bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146010: Does Pre-eclampsia Heighten the Risk of Future Cardiovascular Events? Insights from a Retrospective Study
Authors: Akbar Usman , Muhibullah Fnu , Shafique Nouman , Umer Ahmed Muaaz , Khan Muhammad Aslam , Malik Saad , Rehman Urooj , Kumar Besham , Ahmed Faizan , Rizwan Umer , Cheshire Michael , Dani Sourbha
Published: November 2024

Background:
Pre-eclampsia (PE) affects approximately 4 million women annually, characterized by sudden-onset hypertension (>20 weeks gestation) and proteinuria. It is a leading cause of maternal and perinatal morbidity and mortality and increases long-term cardiovascular risks for mothers and infants. This study examines the long-term risk of arrhythmias in women with PE to improve future cardiovascular outcomes.

Methods:
This observational cohort study utilized the US Collaborative Network to analyze electronic medical records from 64 healthcare organizations. We identified 7,463 women with PE and 7,463 matched women without PE, following them from their first pregnancy to the incidence of arrhythmia, death, or study end. Primary outcomes included heart failure, cardiac arrhythmias, atrial fibrillation/flutter, supraventricular tachycardia, and ventricular fibrillation. Incidence rates and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models over a median follow-up of 1 year.

Results:
Women with PE had significantly higher risks of heart failure (HR 6.39, 95% CI: 3.48–11.74, p = 0.007), cardiac arrhythmias (HR 1.70, 95% CI: 1.35–2.13, p < 0.001), and atrial fibrillation/flutter (HR 2.73, 95% CI: 1.22–6.13, p = 0.011). No significant difference was observed for supraventricular tachycardia (HR 0.93, 95% CI: 0.44–1.98, p = 0.116), while the risk of ventricular fibrillation was 49% higher in the PE cohort (HR 1.49, 95% CI: 1.01–2.19, p = 0.044).

Conclusion:
Women with pre-eclampsia have significantly higher risks of developing heart failure, cardiac arrhythmias, and atrial fibrillation/flutter compared to those without PE. No significant difference was found in the risk of supraventricular tachycardia, while the risk of ventricular fibrillation was moderately higher. These findings underscore the need for targeted cardiovascular monitoring in women with a history of PE.
Abstract 4146044: Evaluating Myeloperoxidase(MPO) as a Predictor of new-onset and recurrent Atrial Fibrillation (AF): A meta-analysis
Authors: Marwah Mehak Preet Singh , Lekkala Sai Prasanna , Vasudevan Srivatsa Surya , Rajani Aayushi , Parekh Ritika , Gupta Ishita , Patel Mipasha , Mehdi Hajra , Desai Rupak
Published: November 2024

Background:
Atrial fibrillation (AF) pathogenesis is strongly linked to inflammation, but the role of inflammatory biomarkers like myeloperoxidase (MPO) levels is inconclusive. This meta-analysis is conducted to evaluate the association of myeloperoxidase (MPO) with atrial fibrillation (AF) onset or recurrence.

Methods:
We conducted a literature search in Pubmed, Scopus, and Google Scholar for studies relevant to predictors of AF onset specifically with MPO. A fixed-effects meta-analysis was performed to pool unadjusted and adjusted odds ratio effects across studies. Sensitivity analysis was performed to analyze the consistency of the overall results. Meta-regression was used to evaluate the confounders associated with the outcomes. p<0.05 was considered statistically significant.

Results:
We included eight studies with a total of 451,884 patients in this meta analysis. Our meta-analysis of the unadjusted model showed statistically significant odds (OR: 1.01, 95% CI: 1.00-1.02, p = 0.003) of AF onset for MPO levels. In the adjusted analysis, the overall OR was 1.00 (95% CI: 0.99-1.01), suggesting no significant association (Z = -0.59, P = 0.55) (Figure 1a). However, on sensitivity analysis of the adjusted model, we found there was a statistically significant association of MLO with AF onset (OR = 1.02, 95% CI: 1.00 - 1.03, p = 0.01) (Figure 1b). Meta-regression analysis with age (Figure 1c), sex, and follow-up shows there was no significant association of these variables with the overall outcomes.

Conclusion:
MPO levels had a significant association with predicting the onset and recurrence of AF. We recommend clinicians use MPO as a potential biomarker and add it to their diagnostic modalities to detect AF onset or recurrence.
Abstract 4146135: NOX2-generated oxidative stress in the epicardial adipose tissue promotes left atrial electrical remodeling in a canine model of atrial fibrillation
Authors: Pfenniger Anna , Mikhailov Aleksei , Yoo Shin , Zhang Wenwei , Benson Lauren , Bhatnagar Ashita , Johnson David , Marszalec William , Ghosh Asish , Knight Bradley , Passman Rod , Arora Rishi
Published: November 2024

Background:
Epicardial adipose tissue (EAT) is increasingly recognized as a key factor in the development of atrial fibrillation (AF). In addition to direct myocardial infiltration by adipocytes affecting conduction properties, EAT may also promote an arrhythmogenic substrate through paracrine and endocrine effects. EAT was shown to preferentially generate oxidase-dependent reactive oxygen species (ROS) when compared to subcutaneous fat. While a role for myocardial ROS in the development of AF is well established, a separate role for EAT oxidative stress remains unexplored.

Hypothesis:
Oxidative stress in the EAT contributes to atrial electrical remodeling and development of AF.

Aims:
Determine the effect of EAT-restricted gene therapy with NOX2 shRNA on atrial electrical remodeling in the short-term canine atrial tachypacing (ATP) model of AF.

Methods:
A single-chamber pacemaker was inserted for the ATP model. Animals developed persistent AF after 4-6 weeks, after which the atria were harvested. Unpaced animals were used as controls. Expression of NOX2 in the EAT was assessed by qPCR. EAT oxidative stress was determined by IHC for 8-OHdG, a marker of DNA oxidative damage. A subset of animals underwent an open-chest gene injection procedure restricted to the EAT (with a plasmid expressing NOX2 shRNA or a scrambled sequence) prior to initiation of ATP for 9 days. A terminal EP study determined regional atrial ERP and AF inducibility.

