bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15540: Single Cell Transcriptional-Epigenetic Profiling and Sub-Cellular Proteomics Demonstrate That HIV-Nef Extracellular Vesicles Modulate Human Macrophage Heterogeneity to Promote Atherosclerosis
Authors: Chelvanambi Sarvesh , Decano Julius , Ge Rile , Yanagihara Yoshihiro , Whelan Mary , Jule Amelie , Kuraoka Shiori , Mukai Shin , Enomoto Takashi , Zimmer Jonas , Bartoli-Leonard Francesca , Sonawane Abhijeet , Tanaka Takeshi , Santinelli-Pestana Diego V , Kasai Taku , Pham Tan , Matamalas Joan T. , Ho Sui Shannan , Aikawa Elena , Singh Sasha A , Aikawa Masanori
Published: June 2023

Background:
In the era of modern Anti-Retroviral Therapy, people living with HIV continue to remain at a higher risk than the general population for cardiovascular diseases including atherosclerosis. We hypothesized that circulating extracellular vesicles (EV) containing HIV-Nef protein promote inflammation by switching the pattern of macrophage heterogeneity towards a pro-inflammatory state that underlies cardiovascular disease.

Methods & Results:
Human primary macrophages were stimulated with EV engineered to contain HIV-Nef. Macrophage heterogeneity was characterized by simultaneous single cell mRNA-seq and single cell ATAC-seq integrated with WNN mapping in 50,931 cells. Among 16 clusters (Fig. A), pseudotime (Slingshot), gene regulatory (DoRothEA and SCENIC) and transcription factor motif accessibility (ChromVar) analyses demonstrated that HIV-Nef regulates 3 inflammatory clusters as gauged by differentially active and accessible transcription factors, e.g., JUN, YY1 and STAT1. Sub-cellular proteomics identified differentially abundant proteins associated with DNA (662 proteins), nucleus (261), cytosol (461), cell surface (72) and EV (132). Pathway enrichment analysis of these proteins revealed changes in biological processes in immune responses, cytoskeletal regulation, and metabolism. Functional phenotyping showed HIV-Nef shifts macrophages towards a pro-inflammatory phenotype by suppressing atheroprotective efferocytosis, promoting chemotaxis and altering metabolic state. Furthermore, short-term injection of HIV-Nef EV into WT mice induced inflammatory chemokine secretion, while long-term injection into

Ldlr
-/-

mice enhanced atherogenesis (Fig.B).

Conclusions:
Persistent Nef in EV of HIV survivors may modulate macrophage heterogeneity to promote chronic inflammation. These findings may help identify patients at risk for cardiovascular complications and develop novel atheroprotective therapies.
Abstract 15551: Pulmonary Hypertension in Patients With Noonan Syndrome Undergoing Cardiac Catheterization
Authors: Collins Shane , Critser Paul , Gauvreau Kimberlee , Roberts Amy E , Mullen Mary P
Published: June 2023

Introduction:
Noonan syndrome (NS) is an autosomal dominant genetic disorder associated with a high incidence of cardiovascular disease. We sought to investigate pulmonary hypertension (PH) in patients with NS, as well as characterize the hemodynamics, cardiovascular interventions, genetics, and transplant-free survival.

Methods:
A retrospective, descriptive cohort study was conducted among patients with NS who underwent cardiac catheterization at Boston Children’s Hospital between 2000 and 2020. Patient demographic, clinical, and hemodynamic data were collected for cohorts of patients with and without PH.

Results:
Eight-seven patients with Noonan syndrome underwent cardiac catheterization in the study period. Fifty-nine (68%) patients had a NS-associated pathogenic variant, while 28 (32%) had a clinical diagnosis of NS. Eleven (13%) patients had PH by 6
th
World Symposium on Pulmonary Hypertension criteria: two patients with Group 1 Pulmonary Arterial Hypertension (PAH), seven Group 2 PH, and two Group 4 PH. There were significant differences in NS-associated causative gene in patients with and without PH, with RAF1 (p=0.013) and KRAS1 (p=0.015) more common among PH patients. A clinical diagnosis of hypertrophic cardiomyopathy (p=0.009) was more common in PH patients, while valvar, subvalvar, or supravalvar pulmonary stenosis (p=0.011) was less common. PH patients were significantly more likely to have aortic-valve interventions (p=0.025) and less likely to have valvar right-sided heart interventions (p=0.037). Transplant-free survival at five years was lower in the PH group (73%) compared to the non-PH group (99%).

Conclusion:
In a cohort of patients with Noonan syndrome undergoing cardiac catheterization, we noted differences among those with and without PH for NS-associated causative gene, associated hypertrophic cardiomyopathy or structural heart disease, interventions, and transplant-free survival. The prevalence of PH among this population demonstrates the need for future studies on the association between NS and pulmonary vascular disease.
Abstract 15557: Missed Diagnosis of Constrictive Pericarditis: Importance of Multimodality Imaging
Authors: Ahmad Soban , Moey Melissa , Ardhanari Sivakumar
Published: June 2023

Introduction:
Constrictive pericarditis is a potentially reversible cause of hypotension that is diagnostically challenging. Multimodality imaging is important in the evaluation of patients for constrictive pericarditis to ensure timely management.

