bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16377: 68Ga-DOTATATE Measurements Predict Progression of Aortic Valve Calcification in Humans
Authors: Aldosoky Wesam , GOUDOT Guillaume , Abohashem Shady , Grewal Simran , Qamar Iqra , Hanlon Erin , Alani Omar , Civieri Giovanni , Gharios Charbel , Osborne Michael , dweck marc , Heidari Pedram , Tawakol Ahmed A
Published: December 2023

Introduction:
Aortic valve (AV) inflammation contributes to calcification (AVca). 68Ga-DOTATATE (GADT), a positron emission tomography (PET) tracer that binds to somatostatin receptors, has emerged as a reliable marker for tissue inflammation. However, the diagnostic and prognostic value of AV GADT uptake in AVca remains unexplored.

Hypothesis:
We aim to investigate the relationships between baseline AV GADT uptake with baseline AVca and its progression.

Methods:
A total of 698 individuals (median age 63, 46% male) underwent clinical GADT PET/computed tomography (CT) imaging from 2017 to 2023; 245 had follow-up scans (median 1.3 yrs interval). AV inflammation was measured as the maximum standardized uptake value of GADT uptake within the AV on baseline PET/CT. AVca was quantified in baseline and follow-up CT scans (HU>130). AVca progression was assessed as the difference between baseline and follow-up AVca. Individuals with a square root difference of annualized AVca change ≥ 2.5 were characterized as “progressors” and <2.5 as “non-progressors”. Demographic and clinical data were collected from medical records.

Results:
Baseline AV
GA
DT correlated with baseline AVca (standardized β=0.11; p=0.004;
Fig 1A
). Further, baseline AV
GA
DT associated with AVca progression (odds ratio [95% confidence interval]=3.1 [1.5, 6.6]; p=0.003,
Fig 1B
) and remained significant after separately adjusting for baseline AVca (3.8 [1.1, 13.8]), hypertension (2.8 [1.3, 6.2]), diabetes (3.0 [1.4, 6.3]), hyperlipidemia (2.4 [1.0, 5.3]), smoking (3.1 [1.5, 6.7]), and chronic kidney disease (2.9 [1.4, 6.3]), but became borderline with adjustment for age and sex (2.4 [0.9, 5.9]; p=0.054;
Fig 1C
).

Conclusions:
Our study highlights the use of GADT for assessing AV inflammation and predicting AVca progression. These findings underscore the role of inflammation in driving AVca progression and have potential implications for risk assessment and evaluating therapies in AV disease.
Abstract 16392: Arrhythmias in Acute Care Cardiology: Prevalence, Therapies, and Outcomes- An Analysis of the Pediatric Acute Care Cardiology Collaborative (PAC
3
) Database
Authors: Nash Dustin , Patel Sonali , Dalal Aarti , Schiller Amy , Giacone Heather , Weinreb Scott J , Headrick Andrew , Malloy-Walton Lindsey , Brateng Caitlin , Tanel Ronn E
Published: December 2023

Introduction:
Arrhythmias are common in pediatric cardiology patients, yet prevalence during hospitalizations and treatments are poorly defined. This descriptive study reports arrhythmia prevalence and medical management from Pediatric Acute Care Cardiology Collaborative (PAC
3
) centers.

Aims
Our primary aim is to describe prevalence and outcomes of treated arrhythmias among acute care cardiology units (ACCU). Secondary aims include comparison of medical vs. post-operative admissions and selection of antiarrhythmics.

Methods:
We performed a multi-center retrospective review of the PAC
3
registry limited to hospitalized patients with an arrhythmia treated from 2/2019-2/2023 among 33 centers. Arrhythmias are classified in the registry as Atrial Tachycardia/Supraventricular Tachycardia (AT/SVT), Junctional Tachycardia (JT), or Ventricular Tachycardia (VT). Descriptive statistics, Wilcoxon-Mann-Whitney, and χ2 testing were used.

Results:
Prevalence of treated arrhythmia in the cohort (n=38,396) was 5.4% (n=2,090 patients) over 2291 hospitalizations. AT /SVT (68.3%) were more frequent than VT (21.5%) or JT (2.8%) (p<0.01). Bradyarrhythmias (7.5%) were infrequent. Of 8,733 CICU transfers, 513 (5.9 %) transfers of 257 patients (2.0 transfers/patient) were due to arrhythmia. Medical and Surgical patients varied in demographics and outcomes (Table). For AT/SVT, propranolol was the most prescribed antiarrhythmic, followed by sotalol. (Figure).

Conclusions:
Treated arrhythmias are prevalent in ACCU patients and are a relatively frequent cause of ICU transfers. Arrhythmia treatment patterns warrant further investigation and could be the subject of QI.
Abstract 16396: A Tale of Two Maladies: An Interplay of Mendelian Principles
Authors: Sanchez Reynaldo H , Rajaram Veena , Hendren Nicholas
Published: December 2023

