bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11335: Mitral Valve Prolapse Increases the Force Exerted on the Papillary Muscles
Authors: Van Kampen Antonia , Park Matthew H , Melnitchouk Serguei , Wilkerson Robert , Wang Hanjay , Zhu Yuanjia , Pandya Pearly , Nagata Yasufumi , Borger Michael A , Levine Robert , Woo Y. Joseph J
Published: June 2023

Introduction:
Recent studies have linked mitral valve prolapse (MVP) to localized myocardial fibrosis, ventricular arrhythmia, and even sudden cardiac death independent of mitral regurgitation (MR). The primary mechanistic theory is rooted in increased papillary muscle (PM) traction force, yet there is no biomechanical evidence to support it.

Thus we aimed to evaluate the biomechanical relationship between prolapse and PM forces, leveraging advances in
ex vivo
simulation technology.

Methods:
We developed an
ex vivo
PM force transduction system
(Fig. A, B)
and a novel neochord length adjustment system
(Fig. C)
capable of modeling targeted prolapse without creating severe MR. Using unique models of bileaflet and posterior leaflet prolapse, we directly measured hemodynamics and forces, comparing optimally coapting (i.e., physiologic) and prolapsing valves.

Results:
Throughout the experiments, hemodynamics and MR severity remained comparable between the physiologic and prolapse conditions. We found that bileaflet prolapse in this experimental setting increases PM forces by 5-15%
(p<0.001)
compared to a physiologic valve. We furthermore observed fundamental differences in the force profiles for prolapsing valves with higher primary peaks
(Fig. D)
. In the isolated posterior leaflet prolapse condition, prolapsing valves had significantly higher primary peak forces (
p=0.044
), with a strong trend towards higher overall PM force magnitudes
(p=0.051
), when compared to physiologic valves.

Conclusions:
Through advances in
ex vivo
heart simulation technology, we discovered that bileaflet prolapse, with MR similar to the physiologic valve, results in significantly elevated forces and altered dynamics on the PMs. Our work carries deeper implications, suggesting that interventions might reduce abnormal PM forces (and subsequent ventricular effects of MVP) in addition to MR correction, with possible benefit even in less-than-severe MR.
Abstract 11336: Optimized Machine Learning Models by Identification of Candidate Predictors for 30-Day Readmission Risk Prediction Among Patients Hospitalized for Acute Myocardial Infarction
Authors: Thiriveedi Likhita Sree , Ricket Iben , Brown Jeremiah R
Published: June 2023

Introduction:
Acute myocardial infarction (AMI) is a leading cause of death in the US. More than 800,000 adults experience an AMI each year, and up to 20% of the patients are rehospitalized within 30 days. Predicting 30-day readmission accurately could help clinicians identify high-risk patients and tailor treatment accordingly.

Hypothesis:
The neural network will generate the best performing model for predicting 30-day readmissions following an AMI.

Methods:
The cohort included adults hospitalized with incident AMI (6,506) at Dartmouth Hitchcock Medical Center between 2011-2016. Patients who died before discharge (236) were excluded, leaving 6,270 patients. Our outcome was 30-day hospital readmissions. Candidate features were selected using an Extra Tree Classifier. Selected features included demographics and clinical characteristics. Multiple imputation using K-Nearest Neighbors was performed. Five machine learning models were implemented: logistic regression, LASSO, neural network, random forest, and XGBoost. Models were evaluated on a hold-out test-set, using AUROC.

Results:
Among the cohort, about 36% were female, the majority were white and non-Hispanic, and the 30-day readmission rate was 6.2%. Neural network was the best performing model with an AUROC of 0.80 (95% CI: 0.75, 0.84). However, the XGBoost and random forest models performed similarly with AUROCs of 0.80 (95% CI: 0.76, 0.85) and 0.79 (95% CI: 0.75, 0.84), respectively. The logistic regression and LASSO models performed poorly, with AUROCs below 0.5, respectively. Important predictor variables were major depression, race, and antidepressant at discharge.

Conclusions:
Neural network, random forest, and XGBoost models predicted 30-day readmission following an AMI with good performance. Across these models, depression was an important feature for predicting 30-day readmissions. Results reinforce the importance of mental health among patients hospitalized for AMI.
Abstract 11376: Catheter-Injectable Hydrogel for the Delivery of a Minicircle Encoding SDF-la as Therapy for Myocardial Infarction
Authors: Navarro Renato S , de Paiva Narciso Narelli , Gilchrist Aidan , Suhar Riley A , Heilshorn Sarah C
Published: June 2023

Myocardial infarction (
MI
) is a leading cause of cardiovascular disease in the U.S. and abroad. Transient delivery of stromal cell-derived factor 1 (
SDF-1
α
) either through the delivery of protein-encoding genes or the protein itself has demonstrated improved cardiac function in preclinical models. However, the delivery of the therapy suffers from two limitations: (1) poor retention when injected into the contracting myocardium, and (2) rapid degradation of the protein, which requires prolonged activity to be therapeutically effective. To mitigate these limitations, we developed a catheter-injectable gel to deliver
SDF-1
α
encoding minicircles (
MC
). Design of gels for injection into the myocardium is historically challenging since traditional chemical strategies result in gels that are either too stiff and not catheter injectable or too weak and quickly ejected out of the contracting heart muscle. To address this challenge, our approach is to use dynamic covalent chemical (DCC) bonds, which are mechanically strong yet reversible, resulting in a shear-thinning gel (hence catheter injectable) and self-healing (hence retained in the contracting heart muscle). This biocompatible gel is chemically defined for future FDA approval and is synthesized from completely biodegradable polymers: recombinant elastin-like protein and hyaluronic acid. Rheological characterization identified several gel formulations that were easily extruded through a catheter (2 m long and .25 mm internal diameter) and rapidly reformed into a gel within 5 seconds after extrusion. To demonstrate the potential for clinical translatability, we evaluated the injectability and retention of the gel within the contracting rat myocardium. Our gel significantly improved the retention of a microparticle cargo by 200% compared to delivery in Matrigel. Current work is focused on evaluating the therapeutic efficacy of the gel in a rat myocardial infarct model when delivering a therapeutic cargo of SDF-1a-encoding MC. This biocompatible, catheter-injectable gel has great potential to significantly improve the delivery and retention of therapeutic cargo within mechanically active tissues, significantly improving the prolonged efficacy of MI therapies.
Abstract 11377: Takotsubo Syndrome Among Patients With Spontaneous Coronary Artery Dissection: A Report of the ISCAD Registry
Authors: Chi Gerald , Kim Esther S , naderi sahar , Leon Katherine , Gibson C M , Grodzinsky Anna , Gornik Heather L , Wells Bryan , Lewey Jennifer , Taylor Angela , Kadian Dodov Daniella , Hess Connie N , Henkin Stanislav , Lindley Kathryn , Wells Gretchen L , Orford James L , Tam Lori M , Kumbhani Dharam J , Norris Samuel , Reyes Cassandra , Alkhalfan Fahad , Vitarello Clara , Wood Malissa
Published: June 2023

