bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13293: Predicting Successful ECMO Decannulation - A Novel Machine Learning Approach
Authors: Hutchins Elizabeth , Rahrooh Al , Feng Jeffrey , Chandra Neha , Hsu Jeffrey J , Bui Alex
Published: December 2023

Introduction:
Extra Corporeal Membrane Oxygenation (ECMO) has emerged as a crucial life support intervention, yet the decision-making process for safe decannulation remains challenging due to a paucity of data.

Methods:
199 patients who underwent venoarterial ECMO for cardiogenic shock between 2015 and 2021 were identified. Demographic, hemodynamic, laboratory, and echocardiographic data obtained within 24 hours of decannulation were collected. Successful decannulation was defined as survival without relapse to mechanical circulatory support or heart transplant within 30 days. The dataset was randomly split into 80/20 train-validation splits, and four machine learning models were employed. 5-fold cross-validation and error analysis were performed. Feature importance was derived from the best performing model.

Results:
103 patients were successfully weaned off ECMO. Table 1 provides patient characteristics, which were used as features in the models. Among the models tested, Random Forest (RF) exhibited the highest performance (accuracy 85.0%, precision 90.0%, recall 85.7%, AUROC 0.94). Figure 1 depicts the performance for each model as well as the ranked feature importance and Receiver Operating Curve for the RF model. The most important features were mixed venous oxygen saturation, systolic blood pressure, ECMO flow rate and pulmonary diastolic blood pressure.

Conclusion:
This study demonstrates the successful application of machine learning in predicting ECMO weaning outcomes. Future research will add features and patients to enhance model performance with the goal of developing a clinical tool to assist physicians caring for ECMO patients.
Abstract 13312: Statin Signature: Using Proteomics to Detect Pharmacological Fingerprints
Authors: Kuzma Jessica , Shrestha Sama , Paterson Clare , Biegel Hannah , Bogren Lori , Hinterberg Michael , Hagar Yolanda , Chadwick Jessica , Williams Stephen A
Published: December 2023

Introduction:
Lowering low-density lipoprotein cholesterol with statin therapy is a primary strategy for reducing cardiovascular morbidity and mortality. Yet, adherence to and persistence with statin medication is generally low, complicating the ability to evaluate whether treatment is effective.

Hypothesis:
Statin treatment may yield significant differences in abundances of proteins detectable in blood samples. Using machine learning and high-throughput proteomics, a blood-based biomarker test can be developed to assess statin medication compliance and demonstrate drug fingerprinting useful for clinical trials.

Methods:
Using modified-aptamer proteomics technology, SomaScan® assay v4.0, we assessed ∼5,000 proteins in 8,395 EDTA plasma samples from individuals aged 29-64 at visit 1 of the Fenland study, totaling ∼42 million protein measurements. A total of 305 individuals (3.6%) reported active statin medication use at this study visit. Predicted statin use was modeled with protein measurements using machine learning methods in 70% of Fenland as a training dataset. A hold-out dataset was used to assess model performance. A predictive model using elastic net logistic regression was optimized based on AUC and robustness to assay noise and sample handling conditions to detect a signature of statin usage.

Results:
A total of 839 proteins differed significantly between the ‘active statin’ and ‘no statin’ use groups in univariate analysis (FDR <0.01). Eight of the top 50 significant proteins have known mechanistic associations with statin pharmacology, including HMGCS1, PCSK9, and APOB. A six-protein model was developed with an AUC of 0.91 (sensitivity=0.82, specificity=0.88) and 0.90 (sensitivity=0.80, specificity=0.87) on the training and hold-out datasets, respectively, to predict whether a statin signature is present or not.

Conclusions:
We successfully developed a blood-based protein-only model that detects mechanistically-relevant protein changes to predict active statin use in adults. The protein model could compliment self-reported medication status in clinical trials and in healthcare.
Abstract 13427: Incidence and Causes of Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A 20-year Study
Authors: Petek Bradley J , Churchill Timothy , Moulson Nathaniel , Kliethermes Stephanie A , Baggish Aaron L , Drezner Jonathan A , Patel Manesh R , Ackerman Michael J , Kucera Kristen L , Siebert David M , Zigman Suchsland Monica L , Salerno Lauren , Asif Irfan , Maleszewski Joseph J , Harmon Kimberly G
Published: December 2023

Background:
The incidence and causes of sudden cardiac death (SCD) among young competitive athletes impact prevention strategies yet remain incompletely understood.

Methods:
National Collegiate Athletic Association (NCAA) athlete deaths from 7/1/2002-6/30/2022 were identified through 4 independent databases/search strategies. Autopsy reports and medical history were reviewed by an expert panel to adjudicate causes of SCD. Poisson regression was used to calculate incidence rate ratios (IRR) for 5-year intervals over the 20-year study.

Results:
A total of 143 SCD cases were identified among 1102 athlete deaths and 9,106,516 athlete-years (AYs). The incidence of SCD among NCAA athletes was 1:63,682 AYs [95% CI 1:54,065, 1:75,010]. Incidence was higher in males compared to females (1:43,348 vs. 1:164,504 AYs) and Black compared to White athletes (1:27,217 vs. 1:74,581 AYs). The highest incidence of SCD was among Division 1 male basketball players (1:8,188; White 1:5,848; Black 1:7,696 AYs). The incidence rate for SCD decreased over the study period (5-year IRR 0.71 [95% CI 0.61,0.82]), whereas the rate of non-cardiovascular deaths remained stable (5-year IRR 0.98 [95% CI 0.94,1.04];
Figure 1A
). Autopsy-negative sudden unexplained death (AN-SUD, 19.5%) was the most common post-mortem exam finding, followed by idiopathic left ventricular hypertrophy/possible cardiomyopathy (CM, 16.9%) and hypertrophic CM (12.7%) in cases with enough information for adjudication (118/143,
Figure 1B
). There were 8 cases of myocarditis, with none attributed to COVID-19 infection. SCD events occurred most commonly during exertion among athletes with coronary artery anomalies (100%) and arrhythmogenic CM (83%), whereas AN-SUD and hypertrophic CM had a higher proportion of non-exertional SCD (44% and 40%, respectively).