A 22-year-old male with no medical history presented in acute decompensated heart failure and cardiogenic shock. Physical exam showed a thin body habitus, reduced muscle bulk, bilateral ptosis, limited extraocular motion, and upper extremity weakness. An echocardiogram revealed severe biventricular dilation and systolic dysfunction. Invasive hemodynamics revealed elevated cardiac filling pressures and low cardiac output. Coronary angiography excluded coronary artery disease and anatomical variants. He was initiated on dobutamine and eventually milrinone given persistently low index and elevated lactate. An evaluation for the etiology of his cardiomyopathy focused on nutritional deficiencies (e.g., Wet Beriberi), myocarditis, genetic mutations, infiltrative cardiomyopathy (e.g., Friedrich’s ataxia), and mitochondrial and myopathy-related cardiomyopathy. CMR had globally elevated T1 and normal T2 values ruling out acute myocarditis or infiltrative processes. Serum thiamine, TSH and B12 were within normal range. Muscle biopsy and mitochondrial genetic testing revealed a pathogenic deletion (m.7416_14556) and 70% heteroplasmy. Physical exam, biopsy and mitochondrial genetics were diagnostic of Kearns-Sayre Syndrome (KSS). Notably KSS does not typically cause severe cardiomyopathy suggesting an alternative cause. A genetic cardiomyopathy panel was sent revealing a pathologic mutation in the plakophilin 2 gene which was the suspected cause of his cardiomyopathy. A heart transplant evaluation was initiated as he developed refractory shock requiring mechanical support via an Impella 5.5, placed via the right innominate artery due to his small body and vessel size. He underwent an uncomplicated heart transplantation and is doing well. This case underscores the significance of a broad differential diagnosis, multidisciplinary collaboration, and a detailed physical examination in diagnosing and managing complex cardiac conditions.
Abstract 16403: Toxoplasma Cardiomyopathy in a 36 Year HIV Positive Female
Authors: Mohan Ayushi , Reddy Srivaibhav , Mirza Noreen , suleiman Addi
Published: December 2023

Introduction:
Cardiac involvement of toxoplasmosis is extremely rare and can present as myocarditis, pericardial effusion, constrictive pericarditis, arrhythmias or heart failure. While acquired primary infection is severe in immunocompetent, it can be life-threatening among immunodeficient patients.

Case:
36 Yr female with PMHx of HIV non-compliant with HAART, Toxoplasma infection in 2019 presented with weakness, dry cough & substernal chest pain x 1-week, sharp type, increasing with lying flat. On presentation vitals were unremarkable. ECG showed diffuse T wave inversions. Troponins elevated at 5000s. MRI brain revealed multiple scattered bilateral cortical and cerebellar enhancing lesion suggestive of toxoplasmosis. Serology was positive for toxoplasmosis. Viral respiratory panel & Sepsis work-up was negative. TTE on admission showed mild pericardial effusion and EF of 50-55%. Follow up TTE (day 7) revealed an EF of 25-30% with mild pericardial effusion pointing towards a toxoplasma induced myopericarditis leading to cardiomyopathy. TEE ruled out possibility of Endocarditis.

Discussion:
Patient was initiated on anti-toxoplasma therapy with pyrimethamine and sulfadiazine after toxoplasma cardiomyopathy was considered. After initial cardiopulmonary decompensation patient was intubated and needed pressor support. Over the course of next 2 weeks her condition improved with anti-toxoplasma therapy and was extubated.

Conclusion:
Toxoplasma myopericarditis is rare and a serious presentation among both immunocompetent and immunodeficient patients. Early intervention and diagnosis of Toxoplasma myopericarditis could prevent the progression of cardiomyopathy and improve overall prognosis.
Abstract 16404: Symptom Perception Predicts Short-Term Prognosis in Patients With Heart Failure
Authors: Hayashi Kanako , Okada Akiko , Tsuchihashi-Makaya Miyuki
Published: December 2023

Background:
The type and severity of symptoms perceived by heart failure (HF) patients may be a useful prognostic predictor, but the impact of symptom perception on clinical events among HF patients has not been fully tested. Aim: To assess the symptoms perceived by HF patients using the Heart Failure Somatic Perception Scale (HFSPS) and to test whether symptom perception predicts short-term prognosis in HF patients.

Methods:
Using the prospective observational design, we collected data from 315 outpatients with HF (mean age 73 ± 13 years, 72% male). Data included sample characteristics, BMI, BNP, comorbidities, ADL, depressive symptoms, symptom perception assessed by HFSPS at baseline, and clinical composite outcomes (readmission, all-cause death, and emergency department visits) at three months. HFSPS is a scale that assesses the degree to which 18 physical symptoms perceived by HF patients are bothersome in daily life. The study subjects were classified into low, medium, and high HFSPS total score groups. The impact of HFSPS on clinical composite outcomes was analyzed using the Cox proportional hazard model, considering the influence of covariates.

Results:
The mean overall HFSPS score was 11.7 ± 12.3 points, with 87 patients (28%) in the low HFSPS group, 151 (48%) in the medium group, and 77 (24%) in the high group. Symptoms reported were nocturia (74.6%), shortness of breath (58.4%), fatigue (54.6%), malaise (44.5%), and cough (42.9%). Three-month composite event rate was 25.7%, with statistically significant differences between the HFSPS groups (16.1% in the low group, 23.2% in the medium group, and 41.6% in the high group (p=0.001). The results of analysis using the Cox proportional Hazard model using age, gender, BMI, BNP, comorbidities, depression, and ADL as covariates, the high HFSPS group had a significantly higher incidence of clinical composite. The incidence of clinical composite outcomes at three months was significantly higher in the high HFSPS group than in the other groups (HR=2.090 (95% CI=1.067-4.096), p=0.032).

Conclusions:
Symptom perception, which can be regarded as a patient-reported outcome, is a promising predictor of short-term prognosis in HF patients.
Abstract 16405: Perm1 Protects the Heart From Pressure Overload-Induced Dysfunction by Promoting Oxidative Metabolism
Authors: Tachibana Shizuko , Yu Nam-Kyung , Fernandez-Costa Carolina , Li Ruixia , Liang Alex , Choi Janet , Jung Dayoen , Kralli Anastasia , Xiao Changchun , Yates John , Ross Robert S , Cho Yoshitake
Published: December 2023

Introduction:
Defects in ATP production lead to cardiac dysfunction and heart failure (HF) while restoring reduced mitochondrial (Mito) function mitigates HF. Previously we showed that a novel Mito protein, Perm1 (PGC-1 and ERR-induced regulator, muscle 1), promotes Mito biogenesis in cardiomyocytes (CM). Here we studied the role of myocardial Perm1
in vivo
.

