bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13799: A Systems Approach to Target Discovery Identifies the Novel Role of lncRNA-SPANXA2-OT1 in Macrophage Chemotaxis
Authors: Jha Prabhash K , Itto Lucas Y , Vijay Aatira , Lupieri Adrien , Chelvanambi Sarvesh , Nakamura Yuto , Barbeiro Miguel C , Le Thanh-Dat , Kasai Taku , Becker-Greene Dakota , Sonawane Abhijeet , Singh Sasha A , Aikawa Elena , Uchida Shizuka , Aikawa Masanori
Published: December 2023

Background:
Coronary artery disease (CAD) remains the leading cause of mortality worldwide. Macrophages play a crucial role in recruiting immune cells and regulating the inflammatory milieu through the release of a diverse array of cytokines and chemokines in CAD. Long noncoding RNAs (lncRNAs) interact with DNA, RNA, miRNA, and proteins which makes them attractive therapeutic targets. We hypothesized that the lncRNA,
SPANXA2-OT1
, regulates macrophage chemotaxis in CAD.

Methods and Results:
Gene-expression meta-analysis and weighted gene co-expression network analysis (WGCNA) of human CAD datasets identified 26 lncRNA-mRNA co-expression modules (Fig A). Network prioritization of top co-expression modules identified the
SPANXA2-OT1
as a potential key candidate. The conservation analysis revealed that
SPANXA2-OT1
is conserved only in primates. We validated the candidate coding-noncoding RNA regulatory triad in primary macrophages derived from healthy human PBMCs (n= 3-10). Loss-of-function experiments using antisense oligonucleotide (ASO) against
SPANXA2-OT1
demonstrated decreased monocyte chemotaxis signature (Figure B and D), as recorded by unbiased global proteomics and RNA expression (IL8, CCL19 and CCL23) data. The expression of
S
PANXA2-OT1
was stimulated by IL1β (Fig C) and RNA
in situ
hybridization demonstrated it to be highly expressed in cytoplasm (Fig E) of macrophages. Luciferase assay established that
SPANXA2-OT1
binds to
miR-338
through its miRNA response elements (Fig F). Gain-of-function (
miR-338
mimic) and loss-of-function (
SPANXA2-OT1
ASO) experiments revealed that
SPANXA2-OT1
:
miR-338
axis regulates the expression of monocyte chemotactic genes (e.g.,
IL-8
) that may contribute to the pathophysiology of CAD (Fig G and H).

Conclusion:
Our results indicate that the lncRNA
SPANXA2-OT1
regulates chemokine signature in macrophages and may provide a molecular basis for the identification of novel therapeutic targets for CAD.
Abstract 13802: Differences in the Incidences and Predictors of Major Adverse Cardiovascular Events Between in Patients With Acute and Chronic Coronary Syndromes
Authors: Kikuchi Shinnosuke , Okada Kozo , Tsutsumi Katsuhiko , Kirigaya Jin , Nakahashi Hidefumi , Minamimoto Yugo , Gohbara Masaomi , Kimura Yuichiro , Matsushita Kensuke , Kosuge Masami , Ebina Toshiaki , Sugano Teruyasu , Hibi Kiyoshi
Published: December 2023

Backgrounds:
Patients with acute coronary syndrome (ACS) have a higher risk of the recurrence of major adverse cardiovascular events (MACE) than those with chronic coronary syndrome (CCS). However, it remains undefined whether contributing factors to recurrent MACE are different between ACS and CCS, which information may be important for the individual patient’s management.

Aims:
This retrospective, single-center analysis aimed to examine and compare incidences and predictors of MACE after PCI in patients with ACS and CCS.

Methods and Results:
A total of 3115 patients (2201 ACS and 914 CCS) who received PCI were enrolled and followed for a median of 2.9 years for MACE, defined as a composite of cardiovascular death, myocardial infarction (MI), revascularization, ischemic stroke, and hospitalization for heart failure (HF). Incidences of MACE, especially cardiovascular death, myocardial infarction, and stroke were significantly higher in ACS than in CCS, whereas the rates of revascularization and HF hospitalization were comparable between the groups (Table 1A). Multivariable regression analyses identified different determinants for MACE between ACS and CCS, except for previous MI (Table 1B). Similarly, risk factors were different between ACS and CCS with respect to each MACE component (data not shown).

Conclusions:
Not only incidences of MACE but also their components and predictors were different between ACS and CCS. Further studies are warranted to investigate whether machine learning of electronic medical records may help enhance further risk stratification of MACE and could lead to improved clinical decision-making after PCI.
Abstract 13906: Electrocardiographic Correlates of Cardiac MRI Findings in Women With MINOCA
Authors: Pleasure Mitchell , Jaspan Vita , Liu Olivia , Lin Emilie , Kwong Raymond , Hausvater Anais , Sedlak Tara , Hashim Hayder , Giesler Caitlin , Bainey Kevin R , Chong Aun-Yeong , Heydari Bobak , Ahmed Mobeen , Smilowitz Nathaniel , Reynolds Harmony
Published: December 2023

Introduction:
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is identified in 6-15% of patients with MI and disproportionately affects women. Cardiac magnetic resonance (CMR) imaging is important to identify the cause of MINOCA but is restricted by its technical complexity and limited accessibility. The electrocardiogram (ECG), a simple, readily available tool, may predict features associated with abnormal CMR.