Case Presentation:
A 68-year-old female with a history of chronic hypotension controlled with midodrine and fludrocortisone, end-stage renal disease, and rheumatoid arthritis was admitted to our hospital following a ground-level fall leading to left femur fracture. At admission, her blood pressure was 100/72 mmHg and heart rate was 84 per minute. No pericardial rub, murmurs, or jugular venous distension were present. Laboratory evaluation revealed normal serum electrolytes, thyroid-stimulating hormone, and morning cortisol levels. A routine transthoracic echocardiogram was performed as part of her perioperative cardiac evaluation that demonstrated a beat-to-beat septal diastolic shudder and annulus reversus suggestive of constrictive pericarditis. These findings were confirmed with cardiac magnetic resonance imaging (CMR) that showed pericardial thickening, tubular-shaped right ventricle with impaired filling, septal bounce as well as respirophasic early diastolic septal flattening. Cardiothoracic surgery was consulted however definitive management with pericardiectomy is pending at the time of this report.

Conclusion:
With recent advances in tissue Doppler imaging, echocardiography can be used in clinical practice to diagnose constrictive pericarditis. Reversal of the relationship between lateral and medial e` velocities (annulus reversus) and respiration-related ventricular septal shift (septal shudder) are suggestive of constrictive pericarditis.
Abstract 15622: Hydro-Pneumopericardium Due to Esophageal-Pericardial Fistula: A Rare Complication of Esophageal Stent Migration
Authors: Talento Suzanna , Schneider Svenja , Ullah Waqas , Marhefka Gregary D
Published: June 2023

Introduction:
Esophageal-pericardial fistulas are rare complications of a variety of conditions ranging from benign esophageal disorders to iatrogenic etiologies such as radiofrequency catheter ablation. Here, we present a unique case of esophageal-pericardial fistula formation following esophageal stent migration in the setting of ulcerative esophagitis and benign esophageal stricture.

Case Presentation:
A 53-year-old woman with a history of ulcerative esophagitis and associated esophageal stricture was managed with esophageal stenting. Following stenting, her course was complicated by esophageal stent migration, resulting in severe dysphagia and multiple gastrointestinal bleeds requiring percutaneous endoscopic gastrostomy (PEG) tube placement. She presented with fatigue, melena, and dark output from her PEG tube and was hypotensive, tachycardic, and tachypneic. An echocardiogram (Figure 1A) showed hydro-pneumopericardium with cardiac tamponade physiology requiring emergent pericardiocentesis and aspirated fluid shown in Figure 1B. A subsequent computed tomography (CT) scan of the chest demonstrated a large complex pericardial effusion with air in the anterior pericardium, a large esophageal-pericardial fistula, and a moderate left hydropneumothorax (Figure 1C). Given the extent of her esophageal defect, the patient was taken for an esophagectomy with esophagostomy formation.

Discussion:
On review, we found only a few cases of hydro-pneumopericardium in the context of spontaneous pericardial herniation due to subcutaneous emphysema, radiofrequency ablation for atrial arrhythmias and esophagectomy for esophageal adenocarcinoma. However, there has been no report of esophageal-pericardial fistula due to esophageal stent migration.

Conclusion:
In an appropriate setting, clinicians should maintain a high index of suspicion for esophageal-pericardial fistulas, as delay in the management of these conditions could be fatal.
Abstract 15649: Terf2ip K240 Sumoylation Drives Endothelial Senescence and Atherogenesis via Activating Parp1
Authors: Chau Khanh , Imanishi Masaki , Li Shengyu , Kotla Sivareddy , Ko Kyung A , Nguyen Minh T , Berrios Turcios Estefani , Abe Rei , Zhang Aijun , McBeath Elena , Fujiwara Keigi , Jin Gi Young , Heo Kyung-Sun , Cheng Jinke , Thomas Tamlyn , Schadler Keri , Gupte Anisha A , Shen Ying H , Lin Steven , Yeh Edward T , Fujiwra Keigi , Hamilton Dale , Cooke John P , Wang Guangyu , Abe Junichi , Le Nhat Tu , Zuo Yong , Sharma Amrish
Published: June 2023

The goal of this study:
Telomeric repeat-binding factor 2 (TRF2) interacting protein 1 (TERF2IP) not only associates with TRF2 to protect telomeres but also associates with RSK to promote senescence. The later has been detected in endothelial cells (ECs) under disturbed flow (DF), which involved TERF2IP S205 phosphorylation. Besides, it has been suggested that TERF2IP K240 can be SUMOylated; however, its role in senescence and atherogenesis remains unknown.

Methods:
We investigated the functional role of TERF2IP K240 SUMOylation utilizing a model of DF-induced atherogenesis in TERF2IP K237R knock-in (KI) (mouse K237 is equivalent to human K240) mouse carotid artery by partial ligation and RNA isolated from mouse lung ECs.

Results:
TERF2IP K240 SUMOylation was increased in ECs under DF and provoked telomere shortening-associated senescence. TERF2IP K240 SUMOylation occurred independently of TERF2IP S205 phosphorylation although both events were blunted by the RSK specific inhibitor (FMK-MEA), and EC senescence as well as related events were abolished by both depletion and point mutation of TERF2IP at S205 or K240 residue. Whereas point mutation of TERF2IP at S205 prevented RSK-associated NF-kB activation, that of K240 exhibited no effect, suggesting that K240 SUMOylation did not involve in EC inflammation. By inducing persistent telomere DNA damage, TERF2IP K240 SUMOylation distinctive provoked telomere shortening-associated EC senescence via inducing persistent DNA damage response and subsequent PARP1 activation. Finally, a mouse model of DF-induced atherogenesis showed that atherogenesis was inhibited in TER2IP K237R KI mice although body weight and cholesterol level were unaltered

Discussions:
These data have revealed that EC senescence plays a critical role in atherogenesis and that TERF2IP K240 SUMOylation can be a novel therapeutic target for atherogenesis.
Abstract 15673: AI-Enabled Prediction of Bleeding in Patients Supported on Extracorporeal Membrane Oxygenation
Authors: Alexander Peta M , DeForte Shelly , Dufek Sally , Gauthier Mitchell , Geppert Jeffrey , Ramirez Jessily , Riedl Michael , White William , Bickel Jonathan , Nemati Hayati Arash , Sleeper Lynn A , Thiagarajan Ravi R , Jenkins Kathy J
Published: June 2023

Introduction:
Clinical data within the electronic health record (EHR) combined with artificial intelligence (AI) and machine learning (ML) offer the promise of rapid advancement of knowledge at the point of care.