Hypothesis:
Perm1 protects the heart from pressure overload-induced dysfunction.

Methods:
First, we generated cardiac-specific Perm1 transgenic mice (Perm1cTG). Next, we induced pressure overload by transverse aortic constriction (TAC) or performed Sham operations on 10-week-old control (CTL) and Perm1cTG male mice. Heart function, histology, and biochemical analyses were performed eight weeks postoperatively. To understand the mechanism of Perm1, the heart protein samples were subjected to quantitative mass spectrometry (MS) analysis, and we also identified Perm1 binding proteins in the heart by MS. Finally, mouse neonatal CM were infected with adenoviruses expressing shMic60 (knock down) or shControl in combination with Perm1 or LacZ, followed by oxygen consumption rate (OCR) analysis.

Results:
Sham-operated Perm1cTG and CTL mice showed no differences in function and morphology. Following TAC, CTL developed severely reduced heart function, while Perm1cTG had only minimal change. Perm1cTG TAC mice also showed reduced cardiac hypertrophy,
Anf
and
Bnp
mRNA expression, and fibrosis, compared to CTL TAC, showing Perm1 protects the heart from hemodynamic stress. Perm1cTG TAC hearts showed significantly increased OCR compared to CTL TAC, suggesting Perm1 preserves TAC-induced CM Mito dysfunction. MS analysis identified MICOS (mitochondrial contact site and cristae organizing system) and oxidative phosphorylation proteins were upregulated in Perm1cTG TAC hearts compared to CTL TAC. Moreover, we found that Perm1 binds to Mic60, which is a core component of the MICOS. Finally, Mic60 was required for Perm1-induced maximal oxidative capacity, suggesting Perm1 acts through Mic60.

Conclusion:
Perm1 protects the heart against pressure overload by restoring oxidative metabolism. Future studies will reveal the role of Perm1/Mic60 in the heart. This work is supported by NIH R01HL151239.
Abstract 16424: Comparative Outcomes of Interventions for Peripheral Arterial Disease in Patients With Different Atherosclerotic Cardiovascular Disease Risk Estimates
Authors: Huttler Joshua , Jamil Yasser , Wu Zhen , Slade Martin , Ochoa Cassius I
Published: December 2023

Introduction:
The atherosclerotic cardiovascular disease (ASCVD) Risk Estimator is an effective tool for predicting cardiovascular events. While peripheral arterial disease (PAD) represents an advanced form of atherosclerosis, ASCVD scores have not been studied in this patient population. This study will evaluate ASCVD risk scores in patients undergoing lower extremity revascularization (LER) for PAD and assess their impact on outcomes.

Hypothesis:
Patients with high ASCVD risk have worse outcomes after LER for PAD compared to those with lower risk.

Methods:
Electronic medical records of patients undergoing LER for PAD in a single center from 2013-2020 were reviewed. The ACC/AHA ASCVD estimator was used to calculate risk and categorize patients into risk groups before initial LER. Patient characteristics and outcomes were compared between those with high (≥20%) and lower (<20%) risk scores. The lower risk group was composed of patients with intermediate, borderline, and low ASCVD risk.

Results:
A total of 635 patients were included and 429 (67.6%) had high ASCVD risk scores. Most patients in the lower risk group had intermediate (78%, N=161) risk, followed by low (12%, N=28), and borderline (8%, N=17) risk scores. High risk patients were more commonly males with more severe comorbidities. (
Table)
Patients with high ASCVD risk had more long-term mortality (29% vs 19%, P=0.010) and inferior amputation-free survival (
Figure
) compared to those with lower risk.

Conclusions:
Most patients with PAD undergoing LER have high ASCVD risk. High ASCVD risk scores correlate with outcomes and may be useful for risk stratification in PAD patient populations with advanced atherosclerosis.
Abstract 16426: A Risk Model to Predict Atrial Fibrillation in Diabetes Using Machine Learning: The ACCORD Study
Authors: Offerman Erik J , Harirforoosh Sarah , Fan Wenjun , Wong Nathan D , Donaldson David M
Published: December 2023

Introduction:
Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice, which necessitates identifying factors that can precipitate this dysrhythmia. We utilized the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to build an AF risk prediction model specifically in the type 2 diabetes (T2DM) population, using machine learning (ML) approaches, and comparing to the established CHARGE-AF risk model.

Methods:
We utilized a patient cohort from the ACCORD clinical trial without prior AF. Baseline characteristics were collected as potential risk factors and incident AF was defined from ECG at follow-up. A random forest (RF) binary classifier was trained with 27 variables, including age, race, sex, smoking, waist circumference, BMI, blood pressure (BP), history of heart disease, medications, cholesterol, renal function, and left ventricular hypertrophy by ECG. All ACCORD subjects had T2DM, therefore this variable was not included. The CHARGE-AF model consisted of a Cox proportional hazard model trained on the following variables: age, race, height, weight, systolic/diastolic BP, current smoking, heart failure, prior MI, and BP medication. Area under ROC curve (AUC) was measured with randomized, stratified, 5-fold cross validation with 80/20 splits. Imputation and resampling methods were used for missing data and class imbalance.

Results:
Out of 9307 patients in the ACCORD cohort, 175 developed AF during the study period of 6.26 years, with a mean time to AF event of 3.68 years. The RF model, with an AUC of 0.912, showed improved prediction of AF over the Cox model, which had an AUC of 0.784. Permutation feature importance revealed age, race, waist circumference, weekly alcohol consumption, sex, and GFR as the most predictive features of the RF model (Fig 1).

