 years, 58% were female, 17% reported Black race, and mean LVEF was 66±6%. 439 incident HF events occurred over 8 [IQR 7-9] year follow-up. Eight of 25 core SASP proteins associated with risk of incident HF at FDR <0.05 (GDF15, IGFBP2, IGFBP7, TIMP2, TIMP1, MMP2, CTSB, CST3; Figure A). Among those, 6 proteins (TIMP1, TIMP2, IGFBP2, MMP2, IGFB7, GDF15) were associated with both incident HFrEF (n=179 events) and HFpEF (n=201 events) at FDR significance, while CST3 was only associated with HFpEF, and CTSB only with HFrEF. These 8 proteins were also generally associated with greater LV size and worse LA reservoir strain but showed differential associations with worse global longitudinal strain (IGFBP2, TIMP2, MMP2, CTSB) versus diastolic measures including E/e, LAVi, and PASP (CST3, IGFBP7; Figure B).

Conclusion:
Plasma values of a subset of core SASP proteins associate with cardiac dysfunction and HF risk in older adults, supporting cellular senescence-related mechanisms as a contributor to late-life HF risk.
Abstract 4144055: Adverse Physical Environment, Housing, and Economic Conditions: Their Impact on Maternal Cardiovascular Health during and Post-Pregnancy
Authors: Awoyemi Toluwalase , Anuforo Anderson , Tolu-Akinnawo Oluwaremilekun
Published: November 2024

Background:
Maternal cardiovascular health is a critical concern, particularly during and following pregnancy. Previous studies have highlighted the influence of social determinants on health outcomes, but the specific impact of adverse Physical Environment, Housing, and Economic Conditions on maternal cardiovascular health remains underexplored.

Methods:
Using the TriNetX global health research network within the US Collaborative Network, we explored how adverse Physical Environment, Housing, and Economic Conditions (ICD10CM: Z58 and ICD10CM: Z59) impact maternal cardiovascular health during pregnancy and within one year postpartum. Using, propensity score matching (PSM) analysis, our study compared two cohorts: women aged 15 to 60 who experienced issues related to Physical Environment, Housing, and Economic Conditions during or after pregnancy from 2008 to 2023, and women in the same age range who did not face such issues, thus representing a favorable physical environment, housing, and economic conditions.

Results:
Challenges related to the physical environment, housing, and economic conditions significantly increased the risk of all-cause mortality (OR: 3.237, 95% CI: 2.064 to 5.075, p<0.001), acute myocardial infarction (MI) (OR: 2.831, 95% CI: 1.422 to 5.634, p=0.002), major adverse cardiac and cerebrovascular events (MACCE) (OR: 2.734, 95% CI: 1.953 to 3.782, p<0.001), and ischemic stroke (OR: 2.082, 95% CI: 1.074 to 4.037, p=0.026). On the other hand, no significant correlation was found between adverse physical environment, housing, and economic conditions and the incidence of peripartum or postpartum preeclampsia (OR: 0.994, 95% CI: 0.904 to 1.093, p=NS), peripartum or postpartum eclampsia (OR: 1.178, 95% CI: 0.852 to 1.629, p=NS), hemorrhagic stroke (OR: 1.202, 95% CI: 0.519 to 2.782, p=NS), or peripartum cardiomyopathy (OR: 0.977, 95% CI: 0.631 to 1.511, p=NS).

Conclusion:
Women exposed to adverse physical environment, housing, and economic conditions conditions experienced higher rates of cardiovascular problems compared to those in more favorable circumstances.
Abstract 4144060: Prevalence, Clinical Characteristics, and Outcomes of Patients with Genotype-Positive Arrhythmogenic Cardiomyopathy Presenting with a Sentinel Sudden Cardiac Arrest
Authors: Swain William , Garmany Ramin , Castrichini Matteo , Bos Johan , Neves Raquel , Ackerman Michael , Giudicessi John
Published: November 2024

Background:
Arrhythmogenic cardiomyopathy (ACM) is a genetic heart disease characterized by proclivity for ventricular arrhythmias and systolic dysfunction. Rarely, sudden cardiac arrest (SCA) is the presenting event in ACM. These individuals may have concealed disease with no appreciable structural manifestations on imaging.