Results:
NOX2 expression was significantly increased in the EAT of animals with ATP-induced AF when compared to unpaced controls (Panel A, p<0.05 by t-test). IHC for 8-OHdG showed that in addition to the atrial myocardium, DNA oxidative damage was also extensively present in the EAT (Panel B, 8-OHdG+ nuclei marked with arrows). Animals having received NOX2 shRNA-expressing plasmids in the EAT had attenuated AF inducibility after short-term ATP when compared to controls (Panel C, p<0.001 by Chi-squared test). This was associated with an attenuation of ERP shortening (panel D, two-way ANOVA p<0.001). Importantly, this effect was not only observed in the posterior left atrium (PLA) but also in the left atrial appendage (LAA), which is devoid of EAT.

Conclusion:
Expression of NOX2 is increased in the EAT of the canine ATP-model of AF. EAT-restricted NOX2 inhibition globally attenuates left atrial electrical remodeling, consistent with an at-a-distance effect of EAT oxidative stress on the formation of an atrial arrhythmogenic substrate.
Abstract 4146137: Cell-free DNA Analysis Profiles End-Organ Injury and Predicts Outcomes with Left Ventricular Assist Device Implantation
Authors: Park Ashley , Andargie Temesgen , Hill Tom , Redekar Neelam , Tian Xin , Park Woojin , Kong Hyesik , Cavagna Isabella , Jang Moon , Rodrigo Maria , Shah Keyur , Valantine Hannah , Shah Palak , Agbor-Enoh Sean
Published: November 2024

Introduction:
Durable left ventricular assist devices (LVADs) improve survival in heart failure but carry high risks of infection, hemocompatibility-related adverse events (HRAE), and death. Current clinical tools use subjective assessments or do not incorporate changes in end-organ injury, limiting their prognostic value with these complications. Plasma cell-free DNA (cfDNA), a potential marker for systemic and tissue-specific injury, holds promise to enhance patient risk stratification and prognosis.

Hypothesis:
LVAD implantation decreases systemic and end-organ injury, measured by cfDNA.

Goal:
We aimed to assess changes in global and organ-specific injury patterns with LVAD implantation via cfDNA, and to determine if pre-LVAD cfDNA levels predict post-LVAD complications.

Methods:
We prospectively recruited 40 LVAD candidates and 40 healthy controls. Pre- and post-LVAD plasma samples were analyzed for nuclear cfDNA (ncfDNA) and mitochondrial cfDNA (mtcfDNA) using digital droplet PCR. Tissue-specific cfDNA levels were measured using bisulfite sequencing and a deconvolution algorithm with a DNA methylation library. Wilcoxon sign-rank tests were used to compare cfDNA levels, and log-rank tests were used to compare outcomes. The clinical outcomes were HRAE-free survival (major bleeding, stroke, device thrombosis, death), and post-LVAD infection. Random forest machine learning analysis ranked tissue-specific cfDNA to identify the tissue patterns of those who develop HRAE and those who develop infection.

Results:
Prior to LVAD implantation, patients had 4-fold higher ncfDNA and 2-fold higher mtcfDNA compared to healthy controls. After LVAD placement, ncfDNA (18980 vs. 10228 copies/mL, p < .001) and mtcfDNA levels (1051882 vs 579609 copies/mL, p < .001) nearly halved, with significant reductions in innate immune and liver cfDNA (Figure). High pre-LVAD ncfDNA levels were associated with worse HRAE-free survival (p = .035) and infection (p < .001). Tissue sources important in determining HRAEs were distinct from those related to infections.

Conclusion:
LVAD placement significantly improves systemic and tissue-specific injury, measured by reductions in cfDNA. While pre-LVAD cfDNA levels predict both post-LVAD HRAEs and infections, the cfDNA tissue contributions influencing these outcomes are distinct. Future studies will need to validate these findings and compare cfDNA to other predictors of poor LVAD outcomes.
Abstract 4146138: Outcomes of Gastrointestinal Bleeding in Acute Myocardial Infarction (AMI): Systematic Review and Meta-analysis
Authors: Rathore Sawai Singh , Syed Saif , Jeswani Bijay , Allam Sanjana , Patel Tirath
Published: November 2024

Background:
Gastrointestinal (GI) bleeding is a significant complication that can occur during acute myocardial infarction (AMI), worsening the patient's condition and complicating treatment. However, the specific impact of GI bleeding on outcomes in AMI patients remains unclear. This meta-analysis aims to clarify the impact of GI bleeding on key clinical outcomes in these patients.

Methods:
A comprehensive literature search was conducted using the PubMed, Embase, and Google Scholar databases. Random effect models were utilized to calculate Mantel-Haenszel odds ratios (ORs) and inverse variance standardized mean differences (SMDs) with 95% confidence intervals (CIs). Statistical significance was set at p < 0.05. The primary endpoints were in-hospital mortality, major adverse cardiovascular events (MACE), stroke episodes, length of hospital stay, and long-term mortality.

Results:
Twenty-one articles, comprising approximately 1.7 million patients with AMI, were included in the meta-analysis. GI bleeding in AMI patients was associated with an increased risk of in-hospital mortality (OR = 4.61; 95% CI 2.95 to 7.20; p<0.001), MACE (OR = 2.39; 95% CI 1.04 to 5.51; p<0.001), stroke (OR = 2.71; 95% CI 1.07 to 6.89, p<0.001) and long term mortality (OR = 5.27; 95% CI 3.95 to 7.04; p<0.001) compared with AMI patient without complication of gastrointestinal bleeding. Furthermore, Patients with GI bleeding in AMI also experienced an increased length of hospital stay (SMD = 0.67; 95% CI 0.46 to 0.88; p<0.001).