Conclusions:
The CHARGE-AF risk model performed modestly on the ACCORD cohort, while a RF model showed superior performance.
Abstract 16452: Targeting Notch3 Pathway and Using Extracellular Vesicles From Induced Pluripotent Stem Cell-Derived Cardiomyocytes is Effective in Porcine Chronic Myocardial Injury Model
Authors: Tzng Eileen , Raygani Sawye , Inoue Hiroyuki , Zhao Chunli , Ueyama Tsuyoshi , Kashipathy Maithri , Cheng Paul , lyins jennifer , Ikeda Gentaro , Yang Phillip C
Published: December 2023

Introduction:
Heart failure is the leading cause of hospital admission in the modern U.S. We previously demonstrated that exosomes (Ex) from iPSC-derived cardiomyocytes (iCMs) significantly restored murine peri-infarct region. We found that miR20/92/363 (CORE miRNA) activated iCM proliferation and myocardial restoration by repressing the Notch3 pathway. However, the optimal pre-clinical method to target the Notch3 pathway through Ex, miRNA, and siRNA remains to be assessed.

Hypothesis:
Exosomes are the most effective biologic for chronic porcine heart failure model.

Methods:
iPSCs were generated from four heart failure patients (Pt 1-4) and differentiated into iCMs. Ex were isolated from the iCM culture media and used to treat iCMs subjected to hypoxia-injury. The in vitro findings were then confirmed in vivo in Yorkshire pigs subjected to myocardial ischemia-reperfusion injury for one hour via balloon occlusion of the left descending artery. One month later, chronic heart failure model was developed, and percutaneous catheter system (Biocardia, Inc) delivered 10
11
Ex, 4200 μg of CORE miRNA, or 4200 μg of siNotch3 into porcine peri-infarct region. MRI and mRNA seq analyzed the porcine myocardium.

Results:
Viability of hypoxia-injured iCMs treated by siNotch3 (132.50% viability ± 23.54% SD)*, CORE miRNA (127.79% ± 10.06%)*, Pt 1 Ex (74.88% ± 3.11%)*, Pt 2 Ex (72.90% ± 4.50%)*, Pt 3 Ex (79.11% ± 7.23%)*, and Pt 4 Ex (77.81% ± 3.31%)* all significantly improved iCM viability compared to non-treated hypoxia-injured iCMs (26.09% ± 10.75%, *p<0.05). In porcine chronic heart failure model (n=4 - 6/treatment group), the mean absolute change in LVEF of PBS (control), siNotch3, CORE miRNA, and Pt 1 Ex treatments were -3.55 ± 3.27, 1.19 ± 3.17*, 2.34 ± 1.53*, and 3.53 ± 3.59*, respectively (*p<0.05). mRNA seq, gene ontology, and KEGG analysis of porcine myocardium suggested that myocardial repair occurred through the TGFβ pathway and cell cycle re-entry of cardiomyocytes.

Conclusion:
siRNA, miRNA, and exosomes are all effective methods to repair the porcine myocardium after chronic myocardial injury. Exosome showed the highest functional restoration. Determination of mechanism and optimal biologic and dose are underway.
Abstract 16458: Long-Term Exposure to Air Pollutants and the Risk of Hypertension: Insights From the Korean Genome Epidemiologic Survey Project
Authors: Cha Jinah , Choi Se Yeon , Rha Seung-Woon , Ahn Woo Jin , Choi Byoung Geol , Byun Jae Kyeong , Hyun Sujin , Lee Min Woo , Kim Suhng Wook , Park Soohyung , Kang Dong Oh O , Park Eun Jin , Choi Cheol Ung
Published: December 2023

Introduction:
The specific relationship between long-term exposure to air pollutants and the risk of HTN requires further investigation. This study aims to assess the association between AP and HTN occurrence and examine whether the effects differ between individuals with and without HTN in a long-term perspective.

Hypothesis:
Based on the previous research linking AP to cardiovascular diseases, we hypothesize that long-term exposure to air pollutants is associated with an increased risk of developing HTN.

Methods:
This study used modeled AP data linked with Korean Genome Epidemiologic Survey (KoGES) cohort data based on participant addresses. Among the 77,048 participants who completed the follow-up, 23,935 subjects had HTN at the baseline, while 53,113 subjects were non-hypertensive. AP exposure concentrations were evaluated using the 1-year and 3-year averages prior to the follow-up date and the average of the entire follow-up period. Logistic regression models were employed to analyze the relationship between HTN and air pollutants in the non-hypertensive group.

Results:
The analysis revealed that non-hypertensive subjects exposed to air pollutants had an increased risk of developing HTN, with the exception of O
3
. Notably, particulate matter 2.5 (PM
2.5
) exposure demonstrated a gradual increase in HTN risk based on the duration of exposure (Odds Ratio [OR] 1.024, 1-year; OR 1.030, 3-year; OR 1.041, average survey period.) These findings suggest that prolonged exposure to high concentrations of PM
2.5
is associated with an elevated risk of HTN. Chronic exposure to other gaseous AP components were also similarly associated with higher risk of development of HTN.

Conclusions:
This study highlights the detrimental association of long-term exposure to air pollutants on the risk of HTN. Managing blood pressure in those exposed to high AP levels, even if not hypertensive is important also with a perspective of public health and environmental policies.
Abstract 16466: Sex-Specific Risks of Air Pollution on Coronary Artery Disease and Adverse Events: Insights From the PROMISE Trial
Authors: Langenbach Isabel L , Mayrhofer Thomas , Langenbach Marcel , Lu Michael T , Karady Julia , Pagidipati Neha J , Shah Svati H , Ferencik Maros , Motsinger-Reif Alison , Douglas Pamela S , Foldyna Borek
Published: December 2023

Introduction:
Sex-specific differences in coronary artery disease (CAD) have significant implications, yet the potential sex-specific impact of air pollution on CAD and adverse outcomes remains unexplored.