Methods:
Women with a diagnosis of MI and <50% angiographic stenosis in all epicardial vessels were enrolled in the Women’s Heart Attack Research Program (HARP), a prospective, multicenter, observational study. Participants had CMR at a median of 6 days from MI (n=116). A CMR core laboratory interpreted images while blinded to clinical data and ECGs. Abnormal CMR findings included late gadolinium enhancement (LGE) or myocardial edema. The patient’s presenting ECG was analyzed. ECGs with ≥2 uninterpretable leads or with bundle branch block were excluded. ECGs were assessed for T-wave inversions (TWI), pathologic Q waves (QW), fractionated QRS (fQRS), and ST segment depression or elevation. The DETERMINE score is 2x the number of leads (#) with QW + # fQRS + # TWI, excluding leads V1 and aVR (maximum score 40).

Results:
(Figure, Table): Among 112 women with MINOCA, CMR abnormality was more likely in women with DETERMINE score ≥3 vs <3 (86% vs 65%, p = 0.01). DETERMINE score ≥3 was associated with abnormal CMR on logistic regression (OR 3.4, p = 0.01). Patients with any TWI were more likely to have abnormal CMR than those with no TWI (84% vs 64%, p = 0.02), and were more likely to have LGE on CMR (61% vs 34%, p = 0.005). In those with a DETERMINE score of 0, CMR was abnormal in 62% vs 78% with DETERMINE score ≥1 (p=0.09), and LGE was present in 28% vs 54%, p = 0.01.

Conclusion:
ECG abnormalities were associated with abnormal CMR among women with MINOCA. The ECG may provide risk stratification for CMR, but the absence of QW, fQRS and TWI does not preclude CMR abnormality.
Abstract 13928: Targeted Atrial Inhibition of Galphaq Signaling With Inhibitory Peptides Attenuates Fibrosis and Inducibility of Atrial Fibrillation in a Canine Heart Failure Model
Authors: Pfenniger Anna , Johnson David , Zhang Wenwei , Ng Justin , Swanson Julia , Mikhailov Aleksei , Yoo Shin , Marszalec William , Passman Rod S , Knight Bradley P , Arora Rishi
Published: December 2023

Introduction:
Endothelial dysfunction, a hallmark of heart failure (HF), is closely associated with atrial fibrillation (AF). However, the precise role of endothelial dysfunction in creating an atrial arrhythmogenic substrate is unknown. Endothelin-1 (ET-1) and its downstream Gα
q
signaling are significantly upregulated in the atria of patients with HF. We therefore hypothesized that ET-1-Gα
q
signaling contributes to adverse structural remodeling in the atria in the setting of HF.

Hypothesis:
Inhibition of atrial ET-1-Gα
q
signaling with Gα
q
inhibitory peptides (Gα
q
-ct) will attenuate the development of atrial fibrosis and AF inducibility in a HF model.

Methods:
Plasmids expressing Gα
q
-ct were injected and electroporated in the left atria of 4 dogs. LacZ or scrambled plasmids were used in 8 control dogs. HF was induced by ventricular tachypacing (VTP) at 240 bpm for 3 weeks. At terminal EP study, left atrial conduction vectors were recorded with high-density mapping and AF inducibility assessed. Left atrial fibrosis was quantified by Masson Trichrome.

Results:
All animals developed clinical HF (prolonged capillary refill time, ascites, reduced activity level) and LV systolic dysfunction by echocardiogram (LVEF 17.5±8.3% in Gα
q
-ct, 13.7±3.1% in controls, p=0.55). Conduction inhomogeneity was reduced in Gα
q
-ct animals (example of posterior left atrium recordings in Fig. A). AF was less inducible in Gα
q
-ct than control animals (4.8% of pacing attempts Vs 17.8%, p<0.001, Fig. B) and AF episodes were shorter (5.6±0.9 sec Vs 63.8±11.9 sec). Left atrial fibrosis was significantly attenuated in Gα
q
-ct animals Vs controls (Fig. C).

Conclusions:
Gα
q
signaling contributes to atrial fibrosis and subsequent AF susceptibility in VTP-induced HF, thereby highlighting an important role for ET-1 signaling in HF-related atrial remodeling. Future optimization of gene therapy targeting ET-1 signaling may lead to novel, mechanism-guided treatments for AF in the context of HF.
Abstract 13981: Computed Tomography Angiography Measures of Carotid Artery Plaque Burden in Patients With Atherosclerotic Carotid Artery Disease Stratified by Status of Chronic Kidney Disease
Authors: Sinharoy Ankita , Gimnich Olga A , NAMBI VIJAY , Kougias Panagiotis , Taylor Addison A , Brunner Gerd
Published: December 2023

Introduction:
Atherosclerotic carotid artery disease (ACAD) is associated with an increased risk of cerebrovascular mortality and morbidity. We have analyzed associations of computed tomography angiography (CTA) measures of carotid artery (CA) plaque burden with chronic kidney disease (CKD).

Hypothesis:
CTA-based measures of CA plaque burden in patients with ACAD differ across stages of CKD.

Methods:
A total of 63 ACAD patients (13 without CKD, 50 with CKD), who completed CTA imaging and had demographic data were included in a retrospective analysis of patients from the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC), Houston, Texas. CA plaque burden measures include the normalized wall index (NWI), wall area (WA), and lumen area (LA) at three distinct CA locations: CA bifurcation (BF), maximum total vessel cross-sectional area (MTVA) of the internal CA (ICA), and ICA peak stenosis (PS). CTA measures and patient demographics were compared across three CKD classes (no disease: n=13; CKD stages 1 and 2: n=31; and CKD stage 3 and above; n=19).

Results:
Baseline characteristics differed among CKD groups for the estimated glomerular filtration rate (p=<0.0001) and the body mass index (p=0.046). Inter-observer variability, assessed by intraclass correlation (ICC) analysis, was excellent for CA lumen area and wall area (0.964 (confidence interval [CI]: 0.946, 0.976); 0.865 (CI: 0.804, 0.908): n=100 CTA slices, both). The mean NWI differed significantly among the CKD groups for two of the three CA locations (BF: p=0.018, MTVA: p=0.01; PS: p=0.057). Similarly, lumen area significantly differed between CKD categories (BF: p=0.045, MTVA: p=0.013; PS: p=0.017) but not the wall area.