Introduction:
Association of takotsubo syndrome (TTS) with spontaneous coronary artery dissection (SCAD) has been described previously. Characteristics and in-hospital prognosis of SCAD patients with concomitant TTS remain unclear.

Methods:
Patients with angiography-confirmed SCAD were selected from the iSCAD Registry and underwent core lab adjudication of left ventriculography (LVG) and coronary angiography including assessment of SCAD lesion characteristics, TIMI Flow Grade (TFG), and TIMI Myocardial Perfusion Grade (TMPG). Classic TTS was defined as wall motion abnormality (WMA) presenting as apical ballooning. TTS variants were defined as non-apical WMA discordant to dissected coronary territory with apical sparing. In-hospital event was defined as composite of recurrent myocardial infarction (MI), cerebrovascular accident, heart failure requiring diuretics, or new arrhythmia.

Results:
On blinded review of LVG from 216 patients, TTS was identified in 38 (17.6%) patients (classic, midventricular, and focal pattern: 86.8%, 2.6%, and 10.5%, respectively). There was no significant difference in age, cardiovascular risk factors, history of anxiety or depression, recreational substance use, emotional or physical stressors, extracoronary vascular abnormalities, peak troponin levels, or TFG of dissected arteries between TTS and non-TTS groups. TTS patients were more likely to present with ST-segment elevation MI (47.4% vs 27.5%; p=0.02), left anterior descending artery (LAD) involvement (89.5% vs 59.0%; p=0.0004), and TMPG < 3 (68.4% vs 48.3%; p=0.02) compared to non-TTS patients. TTS patients had a greater risk of in-hospital events (32.4% vs 15.1%; p=0.01), mainly attributed to new arrhythmia (27.0% vs 6.5%; p=0.0009) and heart failure (11.4% vs 3.0%; p=0.03).

Conclusion:
Coexistence of TTS and SCAD was associated with ST-elevation MI, LAD involvement, impaired microvascular myocardial perfusion, and adverse in-hospital outcomes.
Abstract 11411: Anti-MiR-510-3p Alleviates Endothelial Dysfunction in Preeclampsia Induced Rat Model B\by Regulating PTEN and Its Signalling Pathways
Authors: Selvakumar Sushmaa Chandralekha , K Auxzilia Preethi , Sekar Durairaj
Published: June 2023

Introduction:
Preeclampsia (PE) is a pregnancy complication associated with multi-organ endothelial dysfunction. The hypoxia resulting from vascular remodelling lowers blood flow in placenta leading to high mortality and morbidity in PE. Studies on molecular and signalling pathways involved in PE could pave way for early diagnosis and treatment. miRNAs are crucial regulators of gene expression in various diseases including PE. Our previous studies reported high expression of miR-510 in PE patients compared to normal.

Hypothesis:
We hypothesize that miR-510-3p targets PTEN in regulation of PI3K/AKT/eNOS/mTOR axis in PE and miR-510-3p could be a potential biomarker and therapeutic target. We elucidate the therapeutic role of antimiR-510-3p in PE and its interaction with miR-510-3p and associated signalling pathways in PE induced rat model.
Methodology:
The proliferation, migration, invasion and apoptosis of HTR/SVNeo cells were analyzed for miR-510-3p, PTEN and antimiR-510-3p. Luciferase assay confirmed PTEN as target for miR-510-3p. The expression of miR-510-3p and PTEN/PI3K/AKT/eNOS/mTOR axis was analysed using qPCR and western blot. Deoxycorticosterone (DOCA) (12.5 mg/kg before mating and 6.5 mg/kg after mating twice a week) and 0.9% salt ad libitum were used to develop a PE induced rat model (SD rats). By quantifying miR-510-3p levels in PE group, the doses of antimiR-510-3p for the dose-dependent study were determined. The final effective dose was fixed from the dose-response curve. To examine the hypoxia and hypertrophy, histological analysis was performed in paraformaldehyde fixed tissues.

Results:
Significant changes were observed in the BP, proteinuria and other biochemical parameters between PE and control rats. Our results suggest that miR-510-3p targets PTEN leading to endothelial dysfunction, hypoxia and hypertrophy in PE, while treatment with antimiR-510-3p exhibits a significant reduction in PE in PE induced rat model. The gene and protein expression analysis revealed a significant correlation between miR-510-3p, PTEN and antimiR-510-3p in PE.