Conclusion:
These findings emphasize the significance of promptly recognizing and managing GI bleeding in the context of AMI to minimize its negative impact on patient outcomes.
Abstract 4146184: Gender Disparities in Inpatient Outcomes of STEMI Patients with Obstructive Sleep Apnea
Authors: Millhuff Alexandra , Quazi Mohammed , Goyal Aman , Sheikh Abu Baker
Published: November 2024

Introduction:
Increasing evidence shows that obstructive sleep apnea (OSA) is a significant risk factor for cardiovascular disease. OSA may exacerbate recovery from ST-elevation myocardial infarction (STEMI), as chronic hypoxemia and hypercapnia has been shown to be associated with sympathetic hyperactivity, inflammatory response, endothelial dysfunction, and hypercoagulability. Acute outcomes of STEMI patients who have a diagnosis of OSA has not been well-studied.

Research Question:
Does OSA affect inpatient outcomes in patients with a primary diagnosis of STEMI?

Methods:
We conducted a retrospective analysis using the National Inpatient Sample database from 2016-2021 to examine the inpatient outcomes of STEMI patients in OSA patients compared to patients without OSA. Inclusion criteria encompassed patients diagnosed with acute STEMI and OSA based on ICD-10 codes.

Results:
A total of 1,203,915 STEMI patients were identified; among these, 1,128,880 (93.7%) did not have a diagnosis of OSA, while 75,035 (6.3%) had a known diagnosis of OSA. Patients with OSA had lower in-hospital mortality (aOR=0.86, CI 0.80-0.90, p<0.001) compared to those without OSA but had higher rates of AKI (aOR 1.1), VTE (aOR 1.1), atrial fibrillation (aOR 1.4), atrial flutter (aOR 1.3), and non-invasive mechanical ventilation (aOR 3.1). Women with OSA, compared to men with OSA, were more likely to die in the hospital (aOR=1.17, CI 1.14-1.20, p<0.001) and had higher rates of VTE (aOR 1.2), but were less likely to undergo PCI, CABG, or have an intra-aortic balloon pump or Impella placed. Despite their higher mortality rate, women with OSA were less likely than men with OSA to develop inpatient complications such as sudden cardiac arrest, AKI, ventricular fibrillation, or ventricular tachycardia.

Conclusion:
STEMI patients with a diagnosis of OSA had lower inpatient mortality rates compared to those without OSA, necessitating further investigation to understand this correlation. However, significant gender disparities were observed; women with OSA had higher mortality rates and underwent fewer interventions than men with OSA. Recognizing and addressing these trends is crucial for developing targeted interventions to mitigate these disparities.
Abstract 4146225: Stress Perfusion Cardiac Magnetic Resonance Imaging for Pediatric Patients with Repaired Transposition of the Great Arteries
Authors: Chetan Devin , Thomas Subin , Smaili Hanan , Gill Navjot , Tassos VIvian , Lam Christopher , Yoo Shi-Joon , Valverde Israel , Seed Mike
Published: November 2024

Introduction:
Patients who underwent arterial switch operation (ASO) for d-transposition of the great arteries (TGA) are at increased risk for early myocardial ischemia. Stress perfusion cardiac MR (SPCMR) is used as a non-invasive tool for risk stratification but interpretation is often challenging.

Hypothesis:
There is significant interobserver variability in SPCMR image interpretation in patients with repaired TGA.

Aims:

1. Determine incidence and severity of adverse effects of stress agents.

2. Evaluate incidence of positive SPCMR.

3. Assess agreement amongst reviewers in image interpretation.

Methods:
Patients with repaired TGA with SPCMR imaging from 2013 to 2024 were reviewed. Three patients with previous coronary intervention and one with severe chest pain after adenosine, unable to complete SPCMR, were excluded. 61 studies were performed in 56 patients. Images were independently reviewed by two investigators blinded to initial interpretation and clinical outcome. Perfusion defects were displayed on a circumferential polar plot using standard LV segmentation.

Results:
Median (IQR) age was 15 (11-17) years, weight 55 (36-68) kg, and BSA 1.6 (1.2-1.8) m2. Max heart rate was 110 (100-125) and systolic BP 127 (116-138). Eleven (20%) patients had cardiac symptoms, chest pain in 9 (16%), syncope in 1 (2%), pallor and distress in 1 (2%) infant. Adverse effects from SPCMR in 8/52 (15%) adenosine, 2/4 (50%) dobutamine, and 0/6 (0%) regadenoson were minor and resolved on stress completion. Six (10%) studies were initially interpreted as suspicious (n=5) or definitive (n=1) perfusion defect (Figure). No LGE was detected. Original interpretation did not match blinded reviews for 6 cases (Figure). Blinded reviewers agreed on 3 negative cases but interpretation differed in the other 3 cases (Figure).

Conclusions:
SPCMR is safe and feasible. Significant interobserver variability highlights the challenges in qualitative SPCMR interpretation for TGA. Quantitative perfusion may reduce interobserver variability. Larger multicenter studies would be helpful in further elucidating the risk profile of patient characteristics and coronary artery arrangements to determine whether routine use of SPCMR is warranted for TGA patients.
Abstract 4146227: Combining metabolomic profiling with exome sequencing in the UK Biobank to predict cardiac outcomes and interpret variants of uncertain significance in familial hypercholesterolemia
Authors: Jostins-Dean Luke , Schut Kirsten , Kerminen Sini , Wurtz Peter , Barrett Jeffrey
Published: November 2024

Background:
Familial hypercholesterolemia (FH) is an inherited disorder resulting in high levels of LDL-C from birth. Premeature coronary heart disease occurs in half of affected men by age 50 years. While many genetic variants that cause FH are well understood, many other variants in FH genes are of uncertain clinical significance. Furthermore, the variability in residual cardiovascular risk of FH carriers after statin treatment is not fully understood. We here investigate whether metabolomic and genomic data from the UK Biobank cohort can aid in interpretation of candidate pathogenic FH variants, and characterise future risk of severe cardiac events in FH carriers.