Hypothesis:
The association between air pollution and CT-derived CAD phenotype or cardiovascular (CV) events varies by sex.

Methods:
We assessed annual average exposure to particulate matter (PM
2.5
& PM
10
) and ozone by home zip codes in the CT arm of the PROMISE trial. Pollutant exposure was related to CAD measures on CT (any plaque, obstructive CAD (stenosis ≥50%), high-risk plaque (HRP)) and composite endpoint (death, myocardial infarction, unstable angina), adjusting for age, obesity, ASCVD risk, and Socioeconomic Determinants of Health, using sex-stratified regression analyses.

Results:
We analyzed 2,252 (52%) women and 2,091 (48%) men (62±8 vs. 59±8 years, p<0.001) with intermediate ASCVD risk (12% vs. 17%, p<0.001). Women were less frequently exposed to PM
2.5
≥9.5 μm/m
3
(45.1% vs. 48.8%, p=0.011) but more frequently to ozone >45 ppb (40.5% vs. 36.8%, p=0.011) compared to men. Exposure to PM
2.5
≥9.5 μm/m
3
related to 42% higher odds of obstructive CAD (aOR 1.42, 95%CI: 1.02-1.97, p=0.040) in women but not in men. High PM
10
and ozone exposures did not relate to stenosis or HRP in either sex (p>0.14)
(Figure 1a)
. Exposure to ozone >45 ppb was related to a higher hazard of events in men (aHR 2.20, 95%CI: 1.36-3.55, p=0.001) but not in women (aHR 1.05, 95%CI: 0.58-1.90, p=0.88). Exposure to high PM
2.5
and PM
10
levels was not associated with events in sex-stratified analysis
(Figure 1b)
.

Conclusions:
Sex significantly influences pollutant impact on CAD. High PM
2.5
exposure increases obstructive CAD risk exclusively in women, while high ozone exposure raises CV event risk in men. Findings stress the need for sex-specific strategies in combating pollution's cardiovascular effects.
Abstract 16475: Mitral Valve Transcatheter Edge to Edge Repair: A Real-World Analysis of Racial Differences in Uptake and Outcomes
Authors: Pillai Balakrishnan , Beyene Tariku J , Heidenreich Paul A , Yong Celina M
Published: December 2023

Introduction:
Recently, percutaneous mitral valve transcatheter edge to edge repair (TEER) with the MitraClip system has grown as a treatment option for mitral regurgitation. However, data describing the real-world adoption of this technology are limited, especially regarding differences by race and ethnicity.

Research Question:
What have been the trends in usage of mitral valve TEER during its early uptake in the United States, and has there been equitable adoption across racial and ethnic groups?

Methods:
In a comparative study using the Veterans Affairs (VA) Clinical Assessment Reporting and Tracking database from Jan 1,2017 to Dec 31, 2022, we describe temporal changes in mitral valve TEER use within the VA system, and differences in uptake by race/ethnicity (White non-Hispanic, Black non-Hispanic, Hispanic). We further describe 30-day and 1-year mortality following TEER by race/ethnicity.

Results:
The rate of mitral valve TEER use increased significantly overall (p=0.008), and across each race/ethnic group studied (
Figure 1
). However, relative to White non-Hispanic patients, Black non-Hispanic and Hispanic patients were less likely to receive mitral valve TEER (adjusted OR 0.45 [95% CI 0.28-0.70] and adjusted OR 0.47 [95% CI 0.19 -0.98] respectively) (
Figure 2
). The adjusted 30-day and 1-year mortalities following mitral valve TEER were similar between races/ethnicities.

Conclusions:
Although patients benefit similarly following mitral valve TEER, adoption among non-Hispanic Black and Hispanic patients trails non-Hispanic White patients. This highlights the importance of identifying and addressing barriers to adoption among underrepresented groups.
Abstract 16495: Cellular Senescence and Mitochondrial Dysfunction in Very Low-Density Lipoprotein-Induced Cardio-Lipotoxicity
Authors: Lin Yi-Hsiung , Lee Hsiang-chun
Published: December 2023

Dyslipidemia, the hallmark of the metabolic syndrome, plays an important role in cardiovascular and cardiometabolic diseases. The heart utilizes lipids as major source of ATP and cardiomyocytes expresses abundant receptors for very low-density lipoprotein (VLDL), which is found exhibiting cardio-lipotoxicity in the metabolic syndrome. This study investigates the effects of VLDL in cardiomyocyte senescence and mitochondrial function. VLDL from metabolic syndrome patients was used to treat H9C2 cardiomyocytes for 72 hours. The RNA-sequencing was conducted to find novel senescence-associated signaling pathways in VLDL-induced lipotoxicity. The newly-found targets and regulators were validated using qPCR and Western blot. In addition, the senescence-associated secretory phenotype, the effects of VLDL on mitochondrial ATP production, NAD
+
/NADH, and mitochondrial membrane potential were also determined. The results showed that VLDL upregulated 97 cardiac hypertrophy-related genes expression. Among them, 84 genes were related to senescence, and 30 genes were apoptosis-related. Besides, 63 autophagy genes were also affected by VLDL treatment. The KEGG analysis showed that VLDL induced multiple senescence-related signaling pathways such as TP53, ERK-FOXO4, and TGF-β-related pathway. VLDL also exhibited dose-dependent influence on intra-mitochondrial Ca
2+
, and associated molecule Hmox1, Htt and Xdh expression. This study revealed novel mechanisms for the VLDL-induced cardio-lipotoxicity, which was shown involving multiple senescence-related signaling pathways and mitochondrial function regulators. The results suggested that the senescence signaling is a potential therapeutic target for cardiometabolic diseases.
Abstract 16517: Association of Low Left Atrial Appendage Velocity With Increased Risk of Atrial Fibrillation Recurrence After Catheter Ablation: A Meta-Analysis
Authors: Raval Maharshi , Katukuri Nishanth , Venugopalan Sruthi , Jain Akhil , Majmundar Vidit , Siddiq Sajid , Desai Rupak
Published: December 2023

