bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18594: Symptom Physiology in Postural Tachycardia Syndrome: Prevalence of Dysfunctional Breathing and Preload Insufficiency Using Novel Invasive Cardiopulmonary Exercise Testing
Authors: Honnekeri Bianca , Gupta Mohak , Paul Deborah , Tonelli Adriano , Mayuga Kenneth A
Published: December 2023

INTRODUCTION:
Dyspnea and lightheadedness are debilitating symptoms experienced by POTS patients, yet there is paucity of data on their pathophysiology. Invasive cardiopulmonary exercise testing (iCPET) is a novel investigation which gathers physiologic data and better characterizes these phenomena.

RESEARCH QUESTION:
What is the prevalence of dysfunctional breathing (DB) and preload insufficiency (PI) in POTS patients who undergo iCPET? METHODS: We studied hemodynamics in a cohort of 35 POTS patients who underwent iCPET in a sitting bicycle. The protocol augments CPET with continuous data from pulmonary artery catheterization and arterial line. PI is defined as abnormally low right atrial pressure during exercise and reduced peak cardiac output percentage of predicted. DB is characterized by exercise-induced oscillatory ventilation.

RESULTS:
The study cohort had a mean age of 40.4 years, and 26 of the 35 patients (74.3%) were female. iCPET revealed the prevalence of only DB as 5.7%, only PI as 37.1%, both DB and PI as 37.1%, and neither DB nor PI as 20% (p=0.006). These 4 sub-groups were then compared for analysis. Notably, the cardiac output percentage of predicted at peak exercise was significantly different between the 4 groups (91.6%, 81.1%, 89.5%, 117.4%; p=0.011). The DB alone subgroup had mean PETCO2 at peak exercise of 28.5, mean VE/VCO2 at AT of 37.5, mean respiratory rate of 39.5 cpm and mean maximal ventilation during exercise of 93.7L. DB was more common in older individuals, while PI was more common in younger individuals (p=0.004). Our study suggests that PI and DB are common entities in POTS with distinct hemodynamic characteristics, and may co-occur.

CONCLUSION:
This study is a first step towards elucidating various physiological abnormalities in POTS, where symptoms are often debilitating. iCPET yields hemodynamic information that may provide avenues for targeted interventions that could significantly improve quality of life.
Abstract 186: Regional Cerebral Oxygen Saturation to Predict Neurologic Outcome During Out-of-Hospital-Cardiac -Arrest: An Ancillary Analysis of a Prospective Interventional Study
Authors: Debaty Guillaume , Segond Nicolas , Crespi Christophe , sanchez Caroline , Boeuf Johanna , Duhem Helene , Labarere José , Lurie Keith G
Published: December 2023

Background:
Very few prognosis markers are available to help emergency medical services decide whether to continue or terminate cardiopulmonary resuscitation (CPR). ETCO
2
has been described to predict return of spontaneous circulation (ROSC) but its ability to predict neurologic outcome is poor. Cerebral tissue oxygen saturation (RSO
2
) during CPR, as measured by near-infrared spectroscopy (NIRS) represents hemoglobin oxygenation within the cerebral tissue. The measure is feasible during CPR. It has been associated with the probability of ROSC. The aim of this study was to assess the predictive value of RSO2 regarding 30 days favorable neurologic outcome after out-of-hospital cardiac arrest (OHCA).

Method:
Data were collected during a prospective single center before-after interventional study comparing conventional CPR (C-CPR) with Automated head and thorax elevation CPR (AHUP). C-CPR was performed manually and AHUP-CPR was delivered using a LUCAS Active Decompression (Stryker Medical, USA), an EleGARD Patient Positioning System (AdvancedCPR Solutions, USA), and an impedance threshold device (ResQPOD-16, Zoll, USA). The study was carried out in four fire stations and one physician staffed advanced life support emergency medical services in France. ETCO2 (using an EMMA, Massimo or Lifepack 15, Stryker, USA) and RSO2 (H500, Nonin, USA) were collected as soon as possible during CPR. Favorable neurologic outcome was defined as MRS score of 0 to 3 at 30 days. Results are presented as mean ± standard deviation.

Results:
ETCO
2
was collected in 118 patients (11 with good neurologic outcome) and RSO
2
in 69 patients (6 with good neurologic outcome). Maximum ETCO
2
during CPR was 43±19mmHg in favorable neurologic outcome patients vs. 35±16mmHg (p=0.13). ETCO
2
alone had an AUC of 0,63 (IC95% 0.46-0.79). Maximum RSO2 during CPR was 68±13% for favorable neurologic outcome patients vs. 49±13% (p<0.001). For survival with favorable neurologic outcome, rSO
2
alone had an AUC of 0.85 (IC95% 0.71-0.99). With a maximum RSO
2
value below 51% there was no patient with favorable neurologic outcome.

Conclusion:
In this prospective interventional study, unlike EtCO
2
, RSO
2
values were significantly associated with favorable neurological survival at 30 days.
Abstract 18614: Growth Hormone Releasing Hormone Agonists Reverse the Cardiometabolic Heart Failure With Preserved Ejection Fraction Phenotype via the Hypoxia-Inducible Factor 1 Alpha
Authors: Kanashiro-Takeuchi Rosemeire M , Takeuchi Lauro M , Balkan Wayne , Dulce Raul A , Kazmierczak Katarzyna , Kulandavelu Shathiyah , Cai Renzhi , sha wei , Schally Andrew , Hare Joshua M
Published: December 2023

Introduction:
Heart failure (HF) with preserved ejection fraction (HFpEF) treatment is limited due in large part to lack of understanding of the underlying mechanisms involved. Recently, we showed that growth hormone-releasing hormone-agonist (GHRH-agonist) has cardioprotective effects in a cardiometabolic HFpEF model; however, the mechanism of these therapeutic effects is still unclear. Here, we hypothesize that the anti-HFpEF properties of GHRH-receptor activation are mediated by hypoxia-induced factor (HIF)-1α pathway.