Conclusions:
The incidence of SCD in college athletes has decreased. Male sex, Black race, and basketball are associated with a higher incidence of SCD.
Abstract 13597: Treatment Patterns and Outcomes for Young Adults With Atrial Fibrillation: The KP YOUNG-AF Study
Authors: Solomon Matthew D , Fan Dongjie , Garcia Elisha , Low Deborah , Vinson David R , Liu Taylor , Go Alan S
Published: December 2023

Introduction:
Young adults with atrial fibrillation (AF) may be most vulnerable to adverse outcomes such as cardiac remodeling and stroke, due to exposeure to AF for a longer time over their life course.
Research Question
What are contemporary treatment patterns and outcomes for young adults with AF treated with rate or rhythm control strategies?

Methods:
We identified patients aged 21-60 years with incident AF diagnosed from 2010-2018 within a large, integrated healthcare system caring for >4.5M, and categorized them by treatment strategy within their first year after AF diagnosis: no treatment, rate control (AV nodal blockers only), or rhythm control (cardioversion, anti-arrhythmic drugs, or ablation). We examined crude outcomes of new onset heart failure (HF), stroke or transient ischemic attack (TIA), and use of oral anticoagulants (OAC), and examined multivariable associations between treatment strategy and outcomes using Cox regression.

Results:
Among 11,824 young adults with incident AF (mean [SD] age 51 [8.5] years; 32% female), 31% were treated with rhythm control, 50% with rate control, and 19% with no treatment. Those with no treatment were younger with fewer comorbidities. Crude rates (per 100 person-years) of incident HF and OAC were higher among rhythm control patients (HF: 4.45 for rhythm control, 2.51 for rate control, 0.56 for no treatment; OAC: 41.8 for rhythm control, 15.2 for rate control, 3.8 for no treatment), but rates of stroke/TIA were lower (0.71 for rhythm control, 0.92 for rate control, 0.51 for no treatment) (Figure). In adjusted analyses, no significant association was found for rhythm control (vs no rhythm treatment) for HF or stroke/TIA, but OAC use was higher (HR 1.66, 95%CI:1.57-1.70).

Conclusions:
Less than one third of young adults with AF received initial rhythm control therapy. Adverse outcomes were not associated with treatment strategy, but future studies should further examine long-term outcomes from sustained AF in young patients.
Abstract 13633: Modern Treatment Patterns in Incident Pulmonary Arterial Hypertension (PAH) Patients: Real-World Data From the Pulmonary Hypertension Association (PHA) Registry
Authors: Paoli Carly J , Kime Noah , Williams Kayleen , Gomez-Rendon Gabriela , Tonelli Adriano , Cajigas Hector , Mathai Stephen , Khan Sarah L , Sahay Sandeep
Published: December 2023

Purpose:
New 2022 European Society of Cardiology/European Respiratory Society PAH guidelines recommend treatment guided by a multi-parameter risk assessment.
1
Patients with low/intermediate risk without cardiopulmonary comorbidities should start dual PAH combination therapy; those with cardiopulmonary comorbidities should be reassessed early for rapid escalation to dual therapy. Initial triple therapy is recommended for high-risk patients. We examined use of dual and triple PAH therapy in the US (before guideline update).

Methods:
We used the Pulmonary Hypertension Association Registry (PHAR), a prospective US registry of pulmonary hypertension (PH) patients, enrolled within 6 months of their first outpatient visit at one of 54 participating PH care centers in the US, between Sep 2015-Jun 2022. We included adults (≥18 years at enrollment) with incident PAH (newly diagnosed and treated within 6 months of enrollment) and ≥1 follow-up clinic visit post baseline visit. Chronic thromboembolic PH patients were excluded.

Results:
We analyzed (descriptive statistics) 794 incident patients (baseline characteristics in Table 1). Treatment patterns at baseline (n=794)/last follow-up visit (n=610) were 289 (36.4%)/102 (16.7%) on monotherapy, 419 (52.8%)/314 (51.5%) on dual combination, 83 (10.5%)/179 (29.3%) on triple combination therapy, respectively. Mean time from enrollment to dual and triple combination therapy was 86.1 (standard deviation [SD]: 209.0) and 346.1 days (SD: 430.8), respectively.

Conclusions:
Among incident PHAR patients, half received initial dual and 10% triple upfront combination therapy. At last follow-up, most (>80%) patients had escalated to dual/triple combination therapies.

Clinical Implications:
At PH care centers, most incident PHAR patients are escalated to dual and triple therapy (at last follow-up) per current guidelines.

Reference

1. Humbert M, et al. Eur Heart J. 2022;43:3618-731.
Abstract 13918: Improvement of Pulmonary Arterial Hypertension (PAH) Risk Assessment Model Using Cardiac Magnetic Resonance Imaging Variables
Authors: Correa-Jaque Priscilla , Lin Yeming , Lin Shili , Liu Yongqi , Fauvel Charles , Vanderpool Rebecca , Kanwar Manreet , Kraisangka Jidapa , Perer Adam , Everett Allen D , Alabed Samer , Swift Andew , Kiely David G , Benza Raymond L
Published: December 2023

Introduction:
PAH is a deadly disease without cure. Formalized risk stratification allows therapeutic adjustments that optimize drug utilization. Risk scores, like REVEAL 2.0 recommended by PAH guidelines only offer good discrimination. Our goal was to create risk models with excellent discrimination (C-Index over 0.8), using modern statistical techniques and expanded variable pools including imaging and genomics. The AIM of this study was to demonstrate the improved performance with the addition of cardiac MRI variables.