Hypothesis:
We hypothesized that aggregating clinical data with preservation of relational elements will yield a more precise and less biased representation of patient data for predictive analytics. We leveraged these data to predict clinically significant bleeding in the ECMO-supported population.

Methods:
The data of children 0-19 years managed on ECMO for first run cardiac indications in a single center between 1/2010-12/2020 were analyzed. Bleeding Day was defined as any 24-hour period which included pulmonary, gastrointestinal, intracranial or surgical wound hemorrhage, and/or surgical intervention or Factor VIIa administration for hemorrhage control. EHR data documenting the ECMO episode and embedding relational elements were used to inform 1) a multivariable logistic regression model matching a previously- performed analysis using manually extracted data [1], and 2) a feature-limited graph neural network (GNN) model of bleeding.

Results:
There were 272 patients supported with ECMO for total 2,012 days which informed the analysis, with median age 0.4 [IQR 0.03, 3.30] years, 56% male and 14% of days including a bleeding event. Direct comparison of the EHR-derived logistic regression model with previously published manual results are presented in Table 1. Inclusion of the EHR-derived covariates in a GNN model achieved similar operating characteristics.

Conclusions:
EHR-derived AI-prediction models of bleeding in this complex patient population are at least as accurate as models with manual data and traditional statistical analysis, but with a known pathway to potentially more accurate predictions. This methodology can be replicated to other conditions, allowing rapid insights towards a learning healthcare system.
Abstract 15674: Utilization Rates of Follow-Up Testing With Pyp Scan and Cardiac Mri, and Clinical and Demographic Determinants of Their Use Among Patients With Echocardiographic Features of Cardiac Amyloidosis: A Population-Based Case Control Study
Authors: Fessehaie Nathaniel , Bediako HIlary , Levin Michael , Kallan Michael , Julien Howard , Eberly Lauren A
Published: June 2023

Introduction:
Cardiac amyloidosis (CA) is an underdiagnosed cause of heart failure. Echocardiography provides an excellent screening tool for cardiac amyloidosis. For patients with echocardiographic findings suggestive of cardiac amyloidosis, it is unknown how frequently follow-up imaging such as 99mTc PYP-scan or cardiac MRI is obtained. Diagnosis rates after a suggestive echocardiogram as well as disparities in rates of follow-up imaging and subsequent CA diagnosis are also unknown.

Methods:
We extracted all index cardiac echocardiograms at our institutions of adult patients that were suggestive of a possible diagnosis of CA, which was defined as: moderate or worse left ventricular concentric hypertrophy plus grade II or grade III diastolic dysfunction or diastology could not be determined due to arrhythmia in those with atrial fibrillation. Patients with known diagnosis of amyloidosis were excluded. We determined which patients underwent further testing with
99m
Tc-PYP scan or cardiac MRI. We performed a population based case control study in which we compared clinical and demographic factors between those who underwent follow-up testing with either PYP scan or cardiac MRI (cases) vs those who did not (controls).

Results:
Of 1348 echoes that met inclusion criteria, only 110 (8.2%) underwent PYP scan or cardiac MRI. Of those, 10.0 (11%) patients ultimately were diagnosed with CA. Between cases and controls, there was no difference in age, gender, or race/ethnicity. There were no differences in rates of HFrEF or HFpEF between cases and controls. Cases had lower rates of CKD (27% vs. 40%, p=0.01) and ESRD (8.2% vs 15%, p=0.03) and had higher rates of carpal tunnel disease (12% vs. 6%), p<0.05). The rates of cardiologist ordered echocardiograms were similar between cases and controls. In terms of echocardiogram parameters, there were higher rates of grade III diastolic dysfunction (36.7% vs 20.4%, p=0.002) and more frequent rates of severe hypertrophy (36.7% vs. 21.7% p=,0.004)) among cases vs. controls.

Conclusions:
Among patients with echocardiographic features suggestive of CA, follow-up testing with
99m
Tc -PYP scans and Cardiac MRI, and subsequent diagnosis with CA remain low.
Abstract 15677: Comprehensive Physiological Phenotyping Reveals Deconditioning Among Individuals With Long-COVID-19
Authors: Howden Erin J , Wallace Imogen , Sesa-Ashton Jonathon , Wright Leah , Dawood Tye , Macefield Vaughan , La Gerche Andre
Published: June 2023

Introduction:
Post-acute COVID-19 sequalae (PASC) is a poorly understood constellation of symptoms that persist or emerge following the post-viral convalescent period. We sought to comprehensively evaluate cardiac and autonomic function and deconditioning as possible contributors to PASC associated fatigue.

Methods:
Thirty individuals with PASC (20F:10M; 41±11yrs; 137-730 days post-infection) prospectively underwent measures of autonomic function (heart rate [HR] and muscle sympathetic nerve activity [MSNA] response to passive head-up tilt 60° [HUT]); cardiac function (echocardiogram); arrhythmia burden (24-hour Holter monitor); exercise capacity (cardiopulmonary exercise test); hemoglobin and inflammatory biomarkers (CRP, troponin, IL-6, TNFα, IL-10). Participants were stratified by ongoing fatigue and symptoms of breathlessness (SOB+ or SOB-). Individuals with pre-existing conditions associated with fatigue were excluded.

