bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12412: In Silico Evaluation of Dosing Regimens to Accommodate Coadministration of Mavacamten With Strong Inhibitors of Cytochrome P450 3A4 and Moderate Inhibitors of Cytochrome P450 2C19 in Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: Merali Samira , Bunn Haden , Sychterz Caroline , Chiang Manting , puli Shilpa , Sehnert Amy J , Murthy Bindu , Gobburu Joga
Published: December 2023

Background:
Mavacamten is primarily metabolized by cytochrome P450 enzymes CYP2C19 and CYP3A4 and coadministration with strong CYP3A4 or moderate CYP2C19 inhibitors is contraindicated in patients with obstructive hypertrophic cardiomyopathy (HCM) in the US prescribing information (USPI).

Aim:
To assess the safety and efficacy of accommodating coadministration of mavacamten with strong CYP3A4 and moderate CYP2C19 inhibitors via simulations.

Methods:
Simulations of 5000 virtual patients with obstructive HCM uniformly distributed by CYP2C19 metabolizer phenotypes were performed using population pharmacokinetic and pharmacodynamic models. The USPI posology and variations were simulated to evaluate if short term (1 week) and long term (chronic) coadministration of CYP3A4 or CYP2C19 inhibitors could be accommodated. Analogous to USPI posology development, comparisons were made by evaluating proportions of patients with left ventricular ejection fraction [LVEF] < 50% (safety) and Valsalva left ventricular outflow tract gradient [VLVOTg] < 30 mmHg (efficacy).

Results:
When initiating mavacamten with a CYP3A4 inhibitor, a posology using 2.5 mg starting dose, with coadministration stopped if LVEF < 50% at 2.5 mg, resulted in a similar peak proportion of CYP2C19 poor metabolizers with LVEF < 50% (5.7%) and LVEF < 40% (0.9%) compared to the USPI (2.7% and 0.3% respectively;
Table
). When initiating mavacamten with a CYP2C19 inhibitor, a 2.5 mg starting dose resulted in a similar peak proportion of LVEF < 50% in CYP2C19 ultrarapid metabolizers to USPI. Optimal efficacy was achieved; in some patients, this was delayed owing to dose reduction. Interruption of mavacamten during short term administration of inhibitors transiently increased VLVOTg for the duration of interruption, with no effect on LVEF.

Conclusion:
Coadministration of mavacamten with CYP3A4 or CYP2C19 inhibitors could be accommodated within the titration scheme with dose interruption or down titration.
Abstract 12421: Guided Advanced Cardiovascular Life Support Mobile App Improves Trainee Experience and Performance During Simulated Cardiac Arrest: A Randomized Controlled Trial
Authors: Senter-Zapata Michael J , Neel Dylan V , Colocci Isabella , Alblooshi Afaf , AlRadani Faten , Quach Brian , Lyon Samuel , Coll Maxwell , Chu Andrew , Rainer Katharine , Waters Beth , Baugh Christopher , Dias Roger , Zhang Haipeng , Eyre Andrew J , Isselbacher Eric , Conley Jared , Calile Narath
Published: December 2023

Introduction:
Leading hospital code teams is stressful for resident physicians, and variability in training and experience may result in inconsistent care and outcomes. Nearly all bedside aids like AHA advanced cardiovascular life support (ACLS) pocket cards and third-party ACLS mobile apps lack step-by-step guidance or reminders. Our team designed a guided ACLS mobile app to help trainees lead more effective hospital resuscitations and conducted a randomized controlled trial to assess user experience and performance according to 2020 AHA ACLS guidelines.

Hypothesis:
A guided ACLS app will improve subjective user experience and adherence to AHA ACLS guidelines.

Methods:
The ACLS mobile app was developed using Swift UIKit. Internal Medicine, Emergency Medicine, Surgery, and Anesthesia residents (N = 46) were randomized to lead a simulated code for cardiac arrest due to massive pulmonary embolism using either AHA pockets cards (N = 22) or the ACLS app (N = 24). User experience was assessed via surveys. Code outcomes, guideline adherence, and errors were analyzed from video recordings. A focus group of 22 residents provided feedback. Statistical analysis was conducted using R software and included two-sided t-tests and Fisher exact tests.

Results:
App users showed significantly increased confidence (1.0 vs 0.3; p = 0.005), backboard use (96% vs 27%; p <0.001), end-tidal CO2 monitoring (58% vs 27%; p = 0.042), correct thrombolytic administration (54% vs 23%; p = 0.035), and achieving return of spontaneous circulation (50% vs 18%; p = 0.032) compared to controls. Focus group results showed that 100% of the participants would use the app and that 82% preferred the guided app to AHA pocket cards.

Conclusions:
The guided app improves user confidence and adherence to AHA ACLS guidelines and addresses the need for greater standardization in hospital code management. Validation studies are necessary to confirm its effectiveness in clinical practice.
Abstract 12441: Ambient Fine Particulate Matter Air Pollution but Not Ozone is Associated With Elevated Risk of All-Cause Hospitalization in Patients With a Prior Diagnosis of Atrial Fibrillation
Authors: Horne Benjamin D , Haddad Francois , Joy Elizabeth A , Prunicki Mary , Anderson Jeffrey L , Kim Juyong B , Bride Daniel , Bair Tami L , Nadeau Kari , Knowlton Kirk U
Published: December 2023

Introduction:
Short-term increases (days to weeks) in fine particulate matter (PM
2.5
) air pollution are associated with atrial fibrillation (AF) episodes. We previously reported that PM
2.5
was not associated with severe AF measured as emergency or inpatient hospitalization for the primary diagnosis of AF. Mild AF, though, may influence all-cause hospitalizations. This study evaluated if short-term increases in PM
2.5
and ozone were associated with all-cause hospitalization at 11 Intermountain Health hospitals in patients with AF, and if this differed between wildfire (June-Oct.) and winter inversion (Nov.-March) seasons.