Methods:
PAH patients from the ASPIRE cardiac MRI database were analyzed. Imaging variable (IMV) selection was performed using three machine learning methods: logistic regression, Lasso, and Random Forest. Rankings of the IMVs from these sources were aggregated to arrive at a consensus list. The selected IMVs were added to the set of variables for deriving the REVEAL 2.0 composite score. Bayesian networks (BN) were then built to predict 1-year survival based on the Tree-Augmented naïve Bayes (TAN) algorithm. Five-fold cross-validation was performed to assess the improvement in survival prediction from adding the selected imaging variables.

Results:
A total of 343 PAH previously diagnosed subjects were included in this analysis. The rank aggregation algorithm identified several IMV, including LVSVI, RVCO, LVEDVI, and RVESVI, that were predictive of survival but not the REVEAL 2.0 composite score. Adding these IMV to the REVEAL 2.0 variables, we built a BN model that depicts the non-linear relationships among the predictors and one-year survival (Fig 1). We obtained an average AUC of 0.83 over the five cross-validation test sets, an improvement over the AUC of 0.78 using only the REVEAL 2.0 variables. A Mann-Whitney non-parametric test shows the improvement is statistically significant at the 0.1 level.

Conclusion:
Advanced statistical models that include cardiac IMVs improve performance of PAH risk assessment models.
Abstract 13921: Automated Estimation of Computed-Tomography-Derived Left Ventricular Mass Using Sex-Specific, 12-lead-ECG-Based Temporal Convolutional Network
Authors: Pan Heng-Yu , Hsu Benny , Chou Chun-Ti , Lee Chih-Kuo , Lee Wen Jeng , Ko Taiming , Wang Tzung dau , Tseng Vincent S.
Published: December 2023

Introduction:
Increased left ventricular myocardial mass (LVM) is associated with adverse cardiovascular outcomes. Various rule-based criteria using limited electrocardiogram (ECG) features lacks sensitivity for evaluating LVM. Recent studies using deep learning methods have made progress in LVM evaluation taking advantage of ECG amplitude data.

Hypothesis:
We hypothesized that LVM prediction with deep learning models are improved by adding inter-lead information and building sex-specific models.

Methods:
This study proposed a novel deep learning-based method, the eLVMass-Net, by using ECG-LVM (n=1,459) paired data. ECG signals, QRS duration and axis, demographic features were used as input data. ECG signals were encoded by a temporal convolutional network (TCN) encoder. We adopted a total of four models (non-lead-grouping v. lead-grouping, non-sex-specific v. sex-specific) for LVM estimation. For lead-grouping models, the encoders were constructed based on segregated limb and precordial leads. For sex-specific models, we constructed models on both genders separately. Encoded ECG features and demographic features were concatenated for LVM prediction. To evaluate the performance, we utilized a 5-fold cross-validation approach with the evaluation metrics, mean absolute error (MAE) and mean absolute percentage error (MAPE).

Results:
For non-sex-specific models, eLVMass-Net has achieved an MAE of 14.33±0.71 and an MAPE of 12.90%±1.12%, outperforming the best state-of-the-art method (MAE 19.51±0.82; MAPE 17.62%±0.78%; P < 0.01). Sex-specific models achieved even lower MAPE for both males and females respectively (male MAPE 12.55%±0.88%; female MAPE 12.52%±0.34%), which also surpassed state-of-the-art methods. Adding the information of QRS axis and duration did not significantly improve the model performance (P = 0.28). The saliency map showed that T wave in precordial leads and QRS complex in limb leads are important features with increasing LVM.

Conclusions:
This study proposed a novel LVM estimation method, outperforming previous methods by emphasizing relevant heartbeat waveforms, inter-lead information, and non-ECG demographic features. The sex-specific analysis is crucial in improving LVM prediction.
Abstract 14025: Health Status Profiles in Patients With New or Worsening Peripheral Artery Disease Symptoms and 12-month Hospitalization Risk From the Portrait Registry
Authors: Cleman Jacob , Romain Gaelle , Scierka Lindsey , Labrosciano Clementine , Shishehbor Mehdi H , Safley David M , Jones Philip , Spertus John , Beltrame John F , Mena-Hurtado Carlos , Smolderen Kim G
Published: December 2023

Introduction:
Risk stratification for healthcare utilization in PAD is critical given rising costs. The association between health status measures and hospitalization is unknown. We examined the association between a disease-specific patient-reported outcome measure and risk of hospitalization at 12 months.

Methods:
Patients with new or worsened lower extremity claudication enrolled at US sites in the PORTRAIT registry from 2011 to 2015 were included. The Peripheral Artery Questionnaire, a PAD-specific patient-reported outcome measure, was used to measure health status. PAQ summary scores range from 0 to 100 (better health status). Kaplan-Meier failure curves and adjusted Cox proportional hazards models assessed the association between baseline PAQ summary score and (1) the combined endpoint of all-cause hospital admission and ED visit (AD-ED) and (2) all-cause hospital admission (AD) at 12 months.

Results:
Of the 796 patients (mean age 69 ± 10 years, 42% female, 72% white, mean baseline PAQ summary score 46.8 ± 22.0) included, 349 (44%) had a hospital admission or ED visit at 12 months, with a total of 661 visits. Patients in the lowest PAQ quartile had higher rates of AD-ED at 30 days (16.1% vs. 4.3%), 90 days (29.8% vs. 12.8%), and 12 months (53.3% vs. 22.4%). In the fully adjusted model, lower PAQ score was associated with higher risk for AD-ED (HR per 10-point decrease, 1.12, 95% CI, 1.06-1.19, P<0.001) and AD (HR per 10-point decrease, 1.14, 95% CI, 1.06-1.22, P<0.001).