Results:
Sixteen individuals (53%) reported breathlessness. Other common symptoms were palpitations (n=9; 30%) and light-headedness (n=5; 17%). Exercise capacity normalised for age and gender was lower in breathless subjects (SOB+) than in non-breathless subjects (SOB-); 70±11% vs 85±15%,
p
=0.004. The SOB+ group tended to have a blunted MSNA response to HUT when compared to SOB- (
p
=0.06), with similar prevalence of postural orthostatic tachycardia (SOB+ n=5 vs SOB- n=5). Echocardiography revealed that global longitudinal strain trended higher in the SOB+ group compared with SOB- (
p=
0.075), with similar prevalence of participants who fulfilled diastolic dysfunction criteria (SOB+ 5 vs SOB- 4). There were no significant sustained arrhythmias on 24-hour Holter monitoring. Hemoglobin, troponin and cytokines were all similar (p>0.05), but CRP was higher in the breathless group (
p
=0.016).

Conclusions:
This is the first comprehensive phenotyping of PASC with ongoing fatigue and breathlessness. We found that these symptoms were associated with reduced exercise capacity but without any associated cardiac impairment, arrhythmias, or autonomic dysfunction. These findings suggest that deconditioning may contribute to the pathophysiology of PASC.
Abstract 15735: Acquired Long-QT Syndrome Due to Excessive Loperamide Use
Authors: Saahil Jumkhawala A , Chen Kevin , Hemam Majd , Wengrofsky Perry , Solanki Pallavi
Published: June 2023

Background:
Loperamide is an over-the-counter opioid used primarily to treat diarrhea. Toxicity is known to predispose patients to life-threatening QT-interval prolongation and ventricular dysrhythmias.

Case:
A 42 year-old man with a past medical history of palpitations, tobacco use disorder, chronic back pain, and opioid use disorder presented to the hospital for syncope. In the preceding days, he experienced three episodes of palpitations followed by dizziness that would cause him to lose consciousness and fall, lasting five seconds each. He noted a longstanding opioid use history for chronic back pain, initially treated with oxycodone at a maximum dose of 600mg daily with transition to heroin for a total of three months. The patient then self-managed his opioid dependence with loperamide five years prior to admission, initially using doses of 200 mg daily, followed by three years of taking 768mg of loperamide daily. In attempts to avoid known electrophysiologic complications, he co-administered vitamin C (12,000-14,000 mg daily), magnesium citrate (1200mg/day), D3 (4000u daily), fish oil, centrum multivitamin 2 pills daily, and zinc. In the Emergency Department, the patient was given was given intravenous calcium, amiodarone, and magnesium for recurrent pulseless ventricular tachycardia, ultimately defibrillated and converted to junctional bradycardia. He was admitted to the cardiac care unit. Left heart catheterization demonstrated nonobstructive coronary artery disease; transthoracic echocardiogram was only notable for ejection fraction of 45%. He was treated with transvenous pacemaker (TVP) placement with pacing at 100bpm. Because of increasing intensity of opioid withdrawal, TVP was removed and isoproterenol infusion was started, while initiating transition to suboxone for maintenance treatment.

Conclusion:
This is the highest reported dose of loperamide intoxication as a method to self-manage opioid dependence. Despite low addictive potential, loperamide may be used at higher doses for opioid dependence or its euphoric effects. Treatment of loperamide toxicity should be aimed at reducing the risk of cardiotoxicity and managing withdrawal symptoms during detoxification, given its variable half-life.
Abstract 15761: SMYD1 Regulates OPA1-Mediated Cristae Remodeling and Supercomplex Formation to Protect From Ischemic Injury
Authors: Szulik Marta , Valdez Steven , Walsh Maureen , Davis Kathryn , Bia Ryan , Horiuchi Emilee , O'Very Sean , Nicolova Linda , Sheikh Hanin , Hickenlooper Samuel , Creed Magnus , Miller Mickey R , Wang Li , Garcia-Llano June , Tracy Chris , Drakos Stavros G , Funai Katsuhiko , Chaudhuri Dipayan , Boudina Sihem , Franklin Sarah
Published: June 2023

SMYD1 is a lysine methyltransferase, which has been shown to methylate lysine 4 on histone H3, an established mark of gene activation. SMYD1 is only expressed in skeletal and cardiac muscle and was originally shown to play a significant role in regulating cardiac development. In the adult myocardium, using inducible, cardiomyocyte-specific
Smyd1
knockout mice, loss of SMYD1 leads to massive downregulation of mitochondrial bioenergetics and overt heart failure. However, the effects of SMYD1 gain-of-function in the heart and its molecular function in the cardiomyocyte in response to ischemic stress remains unknown. Here we demonstrate that SMYD1a, the mouse ortholog of human SMYD1, positively regulates cardiac energetics and protects the heart from ischemic injury. To delineate how SMYD1a controls energy efficiency and metabolism in the cardiomyocyte, we generated a novel mouse model capable of inducible cardiomyocyte-specific SMYD1a overexpression. When subjected to ischemic injury these transgenic mice display reduced infarct size and cardiomyocyte death concomitant with enhanced mitochondrial respiratory efficiency. In addition, our molecular analysis revealed that the cardiac tissue in these animals is protected from ischemic injury through SMYD1a’s synergistic regulation of two key mitochondrial pathways. First, through its histone methyltransferase activity, SMYD1a maintains metabolic homeostasis by preserving basal expression of PGC-1α and its downstream targets including electron transport chain subunits. Second, SMYD1a regulates expression of OPA1, a key regulator of cristae morphology which drives the formation of electron transport chain supercomplexes to enhance mitochondrial respiration and ATP production. This work highlights SMYD1a as the only known epigenetic regulator of cristae morphology and identifies a novel molecular pathway by which cardiomyocytes dynamically regulate energy efficiency to protect from ischemic injury.
Abstract 15814: Postoperative Surveillance Imaging Following Elective Aortic Hemiarch Replacement
Authors: Kemp Cenea , Feng Zihan , King R. Wilson , McCabe Leighton , Aftab Muhammad , Reece T Brett B
Published: June 2023