Methods:
Patients carrying an AF diagnosis (N=347,157) were evaluated for all-cause hospitalization and, secondarily, AF hospitalization (N=25,601) and first AF diagnosis (N=77,893). PM
2.5
levels were measured from January 1, 1999 to March 31, 2022 (ozone: 2006-2022) in subjects residing on Utah’s Wasatch Front. Using the case-crossover design that matched individual-level characteristics, Poisson regression also adjusted for weather variables.

Results:
Mean age was 72±15 years and 51.0% were female. Overall, PM
2.5
increases at a lag of 0 days, 1 day, 3-day moving average (mAvg) (days 0-2), and 7-day mAvg (days 0-6) were associated with all-cause hospitalization [respectively: odds ratio (OR)=1.010, 1.008, 1.011, 1.009 per +10 μg/m
3
; p=0.0004, 0.006, 0.0004, 0.028]. Associations differed by seasons (Figure). Regressions entering both ozone and PM
2.5
mildly increased PM
2.5
ORs for all-cause hospitalization. PM
2.5
was not associated with first AF diagnosis. Increases in ozone were not associated with higher risk of any outcome.

Conclusions:
Short-term increases in PM
2.5
air pollution were associated with all-cause hospitalization in patients with a prior AF diagnosis. Lag structure varied for wildfire and inversion seasons, with greater effect sizes in wildfire season. Increases in ozone did not associate with elevated risk.
Abstract 12446: Trajectories of Frailty and Cardiovascular Outcomes Among Medicare Beneficiaries, 2003-2015
Authors: Gong Yusi , Song Yang , Xu Jiaman , Dong Huaying , Kramer Daniel B , Orkaby Ariela R , Dodson John A , Strom Jordan B
Published: December 2023

Background:
Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent role of frailty progression on health outcomes remains uncertain.

Methods:
In Medicare Fee-for-Service beneficiaries ≥ 65 years with continuous enrollment from 2003-2015, we calculated frailty progression or regression, using a continuous, validated Fried phenotype-based frailty index in years 1-5. We used linear mixed effects models and Cox proportional hazards models, adjusting for baseline frailty, to evaluate the influence of frailty trajectory on the risk of adverse health outcomes (death, HF, MI, ischemic stroke, MACE, and days at home [DAH] within the calendar year).

Results:
Among 26,414,887 individuals (mean age 75.4 ± 7.0 years, 57% female, 13% non-white race), 20.4% had frailty progression and 13.6% had frailty regression. Compared to frailty regressors, progressors had a greater risk of mortality (HR 1.59, 95% CI 1.58-1.59) and all cardiovascular outcomes. With increasing quartile of frailty progression and adjusting for baseline frailty, there was a graded risk in mortality (quartile 4 vs. 1, HR 2.21, 95% CI 2.21-2.23, p < 0.001) and all adverse cardiovascular outcomes (Figure). Compared to those in the lowest frailty progression quartile, those in the highest quartile had significantly fewer DAH (270.4 ± 112.3 vs. 308.6 ± 93.0, RR 0.88, 95% CI 0.87-0.88, p < 0.001).

Conclusions:
In this large, nationwide sample of older Medicare beneficiaries, the degree of frailty progression, independent of baseline frailty, was associated with increased risk of all-cause mortality, HF, MI, ischemic stroke, and MACE, and fewer DAH. Frailty progression therefore identifies patients at high risk for adverse outcomes and increased health services utilization.
Abstract 12468: One-Year Effects of Randomized High-Intensity Statin versus Placebo on the Bioactive Lipidome: Findings From the JUPITER Trial
Authors: Hoshi Rosangela , Alotaibi Mona , Liu Yanyan , Ridker Paul M , Glynn Robert , Serhan Charles N , Jain Mohit , Demler Olga , Mora Samia
Published: December 2023

Introduction:
Statin effects extend LDL-C reduction, with the potential to modulate the metabolism of bioactive lipids (BALs), crucial metabolites for biological signaling and inflammation.

Hypothesis:
Statin allocated participants will have a different BAL profile with cardioprotective properties compared to placebo.

Aim:
To investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (NCT00239681), a randomized double-blinded primary prevention trial involving individuals with LDL-C <130 mg/dL and high-sensitivity C-reactive protein ≥ 2 mg/L.

Methods:
Using a non-targeted mass spectrometry approach, over 15500 lipid features were assayed from baseline (BL) and 1-year (Y1) plasma samples from non-CVD cases from 2 nested JUPITER sub-studies: JUPITER
discovery
(N=589) and JUPITER
validation
(N=409). The effect of rosuvastatin 20mg
vs
. placebo on BALs was examined by fitting a linear regression with delta values (ΔBAL=BAL
Y1
-BAL
BL
) that adjusted for age (years) and baseline BAL level. Significant associations in discovery were carried over for validation. Multiple comparisons were adjusted using a two-stage overall False Discovery Rate (FDR) <.05.

Results:
We identified 569 associations significantly validated (overall FDR<.05), including 27 BALs with putative annotation. Statins increased levels of 302 BALs, such as specialized pro-resolving mediators (SPMs) and eicosanoids with anti-inflammatory activity in the vasculature (e.g. 5,6-diHETE), arterial vasodilation properties (hepoxilins), and a precursor of leukotrienes (5-HpETE). Among 267 BALs lowered by statins, there were arachidonic acid and inflammation-related lipid mediators (10 HDoHE, 5-HEPE, 11-HETE, 9-HODE, 11d-TXB2) (Fig1 A and B).

Conclusions:
Statins had pleiotropic effects on BAL metabolites, predominantly increasing anti-inflammatory and pro-resolution BALs and decreasing BALs with pro-inflammatory properties.
Abstract 12485: Cardiovascular Disease Risk, Cognitive Function, and Serum Biomarkers in Older Women Participating in a Lifestyle Intervention
Authors: Halloway Shannon , Volgman Annabelle S , Barnes Lisa , Schoeny Michael , Wilbur Joellen , Pressler Susan J , Laddu Deepika , Vispute Sachin , Hall Gabriel , Arvanitakis Zoe
Published: December 2023

Background:
Cardiovascular disease (CVD), including atherosclerotic CVD (ASCVD) and stroke, increase risk of cognitive dysfunction. Serum biomarkers, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1) may be associated with elevated CVD risk and are also emerging as early indicators of cognitive dysfunction. Yet, few studies have investigated associations among all three: CVD risk, cognitive function, and serum biomarkers.