Methods:
Wild-type (WT) and HIF-1α cardiomyocyte knockout (HIF-1α
CM
KO) mice received a high-fat diet (HFD) plus the nitric oxide synthase inhibitor (L-NAME) for 9 weeks. After 5 weeks of HFD+L-NAME regimen, animals receive daily injections of GHRH-agonist, MR-356, or placebo during a 4-week period. Control animals received no HFD+L-NAME or MR-356 treatment. Echocardiography, blood pressure, glucose tolerance test, and hemodynamic measurements were evaluated.

Results:
The HFD+L-NAME diet produced a HFpEF phenotype, which was reversed in mice with intact HIF-1α treated with MR-356 (Figure 1 A-E). In contrast, following cardiac-specific deletion of HIF-1α
CM
, MR-356 no longer reversed (A) the elevated isovolumetric relaxation time (IVRT), (B) increased E/E’ ratio and (C) reduced global longitudinal strain (GLS). EF was preserved (D) while the slope of the end-diastolic pressure-volume relationship (EDPVR, E) was increased in the placebo group and restored by MR-356 in WT mice but not HIF-1α
CM
KO mice. Figure 1F shows representative pressure-volume loops from WT placebo, HIF-1α
CM
treated with placebo or MR-356.

Conclusions:
Our findings show that cardiac-specific HIF-1α deletion blocks cardioprotective effects of MR-356 suggesting that HIF-1α is necessary for its anti-HFpEF effects.
Abstract 18632: Mechanical Circulatory Support in Patients Without Cardiogenic Shock Undergoing Percutaneous Coronary Intervention
Authors: Miller Elliott , Gordon Aliza , Liu Ying , Ahmad Tariq , Girotra Saket , Davila Carlos D , Crawford Geoffrey , Whitney John , Desai Nihar R
Published: December 2023

Background:
The use of mechanical circulatory support (MCS) devices for high-risk percutaneous coronary intervention (PCI) has increased over the last decade. However, data on outcomes between MCS device type have been mixed and long-term outcomes are limited. Our aim was to examine the association between intravascular microaxial left ventricular assist device (LVAD) or intra-aortic balloon pump (IABP) use in patients without cardiogenic shock undergoing PCI.

Methods:
This retrospective study analyzed administrative claims data from a large, insured population across the United States. Patients who underwent PCI without cardiogenic shock from 4/1/2016 to 7/31/2022 were included. Using inverse probability treatment weighting (IPTW), we assessed for the association between device type and all-cause mortality during the index admission, 30-days, and up to 1-year. Secondary outcomes included stroke, bleeding, incident dialysis, repeat revascularization, and total healthcare costs.

Results:
We identified 2,879 patients undergoing PCI without cardiogenic shock, the mean (SD) age was 68.2 (12.5) years, 27% (n=764) were women, and 61% (n=1,757) had a primary diagnosis of acute myocardial infarction (AMI). After IPTW, intravascular LVAD use was not associated with a statistically significant difference in in-hospital (Odds ratio [OR] 1.30; 95% Confidence interval [CI]: 0.88-1.91,
P
=0.19) or 30-day (OR 1.19; 95% CI:0.84-1.69,
P
=0.33) mortality compared to IABP use. At 1-year, intravascular LVAD use was associated with a significant increase in mortality (Hazard ratio 1.23; 95% CI:1.04-1.46,
P
=0.01). Compared to those receiving an IABP, index admission mean total costs ($81,970 vs. $65,298;
P
<0.001) and mean monthly costs ($11,030 vs. $14,133;
P
<0.001) up to 1-year were significantly higher in those receiving an intravascular LVAD. There was no significant association between device

type and stroke, bleeding, incident dialysis, and repeat revascularization at any timepoint (all,
P
>0.05).

Conclusions:
In patients without cardiogenic shock undergoing PCI, intravascular LVAD use was associated with higher costs but not associated with lower mortality. Randomized data is needed to improve device selection for these patients.
Abstract 18642: GWAS to Function Highlights the Role of REST in Endothelial Biology and Atherosclerosis
Authors: Viskadourou Maria , Reventun Paula , Alcharani Nunzio , Villapudua Gastelum Carlos , Osburn William , Toledano Sanz Pablo , Lowenstein Charles J , Arvanitis Marios
Published: December 2023

Introduction:
Despite the emergence of new lipid-lowering therapies, coronary artery disease (CAD) remains the leading cause of death worldwide. Genome-wide association studies (GWAS) for CAD have discovered multiple novel loci that contribute to CAD pathogenesis. However, limitations in the interpretability of those GWAS associations have hindered the clinical translation of those findings.

Hypothesis:
In this study, we sought to evaluate the mechanisms of the association between chromosomal locus 4q12 and CAD, replicated in multiple independent GWAS for CAD.

Methods:
We utilized a combination of computational methods and in vitro assays to achieve our objectives.

Results:
Meta-analysis of public expression quantitative trait locus (eQTL) data and multi-trait colocalization across atherosclerosis-relevant cell types revealed that the CAD 4q12 locus regulates the expression of REST, a transcriptional repressor, in human aortic endothelial cells (HAEC) and prioritized 2 enhancer variants as candidate causal variants for the GWAS association. CRISPR interference confirmed that the rs6853156 variant regulates REST expression in inducible human endothelial cells. Pathway enrichment analysis in HAEC after REST silencing showed that epithelial to mesenchymal transition was the most upregulated pathway suggesting a potential mechanism via which silencing REST contributes to atherosclerosis. Endothelial to mesenchymal transition (endMT) was confirmed in HAEC after REST silencing at the RNA and protein level by rt-qPCR, western blot, and immunofluorescence. Concordantly, REST silencing increased endothelial permeability and matrix metalloproteinase activity in endothelial cell supernatants in vitro. L1CAM, a known endMT activator was only expressed in HAEC upon REST silencing. Chromatin immunoprecipitation sequencing supports direct binding of REST to the L1CAM promoter. Simultaneous silencing of L1CAM and REST in HAEC inhibited the observed upregulation of mesenchymal genes induced by REST silencing.