Introduction:
The optimal protocol for imaging following aortic hemiarch replacement remains a topic of debate with varied intervals at each institution. For the last 3 years, our institution has surveilled patients at 3 months, yearly for 3 years, and at 5 years.

Hypothesis:
We hypothesize surveillance CT scans performed at 3 months will identify any pathologies related to the ascending aortic repair that will require re-intervention; additional imaging may be superfluous.

Methods:
Using our single institution-maintained database, 348 patients who underwent an elective aortic hemiarch repair between February of 2010 and December of 2021 were identified. One patient with a restricted chart was excluded. The timing for and stability of surveillance imaging was reviewed, paying special attention to pathology associated with the repair.

Results:
Of the 347 patients, 274 completed surveillance imaging. 231 patients had their initial imaging around 3 months following the operation, 126 patients completed imaging around one year, and 72 patients were imaged 2-10 years post-operatively with some patients undergoing multiple scans during this period. Ten patients required re-intervention; of these 10, two patients demonstrated pathology, on CT scan, associated with the actual ascending aortic repair. These two patients developed a pseudoaneurysm (PSA), one at the distal aspect of the repair and one at the left ventricular outflow tract. Another two patients had degeneration of known distal aortic aneurysms. The two PSAs were intervened upon within the first 3 months and the degenerating aneurysms were intervened upon at 1 and 2.5 years post-operatively.

Conclusions:
These data support surveillance imaging completed at 3 months following hemiarch replacement is sufficient to identify pathology related to the repair. While other indications may dictate ongoing surveillance, for most patients, the need for further imaging is potentially zero.
Abstract 15887: Bodyweight Changes and the Incidence of Atrial Fibrillation in Individuals With Obstructive Sleep Apnea
Authors: Turley Jeffery , Friedman Nicolette , Dowling N. Maritza , Barrows Ian , Falk Zachary , Melendez Dorys , Jain Vivek , Mercader Marco
Published: June 2023

Introduction:
Previous studies have demonstrated that obstructive sleep apnea (OSA) and obesity independently increase the risk for development of atrial fibrillation (AF). However, it is unknown whether weight changes in an OSA cohort also increase the risk of AF.

Methods:
This was a case control study from a single tertiary institution analyzing patients with a confirmed OSA diagnosis from 2013-2020. Patients with missing data on any of the key variables were excluded from these analyses. The covariates included smoking history, hypertension, congestive heart failure, chronic obstructive pulmonary disease, heart failure, and coronary artery disease. Patients’ weight at the time of AF diagnosis by electrocardiogram (ECG) was compared to the weight documented one year earlier. Weight at the time of the ECG closest to the sleep study date was compared to the weight one year prior for the control group. ​​Multivariate logistic regression analysis to examine the association between AF cases (versus controls) and weight percent change greater than 5%.

Results:
Among the 182 patients included in the analysis, the incidence of AF was 32.4% and the median weight change was -1.32± 11.69 lb (Table 1). About 36% of those diagnosed with AF had weight changes (gain or loss) above 5% compared to 23% in the control group (p = 0.07). The average weight change for those with diagnosed AF compared to individuals without AF was -2.5 ±11.8 lb vs. -0.76 ± 11.6 lb (p=0.19). The change in the adjusted odds of AF diagnosis among those with more than 5% weight gain or loss was 2.27 (95% CI =1.01, 5.09) compared to those with less or no weight change.

Conclusions:
Among individuals with OSA, those who exhibited weight changes greater than 5% over a one year period have increased odds for developing AF. Further large-scale studies need to be undertaken to understand the link between intentional versus unintentional weight loss.
Abstract 15917: Burden of End Organ Damage Among Patients With Hypertension and Associated Patient- and Facility-Level Factors in Ghana
Authors: Byiringiro Samuel , Hinneh Thomas , SARFO FRED S , Commodore-Mensah Yvonne , Dennison Himmelfarb Cheryl R
Published: June 2023

End-organ damage (EOD) are a serious complication of uncontrolled hypertension stroke, kidney disease, retinopathy, cardiovascular disease, and neuropathy are the most prevalent. The studies of EOD and associated factors are scarce in Sub-Saharan Africa. We explored the burden of EOD and the associated patient- and facility-level factors among patients with hypertension in Ghana.

Methods:
We recruited 14 health facilities and 15 patients with hypertension from each facility. Health facilities with hypertension services and patients on hypertension treatment were eligible for inclusion. The outcome of interest was the self-report of one or more of the most prevalent EOD. The patient-level independent variables were adherence to hypertension treatment, alcohol consumption, employment, and education. At the facility level, we included the facility type, size, ownership, and availability of hypertension guidelines as independent variables. The mixed-effect logistic regression model was used.