Aims:
We examined associations between CVD risk, cognitive function, and serum biomarkers in older women with CVD.

Methods:
Baseline data from an ongoing lifestyle intervention trial for the prevention of cognitive decline in older women with CVD (NCT04556305) were analyzed. Women (
N
=253) aged ≥65 years were recruited from ambulatory cardiology clinics. At baseline, CVD risk factors, including blood pressure, body mass index (BMI), waist circumference, and step test (cardiorespiratory fitness) were assessed. ASCVD and CHA
2
DS
2
-VASc scores were calculated to estimate clinical ASCVD and stroke risk, respectively. Serum biomarkers included BDNF, VEGF, and IGF-1. Neurocognitive tests for global cognition, including episodic memory, executive function, semantic memory, and working memory domains, were administered. Linear regression models adjusted for age, education, and race or ethnicity were used to evaluate associations of individual CVD risk factors, ASCVD and CHA
2
DS
2
-VASc scores with cognitive function and serum biomarkers, separately.

Results:
Of CVD risk factors, waist circumference and BMI were associated with cognition: waist circumference with global cognition, episodic memory, and executive function (
β
= -.14 - -.20); BMI with executive function (
β
= -.13). ASCVD and CHA2DS2-VASc scores were associated with semantic memory (
β
= -.23 and -.16, respectively). Only the ASCVD risk score was associated with BDNF (
β
= .18) and VEGF (
β
= .24) levels.

Conclusion:
In older women with CVD, body composition and CVD risk scores appear to be correlated with cognitive function. Future studies should explore associations prospectively and consider serum biomarkers as mediators of the relation of CVD risk to cognitive dysfunction.
Abstract 12638: The Independent and Joint Associations of Obesity and Hypertension on Incident Heart Failure: A Pooled Cohort Analysis
Authors: Hamid Arsalan , Minhas Abdul Mannan Khan , Kamimura Daisuke , Pandey Ambarish , Rizwan Affan , Tio Maria Clarissa , Howard Candace M , Morris Alanna A , NAMBI VIJAY , Mentz Robert J , Butler Javed , Hall Michael E
Published: December 2023

Introduction:
Obesity and hypertension (HTN) are major risk factors for incident heart failure (HF). Obesity is a major cause of HTN; thus, it is difficult to disentangle the impact of each risk factor on HF incidence. Further, it is not established what factors modify these relationships.

Aims:
To assess the associations of obesity and HTN as well as their potential synergistic effect on incident HF in large, diverse populations.

Methods:
We studied participants of 3 major epidemiologic cohorts: Atherosclerosis Risk in Communities Study, Multi-Ethnic Study of Atherosclerosis, and Jackson Heart Study. Participants were stratified into 4 groups: neither obesity nor HTN (reference), only obesity, only HTN, or both obesity and HTN. HTN was defined as ≥140 mmHg systolic or ≥90 mmHg diastolic blood pressure or use of antihypertensive medications. Obesity was defined as body mass index ≥30 Kg/m2. Cox proportional hazards models adjusted for age, sex, race, smoking, alcohol use, diabetes, coronary heart disease, and estimated glomerular filtration rate were used to assess the association of 4 groups with incident HF.

Results:
18,351 participants (55.1% women and 31.4% black adults) followed over a mean 14 years were included in our analysis. Participants with only obesity (adjusted HR= 1.60; 95% CI 1.36 to 1.88) and only HTN (aHR 2.1; 95% CI 1.87, 2.37) demonstrated an increased risk of incident HF compared with participants with neither obesity nor HTN after adjustment for covariates. The greatest risk of incident HF was in participants with both obesity and HTN (aHR 2.97; 95% CI 2.63 to 3.36; Figure). HTN did not modify the effects of obesity or vice versa (p=0.193).

Conclusions:
Obesity and HTN are associated with incident HF and individuals with both have the highest risk of HF. This is an additive effect. These data emphasize the importance of blood pressure control and weight management in the prevention of HF.
Abstract 12646: Autoantibodies Targeting Endothelin Type-A Receptors Associate With no Reflow After ST-elevation Myocardial Infarction
Authors: Civieri Giovanni , Perazzolo Marra Martina , Masiero Giulia , Vadori Marta , Iop Laura , Cozzi Emanuele , Iliceto Sabino , Tona Francesco
Published: December 2023

Introduction:
No-reflow (NR), where the coronary artery is patent after treatment of ST-elevation myocardial infarction (STEMI) but tissue perfusion is not restored, is associated with worse outcome. Although several mechanisms contributing to NR have been identified, its pathophysiology is still not completely understood. Autoantibodies activating endothelin-1 receptors type A (ETAR-AAs) exert their detrimental effects through vasoconstriction, fibrosis, and inflammation. Interestingly, all these factors are also involved in NR.

Hypothesis:
We hypothesized that, after reopening of the epicardial coronary artery, the preexistence of ETAR-AAs might have detrimental effects on coronary microcirculation, resulting in microvascular obstruction (MVO) and, thus, NR.

Methods:
Our prospective study was conducted at Padua University Hospital between January 2022 and December 2022. Consecutive patients with STEMI who underwent PPCI within 6 h after the onset of symptoms were enrolled. Blood samples were obtained from all patients within 12 hours after the admission for ETAR-AAs level measurement. MVO was assessed by cardiac magnetic resonance imaging, within 15 days after successful PPCI. The seropositive threshold was provided by the manufacturer (>10 U/ml).

Results:
We recruited 50 patients with STEMI. MVO was observed in 24 patients (48%). ETAR-AAs were higher in patients with MVO (8.9 U/mL (interquartile range [IQR] 6.8-16.2 U/mL) vs. 5.7 U/mL [IQR 4.3-7.7 U/mL], p=0.002). The prevalence of MVO was higher in patients with ETAR-AAs seropositivity (72% vs. 38%, p=0.03). ETAR-AAs seropositivity was independently associated with MVO (OR 3.2, 95% CI 1.3-7.1; p=0.03).