Conclusion:
Thus our findings from
in vitro
and
in vivo
suggest miR-510-3p as a potential biomarker and therapeutic target and antimiR-510-3p as a novel therapeutic molecule for PE.
Abstract 11412: Use of Guideline-Directed Medical Therapies After Hospitalization for Heart Failure: Real-World Insights From EVOLUTION HF
Authors: Bozkurt Biykem , Savarese Gianluigi , Adamsson Eryd Samuel , Bodegard Johan , Khordoc Cindy , Thuresson Marcus , Vardeny Orly , Kishi Takuya , Lund Lars H
Published: June 2023

Introduction:
In the period after hospitalization for heart failure (hHF), patients are at high risk of cardiovascular death and rehospitalization. Guidelines for heart failure with reduced ejection fraction (HFrEF) emphasize early initiation of four guideline-directed medical therapies (GDMTs: beta-blocker, renin-angiotensin system inhibitors [RASis] or angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter-2 inhibitors [SGLT2is]). However, real-world data on the concurrent use of these four GDMTs are scarce, particularly after hHF.

Methods:
EVOLUTION HF is an observational, longitudinal cohort study using claims and electronic health record databases to assess the use of GDMTs in patients with a recorded hHF. We report KM estimates of initiation of GDMTs in the 3 months following an incident hHF (index date) with no prior HF diagnosis. Use of GDMTs in the month before the index hHF (e.g. RASis for hypertension) was counted as use at index. The study period started after approval of the first SGLT2i (dapagliflozin) for HFrEF in each country.

Results:
Overall, 49 807 patients were included. Ejection fraction was not recorded for most patients. Mean KM estimates for use of four GDMTs at 1 and 3 months post hHF discharge were 6.5% and 7.8% (Japan), 8.0% and 11.7% (Sweden), and 0.9% and 1.7% (USA), increasing with each consecutive calendar quarter (Figure). This trend was largely explained by an increase in SGLT2i use. In the first and last quarter of each study period, KM estimates of SGLT2i use at 3 months were 15.3% and 21.2% (Japan), 7.2% and 32.6% (Sweden), and 2.3% and 4.8% (USA).

Conclusions:
Uptake of four GDMTs remains low, highlighting an urgent need for earlier and increased GDMT initiation to manage severe risks, especially in the vulnerable post-hHF period. Data on SGLT2i benefits have led to a slow yet steady increase in SGLT2i early use post hHF as part of a four-GDMT approach to treating HF.
Abstract 11441: Triplane Left Atrial Strain
Authors: Hernandez del Rio Jorge Eduardo , Miranda - Aquino Tomas , MACHUCA HERNANDEZ MICHEL , CEPEDA ROCHA MARIA , HERRERA MENDEZ SERGIO , Esturau Ramon , Gonzalez Padilla Christian
Published: June 2023

The objective was to compare the percentage of myocardial deformation of the left atrium evaluated by monoplanar, biplanar and triplanar measurement. A total of 126 healthy patients were collected, of which 71 (56%) were male, the mean age of the population was 38 years (±16). Intraobserver and interobserver variability were adequate.The different values of the left atrium were compared. For the reservoir strain, only a significant difference was found between the apical 3-chamber and apical 2-chamber values reported; in pump strain there were no significant differences in values obtained; for the conduit strain, again the apical 3-chamber view was the lowest, finding a significant difference with the apical 4c, apical 2c and biplane views.The concordance of the reservoir strain of each apical view was independently related to the biplane and triplane views, finding that both apical 2c and 4c views had a good concordance with both biplane and triplane views, however, apical 3c view had a lower concordance. The same was found for pump strain and conduit strain, being Apical 2c and 4c views superior.

Conclusion:
The 3-chamber view has different left atrial strain values than the other apical views and the concordance of all other values of left atrium examination are similar, hence it is not further significant to perform a biplane or triplane examination.
Abstract 11451: Myocardial Neprilysin Expression in Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: Armstrong David W , Su Yan Ru , Shah Ashish S , Absi Tarek , Gupta Deepak K , Wells Quinn , Brinkley D. M , Stevenson Lynne W , Merryman W. David
Published: June 2023

Introduction:
Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and fibrosis, the underlying mechanisms of which remain poorly understood. Neprilysin (NEP) inhibition has been shown to attenuate hypertrophy and fibrosis in animal models of heart failure, and NEP inhibition is an established therapeutic target in dilated and ischemic cardiomyopathy. However, the myocardial expression of NEP in HCM has not been previously reported.

Hypothesis:
The expression of NEP is increased in patients with obstructive HCM (oHCM).

Methods/Results:
We analyzed publicly available gene expression data from two independent cohorts that used myectomy samples from patients with oHCM, and healthy unused donor hearts served as controls. Cohort #1 (NCBI GEO accession number GSE36961) included 107 patients with oHCM and 39 controls and used microarray to assess gene expression. Cohort #2 (NCBI GEO accession number GSE160997) included 18 patients with oHCM and 5 controls and used RNA-Seq to assess gene expression. Both cohorts showed NEP gene expression was significantly increased in oHCM compared to controls (P<0.0001 and P<0.001, respectively). We then examined NEP expression in our surgical cohort (#3), which included 40 patients with oHCM and 8 controls. Using qPCR we showed NEP gene expression was significantly elevated in oHCM compared to controls (P<0.001, see Figure 1).

Conclusions:
Myocardial NEP gene expression is significantly increased in patients with oHCM undergoing septal myectomy. Future studies are needed to determine if increased myocardial NEP gene expression is accompanied by elevated NEP protein expression and/or activity. Furthermore, future studies are required to determine the mechanism of increased NEP, and whether these findings extend to HCM patients who have not progressed to symptomatic obstruction.
Abstract 11452: EHR-Based Machine Learning Model Predicts Drug-Induced QT Prolongation With Superior Performance Compared to Clinical Risk Predictors
Authors: Jing Linyuan , Morland Thomas , Kelsey Christopher , Raghunath Sushravya , Pfeifer John , Ruhl Jeffrey , Fornwalt Brandon , Haggerty Christopher M
Published: June 2023

Introduction:
Many medications are associated with QTc prolongation (LQT). Current LQT predictors, including Tisdale and RISQ-PATH, have limited utility due to lack of generalizability to key use cases and modest model performance. A highly accurate LQT risk predictor utilizing data often available at the time of drug starts could broadly support LQT risk management.

