bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15608: Validation of Enhancer/Silencer Activity of the Intracranial Aneurysm-Associated SNP at SOX17 in Primary Human Endothelia
Authors: Tutino Vincent M , Poppenberg Kerry , Siddiqui Adnan H , Jarvis Jim , Chaves Lee
Published: June 2023

Introduction:
GWAS have identified multiple SNPs that occur more commonly in those with intracranial aneurysms. Many SNPs are located in noncoding genomic regions, suggesting that genetic risk may operate on functional regulatory elements that influence gene expression. However, regulatory elements are most often only indirectly identified through methods such as DNAse hypersensitivity without direct assessment of activity.

Hypothesis:
We hypothesize CRISPR mediated ablation of putative regulatory elements located within intergenic loci associated with IA will result in mRNA transcript modulation of genes located within the respective topology associated domain.

Methods:
We investigated a SNP within a haplotype block near SOX17. The haplotype was predicted to have active enhance activity, and to mediate SOX17 expression, based on assessment of its topologically associated domain. Lentiviral constructs (each with unique antibiotic resistance and fluorescent protein reporters) for the expression of Cas9 nuclease and two gRNAs flanking a putative element located at chr8:54412191-54413910 were transfected into the Lenti-X viral propagating cell line (Figure, left). Viral supernatants were transduced into primary HUVEC cells by spinfection with 5 ug/mL polybrene. After antibiotic selection and fluorescence validation, mRNA was isolated, and transcripts quantified through PCR.

Results:
Lentiviral transduction of HUVECs resulted in CRISPR-mediated removal of the enhancer element located within the haplotype block chr8:54397171-54415556 and resulted in a substantial increase of the SOX17 gene mRNA located within its topology associated domain (Figure, right).

Conclusions:
CRISPR mediated ablation was used to efficiently remove and validate a genomic element with putative regulatory activity in HUVECs. The methods will be employed to study additional regulatory elements with IA associations as well as other primary vascular cells.
Abstract 15609: Neighborhood Socioeconomic Disparities in Infant Out-of-Hospital Cardiac Arrest
Authors: Shekhar Aditya C , Peeler Katie R , Marron Jonathan M , Mann N. Clay , Madhok Manu
Published: June 2023

Introduction:
More than half of all pediatric cardiac arrests involve children under 1 year of age, and intervention prior to the arrival of emergency medical services (EMS) is crucial to prevent irreversible injury in out-of-hospital cardiac arrest.

Hypothesis:
Given other cardiac arrest disparities, we hypothesize that pre-EMS CPR and outcomes for infant cardiac arrest differ across community socioeconomic status.

Methods:
We examined cardiac arrests in 2019 involving patients under 1 year of age contained within a nationally-representative EMS database in the United States (NEMSIS). Data collected included if pre-EMS CPR was performed, if return of spontaneous circulation (ROSC) was achieved, and the ZIP Code where the arrest took place. We grouped arrests based on the socioeconomic characteristics of the ZIP Code where the arrest took place. This allowed us to examine whether rates of pre-EMS CPR and ROSC varied according to community-level poverty.

Results:
A total of 3776 pediatric cardiac arrests met inclusion criteria (Table). Within the total sample, the overall pre-EMS CPR rate was 71.2%, and the overall ROSC achievement rate was 16.6%. Pre-EMS CPR and ROSC achievement were highest in communities where less than 5% of individuals were below the poverty line and were significantly lower in communities where more than 16% of individuals within a ZIP Code were below the poverty line (p<.05).

Conclusions:
Our data show that two important predictors of cardiac arrest survival - Pre-EMS CPR and ROSC achievement - decline significantly as the percentage of individuals below the poverty line increase. Disparities across socioeconomic status may reflect decreased CPR awareness, underperforming systems of prehospital care, or worse infant baseline health statuses. Public health efforts aimed at infant cardiac arrest may see the most benefit when focusing on socioeconomically-disadvantaged communities.
Abstract 15630: Association of Frailty With 30- and 90-day Outcomes in Patients Admitted With Heart Failure With Reduced Ejection Fraction (hfref) and Heart Failure With Preserved Ejection Fraction (hfpef)
Authors: Singh Sumitabh , Mulpuri Neha , Kondamudi Nitin , Zhong Lin , Pandey Ambarish
Published: June 2023

Background:
Frailty is associated with adverse post-hospitalization outcomes among patients admitted with heart failure. Whether frailty associated risk of adverse events among HF patients differs by HF subtype (HFpEF vs. HFrEF) is not well-established.

Methods:
Using Medicare claims data, we identified patients newly hospitalized for HF in 2016 within a cohort of 5% fee-for-service Medicare beneficiaries and used ICD-10 codes to specify HF subtype. Frailty was quantified using the Hospital Frailty Risk Score (HFRS), which computes frailty using 109 ICD-10 codes within 3 months of the index HF hospitalization. The association of HFRS with risk of outcomes were assessed using adjusted Cox proportional hazard models and multiplicative interaction testing was performed for HF subtype and HFRS. Improvement in model discrimination with addition of HFRS was assessed using change in the C-statistic and the integrated discrimination improvement test (IDI).

Results:
The study cohort included 14,276 Medicare beneficiaries hospitalized for HF [mean age (SD), 79 (8.4); 53 % women; 88 % white], among them 6836 (48%) with HFpEF and 3586 (25%) with HFrEF. In adjusted Cox models, higher frailty burden was associated with greater risk of 30- and 90- day mortality among beneficiaries hospitalized for HFrEF and HFpEF (Table 1). For readmission outcomes, higher frailty burden was associated with a significantly higher risk of 30-day and 90-day readmission among patients with HFpEF but not HFrEF (p-interaction HFRS * HF subtypes = 0.03 for both, Table 1). Addition of HFRS significantly improve discrimination to predict readmission. [30-day readmission, IDI (95%CI) = 0.011 (0.006-0.016)].