Conclusions:
ETAR-AAs concentration are associated with MVO in STEMI patients. These findings set the stage for a better pathophysiological understanding of NR and may open new options in the management of myocardial infarction.
Abstract 12665: Hospital Outcomes of Breast Cancer Patients With Concurrent Atrial Fibrillation
Authors: Yeo Yong Hao , Tan Min Choon , Ang Qi Xuan , Tan Jia Yi , Lee Justin , Mehta Nishaki M
Published: December 2023

Background:
It was estimated that 4% of newly diagnosed breast cancer patients had new onset of atrial fibrillation (AF). Data on the impact of AF on the in-hospital outcomes of breast cancer patients are scarce.

Objective:
This study aimed to determine and assess the in-hospital outcomes of breast cancer patients with concurrent AF.

Methods:
Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged 18 years or older with a diagnosis of breast cancer between 2017 and 2020. We categorized the cohort into two groups depending on the occurrence of AF during hospitalization. The primary endpoint of our study was the in-hospital outcomes and complications of breast cancer patients with and without concurrent AF.

Results:
284,226 breast cancer patients were included in this study; 32,289 (11.4%, 76.5 ± 10.1 years of age) with concurrent AF and 251,937 (88.6%, 62.7 ± 14.0 years of age) without. Those with concurrent AF were associated with higher odds of early mortality (adjusted odds ratio [aOR]: 1.19; 95% confidence interval [CI]: 1.12- 1.27, p<0.01), prolonged index hospital stay (aOR: 1.11; CI: 1.06- 1.16, p<0.01), and non-home discharge (aOR: 1.42; CI: 1.35- 1.48, p<0.01). The length of hospital stay was longer in the group with concurrent AF than those without concurrent AF (mean 6.3 days vs. 5.7 days, p<0.01). During hospitalization, those with concurrent AF had higher odds of developing acute heart failure (aOR: 1.54; CI: 1.37- 1.74, p<0.01), cardiogenic shock (aOR: 1.42; CI: 1.04- 1.93, p=0.03), pulmonary edema (aOR: 1.26; CI: 1.06- 1.49, p=0.01), and cerebral infarction (aOR: 1.51; CI: 1.21- 1.89, p<0.01).

Conclusion:
Breast cancer patients with concurrent AF had worse in-hospital outcomes and complications than those without concurrent AF.

Figure
In-Hospital Outcomes and Complications of Breast Cancer Patients with Concurrent Atrial Fibrillation versus without Concurrent Atrial Fibrillation.
Abstract 12668: Prevalence of Phenotypic Hypertrophic Cardiomyopathy Among Students Referred for Sport Pre-Participation Cardiovascular Screening
Authors: Roma Nicholas , Aurshiya Rasha , Ferraro Bruce , Gasimli-Gamache Leyla , Nanda Sudip , Shirani Jamshid
Published: December 2023

Background:
Although rare, sudden cardiac death (SCD) is a tragic event for young sports participants and has catastrophic impact on the community. Hypertrophic cardiomyopathy (HCM) is a leading cause of SCD in sports. Comprehensive initial pre-participation physical evaluation (CIPPE) is mandated for middle school, and junior and senior high school students by Pennsylvania Interscholastic Athletic Association (PIAA) primarily for reducing potential sports-related injuries and SCD. Prospective data has been limited in this age group in regard to the prevalence of HCM.

Methods:
Between 2015 and 2023, we prospectively screened 424 students [age 10-21 (15±2) years, 60% male, 64% Caucasian) referred for cardiovascular disease pre-participation screening based on at least one positive response on the 14-point AHA questionnaire during CIPPE. Evaluation included 12-lead ECG and rhythm strip (100%), transthoracic echo (96.4%), ambulatory heart rhythm monitor (3.8%), treadmill exercise ECG (14.5%), stress echo (2.1%), and cardiac MRI (0.9%).

Results:
Overall, 1 (0.24%) student was diagnosed with definitive and two were diagnosed with probable HCM [Table-1].

Conclusion:
In this prospective cohort of middle school and junior and senior high school students with at least one positive response to the 14-point AHA questionnaire, 1 (0.24%) had definitive and 2 (0.47%) had probable phenotypic HCM.
Abstract 12669: Yield of Systematic Screening for Cardiovascular Disease in Young Sports Participants
Authors: Roma Nicholas , Aurshiya Rasha , Ferraro Bruce , Desai Spandan , Vikram Maheep , Nanda Sudip , Shirani Jamshid
Published: December 2023

Background:
Although rare, sudden cardiac death (SCD) is a tragic event for young athletes. Comprehensive initial pre-participation physical evaluation (CIPPE) is mandated for middle, junior high and senior high school students by Pennsylvania Interscholastic Athletic Association (PIAA) primarily for reducing potential sports injuries and SCD. Those with positive screening for cardiac disease [on 14-element AHA screening questionnaire] are referred for cardiac evaluation. We prospectively evaluated yield of cardiac screening in this age group.

Method:
From 2015 to 2023, 424 students [age 10-21 (15±2) years, 60% male, 64% Caucasian, 43% overweight) referred for cardiac screening. Evaluation included 12-lead ECG and rhythm strip (100%), transthoracic echo (96.4%), ambulatory monitor (3.8%), exercise ECG (14.5%), stress echo (2.1%), and cardiac MRI (0.9%).

Results:
Actionable abnormalities were found in 25 (5.9%) and included hypertension (n=8), bicuspid aortic valve (n=4, Figure:A), ascending aortic aneurysm (n=3, Figure:B*), definite or probable hypertrophic cardiomyopathy (n=3, Figure:C), atrial septal defect (n=2), mitral valve prolapse (n=2), aortic insufficiency (n=1), coronary artery anomaly (n=1) and ventricular tachycardia requiring ablation (n=1).

