bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146935: Ticagrelor Monotherapy in Patients with ACS Undergoing Coronary Stenting: An Updated Meta-Analysis of 3 Month versus 12 Month DAPT
Authors: Haseeb Mohsin , Shafiq Abdullah , mungee sudhir
Published: November 2024

Background:
Current guidelines recommend DAPT for 12 months in patients with ACS undergoing PCI. However, data on ticagrelor monotherapy after early aspirin discontinuation (<3 months, Short-DAPT) is scarce. We conducted an updated meta-analysis to assess the safety and efficacy of
<
3 month of DAPT (aspirin and ticagrelor) in patients with ACS undergoing PCI.

Hypothesis:
Short-DAPT will be more favorable than Standard-DAPT.

Methods:
This meta-analysis reviewed literature obtained systematically. Inclusion criteria encompassed randomized controlled trials of ticagrelor comparing
<
3 month of DAPT with 12 month of DAPT in ACS patients undergoing coronary stenting with a minimum follow up of one year. The primary endpoint was major adverse cardiovascular events (MACE). Secondary outcomes were net adverse clinical events (NACE), all-cause mortality, and major bleeding. We estimated inverse variance pooled hazard ratios using a random-effects model and DerSimonian-Laird method to calculate between-study variance.

Results:
Five trials with 21407 patients of ACS undergoing PCI were included (FIGURE). When comparing Short-DAPT with Standard- DAPT, the pooled hazard ratios and corresponding 95% confidence intervals for MACE, NACE, all-cause mortality, and major bleeding were 0.90 (0.77, 1.06), 0.72 (0.57, 0.91), 0.76 (0.59, 0.99), and 0.44 (0.35, 0.56), respectively

Conclusion:
Patients with ACS undergoing PCI can benefit from superior clinical outcomes, lower bleeding rate and a similar rate of MACE, with aspirin discontinuation at or less than 3 months and maintenance on ticagrelor monotherapy afterwards.
Abstract 4146974: Left Atrial Reservoir Phase Duration: A Novel Marker of Diastolic Function and Successful Cardiac Resynchronization Therapy
Authors: Hammersboen Lars-Egil , Aalen John , Puvrez Alexis , Larsen Camilla , Remme Espen , Kongsgaard Erik , Duchenne Jurgen , Galli Elena , Khan Faraz , Sletten Ole Jakob , Penicka Martin , Donal Erwan , Voigt Jens-Uwe , Smiseth Otto , Stugaard Marie
Published: November 2024

Background:
During left bundle branch block (LBBB), tachycardia causes marked elevation of left ventricular (LV) filling pressures due to insufficient time for LV relaxation. Cardiac resynchronization therapy (CRT) may reduce pulmonary congestion during exercise by facilitating more time for LV filling, thereby reducing the need for increased left atrial (LA) pressures to accelerate blood into the LV.

Purpose:
Investigate if successful CRT increases LV filling time and if this is reflected in shorter LA reservoir phase duration.

Methods:
In a multicenter study of 168 patients, LA and LV global strain was measured by speckle-tracking echocardiography before and 7 ± 1 months after CRT. LA reservoir phase duration was measured from onset shortening in the LV to peak global LA strain, and LV filling time from mitral valve opening to closure. A volumetric response was defined as ≥ 15% decrease in LV end-systolic volume at follow-up.

Results:
The patient in Figure 1 exemplifies LV/LA mechanical interactions in a volumetric responder. In the LV, resynchronization increases filling time (four areas shaded in gray in Figure 1). This is mirrored in the LA, where resynchronization reduces LA reservoir phase duration (white arrows, upper panels).

In all responders, resynchronization was associated with increased LV filling time (p<0.0001) and decreased LA reservoir phase duration (p<0.0001), regardless of heart rate (Figure 2). Reduction in LA reservoir phase duration correlated with a reduction in LV filling time (β=–0.302, p<0.0001 corrected for change in heart rate). These improvements in filling dynamics were not observed in non-responders.

Conclusions:
LA reservoir phase duration mirrors LV filling time and may be an important diastolic marker of successful CRT.
Abstract 4147015: Association between Polysocial Risk Score and Cardiovascular Health among Women of Reproductive Age in the American Heart Association’s Research Goes Red
Authors: Metlock Faith , Kwapong Yaa , Vaidya Dhananjay , Evans Crystal , Ouyang Pamela , Commodore-Mensah Yvonne , Sharma Garima
Published: November 2024

Introduction:
Hypertension (HTN) prevalence is worsening among women of reproductive age (18-44 years), leading to higher maternal morbidity and mortality rates. We sought to evaluate social risks and cardiovascular health (CVH) among women aged 18-44 years, in a national registry.

Methods:
We conducted a cross-sectional analysis of participants enrolled in the American Heart Association Research Goes Red Registry, who responded to questionnaires on heart health and social risks. Adverse social risks were measured using a polysocial risk score ranging from 0 to 16, with higher scores indicating greater social disadvantage. The polysocial risk score included variables from several domains: sociodemographic information, living situation, food security, transportation, utilities, safety, and financial strain. CVH was assessed by the number of CVH risk factors based on Life’s Essential 8: diet, physical activity, smoking, blood pressure, blood sugar, body mass index, and cholesterol, where a lower number of risk factors indicates more optimal CVH. Linear regression models were used to assess the association between polysocial risk score and CVH.