Conclusion:
Higher frailty burden is significantly associated with increased risk of mortality in patients with HFpEF and HFrEF. In contrast, frailty is more strongly associated with risk of readmission (30-day and 90-day) among patients with HFpEF only but not among HFrEF.
Abstract 15633: Differences in Atrial Fibrillation Symptoms Post-Ablation by Age
Authors: Taylor Brittany , Reading Turchioe Meghan
Published: June 2023

Introduction:
The prevalence of atrial fibrillation (AF) increases with age. Although catheter ablation is a recommended treatment for AF and is safe and effective in older adults, symptom outcomes post-ablation have not been well studied among older adults. The objective of this study was to investigate differences in the prevalence of symptoms post-ablation and the need for repeat ablation by age group.

Methods:
From electronic health records, we used International Classification of Diseases billion codes to identify all patients with an admitting diagnosis of paroxysmal AF who were treated at NewYork-Presbyterian Hospital between 2010 and 2020. We then used Current Procedural Terminology Codes to identify patients who underwent catheter ablation. We extracted age, gender, race, ethnicity, and prevalence of repeat ablations using structured queries. We extracted symptoms post-ablation from unstructured clinical notes using natural language processing. We separated patients into five age groups and evaluated associations between demographics, symptoms, repeat ablations and age group using Chi-square tests.

Results:
Of the 1,414 patients studied, 34.4% were female and 58.6% were white, and 4.1% were Hispanic or Latino. Significantly more female patients were age 61-80, and significantly more non-White participants were age 51-70, compared to other age groups. There was a clinically but not statistically significant difference in the prevalence of repeat ablations by age, with nearly half of those with repeat ablations being age 61-70. There were no significant differences in symptom prevalence 6 and 12 months post-ablation.

Conclusion:
A greater proportion of female and non-White patients undergoing ablation are older adults compared to younger or much older (>80 years) patients. There were no differences in repeat post-ablation symptoms by age, suggesting older adults may experience similar symptom reduction following ablations as younger adults.
Abstract 15639: Infected Thrombus - An Unusual Etiology of Acute Coronary Syndrome in a Patient With New Onset Atrial Fibrillation
Authors: Okunade Adeniyi , Fatunde Olubadewa , smith maxwell L , Naqvi Tasneem Z
Published: June 2023

Background:
Coronary embolism (CE) is an uncommon (3%) cause of acute coronary syndromes (ACS) and is often missed.

Case Presentation:
A 68-year-old woman with a h/o hypertension & breast cancer post lumpectomy 10 yrs ago, presented with generalized weakness, fever (101F), & vomiting without chest pain, dyspnea, or palpitations. She was afebrile, tachycardic (158 beats/min), tachypneic (26 breaths/min) with BP of 98/64 mmHg. Cardiac exam revealed irregularly irregular rhythm, 5 cm jugular venous distension & 3+ bilateral pretibial edema. Labs revealed thrombocytopenia, lactic acidosis, & hyponatremia. High sensitivity-Troponin was 1023 & NT-pro-BNP 19854. EKG showed atrial fibrillation (AF), diffuse ST elevations in the precordial leads & aVR, poor R wave progression & inferior Q waves. Her cardiac cath revealed a large thrombus from mid-left main extending into the LAD with minimal atherosclerotic burden. Intraoperative transesophageal echocardiogram for emergent surgical resection of the thrombus revealed a highly mobile thrombus 2.32x0.6 cm on the aortic aspect originating between L and R coronary cusps and a left atrial appendage thrombus (1.1 cm) with marked spontaneous contrast in LA appendage & LA which was surgically resected. Blood cultures & of coronary thrombus grew
Methicillin sensitive
Staphylococcus Aureus (MSSA)
. Anticoagulation & appropriate antibiotics were initiated. but after a protracted, complicated ICU stay, patient was made comfort care.

Discussion/Conclusion:
CE should be considered in cases of recurrent coronary thrombus or in the setting of heavy thrombus burden despite a relatively normal coronary vessel. AF is the most common underlying cause of CE causing ACS. Aspiration or surgical thrombectomy should be performed with a high thrombus burden. Thrombus should be sent for pathology to further delineate the source of thrombus.
Abstract 15642: Transient Brugada Pattern in an Afebrile Patient With Covid Myocarditis
Authors: Olanipekun Olalekan , Akhigbe Esiemoghie , Panta Utsab , Sam Riya , Okoro Kelechukwu
Published: June 2023

Introduction:
SARS-CoV2 infection has been associated with cardiovascular manifestations, including myocarditis and arrhythmias. Asymptomatic brugada pattern of EKG has been reported and usually associated with fever, sodium channel blockers, and psychotropic drugs. There have been few reported cases of brugada pattern unmasked by fever in patient with covid-19 infection. We present a unique case of a patient with brugada pattern of EKG in an afebrile patient with Covid 19 myocarditis.

Case presentation:
Patient is a 58 year old male with PMHx significant for ITP, HTN who was admitted on account of dyspnea and dysphagia. Patient was subsequently with covid-19 infection/pneumonia and epiglottitis.