Conclusion:
Although uncommon, a systematic approach to screening in young sport participants can lead to identification of serious unsuspected cardiovascular disorders in 1 out of 17 students.
Abstract 12679: Thirty-Day Readmissions for Recurrent Ventricular Tachycardia Following Catheter Ablation of Ventricular Tachycardia: Predictors and Outcomes
Authors: Ang Qi Xuan , Tan Min Choon , Yeo Yong Hao , Deshmukh Abhishek , Scott Luis R , Hussein Ayman , Sroubek Jakub , Santangeli Pasquale , Wazni Oussama M , Lee Justin
Published: December 2023

Background:
Despite the optimal efficacy of catheter ablation for ventricular tachycardia (VT), recurrence of VT can occur post-procedurally. However, data on the high-risk population for VT recurrence and the in-hospital outcomes remain scarce.

Objective:
This study aimed to determine the predictors of 30-day readmission for recurrent VT after catheter ablation of VT and assess the in-hospital outcomes.

Method:
Using the all-payer, nationally representative Nationwide Readmissions Database, we identified the patients aged ≥18 years who underwent catheter ablation for VT and were readmitted within 30 days because of recurrent VT from 2017 to 2020. We performed unweighted univariable and multivariable analyses to determine the outcomes and to identify the patient and hospital variables that were predictive of 30-day readmissions for recurrent VT. A p-value of <0.05 is considered statistically significant.

Results:
In our analysis, a total of 4,102 patients were discharged alive after VT ablation, of which 278 (6.8%) were readmitted within 30 days for recurrent VT. Recurrent VT was also the most common cause of 30-day readmission (47.7%, n=278/583). Compared to non-recurrent VT readmission, readmission due to recurrent VT had higher mortality during rehospitalization (7.55% vs 3.72%, p<0.01) and higher cumulative hospitalization cost ($57584 vs $37846, p<0.01). Via multivariable analysis, congestive heart failure (aOR: 1.84; 95% CI: 1.07-3.17; P=0.03) and non-elective index admissions (aOR: 1.88; 95% CI: 1.32-2.68; P<0.01) were the independent predictors of 30-day readmission for recurrent VT.

Conclusion:
Recurrent VT was the most common cause of 30-day readmission following VT ablation. Congestive heart failure and non-elective index admissions were the independent predictors of 30-day readmissions for recurrent VT. These highlight the importance of further research in ablation strategies to improve the efficacy of VT ablation.
Abstract 12681: Sex-Specific Predictors of Pacemaker Implantation After Transcatheter Aortic Valve Implantation
Authors: IRIBARREN ANA C , Cook-Wiens Galen , Cingolani Eugenio , Ehdaie Ashkan , Shehata Michael M , Wang Xunzhang , Chakravarty Tarun , Makkar Raj , Bairey Merz C Noel N , Sandhu Roopinder
Published: December 2023

Introduction:
Permanent pacemaker (PPM) remains a common complication after transcatheter aortic valve implantation (TAVI). Despite recognition of sex-specific differences in the electrophysiological structure of the heart, there is a paucity of data examining whether predictors for PPM after TAVI differs among women and men to facilitate a precision medicine approach.

Hypothesis:
To examine incidence rates and predictors of PPM after TAVI according to sex.

Methods:
We retrospectively examined incidence rates and characteristics of women and men requiring PPM within 30-days after TAVI between 2012 to 2021. Predictors of PPM were identified using logistic regression.

Results:
A total of 3323 patients underwent TAVI, of which 407 (12.3%) required PPM within 30-days after TAVI. A PPM was required in 12.3% (170/1377) of women and in 12.2% (237/1946) of men (p=0.89). Baseline characteristics are shown in the Table. Compared to women, men requiring a PPM were more likely to have a history of myocardial infarction (MI), prior bypass surgery, reduced systolic function, first degree atrioventricular block (1
st
AVB), normal renal function, balloon expandable prosthesis, and larger prosthesis size. In multivariable analysis, right bundle branch block and self-expandable prosthesis were significant predictors for both sexes (Figure). Men had relatively more exclusive predictors (age, prior MI, atrial fibrillation, 1
st
AVB, left bundle branch block, prosthesis size) compared to women (Figure).

Conclusions:
PPM incidence rates after TAVI are similar for women and men however, sex-specific predictors for PPM exist and may be used guide pre- and post-procedural management.
Abstract 12697: Identifying Patients at Low Risk for Cancer Therapy Related Cardiac Dysfunction in Patients Treated With Trastuzumab for HER 2+ Breast Cancer
Authors: Ali Abdelrahman , Koutroumpakis Efstratios , Song Juhee , Palaskas Nicolas L , Deswal Anita
Published: December 2023

Introduction:
Frequent monitoring every 3 months for Cancer Therapy-Related Cardiac Dysfunction (CTRCD) is recommended in patients who receive trastuzumab (tras) for cancer therapy.

Aims:
We examined the frequency and predictors of asymptomatic and symptomatic CTCRD in a contemporary cohort of patients with breast cancer treated with tras with or without anthracyclines (AC).

Methods:
Breast cancer patients who received tras with/without AC and had at least one baseline and one follow-up echocardiogram (echo) performed at our tertiary cancer center (2013-2022) were included. CTCRD was defined as left ventricular ejection fraction (LVEF) decline (Simpson’s bi-plane quantitative assessment) of at least 10% to < 50%. Risk factors for CTCRD were examined using univariable and multivariable Fine-Gray models.

Results:
The cohort included 502 patients with mean ± SD age 52.1±13.2 years, mean baseline LVEF 61.2±4.1%, and a median follow-up of 52.6 months. Patients had a mean of 5.5 ± 2.7 echocardiograms; 25 patients (5%) had CTCRD as defined above during follow-up, 3.4% (95% CI, 1.8-5.9) in the Tras only and 8.7% (95% CI, 4.7-14.5) in Tras + AC group. Only 8 patients (1.6%) developed new clinical HF at any time during follow-up, 6 of whom were associated with a concomitant decline in LVEF. Increasing age (HR, 95% CI, 1.03 1.01-1.06), baseline LVEF <55% (HR 7.3, 2.9-18.2), history of HF (HR 6.2, 1.5-25.2) and AC therapy (HR 4.5, 1.8-11.4) were independently associated with CTCRD. On follow-up, 1.1% of Tras-only vs 2.7% of Tras + AC group had a persistently decreased LVEF. In a low-risk group without any of the risk factors for CTCRD, only 1 % of patients had CTCRD without clinical HF.