Background:
Catheter ablation (CA) is an effective and potentially curative treatment in patients with atrial fibrillation (AF). However, the recurrence of AF following CA treatment in cases of persistent atrial fibrillation (PeAF) remains a significant concern. This study aims to establish a correlation between the peak flow velocity of the left atrial appendage (LAAV) and the AF recurrence post-CA for PeAF.

Methods:
PubMed/Medline, EMBASE, and SCOPUS databases were systematically reviewed to find studies through June 2023 reporting data on the relationship between the LAAV and the recurrence of AF in individuals who have undergone CA for PeAF. Binary random effects models were used to estimate pooled outcomes. I2 statistics were used to interpret heterogeneity, with I
2
>75% indicating substantial inter-study variation. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate. A p<0.05 was considered statistically significant.

Results:
A total of 9 studies between 2000-2023 were included in our meta-analysis. The pooled univariate analysis revealed no association between LAAV and recurrence of AF in individuals who have undergone CA with a pooled OR of 1.09 (95CI 0.96-1.22) p=0.45, I2=86.59%. The multivariate analysis, after adjusting for overall modifiable risk factors, yielded significant results, with an adjusted odds ratio (aOR) of 1.41 (95CI 1.15-1.74) p<0.01, I2=85.24%. Sensitivity analysis, using the leave-one-out method demonstrated the robustness and stability of the results, indicating that no single study disproportionately influenced the overall findings with aOR 1.41 (95CI 1.15-1.74) p<0.01.

Conclusions:
This meta-analysis revealed that low LAAV is associated with high-risk of AF recurrence following CA. Identifying a specific subgroup of individuals at high risk of AF recurrence with the help of pre-CA LAA velocity will facilitate the early institution of alternative treatment strategies.
Abstract 16549: Longitudinal Associations of Accelerometer-Based Sedentary Time and Physical Activity With Blood Pressure Progression From Childhood Through Young Adulthood: A 13-year Mediation and Isotemporal Substitution Study of 2513 Children
Authors: Agbaje Andrew O
Published: December 2023

Introduction:
Randomized controlled trials in the young population concluded that moderate-to-vigorous physical activity (MVPA) was ineffective in lowering blood pressure (BP). The associations of cumulative sedentary time (ST), light physical activity (LPA), and MVPA with BP from ages 11 - 24 years, the isotemporal substitution of ST with LPA or MVPA, and the mediation path through which movement behaviour exact their impact on BP was examined.

Hypothesis:
Increased ST would be associated with increased BP while cumulative LPA and MVPA would be associated with decreased BP.

Methods:
Altogether 2513 children (61% female) from the Avon Longitudinal Study of Parents and Children birth cohort, UK who had data on at least one time-point measure of accelerometer-based movement behaviour across the follow-up and complete BP measures at ages 11, 15, and 24 years clinic visits were studied. MVPA was categorized into ≥60mins/day or less according to WHO’s PA guidelines. Longitudinal associations and isotemporal substitutions were examined with generalized linear-mixed effect models whereas the mediation path was examined using structural equation models, adjusting for cardiometabolic and other lifestyle factors.

Results:
After full adjustment, a 1-minute cumulative ST from ages 11-24 years was positively associated with increased systolic BP (0.009 mmHg [95% CI 0.007 - 0.011]; p<0.001), and diastolic BP. A 1-minute cumulative LPA was associated with decreased systolic BP (-0.007 mmHg [-0.009 - -0.004]; p<0.001), but not diastolic BP. Persistent MVPA of ≥60mins/day was not associated with reduced systolic BP but paradoxically associated with increased diastolic BP (0.007 mmHg [0.002 - 0.013]; p=0.008). The longitudinal replacement of 10 minutes of ST with equal time in LPA during childhood, adolescence, and young adulthood cumulatively decreased systolic BP by -3 mmHg and diastolic BP by -2 mmHg during the 13-year follow-up period. Replacing 10 minutes of ST with 10 minutes of MVPA had no statistically significant effect. The positive association of ST with BP was fully mediated by lean mass (93% mediation).

Conclusions:
Future guidelines may emphasize the importance of early LPA intervention from childhood for the prevention and treatment of elevated BP.
Abstract 16577: Unraveling T-cell and Macrophage Chemokine Crosstalk in Immunotherapy-Induced Myocarditis
Authors: Huang Yuhsin V , Lee Daniel , Branche Corynn , Lin Zachary , Wang Emma , Banga Natasha , Neal Joel , Maecker Holden T , Witteles Ronald M , Nguyen Patricia K , Alcaide Pilar , Berry Gerald J , Wu Sean M , Zhu Han
Published: December 2023

Introduction:
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate immunity against tumor cells but can cause immune related adverse events such as myocarditis, a rare but serious side effect with up to 40% mortality.

Hypothesis:
Macrophages contribute to recruitment of cytotoxic T-cell subsets to the heart in the setting of ICI, causing myocarditis.