Decision Making:
Physical examination findings showed a hyperemic epiglottis. Initial labs were positive for covid 19 with elevated troponins (>3000). Initial EKG showed ST elevation on V1-V4 (figure 1a) raising suspicion for possible STEMI vs covid myocarditis with brugada pattern. Echocardiogram performed showed a severely reduced ejection fraction at 20% with global hypokinesis. Emergent left heart catherization was performed which showed no angiographic evidence of coronary artery disease. The patient was started on guideline therapy for covid 19 infection and also antibiotics for presumed epiglottitis. Inflammatory markers continued to trend downwards. Patient was also started on guideline directed medical therapy for heart failure. Repeat EKG showed resolution of Brugada pattern (figure 1c). Clinical course improved throughout hospital stay.

Conclusion:
There has been few reported cases of brugada pattern un-masked by Covid-19 infection. These reported cases are commonly associated with the occurrence of fever, which has been attributed to the dysregulation of Na channels. This case presents a diagnostic dilemma as most patient with covid and brugada have documented febrile episodes prior to the unmasking of this rare arrhythmia.
Abstract 15666: Survival Benefit of Implantable Cardioverter Defibrillators in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Kukavica Deni , Trancuccio Alessandro , Marino Maira , Giannini Gala , Rossetti Luca , Mohsin Muhammad , ORANI PIETRO , Esposito Alessandro , Memmi Mirella , Bloise Raffaella , Morini Massimo , Mazzanti Andrea , Priori Silvia G
Published: June 2023

Introduction:
The effectiveness of implantable cardioverter-defibrillators (ICDs) in reducing mortality in patients with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is debated.Hypothesis. The ICD confers survival benefit in patients with CPVT.

Methods:
We included n=238 genotype-proven CPVT patients, of whom 91 (38%) had an ICD implanted. All patients were treated with beta-blocker (BB) monotherapy. Survival probability at the occurrence of a first Life-threatening Arrhythmic Event (LAE, defined as: sudden cardiac death, aborted cardiac arrest or hemodynamically non-tolerated ventricular tachycardia) was compared between ICD carriers and non-ICD carriers. In ICD carriers, the benefit-to-harm ratio (rate of appropriate shocks on LAE over rate of major complications) was investigated.

Results:
During 1,643 person-years of follow-up, 35/238 (15%) patients experienced a first LAE on BB monotherapy (annual LAE rate 2.1%, 95%CI: 1.5-3.0%). Of the 35 individuals who experienced an LAE, 23 patients had an ICD when the LAE occurred, and all survived after ICD shock. Of the remaining 12 patients who were not carriers of an ICD, 4/12 (33%) died suddenly, 2/12 (17%) survived but suffered anoxic brain injury, while 6/12 (50%) survived without consequences. The probability of dying at the occurrence of a first LAE was 25-fold higher (OR: 24.9, 95% CI: 1.2-513.0; p=0.037) in patients without an ICD, as compared to patients with an ICD. Major complications occurred in 17/91 (19%) patients with an ICD (2.6% per year, 95%CI: 1.5%-4.1%). Comparing the rate of major complication to the rate of appropriate ICD shocks on LAE (LAE rate 5.2% per year, 95%CI: 3.5-7.4%), the benefit-to-harm ratio was 2, favoring the benefit of ICD therapy.

Conclusion:
The ICD conferred a significant survival benefit in terms of arrhythmic mortality at the occurrence of the first LAE in BB monotherapy.
Abstract 15686: Prevalence and Effects of Deep Vein Thrombosis on Hospital Outcomes Among COVID-19 Patients
Authors: Appunni Sandeep , Ramamoorthy Venkataraghavan , Ahmed Md Ashfaq , Zhang Zhenwei , McGranaghan Peter , Morcos Ramez , Salami Joseph , Rubens Muni , Saxena Anshul , Veledar Emir , Chaparro Sandra , Jimenez Javier
Published: June 2023

Introduction:
Current estimates show that, globally, there are 531 million cases and 6.3 million deaths due to COVID-19. Studies have shown that COVID-19 could lead to deep vein thrombosis (DVT) resulting in increased morbidity and mortality. In this study we sought to estimate the prevalence of DVT among COVID-19 hospitalizations as well as its effects on hospital outcomes using a large administrative database.

Hypothesis:
The adverse in-hospital outcomes of COVID-19 will be significantly higher among DVT hospitalizations.

Methods:
We conducted a retrospective analysis of the 2020 California State Inpatient Database. All hospitalizations with age 18 and above and primary diagnosis of COVID-19 were included for the study. They were classified into those with and without DVT. The main outcomes of the study were in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and ICU admission. Length of stay ≥75th percentile was grouped as prolonged length of stay. Multivariate logistic regressions with covariate adjustments were conducted to compare COVID-19 related outcomes between those with and without DVT.

Results:
We included a total of 94,114 primary COVID-19 hospitalizations for the analysis. Among them 1575 (1.7%) had DVT. The prevalence of mortality (27.5% versus 11.1%, P<0.001), prolonged length of stay (62.2% versus 27.8%, P<0.001), vasopressor use (7.9% versus 2.1%, P<0.001), mechanical ventilation (36.2% versus 9.7%, P<0.001), and ICU admission (35.7% versus 9.3%, P<0.001) were significantly higher among those with DVT.

After adjusting for covariates, regression analysis showed that those with DVT had significantly greater odds for mortality (aOR, 2.34, 95% CI: 2.07-2.65), prolonged length of stay (aOR, 3.51, 95% CI: 3.16-3.91), vasopressor use (aOR, 4.23, 95% CI: 3.78-4.74), mechanical ventilation (aOR, 2.90, 95% CI: 2.38-3.53), and ICU admission (aOR, 4.32, 95% CI: 3.85-4.84).