Conclusions:
The incidence of asymptomatic and symptomatic CTCRD was low in patients receiving tras only. Patients without any risk factors receiving tras only could be considered for less frequent monitoring of asymptomatic CTCRD.
Abstract 127: Trends of Racial Disparities and the In-Hospital Outcomes of Patients With Pulmonary Artery Catheterization for Cardiogenic Shock
Authors: antia Akanimo , Markson Favour , Alviar Carlos L
Published: December 2023

Introduction:
The use of pulmonary artery catheterization (PAC) in patients with cardiogenic shock (CS) has been associated with improved outcomes in non-randomized studies. However, the racial difference in PAC utilization and outcomes in CS have not been assessed.

Methods:
We identified all patients with CS who had PAC from the national inpatient sample of the Health Care Utilization Project database between 2016 - 2020. Patients were classified according to ethnic groups as white, black, Hispanic, and Asians Outcomes of interest included in-hospital mortality and use mechanical circulatory support (MCS) by ethnic group.

Result:
From 76,815 patients who underwent PAC during CS admission 64.18% of were Whites, 24.78% Blacks, 8.19% Hispanics, and 2.85% Asians. Black patients were younger, had higher prevalence of obesity, CHF, nicotine use and oxygen dependence. Compared to whites, blacks had lower mortality (aOR: 0.79; CI: 0.69 - 099, p=0.043), respiratory failure (aOR: 0.67; CI: 0.59 - 0.81, p<0.001), mechanical support device utilization (aOR: 0.73, CI; 0.67 - 0.81, p<0.001), and pacemaker utilization (aOR: 0.37; CI: 0.18 - 0.78, p=0.008). Hispanics had a longer length of stay (21 days vs 17.7 days). Blacks had higher rates of PAC use than other racial minorities between and mortality rates in blacks were noted to decline significantly in patients that had PAC during hospitalizations for CS (aOR: 0.49, CI; 0.46 - 0.52, p<0.001).

Conclusion:
The utilization of PAC in patients with CS is associated with better outcomes, including mortality and this was noted as well in the individual racial subgroups. Despite these findings, racial disparities persist. These disparities could be alleviated by equitable distribution of healthcare resources.
Abstract 12716: Left Ventricular Hypertrophy Phenotype to Predict Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis
Authors: Wang Lili , Yi Jiayi , Zheng Xin
Published: December 2023

Introduction:
Left ventricular hypertrophy (LVH) has been shown to be associated with the occurrence of atrial fibrillation (AF). However, due to the heterogeneous nature of LVH, the predictive value of the LVH phenotype for incident AF remains uncertain.

Methods:
We utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA). In this study, participants who underwent cardiac magnetic resonance imaging examination were included for analysis. LVH was defined as LV mass index ≥ 85.3 g/m
2
for females and ≥ 107.8 g/m
2
for males. Isolated LVH was determined as LVH without elevated cardiac biomarkers, and malignant LVH was determined as LVH with elevated hs-TnT level of ≥14 ng/L, or/and NT Pro-BNP level of ≥125 pg/mL.

Results:
A total of 4983 participants were included in the final analysis, with a mean age of 61.5 years. 272 (5.6%) had isolated LVH, and 222 (4.5%) had malignant LVH. During a median follow-up of 8.5 years, 272 cases of AF were observed. Compared to participants without LVH or elevated cardiac biomarkers, those with isolated LVH (HR, 1.82; 95% CI, 1.03-3.20) and malignant LVH (HR, 4.13; 95% CI, 2.77-6.16) had higher AF risks after adjusted for age, sex, race, body mass index, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes. Malignant LVH carried a 1.5-fold increased risk (HR: 2.48, 95% CI: 1.30-4.73) of AF compared to isolated LVH (Panel A). Kaplan-Meier cumulative AF incidence curves showed that malignant LVH had a significantly higher incidence of AF than those in other phenotypes (Panel B). Including the LVH phenotype in the CHARGE-AF model improved model discrimination (areas under the curves[AUC] increase: 0.03, p<0.001) (Panel C).

Conclusions:
The risks of AF incidence varied across LVH phenotypes, showing that malignant LVH carried a higher risk compared to other LVH phenotypes. LVH phenotype could provide additional predictive power for AF occurrence above the CHARGE-AF model.
Abstract 12727: Liver Elasticity in Elderly Heart Failure Patient
Authors: Sugawara Hirohito
Published: December 2023

Introduction:
Liver elastography is a novel ultrasound technique assessing elasticity of liver tissue. Clinical indication of liver elastography remains unrevealed. Moreover, reports about relationship between liver stiffness and heart failure subtypes haven’t well been published.

Hypothesis:
We have investigated the cardio-hepatic interaction using liver elastography in heart failure subtypes.

Methods:
We prospectively enrolled 58 consecutive patients with heart failure admission from April 2022 to March 2023. Liver elastography, transthoracic echocardiography and blood sampling were done at the time of discharge from heart failure treatment.

Results:
Patients were divided into two groups according to the left ventricular ejection fraction (LVEF) of echocardiography: heart failure with reduced ejection fraction (HFrEF) group (EF ≦40%, n = 11) and non-HFrEF group (EF >40%, n = 31). The mean age of all patients was 83 ± 11 years. The mean age and the prevalence of hypertension and diabetes mellitus was higher in non-HFrEF group than in HFrEF group. The prevalence of taking sodium glucose co-transporter 2 (SGLT2) inhibitors was lower in non-HFrEF group than in HFrEF group. LV end-diastolic diameter, LV end-systolic diameter was larger in HFrEF group than in non-HFrEF group. Tricuspid regurgitation pressure gradient (TRPG) was higher in non-HFrEF group than in HFrEF group. Inferior vena cava diameter was not different between two groups. The mean values of almost liver function tests of all patients were within the normal range. eGFR was lower in non-HFrEF group than in HFrEF group. Liver elasticity was higher in non-HFrEF group than in HFrEF group (7.1 ± 2.7 vs. 5.1 ± 1.5 hPa; P=0.008) indicating liver stiffness. Pearson’s correlation coefficient showed that liver elasticity was positively correlated with the prevalence of diabetes mellitus, LVEF, TRPG, serum creatinine, aspartate aminotransferase, γ-glutamyl transpeptidase and was negatively correlated with LV end-diastolic diameter, LV end-systolic diameter.