Methods:
We have quantified 249 metabolomic parameters in 490,830 blood samples from UK Biobank cohort. Among 186,483 participants with exome sequence data we identified 896 who carried known pathogenic FH variants and 405 who carried variants of unknown significance in an established FH gene. We fitted a logistic predictive model to identify pathogenic mutations using LDL levels, statin use and 17 principal components of the metabolomic parameters. We further tested whether metabolomic and genomic scores for predicting future risk of myocardial infarction (MI), trained in the general population (i.e. individuals without FH), could predict risk in FH carriers.

Results:
A model including all metabolites had a higher accuracy at identifying known pathogenic FH variants compared to LDL and statin use alone. Our model identified 8 FH variants marked as uncertain significance in ClinVar with significant evidence of predicted pathogenicity. We found that our metabolomic risk score predicted 10-year risk of MI among FH carriers (HR=1.96 per SD, p = 0.0011). This was stronger than the effect in the general population (HR = 1.64 per SD, p = 2.5e-168). A combined metabolomic and polygenic risk score had an even larger effect at predicting MI in carriers (HR = 3.06 per SD, p = 2.0e-6), and was significantly better at predicting MI in carriers than in non-carriers (HR = 3.06 vs 1.88 per SD, interaction p = 0.042).

Conclusion:
Familial hypercholesterolemia is an important source of risk for early cardiovascular disease. Population-scale metabolomics can help distinguish pathogenic from benign variants that have not yet been characterised. Metabolomic and genomic scores can also identify individuals at most elevated risk, and provide even more information to FH individuals than in the general population.
Abstract 4146264: A Meta-analysis of the Right Ventricle Changes in Cancer Therapy-Induced Cardiotoxicity - The Forgotten Ventricle in Cardio-Oncology
Authors: De Oliveira Fischer Bacca Caroline , HUNTERMANN RAMON , Gomes Rodrigo , Alexandrino Francisco , YOSHIE SATO MARIANE , de Sant Anna Melo Edielle
Published: November 2024

Introduction:
Cancer therapy-induced cardiotoxicity (CTRCD) is one of the most significant adverse effects of oncologic treatment, responsible for considerable morbidity and mortality. Heart failure stands out due to its higher frequency and severity with the focus of most studies being left ventricular dysfunction and remodeling. The right ventricle (RV) may also be damaged by CTRCD, however the effects on RV function have not been elucidated.

Research Question:
What are the echocardiographic changes in RV due chemotherapy treatment?

Objective:
To conduct a systematic review and meta-analysis evaluating the RV echocardiographic parameters in patients undergoing chemotherapy treatment.

Methods:
Pubmed, Embase and Cochrane were systematically searched for studies that assessed RV echocardiographic changes in patients due to chemotherapy treatment. Statistical analysis was performed using the R statistical environment, with a summary estimate using Mean Differences (MD), adopting a random-effects model to account for variability among studies and a two-tailed significance level of 5%. A correlation coefficient of 0.5 was assumed for the paired measurements. Heterogeneity was assessed using the I2 statistic.

Results:
We included 641 patients from 11 studies, 75.5% of whom were women and with a mean age of 50.2±6.1 years. RV function was significantly lower after cancer treatment, with reduction in the fractional area change (MD -3.53%; CI -5.25, -1.41; p<0.0011 - Figure 1A), RV global longitudinal strain (MD 2.27%; CI 1.24, 3.29; p<0.0011 - Figure 1B) and in RV free wall strain (MD 3.22%; CI 1.76, 4.67; p<0.0001 - figure 1C). Additionally, the pulmonary artery systolic pressure was significantly higher (MD 1.36mmHg; CI 0.32, 2.4; p=0.01 - Figure 1D) and the tricuspid annular plane systolic excursion was significantly reduced (MD -1.98mm; CI -3.27, -0.68; p=0.0027 - Figure 1E) after chemotherapy.

Conclusion:
RV dysfunction is common in CTRCD and its echocardiographic quantification should be included in clinical practice follow-up during cancer treatment. Further research is needed to elucidate the underlying factors contributing to RV dysfunction in CTRCD and to develop methods for its early detection.
Abstract 4146331: Unraveling the Enigma of Acute Myocardial Infarction-Related Mortality in Malignancy Among Older Adults (≥65 years), A Decadal Dive into U.S Trends (1999-2020): A CDC WONDER Database Analysis
Authors: Naveed Muhammad Abdullah , Iqbal Rabia , Ali Ahila , Omer Rehan Muhammad , Azeem Bazil , Ahmed Faizan , Cheema Mustafa Sajjad , Sattar Yasar , Patel Brijesh , Ahmad Muhammad
Published: November 2024

Background:
Acute Myocardial Infarction (AMI) in malignancy is a significant cause of mortality globally. This study analyzed demographic trends and disparities in mortality rates due to AMI in malignancy among adults aged 65 and older from 1999 to 2020.

Methods:
A retrospective analysis was performed using death certificate data from the Centers for Disease Control and Prevention database from 1999 to 2020. The analysis utilized ICD* codes I21 for AMI and C00-C97 for malignancies. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 persons, and trends were assessed using Average Annual Percentage Change (AAPC) and annual percent change (APC). Data were stratified by year, sex, race/ethnicity, and geographical regions.