Conclusion:
Lower PAD-specific health status is associated with an increased risk in the combined endpoint of hospital admission or ED visits and all-cause hospital admission. These results support the use of baseline health status as a strong predictor for healthcare utilization in a high-risk population and may help to offset costs.
Abstract 14046: Cardiac Tamponade: A Handy Case of Early Detection
Authors: Tranvu Khanhphi C , Faturos Andrew , Southard Jeffrey A , Rogers Jason
Published: December 2023

Case Presentation:
A 63-year-old man with severe bicuspid aortic valve stenosis underwent surgical aortic valve replacement and the post operative echocardiogram was normal.In the month after discharge, the patient developed progressive episodes of lightheadedness, fatigue, and exertional weakness. He had no associated dyspnea on exertion, chest pain or fever. He was alerted of new sinus tachycardia on his Apple Watch, and the ECG morphology began changing with an overall decrease in QRS amplitude as well as alternating QRS amplitudes consistent with electrical alternans (Figure 1). These ECG strips were sent to the patient’s cardiologist who suspected a pericardial effusion due to these characteristic ECG findings.The patient underwent outpatient echocardiography which showed a normal functioning bioprosthetic valve with new large circumferential pericardial effusion and signs of cardiac tamponade physiology. The patient was admitted and underwent urgent pericardial drain placement with removal of 250cc of serosanguineous fluid. He recovered and was discharged with 3 months of colchicine.

Discussion:
Pericardial effusions are a known potential complication after cardiac surgery and often have an occult presentation making detection difficult. Smart watches with ECG capabilities provide valuable data because they can be used to detect the development of a new tachycardia and changes in QRS morphology. By observing the progressive changes in the QRS morphology from baseline, it is possible to monitor for the development of electrical alternans. This finding coupled with the patient’s clinical presentation prompted rapid evaluation and treatment.

Conclusions:
The Apple Watch can perform single-lead ECGs which are capable of diagnosing arrhythmias including atrial fibrillation. This case now opens the door to the early detection of postoperative pericardial effusions by monitoring the Apple watch for electrical alternans.
Abstract 14087: Physical Activity is Associated With Monocytes and Monocyte Subsets in Low-Resourced Neighborhoods: Data From the Step It Up Physical Activity Intervention
Authors: Saurabh Abhinav , Tarfa Hannatu , Baumer Yvonne , Dave Ayushi , Pita Mario , Cintron Manuel , Ortiz-Whittingham Lola , Reynolds Sandy , Potharaju Kameswari , Baez Andrew , Thompson Keitra , Osei Baah Foster , Ayers Colby , Neally Sam , Curlin Kaveri , Vijayakumar Nithya , Mitchell Valerie , Wells Ayanna , Marah Marie , Collins Billy , Powell-Wiley Tiffany M
Published: December 2023

Background:
Physical activity (PA) reduces cardiovascular disease (CVD) risk; those living in lower-resourced neighborhoods have higher CVD risk in part due to limited PA access. Monocyte subsets (classical, intermediate, and non-classical) with their platelet aggregates (PlAgg) are key in CVD, but less is known about relationships between PA and monocytes. We investigated associations between PA and monocyte subsets with PlAgg in African American (AA) women at risk for CVD living in resource-limited Washington, DC areas.

Methods:
Participants were enrolled in Step It Up, a technology-enabled, community-engaged PA intervention. Baseline PA was measured as daily step counts using a FitBit Charge 2. Monocyte subsets and PlAgg were measured in fasting blood samples by flow cytometry. Multivariable linear regression was used to determine relationships between PA and monocytes adjusting for BMI and ASCVD 10-year risk score. We examined neighborhood deprivation index (NDI), a 2018 Census-tract based measure of neighborhood socioeconomic deprivation, as a moderator of associations between PA and monocytes.

Results:
The study cohort was a sample of AA women with overweight/obesity enrolled in Step It Up (N=106, age=57±12 y, BMI=34.8±6.3kg/m2). Higher baseline PA associated with monocyte subsets, but not overall monocyte presence (Table). Furthermore, higher baseline PA negatively associated with PlAgg on all monocytes. PA and monocyte subsets were most associated among those residing in higher deprivation neighborhoods (Table).

Conclusion:
Baseline PA was associated with monocyte subsets and lower monocyte-PlAgg formation among AA women living in lower-resourced conditions. Future work should examine the relationship between PA changes and changes in monocyte subsets in community engaged PA interventions like Step It Up, particularly among those residing in limited resource communities.
Abstract 14114: An Extreme Case of Calcific Constrictive Pericarditis
Authors: Suppah Mustafa , Narayanasamy Hema , Appleton Chris P , Alsidawi Said
Published: December 2023

Introduction:
Constrictive pericarditis (CP) can lead to cardiac dysfunction and a range of clinical symptoms. However, differentiating it from conditions like restrictive cardiomyopathy can be challenging due to the overlapping features.

Case Presentation:
We present a case of a 61-year-old female with a history of atrial flutter and subsequent atrial fibrillation, experiencing worsening dyspnea on exertion, lip cyanosis, and upper abdominal constriction. Extensive diagnostic workup, including Echo, CT scan, and cardiac MRI, revealed severe biatrial enlargement, ventricular interdependence, elevated filling pressures, reduced cardiac output, and extensive pericardial thickening and calcifications (
Figures 1.a
and
1.b
). These findings supported the diagnosis of extensive CP.