Conclusions:
Liver stiffness was elevated in EF-preserved heart failure patients. Liver elasticity was correlated with parameters of congestion (TRPG) and useful for the assessment of congestion in patients with heart failure.
Abstract 12736: Prevalence, Characteristics, and Outcomes of Infective Endocarditis in Patients With Liver Disease in the United States
Authors: Khayata Mohamed , Grimm Richard A , Griffin Brian P , Xu Bo
Published: December 2023

Introduction:
Infective endocarditis (IE) is common in patients with liver disease. Data regarding IE in liver disease are limited.

Hypothesis:
We analyzed IE admissions to determine inpatient outcomes among patients with liver disease in the United States.

Methods:
We used the 2017 National Readmission Database to identify index admission of adults with IE, based on the International Classification of Disease, 10th revision codes. The primary outcome was 30-day readmission. Secondary outcomes were mortality and predictors of hospitalization readmission.

Results:
We identified 40,413 IE admissions. Figure 1 presents prevalence of variables associated with liver disease in this cohort. Patients who were readmitted were more likely to have a history of hepatitis C virus (19.4% vs 12.3%, p < 0.001), hyponatremia (25% vs 21%, p < 0.001), and thrombocytopenia (20.3% vs 16.3%, p <0.001). After adjusting for age, hypertension, heart failure, diabetes mellitus, and end stage renal disease, hyponatremia (odds ratio (OR): 1.25; 95% confidence intervals [CI]: 1.17 to 1.35; p < 0.001) and thrombocytopenia (OR: 1.16; 95% CI: 1.08 to 1.24; p < 0.001) correlated with higher odds of 30-day readmission. Mortality was higher among patients with hyponatremia (29% vs 22%, p < 0.001), thrombocytopenia (29% vs 17%, p < 0.001), coagulopathy (12% vs 5%, p < 0.001), cirrhosis (6% vs 4%, p < 0.001), ascites (7% vs 3%, p <0.001), liver failure (18% vs 3%, p < 0.001), and portal hypertension (3% vs 1.5%, p < 0.001) (Figure 2).

Conclusions:
Important liver disease related variables correlate with higher risks of hospital readmission and mortality in patients with IE. Targeting such variables may improve outcomes in this patient population.
Abstract 12740: Efficacy and Safety of Empagliflozin in Acute Heart Failure: A Systematic Review and Meta-Analysis
Authors: Afzal Muhammad Adil , Abdullah Muhammad , Khalid Noman , Collins Rovena , Gashi Taulant , Hassan Mubariz , Haiy Ata Ul , Elkattawy Sherif , Michael Patrick , Vasudev Rahul , shamoon fayez
Published: December 2023

Introduction:
Acute heart failure (AHF) significantly burdens healthcare systems, leading to hospitalizations, morbidity, and mortality in older adults. Among patients suffering from chronic heart failure, empagliflozin, which is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, has shown positive cardiovascular effects. While several studies have investigated SGLT-2 inhibitor use in hospitalized AHF patients, there is a lack of meta-analysis specifically focused on empagliflozin. To ascertain the efficacy and safety of empagliflozin in AHF, the following systematic review plus meta-analysis was conducted.

Methods:
We comprehensively searched Cochrane, Clinicaltrials.gov, and MEDLINE databases. After title, abstract, and full-text screening, the data discussing relevant safety and efficacy outcomes of empagliflozin were extracted, and a random-effects meta-analysis odds ratio was calculated. We conducted a sensitivity analysis by removing the post-hoc study.

Results:
We retrieved 852 documents after initial database searches, and after the screening, 3 RCTs were included with 824 participants. Empagliflozin significantly reduced the odds of all-cause mortality (OR: 0.47, 95%CI: 0.29-0.78, p=0.004) and cardiovascular death (OR: 0.56, 95%CI: 0.38-0.82, p=0.003) when compared to placebo. Furthermore, empagliflozin demonstrated a lower serious adverse event risk (OR: 0.62, 95% CI: 0.44-0.87, p=0.005) without exacerbating adverse drug effects such as acute kidney injury, diabetic ketoacidosis, hypotension, and urinary tract infections significantly. Sensitivity analysis confirmed these findings.

Conclusion:
Our study suggests that empagliflozin holds promise in reducing cardiovascular and all-cause mortality in AHF patients. However, its impact on rehospitalizations remains uncertain. Larger and more diverse clinical trials are warranted to establish further the role of empagliflozin in managing heart failure.
Abstract 12741: Malignant Left Ventricular Hypertrophy and Risk of Cognitive Impairment or Probable Dementia: A Post Hoc Analysis of the SPRINT Trial
Authors: Ahmad Muhammad , Hughes Timothy M , Kazibwe Richard , Chen Lin Y , Soliman Elsayed Z
Published: December 2023

Background:
Left ventricular hypertrophy (LVH) accompanied by biomarker of myocardial injury as measured by high sensitivity cardiac troponin (hs-cTnT) and neurohormonal activation, as measured by N-terminal pro-B-type natriuretic peptide (NT-proBNP), indicates a malignant form of LVH. While malignant LVH has been linked to poor CVD outcomes, its association with cognitive outcomes is unclear.

Aim:
To examine the association of malignant LVH with cognitive outcomes in the Systolic Blood Pressure Intervention Trial (SPRINT).

Hypothesis:
Malignant LVH is associated with incident cognitive outcomes.