Results:
Between 1999 and 2020, AMI in malignancy caused 172,691 deaths among U.S. older adults aged ≥65 years. The majority of deaths occurred in medical facilities (56.9%) and at decedents’ homes (24.2%). The overall AAMR for AMI in malignancy-related deaths decreased from 30.2 in 1999 to 14.2 in 2020, with an AAPC of -3.90 (p < 0.000001). Men showed higher AAMRs than women (28.6 vs. 12.3), with a more pronounced decrease in men (AAPC: -4.22, p < 0.000001) compared to women (AAPC: -3.78, p < 0.000001). Racial disparities were significant, with Black individuals having the highest AAMR (22.7), followed by Whites (19.3), American Indians or Alaska Natives (14.4), Hispanics (12.2), and Asians or Pacific Islanders (10.8). The decline in AAMR throughout the study was most pronounced in Black individuals (AAPC: -4.30, p < 0.000001). Geographically, the highest AAMRs were observed in Arkansas (32.3) and the lowest in Nevada (8.1). The Northeastern U.S. had the highest regional AAMR (20.2), followed by the Midwest (19.9), South (18.3), and West (17.4). Nonmetropolitan areas had higher AAMRs than metropolitan areas, though both saw significant declines from 1999 to 2020 (Metropolitan: AAPC: -3.97, p < 0.000001; Nonmetropolitan: AAPC: -2.64, p < 0.000001).

Conclusion:
This study reveals significant demographic disparities in mortality rates related to AMI in malignant older adults. These findings emphasize the need for targeted interventions and improved access to care to reduce mortality and enhance outcomes in this vulnerable population.
Abstract 4146352: Development and Validation of Machine Learning-based Ischemic Outcome Prediction Using Clinical and Genetic Data in Patients with Percutaneous Coronary Intervention
Authors: Grant Caroline , Kowlgi Gurukripa , Lennon Ryan , Cavallari Larisa , Lee Craig , Beitelshees Amber , Angiolillo Dominick , Franchi Francesco , Duarte Julio , Rossi Joe , Stouffer George , Klee Eric , Gulati Rajiv , Lerman Amir , Rihal Charanjit , Farkouh Michael , Athreya Arjun , Pereira Naveen
Published: November 2024

Introduction:
Identifying patients at risk for ischemic events after percutaneous coronary intervention (PCI) relies on traditional analysis of limited clinical and imaging variables. Machine learning (ML) has shown promise in effectively predicting cardiovascular risk in population studies. While existing ML models mainly predict mortality and incorporate clinical variables, there is a lack of tools that have utilized genetic data and that predict ischemic events.

Aims:
This study aims to develop and validate a ML model incorporating genotyping and clinical data to enhance prediction of ischemic outcomes for PCI patients utilizing large prospectively derived diverse datasets.

Methods:
Patients from the TAILOR-PCI trial (n=5302) were utilized for model development. 50% of the sample was utilized for Boruta feature selection and 50% for training and testing using cross validation. Features included demographics, medical history, medications, PCI characteristics, and genetic data (specifically, CYP2C19 *2, *3, *17 alleles). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. Multiple ML classification algorithms, including Support Vector Machine (SVM) polynomial, Random Forest, Light gradient boost, XG Boost, among others, were benchmarked for their prediction performance on rare events. The top performing classifiers were externally validated on an independent dataset from the PRECISION PCI study (n=3,745).

Results:
Mean participant age of the training set was 64.2 ± 11.0 years, with 75.4% being male. During follow-up of 12 months, among 4,572 patients in the entire cohort 343 (7.5%) met the primary outcome. The SVM polynomial model demonstrated the highest area under the curve (AUC) of 0.67 for predicting the primary outcome with test dataset. The sensitivity, specificity, precision, and recall were 0.87, 0.28, 0.07, and 0.87 respectively (Figure). Peripheral arterial disease, body mass index, and age were among the top variables by feature importance.

Conclusion:
ML models incorporating both clinical and genetic data are feasible and highly promising in predicting major adverse cardiac events that may help guide use of anti-platelet drug therapy. The AUC values are reasonable given imbalances and misclassifications in datasets, and further model optimization with prospective utilization of the model will be paramount.
Abstract 4146355: Sex Disparities In Mortality From Ischemic Heart Diseases In Europe, 2005-2019
Authors: Romeo Benedetta , Bergami Maria , Cenko Edina , Manfrini Olivia , Bugiardini Raffaele
Published: November 2024

Background:
Ischemic heart disease (IHD) is the leading cause of death in the European Union (EU). Understanding variations by sex, income, and geography can help in tailoring effective public health policies.

Methods:
We conducted a cross-sectional analysis of IHD using the Global Burden of Disease Study Database to examine trends in sex specific age-standardized mortality rate (ASMR)-to-age-standardized prevalence rate (ASPR) ratio (ASMR-to-ASPR index) per 100,000 inhabitants/year across the EU from 2005 to 2019.

Results:
Men showed higher ASMR than women. However, the ASMR-to-ASPR index was notably higher in women than in men indicating that women who develop IHD have a higher risk of dying from the disease compared with their male counterparts. Despite a significant decline in ASMR across EU from 2005 to 2019 both among women and men, sex disparities in ASMR-to-ASPR index persisted with a women-to-men ratio ranging from 1.05 to 1.36. No significant relationship was found between country-specific ASMR or country income status and ASMR-to-ASPR index. Examples include Romania which displayed higher ASMR (men: 219.87, women: 143.54) compared with Germany (men: 107.22, women: 60.76), yet with smaller differences in ASMR-to-ASPR index between women and men (Romania: 6.54% vs 5.85%; ratio: 1.12 and Germany: 4.79% vs 3.80%; ratio: 1.26).

Conclusions:
Mortality from IHD has decreased substantially among EU countries. However, the declines were accompanied by a persistently higher ASMR-to-ASPR index in women, indicating significant potential for further gains in closing the gender gap in IHD mortality.
Abstract 4146392: Prognostic Models for Mortality in an Obese Cohort of Heart Failure with Preserved Ejection Fraction
Authors: Jani Vivek , Fisher Eli , Tajdini Masih , Tanacli Radu , Hahn Virginia , Kass David , Sharma Kavita
Published: November 2024

Introduction:
Prognostic metrics like NT-proBNP are often low or even normal in patients in Heart Failure with Preserved Ejection Fraction (HFpEF), particularly in HFpEF patients with severe obesity. Here, we use machine learning survival prediction models to investigate predictors of outcomes in HFpEF.