Results:
Among the 637 women (mean age range 18-29 years, 30% Non-Hispanic Black), 64% had polysocial risk scores less than 7, while 36% had scores greater than 7. Most participants were married or cohabitating (66%) and had some college education or higher (87%). Financial strain was reported by 51%, with 47% earning less than $50,000 annually. In terms of cardiovascular health, 33% had diabetes, 46% had high cholesterol, 44% had high blood pressure, and 69% had a high body mass index. High polysocial scores (scores > 7) were significantly associated with increased cardiovascular health risk factors (coefficient = 0.4733, p < 0.001), while lower polysocial scores (scores < 7) were not significantly associated with cardiovascular health risk (coefficient = 0.0357, p = 0.229). Additionally, Spearman’s rank correlation showed a moderate positive relationship (Spearman's rho = 0.2395, p = 0.0000), indicating that as polysocial scores increase, the number of CVH risk factors also increases
(Figure).

Discussion:
Women of reproductive age with high number of social risks are at a significantly increased risk of suboptimal cardiovascular health. Screening for social needs and developing public health interventions tailored for women with high social burdens must be prioritized to improve cardiovascular health.
Abstract 4147025: Obesity as an Underlying Driver of Differences in Racial and Socioeconomic Disparity Associated Cardiac DNA Methylation Among Men with End-stage Heart Failure
Authors: Chang Samuel , Preuss Kerstin , Lin Benjamin , Bakshi Sayan , Miller C. Ryan , Wende Adam
Published: November 2024

Heart failure (HF) treatment advances have improved outcomes but HF heterogeneity leads to ~50% response to standard therapies, emphasizing a need to further study mechanisms of disparate outcomes. One serious disparity is increased cardiovascular disease risk and mortality in African Americans (AA) compared to Caucasian Americans (CA). Race is a social construct and thus poor proxy for physiology; hence, our lab studies epigenetics, stable yet reversible changes to DNA serving as a possible interface of how environment impacts gene regulation. We’ve previously implicated cardiac DNA methylation as a new indicator of socio-economic disparities in HF outcomes. Related to HF, US adult obesity rates are 40% and similar disparities exist with AA having higher rates, and studies on obesity show how inequity leads to disparate rates. Thus, our secondary analysis investigates the role of obesity, through its impact on cardiac epigenetics and transcription, as an underlying environment/molecular driver within HF disparities.

Multi-omics data of left ventricular assist device placement biopsies of age-matched males were from our previous publication’s public dataset. Cardiac DNA methylation (850k-array) analyzed via minfi, and differential gene expression (RNA-seq) via DESeq2.

Two-year survival is decreased in non-obese (NO) vs. obese (OB) patients (p<0.01); specifically, decreased survival in AA-NO patients vs. CA-NO patients (Hazard Ratio=0.26, 0.08-0.91). Subgroup analyses reveal 2632 gene-associated differentially methylated CpG-probes between AA-NO vs. OB, and 5309 between CA-NO vs. OB (p<0.05, |methyl-change|>5%). Additionally, 19 differentially expressed genes between AA-NO vs. OB, and 236 between CA-NO vs. OB (q<0.1, |Log FC|>1.5); one key gene, TNFa induced protein 8 (
TNFAIP8
), is increased in AA-NO vs. OB, but decreased in CA-NO vs. OB. Furthermore, the differential expression in each group correlates with canonical significant inverse DNA methylation at
TNFAIP8
.

Our survival data supports the literature of an “Obesity Paradox” where obese HF patients have better prognoses than non-obese patients. Through our analyses, we characterized impacts of obesity status on DNA methylation and gene expression within disparate HF outcomes and identified
TNFAIP8
as a marker related to increased apoptosis in pathology progression. Thus, our work contributes molecular characterization of a possible effector of the differences seen in these specific patient populations.
Abstract 4147041: Genetic evidence implicating collagen type VI a3 in heart failure risk and aortic health
Authors: Dib Marie-Joe , Azzo Joe David , Salman Oday , Tavolinejad Hamed , Beeche Cameron , Gill Dipender , Chirinos Julio
Published: November 2024

Background:
Endotrophin, a peptide derived from the COL6A3 chain that is released during COL6 formation, has been associated with cardiorenal outcomes in human observational studies and has demonstrated a strong association with adverse outcomes in heart failure with preserved ejection fraction. Endotrophin may modulate various biologic processes, but its potential causal cardiovascular effects are at present poorly understood.

Research Questions/Aims:
We aimed to investigate the potential causal effects of COL6A3-derived endotrophin on cardiorenal outcomes in humans, and its mediating mechanisms.

Methods:
Using genetic summary data from the UK Biobank (Olink, N=51,637) and deCODE (SOMAScan, N=35,365) studies, we first validated genetic instruments for COL6A3-derived endotrophin. We then leveraged those genetic instruments to investigate the effects of endotrophin inhibition on primary cardiorenal outcomes, including coronary artery disease, abdominal aortic aneurysm (AAA), chronic kidney disease, and heart failure (HF). Results informed our secondary analyses, where we investigated the effects of endotrophin on pulse pressure and aortic diameter. Next, using independent genetic association summary statistics (N=200,000-1,000,000), we explored the human proteome to gain insights into mechanisms of action, and the human phenome to assess the widespread health implications of COL6A3-derived endotrophin. We adjusted for multiple comparisons using the false discovery rate method.

Results:
MR findings revealed a significant association between COL6A3-derived endotrophin inhibition and reduced risk of HF (OR=0.60; 95%CI=0.51, 0.77) and AAA (OR=0.49; 95%CI=0.31, 0.77). Proteome-wide MR suggested that genetically proxied COL6A3-derived endotrophin inhibition was significantly associated with reduced COL28A1 (β=-0.71; 95%CI= -0.88, -0.53) and MAM domain containing-2 (MAMDC2; β=-0.71; 95%CI=-0.84, -0.57) levels. Phenome-wide association MR analyses suggested that genetically proxied COL6A3-derived endotrophin inhibition was associated with reduced risk of thoracic aortic aneurysm (OR=0.35, 95%CI=0.21, 0.59) and bronchiectasis (OR=0.26, 95%CI=0.14, 0.48).