Conclusion:
CTA-based measures of carotid plaque burden in ACAD patients are highly reproducible and differed across CKD groups. Imaging-based measures of CA plaque burden may be of interest in stratifying risk assessment of ACAD patients with concomitant CKD.
Abstract 13994: PKM2 Ablation Increases Pro-Inflammatory Signaling in Mice
Authors: Lee Katie , Williams Allison L , Shohet Ralph V
Published: December 2023

Introduction:
The predominant isoform of pyruvate kinase (PKM1) promotes oxidative metabolism in the healthy heart. We previously described a hypoxia and ischemia-mediated switch to the alternatively spliced isoform PKM2, known to promote glycolysis. Pkm2 has also been shown to reduce oxidative damage and promote cardiomyocyte cell proliferation after myocardial infarction (MI). PKM2 is also a metabolic regulator of immune cell differentiation.

Hypothesis:
We hypothesize that PKM2 has a role in limiting inflammatory stress by regulating the migration and activity of immune cells.

Methods:
PKM2 control and global KO mice were subjected to permanent ligation of the left anterior descending coronary artery to mimic an MI (n=3). Hearts were excised after 3 days and the transcriptomes and gene ontologies (GO) were then assessed by RNA-sequencing and pathway analysis. Circulating C-reactive protein (CRP) was assessed using an ELISA (n=12) and cytokines in plasma and heart tissue were assessed using a multiplex assay (n=3-5). Neutrophil myeloperoxidase secretion and differentiated cardiac macrophages were analyzed by immunofluorescent staining (n=3).

Results:
GO term enrichment analysis of RNA-seq results showed increased abundance of genes for neutrophil chemotaxis and apoptosis, regulation of cytokine production, and the inflammatory response in PKM2 KO hearts after MI compared to controls. PKM2 KO hearts showed increased neutrophil myeloperoxidase secretion and Ly6G/C staining for neutrophils and monocytes compared to controls. Similarly, M1 macrophages appeared to be more abundant in PKM2 KO hearts compared to controls. IL-6 levels were elevated in PKM2 KO plasma at baseline compared to controls, while CRP was elevated in PKM2 KO plasma across all conditions. IL-6 was also substantially elevated in PKM2 KO hearts after MI compared to controls.

Conclusions:
Loss of PKM2 increased pro-inflammatory signaling in the heart of KO mice. We saw increased cardiac and plasma IL-6 and CRP, likely related to the polarization of macrophages towards the M1 phenotype, and increased neutrophil activity in PKM2 KO hearts. We suggest that PKM2, induced by a hypoxia-related splicing event, protects the heart against the inflammation that accompanies infarction.
Abstract 14000: Elevated Galectin-3 Levels Are Associated With Higher Mortality in Patients With Atrial Fibrillation
Authors: Vavuranakis Michael A , Dagher Lilas , Chen Yunyun , Ko Yi-An , Quyyumi Arshed A
Published: December 2023

Introduction:
Atrial fibrillation (Afib) is associated with structural and electrical atrial remodeling. Galectin-3 (Gal-3) is a mediator of atrial fibrosis and higher levels have been associated with new onset Afib. Whether Gal-3 levels are prognostic in Afib remains unknown.

Research Question:
Investigate whether higher Gal-3 levels are associated with higher mortality in Afib.

Methods:
Patients with a history of Afib, enrolled in the Emory Cardiovascular Biobank of patients undergoing coronary angiography for suspected or confirmed CAD were included. Primary outcomes were all-cause and cardiovascular (CV) mortality. Kaplan-Meier and Cox regression analyses were used to compare survival between different Gal-3 levels.

Results:
We included 767 patients (mean age 68 years, 69.8% males) who were followed for a mean of 4.4 years. There were 234 (30%) all cause and 149 (19%) CV deaths. Third and fourth quartiles of Gal-3, were associated with higher hazard, when compared to the first quartile, with hazard ratios (HR) of 2.1 (1.4, 3.3) (Q3) and 3.5 (2.3, 5.3) (Q4) for all-cause mortality and 2.8 (1.5, 5.2) (Q3) and 4.9 (2.7, 8.7) (Q4) for cardiovascular mortality respectively. A one unit increase in Gal-3 was associated with HR of 1.4% and 1.8% for all-cause and CV mortality respectively, after adjusting for age, NT-proBNP, hypertension, stroke, MI, PVD, absence of coronary artery disease on left heart catheterization, history of HF and anti-coagulation therapy.

Conclusions:
Higher levels of Gal-3 are associated with higher incidence of all-cause and cardiovascular mortality in patients with Afib. Gal-3 can be used to identify high risk patients with Afib.
Abstract 14009: Plasminogen Activator Inhibitor-1 (PAI-1) is an Essential Driver of Cardiovascular Aging in Mice
Authors: Kalousdian Anthony , Soberanes Saul , Eren Mesut , Jorgensen Emily , Lux Elizabeth , Wilsbacher Lisa D , Vaughan Douglas E
Published: December 2023

Introduction:
PAI-1 is the protein product of the gene
Serpine1
. PAI-1 is a key contributor to cellular senescence in humans and mice, and elevated PAI-1 predicts the development of aging-related disorders including Type 2 diabetes and hypertension. GrimAge, a composite measure of epigenetic age, includes a DNA methylation estimator of plasma PAI-1 levels that independently predicts the development of cardiovascular (CV) morbidity including hypertension and time to heart failure. While many mechanistic contributions of PAI-1 to senescence and aging are well documented, its fundamental role in CV aging has not been fully investigated.