Conclusions:
In summary, our data reveal a novel role of REST as a repressor that functions as a constitutive inhibitor of endMT in human arterial endothelial cells.
Abstract 18651: Case Report: Transcatheter Edge-to-Edge Repair in a 59-Year-Old Patient With Mitral Regurgitation and Challenging Anatomy
Authors: Mubarak Fathima Shafra , Seligman Henry , Akhtar Mohammed Majid , Duncan Alison , Vazir Ali , Connolly Lauren , Good Katherine , Asimakopoulos George , Heng Ee Ling , Smith Robert D
Published: December 2023

Re-intervention for patients with mitral valve disease is a growing challenge. We present a 59-year-old male with a history of a congenitally bicuspid aortic valve. He had valve and root replacement for aortic regurgitation in his 30s and two subsequent sternotomies for prosthesis failure and endocarditis. After admission with acute pulmonary edema, there was persistent NYHA class II-III dyspnea. Echo showed severe (grade IV) mitral regurgitation due to the dehiscence of a 32mm mitral annuloplasty ring. The coaptation point of the leaflets was posterior to the posterior aspect of the ring. No regurgitation was observed through the ring’s central orifice, but the tissue was seen on its posterior aspect, suggesting torn posterior leaflet or healed vegetation. The left ventricle was mildly dilated, and the LVEF was 53%. The right ventricle was moderately dilated with severe functional tricuspid regurgitation with a normally functioning aortic valve prosthesis. After extensive discussion, due to his multiple previous surgeries and challenging anatomy, the patient was deemed unsuitable for surgical treatment. There is some limited registry data to support TEER as a safe and feasible alternative to surgery in this cohort. He underwent successful implantation of two clip devices in the A2/P2 and A2/P2b positions via a trans-septal approach under a general anesthetic. Femoral venous access was used. Some useful learning points relate to the challenges posed by the unusual anatomy in terms of imaging and trajectory. No MVARC complications. Postoperatively the LVEF was 55% with a mean transvalvular gradient of 5mmHg and only mild (grade I) transvalvular MR. At three months the patient reported an improvement of overall functional status. This successful case of “clip-in-ring” TEER illustrates one of the expanding indications for existing trans-catheter valvular therapies as well as the potential for creative application of TEER in helping patients with high surgical risk.
Abstract 18674: Deep Phenotyping Arrhythmogenic MVP With Imaging and Genotyping Reveals Important Shared Genetic Etiology With Arrhythmia and Cardiomyopathy Genes
Authors: Sharaf Dabbagh Ghaith , Agnihotri Ruchi , Kaur Gurpreet , Fazio Gregory , Singleton Matthew , Lee Jefferson , Schuler Brian , Malik Adnan , Obeng-Gyimah Edmond , Chahal C. Anwar
Published: December 2023

Introduction:
Mitral valve prolapse (MVP) has a high population prevalence 2-4% with an arrhythmogenic subtype presenting with premature ventricular complexes (PVC) ventricular tachycardia (VT) and sudden death. There is a continued search for markers of MVP to help risk stratify patients.

Hypothesis:
Arrhythmogenic MVP shares genetic etiology with Mendelian causes of arrhythmia and cardiomyopathy

Methods:
Consecutive adult patients with arrhythmogenic MVP patients prospectively evaluated

Results:
A total of 33 cases (age 55±15 years, female 51.5%) presented with history of hypertension (33%), diabetes (3%), coronary disease (12%), atrial fibrillation (45%), bileaflet MVP (58%) and syncope (18%). ECG findings include inverted T-waves in inferior leads in 6%, pleomorphic PVC in 6%, Ventricular couplets in 51.5%, non-sustained VT in 73% and sustained VT in 33%; High PVC burden was seen in 55% of cases with burden 15±14%. Echocardiography noted LV ejection fraction of 55±8%, mitral regurgitations in 70% (severe 18%, moderate 27%, mild 24%), mitral annular disjunction in 39%, and Pickelhaube sign in 9% of cases. Cardiac magnetic resonance showed LVESV 113±119mm, LVEDV 117±70mm, and late Gadolinium enhancement in 48% with highest prevalence in basal inferolateral segment. PET-CT performed in 17 cases and showed fluorodeoxyglucose uptake in 24% cases, mostly in basal inferolateral segment as well. Genetic testing was performed in 23 cases and reported a putative pathogenic variant in 21.7%:
FLNC
(Exemplar case,
Figure 1
) cause of dilated cardiomyopathy,
TBX5
cause of Holt-Oram syndrome,
DSP
cause of arrhythmogenic cardiomyopathy
, TTN
causes of dilated cardiomyopathy,
MTO1
cause of mitochondrial hypertrophic cardiomyopathy.

Conclusion:
Full evaluation of arrhythmogenic MVP with multimodality imaging and genetic testing reveals high burden of fibrosis, inflammation, and candidate pathogenic variants.
Abstract 18683: Prevalence of Obesity in Transgender Adults and Its Impact on Major Adverse Cardiac and Cerebrovascular Events and Pulmonary Embolism: A Population-Based Analysis
Authors: Pingili Adhvithi , Sunkara Praveena , vempati Roopeessh , Madhavaram Hasmitha J , Vemula Madhusha , Lakkimsetti Mohit , Vasudev Ishita , Gummadi Jyotsna , Sagoo Gurbina , Majooju Mounica , Nanjundappa Athmananda , Singh Sandeep , Desai Rupak
Published: December 2023

Introduction:
Although obesity and its impact on major adverse cardiac and cerebrovascular events (MACCE) and pulmonary embolism(PE) have been extensively studied, little is known about obesity’s impact on MACCE and PE in the transgender population. Through this study, we sought to establish the prevalence of obesity and its impact on MACCE outcomes and PE in this population subset.