Results:
The study included two hundred and nine (209) patients. 172 (82%) were female, and the mean (±SD) age of participants was 61 (±12.7). 80 (38%) participants reported having suffered at least one EOD, the most prevalent being retinopathy, 38 (18%), followed by cardiovascular complications, 24 (11%). Employment was associated with lower odds (Odds Ratio: 0.42, 95% CI: 0.19, 0.90) of EOD than unemployment and tertiary or higher education was associated with lower odds (Odds Ratio: 0.32, 95% CI: 0.14, 0.74) of EOD than primary or lower educational level. Higher adherence to hypertension treatment was associated with lower odds (Odds Ratio: 0.88, 95% CI: 0.79, 0.97) of EOD.

Conclusion:
The prevalence of EOD is high. Patient-level interventions to improve hypertension care are needed with a focus on socio-determinants of health. Largescale studies are recommended to explore the facility-level factors that impact the development of EOD in Ghana.
Abstract 206: Easily Created Prediction Model Using Deep Learning For Termination Of Resuscitation (tor) In Out Of Hospital Cardiac Arrest (ohca) Cases: The All-japan Utstein Registry Experience.
Authors: Kajino Kentaro , Ong Marcus , Daya Mohamud R , Onoe Atsunori , Kuwagata Yasuyuki
Published: June 2023

Background:
Correct identification of futile prehospital resuscitation in out-of-hospital cardiac arrest (OHCA) may reduce unnecessary transports. Reliable prediction variables are needed for 'termination of resuscitation' (TOR) rules in OHCA. However, making such prediction models requires a large number of samples and time-consuming statistical analysis. Deep learning (DL), a form of artificial intelligence (AI), is attractive for building such prediction models. We made a TOR prediction model using a DL software, Prediction One (Sony Network Communications Inc., Tokyo, Japan). The purpose of this study was to evaluate the efficacy of this predictive model using general purpose AI compared to the Universal TOR rule for out - of hospital cardiac arrest.

Methods:
A retrospective, population-based review of OHCA victims without prehospital ROSC from January 1, 2010 to December 31, 2017 in the All-Japan Utstein Registry. We divided half (2010-2014) as a training dataset and half (2015-2017) as an external validation dataset. Prediction one made the prediction model using the training dataset with internal cross-validation. We used both the created model and the Universal TOR rule to predict outcomes using the external validation set.

Results:
989,929 OHCA cases, 18 years of age or older, were registered in the All-Japan Utstein Registry and 575,346 cases were of presumed cardiac origin. Of these, 354,356 cases were used as the training dataset and 220,990 cases were used as the external validation dataset. The model made by Prediction One using 11 variables had AUC of 0.969 and F value of 0.969, and its AUC for the validation cohort was 0.964 (95%CI 0.963-0.966) with 99.3% accuracy. The model made by Prediction One using three variables of universal TOR rule had AUC of 0.948 and F value 0.967, and its AUC for the validation cohort was 0.939 (95%CI 0.936-0.942) with 99.1% accuracy.

Conclusions:
The accuracy of prediction models using Prediction One was good. More research into the utility of using AI for TOR prediction is required.
Abstract 242: Association Of The Nearest Static AED With Treatment And Outcome Of OHCA In Forsyth County, North Carolina
Authors: Patel Jerishma , Yow Eric S , Rahim Faraan , Yellanki Sreekanth , Choi Hanul , Simmons Denise , Krychtiuk Konstantin , Blewer Audrey L , Green Cynthia , Nelson Darrell , Clark Tyson , Pun Patrick H , Granger Christopher , Mark Daniel B , Starks Monique A
Published: June 2023

Introduction:
Over the last two decades, publicly accessible AEDs have become available in communities across the US, allowing bystanders to rapidly intervene during OHCA. The impact of static AEDs on rates of bystander AED application and OHCA outcomes is poorly understood.

Methods:
We created a static AED registry for Forsyth County, NC (mixed rural-urban county with population ~ 380,000
)
primarily through phone-based surveys of businesses. These data were linked to the Cardiac Arrest Registry to Enhance Survival and geocoded to calculate proximity between OHCA and nearest static AED. The AHA recommends that publicly accessible AEDs be placed to achieve bystander retrieval within 100 meters (m) of OHCA. Multivariable logistic regression modeling examined the relationship between AED proximity and survival to hospital discharge.

Results:
Included were 2078 patients >18 years old with OHCA between 2013-2019 and 573 businesses with at least one AED. There were 219 (10.5%), 190 (9.1%), 1669 (80.3%) OHCAs with an AED within <100m, 100-200m, and >200m, respectively. OHCA incidence was highest where static AEDs were closest. Static AEDs within 100m of OHCA were primarily at residential facilities (41.1%), health care clinics (26.5%), churches (9.1%), and schools (6.8%). Among OHCAs with nearest AED >200m, AEDs were primarily owned by schools (32.2%), healthcare facilities (15%), industrial facilities (10.6%), and churches (10.4%). Bystander CPR was highest for OHCAs in closest proximity to an AED (<100m: 61.2%; 100-200m: 51.6%; >200m: 39.5%, p<0.001). Bystander AED application was highest where static AEDs were closest to OHCA (28.3%, 14.2%, and 3.8% at <100m, 100-200m, and >200m, respectively, p<0.001). Among patients who were defibrillated, bystander defibrillation was 18.1%, 20%, and 3.9% (p<0.001). There was no difference for survival to hospital discharge (<100m: 15.1%; 100-200m: 15.3%; >200m: 13.1%, p=0.54), even after adjustment (aOR 1.002, 95% CI 0.995-1.008 per 10m decrease).