Hypothesis:
PAI-1 overexpression in mice promotes CV aging, while PAI-1 deficiency attenuates this phenotype in the presence of a stressor.

Methods:
To assess the effect of PAI-1 overexpression on CV aging, mice transgenic for a stable variant of human PAI-1 (n=14 transgenics, n=8 wild-type littermates) were characterized at 2 months and 7 months. To assess the effect of PAI-1 deficiency, mice heterozygous for a
Serpine1
frame-shifting loss-of-function mutation (n=9) and wild-type littermates (n=10) were assessed; these mice underwent cardiovascular stress using N(ω)-nitro-L-arginine methyl ester (L-NAME) (1mg/L) for 8 weeks. Cardiovascular phenotyping included treadmill, pulse-wave velocity (PWV), echocardiography, and blood pressure (BP) measurement at the beginning and end of study. Histology was performed on aortas using Masson’s Trichome and analyzed for fibrosis quantification.

Results:
PAI-1 transgenic mice exhibited worse diastolic (E/e’) and vascular function (PWV, systolic and diastolic BP) compared to their wild-type counterparts. Histology showed more extensive peri-aortic fibrosis. In contrast, PAI-1 loss-of-function heterozygotes were broadly resistant to the vascular aging effects of L-NAME compared to wild-type mice. Molecular profiling of vascular tissues collected from animals is underway and includes bulk aorta RNAseq and measures of epigenetic age.

Conclusion:
PAI-1 is necessary and sufficient for the development of a CV aging phenotype in mice while PAI-1 deficiency attenuates stress-induced CV aging. Inhibition of PAI-1 will likely be tested for preventing CV aging in humans.
Abstract 14010: Synergistic Influence of Rivaroxaban on Platelets, Inflammation and Coagulation Biomarkers in Patients With CAD and/or PAD on Aspirin Therapy
Authors: Tantry Udaya , Cummings Charles , Bliden Kevin , Gurbel Paul
Published: December 2023

Background:
Cardiovascular benefits of 2.5 mg twice daily rivaroxaban plus aspirin therapy (RIV+ASA) has been demonstrated in patients with arterial diseases.

Hypothesis:
RIV+ASA is associated with reduced platelet activation and plasma inflammation and coagulation activation markers in patients with CAD and/or PAD who were on ASA.

Methods:
In this open-label biomarker study, patients on 81 mg/day ASA were randomized to continue ASA or RIV+ASA for 12 weeks. We assessed ADP-, α-thrombin-, and tissue factor-induced platelet aggregation (PA) using conventional aggregometry, platelet-fibrin clot strength (PFCS) by INTEM (intrinsic pathway activator) and EXTEM (extrinsic pathway activator) using thromboelastometry, shear-induced PA by platelet function analyzer-100, D-dimer and fibrinogen using coagulation analyzer, hs-CRP and interleukin-6 using ELISA method at baseline, and four weeks and 12 weeks post-randomization.

Results:
Data was available in 9 patients with RIV + ASA and ten patients with ASA-only therapy. Most patients were male, Caucasians, obese and older. There were no differences in baseline demographics, medications, and laboratory values between groups, except patients in RIV + ASA group had higher white blood cell counts (p=0.028) and lower baseline 2uM ADP-induced PA (p=0.03). There were no differences in other laboratory measurements between baseline and post-randomization time points within the group or at 4- and 12-week time points between groups, except D-dimer values were significantly lower at 12 weeks (p=0.038) in the RIV + ASA vs. ASA-only group. No significant adverse events were observed.

Conclusions:
Twelve weeks of rivaroxaban plus aspirin vs. aspirin was associated with similar levels of platelet aggregation, platelet fibrin clot strength, fibrinogen and inflammation markers, and lower d-dimer levels.
Abstract 14027: The Use of Anthropometric Indices as Indicators of Hypertension in Patients With Diabetes Types 2: A Large-Scale Cross-Sectional Study
Authors: Keykhaei Mohammad , Farrokhpour Hossein , Rashedi Sina , Ayati Aryan , Anvari Anahita , Zokaei Shaghayegh , Rabizadeh Soghra , Nakhjavani Manouchehr
Published: December 2023

Introduction:
Obesity is associated with hypertension and diabetes mellitus (DM), increasing cardiovascular disease risk and mortality. While body mass index (BMI) is widely used to measure obesity, it has several limitations. Therefore, alternative anthropometric indices such as waist circumference (WC), waist-to-height ratio (WHtR), body roundness index (BRI), and a body shape index (ABSI) have been suggested.

Hypothesis:
This study aims to identify the most effective anthropometric index for predicting hypertension in patients with type 2 DM.

Methods:
In this cross-sectional study, patients with type 2 DM were included and classified into two groups based on the presence or absence of hypertension. Demographic and clinical data were collected and anthropometric measurements were taken. Multivariate logistic regression analysis was used to identify factors associated with hypertension. Receiver operating characteristic (ROC) curves were performed to determine the diagnostic performance of various anthropometric indices, with a subgroup analysis based on the status of patients DM.

Results:
The study population included 977 male and 1454 female patients with DM, among whom 50.3% and 67.1% had hypertension. Both male and female patients with hypertension were older, had a longer duration of DM, and had higher anthropometric measurements, blood pressure, and lipid profiles. ROC curve analysis revealed that although all indices could significantly predict hypertension (0.55-0.76 in men and 0.68-74 in women), WHtR and BRI had the highest ability to identify patients with hypertension in men irrespective of DM status being controlled or not. (WHtR: 0.76, 95% confidence interval (CI): 0.73-0.79, BRI: 0.76, 95% CI: 0.73-0.79). WC had the highest diagnostic performance in all female patients and female patients with uncontrolled DM (0.75, 95% CI: 0.72-0.75 and 0.75, 95% CI: 0.72-78, respectively). All indices remained significant in the logistic regression after adjusting for potential confounders.