Discussion:
CP is often missed and delayed in diagnosis due to its complex hemodynamics and the non-specific symptoms. Typically, the initial imaging modality to be performed is an Echo. Specific findings such as dilated vena cava, preserved tissue velocity with annuls paradoxus, abnormal respiratory septal shift, and respiratory variations in mitral/tricuspid inflow should be first clues for potential diagnosis. Furthermore, evaluation of the hepatic vein with diastolic flow reversal during expiration is a key finding. Lack of respiratory variation in the SVC is also important. Cardiac CT will assess pericardial thickness and calcification, while cardiac MRI is key for the diagnosis by showing the pericardial thickness and fibrosis as well as the septal respiratory shift and venous congestion. An invasive hemodynamic study might be required if imaging is inconclusive. this patient’s presentation, imaging findings, exercise test results and collectively supported considering radical pericardiectomy.

Conclusions:
This report highlights the diagnostic challenges related to CP and the importance employing a multimodality imaging approach for accurate diagnosis.
Abstract 14129: Identification of Highly Correlated Sub-Networks of Cardiovascular Ageing Imaging Markers With 10-Year Predicted Risk Scores
Authors: Tan Kieran , Basker Gayathri , Thangaraja Keerthana , Gao Fei , Yeo Si Yong , Teo Loon Yee , Ewe See H , Tan Ru S , Koh Angela S
Published: December 2023

Introduction:
While Framingham 10-year risk scores (FRS) estimates cardiovascular disease (CVD) risk in older adults, few studies have benchmarked these estimates against age-related changes in cardiac structure and function, which are complex and highly inter-related. We investigated associations between cardiovascular (CV) imaging markers and FRS, vascular age, calculated regression, and determined connectivity between them in a network analysis.

Methods:
Participants recruited from a community-based cohort without CVD completed standardized questionnaires that collected baseline clinical factors, from which FRS, vascular age and calculated regression were derived. Cardiac structural and functional parameters were obtained via echocardiography.

Results:
202 participants (46.0% women, mean age 70.2 SD8.8) were included in this analysis. CV imaging markers correlated across a spectrum with FRS, vascular age and calculated regression. Predictive features and their associations by pearson correlation (nodes containing the variables; edges denoting links) (Fig 1) show significant associations. In ageing, this network showed that E/A ratio is inversely linked to FRS, vascular age and calculated regression while LVEF has a weak association with FRS and vascular age, without direct relationship with E/A ratio. While LAVI is associated with FRS and vascular age, LAVI is associated with E/E1 and not E/A ratio nor LVMI. Multivariate regression confirmed independent associations between FRS and vascular age with E/A ratio (b=-7.03, 95% CI -10.55, -3.52, p < 0.001; b= -15.13, 95% CI -19.33, -10.93, p < 0.001) and E/E prime ratio (b= 0.33, 95% CI 0.03 - 0.63, p = 0.033; b=0.66, 95% CI 0.30 - 1.02, p < 0.001).

Conclusion:
This structural collation of associations depicted different sub networks of cardiovascular imaging features into context. FRS, vascular age and calculated regression were associated with imaging markers of CV ageing at various network levels.
Abstract 14172: Surgical Aortic Valve Replacement Using Contemporary Mechanical versus Bioprosthetic Valves in Patients Aged 50 to 70 Years: Long-Term Outcomes
Authors: Fath Ayman R , Aglan Amro , Eldaly Abdullah S , Abraham Bishoy , Almomani Ahmed
Published: December 2023

Background:
Choosing either a mechanical or a bioprosthetic valve during surgical aortic valve replacement (AVR) in middle-aged patients is still controversial, especially with contemporary advancements in valve technology.

Aims:
To evaluate long-term survival and major morbidity in patients aged 50-70 years undergoing AVR using contemporary mechanical and bioprosthetic valves.

Methods:
A retrospective study was performed using the TriNetX global database to identify patients aged 50 to 70 years who had primary isolated surgical AVR from 2014 to 2020. Patients who had transcatheter AVR, concomitant, or prior cardiac surgery were excluded. Patients were stratified into 2 groups: mechanical and bioprosthetic. A 1:1 propensity-score matching was performed to control for baseline differences between the two cohorts. The primary endpoint was all-cause mortality and secondary endpoints were stroke, major bleeding, and reoperation over a follow-up period of 8 years.

Results:
A total of 1,138 propensity-matched patients were included in each group. There was no significant difference in survival, stroke, or reoperation rates between the two groups. Survival probability at the end of the follow-up period was 76.6% in the mechanical group and 80.1% in the bioprosthetic group (HR, 0.946 [95% CI, 0.702, 1.276]) (Figure 1). A total of 137(12%) vs 119 (10.4%) patients had stroke in the mechanical vs the bioprosthetic group, respectively (HR, 1.08 [95% CI, 0.851-1.392]). A total of 19 (1.7%) vs 17 (1.5%) patients had reoperation in the mechanical, and the bioprosthetic valve group, respectively (HR, 1.01 [95% CI, 0.526, 1.951]). There were higher major bleeding events in the mechanical group, 266 (23.4%) vs 163 (14.3%) in the bioprosthetic group, (HR, 1.64 [95% CI, 1.353, 1.999]).

Conclusion:
Contemporary bioprosthetic valves could be a reasonable option for AVR in patients aged 50 to 70 years with less major bleeding risk and similar survival, stroke, and reoperation rates.
Abstract 14242: The Potential Impact of Inflammation on the Lipid Paradox in Patients With Acute Myocardial Infarction: A Multicenter Study
Authors: Zeng Guyu , Yuan Jinqing
Published: December 2023

Introduction:
Low-density lipoprotein cholesterol (LDL-C) is a well-recognized risk factor for cardiovascular diseases. However, several clinical studies demonstrated that LDL-C was inversely associated with mortality risk in patients with acute myocardial infarction (AMI), which is known as lipid paradox.