Conclusions:
In our cohort, only few COVID-19 hospitalizations had a diagnosis of DVT. However, among those with DVT, the risk for adverse outcomes were significantly higher. Since DVT among COVID-19 is uncommon but associated with adverse hospital outcomes, healthcare providers should promptly monitor for DVT and manage it.
Abstract 15690: Bioactive Fumarate Improves Cardiac Function and Expands Lifespan in Friedreich's Ataxia
Authors: Salinas Lili , Figueroa Francisco , Montgomery Claire , Thai Phung , Chiamvimonvat Nipavan , Dugar Sundeep , Sen Somdutta , Cortopassi Gino , Dedkova Elena N
Published: June 2023

Introduction:
Friedreich ataxia (FA) is a monogenic recessive ataxia caused by reduction of a single mitochondrial protein, frataxin (FXN). Although the name of FA refers to the neurodegenerative ataxia, the lethal event is cardiomyopathy, caused by deficient FXN expression in the heart. Previously, we identified that bioactive fumarates are protective in FA cell models. We have developed a novel monomethyl fumarate prodrug, IMF, which has much improved pharmacokinetic profile and compared its effect to the known fumarate prodrug dimethyl fumarate (DMF, Tecfidera).

Aim:
To test the hypothesis that novel bioactive fumarate improves cardiac function and survival via Nrf2 and HCA
2
signaling pathways activation.

Methods and Results:
Cardiospecific FXN knockout (FXN Mck-Cre KO) mice were used as a model of severe cardiomyopathy which is characteristic for the late stage of FA. Animals of either sex were randomly split in vehicle and fumarate-treated groups. Animals were treated by IMF or DMF at concentrations which release equimolar amount of monomethyl fumarate. Treatment started at 3 weeks of age and continued for 5 weeks in the cross-sectional study or until animal death in the survival study. Cardiac function was examined
in-vivo
by echocardiography. We found that FXN Mck-Cre KO mice developed severe heart failure with 45% reduction in ejection fraction, increased left ventricular (LV) mass (+80%) and diameter (+308%), decreased stroke volume (-26%) and cardiac output (-38%, n=10) as compared to WT mice (n=12). Cardiac deficits were more pronounced in FA males compared to females. Both DMF and IMF partially recovered cardiac deficits in FXN Mck-Cre KO mice but only IMF extended the lifespan in these mice by 13%. Expression of genes in Nrf2 (NQO1, SOD2, glutathione S-transferase) and HCA
2
(HCA
2
and Sirt1) signaling pathways were decreased in FXN Mck-Cre KO and restored to a different degree by DMF and IMF. Aconitase activity, used as a surrogate measure of frataxin's iron-sulfur biogenesis function, was decreased in FA by 49% and recovered 18% by IMF only.

Conclusions:
Novel fumarate prodrug IMF improved cardiac function and expanded the lifespan in FXN Mck-Cre KO mouse model of FA more effectively than DMF.
Abstract 15699: High-Dose Anthracycline Administration and Development of Cardiotoxicity in Women With Breast Cancer: An Analysis of Real-World Data From a Nationwide Claims Database in Japan
Authors: Ohtsu Hiroshi , Shimomura Akihiko , Miyazaki Sakiko , Ueda Shinichiro , Yonemoto Naohiro , Shimizu Chikako , Sase Kazuhiro
Published: June 2023

Introduction:
Breast cancer is the most common malignancy affecting women, and the number of survivors is increasing with the advent of new therapies. However, Anthracyclines (ACs) retain an essential role in the drug treatment of breast cancer, despite their known cardiotoxicity. Although dexrazoxane, a cardioprotective agent for high-dose AC administration, has been approved in the US and Europe, it remains one of the drug-lag issues in Japan.

Objective:
To evaluate real-world data on the proportion of high-dose anthracycline administration and the incidence of cardiotoxicity in Japanese patients with breast cancer using a nationwide claims database.
Methods.
This study is a retrospective observational analysis using the Japan Medical Data Centre (JMDC, Tokyo, Japan) database, an anonymized patient-level claims database younger than 75 years old. We first identified women diagnosed with breast cancer and treatment with AC. Patients with a history of heart failure and a treatment start record of fewer than six months were excluded. After adjusting for patient background factors by propensity score matching (PSM), cardiotoxicity risk factors and outcomes were compared between the high-dose group (AC-H) and the low-dose group (AC-L).

Results:
Among women with breast cancer who underwent AC treatment between January 2015 and September 2020, 5.3% (255/4,831) were classified to the high-dose group. After PSM, the number of cases, age (years) and follow-up (months) in each group were as follows: AC-H group (n=254, median 51.0 [IQR: 46.0-55.0], 26.0 [14.0-52.0]), AC-L group (n=254, 51.0 [46.0-57.0], 32.5 [15.0-59.0]). The 5-year rates of mortality and heart failure in AC-H and AC-L groups were 33.1% vs 4.5% (Log-rank p < .0001) and 11.0% vs 4.3% (Log-rank p=0.003), respectively.

Conclusion:
The proportion of women with breast cancer who received AC in the high dose group was approximately 5%. However, compared with the low-dose group, the high-dose group had a lower survival rate and a higher incidence of heart failure. Therefore, in Japan, clinical development of cardioprotective agents for patients with metastatic or recurrent breast cancer who require high doses of AC is warranted.
Abstract 15703: Outcomes of Non-ST Segment Myocardial Infarction in Patients With Heart Failure and End Stage Renal Disease
Authors: Alhuarrat Majd Al Deen , Varrias Dimitrios , Patel Snehal R , Sims Daniel B , Latib Azeem , Jorde Ulrich P , Saeed Omar
Published: June 2023

Introduction:
Non-ST Segment Myocardial Infarction (NSTEMI) occurs frequently in patients with pre-existing Heart Failure (HF) and End Stage Renal Disease (ESRD). However, outcomes with invasive approaches such as percutaneous coronary intervention (PCI) or medical management remain uncertain.