Hypothesis:
An electronic health record (EHR)-based machine learning (ML) model is superior in predicting drug-induced LQT in a clinical population vs. Tisdale and RISQ-PATH.

Methods:
We identified all patients who began taking QT-prolonging medications (‘QTdrug’, per CredibleMeds) at Geisinger and had a follow-up 12-lead ECG within 1 year of medication start date while still on the drug. In case of multiple QTdrugs with overlapping dates, the last start date was used. Using 5-fold cross-validation, we trained an XGBoost ML model to predict LQT (QTc >500 ms) within 1 year of QTdrug start date using EHR data as input, including 131 features across age, sex, smoking history, vitals, lab tests, comorbidities, baseline ECG metrics (within 3 years before drug start date) and QTdrug usage (ever on QTdrug, number of current QTdrugs).

Results:
QTdrug records were identified for 362,086 patients, and 6% had LQT within 1 year. The ML model demonstrated superior performance (Figure A) in predicting LQT (area under the curve (AUROC): 0.86, average precision score (AUPRC): 0.41) compared to RISQ-PATH (AUROC: 0.70, AUPRC: 0.19) and Tisdale (AUROC: 0.76, AUPRC: 0.21, calculated in a hospitalized subset N=113544). At the same specificity as RISQ-PATH (98%), the ML model had higher sensitivity (30% vs 10%) and positive predictive value (55% vs 29%). Similar comparisons were observed for Tisdale (Figure B).

Conclusions:
An EHR-based ML model outperforms commonly used risk calculators for predicting drug-induced LQT. This model can be used to stratify patients by risk of developing drug-induced LQT in a clinical setting.
Abstract 11460: Sleep Duration, Quality, and Risk of Peripheral Artery Disease: Multinational Cohort and Mendelian Randomization Studies
Authors: Yuan Shuai , Levin Michael G , Titova Olga , Chen Jie , Sun Yuhao ,   VA Million Veteran Program, Akesson Agneta , Li Xue , Damrauer Scott M , Larsson Susanna
Published: June 2023

Introduction:
Sleep duration and quality have been linked to atherosclerosis, however the effects on peripheral artery disease (PAD) specifically have not been well characterized. We conducted cohort, case-control, and Mendelian randomization analyses across three large multinational samples (Sweden, United Kingdom, United States) to evaluate associations between sleep traits and risk of PAD.

Hypothesis:
Abnormal sleep duration and poor sleep quality are associated with increased risk of PAD.

Methods:
Sleep traits (including duration, subjective quality, daytime napping, snoring, apnea, and insomnia) were assessed for associations with incident PAD using Cox proportional hazards regression within a cohort of 53,416 Swedish adults. Replication was sought in a case-control study of 28,123 PAD cases and 128,459 controls from the VA Million Veteran Program (MVP) and a cohort study of 452,028 individuals from the UK Biobank (UKB). Two-sample Mendelian randomization (MR) was used to estimate causal effects of sleep-related traits on PAD (31,307 PAD cases 211,753 controls).

Results:
Observational analyses demonstrated a U-shaped association between sleep duration and PAD risk. In Swedish adults, incident PAD risk was higher in those with short sleep (<5 hours; hazard ratio (HR) 1.74; 95% confidence interval (CI) 1.31-2.31) or long sleep (≥8 hours; HR 1.24; 95% CI 1.08-1.43), compared to individuals with a sleep duration of 7 to <8 hours/night. This finding was supported by case-control analysis in MVP and cohort analysis in UKB. Observational analysis also revealed positive associations between poor sleep quality (HR 1.81; 95% CI 1.13-2.90) and daytime napping (HR 1.32; 95% CI 1.18-1.49) with PAD. MR analysis supported an inverse association between sleep duration (odds ratio per hour increase, 0.79, 95% CI, 0.55, 0.89) and PAD, and an association between short sleep and increased PAD (odds ratio, 1.20, 95% CI, 1.04-1.38). MR also found an association between insomnia with PAD (OR 1.10; 95% CI 1.05-1.15) and a reverse association of PAD on shorter sleep (OR 1.05; 95% CI 1.01-1.10).

Conclusions:
Short sleep duration and measures of poor sleep quality may be causal risk factors for PAD. Maintenance of healthy sleep habits may help prevent PAD.
Abstract 11461: The Hemodynamic Gain Index is an Independent Predictor of Adverse Outcomes, and Comparable to Peak Oxygen Consumption in Patients With Chronic Heart Failure With Reduced Ejection Fraction
Authors: Chaikijurajai Thanat , Engelman Timothy , Wu Yuping , Finet J. Emanuel , Morales Oyarvide Vicente , Grodin Justin L , Tang Wai Hong W
Published: June 2023

Introduction:
The hemodynamic gain index (HGI) is a novel simple parameter calculated from resting and peak systolic BP (SBP) and heart rate (HR) during exercise testing. It is a predictor of mortality in population-based cohorts. However, the prognostic significance of the HGI in chronic HFrEF has not been well studied.

Hypothesis:
The HGI is independently associated with adverse outcomes, and is comparable to other cardiopulmonary exercise testing (CPET) parameters.

Methods:
Medical records of 1,067 consecutive HFrEF patients (EF ≤ 40%) undergoing CPET for symptom evaluation from 12/2012 to 9/2020 were reviewed. HGI was calculated using the formula, [(SBP
peak
x HR
peak
)-(SBP
rest
x HR
rest
)]/(SBP
rest
x HR
rest
). Patients with missing vital signs, hypotensive or bradycardic response to exercise were excluded. Primary outcome was the composite endpoint of all-cause mortality, LVAD implantation, and heart transplantation. Multivariable Cox proportional hazard models were used with subgroup analyses based on median age, sex, BMI of 35 kg/m
2
, respiratory exchange ratio (RER) of 1.05, and beta-blocker use. ROC curves with AUCs were used to compare HGI, peak VO
2
, VE/VCO
2
slope and peak end-tidal pressure of CO
2
(PEtCO
2
).