Aims:
To determine the prevalence, clinical features, and outcomes of patients with genotype-positive ACM who presented with a sentinel SCA.

Methods:
In this retrospective study, 445 genotype-positive ACM patients evaluated from 1/2015-4/2024 were analyzed to identify those whose initial presentation was SCA. Pertinent demographic, clinical, genetic, and outcome data were extracted from the electronic medical record. Structural manifestations were defined by having one of the following on baseline TTE: EF < 50%, LVEDV >56 mL (male) or >51 mL (female), or regional RV akinesia, dyskinesia, or aneurysm. Categorical variables are presented as number (%), and continuous variables as median (IQR). Statistical analysis was done using Fisher’s exact test (categorical), t-test (continuous), and Logrank test (survival). Patients were censored at time of transplant, death, or last followup.

Results:
Overall, 14/445 (3%) ACM patients presented with sentinel SCA [71% male; median age at SCA 39 (IQR 30-46)]. The most common genetic substrates were
DSP
-encoded desmoplakin (n=4; 29%),
LMNA
-encoded lamin A/C (n=3; 21%), and
PKP2
-encoded plakophilin-2 (n=3; 21%). During a median followup of 8.4 years, 12 (86%) experienced appropriate ICD shocks, 8 (57%) required catheter ablation for ventricular arrhythmias, 6 (42%) underwent transplant, and 2 (14%) died of cardiac causes. Notably, 5 (35%) patients did not have evidence of structural disease during baseline evaluation. Compared to those with structural disease, this group was younger [median age 28 (IQR 21-29) vs 45 (IQR 41-48), p = 0.002] and less likely to undergo transplant [0 (0%) vs 6 (42%), p = 0.03].

Conclusions:
Sentinel SCA is a rare presentation in ACM and may precede overt structural cardiac changes in a subset of younger patients. This population remains at increased risk for recurrent ventricular arrhythmias and often require advanced therapies.
Abstract 4144096: Outcomes of Left Atrial Appendage Occlusion in Patients with Atrial Fibrillation and Gastrointestinal Bleeding: Insights from a Multicenter Registry
Authors: Ayub Muhammad Talha , Preisendorfer Stefan , Wann Dan , Howard Ato , Thoma Floyd , Zhu Jianhui , Sheth Aakash , Jabbour George , Singh Madhurmeet , patel chinmay , Gada Hemal , Bhonsale Aditya , Estes Nathan , Kancharla Krishna , Shalaby Alaa , Singla Virginia , Naniwadekar Aditi , Voigt Andrew , Saba Samir , Jain Sandeep
Published: November 2024

Background:
The patient population undergoing left atrial appendage occlusion (LAAO) in the US is older and at a higher bleeding and thromboembolic risk than that enrolled in the initial trials that led to FDA approval. Real world outcomes in this population have implications for the use of LAAO.

Goals:
We sought to compare clinical outcomes of LAAO in patients with atrial fibrillation (AF) with prior major gastrointestinal (GI) bleeding to continued oral anticoagulation (OAC).

Methods:
Using data from a large US hospital system, patients with AF who underwent LAAO from 01/2016 to 11/2022 with a history of at least one major (requiring admission or transfusion) GI bleed event (LAAO group) were identified and compared to a control group with prior GI bleed with continued OAC. Controls were selected in a 1:2 fashion using propensity score matching based on 17 variables. Hospital admissions for major bleeding, ischemic stroke or transient ischemic attack (TIA) as well as survival were tracked during follow-up.