Methods:
Patients enrolled in the Johns Hopkins Hospital HFpEF registry from July 2014 to May 2024 were included. HFpEF was defined based on clinical signs and symptoms, echocardiographic and laboratory findings, or by right heart catheterization. Starting with 44 features, a two-stage model, in which variables associated with at least a 15% change in hazard ratio by univariate Cox regression were included for subsequent machine learning. Models tested include a random survival forest with and without gradient boosting. Model accuracy was assessed on the test set with a C-statistic.

Results:
A total of 356 HFpEF patients were included, with 284 (80%) assigned to a train set and 72 (20%) to the test set. A gradient boosted random survival forest was found to be the best model with hyperparameter tuning, with a C-statistic of >0.99 and 0.87 in the train and test set, respectively. The most important prognostic features include N-terminal brain natriuretic peptide, systolic blood pressure, age, and the ratio of cystatin C to albumin. Individually, each of these features associate with survival with a C-statistic < 0.70, which is worse compared to collective model performance (
Fig 1A
). Other relevant features are shown in
Fig 1B
. For more effective clinical translation, models including the top 15, top 10, and top 5 features were subsequently trained and were found to have similar performance to the model with all features.

Conclusion:
Here we report a prognostic model for mortality prediction in a cohort of obese HFpEF patients. Efforts to benchmark this model against other HFpEF prognostic models and test in an external HFpEF patient cohort are underway.
Abstract 4146403: Direct Oral Anticoagulants vs Vitamin K Antagonists for Cardiovascular Interventions: A Systematic Review and Meta-Analysis
Authors: Calderon Martinez Ernesto , Salazar Ore Jonathan Victor , Miret Durazo Carla Isabella , Zuniga Gonzalez Noe Alejandro , Zurita Salas Yuriana , Mabel Navarro Evelyn , Betances Clara , Garcia Rodriguez Ernesto Enrique , Floridia Lautaro , Navarrete Gutierrez Gabriela , Afreen Sabia , Arruarana Victor
Published: November 2024

Introduction:
Anticoagulation therapy is crucial in enhancing perioperative outcomes, yet uncertainty persists regarding the optimal use of Direct Oral Anticoagulants (DOACs) and Vitamin K Antagonists (VKAs) in cardiovascular interventions. Key outcomes such as bleeding, thromboembolic events, and mortality are critical. Conducting a thorough review is essential to make well-informed decisions that improve patient quality of life and mitigate complications.

Hypothesis:
This meta-analysis aimed to investigate whether Direct Oral Anticoagulants (DOACs) reduce perioperative complications such as bleeding, thromboembolic events, and mortality compared to Vitamin K Antagonists (VKAs) in patients undergoing cardiovascular procedures.

Methods:
The present study was conducted in accordance with PRISMA guidelines. A systematic search was conducted in PubMed, MEDLINE, Scopus, Web of Science, Cochrane, and EMBASE databases on 05/14/2024. Data extraction was rigorously performed, and a random-effects model was used for data synthesis.

Results:
The review included 25 studies involving a total of 25,754 patients. For bleeding risk, the meta-analysis showed that DOACs are associated with a lower risk compared to VKAs, with a relative risk (RR) of 0.69 (95% CI: 0.51 to 0.94, p = 0.0457, I
2
= 60%). Thromboembolic events showed no significant difference between DOACs and VKAs (RR: 1.13, 95% CI: 0.74 to 1.73, p = 0.5313, I
2
= 15%). Mortality outcomes also showed no significant difference (RR: 0.53, 95% CI: 0.20 to 1.43, p = 0.1622, I
2
= 68%).

Conclusion:
The systematic review and meta-analysis demonstrate that DOACs are associated with a lower risk of bleeding compared to VKAs, with no significant difference in thromboembolic events and mortality. This evidence supports the substantial benefit of DOACs in cardiovascular interventions. Further research is needed to consolidate these findings and improve patient outcomes. PROSPERO registry— CRD42024547465
Abstract 4146425: Impact Of Sodium-Glucose Co-Transporter-2 Inhibitors and Glucagon-Like-Peptide-1 Agonists On Cardiovascular and Renal Outcomes In Patients With Type 2 Diabetes Mellitus (T2DM) and Autoimmune Diseases: A Global Retrospective Study
Authors: Anuforo Anderson , Somerville Alexander , Bhandari Jenish , Sherazi Mahnoor , Gautam Kamal , Olojakpoke Eloho , Awoyemi Toluwalase , Makri Helena , poudyal bhavya , kadel anuj , Sandhu Prabhjeet , Draytsel Dan , Melfi Michelle , Perl Andras , Taub Cynthia
Published: November 2024

Background:
Type 2 diabetes mellitus (T2DM) and autoimmune diseases are independent risk factors for cardiovascular disease. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and Glucagon-like-peptide-1 agonists (GLP1a) have shown cardiovascular benefits. This study compared the cardiovascular impacts of these medications in patients with autoimmune disease and T2DM.

Methods:
In May 2024, we queried the TriNetX Global collaborative network across 120 healthcare organizations for adults ≥18 yo diagnosed with T2DM and any of 28 autoimmune (15 connective tissue and 13 organ-specific) diseases between 01/01/05 and 06/30/23. We created 3 cohorts based on at least 3 months of SGLT2i use alone or GLP1a use alone, or neither SGLT2i nor GLP1a use during the study period (control). We conducted propensity score matching (PSM) for over 30 covariates and compared outcomes between cohorts. Cox Model analysis was used to calculate the hazard ratios (HR), 95% confidence intervals (CI), and log-rank p-values at five years.