Conclusions:
This is the first study to validate genetic instruments for COL6A3-derived endotrophin, and to provide genetic evidence supporting a causal role for endotrophin on HF and AAA risk. Clinical trials are required to further explore the effect of pharmacologically perturbing COL6A3-derived endotrophin levels.
Abstract 4147066: Octacosanol Reduces Lipopolysaccharide Induced Loss of Cellular Integrity of Primary Human Aorta Endothelial Cells
Authors: Tang Jingrong , Lucero Diego , Li Wenling , Liu Huaitian , Xie Hairui , Kun Julia , Sviridov Denis , Yang Zhihong , Mukoyama Yosuke , Remaley Alan
Published: November 2024

Atherosclerosis, a complex process involving chronic systemic inflammation, endothelial dysfunction, retention of lipoproteins, plaque formation in large and medium-sized arteries, is one of the most common causes of morbidity and mortality. Octacosanol, a very long chain saturated (C28) aliphatic alcohol is a major active ingredient in the Policosanol, which is extracted from plants like sugar cane and wheat germ. Policosanol has been proposed as dietary supplement for obesity and for lowering serum lipids. Previous animal studies have shown that both Policosanol and Octacosanol can significantly ameliorate formation of atherosclerotic lesions. To further explore the possible mechanism of Octacosanol on the formation of atherosclerosis, we examined the anti-inflammatory effects of Octacosanol on HAEC treated with LPS at 100ng/ml FBS-free cell culture medium. LPS treatment significantly enhanced human monocyte (THP1) adherence to HAEC cells in time-dependent and dose-dependent style, but Octacosanol at 1.25 or 2.5 µM markedly blocked the adhesion of THP1 to HAEC. ELISA showed that LPS can significantly increase the expression of pro-inflammatory cytokines and adhesion molecules by HAEC at 100ng/ml within 4 hours. LPS stimulated more than 3-fold the release of IL-6, IL-8, MCP-1 at 4 hours. By flow cytometry and ELISA, LPS markedly increased the expression of PE-Selectin and VCAM-1. Pretreatment of HAEC with Octacosanol (1.25µM or 2.5µM) significantly reduced the release of inflammatory cytokines, such as MCP-1(p<0.01), IL-6 (p<0.001) and IL-8(P<0.001)> It also inhibited the expression of PE-selectin(p<0.001) and VCAM-1(P<0.001). By QRT-PCR analysis, Octacosanol reduced the transcription of TRAF-6, MYD88 which are associated with LPS triggered TLR-4 involved pro-inflammatory pathway. Confocal imaging analysis of HAEC cells also confirmed Octacosanol the inhibition of the expression of PE-Selectin and VCAM-1 and VE-Cadherin, leading to the maintenance of cell membrane integrity and underlying ECM and the prevention of THP1 cell adherence. A test of HAEC cell membrane permeability using fluorescent intensity of FITC-Dextran (40kD) showed that Octacosanol can significantly improve cell integrity to damage induced by LPS at 100ng/ml for 4 hours. In summary, Octacosanol appears to have multiple potential beneficial functions related to endothelial cell integrity, which could explain its anti-atherogenic properties observed in animal studies.
Abstract 4147094: Efficacy and Safety of Direct-Acting Oral Anticoagulants Compared to Vitamin K Antagonists for Atrial Fibrillation in Patients with Liver Cirrhosis: A Meta-Analysis
Authors: Ramos Miranda Maria Clara , Santos Charles Karel , Barbosa Gabriel , Nogueira Thallys , da Silva Menezes Junior Antonio
Published: November 2024

Background:
Direct-acting oral anticoagulants (DOACs) have emerged as a preferred alternative to Vitamin K Antagonists (VKAs) for patients with atrial fibrillation (AF). However, the exclusion of patients with liver cirrhosis (LC) from recent clinical trials leaves the efficacy and safety of DOACs in this population unclear.

Hypothesis:
DOACs are more effective and have a better safety profile compared to VKAs in patients with AF and LC.

Methods:
Following the PRISMA guidelines, we searched PubMed, Cochrane Library, Embase, Scopus, Web of Science, and CNKI databases for randomized clinical trials (RCTs) and observational studies comparing DOACs and VKAs in patients with AF and LC. Statistical analysis was performed using the metafor package in R software. Heterogeneity was assessed using the I2 statistic, and a random-effects model was employed to calculate pooled Hazard Ratios (HRs). For trivial heterogeneity (I2<25%), a fixed-effect model was used. The confidence interval (CI) was set at 95%.

Results:
A total of one RCT and eight observational studies, encompassing 21903 patients, were included. Of these, 9882 patients were treated with DOACs and 11211 with VKAs. In 10105 patients with AF and LC, the incidence of major bleeding events was significantly lower in the DOAC group compared to the VKA group (HR 0.64; 95%CI 0.55-0.74; p<0.001; I2=0%) (Figure 1A). The pooled adjusted effect estimates from multivariable analysis and inverse probability weighting for major bleeding were consistent (HR 0.71; 95%CI 0.61-0.82; p<0.001; I2=7%) (Figure 1B). Additionally, the DOAC group exhibited lower rates of gastrointestinal (GI) bleeding (HR 0.76; 95%CI 0.69-0.85; p<0.001; I2=18%) and intracranial hemorrhage (ICH) (HR 0.71; 95%CI 0.59-0.85; p<0.001; I2=0%). There were no significant differences in thromboembolic events (Figure 2A) and all-cause mortality (Figure 2B) between the groups. Meta-regression analyses showed no significant impact of age, sex, follow-up duration, or baseline antiplatelet therapy on major bleeding events.