Results:
We included 954 HFrEF patients (mean age was 56.3 ± 12.0 years, 72% men, 17% with BMI ≥ 35 kg/m
2
, 86% on beta-blockers, and 73% with RER > 1.05). During a median follow up time of 946 days, the incidence of the composite outcome was 331 (34.7%). After adjustment for age, sex, BMI, comorbidities, and EF, higher HGI was independently associated with lower risk of the adverse outcomes in the main cohort (hazard ratio per unit increase 0.46, 95%CI 0.35 to 0.59,
p
< 0.001), and all subgroups, except for patients with BMI ≥ 35 kg/m
2
(
Figure 1A
). The HGI was also comparable to peak VO
2
, and outperformed VE/VCO
2
slope and PEtCO
2
(
Figure 1B
).

Conclusions:
The HGI is an independent predictor of adverse outcomes, and comparable to peak VO
2
in patients with chronic HFrEF.
Abstract 11473: An EHR-Based Machine Learning Model Predicts Myocardial Infarction Better Than an ECG-Based Machine Learning Model and the Pooled Cohort Equations
Authors: Jing Linyuan , Pfeifer John , Kang Martin , Hartzel Dustin , Raghunath Sushravya , Fornwalt Brandon , Haggerty Christopher M
Published: June 2023

Introduction:
Patients at high risk for myocardial infarction (MI) benefit from treatments designed for primary prevention, especially cholesterol lowering therapy. The pooled cohort equations (PCE) are the most commonly used risk predictor for future MI but show only modest performance.

Hypothesis:
Electronic health record (EHR)-based, and ECG-based machine learning models are better at predicting MI as compared toPCE.

Methods:
We retrospectively included all patients (age 40-79) with clinical encounters in Geisinger, having at least 1 clinically acquired ECG and no prior history of MI. Incident MI within 10 years of an index ECG was identified. The ability of 2 machine learning models to predict MI were compared to the PCE: 1) an XGBoost model with EHR data (age, sex, race, smoking history, vitals, 24 lab tests) as input features; and 2) a deep neural network (DNN) that used ECG traces, age, and sex as inputs. Models were compared based on area under the receiver operating characteristic curve (AUROC).

Results:
A total of 103,933 ECGs from 34,932 patients had sufficient follow-up, 21% of ECGs were followed by an MI event within 10 years. The EHR-based XGBoost model had the best performance (AUROC 81%) in comparison with both the ECG-based DNN model (AUROC 68%) and the PCE (AUROC 72%). 9% of the total encounters were predicted to be ‘high risk’ by the EHR-based model and not by the pooled cohort equations. In that subgroup, 60% of patients were not on a statin and the 10-year MI event rate was 26%. 20% of encounters were predicted to be ‘high risk’ by the PCE and not by the EHR-based model. The event rate in that subgroup was 12%.

Conclusions:
An EHR-based XGBoost model, but not an ECG-based DNN, is superior to the PCE in predicting future MI. Patients identified as high risk by the EHR-based model but missed by the PCE, have a high rate of future MI. Statin use in that group is low, suggesting ample opportunity for intervention.
Abstract 11494: Electrophysiological Effects of Sympathoexcitation are Mitigated by Blockade of Neuropeptide Y Y2 Receptors on Cardiac Parasympathetic Nerve Terminals
Authors: Van Weperen Valerie Y , Hoang Jonathan D , Jani Neil R , Lokhandwala Zulfiqar A , Emamimeybodi Maryam , Chan Christopher A , Swid Mohammed A , Vaseghi Marmar
Published: June 2023

Introduction:
Sympathetic activation releases both norepinephrine and co-transmitter neuropeptide Y (NPY). NPY can predispose to ventricular arrhythmias via receptors on cardiomyocytes. Ex vivo studies suggest that NPY may concomitantly reduce vagal tone via activation of NPY Y2 receptors (Y2R) on parasympathetic nerves, reducing acetylcholine release and further augmenting pro-arrhythmic sympathetic effects. We evaluated if parasympathetic Y2R blockade can prevent NPY-induced vagal inhibition, restore autonomic balance and stabilize cardiac electrophysiology.

Methods:
Yorkshire pigs (n = 12) underwent bilateral stellate ganglia stimulation (BSGS; 10 Hz, 4 ms) for 45 secs, before and after administration of selective Y2R antagonist BIIE0246 (BIIE; 32 nmol/kg bolus + 2 nmol/kg/min infusion). Hemodynamic and electrophysiological recordings were obtained with a left ventricular pressure (LVP) catheter, surface electrogram and a 56-electrode sock placed over the ventricles to measure activation recovery intervals (ARI), a surrogate of local action potential duration, from unipolar electrograms. Heart rate variability parameters, including low to high frequency ratio (LF/HF), were analyzed pre- and post-BIIE.

Results:
BSGS significantly increased heart rate (HR) and LVP, and shortened ventricular ARIs. BIIE significantly reduced both the rate of change and the maximal changes in HR and ARIs during BSGS. As anticipated, BSGS significantly increased LF/HF ratio, but this effect was abolished after BIIE. BIIE did not affect BSGS related increases in LVP.