Results:
In the control cohort, we identified 692,259 eligible patients, 49,458 patients on GLP1a, and 25,002 patients on SGLT2i. Compared to the control cohort, the SGLT2i cohort had a 28% lower risk of the primary composite outcome (HR 0.72; 95% CI: 0.68 – 0.76) and reduced all-cause mortality (HR 0.59; 0.56 – 0.63), acute MI (HR 0.86; 0.79 – 0.94) and ischemic stroke (HR 0.84; 0.77 – 0.91). Compared to the control cohort, the GLP1a cohort had a 28% lower risk of the primary composite outcome (HR 0.72; 95% CI: 0.69 – 0.75) as well as all-cause mortality (HR 0.54; 0.51 – 0.57), acute MI (HR 0.85; 0.80 – 0.91) and ischemic stroke (HR 0.90; 0.85 – 0.95) but higher risk of gastroparesis (HR 1.24; 1.12 – 1.38). We observed lower risks of cardiac arrest, heart failure, venous thromboembolism (VTE), adverse renal outcomes, and hospitalizations in both SGLT2i and GLP1a cohorts compared to controls.

Further analysis between the SGLT2i and the GLP1a cohorts revealed lower risks of heart failure, acute kidney injury, end-stage renal disease (ESRD), or dialysis dependence in the SGLT2i cohort but higher risks for ventricular arrhythmias, and diabetic ketoacidosis. Wrist sprain was used as a falsification endpoint.

Conclusion:
Among patients with T2DM and autoimmune disease, SGLT2i and GLP1a use correlated with a significant reduction in cardiovascular morbidity and all-cause mortality and were associated with a reduced risk of renal failure, VTE, and hospital admission.
Abstract 4146439: Predictors of Cardiovascular-Kidney-Metabolic (CKM) Syndrome Progression Among Atherosclerosis Risk in Communities (ARIC) Study Participants
Authors: Belanger Matthew , Ozkan Bige , Zhang Sui , Nambi Vijay , Rangaswami Janani , Echouffo Justin , Blumenthal Roger , Ballantyne Christie , Khan Sadiya , Coresh Joseph , Ndumele Chiadi
Published: November 2024

Background:
Progression along Cardiovascular-Kidney-Metabolic (CKM) stages confers greater cardiovascular disease (CVD) risk. However, the factors associated with CKM stage progression over time are not yet defined.

Methods:
We evaluated ARIC Visit 4 (1996-98) participants without CVD at Visit 1 (1987-89) and with available data to define CKM stages at both Visits 1 and 4. CKM stages were defined as: stage 0, no CKM risk factors; stage 1, excess/dysfunctional adiposity; stage 2, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, or diabetes) and/or moderate- to high-risk chronic kidney disease (CKD); stage 3, ≥20% predicted CVD risk per the PREVENT calculator or very high-risk CKD; and stage 4, clinical CVD. Among those in CKM stages 0-3 at Visit 1, we used logistic regression to concurrently assess the association of age, sex, race, area deprivation index (ADI, a measure of neighborhood deprivation), education, household income, physical activity (categorized as consistently ideal, intermediate, or consistently poor per AHA recommendations), and diet (per Life’s Essential 8 healthy diet score) with progression to a higher CKM stage from Visit 1 to Visit 4.

Results:
Among 8,376 participants, the mean age at Visit 1 was 55 years, with 52% female and 21% Black adults. Older individuals had higher odds of CKM progression (OR: 1.49 [95% CI 1.42-1.56] per 5-years of age), whereas females had lower odds (OR: 0.72 [0.64-0.80]) and Black race did not have an independent association (
Figure
). More adverse social determinants of health were associated with higher odds of CKM progression, including higher ADI (deciles 7-10 vs deciles 1-3 OR: 1.39 [1.23-1.57]), lower income (<$12,000 vs ≥$50,000 OR: 1.40 [1.12-1.75]) and less education (grade school vs graduate school OR: 1.36 [1.10-1.67]). Higher physical activity levels were associated with lower odds of CKM progression (ideal vs poor OR: 0.82 [0.70-0.96]), while healthy diet score was not significantly associated with CKM stage progression.

Conclusion:
Several sociodemographic and behavioral factors are associated with CKM stage progression. This understanding can help to guide population strategies to preserve and improve CKM health.
Abstract 4146445: The critical role of CD206+ pro-PAH macrophages in contributing to severe pulmonary arterial hypertension and obliterative vascular remodeling
Authors: Dai Jingbo
Published: November 2024

Rationale:
Previously we identified a mouse model
Tie2Cre
-mediated disruption of
Egln1
of Pulmonary arterial hypertension (PAH) with progressive obliterative vascular remodeling including vascular occlusion and plexiform-like lesions and right heart failure. Tie2Cre-meidated disruption of
Egln1
in bone marrow contributes to the severity of PAH indicating the importance of the immune cells in the pathogenesis of PAH. We
hypothesized
that Macrophage accumulation and polarization due to
Egln1
deficiency contributes to obliterative pulmonary vascular remodeling and severe PAH in

Egln1
Tie2Cre

(CKO) mice.

Methods:
We utilized single-cell RNA sequencing (scRNAseq) to provide transcriptome insights into cellular composition changes in the lungs of in Egln1
Tie2Cre
mice.

Egln1
Tie2Cre

mice with CD68-FlpERT2/CD206-frt-stop-frt-Dre/Rosa26-rox-stop-rox-DTR (CKO/Dep) transgene were generated and received tamoxifen and diphtheria toxin to deplete the CD206+ macrophages during the development of PAH. RVSP and RV/(LV+S) ratio were measured. Russell-Movat pentachrome staining was carried out to assess pulmonary vascular remodeling.
Igf1
/

Egln1
Tie2Cre

double knockout mice and IGF1R inhibitor treatment were employed to delineate the molecular mechanism.