Conclusions:
While WHtR and BRI were better predictors of hypertension in men with DM, WC had a better diagnostic performance in women with DM.
Abstract 14032: Transcatheter Palliation With Pulmonary Artery Flow Restrictors in Neonates With Congenital Heart Disease: Feasibility, Outcomes, and Comparison With a Historical Hybrid Stage 1 Cohort
Authors: Sperotto Francesca , Lang Nora , Nathan Meena , Kaza Aditya K , Hoganson David , Valencia Eleonore , Allan Catherine K , Da Cruz Eduardo , Del Nido Pedro J , Emani Sitaram , Baird Chris , Maschietto Nicola
Published: December 2023

Introduction:
Neonates with complex congenital heart disease (CHD) and pulmonary overcirculation have been historically treated surgically. However, sub-cohorts may benefit from less invasive procedures. Data on transcatheter palliation are limited to case reports.

Hypothesis:
Transcatheter palliation with pulmonary flow restrictors (PFR) may represent an effective palliation strategy in neonates with CHD, especially those at high surgical risk.

Methods:
We present our experience of PFR palliation in neonates with CHD, including procedural feasibility, technical details, and outcomes. We then compared our sub-cohort of high-risk single ventricle (SV) neonates palliated with PFRs with a historical cohort of high-risk SV neonates palliated with a hybrid Stage 1. Cox regression was used to evaluate the association between palliation strategy and mortality at 6 months.

Results:
From 2021 to 2023, 17 neonates (median age 4 d [IQR 2-8]; median weight 2.5 kg [IQR 2.1-3.3]) underwent a PFR procedure; 15 (88%) had SV physiology, 15 (88%) were high-risk surgical candidates. All procedures were technically successful. At a median follow-up of 5.2 mo (IQR 2.7-9.9), 13 patients (76%) were either successfully bridged to surgery (n=12, 71%) or are awaiting surgery (n=1, 6%). Patients underwent target surgery at a median of 2.5 mo (IQR 1.1-3.4) since the PFR procedure (median weight 4.6 kg [IQR 3.3-5.6]). Pulmonary arteries were found to have grown adequately for age. All PFR devices were easily removed with no need for arterioplasty. The all-cause mortality rate before target surgery was 24% (n=4). Compared to a historical cohort of high-risk SV neonates palliated with a hybrid Stage 1 (n=23), after adjustment for main confounding (age, weight, intact atrial septum/severely restrictive foramen ovale or left ventricle to coronary fistulae), the PFR procedure was associated with a significantly lower all-cause 6-month mortality risk (adjHR=0.30 [95% CI 0.10-0.93]).

Conclusions:
Transcatheter PFR palliation in high-risk neonates with CHD is feasible, safe, and may represent an effective alternative strategy to bridge such high-risk neonates to surgical palliation, complete repair, or transplant while allowing for clinical stabilization and somatic growth.
Abstract 14036: Trends, In-Hospital Outcomes and Independent Predictors of Acute Kidney Injury in Patients Admitted for Myocardial Infarction With Percutaneous Coronary Intervention
Authors: Antia Akanimo , Evbayekha Endurance O , Markson Favour , Ubokudom Daniel A , Daniel Emmanuel , Onuegbu Chinwendu , Adabale Olanrewaju , Gongora Carlos
Published: December 2023

Introduction:
Acute kidney injury (AKI) is an important risk factor associated with adverse outcomes in cardiovascular illnesses; more importantly, myocardial infarction (MI). This study describes the Trends and in-hospital outcomes, and independent predictors of Acute Kidney Injury (AKI) in patients admitted for Myocardial infarction with Percutaneous Coronary Intervention (PCI).

Methods:
This was a retrospective study using records from the 2016-2020 National In-patient Database (NIS). We identified patients who were admitted for the management of an MI who had a PCI procedure and developed an AKI, evaluated their associated socio-demographic and comorbid factors using ICD-10 codes. We utilized the chi-square test to compare baseline characteristics between our populations with and without AKI and multivariate logistic regression to identify outcomes.

Results:
1,551,630 patients admitted for an MI and PCI with 15% having an AKI compared to 85% without AKI. Our population with AKI had a mean age of 69 years on admission and were more likely to be whites. A higher percentage were males. Our subpopulation was more likely to have HF, atrial fibrillation, COPD, prior history of CABG, obesity, CKD, Charlson comorbidity index (CCI) ≥ 3 and anemia. The independent Predictors of developing AKI in our cohort included: CKD, cardiogenic shock, cardiac arrest, CCI of ≥3 and HF. The development of AKI was associated with higher in-hospital mortality rates (aOR: 2.84, CI: 2.7 - 3.02, p<0.001), longer mean Length of Stay (7.1 vs 3.0 days) and higher hospital costs ($183,785.8 vs $101,291.2). We noted an increasing trend in the rates of patients who had an AKI from about 13.5% in 2016 to 16.5% in 2020.