Methods:
Using the National Inpatient Sample 2020 database, we identified admissions of transgender patients or patients with prior sex reassignment surgery using ICD-10 CM Codes. Later, all these patients were divided into obesity and non-obesity cohorts. Multivariate regression analysis was then performed for in-hospital MACCE and PE to calculate the odds ratio (OR). Predictors for MACCE were also identified in transgender patients with obesity.

Results:
In 2020, 19,345 transgender patients or patients who had sex reassignment surgery were admitted to the hospital; 16,390 (84.7%) had no obesity, and 2,955 (15.3%) had obesity. In the obesity cohort, 64.5% of patients had a mean age between 18-44 years, 66.5% were white, 47.9% were transgender males, and 52.1% were transgender females. The most common comorbidities include hypertension (43.5%), diabetes (32.5%), and chronic pulmonary disease. (27.7%). Among the transgender patients with obesity, 5.4% had MACCE events, and 1.2% had cardiac arrest. A statistically significant association was observed in MACCE [OR 2.1, 95% confidence interval (CI) 1.24-3.55, p=0.006] and cardiac arrest (OR 3.92, 95% CI 1.11-12.63, p=0.022 among obesity cohort, with age being the important predictor of MACCE. However, no statistically significant association was observed in acute myocardial infarction (OR 1.82, 95% CI 0.8503.93, p=0.125), acute ischemic stroke (1.34, 95% CI 0.39-4.62, p=0.638) and PE (2.18, 95% CI 0.83-5.72, p=0.113).

Conclusion:
We observed increased odds of MACCE and cardiac arrest in transgender patients with obesity in our large population-based analysis. This observation could be a result of hormonal treatment that transgender adults receive or associated disparities with transgender care. Further large-scale studies are needed to understand the impact of obesity and MACCE events, and PE in this population.
Abstract 18686: Distinct Proteomic Signatures in Subjects With Elevated Lipoprotein(a) Levels With and Without Coronary Artery Disease
Authors: Goonewardena Sascha N , Malick Waqas , DAMODARAN DILNA , Katragadda Jay Krishna , Grushko Olga , Cady Gillian , Murthy Venkatesh L , Rosenson Robert S
Published: December 2023

Introduction:
Genetic and observational studies suggest a causal link between an elevated lipoprotein(a) [Lp(a)] and coronary artery disease (CAD). Although Lp(a) is one of the strongest genetic risk factors for CAD, not all subjects with an elevated Lp(a) develop CAD.

Hypothesis:
We hypothesized that in subjects with an elevated Lp(a) (>150nmol/L), proteomic signatures could differentiate between those with and without CAD.

Methods:
Outpatients with known Lp(a) levels and a coronary CT between April 2021 to April 2023 were enrolled and circulating biomarkers were measured using Olink proteomic platform. This study was approved by the IRB at the Icahn School of Medicine, New York, NY.

Results:
First we analyzed clinical markers and proteomic signatures in subjects with and without CAD. An elevated Lp(a) level was a critical feature between the two groups. We then focused our analysis on differences in clinical and proteomic signatures in subjects with an elevated Lp(a). High Lp(a) subjects with (n=28) and without CAD (n=7) were well matched with respect to clinical characteristics including age (66 vs 52y; NS) and median Lp(a) levels (228; [203-270] vs 222; [204-323]). Additionally, hsCRP and LDL-C levels were well matched between groups. 2907 unique proteomic markers were detected and there were 29 markers that were significantly different in high Lp(a) subjects with CAD compared with those without CAD. An unsupervised principal component analysis was performed, and we found that markers of thrombosis (PARP1, tissue factor), inflammation (CCL3, CD40) were key proteomic markers that separated high Lp(a) subjects with and without CAD, suggesting a bidirectional relationship between inflammatory and thrombotic pathways in Lp(a)-driven CAD.

Conclusions:
To our knowledge, this is the first prospective study to examine proteomic differences in high Lp(a) subjects with and without CAD. Profiling over 3000 unique proteomic markers, we found that in high Lp(a) subjects, there were differences in thrombotic and inflammatory markers in those with CAD compared to those without CAD. These findings have important implications to understanding the mechanisms through which Lp(a) drives CAD and in risk stratifying high Lp(a) subjects susceptible to CAD.
Abstract 18696: Berberine as a Supplement to Guideline-Based Lipid Management of a Patient With Heterozygous Familial Hypercholesterolemia: A Case Presentation
Authors: Epstein Elizabeth S , Goel Kunal , Triffon Douglas W
Published: December 2023

Description of Case:
A 62-year-old female presented for a lipidology consult. Labs revealed total cholesterol >450 mg/dL, Lp(a) 42 mg/dL, and LDL-P 2938. She was not on any lipid lowering therapy. A clinical diagnosis of heterozygous familial hypercholesterolemia (HeFH) was made. She reported occasional chest pain with both cardiac and noncardiac features. She had no personal history of CAD, and her family history revealed a mother and maternal grandfather with CAD in their 50s. A CCTA was performed, which revealed mild-moderate plaque in the ostial left circumflex (25-49%) and a CAC score of 124 (90-95th percentile). She was started on rosuvastatin 10mg daily and alirocumab with reduction of her LDL-C to 247 mg/dL. Given documented CAD, LDL-C <55 mg/dL was targeted. She had intolerable side effects to combination ezetemibe plus bempadoic acid and lomitapide. Evinacumab or LDL pheresis were offered, and the patient preferred to start evinacumab. Alirocumab was stopped. With rosuvastatin plus evinacumab, her LDL-C improved to 198 mg/dL. Berberine 1000mg was added to her regimen and resulted in further reduction of her LDL-C to 117 mg/dL.