Conclusion:
Only 10% of OHCAs in Forsyth County were within 100 meters of a static AED. Bystander CPR and AED application were highest where static AEDs were <100m from OHCA. Despite this, there was no association between AED proximity and survival to hospital discharge.
Abstract 244: Accelerating AED Use In Out-of-Hospital Cardiac Arrest With Combinations Of First Responder And Drone Delivery To Achieve 5-minute AED Deployment
Authors: Starks Monique A , Chu Jamal , Leung Benjamin , Chan Timothy , Blewer Audrey L , Simmons Denise , Joiner Anjni , Cabanas Jose G , Harmody Matthew , Nelson Darrell , Clark Tyson , McNally Bryan , Granger Christopher B , Mark Daniel B
Published: June 2023

Background:
Defibrillation in the critical first minutes of out-of-hospital cardiac arrests (OHCAs) can significantly improve survival rates but getting timely access to AEDs is a major barrier. We estimated the potential of a statewide program for drone-delivered AEDs in North Carolina (NC) when integrated into EMS response that includes police and fire first responders (FR).

Methods:
Using CARES registry data, we included all patients >18 years with OHCA occurring between 1/1/2013-12/31/2019 in 44 NC counties. We determined the improvement in AED arrival time by providing AEDs to all FR, who routinely arrive earlier than EMS but currently may not have an AED. We developed mathematical models to place drones within each county to achieve 5-min AED arrival times for 75% of OHCAs in each county. We predicted ambulance response times and resulting drone dispatch decisions using linear regression. Models were trained using 2013-2018 OHCA data and were validated with 2019 data. Mean response times were compared with historical response using the Wilcoxon signed-rank test.

Results:
We identified 27,199 OHCAs with historical median county-level response times of 6.7 [IQR: 5.9-7.5 mins]. Providing all FR with AEDs reduced response times to 5.9 [IQR: 5.3-6.9] mins and increased OHCAs with AED arrival times of <5 min to 35.6% [IQR: 26.1-43.4%]. Mathematical models estimated that 273 optimally located drones across the 44 counties would reduce response times for out-of-sample OHCAs to 3.7 [IQR: 3.4-3.9] mins and increase OHCAs with AED arrival times of <5 min to 73.0% [IQR: 65.4-78.8%]. The drone network improved response times (p<0.05) compared to historical response times in 43 out of 44 counties.

Conclusion:
Full deployment of AEDs by FR plus optimized drone AED delivery was estimated to significantly improve response times based on historical patterns of OHCA in NC. The number of drones and their impact varies across counties based on OHCA incidence rates and population density.
Abstract 9225: The Role of Leucine/Alpha-KIC/HMB Metabolism Pathway in Vascular Aging
Authors: Chen Li , Chen Xuanyu , Sun Jianghao , Yang Qiuhua , Huang Ying , Dong Yanbin , Zhu Haidong
Published: June 2023

Introduction:
Vascular aging, starting from youth, encompasses arterial degeneration and hardening that impairs vascular function, and ultimately causes end-organ damage, predominantly in the heart, brain, and kidney. Leucine (Leu) is an essential amino acid in the biosynthesis of proteins. It is initially catalyzed to α-ketoisocaproate (α-KIC), and then further metabolized to β-hydroxy-β-methylbutyrate (HMB). Our prior work showed a significant decrease in circulating HMB in response to additional sodium intake, a key risk factor for accelerated vascular aging.

Hypothesis:
We aimed to test the hypotheses that Leu/α-KIC/HMB metabolic activity declines with chronological aging, and that Leu/α-KIC/HMB metabolism is inversely associated with vascular aging in a young population.

Methods:
Global metabolomic profiling was performed in blood samples from 65 black adolescents and young adults, aged 25.9 ± 9.4 yrs and 85% were female. Blood levels of leucine, α-KIC, and HMB were extracted and log-transformed. Associations of leucine, α-KIC, and HMB with age, carotid-femoral pulse wave velocity (cfPWV), and intima-media thickness (IMT) were determined by pairwise correlations. A
p
-value smaller than 0.05 was considered significant.

Results:
Among 65 subjects with an age range of 13 to 45 yrs, older age was associated with lower levels of HMB (r=-0.37,
P
=0.002) and α-KIC (r=-0.30,
P
=0.016), but not leucine (r=-0.22,
P
=0.078). Higher levels of HMB and α-KIC, but not leucine, were associated with lower cfPWV (HMB: r=-0.33,
P
=0.010; α-KIC r=-0.31,
P
=0.018). Metabolites in the Leu/α-KIC/HMB metabolism pathway were also inversely associated with IMT, but only HMB showed a borderline statistical significance (r=-0.23,
P
=0.072).

Conclusions:
Our findings indicated a potential role of Leu/α-KIC/HMB metabolism in vascular aging, even in a young black population.
Abstract 9446: Psychosocial Readiness Assessment for Heart Transplant Candidates
Authors: Kleet Audrey C , Farr MaryJane A , Alvarez Carmen
Published: June 2023

Background:
Psychosocial evaluation for heart transplant suitability has long been required by the Centers for Medicare and Medicaid Services as a condition of participation for transplant programs in the US. There is no regulation regarding follow-up psychosocial care and re-assessment of patients waitlisted for transplantation. Heart transplant candidates require a thorough initial evaluation of multiple psychosocial factors and are at risk of negative outcomes with mental health problems and/or unstable socioeconomic resources.

Purpose:
A descriptive surveillance quality improvement project was developed to evaluate the effects of psychosocial readiness assessments for waitlisted United Network for Organ Sharing status 3, 4, and 5 adult heart transplant candidates in the outpatient setting, addressing basic socioeconomic needs and mental wellness in preparation for transplantation.