Conclusion:
In patients with AF and LC, DOACs are associated with a safer bleeding profile compared to VKAs, showing a reduced risk of major bleeding, GI bleeding, and ICH. However, no significant differences were observed in thromboembolic events or all-cause mortality. These findings suggest the potential of DOACs as a safer alternative in this patient population, warranting further validation through well-designed clinical studies.
Abstract 4147100: The Association between Perceived Stress and Left Ventricular Mass Index (LVMI)
Authors: shurovi sumayya , David Michelle , Fernandez Sedano Brandon , Cornelius Talea , Schwartz Joseph , Abdalla Marwah
Published: November 2024

Introduction:
Perceived stress is known as the feeling of uncontrollability in one’s life and the inability to cope with the amount of stress one is experiencing due to one’s circumstances. There is evidence indicating that perceived stress may be a risk factor for cardiovascular disease (CVD). However, it is unclear whether perceived stress is associated with higher left ventricular mass index (LVMI), a measure of target organ damage and strong predictor of CVD.

Aim:
We examined the association between perceived stress and LVMI.

Methods:
The Masked Hypertension Study is a multi-site study that assessed the prevalence and predictors of masked hypertension in working adults from the New York Metropolitan area. A total of 1011 participants were recruited for the study; 826 participants completed the Perceived Stress Scale questionnaire and an echocardiogram. The perceived stress scale is a 14-item likert scale that assesses different situations that affects our perceived stress or our feelings in certain situations. It has a scale of 1 to 5 with 1 being never to 5 being very often. LVMI was determined according to the 2D method based on the American Society of Echocardiography (ASE) recommendations.

Linear regression models were specified predicting LVMI from perceived stress. Covariates were sex, race/ethnicity, age, BMI, systolic bp, diastolic bp, and caregiving status.

Results:
Of the 826 participants, 40.7% were male, 6.9% were Black, 11.9% were Hispanic/Latinx , and 48.79% were caregivers. Mean (SD) age was 45.3 (10.3) years, mean body mass index was 27.6 (5.3) kg/m
2
, and mean SBP and DBP were 114.7 (12.0) and 74.8 (8.5). Mean perceived stress score was 21.8 (7.6) and mean LVMI was 63.3 (15.7) gm/m
2
.

Contrary to our hypothesis, perceived stress was not significantly associated with LVMI, B = -0.00, 95% CI: -0.13, 0.13, p= 0.98.

Conclusion:
There was not an association between perceived stress and LVMI. Future research should examine whether other types of stresses/stressors are related to LVMI and the implications of this for patients and their health.
Abstract 4147107: Diagnostic and Therapeutic Yield of Routine Esophagogastroduodenoscopy in Patients with Fontan Palliation
Authors: Diaz-Frias Josue , Conjeevaram Hari , Norris Mark , Joynt Michael , Yu Sunkyung , Duimstra Ashley , Lowery Ray , Cotts Timothy
Published: November 2024

Introduction:
Fontan associated liver disease (FALD) is an important complication of the Fontan Circulation. The presence of esophageal varices is associated with increased morbidity and mortality in patients with underlying cirrhosis. The diagnostic yield of routine esophagogastroduodenoscopy screening (EGD) in Fontan patients with clinical/radiographic suggestion of cirrhosis is unknown with wide practice variation across centers. At our center, the institutional strategy is to refer patients with clinical or radiographic evidence of FALD to the hepatology service. All patients seen by hepatology undergo EGD if they have clinical/radiographic suggestion of cirrhosis and they are clinically stable and without contraindications to the procedure. The purpose of this study was to evaluate the yield of EDG in Fontan patients and inform a strategic surveillance approach.

Methods:
We performed a single-center retrospective chart review of all patients with Fontan circulation who underwent an EGD from February 1, 2020 to October, 31 2023 at our center.

Results:
During the study period, a total of 66 patients (51.5% male) with Fontan circulation underwent routine EGD at a median age 30.2 years (range 19.8-60.4 years). The median time from Fontan palliation to initial screening EGD was 27.1 years. Fontan type was lateral tunnel in 41 patients (62.1%), atriopulmonary in 14 (21.2%), and extracardiac in 11 (16.7%). About half (48.5%) of the patients had a systemic left ventricle. At the time of the EGD, 12 (18.2%) patients had a New York Heart Association (NYHA) functional class I, 35 (53.0%) had a functional class II, 19 (28.8%) had a functional class III. The esophageal varices were present in 41 (62.1%) patients, of which 35 (53.0%) had grade I esophageal varices, and 6 (9.1%) had grade II. Additional findings included portal hypertensive gastropathy in 33 (50.0%) patients, erythematous mucosal changes in 16 (24.2%), non-bleeding erosive gastropathy in 4 (6.1%) and gastric vascular ectasia in 1 (1.5%).

Conclusion:
This study showed a high prevalence of esophageal varices in our Fontan patients, suggesting a role for routine EGD as a screening tool in this population.
Abstract 4147134: Statin Use and Its Association with Lower LDL Levels in STEMI and NSTEMI Patients at the Time of MI
Authors: Kahe Farima , Lawand Jad , Momenzadeh Kaveh
Published: November 2024

Introduction:
Elevated LDL cholesterol is linked to microvascular injury and adverse cardiac events in STEMI patients. Statins, or HMG CoA reductase inhibitors, lower LDL levels and reduce cardiovascular risk. This study examines the impact of prior statin use on LDL levels at the time of MI, focusing on NSTEMI and STEMI patients. We hypothesize that patients on statins before an MI will have lower LDL levels and a reduced likelihood of elevated LDL (≥100 mg/dL) compared to those not on statins.