Discussion:
Long used in Traditional Chinese and Ayurvedic medicine, Berberine is an alkaloid found in plants such as barberry and tree turmeric. Berberine suppresses PCSK9 transcription by regulating hepatocyte nuclear factor 1 alpha, a binding site located upstream from the PCSK9 gene promoter. The role of supplements in lipid management remains unknown. We describe a case of HeFH in which berberine yielded an 81 mg/dL absolute reduction (41% relative reduction) in LDL-C when added to guideline-based therapy. In a dedicated integrative lipidology practice, berberine may be an effective supplement to the pharmaceutical management of severe hyperlipidemia.
Abstract 18713: The Impact of ECG-AI Design Choices on Clinical Utility: A Deep Dive Into Left Ventricular Hypertrophy, Hypertrophic Cardiomyopathy, and Cardiac Amyloidosis
Authors: Asfahan Shahir , Anto Ausath , Verma Shiva , Gupta Yash , Noseworthy Peter A , Attia Zachi , Friedman Paul , Barve Rakesh , Lopez-Jimenez Francisco , Siontis Konstantinos , Awasthi Samir
Published: December 2023

Introduction:
Artificial intelligence applied to electrocardiograms (ECG-AI) enables early and efficient detection of cardiovascular disease. The technical and clinical impact of different approaches to designing ECG-AI remains under-explored. We consider left ventricular hypertrophy (LVH) and examine the impact of disease-specific labeling of minority etiologies of left ventricular wall thickening- hypertrophic cardiomyopathy (HCM) and cardiac amyloidosis (CA) - on ECG-AI performance.

Hypothesis:
ECG-AI designed to detect HCM or CA outperforms ECG-AI broadly trained to identify LVH due to differences in attention to key ECG features associated with HCM or CA.

Methods:
Independent neural networks were trained to identify HCM, CA, and LVH. HCM and CA patients were identified using the full depth of EHR data and validated via clinician adjudication (N = 3,025 and 4,251 patients, respectively). Moderate and severe LVH patients (N = 98,144) were identified using echocardiogram results and international LVH criteria. We compared the ability of disease-specific ECG-AI vs. LVH ECG-AI to detect HCM (or CA) by examining model performance within each of the three test sets.

Results:
52.6% of HCM patients and 49.5% of CA patients met LVH criteria. Within the HCM test set, the AUROC, sensitivity, specificity, and positive predictive value (PPV) of the HCM ECG-AI were 0.94, 0.88, 0.85, and 60%, respectively, whereas the same for LVH ECG-AI were 0.83, 0.83, 0.64, and 37%. Within the CA test set, CA ECG-AI achieved AUROC, sensitivity, specificity, and PPV of 0.94, 0.81, 0.91, and 69%, respectively, whereas the same for LVH ECG-AI were 0.75, 0.73, 0.68, and 31%. ECGs positive for HCM exhibited higher P wave area, QRS deflection and R wave amplitude compared to LVH-positive ECGs (Cohen's D > 0.75). ECGs positive for CA exhibited lower R wave amplitude/area, QRS deflection and QRS areas (Cohen's D > 0.6).

Conclusion:
Models trained using carefully labeled HCM or CA identify distinct signals associated with the diseases, resulting in improved disease discrimination compared to a model trained to identify echocardiographic left ventricular thickening. Labeling choices should be communicated transparently to clinicians to ensure safe and effective use of ECG-AI.
Abstract 18719: Trends in Representation of Authorship From Low and Low-Middle-Income Countries in Cardiology Journals Over the Last Two Decades: We Need More Representation
Authors: Martinez de Majo Alfonso , Guilliod Christian , lam victoria , De Oliveira Gomes Diana
Published: December 2023

Background:
Authors from developing countries encounter unique publishing barriers that limit their research output in international journals. The authorship representation from low and low-middle-income countries (LIC and LMIC) in cardiology journals remains unexplored. We examined publishing trends from authors affiliated with LICs & LMICs in three distinguished cardiology journals from 2000 to 2022.

Methods:
We collected retrospective data using PubMed on the authorship affiliation of all articles published between 01/01/2000 and 12/31/2022 in the journals Circulation, European Heart Journal (EHJ), and Journal of the American College of Cardiology (JACC). Using the World Bank country classification list, we classified authors affiliations.

Results:
61257 articles were published between 2000 and 2022 (24812 in Circulation, 16110 in EHJ, and 20335 in JACC), of which only 555 (0.91%) had one or more authors affiliated with institutions from an LMIC or LIC (180 in Circulation, 164 in EHJ, and 175 in JACC): 36 (0.06%) from LIC, and 519 (0.85%) from LMIC. The total number of authors from LIC was 63, more than 1/3 from Mozambique (N=22, 35%); meanwhile, 664 authors were from LMIC, the majority from India (N=287, 43%), followed by Lebanon (N=15.9%). The trend of authorship from LIC and LMIC is increasing in the last decade (Figure 1)

Conclusion:
Less than 1% of articles published over the last two decades in three distinguished cardiology journals have one or more authors affiliated with institutions from LIC and LMIC. Our results suggest remarkable obstacles for these authors to publish in top journals in the USA and Europe. The study indicates an upward trend in authorship during the last decade, implying a potential shift towards more inclusive publishing opportunities. Further endeavors should seek to understand structural barriers and that limit research output in developing countries to minimize healthcare gaps and promote more inclusive research.
Abstract 18742: Matrilysin (MMP7) as a Robust Predictor of Hypertension Incidence and Complications: Findings From a Proteomic Analysis in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Mathews Lena , Hu Xiao , Wang Frances M , Chen Jingsha , Yu Bing , Hoogeveen Ron C , Ballantyne Christie M , Selvin Elizabeth , Shah Amil M , Ndumele Chiadi E , Coresh Josef , Matsushita Kuni
Published: December 2023

Introduction:
Proteomic techniques can be applied for the discovery of common pathways underlying both incident hypertension and hypertension-related cardiovascular outcomes.
Research Questions:
To identify and validate proteins associated with incident hypertension and to examine the association of these validated proteins with hypertension-related cardiovascular events.