Conclusions:
Cardiac effects of sympathetic activation are mediated, at least in part, by suppression of vagal tone through binding of NPY to parasympathetic Y2Rs. Blockade of this receptor partially counters pro-arrhythmic electrophysiological effects of BSGS and suggests a possible novel adjuvant role for Y2R blockade as a therapy for reducing consequences of sympatho-excitation.
Abstract 11496: Radial Access for Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From the PROGRESS-CTO Registry
Authors: Simsek Bahadir , Gorgulu Sevket , Kostantinis Spyridon , Karacsonyi Judit , Alaswad Khaldoon , Reddy Niranjan , Jaffer Farouc A , Doshi Darshan , Khatri Jaikirshan , Young Laura , Poommipanit Paul , GOKTEKIN OMER , Krestyaninov Oleg , Davies Rhian , El Guindy Ahmed , Kerrigan Jimmy , PATEL MITUL P , Elbarouni Basem , Rinfret Stephane , Jaber Wissam , Nicholson William , Dattilo Philip , Abi Rafeh, MD, FACC Nidal , Rangan Bavana V , Mastrodemos Olga , Allana Salman S , Burke M Nicholas , KUTUZIS MICHAEL , Brilakis Emmanouil S
Published: June 2023

Introduction:
Use of radial access for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has been increasing.

Methods:
We examined the clinical characteristics and procedural outcomes of patients who underwent CTO PCI with radial versus femoral access in the Prospective Global Registry for the Study of CTO Intervention (PROGRESS-CTO, NCT02061436).

Results:
Of 10,954 patients who underwent CTO PCI at 55 centers in 7 countries between 2012 and 2022, 2,578 (24%) had a radial-only approach. Patients who underwent radial-only access were younger (63 ± 10 vs. 65 ± 10, years, p<0.001), more likely to be men (84% vs. 81%, p=0.001), and had a significantly lower prevalence of comorbidities compared with the femoral group, including diabetes mellitus (39% vs. 45%, p<0.001) and coronary artery bypass graft surgery (57% vs. 64%, p<0.001). In addition, radial-only cases had lower angiographic complexity with lower J-CTO (2.0 ± 1.3 vs. 2.5 ± 1.2, p<0.001) and PROGRESS-CTO (1.2 ± 1.0 vs. 1.3 ± 1.0, p<0.001) scores. After adjusting for potential confounders, radial-only access was associated with a lower risk of access site complications (odds ratio [OR]: 0.45, 95% confidence interval [CI], 0.22-0.91), similar technical success (OR: 0.87, 95% CI, 0.74-1.04) and major adverse cardiovascular events (MACE) (OR: 0.65, 95% CI, 0.40-1.07), compared with the femoral access group (Figure 1).

Conclusions:
Radial-only access was used in 24% of CTO PCIs and was associated with lower access site complications, and similar technical success and MACE compared with the femoral access group.
Abstract 11522: Impact of Chronic Glucagon-Like Peptide-1 Receptor Agonist and Sodium Glucose Cotransporter-2 Inhibitor Therapy on In-Hospital Outcomes of Patients Hospitalized With Acute Myocardial Infarction
Authors: Trombara Filippo , Cosentino Nicola , Genovese Stefano , Bonomi alice , ludergnani monica , Poggio Paolo , Agostoni Piergiuseppe , Marenzi Giancarlo
Published: June 2023

Introduction:
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated cardiovascular and renal protection in addition to their glucose-lowering effect. Whether their benefits occur also in patients with diabetes mellitus (DM) during hospitalization with acute myocardial infarction (AMI) has not been investigated yet.

Methods:
We evaluated in-hospital outcomes of patients hospitalized with AMI according to their chronic use (before hospitalization) of GLP-1 RA and SGLT-2i therapy. Using administrative healthcare databases, we analyzed patients hospitalized with a primary diagnosis of AMI from 2010 to 2019 in the Lombardy region, Italy. Patients were stratified according to their DM status, then divided into three cohorts: Group 1 (non-DM patients); Group 2 (DM patients taking GLP-1 RA or SGLT-2i); and Group 3 (DM patients not taking GLP-1 RA and/or SGLT-2i). Patients were matched in a 1:1:1 ratio using a propensity score including all available variables. The primary endpoint of the study was the composite of in-hospital mortality, acute heart failure, and acute kidney injury requiring renal replacement therapy.

Results:
We identified 146,800 patients hospitalized with AMI (26% of them with DM). After propensity score matching, 1,030 patients were included in each group. The primary endpoint rate in the overall population was 16% (n=502) and it significantly increased going from Group 1 to Group 3 (13%, 16%, and 20% respectively; p for trend <0.0001). The risk of the composite endpoint significantly increased from Group 1 to Group 3 (P for trend <0.0001). In comparison with Group 2, Group 3 had a significant higher risk of the composite endpoint (OR 1.40 [95% CI 1.11-1.77]).

Conclusions:
Our study shows that DM patients hospitalized with AMI and on chronic GLP-1 RA and/or SGLT-2i therapy have a better in-hospital clinical outcome than DM patients without them.
Abstract 11529: Sociodemographic and Clinical Variables Predict Acute Coronary Syndrome Symptom Knowledge, Attitudes, abd Beliefs in Adults Without Diagnosed Heart Disease
Authors: Blakeman John R , Kim MyoungJin , Prasun Marilyn A
Published: June 2023

Introduction:
Little research has focused on the acute coronary syndrome (ACS) symptom knowledge, attitudes, and beliefs of younger individuals and those without diagnosed heart disease, even though most ACS events are first-time events, and ACS rates are increasing in the young.
Purpose:
To identify predictors of ACS symptom knowledge, attitudes, and beliefs in younger people without diagnosed heart disease.

Methods:
Participants were recruited from social media platforms in fall 2020 and completed an online survey including the ACS Response Index instrument. Multiple linear regressions were run to model ACS symptom knowledge, attitudes, and beliefs as a function of selected demographic and clinical variables that have documented or theoretical importance.