Methods:
We performed a post hoc analysis of 8,027 SPRINT participants with at least one cognitive assessment. Participants were classified into six groups based on the presence or absence of LVH assessed by 12-lead electrocardiogram (ECG), and elevations in levels of hs-cTnT ≥14 ng/L or NT-proBNP ≥125 pg/mL at baseline visit. The adjudicated outcome of incident probable dementia or mild cognitive impairment (MCI) or a composite outcome of probable dementia or mild cognitive impairment. Cox proportional hazard models were used to examine the association of baseline LVH/biomarker groups with incident cognitive outcomes.

Results:
During a median follow-up of 5 years, 597, 306, and 818 participants developed MCI, dementia, and composite outcome respectively. Compared with participants without LVH or elevated biomarkers, participants with LVH or elevated biomarkers, either in isolation or combined, had a higher risk of MCI and composite outcome. Highest risk for composite outcome was observed in those with concomitant LVH and elevated levels of both biomarkers. There was no significant association between LVH/biomarkers with incident probable dementia except for those with concomitant LVH and elevated levels of both biomarkers (
Table
).

Conclusions:
Among SPRINT participants, malignant LVH is associated with mild cognitive impairment and probable dementia.
Abstract 12784: Ischemic Cardiac Autophagy/Mitophagy is Regulated by TRPML1 and Mitochondrial Reactive Oxygen Species
Authors: Xie An , Kang Gyeoung-Jin , Kim Eun Ji , Feng Feng , Dudley Samuel C
Published: December 2023

Introduction:
In myocardial infarction (MI), activated autophagy/mitophagy helps degrade cytoplasmic macromolecules/proteins/ organelles (especially damaged mitochondria), recycle breakdown products, and prevent oxidative damage and cell death. It had reported that reactive oxygen species (ROS) activates the transcription factor EB (TFEB) via a lysosomal transient receptor potential mucolipin 1 (TRPML1) Ca
2+
efflux. TFEB is thought to be the master regulator of lysosome biogenesis.

Hypothesis:
We investigated whether lysosomal TRPML1 was activated by ROS and contributed to ischemic cardiac autophagy/mitophagy.

Methods:
MI was induced in wild type C57BL/6J mice by ligated left anterior descending coronary artery. Mice were studied at three weeks after MI surgery.

Results:
The lysosomal-restricted TRPML1 Ca
2+
release channel was significantly upregulated by 84.8% in cardiac border zone (BZ) and 55.4% in a remote zone after MI. As expected, dephosphorylated TFEB (i.e., active TFEB), mitophagy marker Parkin, autophagy marker LC3II, and lysosome marker LAMP1 increased substantially after MI. Autophagy degradation was upregulated as measured by SQSTM1/p62. TRPML1 protein expression was reduced in a dose-dependent manner by TRPML1 shRNA AAV9 (AAV9 was injected 1 week after MI for two weeks). The protein levels of LC3II and LAMP1 significantly decreased in MI BZ after AAV9 transfection. Mitochondrial ROS scavenger (mitoTEMPO, 1 mg/kg/day, i.p.) treatment for two weeks (starting at 1 week after MI) significantly inhibited TRPML1, LAMP1, LC3II and Parkin expression in the MI BZ. Conversely, when TRPML1 was overexpressed in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), the protein levels of LC3II/Parkin were increased. Speaking to human relevance, TRPML1 was significantly increased in human patients with ischemic cardiomyopathy.

Conclusion:
Autophagy and mitophagy after MI are regulated by TRPML1 and mitochondrial ROS.
Abstract 12785: Abnormal Dynamic Remodeling of the 12-Lead Electrocardiogram is a Risk Marker for Sudden Cardiac Death
Authors: Pham Hoang Nhat , Holmstrom Lauri , Chugh Harpriya , Uy-Evanado Audrey , Nakamura Kotoka , Zhang Zijun , Fortmann Stephen P , Salvucci Angelo , Jui Jonathan , Reinier Kyndaron , Chugh Sumeet S
Published: December 2023

Introduction:
The ECG has always been evaluated as static risk factor for sudden cardiac death (SCD). The importance of dynamic ECG remodeling has not been investigated.

Hypothesis:
Abnormal ECG remodeling over time is associated with increased risk of SCD.

Methods:
We investigated pre-SCD ECG remodeling in SCD cases from 2 ongoing population-based studies of out-of-hospital SCD in Portland, OR (discovery) and Ventura County, CA (validation). Two archived pre-SCD ECGs performed at least 1 year apart were obtained from lifetime health records. Controls were matched on geographical region, age, sex, and duration between the 2 ECG recordings. Dynamic ECG remodeling was measured as the change in a previously validated cumulative 6-variable ECG electrical risk score (ERS) between the 1st and 2nd ECG.

Results:
A total of 231 SCD cases (66.5±13.6 years, 61% male), and 234 controls (65.8±11.1 years, 61% male) were included in the discovery cohort, and 203 SCD cases (70.3±14.4 years, 54% male), and 203 controls (68.4±11.8 years, 54% male) in the validation cohort. The mean time between the 2 ECG recordings in SCD cases and controls was 6.0±4.0 years vs 6.2±4.5 years (discovery) and 3.7±2.6 years vs. 3.7±1.6 years (validation), respectively. In both cohorts, SCD cases compared to controls had greater dynamic ECG remodeling over time: Discovery cohort ERS change +1.06 (95% CI +0.89 to +1.24) vs. -0.05 (-0.21 to +0.11; p<0.001) and validation cohort ERS change +0.87 (+0.7 to +1.04) vs. -0.11 (-0.27 to 0.05; p<0.001). In a multivariate model including clinical SCD risk factors, a 1-unit increase in the ERS was an independent risk marker for SCD: Discovery cohort OR 1.89 (95% CI 1.58-2.26; p<0.001), validation cohort OR 2.17 (95% CI 1.63-2.91; p<0.001).

Conclusions:
SCD cases were observed to have abnormal dynamic ECG remodeling prior to the SCD event, not observed in matched controls. These findings warrant further investigation of dynamic ECG remodeling as a novel risk marker for SCD.