Methods:
We quantified the association of 4,955 plasma proteins (measured by SomaScan® Version 4 Assay) with incident hypertension (defined as systolic blood pressure (BP) ≥140, diastolic BP ≥ 90 mmHg, or hypertension medication use) in participants free of hypertension at ARIC visit 3 (1993-95) using Cox regression models adjusted for demographics, clinical characteristics and baseline BP. Significant associations were validated using proteomic measurements at ARIC visit 2 (1990-92). We then examined the association of validated proteins with incident coronary heart disease (CHD), stroke, and heart failure (HF) among participants with hypertension at visit 3 using Cox regression models additionally adjusted for hypertension duration and treatment.

Results:
There were 5,080 participants in the discovery cohort (mean age 59y, 13% Black, 54% women, median follow up 11 y) and 6,810 in the validation cohort (median follow up 3.1y). Four proteins were significantly associated with incident hypertension in the discovery cohort. One protein, Matrilysin (MMP7), remained significantly associated in the validation cohort (HR 1.22 [1.11-1.34]) (Figure1A). MMP7 was also significantly associated with all hypertension-related complications (Figure 1B-D).

Conclusions:
MMP7, a protein involved in extracellular matrix degradation, was robustly associated with incident hypertension and cardiovascular events. Future research examining the pathophysiologic mechanism of MMP7 could potentially yield drug targets for the prevention and treatment of hypertension.
Abstract 18748: Prevention of Skeletal Muscle Atrophy and Fibrosis in Congestive Heart Failure by Skeletal Myoblast-Targeted Overexpression of Angiotensin II Type 2 Receptor
Authors: Yoshida Tadashi , Lott C. S , Delafontaine Patrice
Published: December 2023

Introduction:
We have previously shown that angiotensin II (Ang II) type 2 receptor (AT2R) positively regulates skeletal myoblast differentiation. Systemic angiotensin II (Ang II) increase or congestive heart failure suppress AT2R expression, likely contributing to the development of skeletal muscle atrophy and fibrosis associated with these conditions.

Hypothesis:
We hypothesized that AT2R overexpression in skeletal myoblasts could prevent skeletal muscle atrophy and fibrosis associated with congestive heart failure (CHF).

Approach:
Two mouse models, systemic Ang II infusion and left anterior descending coronary artery (LAD) ligation were used in this study. Myoblast differentiation, muscle atrophy and muscle fibrosis were assessed by analyzing gene expressions (e.g. myogenin and atrogin-1), myofiber cross sectional area, and the collagen deposition (picrosirius red staining). Primary myoblasts were isolated from mouse hindlimb muscles. Myoblast-specific AT2R-overexpressing transgenic mice were generated by crossing Pax7
CreER/+
mice (tamoxifen-inducible cre recombinase is expressed under Pax7 promoter) and CAG-stop
flox
-AT2R mice (AT2R is expressed under CMV early enhancer element, chicken β-actin gene promoter upon cre-mediated excision of floxed stop codon).

Results:
AT2R expression was robustly increased during myoblast differentiation both
in vitro
and
in vivo
. siRNA-mediated AT2R knockdown significantly suppressed myoblast differentiation
in vitro
and skeletal muscle regeneration
in vivo
. In both Ang II infusion and LAD ligation models, AT2R induction during myoblast differentiation was significantly suppressed, associated with reduced muscle regeneration and increased atrophy and fibrosis. Myoblast-specific AT2R overexpression
in vivo
restored muscle regenerative capacity, and prevented muscle atrophy and fibrosis.

Conclusions:
AT2R induction in skeletal myoblast is suppressed in CHF, possibly via increased Ang II. Decreased AT2R expression and its downstream signaling in myoblast lead to lowered muscle regenerative capacity and increased muscle atrophy and fibrosis. Restoration of myoblast AT2R expression could lead to a novel therapy to prevent muscle atrophy and fibrosis in CHF condition.
Abstract 18756: Impact of Hospital Teaching Status on In-Patient Outcomes of Acute Myocardial Infarction
Authors: Khanal Smriti , Poudyal Abhushan , Poudel Ayusha , Sharma Bharosa , Baral Nischit
Published: December 2023

Introduction:
Prior studies have shown better outcomes for acute myocardial infarction (AMI) patients admitted to teaching compared to non-teaching hospitals. Similar trend was seen in studies limited to ST elevation myocardial infarction (STEMI) patients. We examined the impact of hospital teaching status on in-patient outcomes in AMI patients usingcurrent data and International Classification of Diseases 10
th
Revision (ICD-10) system.

Hypothesis:
Acute myocardial infarction patients treated in teaching hospitals have better outcomes compared to patients treated in non teaching hospitals.

Methods:
We queried the 2016 and 2017 NIS databases to identify all patients over 18 years of age hospitalized for AMI. With hospital teaching status as an independent variable, multivariate logistic regression was used to compare mortality rates in AMI patients (primary outcome) and likelihood of revascularization within 24 hours for NSTEMI (secondary outcome); linear regression was used to compare length of stay(LOS) for NSTEMI patients (secondary outcome).

Results:
Of 1,308,314 patients with AMI (351,970 with STEMI and 955,314 with NSTEMI), 66.5% were admitted to teaching hospitals. In-patient mortality rate was higher in teaching (4.8%) compared to non-teaching (4.5%) hospitals [adjusted odds ratio (aOR) 1.16, 95% CI 1.12 to 1.21, p < 0.001]. This was true for both STEMI [aOR 1.1, 95% CI 1.03 to 1.17, p = 0.004] and NSTEMI [aOR 1.16, 95% CI 1.10 to 1.22, p < 0.001] patients. NSTEMI admitted to teaching hospitals were more likely to be revascularized within 24 hours of admission [aOR 1.27, 95% CI 1.22 to 1.33, p < 0.001] compared to non-teaching hospitals. LOS for NSTEMI patients admitted to teaching hospitals was longer compared to non-teaching hospitals [4.9 vs 3.9 days, p < 0.001].