Results:
A typical participant from the sample (n=765) was 36.4 years old (SD = 16.7), a woman (n=573; 74.9%), white (n=686; 89.7%), and non-Hispanic/Latino (n=706; 92.3%). Hispanic/Latino participants had lower ACS symptom knowledge and attitude scores than non-Hispanic/Latino participants, (β = -.26,
t
(757) = -7.79,
p
= .000; β = -1.32,
t
(755) = -2.86,
p
= .000, respectively), and white participants had substantially higher ACS symptom attitude scores than non-white, (β = 1.21,
t
(755) = 3.35,
p
= .001). Men had lower knowledge scores than women, (β = -6.48,
t
(757) = -4.41,
p
= .000). Additionally, participants who reported being taught by a healthcare professional about signs and symptoms of ACS had substantially higher symptom knowledge and attitude scores compared to those who had not, (β = 3.70,
t
(757) = 3.01,
p
= .003; β = 2.15,
t
(755) = 11.68,
p
= .000, respectively) and so did those who reported exposure to information about these symptoms in the media compared to those who did not, (β = 6.68,
t
(757) = 4.37,
p
= .003; β = 1.07,
t
(755) = 4.58,
p
= .000, respectively). Other variables, such as use of avoidance coping, self-perceived risk of heart disease, nicotine use, and self-perceived health, also predicted knowledge, attitude, and/or belief scores.

Conclusions:
Gender, race, and previous exposure to information about ACS symptoms were particularly important predictors of ACS symptom knowledge and attitudes, though others were significant. Additional research is needed in more diverse samples.
Abstract 11573: Refractory Ventricular Tachyardia Storm: Treatment With Sympathetic Denervation in Patient With Non-Ischemic Cardiomyopathy
Authors: Salam Mohammad Fahad , Martinez Salazar Adolfo , Jamal Shakeel , Al-abcha Abdullah , Radwan Yasser , Sheikh Ali
Published: June 2023

Introduction:
Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia commonly present in cardiomyopathy. Implantable cardioverter-defibrillator (ICD) placement can decrease mortality in patients with VT. However, when an ICD shocks it can cause direct myocardial injury, contraction band necrosis, fibrosis, and significant morbidity. Antiarrhythmic medications and catheter ablation can decrease arrhythmia burden and ICD shocks. Cardiac sympathetic denervation has been effective in a few refractory cases, but prospective data is scarce, especially in non-ischemic cardiomyopathy.

Case description
We present the case of a 59-year-old gentleman with a past medical history of hypertension, diabetes, hypothyroidism, atrial fibrillation, and non-ischemic cardiomyopathy, who presented to the hospital with recurrent ICD shocks. The patient had an ICD placed due to an episode of non-sustained VT resulting in presyncope. The patient had an arrhythmia-free period of 10 years followed by frequent VT. He was managed in the outpatient setting with amiodarone, dofetilide, and mexiletine which did not suppress his arrhythmia burden. Cardiac MRI showed multi-segment transmural late gadolinium enhancement consistent with a non-ischemic pattern. He underwent three endocardial and epicardial ablations over eight months before this admission. He was started on amiodarone and lidocaine infusions. With his history of recurrent VT despite multiple ablations, the patient underwent bilateral thoracoscopic sympathetic denervation. He was discharged from the hospital six days post-op without any episodes of VT. His latest ICD check which was ten months post-operatively did not show any VT or VT-induced ICD shock.

Conclusion
VT storm may be associated with a catecholaminergic surge and be refractory to traditional therapy. Due to this, sympathetic denervation is a viable option to prevent morbidity of frequent defibrillator therapy. This case highlights the utility of sympathetic denervation as a treatment of refractory ventricular arrhythmias in non-ischemic cardiomyopathy.
Abstract 11618: Angiopoietin-2 is Associated With Capillary Leak and Complications After Cardiac Surgery
Authors: Wollborn Jakob , Zhang Zilu , Justice Samuel , Reker Daniel , Muehlschlegel J Daniel , Goebel Ulrich , Ulbrich Felix
Published: June 2023

Introduction:
Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation.

Hypothesis:
Markers of endothelial injury and inflammation are associated with capillary leak (CLS), ultimately increasing the risk of perioperative complications.

Methods:
In a prospective, observational trial 405 cardiac surgery patients were evaluated using daily body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of biomarkers. Multivariable models and machine learning (ML) were used to study the association of angiopoietin-2 (Ang-2) with extracellular water (ECW) as well as common complications after cardiac surgery.

Results:
Across all surgical groups, ECW increased postoperatively (20±6 preoperatively to 29±7L on POD2;
P
<0.001). Concomitantly, the levels of Ang-2 rose, showing a strong correlation based on the time points of measurements (r=0.959,
P
=0.041). Inflammatory (IL-6, IL-8, CRP) and endothelial biomarkers (VE-Cadherin, syndecan-1, ICAM-1) suggestive of CLS were increased. After accounting for common risk factors of edema formation in cardiac surgery, we found a significant association of Ang-2 and ECW (Table 1). Furthermore, high Ang-2 patients showed an increased odds for developing acute kidney injury (OR 1.095 [1.032-1.169];
P
=0.004), and high Ang-2 was associated with delayed extubation, longer time in the ICU, and a higher chance of prolonged dependence on vasoactive medication. ML predicted postoperative complications well if CLS was added to standard risk factors.

Conclusions:
CLS is a relevant problem after cardiac surgery. Ang-2 in combination with ECW shows promising potential to reliably anticipate CLS and postoperative complications after cardiac surgery.
Abstract 11620: Time Course of Pericardial Effusion After Catheter-Free Ventricular Ablation With Proton Beam in Swine Normal Heart
Authors: Hirao Tatsuhiko , Imamura Kimitake , SUZUKI Atsushi , Rettmann Maryam E , Yasin Omar Z , Kowlgi N Gurukripa N , Hohmann Stephan , Konishi Hiroki , Otsuka Naoto , Packer Douglas L , Miller Alexa
Published: June 2023

Background:
Cardiac proton beam ablation therapy has emerged as a promising tool for catheter-free arrhythmia ablation. The time course of the lesion change was demonstrated in MRI 8 weeks following the ablation; however, the pericardial effusion after the ablation has not been fully analyzed.