Methods:
We utilized TriNetX, a comprehensive database of de-identified electronic medical records aggregated from 64 healthcare organizations in the US Collaborative network. The study included patients who sustained either STEMI or NSTEMI for the first time and had a documented LDL cholesterol measurement on or within 24 hours of their MI. Patients were stratified based on whether they had received HMG CoA reductase inhibitor medications at least one month before their MI. The primary outcome was the incidence of LDL levels equal to or greater than 100 mg/dL at the time of the MI.

Results:
A total of 345,934 patients were included, divided into four cohorts based on their diagnosis (NSTEMI or STEMI) and statin treatment status. The analysis revealed that statin-treated patients had significantly lower LDL levels at the time of MI compared to untreated patients. For STEMI, the treated group had an average LDL level of 87.8 ± 42 mg/dL versus 103 ± 41.2 mg/dL for the untreated group (P<0.0001). For NSTEMI, the treated group had an average LDL level of 84.3 ± 41.5 mg/dL versus 97.6 ± 41 mg/dL for the untreated group (P<0.0001). After propensity matching, the risk of elevated LDL levels was significantly lower in statin-treated patients, with a risk difference of -14.6% and an odds ratio (OR) of 0.54 for STEMI, and a risk difference of -12.8% and an OR of 0.55 for NSTEMI (P<0.0001 for both).

Conclusion:
This study confirms that proactive statin use is associated with lower LDL cholesterol levels at the time of MI in both NSTEMI and STEMI patients. The significant differences observed between treated and untreated groups highlight the importance of statin therapy in managing patients at risk of myocardial infarction. The marked reduction in LDL cholesterol levels among treated patients suggests that statins could be a critical factor in mitigating the severity of an MI by effectively controlling cholesterol levels.
Abstract 4147213: Does Well-Controlled, Recent-Onset Diabetes Increase Stroke Hazard in Atrial Fibrillation? A Population-Based Cohort Study
Authors: Gunn Madison , Chen Yue , Chu Anna , Fang Jiming , Abdel-Qadir Husam
Published: November 2024

Introduction:
Stroke prevention with anticoagulation is an important aspect of atrial fibrillation (AF) management. Anticoagulation is often based on the premise that the risk of stroke increases with each additional CHA2DS2VASc risk factor. Diabetes is accepted as a risk factor for stroke in AF, but the threshold at which stroke risk increases is uncertain. Specifically, it is unknown if AF patients with recent-onset well-controlled diabetes (ROWCD) are at increased risk of stroke in AF compared to AF patients without diabetes.

Hypothesis:
We hypothesize that patients with AF and diabetes of <5 years’ duration with glycated hemoglobin (HbA1c) ≤7% who do not use insulin (henceforth designated as the ROWCD group) do not have a significantly different adjusted hazard of stroke than AF patients without diabetes.

Methods/Approach:
Using linked administrative databases in Ontario, Canada, we conducted a population-based retrospective cohort study of patients ≥66 years who had a new AF diagnosis between Apr 1 2013 and Mar 31 2022. Exclusion criteria included insulin use. Cause-specific hazard regression was used to quantify the adjusted hazard ratio (HR) for stroke over 2 years of follow-up in patients with AF plus diabetes relative to AF patients without diabetes (adjusting for baseline stroke risk factors and time-varying anticoagulation status). The analysis was repeated after excluding people with diabetes of ≥5 years duration, HbA1c >7%, or missing HbA1c data (to generate the ROWCD subset).

Results/Data:
The primary analysis included 233,692 patients with AF (mean age 78.8 years, 50.9% male), of whom 64,972 (27.8%) had diabetes. Diabetes was associated with an adjusted HR of 1.15 (1.08-1.22) for stroke in the full cohort (p< 0.001). After excluding people with diabetes of ≥5 years duration, HbA1c >7% or missing HbA1c, there were 7,415 patients with ROWCD. Mean diabetes duration was 3.0 years, mean HbA1c was 6.2%, with 38.5% metformin use, 10.6% dipeptidyl peptidase-4 inhibitor use, and 5.3% sulfonylurea use. There were 3,503 (2.1%) strokes in the non-diabetes group and 139 (1.9%) in the ROWCD group. ROWCD was not significantly associated with adjusted stroke hazard (HR 0.96, 95% CI 0.81-1.13, p=0.61).

Conclusions:
These findings suggest that people with AF who have ROWCD may not warrant a point on the CHA2DS2VASc score, as this subset of diabetes is not associated with increased hazard of stroke in AF.
Abstract 4147246: Establishing Correlation of Non-Invasive Monitoring Techniques in Xenotransplantation
Authors: Cipriano Sarah , Mohiuddin Muhammad , Tully Andrew , Galindo Javier , Hong-Zohlman Susie , Oldsman Marco , Hicks Albert , Dickfeld Timm , Gupta Anuj , Grazioli Alison , Lankford Allison , Feller Erika , Griffith Bartley , Ananthram Manjula
Published: November 2024

Introduction:
Non-invasive
s
urveillance of cardiac allograft health has included biomarkers such as NT-proBNP, and donor-derived cell-free DNA (dd-cfDNA). It has previously been shown that these biomarkers when elevated, indicate graft complications such as rejection, coronary artery vasculopathy, or donor-specific antibody production. As xenotransplantation enters the arena as a potential option for those with advanced heart failure, noninvasive monitoring techniques need to be investigated. Our institution performed the second porcine to human cardiac xenotransplant with a 10 gene edited porcine cardiac xenograft under FDA compassionate use authorization. After requiring perioperative transfusions, by post operative day (POD) 13, endomyocardial biopsy (EMB) revealed antibody and complement deposition without damage. Hemodynamic decompensation on POD 29 prompted EMB, revealing antibody mediated rejection (AMR).