Hypothesis:
Given severe comorbidity burden, patients with HF and ESRD admitted for NSTEMI may experience higher in-hospital mortality with an invasive strategy of PCI.

Methods:
We utilized the National Inpatient Sample to capture hospitalizations in the United States from 2006-2014. Admissions for NSTEMI were identified by the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) code 401.7x. The sample was further narrowed by coexisting diagnoses of HF (ICD-9-CM: 428.xx) and ESRD (ICD-9-CM 585.6). The cohort was divided into those that received PCI or medical management only. Multivariable logistic regression was used to compare the primary outcome of in-hospital mortality between invasive and medical management only groups.

Results:
During the study period, 14,333 hospitalizations were identified for NSTEMI in patients with coexisting HF and ESRD. Within this cohort, 3,549 (25%) underwent PCI (age: 66±11 years,42% female) and 10,784 (75%) were managed with medications (age: 69±12 years, 45% female) only. In-hospital mortality was 5% in the PCI group in comparison to 10% in those managed with medications only (p<0.01). After adjustment for clinical covariates including age, sex and diabetes mellitus, PCI was associated with lower odds of death during hospitalization (aOR: 0.52, 95% CI: 0.44-0.61, p<0.01).

Conclusions:
Patients with HF and ESRD admitted for NSTEMI do not incur greater in-hospital mortality with PCI, despite a high burden of comorbidities. Invasive percutaneous revascularization may be reasonable for appropriately selected patients with HF and ESRD.
Abstract 15713: A Novel Chest Pain Pathway Triaging Low-Risk Emergency Department Patients via Ambulatory Care Reduces Hospital Admissions Without Increased 30-Day Readmissions or All-Cause Mortality
Authors: Reddy Rohin K , Wang Brian X. , Gwyther Bethany , Chakraborty Turja , Toia Diana , Britton Clemency , Chen Jun Yu , Sayfoo Mohammad Farez , James Arissa , Khan Faria Ashraf A , Thapa Jagadeep , Gothandaraman Balaji
Published: June 2023

Introduction:
Chest pain is a common presentation to the Emergency Department (ED). Current international guidelines emphasise the importance of triage pathways involving patient-centric algorithms. In 2019, a front-door ED pathway (Figure 1) was created to direct low-risk chest pain towards ambulatory care. We aimed to characterise clinical outcomes with this pathway in a real-world UK ED cohort presenting with cardiac chest pain.

Methods:
The chest pain pathway stratified patients as low-, intermediate- and high-risk at presentation. Patients presenting to the ED at our institution in London, UK, were consecutively included in two groups: a pre-pathway group prior to implementation of the chest pain pathway and a post-pathway group following implementation. Baseline demographics were compared using Pearson’s χ
2
test for categorical variables and unpaired t-tests for continuous variables. Primary endpoints were 30-day readmissions, and all-cause mortality. Multiple logistic regression models were constructed to assess the impact of the pathway on the primary outcomes, adjusting for age, sex, risk category and HEART score.

Results:
Baseline demographics were similar between pre-pathway and post-pathway groups, except for presence of a smoking history (
p
= 0.04). Smoking was therefore adjusted for in multivariable analyses. Approximately 10% (13/136) of post-pathway patients avoided hospital admission and were triaged towards ambulatory care. There was no significant difference in 30-day readmissions: 18/139 post-pathway vs 12/167 pre-pathway (OR 1.79, 95% CI 0.79 - 4.22,
p
= 0.17); or all-cause mortality: 2/167 pre-pathway vs 5/139 post-pathway (OR 2.96, 95% CI 0.49 - 25.68,
p
= 0.26).

Conclusions:
This novel chest pain pathway demonstrated a 10% reduction in hospital admissions without concurrent increases in 30-day readmissions or all-cause mortality. This is likely to reduce burdens on hospital resources and patient flow whilst maintaining safety.
Abstract 15720: Single Cell Spatial Transcriptomics of the Ischemic Borderzone
Authors: Calcagno David , Taghdiri Nika , Ninh Van K , Fu Zhenxing , King Kevin R
Published: June 2023

Introduction:
Myocardial infarction (MI), leads to development of an infarct borderzone (BZ) separating areas of cell death (ischemic zones, IZ) from surviving myocardium (remote zones, RZ). The BZ is a geographically complex and biologically enigmatic territory thought to play critical roles in infarct expansion, ventricular remodeling, arrhythmias, and provisional regeneration; however, its cellular and molecular processes are not well understood because previous studies have relied on microdissection, which combines zones in uncontrolled and unmeasured proportions.

Hypothesis:
We hypothesize that the BZ can be redefined using single cell spatial transcriptomics.

Methods:
We used single cell and single nuclei RNA-seq, capture-based spatial transcriptomics, and multiplexed RNA fluorescence in situ hybridization (mFISH) to redefine the BZ into functional subunits.