Objective:
The purpose of this study was to evaluate the pericardial effusion after pencil-beam scanned proton therapy on normal myocardium in swine in MRI.

Methods:
32 domestic swine were irradiated with pencil-beam scanned proton therapy using irradiation doses of 30/40Gy to the left ventricle (LV) anterior wall, posterior wall, and apex. Each swine was subjected to monthly contrast-enhanced cardiac MRI to evaluate the post-irradiation effects.

Results:
Moderate to significant pericardial effusion (PE) was observed in 10 swine (31%), starting at 4 weeks, and increasing from 8-16 weeks until 24 weeks. With the exception of one case,, improvement was observed in all animals within a month from when the PE first became moderate or significant. . In the case where the significant PE did not improve, the PE was non-septic and transudate. Clinically, the PE did not cause cardiac tamponade and did not correlate to sudden death. Also, there was no correlation between animals with larger tissue volumes receiving higher dose (more than 20Gy) and the grade of PE .

Conclusion:
Proton beam radiation caused various grades of pericardial effusion, but in 90% of the animals, it resolved without intervention within a month with no major adverse events.
Abstract 11624: Family Income and Cardiovascular Disease Risk in American Adults
Authors: Minhas Abdul M , Jain Vardhmaan , Li Monica , Ariss Robert , Fudim Marat , Michos Erin D , Virani Salim S , Sperling Laurence , Mehta Anurag
Published: June 2023

Background:
Socioeconomic status is an often-overlooked risk factor for cardiovascular disease (CVD). Low family income is a measure of socioeconomic status and may portend worse CVD burden. Therefore, we assessed the association of family income with cardiovascular risk factor and disease burden in American adults.

Methods:
This retrospective analysis included data from participants aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Family income to poverty ratio (PIR) was calculated by dividing family (or individual) income by the poverty guidelines specific to the survey year and used as a measure of socioeconomic status. The association of PIR with the presence of cardiovascular risk factors and CVD as well as cardiac mortality and all-cause mortality was examined.

Results:
We included 35,932 unweighted participants corresponding to 207,073,472 weighted, nationally representative participants. Participants with lower PIR were often female and more likely to belong to race/ethnic minorities (non-Hispanic Black, Mexican American, other Hispanic). In addition, they were less likely to be married/living with a partner, to attain college graduation or higher, or to have health insurance. In the adjusted analysis, the prevalence odds of diabetes mellitus, hypertension, coronary artery disease (CAD), congestive heart failure (CHF), and stroke largely decreased in a step-wise manner from highest (≥5) to lowest PIR (<1) (Table 1). In the adjusted analysis, we also noted a mostly dose-dependent association of PIR with the risk of all-cause and cardiac mortality during a mean 5.7 and 5.8 years of follow up, respectively.

Conclusions:
Public policy efforts should be directed to alleviate these disparities to help improve cardiovascular outcomes in this vulnerable subgroup.
Abstract 11637: Myocardial Metabolic Dysregulation and Right Ventricular Outcomes After Surgery for Advanced Heart Failure
Authors: Ghadimi Kamrouz , Giamberardino Stephanie , Nguyen Maggie , Parikh Jhana , Schroder Jacob , Lorenzana-Saldivar Erick , Thompson Will , Rajagopal Sudarshan , Bryner Benjamin , Milano Carmelo A , Shah Svati H
Published: June 2023

Introduction:
Inhaled pulmonary vasodilators (iPVD) help prevent right heart failure (RHF) by lowering PVR after surgery. However, variable change in PVR is seen in response to iPVD. As metabolism is central to cardiomyocyte function, we evaluated the role of right ventricular (RV) myocardial metabolism in iPVD response heterogeneity.

Hypothesis:
We previously identified plasma metabolic biomarkers as potential reporters of response heterogeneity and posited here that these key metabolites change in parallel with changes in RV phenotypes.

Methods:
We evaluated 63 LVAD or heart transplant recipients with precapillary pulmonary hypertension before surgery from a recent randomized trial (INSPIRE-FLO, NCT03081052). All participants received iPVD after heart-lung bypass through postoperative day 1 (pod 1). Targeted profiling of > 500 metabolites (MxP® Quant 500, Biocrates) was performed in baseline and pod 1 plasma, and in RV free-wall full-thickness biopsies from LVAD recipients. Principal components analysis (PCA) was used for metabolite dimensionality reduction. Generalized linear models were used to assess the association of percent change (%Δ) in metabolite factors with (1) %Δ PVR (baseline to pod1); (2) responder, PVR < 3 Wood U vs. non-responder, PVR ≥ 3 Wood U, on pod 1); (3) RHF after surgery.

Results:
PCA identified 21 factors with 204 metabolites clustering in biologically consistent pathways. Of these, %Δ in factor 8 (glycine and eight glycerophospholipids, GPs) were positively correlated with %Δ PVR (P < 0.05). There was a trend for association in %Δ in factors 1 and 12 (ceramides, other GPs, amino acids: glutamate, aspartate, alanine, glutamine) and %Δ PVR (both P < 0.10, negatively correlated). There was a trend for association in %Δ in factor 7 (long chain acylcarnitines) and subsequent RHF (P = 0.08, positively correlated). No metabolites were associated with responder status. Plasma levels of select metabolites in factors 1 and 12 were positively correlated with RV myocardial levels (P < 0.05), suggesting a myocardial source.

Conclusions:
Leveraging a unique clinical trial cohort, we identified substrates of amino acid and fatty acid mitochondrial ß-oxidation metabolism in RV myocardium that may serve as biomarkers of metabolism in RHF.