Conclusions:
Patients with AMI admitted to teaching hospitals had higher mortality rates compared to non-teaching hospitals. This contradicts the results of prior studies. Further research is warranted in this regard. NSTEMI patients admitted to teaching hospitals were more likely to be revascularized within 24 hours compared to non-teaching hospitals, but this did not translate to better mortality outcome. LOS was longer for NSTEMI patients admitted to teaching hospitals.
Abstract 18766: Optimizing Stroke Prophylaxis in the Emergency Department With an Electronic Clinical Decision Support Tool: A Preliminary Analysis of a Multi-Stage Multi-Center Stepped-Wedge Cluster Randomized Trial
Authors: Hopkins Bradley J , Nguyen Thuan , Kinney Erin , Kim Joy , McCracken Caitlin , Bissell Ky , Gosman Andreea , DeCarlo Anya , Anwar Mariam , Neth Matthew R , Schnittke Nikolai , Sun Benjamin , Kea Bory
Published: December 2023

BACKGROUND:
Atrial fibrillation (AF) is a common arrhythmia that is often first diagnosed in the Emergency Department (ED). AF is associated with an increased risk of stroke that can be reduced by 64% if an oral anticoagulant (OAC) is prescribed appropriately.

RESEARCH QUESTION:
Will education and implementation of a clinical decision support (CDS) tool in the ED increase OAC prescription for appropriate candidates diagnosed with new-onset or paroxysmal AF (pAF)?

METHODS:
This is the first phase of a multi-stage multi-center stepped-wedge cluster-randomized clinical trial implementing a CDS tool into the electronic health record (EHR). Step one implements an external browser link to the CDS tool in the EHR with targeted provider education, whereas steps 2 and 3 will motivate provider engagement with triggers. Data were collected from an urban academic tertiary care center and a community hospital. Patients aged greater than 17 years were selected if they had a primary diagnosis of AF/pAF during ED visits from Jan 2020-Apr 2023. The academic and community sites transitioned from the retrospective phase to Step 1 in Jan 2022 and Apr 2022, respectively. Appropriate OAC prescription was determined based on elevated stroke risk and low-moderate bleed risk. A logistic GEE model was used to study the effect of the proposed intervention on OAC prescription. ED providers were treated as a random effect to capture clustering. The model includes the CDS intervention, site, and patient characteristics sex, race, ethnicity, and age.

RESULTS:
Of 2031 patients, 312 met inclusion criteria and 150 were selected as appropriate OAC candidates, with 72 (52% male, median age 74) in the retrospective step and 78 (52% male, median age 76) in Step 1. Below are odds ratio estimates with corresponding 95% CI’s: CDS intervention 3.12 [1.57, 6.21] and sex female vs male 2.04 [1.04, 4.00]. Non-significant variables site, race, ethnicity, and age were included as adjusting covariates.

CONCLUSIONS:
Limited CDS tool education and integration is associated with improved OAC prescribing for appropriate AF/pAF patients. Future studies should assess the impact of additional CDS integration on OAC prescribing and patient outcomes.
Abstract 18776: ECG-GPT: Automated Complete Diagnosis Generation From ECG Images Using Novel Vision-Text Transformer Model
Authors: Khunte Akshay , Sangha Veer , Holste Gregory , Dhingra Lovedeep S , Aminorroaya Arya , Wang Zhangyang , Khera Rohan
Published: December 2023

Background:
Artificial intelligence can automate the diagnosis of a multitude of rhythm and conduction disorders from ECGs, but is limited by a dependency on discretely defined labels. Moreover, most models also frequently rely on signal data, limiting their application in low-resource settings, where such models are needed most and ECGs are available in image form.

Methods:
1.4 million 12-lead ECGs and accompanying cardiologist diagnosis statements from Yale were used to develop a model capable of generating ECG report statements. This encompassed a wide array of conditions. To develop a model capable of report generation across ECG layouts, 12-lead signal recordings were plotted randomly in multiple formats. The gold-standard diagnosis statements were processed using to remove identifiable information and standardize diagnosis reporting. An ECG-specific vision encoder-decoder model with a pretrained BEiT transformer encoder with a 384x384 pixel input size and a generative pretrained transformer, GPT-2, as a decoder was developed (B).

Results:
In a held-out test set of 100,000 ECGs, representing ECG interpretation with up to 255 tokens and over 41 distinct cardiovascular conditions, the model performed well across conventional metrics, with ROUGE-L and BLEU-1 scores of 0.695 and 0.502, respectively (C). The model’s clinical validity was assessed by computing agreement between cardiologist and model-generated diagnosis statements. The model generated text reports with accurate identification of diverse set of rhythm and conduction disorders, with AUROCs for predicting atrial fibrillation, right bundle branch block, and sinus tachycardia of 0.95, 0.94, and 0.96, respectively (D).

Conclusions:
Our vision encoder-decoder model generates an ECG report from ECG images in any layout. This approach represents an automated and accessible strategy for generating cardiologist-level reporting on ECGs, useful for low-resource settings.
Abstract 18786: The Association Between Aortic Abdomen Calcification, Systemic Immune Inflammation Index, Estimated Pulse Wave Velocity, Atherogenic Index of Plasma and Triglyceride-Glucose Index Among Non-Diabetic Patients: A NHANES 2013-2014 Cross Sectional Study
Authors: Sawaf Bisher , Swed Sarya , Alibrahim Hidar , Bohsas Haidara , Nasif Mohamad Nour , Hossam El Din Moawad Mostafa , Jawish Nagham , Qadir Shayan , Al Hennawi Hussam , Naguib Mervat , Mahmoud Mahmoud , Battikh Naim , Zaidi Abdul Rehman Zia , alghalyini Baraa , Hafez Wael
Published: December 2023

Background:
Not enough studies showed the predictive value of systemic immune inflammation (SII) index, estimated pulse wave velocity (EPWV) index, atherogenic index of plasma (AIP) and triglyceride glucose (TyG) index for developing abdominal aortic calcification (AAC). This study assesses the relationship between the previous indexes and the risk of AAC.