Research Questions/Goals:
The authors sought to investigate if NT-proBNP and dd-cfDNA positively correlate in the patient with cardiac xenograft.

Methods/Approach:
NT-proBNP was checked periodically and dd-cfDNA was assessed once to twice weekly post-transplant. A retrospective review was completed including Pearson’s correlation coefficient analysis.

Results/Data:
There was a weak negative correlation between the NT-proBNP and dd-cfDNA (r=-0.28). After the initial spike in the perioperative period, NT ProBNP levels declined. NT Pro-BNP did not rise as dd-cfDNA did at the time of biopsy proven antibody mediated rejection (AMR). See the graphic below for details

Conclusion:
Noninvasive surveillance of cardiac xenografts needs further investigation. Biomarkers such as NT-proBNP negatively correlated with dd-cfDNA, which increased as expected at the time of biopsy proven antibody mediated rejection. Porcine xenografts are accustomed to a low-pressure circulatory system in contrast to the human recipient milieu. Despite this increased load to the xenograft, NT-proBNP levels decreased significantly after the initial postoperative phase. The NT proBNP values could have been lower than expected due to the effects of continuous renal replacement therapy. It is interesting to also note that the human assay detected xeno NT-proBNP.
Abstract 4147261: Explainable AI Better Predicts 3-Year MACE Risk Compared to Clinical and ASCVD Models in the UK Biobank Cohort
Authors: Singh Amritpal , Dhamdhere Rohan , Modanwal Gourav , Sil Kar Sudeshna , Al-Kindi Sadeer , Madabhushi Anant
Published: November 2024

Hypothesis:
Artificial intelligence (AI)-derived retinal microvascular architecture from fundus images predicts time to MACE events.

Objectives:
To establish associations of retinal vessel features with 3-year MACE risk, and compare AI-derived retinal vessel-based MACE risk with Atherosclerotic Cardiovascular Disease (ASCVD) risk calculator.

Methods:
Baseline retinal fundus scans were identified for 2120 patients with no prior CVD events, from UK Biobank Cohort. Retinal features such as angle, tortuosity, curvature, and caliber, were extracted (Fig. A). A Cox proportional hazards model was trained using demographics and clinical risk factors (M
clin
). AI-derived top 6 features extracted from retinal vessel analysis (M
clin+AI
) were integrated and compared with ASCVD risk calculator. The models were trained on 1060 individuals (50%) and validated on a holdout set of 1060 individuals (50%). Performance was assessed using the concordance index (C-Index), hazard ratio (HR), and Kaplan-Meier (KM) curves, and models were compared using the Likelihood Ratio Test (L.R.T.)

Results:
In the holdout set, M
clin+AI
risk score achieved a C-index of 0.688, HR of 4.59 (2.66 -7.93, p<0.001) for 3-year MACE event prediction compared to M
clin
(C-index=0.667, 3.30 (95% CI: 2.05-5.32), p<0.001). M
clin+AI
was significantly better (L.R.T p<0.001) than ASCVD risk calculator (C-index=0.640, 3.21 (95% CI: 1.84-5.60), p<0.001), suggesting that retinal features hold promise for capturing novel information not included in current risk assessment tools, enabling improved immediate risk evaluation. M
clin+AI
demonstrates a notable advantage over other models for MACE risk prediction over 3, 5, and 10-year periods, with highest predictive power in the shorter term.

Conclusion:
AI-derived retinal features are strongly associated with 3-year MACE. Further multisite prospective validation is warranted.
Abstract 4147267: Utilization, Risk Stratification, and Management of Lipoprotein(a) Results in a Large Academic Medical Center
Authors: Zirille Francis , Clair Victoria , Saxon David , Simon Steven , Gill Ed
Published: November 2024

Introduction:
Evidence has grown around the relationship between lipoprotein(a) [Lp(a)] and cardiovascular disease risk. The 2024 focused update on Lp(a) from the National Lipid Association recognizes elevated plasma Lp(a) as an important independent, causal risk factor for atherosclerotic cardiovascular disease and aortic valve stenosis, as well as delineates risk classifications. It is now recommended for patients to have Lp(a) measured at least once in their adult life, with Lp(a) levels <75 nmol/L (30 mg/dL) classified as low risk, individuals with Lp(a) levels ≥125 nmol/L (50 mg/dL) as high risk, and individuals with Lp(a) levels between 75 and 125 nmol/L (30–50 mg/dL) as intermediate risk.

Aims:
With Lp(a) lab testing recommendations changing and leading to a steady increase in patients who have had Lp(a) drawn, we aimed to understand these patients’ relative risk of cardiovascular comorbidities and events, in addition to current management.

Methods:
Within a university-based health system, a large data extraction model was used to identify all patients who had undergone Lp(a) testing. In a system of roughly 4,553,100 patients, 1,976 unique patients have had Lp(a) drawn since 2013. This population was then subclassified by risk groups, as outlined above.

Results:
Testing thus far, using new recommendations for classifications of patients, places 1491 patients in the low-risk category, 241 in the intermediate-risk category, and 211 in the high-risk category, summarized in Table 1. In this population, patients in the high risk Lp(a) group, tended to have higher rates of CAD, PAD, ACS and CVA events. Notably, no significant differences exist regarding more aggressive management of these patients with either escalation of lipid lowering therapy including high-intensity statins, ezetimibe and PCSK9-i or with subspecialist referrals. There are, however, 7 patients undergoing apheresis from the high-risk group.