Aims:
To verify the association between LDL-C and mortality risk among AMI patients.

Methods:
A total of 5,358 patients with AMI from a nationwide cohort were included in our analysis. All individuals were stratified according to LDL-C quartiles (≤2.00 mmol/l, 2.00-2.54 mmol/l, 2.54-3.19 mmol/l, >3.19 mmol/l) and hsCRP levels (hsCRP≤3 mg/l & hsCRP>3 mg/l). Primary outcome was cardiac mortality. Secondary endpoint was all-cause mortality.

Results:
During a median follow-up of 2.1 years, 297 deaths and 227 cardiac deaths occurred. Patients in the lowest LDL-C quartile experienced the highest incidence of cardiac and all-cause mortality. The association between mortality risk and LDL-C levels appeared to be U-shaped. Patients in the highest LDL-C quartile had increased incidences of cardiac and all-cause mortality in patients with hsCRP≤3 mg/l. However, higher incidences of both cardiac and all-cause mortality were observed in the lowest LDL-C quartile group among those with hsCRP>3 mg/l. Multivariable COX regression analysis demonstrated that compared with the lowest quartile, the highest LDL-C quartile was significantly associated with a higher risk of cardiac mortality in patients with hsCRP≤3 mg/l (HR 3.04, 95%CI 1.33-6.96, p=0.008), but in patients with hsCRP>3 mg/l, the other three LDL-C quartiles showed a trend for lower cardiac mortality risks, and the second LDL-C quartile met the statistical significance (HR 0.62, 95%CI 0.40-0.95, p=0.027).

Conclusion:
AMI patients with lower LDL-C levels had a higher risk of mortality. However, this association was only observed in those with high inflammation risk.
Abstract 14313: A Proteomic Atlas of Human Coronary Artery Reveals the Pathological Progression of Atherosclerosis
Authors: Xu Xinjie , Chen Liang
Published: December 2023

Introduction:
The key molecular mechanisms associated with human atherosclerotic plaque progression, atherosclerotic lesion initiation and plaque destabilization are not fully understood.

Hypothesis:
Different stages of atherosclerosis (AS) progression have distinct pathological processes. Some key proteins induce AS progression.

Methods:
We employed 20 coronary artery samples among 4 explanted hearts from coronary heart disease patients. Each heart contains stages of unaffected control (NC), pathological intimal thickening (PIT), fibroatheroma (FA), transition to thin-cap fibroatheroma (TCFA) and ruptured plaque (RP), which were validated by hematoxylin and eosin (H&E) staining. We performed quantitative proteomics in each of the samples based on tandem-mass-tags and liquid chromatography-tandem mass spectrometry. Furthermore, we measured proteins in human coronary artery tissue via immunofluorescence.

Results:
Proteomics revealed that extracellular matrix (ECM) organization was the most significantly enriched pathway in PIT. FA exhibited an enrichment of immunologic processes, such as neutrophil degranulation, myeloid leukocyte activation and innate immune response. Molecular profiles of TCFA and RP are similar, with complement and coagulation cascades pathway as a hallmark of these stages. Clustering analysis of DEPs displayed 4 clusters, notably cluster 2 had a precipitous elevation from FA to TCFA. Within this cluster, we identified a high-rank molecule: macrophage-capping protein (CAPG). Immunohistochemistry and immunofluorescence revealed that CAPG is highly elevated in plaque compared to NC and is specifically expressed in the plaque.

Conclusions:
ECM organization was continuously dysregulated in AS progression. Immune response might initiate the atherosclerotic plaque. Complement and coagulation cascades pathway was a hallmark of TCFA and RP. CAPG might be a therapeutic target for AS progression.
Abstract 14603: Post-Myocardial Infarction Secondary Mitral Regurgitation Elevates Circumferential Strain in the Remote Zone and Contractile Dyssynchronicity in a Swine Model
Authors: Kikuchi Yuta , Onohara Daisuke , Silverman Michael , King Chase , Tom Stephanie , Govin Riya , Guyton Robert A , Padala Muralidhar
Published: December 2023

Introduction:
Post-myocardial infarction (MI) secondary mitral regurgitation (SMR) worsens left ventricular function and mortality, due to the volume overload it imposes on the ventricle. In this study, we sought to investigate the effects of the volume load from SMR on regional myocardial mechanics and dyssynchrony.

Methods:
Ten Yorkshire swine were induced with MI by occluding the left circumflex branch. Cardiac MRI and PV loop were performed at baseline (prior to MI), and at termination (3 months after MI). SMR was quantified using epicardial echo. Pigs were divided into 2 groups: no/mild MR (nmMR, n=4) and moderate/severe MR (msMR, n=6). MRI images were analyzed to measure infarction size, end-diastolic (EDV) and end-systolic volume (ESV), circumferential strain (CS), and standard deviation of time to peak of CS as systolic dyssynchrony index (SDI) to evaluate the dyssynchrony. The myocardial region was divided into the infarction, border, and remote zone, based on the LCx-supplied region
(Fig. A and B1)
.

Results:
There were no differences in infarction size between the two groups. The changes (Δ) of EDV and ESV from baseline to 3M were greater in msMR compared to nmMR (63.8±24.6mL vs 33.5±9.2 mL, p<0.05, and 48.1±18.9 mL vs 23.0±4.9 mL, p<0.05, respectively)
(Fig. B)
. Group-wise comparison of CS between baseline and 3M for each zone demonstrated that CS in the infarction zone decreased in both groups. However, CS in the remote zone was elevated at 3M only in msMR (-12.07±3.65 % vs -16.36±3.07 %, p<0.01) and there was a strong correlation between EDV and CS in the remote zone (Pearson r=-0.6614, p=0.01)
(Fig. C)
. Also, SDI of CS was significantly elevated at 3M in msMR (0.09741 vs 0.1255, p=0.015)
(Fig. D)
.