Results:
Single cell RNA sequencing and FACS analyses identified marked accumulation of the CD206+ macrophage subpopulation in
Egln1
Tie2Cre
mouse lungs. CD206
+
Macrophages were accumulated in the pulmonary vessel adventitia of idiopathic PAH (IPAH) patients as well as
Egln1
Tie2Cre
mice. Genetic depletion of CD206+ macrophages using the

Egln1
Tie2Cre

/MaFIA mouse model markedly inhibited obliterative pulmonary vascular remodeling and PAH and promoted survival. These macrophages were PHD2-deficient and expressed elevated levels of pro-PAH factors such as IGF-1 and thus promoted SMC proliferation in co-culture study. Genetic disruption of the
Igf1
in
Egln1
Tie2Cre
mice inhibited IGF-1 production and attenuated PAH and pulmonary vascular remodeling. Treatment of IGF1 receptor inhibitor attenuated PAH in

Egln1
Tie2Cre

mice and MCT-rats.

Conclusions:
PHD2 deficiency in hematopoietic cells induced accumulation of CD206+ macrophages in the adventitia of pulmonary vascular lesions of
Egln1
Tie2Cre
mice and IPAH patients, which contributed to severe PAH though the Igf1 signaling. Thus, targeting abnormal macrophage function and signaling pathways is a potential effective therapeutic strategy for treatment of PAH patients and promotion survival.
Abstract 4146464: The Clinical and Electrocardiographic Phenotype of Genotype Negative Long QT Syndrome
Authors: Karlinski Vizentin Vanessa , Neves Raquel , Bains Sahej , Ferreira Felix Iuri , Bos Johan , Tester David , Giudicessi John , Ackerman Michael
Published: November 2024

Background:
LQTS is a genetic heart disease associated with an increased risk of sudden death. Despite advances in genetic testing, a small subset of patients still lacks identifiable genetic markers. Consequently, the true prevalence and clinical phenotype of genotype negative remains to be determined.

Objective:
To determine the prevalence and clinical characteristics of patients with a clinical diagnosis of LQTS but a negative genetic test.

Methods:
A retrospective review was conducted on patients evaluated and treated at a tertiary hospital between 2000 and 2024, focusing on those with a clinical diagnosis of LQTS, but a negative genetic test for all LQTS-associated genes, with available follow-up of at least 1 year.

Results:
After exclusion for follow-up and lack of genetic testing, the study cohort consisted of 1834 patients with LQTS including 1708 (93%) with a (likely) pathogenic (LP/P), LQTS-causative variant. Also, in 95 patients (5%), their variant of uncertain significance was clinically upgraded to a LP/P-variant, leaving only 31 patients classified as phenotype positive but genotype negative (1.6%). Of these, 16/31 underwent next-generation genetic sequencing, revealing the genetic cause in 6/16 cases (37%; 0.3% of all patients). For the remaining 25 genotype negative LQTS patients (1.3%), the mean age at diagnosis was 26 ± 15 years, with 19 (76%) being female, and an average initial QTc of 497 ± 41 ms. In total, 11 patients (44%) experienced a cardiac event before diagnosis [1 sudden cardiac arrest (SCA), 1 Torsades, 1 VT, 8 syncopes] and 1 patient had his first cardiac event during follow-up; 7/12 patients had more than one subsequent event. Twenty patients were proband (80%) and 6 had a family history of SCA. Eleven patients received an ICD (44%), left cardiac sympathetic denervation was performed in 4 (16%), and 2 patients experienced arrhythmia-related deaths (8%). The mean follow-up since diagnosis was 7 ± 5 years.

Conclusion:
With a prevalence of genotype-negative LQTS of 2%, the number of these patients is much lower than previously suggested, underscoring the advancements in identifying new genetic markers and the role of phenotype-enhanced variant adjudication and next-generation sequencing. Additionally, significant disease severity was observed in the remaining patients, emphasizing the pivotal role of genotype-phenotype correlations and risk stratification in managing and counseling patients lacking identified LQTS-causing mutations.
Abstract 4146495: Branched Chain Amino Acids Modulate Lung-Liver Axis in Pulmonary Arterial Hypertension
Authors: Blake Madelyn , Moon Ryan , Blake Jeffrey , Mendelson Jenna , Annis Jeffrey , Prisco Sasha , Provencher Steeve , Bonnet Sandra , Brittain Evan , Bonnet Sebastien , Prins Kurt
Published: November 2024

Background:
Valine, leucine, and isoleucine are the branched amino acids (BCAA). Elevated BCAAs predict worse outcomes in several cardiovascular diseases with metabolic origins, but the role of BCAAs in pulmonary arterial hypertension (PAH) remains unclear. Moreover, the effects of BCAAs on the emerging lung-liver axis are unexplored.

Methods:
The effects of small molecule (BT2) activation of BCAA catabolism and a low BCAA diet were evaluated in monocrotaline rats. Multi-omics analyses of the lung and liver were conducted in the BT2 arm. Confocal microscopy evaluated hepatocyte nuclear size in rodents and humans with PAH. Human livers were subjected to proteomic analysis. Human single nucleotide polymorphisms (SNPs) associated with elevated BCAAs and their relationship with PAH were investigated in the BioVU database.

Results:
Proteomics and metabolomics profiling demonstrated BT2 restructured lung fat metabolism, which increased exercise capacity, reduced PAH severity, and improved RV function. A low BCAA diet also mitigated PAH severity and improved RV function. Pathological hepatic shear stress phenotypes induced by RV dysfunction (nuclear hypertrophy, AKT signaling, electron transport chain (ETC) homeostasis, and ceramide accumulation) were blunted by BT2. Human PAH livers partially phenocopied the rodent hepatic shear stress phenotype (nuclear enlargement, AKT activation, and ETC protein downregulation). Finally, patients harboring SNP rs117643180 had increased risk of PAH.

Conclusion:
Rodent and human data link altered BCAA catabolism to the pathogenic lung-liver axis in PAH.