Conclusions:
AKI is strongly associated with worse hospital outcomes in patients admitted for MI and PCI. A more concise look into preventive measures is recommended to minimize these outcomes.
Abstract 14044: Association Between Home Diuretic Dose and Optimal Initial Intravenous Diuretic Dosing in Acute Decompensated Heart Failure
Authors: Jacobs Joshua A , Carter Spencer J , Bullock Griffin , Carey Jessica R , Pan Irene Z , Kinsey Mary Shea , Zheutlin Alexander R , Kapelios Chris J , Raju Shilpa , Fang James C , Shah Kevin S , Bress Adam P
Published: December 2023

Introduction:
Nearly half of adults admitted with acute decompensated heart failure (ADHF) are discharged with a patient-reported or objective physical evidence of unrelieved congestion, which increases the re-hospitalization risk. This may be due to suboptimal initial intravenous (IV) loop diuretic dosing upon admission, which is often based on a patient’s home diuretic regimen.

Methods:
We performed a cross-sectional analysis of adults admitted to a large, quaternary healthcare system for ADHF between Jan. 1, 2014 and Dec. 21, 2021 to determine the association between oral home loop diuretic dose and receiving optimal initial IV dosing, as well as receiving optimal initial IV dosing and hospital length of stay (LOS). Patients were categorized based on home oral loop diuretic dose: low (≤40 mg furosemide equivalents [FEs]) and high (>40 mg FEs). We defined optimal initial IV dosing at least twice the home oral diuretic dose. Multivariable Poisson regression models estimated prevalence ratios (PRs) and confidence intervals (CIs) for the association between home oral diuretic dose and receiving optimal initial IV diuretic dosing.

Results:
Among 3,269 adults (mean age 63 years, 62% male, 82% non-Hispanic White, 51.7% ejection fraction ≤40%, mean home oral diuretic dose 71.8 mg FEs) admitted for ADHF, optimal initial IV loop diuretic dosing occurred in 2,218 (67.9%) patients. Optimal initial IV diuretic dosing was more likely to occur among patients on a low (95.5%) vs. high home dose (35.9%; PR 0.46; 95% CI 0.42-0.50). Among those who were on low oral home diuretic doses, LOS was decreased in those who received optimal initial IV dosing (estimate 0.84; 95% CI 0.77-0.91; P<0.001).

Conclusion:
Despite loop diuretics being the primary initial therapy for ADHF, there is significant heterogeneity in practice patterns. Understanding why clinicians use suboptimal doses and patients who are at risk of undertreatment may improve outcomes for patients admitted with ADHF.
Abstract 14047: Comparison of Left Bundle Branch Area Pacing and Biventricular Pacing in Patients With Left Ventricular Systolic Failure: A Systematic Review and Meta-Analysis
Authors: Ahmad Soban , Yousaf Amman , Peltz Joshua , Ahsan Muhammad Junaid , Abbas Kirellos Said , Ahsan Muhammad Zoraiz , Watson Christopher , Asad Zain Ul Abideen , Kim Michael H
Published: December 2023

Introduction:
There is limited data comparing the effectiveness of Left Bundle Branch Area Pacing (LBBAP) and traditional Biventricular Pacing (BiVP) in patients with left ventricular systolic failure. The aim of this study was to assess the electromechanical and clinical outcomes of both cardiac resynchronization (CRT) techniques.

Hypothesis:
LBBAP offers comparable or superior clinical outcomes compared to BiVP in patients with systolic left ventricular failure

Methods:
We conducted a systematic review of PubMed (MEDLINE), Embase, Google Scholar, Scopus, and Cochrane Central Register of Control Trials (CENTRAL) for studies comparing LBBAP with BiVP from inception till May 22, 2023. To evaluate categorical and continuous outcomes, risk ratios (RRs) and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated using RevMan version 5.4 software.

Results:
We selected 12 studies involving 3,004 patients (LBBP=1,242; BiVP=1,762) for our meta-analysis. The pooled results demonstrated significant improvements with LBBAP in left ventricular ejection fraction (LVEF) (SMD=0.40, 95%CI[0.25, 0.54], P<0.00001), NYHA functional class (SMD=-0.44, 95%CI[-0.65, -0.23], P<0.0001), reduction in QRS duration (SMD=-0.90, 95%CI[-1.14, -0.66], P<0.00001), fewer heart failure hospitalizations (RR=0.72, 95%CI [0.62, 0.85], P<0.0001), and improved survival (RR=0.73, 95%CI [0.58, 0.92], P=0.007). Additionally, LBBAP was associated with a lower pacing threshold at implantation (SMD=-1.03, 95%CI[-1.32, -0.74], P<0.00001) as compared to BiVP.

Conclusions:
LBBAP was associated with significant improvements in both electromechanical and clinical outcomes, including LVEF, reduction in QRS duration, NYHA class, heart failure hospitalizations, and all-cause mortality in patients with systolic left ventricular failure.
Abstract 14091: Subclinical Cardiac Dysfunction in the Patients Treated With Anthracycline-Containing Chemotherapy in the Chronic Phase
Authors: Tani Tetsuya , Oikawa Masayoshi , Ohara Himika , Yaegashi Daiki , Sato Yu , Yokokawa Tetsuro , Miura Shunsuke , Misaka Tomofumi , Ishida Takafumi , Takeishi Yasuchika
Published: December 2023

Background:
Anthracycline-induced cardiotoxicity is a concerning problem in the treatment of a variety of cancers. The highest incidence of anthracycline-induced cardiotoxicity was observed during the first year after the completion of chemotherapy, but the changes in cardiac function and biomarkers after the first year have not been adequately investigated.

Methods:
We analyzed 105 consecutive patients who were followed up for 24 months after starting anthracycline-containing chemotherapy in our hospital from June 2018 to April 2021. Echocardiography and blood test for troponin I and B-type natriuretic peptide (BNP) were performed at baseline, 3 months, 6 months, 12 months, and 24 months after starting the chemotherapy.