Conclusions:
Elevated CS in the remote zone and dyssynchrony due to volume load could impair LV function, potentially increasing oxygen demand and reducing pumping efficiency.
Abstract 14614: Effect of SGLT2 Inhibitors on Renal Outcomes Across Various Patient Populations
Authors: Siddiqi Tariq J , Usman Muhammad Shariq , Siddiqui Hasan F , Butler Javed
Published: December 2023

Background:
The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on renal outcomes in patients with varying combinations of heart failure (HF), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) remains unclear.

Methods:
Online databases were queried up to May 2023 for primary and secondary analysis of trials of SGLT2i in patients with HF, CKD, or T2DM. Outcomes of interest were composite renal endpoint (defined as an eGFR <15 mL/min/1.73 m2, doubling of serum creatinine, some percent change in eGFR, and/or need for kidney replacement therapy) and change in estimated glomerular filtration rate (eGFR) slope. Hazard ratios (HR) and mean difference with their 95% confidence intervals were pooled using the generic inverse variance method and a random-effects model.

Results:
10 trials (n=70,117 patients) were included. Compared with placebo, SGLT2i reduced the risk of composite renal endpoint by 35% in HF (HR: 0.65; 95% CI: 0.50-0.84), 38% in CKD (HR: 0.62; 95% CI: 0.54-0.71), and 37% in DM (HR:0.63; 95% CI: 0.54, 0.73). A similar pattern of benefit was observed in different combinations of these diseases (
Figure 1
), as well as patients without baseline HF (HR:0.57; 95% CI: 0.51, 0.63), CKD (HR:0.64; 95% CI: 0.42, 0.98) and T2DM (HR:0.62; 95% CI: 0.45, 0.86). Findings were similar for change in eGFR slope.

Conclusions:
SGLT2i improve renal outcomes in cohorts of HF, CKD and T2DM and these effects appear consistent across patients with different combinations of these conditions.
Abstract 14621: High-Density Lipoprotein Lipid and Protein Cargo and Cholesterol Efflux Capacity Before and After Bariatric Surgery
Authors: Zahid Sohail , Schlamp Florencia , Gildea Michael , Lin BingXue , parikh manish , Fisher Edward , Hornemann Thorsten , Vaisar Tomas , Heffron Sean P
Published: December 2023

Introduction:
Cholesterol efflux capacity (CEC) is inversely associated with incident CV events, independent of HDL-C. Obesity is characterized by low HDL-C and impaired HDL function. Bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), improves CV risk, but we have shown that the impact on CEC may differ by procedure over time post-op.

Hypothesis:
We hypothesized that RYGB and SG significantly affect HDL protein/lipid cargo and mediate CEC.

Methods:
We prospectively studied severely obese, nondiabetic women undergoing RYGB (n=31) or SG (n=36) before and at 6 and 12 months after surgery. Statistical analyses included Wilcoxon tests of log fold change in HDL proteins/lipids, hierarchical clustering to identify HDL protein/lipid clusters, and network mediation tests to identify cargo associated with CEC changes.

Results:
Subjects experienced similar weight loss regardless of procedure (38.0±10.4 kg at 12mo). Concentrations of 40 proteins (11 up, 29 down) and 95 lipids (46 up, 49 down) in HDL changed significantly following bariatric surgery. Proteins and lipids clustered into 9 and 14 groups of similar post-operative trajectories, respectively (Figure A). All clusters, other than 2 lipid clusters, showed similar responses regardless of procedure (Figure B). Despite similarities in cargo, changes in CEC differed depending upon time point and efflux pathway (Figure C). Network mediation analyses suggested that changes in 4 protein and 2 lipid clusters associated with post-operative changes in ABCA1-mediated CEC and changes in 1 lipid cluster associated with changes in non-ABCA1-mediated CEC (Figure D).

Conclusions:
In conjunction with substantial weight loss, bariatric surgery results in altered HDL protein/lipid cargo and CEC, possibly mediated by distinct HDL cargo. Further study of the mechanisms influencing HDL cargo in obesity and after bariatric surgery may lead to better understanding of CEC and management of CVD.
Abstract 14697: Developing a Machine Learning Algorithm Using Routine Clinical Data for the Detection of Hard Cardiovascular Disease Events
Authors: Kelly Ian , Whitehill Jacob R , Goldberg Robert
Published: December 2023

Introduction:
Machine learning (ML) may enhance prediction of hard cardiovascular disease (CVD) events (e.g., myocardial infarction, stroke, cardiac arrest). Developing ML algorithms using routinely-collected clinical data offers a practical method to improve CVD event prediction. This study aimed to train ML algorithms to predict 10-year risk of hard CVD events using common clinical variables and compare performance to pooled cohort equations (PCEs).

Hypothesis:
ML algorithms trained on data from the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerotic Risk in Communities (ARIC) would outperform PCEs in predicting 10-year risk of hard CVD events when tested on a PCE-valid subset.

Methods:
Data from MESA and ARIC were obtained. Pooled baseline data were used for algorithm training. Patients with prior CVD or lacking 10-year follow-up were excluded. The primary endpoint was hard CVD event within 10 years of baseline. Variables of interest included patient history, anthropometry, and serum lipid levels. Cohort data was split into training (75%) and test (25%) sets. Models trained were neural network, gradient boost machine, k-nearest neighbors, and an ensemble model.