Methods:
To study the role of macrophage depletion on ICI myocarditis, we treated MRL/Pdcd1-/- mice with liposomal clodronate. To identify timing of immune infiltration, we performed serial single cell T-cell receptor and RNA sequencing of CD45+ cells from the hearts/blood of MRL/Pdcd1-/- myocarditis mice at 1, 2, and 4 weeks of age. We treated MRL mice with anti-PD1/CTLA4 to induce myocarditis and assessed if anti-CXCR3 could decrease effector CD8+ T-cell cardiac infiltration and mitigate myocarditis. We studied the effects of in vitro CXCR3 blockade on CXCR3+ T-cell migration in a transwell assay.

Results:
Serial single-cell TCR sequencing/scRNA-seq of immune cells from MRL/
Pdcd1-/-
vs. MRL control hearts showed infiltration of CXCL9/10+ macrophages (
Fig. 1, A
) along with progressive clonal expansion of CXCR3+ effector CD8+ T-cells in the heart starting at 2 weeks of age, prior to clinical onset of myocarditis. Macrophage depletion with liposomal clodronate reduced myocarditis and improved survival in MRL/
Pdcd1-/-
mice (
Fig. 1, B-C)
. CXCR3 blockade with anti-CXCR3 antibody reduced myocarditis, decreased CXCR3+ CD8+ T-cell infiltration, and improved survival in mice treated with anti-CTLA4/anti-PD1 antibodies
(Fig. 1, D-E)
. CXCR3 blockade in transwell assay also reduced migration of CD8+CXCR3+ T-cells towards the macrophage compartment
(Fig. 1, F)
.

Conclusions:
CXCL9/10+ macrophages likely play a critical role in development of ICI myocarditis through the recruitment of CXCR3+ effector T-cells into the heart, making this pathway an attractive therapeutic target.
Abstract 16589: Predicting Cardiovascular Risk in Participants Treated With Tirzepatide in the SURPASS 1-5 Trials
Authors: Wiese Russell J , Wang Hui , Mody Reema , Benneyworth Brian D
Published: December 2023

Predicting atherosclerotic cardiovascular disease (ASCVD) risk considers factors that individually influence the likelihood of experiencing a major cardiovascular (CV) event. Tirzepatide (TZP) is a GIP and GLP-1 receptor agonist that improved risk factors such as lipid profile and systolic blood pressure across the Phase 3 SURPASS T2D program. We compared the effect of TZP versus the comparator on calculated ASCVD risk from baseline to endpoint in each of the 5 SURPASS (S) studies.

We assessed the ASCVD risk in T2D participants without CVD history from S 1-5 studies using an American College of Cardiology/American Heart Association risk engine. The risk engine considers the factors: sex, age, race, total cholesterol, high density lipoprotein, systolic blood pressure, antihypertensive medication use, smoking and diabetes status. Risk scores and categories are summarized by treatment group.

The baseline characteristics vary between studies (female sex ranges from 44.9% to 54.6%, mean age in years ranges from 53.6 to 64.3) but were similar among treatment groups within each study. The median baseline risk score across the TZP dose range were 6.5-11.5 for S-1, 9.3-10.8 for S-2, 12.4-15.4 for S-3, 22.9-26.0 for S-4, and 14.8-19.1 for S5. At the primary endpoint (40 or 52 Weeks), the ASCVD risk category for 10.9-21.4% of TZP-treated participants improved versus 2.9-12.7% for placebo/comparator (Table). Also, the risk category for 1.2-9.4% of TZP-treated participants worsened versus 6.3-14.9% for placebo/comparator. The median CV risk score was decreased in all TZP treatment groups while the median CV risk score was increased in the placebo/basal insulin groups. In SURPASS-2, the decreases in CV risk score were qualitatively greater in the TZP groups compared to the semaglutide group.

TZP treatment lowers CV risk and significantly more participants shift to a lower CV risk category when compared to placebo, basal insulins, and semaglutide.
Abstract 166: Novel Mechanism of Docosahexaenoic Acid Reducing Tissue Injury by Targeting Immune Cells and HMGB1 Release
Authors: Choudhary Rishabh C , Yin Tai , Shoaib Muhammad , Nishikimi Mitsuaki , Singh Parmeshar S , Becker Lance B , Kim Junhwan
Published: December 2023

Introduction:
Dysregulated immune blood cell response has been implicated in contributing to brain injury following cardiac arrest (CA). Specifically, increased plasma HMGB1 has emerged as a critical mediator of brain damage. However, the underlying mechanisms of the dysregulated immune response and increased HMGB1 after CA remains unclear. Moreover, limited efforts have been made to develop therapeutic interventions targeting this dysregulated immune response.

Objective:
To elucidate the pathologic immune response during early phase of post-resuscitation and explore this as a targeted therapeutic potential using LPC(22:6), a previously shown neuroprotective compound.

Methods and Results:
We examined changes in lymphocytes, neutrophils, and monocytes in blood samples obtained from human CA patients. Subsequently, we conducted a time course study in rat CA model to examine changes in these cell populations and investigate the mechanisms underlying the increased HMGB1 levels in post-CA blood with/without plasma supplementation of LPC(22:6). We observed an increase in lymphocytes and neutrophils within one-hour post-resuscitation in human patients and rats. In rats, the increased levels of lymphocytes and neutrophils were followed by an increase in plasma HMGB1 level and monocytes. We further, identified that HMGB1 was significantly upregulated in CD4-positive cells, indicating that T cell-released HMGB1 is the primary source for its elevation. Intriguingly, supplementation of LPC(22:6) prevented the overexpression of HMGB1 in CD4-positive cells, the increase in plasma HMGB1 levels, and the number of monocytes. These findings support the sequential events of dysregulated blood immune response initiated by lymphocyte activation, leading to increased HMGB1 levels and subsequent monocyte activation during early phase of resuscitation after CA. Thus, our results demonstrate the efficacy of LPC(22:6) in inhibiting the expression of HMGB1 in CD4-positive T cells, thereby mitigating this inflammatory cascade.