Results:
The cancer types included 71 breast cancers, 18 hematologic cancers, 11 gynecologic cancers, and 5 soft tissue tumors. Compared to baseline, troponin I levels were increased at 3 months (0.011±0.007 ng/ml vs. 0.021±0.021 ng/ml, P<0.05) and 6 months (0.023±0.047 ng/ml, P<0.001), then, recovered to baseline levels. In contrast, BNP levels remained unchanged for 12 months but increased at 24 months compared to baseline (31.9 [5.8-625.7] pg/ml vs. 15.5 [5.8-89.2] pg/ml, P<0.01). In addition, the left ventricular ejection fraction was decreased from baseline to 6 months (65.4±4.8% vs. 63.6±4.5%, P<0.05) and 24 months (63.6±4.7%, P<0.05). Multivariate logistic analysis revealed that age (OR 1.049, 95% CI [1.006-1.097], P=0.029) and total anthracycline dose (OR 1.011, 95% CI [1.002-1.022], P=0.026) were predicting factors for elevated BNP levels above the normal range (>18.2 pg/ml) at 24 months.

Conclusion:
Subclinical cardiac dysfunction was developed after more than one year. Long-term follow-up is desirable to detect cardiac dysfunction in patients treated with anthracycline-containing chemotherapy.
Abstract 14122: Evaluating Gender Diversity in Principal Investigators of Cardiac Electrophysiology Clinical Trials
Authors: Sadri Shirin , Soontornviwath Grace A , Ku Alice , Bernardez Crystal O , Ali Tawfique , Khosla Ananya , Adhikari Khusbu K , Duran Angelina S , Igwe Joseph-Kelvin , Clark Kira , Cruz Erin Rose R , Idris Muhammed Y , Poullos Peter , Periyakoil VJ , Lin Bryant , Palaniappan Latha , Yong Celina M , Onwuanyi Anekwe , Echols Melvin , Wang Paul J , Kapoor Ridhima
Published: December 2023

Background:
Importance of diversity in clinical trial participants has been recently highlighted. Though clinical trials led by women principal investigators (PIs) are more likely to enroll diverse participants, the proportion of trials led by women PIs is unknown.

Objective:
To evaluate gender distribution among PIs who conduct NIH and industry-funded clinical trials in cardiac electrophysiology (EP).

Methods:
NIH and industry-funded trials in the clinicaltrials.gov registry completed between 1/1/2002 and 12/31/2021 in atrial fibrillation (AF), implantable cardioverter defibrillators (ICDs), pacemakers (PPMs), sudden cardiac arrest (SCA), and ventricular tachycardia (VT) were included. PI names and associated institutions were used to determine gender pronouns on institutional websites or social media. Trials with unidentifiable PI gender were categorized as unknown.

Results:
51 NIH-funded and 429 industry-funded trials in AF, SCA, VT, ICDs, and PPMs and 573 total PIs were identified. 128 trials (26.7%) and 123 PIs (21.5%) had unknown PI gender. 16.4% of all trials in which PI gender was known were led by women. 9/49 (18.4%) NIH and 49/295 (16.6%) industry trials were led by women. VT trials had the lowest proportion women-led (NIH: 0/4, 0%; industry: 3/26, 11.5%), whereas PPM trials had the highest proportion women-led in both NIH (3/5, 60%) and all trials (12/48, 22.2%). Of the group with the largest number of trials (AF), 12.9% were women-led (22/170) (Table). Of 450 PIs across all trials whose gender was identified, 14.4% were women. The proportion of women PIs decreased non-significantly over time. Studies between 2002-2011 were 16% women-led, and in 2012 or later this reduced to 13%
X
2
(1, N = 450) = 0.81, p > .05.

Conclusion:
The proportion of cardiac EP clinical trials led by women PIs remains low and has not increased. Urgent efforts are needed to implement strategies to increase leadership roles in clinical trials for women in cardiac electrophysiology.
Abstract 14137: Stress-Induced Cardiomyopathy After Uncomplicated Permanent Pacemaker Implantation
Authors: Seo Jiyeon
Published: December 2023

Stress-induced cardiomyopathy (SCMP) after permanent pacemaker (PPM) implantation is rare. Here, we report an additional case which was initially misdiagnosed as another disease due to atypical symptoms after PPM implantation.

Case presentation:
A 79-year-old woman with dizziness and dyspnea for one month visited Cardiology Department. She had a history of hypertension, dyslipidemia, diabetes-mellitus and stage IV chronic kidney disease. We confirmed complete atrioventricular block. Left ventricular ejection fraction (LVEF) was normal. PPM implantation was successfully performed without complications. The next day she felt very well with no symptoms. On the second day, she suddenly developed a fever and complained severe left neck pain. She had cough, sputum and general weakness without chest pain. C-reactive protein level increased and systolic blood pressure was decreased. We started antibiotics considering infection. We also checked implantation site, but there were no signs of infection. On the third day, echocardiography showed decreased LVEF (30%), akinesia of apical and medium segments of LV wall with preserved kinetics of basal segments without pericardial effusion (Figure 1). There was no significant stenosis on coronary angiography and we confirmed SCMP. After few days, her blood pressure and symptoms were improved. We prescribed sacubitril-valsartan, bisoprolol and furosemide. At 10 days after implantation, she was discharged with improved symptoms.

Conclusion:
Our case emphasizes that even successful implantation of PPM without complications can be a potential risk of SCMP. In the absence of typical cardiac symptoms after PPM implantation, a poor general condition may also be considered as a sign of SCMP. Therefore, it is necessary to monitor the patient for at least three more days after PPM implantation.
Abstract 14142: Patterns of Renin Angiotensin Aldosterone Inhibitor Use in Patients After Hospitalization With Acute Kidney Injury
Authors: Krishnan Dhruv M , Fang Jiming , Ko Dennis T , Lee Douglas , Naimark David , Tu Karen , Kapral Moira K , Udell Jacob A , Jackevicius Cynthia
Published: December 2023

Background:
Renin-angiotensin system inhibitors (RASi, i.e., ACEIs and ARBs) are vital to chronic disease management and they are often held in the setting of AKI. Reinitiation after hospital discharge requires careful coordination and puts patients at risk of inappropriately remaining off RASi.