Conclusions:
Consistent with current literature, patients stratified to the higher risk lp(a) group had higher rates of cardiovascular comorbid conditions and events, though do not seem to be managed more aggressively than those in lower risk groups. Opportunity exists in escalating therapy and referring to subspecialists for consideration of therapies like PCSK9-inhibitors, lipoprotein apheresis, and soon, direct Lp(a) lowering medications.
Abstract 4147280: Combined BMP9 and BMP10 inhibition elicits Hereditary Hemorrhagic Telangiectasia (HHT)-like phenotypes in susceptible mice
Authors: Rajesh Shreyas , Gipson Gregory , Zeghibe Ana , Brackin Riley , Lees-Shepherd John , Hatsell Sarah , Economides Aris , Yu Paul
Published: November 2024

Background:
Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are congenital vascular syndromes arising from mutations in a common set of genes of the bone morphogenetic protein (BMP) and TGFβ signaling pathway. Sotatercept, a novel therapy for PAH targeting activin signaling, is associated with telangiectasias and arteriovenous malformations (AVM), suggesting perturbation of BMP or activin signaling in PAH can lead to HHT mimicry. To identify the ligands responsible for HHT-mimicry, we tested a panel of molecules with different activities against BMP and activin ligands in HHT-prone mice for the ability to induce AVMs.

Methods:
Several recombinant proteins or antibodies with potential therapeutic effects in experimental or human pulmonary hypertension—anti-BMP9, anti-BMP10, ALK1-Fc (a BMP9/BMP10 ligand trap), ACTRIIA-Fc a.k.a. sotatercept (an activin/GDF/BMP10 and mild BMP9 ligand trap), ACTRIIB-Fc (an activin/GDF/BMP9/BMP10 ligand trap), or isotype control—were administered to HHT-prone 129X1/SvJ mice, at either 3- or 6-week of age for fifteen weeks (5-10 mg/kg twice weekly), with weekly paw and digital skin surveys, and blood counts taken at time of euthanasia.

Results:
Treatment with ACTRIIB-Fc or ALK1-Fc led to prominent hindlimb digital AVMs and bleeding at high frequency, while anti-BMP10 induced tail AVMs. AVMs occurred within 30 days when treatment was initiated at 3 weeks of age, and 60 days when initiated at 6 weeks of age. Treatment with ACTRIIB-Fc promoted weight gain, consistent with known anabolic effects of this ligand trap on muscle and bone.

Conclusions:
Combined antagonism of BMP9/BMP10 via ACTRIIB-Fc or ALK1-Fc exerted the strongest HHT mimicry in susceptible mice, while selective or weaker antagonism of BMP9 or BMP10 via neutralizing antibodies, ALK1-Fc, or ACTRIIA-Fc was less potent. HHT-susceptible strains of mice challenged with prospective PAH therapies can be used to reveal potential for HHT-mimicry due to BMP9/BMP10 antagonism in an age-dependent fashion. This pre-clinical model may be helpful to screen for the risk of AVMs in prospective therapies modulating BMP/activin signaling for PAH or other conditions.
Abstract 4147282: Systemic inflammation after STEMI – impact on infarct size and outcome –
Authors: Graesser Christian , Krefting Johannes , Voll Felix , Trenkwalder Teresa , Kufner Sebastian , Xhepa Erion , Joner Michael , Cassese Salvatore , Von Scheidt Moritz , Schunkert Heribert , Ndrepepa Gjin , Kastrati Adnan , Kessler Thorsten , Sager Hendrik
Published: November 2024

Background:
Systemic inflammation due to acute myocardial infarction (MI) leads to leukocyte accumulation inside cardiac tissue. Three days after MI the reparative phase is initiated, where cardiac macrophages adopt anti-inflammatory phenotypes and support scar formation and cardiac healing. Delayed resolution of inflammation leads to adverse cardiac remodeling after MI.

Objective:
To correlate persistent inflammation and delayed resolution of inflammation with infarct size and mortality in patients with ST-elevation myocardial infarction (STEMI).

Methods and Results:
This retrospective study, included data of STEMI patients treated with primary percutaneous coronary intervention (PPCI) from a historical (n=1155, 2002-2007) and contemporary (n=698, 2014-2022) cohort. Patients were grouped in tertiles according to leukocyte counts on day 3 after MI, as a surrogate parameter for delayed resolution of inflammation. In the historical cohort Serial single-photon emission computerized tomography imaging was available on admission and 7 to 14 days. Patients with elevated leukocyte counts after 72 h (T3 group) showed greatest area at risk (AAR) before PPCI (T1, AAR (median): 20.0% (IQR 11.0–36.0%); T2, AAR (median): 25.0% (IQR 14.0–40.0%), T3, AAR (median): 27.4% (IQR, 15.0–51.0%) and final infarct size (FIS) after 7 to 14 days after MI (T1, FIS (median): 7.0% (IQR 1.0–17.0%); T2, FIS (median): 12.0% (IQR 3.0–24.7%); T3, FIS (median): 13.0% (IQR 5.0–30.0%)) of the left ventricle. In line with these scintigraphic findings, peak creatine kinase myocardial band (CK-MB) values, as an enzymatic estimate of the infarct size, were also highest in T3. Additionally left ventricular ejection fraction (LV-EF) was lowest in the T3. At one year, 8 patients in T1, 7 patients in T2, and 22 patients in T3 had died (Kaplan–Meier estimates of 1-year mortality: 2.6%, 2.3%, and 7.3%, respectively (log-rank test: T1 vs. T3: p=0.01; T2 vs. T3: p=0.03). In the contemporary cohort we also found that patients with elevated leukocyte counts after 72 h (T3 group) showed greatest enzymatic infarct size, estimated by peak CK-MB values and reduced LV-EF. At one year, 6 patients in T1, 13 patients in T2 and 25 patients in T3 had died (Kaplan–Meier estimates of 1-year mortality: 3.8%, 8.3%, and 15.9%, respectively (log-rank test: T1 vs. T3: p<0.005, T2 vs. T3: p=0.004).