Conclusion:
These findings provide novel insights into the mechanisms underlying the dysregulated immune response after CA and highlight the therapeutic potential of targeting this immune response to improve brain function.
Abstract 16620: Long-Term Prognostic Factors for Cardiovascular Events in Patients With Chest Pain Without Diabetes Mellitus and Significant Coronary Stenosis
Authors: Rha Seung-Woon , Choi Byoung Geol , Ahn Woo Jin , Choi Se Yeon , Byun Jae Kyeong , Cha Jinah , Hyun Sujin , Park Soohyung , Kang Dong Oh , Park Eun Jin , Choi Cheol Ung
Published: December 2023

Background:
Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD and DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited.

Methods:
A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiovascular events (MACE) were defined as the composite of total death, myocardial infarction (MI), and revascularization. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of MACE, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years.

Results:
Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a recurrent chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia, ICS, the use of aspirin and nitrates were associated with long-term MACCE.

Conclusions:
Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with anti-anginal medications.
Abstract 16629: Comparison of Clinical and Genetic Risk Model for Ischemic Stroke After Atrial Fibrillation Catheter Ablation
Authors: Park Je W , Kim Daehoon , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-sun , JOUNG BOYOUNG , LEE Moon Hyoung , Pak Hui-Nam
Published: December 2023

Introduction:
CHA
2
DS
2
-VASc score (CVS) is used to estimate risk of stroke in atrial fibrillation (AF) patients. But, CVS does not include genetic risk. We explored clinical and genetic risks for ischemic stroke (IS) after AF catheter ablation (AFCA).

Methods:
We used genome-wide association study (GWAS) data in European (34217 IS, 406111 controls) and Asian (22664 IS, 152022 controls) to develop polygenic risk score (PRS) for IS in 2897 independent Korean AF patients (Median 60 years, male 74.0%, paroxysmal AF 66.3%, anticoagulation rate 60% in 1367 patients with CVS ≥ 2 who underwent AFCA. Patients with IS within 2 weeks after AFCA were excluded. In the independent AF cohort during median 50 [IQR 28-94] months follow-up, 48 experienced IS after AFCA. We developed two different CVS-combined PRS models in the independent cohort using European and Asian GWAS data. Using p-value <5e-8, rs635634 and rs671 were used in CVS-combined European PRS (CVS-EPRS) and CVS-combined Asian PRS (CVS-APRS) model, respectively in the independent cohort. We compared C index of risk models to investigate prediction power for IS.

Results:
CVS was higher in patients with IS than in their counterparts (3.0 IQR [1.0, 4.0] vs. 1.0 [1.0, 2.0], p<0.001). Overall C index was 0.716 in CVS model, 0.711 in CVS-EPRS model, and 0.725 CVS-APRS model. For 1-year IS after AFCA, CVS-APRS model improved C index as compared to CVS model (0.834 vs. 0.813, p=0.037). For 3-year IS after AFCA, C index was higher in CVS-APRS model rather than CVS-EPRS model (0.746 vs. 0.721, p=0.030). In patients with CVS < 2, both CVS-APRS (0.849, p=0.013) and CVS-EPRS (0.766, p=0.027) models showed better prediction for 1-year IS compared to CVS model (0.523).

Conclusions:
In AF patients with AFCA, genetic polymorphism with clinical risk factors contributed to predict 1-year IS. Genetic contribution was more obvious in AF patients with CVS <2. However, ethnicity might be an important factor in adapting genetic contributions to predicting IS.
Abstract 16962: A Polygenic Predictor of Baseline QT is Associated With Sotalol-Induced QT Prolongation
Authors: Lancaster Megan C , Davogustto Giovanni E , Prifti Edi , Perret Claire , Funck-Brentano Christian , Roden Dan M , Salem Joe-Elie
Published: December 2023

Background:
Drug-induced QT interval prolongation raises the risk of fatal arrhythmia and is a central issue in safety pharmacology. Yet individual QT drug response is highly variable, and risk stratification remains a challenge. We hypothesized that genetic factors underlying the baseline QT influence this variation in QT drug response.

Methods:
A cohort of 990 healthy subjects was prospectively challenged with a single 80 mg oral sotalol dose. Exclusion criteria included abnormal ECG, cardiac disease, and QT-prolonging drug use. ECGs were obtained at baseline and 3 hours post-dose. QT response was defined as absolute change in Fridericia heart-rate corrected QT (ΔQTc). Plasma sotalol was measured 3 hours post-dose. Subjects were genotyped on the MEGA array. Principal component analysis of genotypes was used to define genetic ancestry. A polygenic score (PGS) for the baseline QTc comprised of 465,399 common variants was calculated from assayed and imputed genotypes. The difference in PGS between subjects with high QT response (ΔQTc≥60 ms) and those with ΔQTc<60ms was assessed by Mann Whitney test. A multivariable regression model was used to assess the association between PGS and ΔQTc after covariate adjustment.

Results:
Of the 990 subjects, 952 (96%) passed genomic quality control and were included in analysis. 62% were female (n=590), with median age 23 (interquartile range (IQR) 21-32). Self-reported ancestry was 89% European (n=850) and 11% North African (n=102). The median ΔQTc 3 hours post-sotalol was 21 ms (IQR 12-30). Ten subjects (1%) had ΔQTc≥60 ms, and their PGS was significantly higher compared to those with ΔQTc<60 ms (
P
=0.0097, Figure 1A). In the regression model, PGS was positively associated with ΔQTc (
P
=0.0007, Figure 1B).

Conclusion:
Common genetic variants associated with the baseline QT also capture part of the repolarization response to sotalol. This adds to the emerging concept that the genetic architecture of a trait can predict drug response.