Results:
Transcriptomic data from more than 300,000 cells reveal that the BZ is comprised of multiple spatially defined niches characterized by distinct structural, morphological, transcriptional, and functional subsets of cardiomyocytes, fibroblasts, monocytes/macrophages, and neutrophils. We identified two distinct BZ populations of cardiomyocytes (CMs): BZ1 (Nppa+Xirp2-), which forms a hundreds-of-microns-thick transitional layer adjacent to the RZ, and BZ2 (Nppa+Xirp2+), which forms a tens-of-microns-thick layer that decorates the complex peninsulas and islands adjacent to the dead myocardium of the IZ. Compared to BZ1 CMs, BZ2 CMs have significantly reduced contact area with neighboring CMs; express elevated levels of genes involved in mechanotransduction; and preferentially colocalize with matricellular-protein-expressing myofibroblasts. The transcriptional BZ is detectable within an hour of ischemia, prior to immune infiltration or fibroblast activation. We propose a unifying "loss of neighbor" hypothesis to mechanistically explain the results.

Conclusions:
Our work demonstrates that harmonizing multi-modality single cell and spatially resolved datasets has the potential to uncover new biology in the ischemic borderzone.
Abstract 15758: Association of Socioeconomic, Racial, and Regional Factors in In-Hospital Mortality Among Acute Myocardial Infarction Patients in the United States: A National Analysis of 2.8 Million Admissions
Authors: Haldenby Olivia , Garg Pallav , Ali Shehzad
Published: June 2023

Background:
Socioeconomic, racial, and regional disparities have been associated with worse clinical outcomes among patients with coronary disease. We evaluated the association of income, race, and geographic variation and in-hospital mortality among acute myocardial infarction (AMI) admissions in the United States.

Methods:
We conducted a retrospective cohort study using the Nationwide Inpatient Sample from 2015 to 2019. A multi-level logistic regression model was used (with sampling weights) to investigate the association between in-hospital mortality and income quartiles by patient’s ZIP code, race, and hospital regions, while adjusting for hospital clustering, lifestyle factors, clinical history, and hospital-level factors.

Results:
A total of 2,798,225 hospitalizations (≥18 years) with a principal diagnosis of AMI were identified. In multivariable analysis, compared with the highest income quartile, residents in the lowest income quartile (OR=1.10 [1.08–1.13]
P
<0.001) or second lowest income quartile (OR=1.07 [1.05–1.09]
P
<0.001) had higher odds of in-hospital mortality. Compared with those identifying as White, Black (OR=0.89 [0.87–0.91]
P
<0.001) and Hispanic (OR=0.91 [0.88–0.93]
P
<0.001) groups had lower odds of mortality, while Asian or Pacific Islander (OR=1.07 [1.03–1.11]
P
<0.001), Native American (OR=1.11 [1.02–1.21]
P
<0.05), and Unspecified groups (OR=1.09 [1.05–1.13]
P
<0.001) had higher odds of mortality. Residents in the South had higher mortality than those in the Northeast (OR=1.06 [1.00–1.12]
P
<0.05).

Conclusion:
Our large contemporary study shows that lowest income residents, Whites, Asian or Pacific Islanders, and Native Americans and residents of South had higher in-hospital mortality compared with highest income residents, Blacks and Hispanics, and residents in the Northeast. Additional studies are needed to better understand the complex mechanisms that underpin disparities in outcomes among AMI patients.
Abstract 15788: Patent Foramen Ovale With Platypnea-Orthodeoxia Precipitated by Large Hepatic Cyst Requiring Closure: Novel Approach
Authors: Moras Errol , Gandhi Kruti , Sharma Apurva , Romeo Francisco , Tabrizian Parissa , love barry A , Ahmadi Amirali
Published: June 2023

Case Presentation:
A 71-year-old female with history of liver cyst presented with severe epigastric and RUQ pain. Abdominal CT demonstrated interval worsening of the liver cyst (largest cyst 18cm) causing right hemi-diaphragmatic elevation. She was hemodynamically stable, and plan was for elective surgical cyst fenestration in 2 weeks. However, her pain worsened, and was readmitted with severe dizziness and hypoxia. Chest CTA workup revealed subsegmental pulmonary emboli (PE) bilaterally and lower extremity dopplers showed deep vein thrombosis. She was started on anticoagulation, but her hypoxemia worsened, requiring maximum high flow oxygen. Persistent hypoxia disproportionate to the PE that worsened in the right lateral decubitus position led to repeat transthoracic echocardiogram with bubble study, that demonstrated a large patent foramen ovale (PFO) and a normal right ventricle. Mechanism of this severe hypoxemia was largely attributed to the shunting from the IVC directly across the PFO and couldn’t be explained by a small PE. Given the high risk for paradoxical emboli, the need for PFO closure versus debulking the liver cyst was discussed at the time. Aspiration of the cyst was attempted initially to avoid PFO closure, with temporary improvement in her hypoxemia. Hence a decision was made to close the PFO before further definitive management of the cyst. The PFO was closed with 30mm Amplatzer Talisman occlude device and post operatively her oxygen was weaned down to room air sating 95%. However, her abdominal fullness continued to be present, and she underwent successful fenestration of her cyst.

Discussion:
There have been cases where large hepatic cysts causing compression of the right atrium were treated either with surgical drainage or cyst resection. Rare cases have the need for a PFO closure with hemodynamic changes, as this one, where it was successfully done, leading to significant improvement.
Abstract 15792: Unchecked Cytokinesis Generates Highly Proliferative Mononuclear Cardiomyocytes at the Expense of Contractility
Authors: Lam Nicholas T , Elhelaly Waleed M , Menendez-Montes Ivan , Hsu Ching-Cheng , Nguyen Ngoc , Xiao Feng , Ahmed Mahmoud S , Li Shujuan , Thet Suwannee , Zangi Lior , Sadek Hesham A
Published: June 2023

Introduction:
A few days after birth in mouse cardiomyocytes, DNA synthesis occurs without cytokinesis leading to the majority of cardiomyocytes becoming binuclear instead of generating 2 daughter cells with one nucleus each. This results in cell cycle arrest of cardiomyocytes and the mouse heart is no longer able to regenerate.