Conclusion:
Delayed resolution of inflammation following MI, is associated with poorer outcomes at one year in STEMI patients.
Abstract 4147288: Social determinants and healthcare utilization among adults with hypertrophic cardiomyopathy: data from the All of Us Research Program
Authors: Arabadjian Milla , Zhang Jielu , Zhang Donglan , Islam Shahidul
Published: November 2024

Background:
Individual-level social determinants of health (SDoH) and healthcare utilization (HCU) are understudied among adults with hypertrophic cardiomyopathy (HCM).

Objective:
To examine SDoH and HCU among adult participants in the All of Us Research Program, who have a diagnosis of HCM.

Methods:
We conducted a cross-sectional analysis All of Us Research Program data, overall, stratified by race and ethnicity, and by self-identified gender. Eligible individuals included those with an ICD-9, or ICD-10 diagnostic codes for HCM. We used chi square tests and t-tests to examine differences in SDoH and HCU among the study population.

Results:
The sample was N=1,110 (51% women, 21% non-Hispanic Black [NH] adults, 11% Hispanic adults, 39% with obstructive HCM). Median [interquartile range] was 69 years [59;77]. Seventeen percent had Medicaid, 38% among Hispanic adults, vs 35% among NH Black adults and 6.8% among NH White adults, p<0.001. Medicaid % was similar among women and men. The lowest education level (high school or below) was among Hispanic adults, 81%, vs 78% among NH Black adults, and 38% among NH White adults, p<0.001, and among women 56%, vs men, 46%, p<0.001. Seventy-nine percent of Black adults had a yearly income <$50,000, vs 73% among Hispanic adults, and 35% among NH White adults, p<0.001. Fifty-four percent of women had this income vs 41% of men, p<0.001.

HCU data was available for 50% of the sample. There were no racial or ethnic differences related to usual place of care or number of health visits over the last year. However, 27% of NH Black adults reported not being able to afford their prescriptions, vs 11% among Hispanic adults, and 9.4% among NH White adults, p=0.003. Women were more likely to delay care due to work, 7.5% vs men, 2.9%, p=0.023, and caregiving responsibilities, 4.5%, vs men, 0.9%, p=0.032. Geospatial analysis found that most participants resided at least 28 miles away from an HCM specialty center.

Conclusions:
This analysis identified individual-level SDoH and HCU patterns among a diverse cohort of community-dwelling adults with HCM. Findings may inform future intervention targets and intervention strategies to improve access and care for individuals with HCM.
Abstract 4147292: An ECG-based Heart Failure Screening Tool for People with Sickle Cell Disease
Authors: Karabayir Ibrahim , Davis Robert , Chinthala Lokesh , Rai Parul , McGuir Dan , Hankins Jane Silva , Akbilgic Oguz
Published: November 2024

Background:
Tissue hypoxia and chronic anemia associated with sickle cell disease (SCD) leads to structural and physiological alterations in the heart. Early detection of heart failure (HF) in patients with SCD can assist with timely interventions, but current methods (e.g., echocardiogram and heart MRI) are not easily accessible in resource-deprived settings. The integration of artificial intelligence (AI)-powered tools utilizing low-cost ECG data to increase the power to detect more patients eligible for early treatment, thus improving patient outcomes, and needs to be validated.

Hypothesis:
We hypothesize that ECG-AI models developed to detect incident HF in the general population can detect HF in SCD patients.

Methods/Approach:
We previously developed an ECG-AI model employing convolutional neural networks to classify patients with HF using a large ECG-repository at Wake Forest Baptist Health (WFBH). This model was developed using 1,078,198 digital ECGs from 165,243 patients, 73% White, 19% Black, and 52% female individuals, with a mean age (SD) of 58 (15) years. The hold-out AUC of this previous model in distinguishing ECGs of HF patients from controls was 0.87. In this study, we externally validated this ECG-AI model using SCD patients’ data from the University of Tennessee Health Science Center (UTHSC). Additionally, a logistic regression (LR) model was constructed in the UTHSC cohort by incorporating other simple demographic variables with the outcome of ECG-AI model.

Results/Data:
The UTHSC external validation cohort included data from 2,107 SCD patients (188 HF and 1,919 SCD patients with no HF), 98% were Black, 72% were female, with a mean age of 39 (14) years. Despite demographic differences between the validation (more Blacks) and derivation cohorts (lower age), our ECG-AI model accurately identified HF with an AUC of 0.80 (0.77-0.82) in the UTHSC SCD cohort. When incorporating ECG-AI outcome (an ECG-based risk value between 0 and 1), age, sex, and race in a LR model, the AUC significantly improved (DeLong Test, p<0.01) to 0.84 (0.82-0.87) with a sensitivity of 0.76 (0.73-0.79) and specificity of 0.76 (0.74-0.79).

Conclusion:
The ECG-AI model can detect HF in SCD patients from ECG data alone with moderately high accuracy. The accuracy improves with incorporation of simple demographic data. Future studies will incorporate other clinical risk factors of HF and sickle cell genotype data for further improved accuracy allowing its use for surveillance.