Methods:
National Health and Nutrition Examination Survey (NHANES) data was utilized. The study included data from 2013 to 2014. We included non-diabetic participants aged 18 years or older. All studied indexes were divided into four quartiles, except AIP, into two categories. SPSS was used for the analysis. The sensitivity and specificity of the included indexes in predicting AAC were calculated by receiver operating characteristic (ROC) analysis. We performed univariate and multivariate logistic regression to analyze the associated factors with higher values of studied indexes.

Results:
The analysis included 1315 non-diabetic patients, of which 324 had AAC, and 74 had severe AAC. Except for SII index, all indexes showed a statistically significant association with the presence of AAC (P < 0.05). AAC was more prevalent among patients in the third and fourth quartiles of all Triglyceride-Glucose Index models, p-value<0.05. Participants in the second quartile of the AIP were more likely to be affected by AAC, p-value<0.05. In addition, all unadjusted regression models showed that higher values of the inquired indexes were significantly associated with the risk of abdominal aortic calcification. The areas under the curve (AUC) for TyG index, AIP, and EPWV were 0.558 (95% CI 0.52-0.59), 0.551(95% CI 0.51- 0.58), 0.692 (95% CI 0.65- 0.72) (p-value ≤ 0.05), respectively.

Conclusion:
Among all involved indexes, the estimated pulse wave velocity index was the best indicator for abdominal aortic calcification.
Abstract 18797: Use of Convolutional Neural Networks to Detect Overweight and Obesity and Estimate Body Mass Index
Authors: Greason Grace , Mangold Kathryn , Medina-Inojosa Betsy , Naser Jwan , Lopez-Jimenez Francisco , Attia Zachi
Published: December 2023

Background:
Our team has previously developed convolutional neural networks (CNNs) to estimate age and sex from a 10-second, 12-lead ECG as indicators of patient wellness. Here, we develop an additional wellness network to estimate body mass index (BMI) from the ECG input signal.

Aims:
To evaluate the performance of neural networks trained to classify and directly estimate BMI.

Methods:
We identified all adult patients in the Mayo Clinic system who had a 10-second, 12-lead ECG within 15 days of a BMI measurement. Of the 174,863 patients in the cohort, 2,895 were underweight (BMI < 18.5), 42,387 were of normal weight (BMI 18.5-24.9), and 57,939 were overweight only (BMI 25.0-29.9). Among patients categorized as obese, 39,788 had class I obesity (BMI 30.0-34.9), 18,978 had class II obesity (BMI 35.0-39.9), and 12,876 had class III obesity (BMI ≥ 40.0). The cohort was split into training, validation, and testing datasets in an 8:1:1 ratio to develop networks for BMI classification and a direct estimation of BMI.

Results:
In detecting overweight in the testing set, the model achieved an AUC of 0.86 (95% CI 0.85, 0.87). In detecting class I, class II, and class III obesity, the model yielded AUCs of 0.84 (95% CI 0.83, 0.85), 0.84 (95% CI 0.83, 0.85), and 0.85 (95% CI 0.85, 0.86), respectively. The model to estimate BMI achieved a mean absolute error of 3.70.

Conclusions:
AI-enabled ECGs demonstrate efficient detection of overweight patients and all classes of obesity. Further research is needed to determine if discrepancies between the traditionally measured BMI and the AI-ECG BMI reflect the presence or lack of metabolic abnormalities.
Abstract 18803: Extended Duration Impella Support: A Review of 107 Patients Successfully Supported With Impella 5.5 Device at a Single Institution
Authors: Wald joyce , Brown Alyson , Jackson Andrea , Gray Kathryn , Cevasco Marisa
Published: December 2023

Introduction:
Impella 5.5 is an FDA-approved microaxial, continuous flow pump intended to provide left ventricular hemodynamic support for 14 days. We report 107 consecutive patients supported with this device, many for extended durations.

Methods:
The outcomes of consecutive patients supported with Impella 5.5 at an academic hospital from March 2021 to June 2023 are included.

Results:
107 patients required 112 Impella 5.5 devices. The majority of patients had a heart failure etiology of NICMP (57, 53%), followed by ICMP (36, 34%), post cardiotomy shock (6, 5%), other (4, 4%), planned post cardiotomy cardiac protection (3, 3%), and congenital heart disease (1, 1%). 60 patients (56%) were SCAI D, 30 patients (28%) SCAI E, and 17 patients (16%) were SCAI C. The majority patients (70,65%) were Intermacs 2. The majority of Impella 5.5 devices were placed as a bridge to decision (55 patients, 51%), followed by BTT (28 patients, 26%), BTR (16 patients, 15%), Bridge to LVAD (7 patients, 7%), and one patient (1%) device was placed for post cardiotomy cardiac protection. 11 patients required interval escalation to concomitant VA-ECMO. Patients requiring ECPELLA were placed on PVA ECMO after an average of 22 days of impella support, and average time of support on ECPELLA was 5.4 days. All patients transitioned to cardiac replacement therapy. Among patients with explant data, 43 supported for < 2 weeks, 38 for 2-4 weeks, and 17 for > 4 weeks. Longest duration of support was 92 days. Of patients reaching a primary endpoint, 42 were transplanted (39%), 21 patients died (20%), 18 patients received durable VAD (17%), 12 were discharged without transplant or VAD (11%), 10 were transferred while on support (9%) and 4 patients are still supported (4%). With respect to complications, 5 patients suffered from strokes, 3 pump thrombosis, 2 had fiber optic cable malfunctions, 2 had purge line leaks, and there were 3 patients with a broken optical sensor, and 2 arterial (brachial and axillary) thrombus.

Conclusion:
The Impella 5.5 device is a left ventricular support device placed most frequently to successfully stabilize patients undergoing evaluation for advanced therapies who were failing despite inotropic therapy.