Hypothesis:
A long-standing unanswered question in the field is whether multinucleation of cardiomyocytes is a result of cytokinesis failure.

Methods and Results:
To address this, we generated several transgenic mouse models to determine whether forced induction of cardiomyocyte cytokinesis generates mononuclear cardiomyocytes and restores the endogenous regenerative properties of the myocardium. We focused on two complementary regulators of cytokinesis, namely Polo-like kinase 1 (Plk1) and epithelial cell-transformation sequence 2 (Ect2), Here we report that cardiomyocyte-specific transgenic overexpression of constitutively active Plk1(T210D) alone promotes mitosis and cytokinesis in adult hearts, while overexpression of Ect2 alone promotes cytokinesis. Intriguingly, cardiomyocyte-specific overexpression of both Plk1(T210D) and Ect2 concomitantly (double transgenic) prevents binucleation of cardiomyocytes postnatally and results in widespread cardiomyocyte mitosis, cardiac enlargement, contractile failure and death before two weeks of age. Similarly, high-dose doxycycline inducible cardiomyocyte-specific overexpression of both proteins (inducible double transgenic) in the adult heart results in reversible widespread cardiomyocyte mitosis, cardiac enlargement, and contractile failure, while low-dose transient induction also results in significant cardiomyocyte proliferation and lower ejection fraction that is reversible after doxycycline is removed. Finally, we show that transient low-dose induction of both genes in adults improves left ventricular systolic function following myocardial infarction.

Conclusion:
Collectively, these results demonstrate that cytokinesis failure mediates cardiomyocyte multinucleation and cell cycle exit of postnatal cardiomyocytes but may be a protective mechanism to preserve the contractile function of the myocardium.
Abstract 15793: Gender-Specific Pathophysiologic Differences in All-Cause Mortality Among Patients With Atrial Fibrillation
Authors: Senapati Sidhartha , Lee Hon-chi , Oh Jae K , Greene Eddie L , Melduni Rowlens M
Published: June 2023

Introduction:
Although the prevalence of atrial fibrillation (AF) is higher in men than in women, the onset of AF appears to diminish the survival advantage in women. The pathophysiologic factors underlying survival outcome in AF are not well understood.

Methods:
A cohort of 3480 Olmsted County, Minnesota residents (mean age 72.8±14 years, 51.8% female) with incident AF who underwent transthoracic echocardiography within 30 days of AF diagnosis [median (IQR) 1, 1-6 days] were retrospectively studied. We examined the association of clinical parameters and survival according to gender. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival in males and females.

Results:
Females were older and slimmer than males and more frequently had hypertension, prior stroke, and had higher CHA
2
DS
2
vasc score, pulse pressure and effective arterial elastance. Women also had smaller LV end diastolic dimension with higher LV ejection fraction, LA volume index, E/e prime ratio, and PASP (43.6±13.8 vs 39.1±13.3; <.001). During a mean follow-up of 7.4±6.2 years (median 6.6 years), 2569 patients died. Women had a lower 5-year survival compared to men. The probability of 1- and 5-year survival rates for women vs men were 80.2% vs 84.1% at 1 year and 54.4% vs 63.7% at 5 years (log-rank
P
<.001). In multivariable Cox regression analysis, after accounting for potential confounders, the independent predictors of mortality were age (HR 1.07 [95% CI 1.06-1.08]), PASP (per 5 unit increment) (HR 1.11 [95% CI 1.09-1.12]), effective arterial elastance (HR 1.06 [95% CI 1.01-1.12]), previous heart failure (HR 1.34 [95% CI 1.20-1.49]), diabetes (HR 1.33 [95% CI 1.20-1.48]), prior stroke (HR 1.26 [95% CI 1.13-1.41]), smoking (HR 1.13 [95% CI 1.06-1.20]), chronic lung disease (HR 1.32 [95% CI 1.20-1.45]), peripheral arterial disease (HR, 1.32 [95% CI 1.18-1.48]), and chronic kidney disease (HR, 1.52 [95% CI 1.38-1.69]).

Conclusions:
In a community-based cohort of patients with incident AF, markers of arterial stiffness and diastolic dysfunction were more prevalent in women compared to men and were strongly predictive of mortality. Our findings suggest that vascular stiffness may underlie the increased risk of mortality observed in women after a new diagnosis of AF.
Abstract 158: Adult Defibrillation Shocks Do Not Cause Cardiac Damage In A Pediatric Porcine Model
Authors: McCartney Ben , Harvey Adam , Kernaghan Amy , Crawford Paul , Bond Raymond , Finlay Dewar , McEneaney David
Published: June 2023

Introduction:
AEDs often utilize specific modes for treating pediatric patients, enabling reduced energy defibrillation and pediatric specific guidance on performing CPR. If a pediatric mode is not available, current guidelines recommend use of adult mode. It is not fully understood if delivery of adult mode shocks or CPR results in cardiac damage in children. The aim of this pilot study was to observe the effects of delivering either adult shocks or CPR during sinus rhythm in pediatric weight swine.