Methods:
To determine acceptability, rescheduled readiness visits and no-show rates were measured. A post-implementation period Qualtrics
RM
survey was administered to measure team member perceptions of feasibility. Socioeconomic elements of caregiver support, housing, transportation, and insurance status were assessed by simple using “yes/no” questions. The General Anxiety Disorder-7 questionnaire and the Patient Health Questionnaire-8 were used to assess anxiety and depression, respectively.

Results:
Fifty-seven patients were assessed during the 12-week period. The primary aim of feasibility was achieved with 93% of visits performed with freedom from rescheduling or patient no-show. Seventy five percent of team members reported the readiness assessments were achievable. More than twenty-four percent (24.56%) of patients required follow-up from a transplant Social Worker with 94.74% of those referrals due solely to elevated mental health questionnaire scores.

Conclusion:
Addressing non-medical and mental health needs in waitlisted heart transplant patients allows transplant programs to maintain candidates with necessary resources. The readiness assessments are feasible in practice and may serve to reduce untoward outcomes in the post-transplant phase by providing targeted care prior to the time of transplant.
Abstract 9465: A New Score for Predicting Results After Catheter Ablation for Atrial Fibrillation
Authors: Alexandrina Nastasa , Nirlu Luminita , Iorgulescu Corneliu , Radu Dan-andrei , Bogdan Stefan , Cojocaru Cosmin , Dardari Mohamed , Vatasescu Radu G
Published: June 2023

Introduction:
Cateter ablation (CA) for atrial fibrillation (AF) has been proven to be extremely effective in maintaining sinus rhythm but success rates still vary widely. Procedural costs are not negligible and a low, but nonetheless present, rate of potentially severe complications exists, therefore an accurate estimation of results is necessary in order to assess the risk-benefit ratio. Several studies have proposed different scores for predicting post-procedural success, such as APPLE, CAAP-AF, MB-LATER, SUCCESS, but most have not been validated yet in external cohorts, hence further research for the optimal formula is justified.

Hypothesis:
Our objective was to find independent predictors of recurrence after CA for AF and group them into a new, easy to calculate composite score.

Methods:
A total of 263 consecutive patients with AF who underwent CA in our centre were retrospectively analyzed. Variables that were significantly associated with recurrence risk according to univariate analysis were introduced in a Cox multivariate regression. The independent predictors of recurrence were used to create a new predicting score, after empirically assigning them different weights.

Results:
The mean follow-up period was 37.6 ± 23.4 months. The type of AF (persistent), f-waves < 0.1mV, indexed LA volume, the presence of type II diabetes and smaller height were found to be independent predictors of recurrence and were used to create the new scoring model, VAT-DHF. The ROC curve for this new score showed an AUC 0.869, p<0.0001, 95%CI [0.802-0.936] while those for APPLE and CHA
2
DS
2
Vasc showed AUC 0.765, 95% CI [0,637-0.893] and respectively, AUC 0.655,95%CI [0,580-0.730]. Patients who had a VAT-DHF score between 0-3.25 had a rate of success of 95.7%, those with a score between 3.25-6 of 76.3%, and those with a score ≥6 had a rate of success of 25% (p <0.0001). A cut-off value of 5,75 gives the score a sensitivity of 87% and a specificity of 75%.

Conclusions:
The novel and simple VAT-DHF score is superior to the APPLE and CHA2
DS2
-VASc scores in predicting outcomes after catheter ablation for AF. It may provide a useful clinical tool to identify patients with low, intermediate or high risk of AF recurrence, but further validation is necessary.
Abstract 9500: Patients’ Perspectives Regarding Generator Exchanges of Implantable Cardioverter-Defibrillators
Authors: Rao Birju , Montembeau Sarah C , Speight Candace , Matlock Dan D , Merchant Faisal M , Kramer Daniel B , Horny Michal , Dickert Neal W
Published: June 2023

Background:
Shared decision-making (SDM) is mandated for patients receiving primary prevention implantable cardioverter-defibrillators (ICD). Less attention has been paid to ICD generator exchange (GE) decisions. At the time of GE, patients’ risk of sudden cardiac death (SCD), risk of procedural complications, quality of life, or prognosis may have changed. This study was designed to explore how patients view GE decisions.

Methods:
In-depth interviews about perspectives regarding GE decisions were conducted with patients who had primary prevention ICDs implanted at Emory Healthcare from 2013-2021. Patients were also presented a hypothetical scenario where their ICD battery was depleted but their risk of SCD over 5 years at the time of battery depletion varied (10%, 5%, 1%). Patients were asked about their willingness to undergo GE under each of these conditions. Transcribed interview text was qualitatively coded using a multilevel template analytic method.

Results:
Fifty patients were interviewed, of whom 19 had a prior GE, 16 had no prior ICD therapies and 14 had improved left ventricular ejection fraction. Overall, even with low SCD risk, patients’ willingness to undergo a GE remained high (Figure). If their doctor recommended deferring GE, 15/49 patients still would not defer a GE. Many patients reported not relying on risk/benefit estimates to make GE decisions. Most also reported deferring the decision to their doctor, and many exhibited significant therapeutic inertia. One patient stated, “since I’m already wired for it⋯wouldn’t make sense to disregard it.”

Conclusion:
Strong default preferences push patients towards a GE. Risk stratifying patients for SCD at the time of GE may facilitate SDM and may reduce GE in very low-risk patients. However, even at 1% risk of SCD, which would not meet thresholds for ICD therapy, most patients would choose GE. This highlights provision of risk information alone seems unlikely to drive substantially different GE decisions.