Results:
Patients in the LAAO group (n=642, age 76.5±8.2 years, 47.8% female) had higher CHA
2
D
2
-VASc (4.3±1.7 vs. 4.1±1.6, p=0.003) and lower HAS-BLED (3±0.9 vs. 3.3±0.9, p<0.001) scores than the control group (n=1273, age 76.3±10.1 years, 47.8% female) but were otherwise comparable. At baseline, a higher proportion of patients in the LAAO group was on a direct oral anticoagulant (59.7% vs. 44.9%, p<0.001), while fewer patients were on warfarin (15.9% vs. 53.3%, p<0.001). Over a median follow-up of 2.95 (1.53-4.89) years, patients in the LAAO group had lower rates of a major bleeding event (97.8 vs. 140 events per 1,000 person-years, p<0.001) as compared to the control group. Similarly, fewer patients in the LAAO group were admitted for ischemic stroke or TIA (15.4 vs. 26.1 events per 1,000 person-years, p=0.016) when compared to the control group. Finally, survival rates in the LAAO group were improved as compared with the control group (89.4 vs. 119.9 events per 1,000 person-years, p<0.001), Figure 1.

Conclusions:
In patients with prior major GI bleeding, LAAO is associated with superior clinical outcomes with lower bleeding and stroke rates when compared to OAC.
Abstract 4144098: Mechanisms Of Reduced IgG Autoantibodies Specific to the ApoB-100 Peptide P210 Associated With Increased Risk For Myocardial Infarction
Authors: Dimayuga Paul , Chyu Kuang-Yuh , Farina Christopher , Zhao Xiaoning , Zhou Jianchang , Cercek Bojan , Berman Daniel , Shah Prediman
Published: November 2024

Background:
Reduced level of IgG autoantibodies specific for the apoB-100 peptide P210 is associated with increased risk for myocardial infarction (MI). However, the underlying mechanism for reduced P210 IgG levels in patients at risk of MI is unknown.

Methods:
We evaluated the baseline P210 IgG and immune complex (P210 IgG-IC) levels using ELISA of plasma samples of a sub-cohort of volunteers having coronary artery calcium scans (CACS) as part of the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) trial. The sub-cohort selected were those that did not have MI (No MI, N=90) and those that had a future MI (FMI, N=23) during follow-up (13.2±2.1 years). We also evaluated plasma samples collected from patients admitted to Cedars-Sinai for acute coronary syndrome (ACS, N=15). ELISA for P210 IgG and ICs were standardized against a pool of healthy control plasma and expressed as adjusted optical density (Adj OD). Flow cytometry evaluation of CXCR5+ T follicular helper (Tfh) cells that regulate IgG levels was performed in peripheral blood mononuclear cells (PBMCs) from ACS patients (N=8) in response to in vitro stimulation with P210. Specimen and data collection were IRB approved.

Results:
P210 IgG was significantly lower in FMI patients compared to No MI and ACS patients (FMI=0.6±0.6 vs No MI=1.5±1.6 and ACS=1.4±0.9 Adj OD; P<0.001). Plasma LDL was significantly higher in FMI patients compared to No MI and ACS patients (FMI=160.7±25.2 vs No MI=126.0±40.6 and ACS=114.9±53.4 mg/dL; P<0.0001). Since P210 is a peptide antigen of LDL apolipoprotein apoB-100 and considering that P210 IgG may form ICs with LDL, we evaluated plasma P210 IgG-ICs using a P210 capture monoclonal antibody. The No MI group for P210 IgG-IC ELISA only included subjects with the lowest risk of MI (CACS 0; N=23) to minimize variability within the group. FMI patients had significantly higher P210 IgG-ICs (FMI=3.3±2.4 vs No MI=2.0±2.0 and ACS=2.2±2.9 Adj OD; P<0.01), suggesting P210 IgG may have been depleted in FMI plasma by forming ICs with LDL. CD4+CD154+CXCR5+ Tfh cell response to P210 in PBMCs from ACS patients was significantly reduced compared to cells with no peptide stimulation (P<0.05).

Conclusion:
The results suggest that increased P210 IgG-IC formation may account for reduced P210 IgG in FMI patients. Reduced CD4+CD154+CXCR5+ Tfh cells in response to P210 stimulation may underly the lack of compensatory increase in P210 IgG in ACS patients.