Methods:
Six anesthetized swine (10-12 kg) were studied. Four received three adult unsynchronized shocks (150-150-200 Joules) (HeartSine, UK) without induction of VF to isolate the effect of shocks alone. Two received three, two-minute episodes of CPR. A Philips MRx (Philips, USA) recorded CPR depth. ST-segment deviation was recorded before shocks and at 10-seconds and 60-seconds post-shock. Animals then entered a 4-hour monitoring period were blood samples and echocardiographic images were taken at +2 hours and +4 hours.

Results:
No shock (0/12) or episode of CPR (0/6) delivered during sinus rhythm resulted in conversion to an arrest rhythm. CPR was delivered at depths between 21 and 39 mm. There was no significant change in ST-segment deviation, cardiac troponin I, creatine phosphokinase or left ventricular ejection fraction from baseline values for either group (Table 1). Additionally, there were no significant differences between the two groups for any endpoint.

Conclusions:
Neither adult energy shocks nor CPR delivered to pediatric weight pigs resulted in significant adverse effects by any metric analyzed. This suggests that application of adult shock energies and CPR without experimental confounders (e.g. ischemia, metabolic disturbance) does not result in significant myocardial damage in this model of pediatric resuscitation. Future studies should investigate the effect of guideline depth CPR in this model. Note: this is a pilot study with a limited sample size.
Abstract 15804: Gender-Specific Analysis of Current Trends in Primary Prevention of ASCVD
Authors: Nisly Haven , Moran Ryan
Published: June 2023

Introduction:
Cardiovascular disease is the leading cause of death in the U.S. for both men and women. Disparities exist not only in women’s outcomes from atherosclerotic cardiovascular disease (ASCVD) but also in assessment of their risk of disease development. This can be attributed in part to the historical misperception that ASCVD affects males at a greater rate than females. This study examines whether female patients are appropriately prescribed statin medication for primary prevention of ASCVD at the same rates as male patients of equivalent risk.

Methods:
Data were gathered from 11,871 de-identified UC San Diego patient medical records, which included primary care patients ages 40 to 75 without prior ASCVD. The ACC/AHA 10-Year ASCVD Risk Estimator was used to calculate risk scores. The groups of elevated-risk patients, defined by a score greater than or equal to 7.5, of each gender who were and were not prescribed statins were compared using a Chi-Square analysis, conducted in SPSS, in order to determine whether a significant difference existed in appropriate statin prescription between male and female patients. Significance was assessed using the Pearson Chi-Square value compared to a 0.05 significance threshold.

Results:
In the group of male patients, 796 were on a statin when indicated, compared to the expected value of 803.1, and 807 were not, compared to 789.9 expected. For the female group, 305 patients were on a statin when indicated, compared to 287.9 expected, and 266 were not, compared to 283.1 expected. The Pearson Chi-Square value comparing the groups was 0.095, which is greater than the 0.05 significance threshold.

Conclusions:
Because of evidence that physicians may be influenced by biases about women’s heart disease risk, this study assessed the hypothesis that there would be a significant difference in appropriate prescription of statins for primary ASCVD prevention between male and female patients. This analysis did not show evidence of a statistically significant difference between the rates of untreated elevated-risk men versus women in this patient population. Though a single-institution study, these findings may signal increasing awareness of women's heart disease risk among primary care physicians.
Abstract 15805: Content Validity of a Measurement Tool to Assess Provider Concordance to the 2017 High Blood Pressure Clinical Practice Guidelines
Authors: Tedla Yacob , Greenland Philip , Roumie Christianne , Harrison David G , Paparello James , Beckman Joshua , Luther James M , Rothman Russell
Published: June 2023

Introduction:
The AHA/ACC 2017 High Blood Pressure clinical practice guidelines included numerous changes, including a new definition of hypertension (≥130/80 mm Hg) and lower thresholds for medication initiation, that may be challenging for clinicians to adopt. Developing and validating a tool to measure provider compliance to the guidelines is valuable for ascertaining compliance as a metric of healthcare quality.

Methods:
A five-step process was conducted.
1) Constructing items
: 31 items that include five domains (screening, lifestyle, drug therapy, follow-up, laboratory) were compiled by the study investigators from the 2017 guideline.
2) Expert evaluation
: A panel of five physicians with expertise in hypertension management reviewed and scored the items on how well they match to the guideline on a scale of 1 to 4 (1=does not match at all, 2=matches somewhat, 3=matches, 4=matches very well). The panel subsequently met face-to-face and came to a consensus on items that received <3 score by any reviewer.
3) Refining items
: Using information gathered during step 2, the tool was subsequently modified.
4) Expert reevaluation
: experts rescored the match of the refined items to the guideline.
5) Validity score
: Item Content Validity Index (I-CVI) was calculated as the proportion of experts who gave a score of ≥3 for an item and Scale Content Validity Index (S-CVI) as the proportion of items that received a score of ≥3 out of total items. I-CVI and S-CVI ≥0.80 were included in the final tool.

Results:
Twelve out of 31 items had a score of <3 by at least one panel member. After the panel discussion, the contents of 9 of the 12 items were modified. The expert panel eliminated 2 of the 12 items because they were not clearly recommended in the guidelines. One item with ICV-I <80% was eliminated. Each of the remaining 28 items had I-CVI ≥80% (10 had 80% and 18 had 100% I-CVI) and were included in the final tool. S-CVI for all items was 91%. Of 28 items, 3 were related to screening, 1 to lifestyle, 17 to drug therapy, 1 to laboratory, and 7 to follow-up.

Conclusions:
We developed and refined a measurement tool to evaluate provider level of compliance to hypertension treatment guidelines. This tool will be applied to identify patients at risk of receiving care inconsistent with current guidelines.