Results:
In total, 17,775 patients (5,703 MESA, 12,072 ARIC) with mean age of 56.2 (
+
8.2) years and 54.6% female were included. During the 10-year follow-up period, 1,344 (7.6%) had a first-time hard CVD event. The ensemble model had the highest AUC on the full test set (0.783 [95% CI 0.76-0.81]), followed by the gradient boosting machine (0.781 [0.76-0.81], neural network (0.780 [0.76-0.81]), and k-nearest neighbors (0.737 [0.71-0.76]). The gradient boosting machine demonstrated highest sensitivity (76.0%), while the ensemble had highest specificity (78.6%). In the PCE-valid subset, the ensemble model had the highest AUC (0.780 [0.75-0.81]) and outperformed PCE (AUC = 0.757 [0.73-0.78], p = 0.001), as did the gradient boosting machine (AUC = 0.779 [0.75-0.81], p = 0.003]) and neural network (AUC = 0.776 [0.75-0.80], p = 0.007).

Conclusions:
The ensemble, gradient boosting machine, and neural network improved prediction of hard CVD events over PCEs within a PCE-valid subset despite training on a broader cohort. Future studies should validate results on an external dataset.
Abstract 14717: Gene Therapy Mediated Rescue of Chronic Non-Ischemic Cardiomyopathy in Minipigs
Authors: Li Jing , Balmaceda Pia , Ha Thuy , Accad Michel , Shaw Robin M , Hong Tingting
Published: December 2023

Heart failure (HF) is a major cause of morbidity and mortality worldwide, yet with limited therapeutic options. Recent evidence indicates that the cardiac bridging integrator 1 (cBIN1)-organizes transverse tubule microdomains which organize the calcium handling machinery important for cardiac function. In rodent models, adeno-associated virus 9 (AAV9)-cBIN1 effectively reconstitutes microdomains and rescues HF. Here we explored the therapeutic efficacy of AAV9-cBIN1 in a minipig model of non-ischemic HF. 6-7 months old Yucatan minipigs were subjected to continuous right ventricular rapid pacing (RVP) at 170 bpm. After continuous RVP for 5.7 ± 1.0 weeks (N=10), minipigs developed dilated cardiomyopathy with increased left ventricular (LV) end diastolic volume (EDV, 70.7 ± 4.5 vs. baseline 45.5 ± 1.6 mL) and reduced ejection fraction (EF, 36.5 ± 1.2 vs. baseline 71.3 ± 1.5 %). Once EF ≤ 40% over a week, pigs were randomized to receive intravenous AAV9-cBIN1 or control (AAV9-GFP or PBS). Pacing was continued throughout the study period. In control animals (N=5 with 4 PBS and 1 AAV9-GFP treatment), LV further dilated (78.0 ± 8.7 mL) with EF declining to 27.6 ± 6.7 % by four weeks post injection. The first three control animals already died of severe HF symptoms by 7 weeks post injection (Figure 1A) and the other two animals are currently at 4 weeks post injection with EF reduced to 27 and 33 %, respectively. Despite of continuous RVP, AAV9-cBIN1 rescued HF with EF recovered to 52.6 ± 4.0 % and EDV at 67.3 ± 6.6 mL at 4 weeks post injection. Three cBIN1-treated animals survived the full protocol of 6-month monitoring with EF maintained at 57.5 ± 15.5 % (Figure 1B-C), with two ongoing pigs currently surviving at 4 weeks post-injection with normal EF. Figure contains data of the animals who died or have already completed the 6-month protocol (N=3 per group). No toxicity was observed. In conclusion, intravenous cBIN1 gene therapy rescues non-ischemic HF and improves mortality in pigs.
Abstract 14831: Low Positive Social Determinants of Health Exposure Amplifies the Association Between Allostatic Load and Risk of Cardiovascular Mortality in Cancer and Non-Cancer Patients
Authors: Bhave Aditya , Reddy Ritu , Moore Justin , Nain Priyanshu , Datta Biplab , Nettles Darryl , Seth Lakshya , Jiang Stephanie , Patel Vraj , Malik Sarah , Weintraub Neal L , Al-Kindi Sadeer , Ganatra Sarju , Dani Sourbha , Gomez Valencia Javier , Wang Xiaoling , Guha Avirup
Published: December 2023

Introduction:
Allostatic load (AL) is a measure of the biological “wear and tear” or physiological effects of chronic toxic stress exposure and the body’s adaptive responses over time. High AL is associated with an increased risk of death from cardiovascular disease and cancer.

Hypothesis:
We examined Positive Social Determinants of Health (PSDOH) exposure as a moderator for the effect of AL on the risk of cardiovascular-related death (CVD) among adults with and without a history of cancer.

Methods:
We conducted a retrospective cohort analysis of the National Health and Nutrition Examination Survey (NHANES) years 1999 through 2010 linked and followed up with the National Death Index through December 31, 2019. We fit age, race, and sex-adjusted Fine & Gray models to calculate sub-distribution hazard ratios (SHR) of CVD among adults exposed to high versus low levels of PSDOH, stratified by high and low AL status. AL was calculated using a nine-point score previously defined in NHANES literature that uses a combination of serum biomarkers as well as body mass index and blood pressure. PSDOH was calculated using a seven-point score previously defined in NHANES literature examining positive exposures of home ownership, health insurance, educational attainment greater than high school, food security, being above the federal poverty level, health care access, and living with a partner.

Results:
Among 22,775 eligible participants in this study, 1,939 (8.5%) had a history of cancer. In the full cohort, age, race, and sex-adjusted models found that low PSDOH exposure was associated with a 38% increased risk of CVD among high AL adults (SHR: 1.38, 95% CI: 1.22 - 1.56) and a 57% increased risk among low AL adults (SHR: 1.57, 95% CI: 1.32 - 1.87). Cancer history-stratified adjusted models are presented in Table 1.

Conclusions:
Low PSDOH exposure amplified the association between AL and CVD in all cohorts, with the highest increases in risk being seen among adults with a history of cancer.