Aims:
Characterize patterns of RASi use post-AKI hospitalization and identify factors associated with RASi discontinuation and reinitiation after discharge.

Methods:
A retrospective cohort study using ICES administrative data was conducted among adults ≥66 on RASi and discharged after hospitalization with AKI in Ontario (2015-2019). Prescription claims were used to identify patients who experienced RASi discontinuation (no RASi script renewal) after discharge. These patients were then followed for an additional 6 months to monitor for reinitiation. Modified Poisson and Cox regression models were used to identify factors associated with discontinuation and reinitiation, respectively, censoring those who died or were readmitted prior to reinitiation.

Results:
The cohort included 84,598 patients, mean age 80.3 years, 50.8% male. Overall, 42.2% continued their RASi, 37.1% discontinued, and use was indeterminable for the 20.7% who were readmitted or died before their prescription elapsed. Of the 31,390 patients with RASi discontinuation, 47.4% did not reinitiate and 34.8% reinitiated. Discontinuation was more likely in patients with CKD (RR = 1.13, 95% CI 1.10-1.16) or on diuretics (RR = 1.06, 95% CI 1.03-1.09). Reinitiation was more likely in patients in the highest income quintile (HR 1.08, 95% CI 1.02-1.15) or on diuretics (HR = 1.09, 95% CI 1.04-1.13), and less likely in patients with HF (HR = 0.89 95% CI 0.85-0.93), dementia (HR = 0.72, 95% CI 0.67-0.76), or rural residence (HR = 0.88, 95% CI 0.82-0.94).

Conclusions:
After hospitalization with AKI, nearly 2 in 5 patients discontinued their RASi at discharge, with one-third of these patients restarting within 6 months. Several patient-, provider-, and system-level factors were associated with patterns of RASi use after discharge. These can be used to identify patients at higher risk of experiencing RASi interruption, which may highlight opportunities for optimization of RASi use to improve patient care.
Abstract 14148: Left Ventricular Outflow Tract Pseudoaneurysm in a Pediatric Patient: An Unusual Presentation of Endocarditis
Authors: Gungor Sara , Broadus Dalia , Kosiv Katherine , Karnik Ruchika , Steele Jeremy M , Ferdman Dina
Published: December 2023

Description of Case:
A 12-year-old male with known bicuspid aortic valve presented with one month of progressive weight loss and subjective fevers. Transthoracic echocardiogram was concerning for a new left ventricular outflow tract (LVOT) aneurysm (figure 1). His aortic valve stenosis and regurgitation had notably progressed compared to a prior study one year ago. He was urgently referred for cardiac computed tomographic angiography (CCTA), which demonstrated a pseudoaneurysm of the LVOT inferior to the aortic valve and irregularly thickened aortic valve leaflets with a notable perforation (figure 2). Blood cultures were positive for Viridans streptococci, confirming the diagnosis of infective endocarditis. The patient was referred for a Bentall procedure with LVOT pseudoaneurysm repair. Pre-operative transesophageal echocardiogram demonstrated a communication of the non-coronary cusp of the aortic valve and LVOT. Ultimately, aortic root replacement was performed with a 23mm homograft. Our patient recovered well from surgery and now has excellent clinical status with normal aortic valve function.

Discussion:
Pseudoaneurysm of the LVOT as a result of infective endocarditis is a rare diagnosis, especially in the pediatric population. Of the case reports published, it is most seen in the setting of infection involving the native aortic valve but has also been reported after aortic valve replacement. As in our patient, the most commonly reported location involves the mitral-aortic intervalvular fossa. Symptoms have insidious onset and the diagnosis requires a high level of suspicion. A multimodal imaging approach is warranted for optimal diagnosis and treatment.
Abstract 14155: Handgrip Exercise Provoked High Sensitivity Cardiac Troponin I Increase in Women With No Obstructive Coronary Artery Disease: Relations to Myocardial Function
Authors: IRIBARREN ANA , Nelson Michael D , Maughan Jenna , Obrutu Okezi , Cook-Wiens Galen , Mastali Mitra , Van Eyk Jennifer E , Handberg Eileen M , Pepine Carl , Bairey Merz C Noel N , Wei Janet
Published: December 2023

Background:
Among women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) around 10% develop heart failure with preserved ejection fraction (HFpEF). Mechanisms contributing to AMI and HFpEF progression in INOCA are poorly understood.

Purpose:
To characterize clinical profile and stress cardiac magnetic resonance imaging (CMRI) myocardial features of INOCA patients with and without increased troponin levels in response to handgrip exercise.

Methods:
Women with suspected INOCA underwent cardiac MRI and invasive coronary function testing (CFT), including coronary sinus (CS) cannulation, handgrip exercise testing, and serial CS plasma sampling before, after 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction, and after 5 minutes of recovery. High sensitivity cardiac troponin I (hsTnI) was measured using commercial immunoassay (R-PLEX, Meso Scale Discovery, Rockville, MD) and compared using t-tests.

Results:
A total of 51 women with complete data were included, of whom 31 (60.7%) had handgrip provoked increases in hsTnI levels from baseline, while 20 (39.2%) did not. Baseline characteristics are shown in
Table.
Patients with increased hsTnI levels had greater impaired global longitudinal strain rates and early diastolic strain rates (radial and circumferential) compared to those without increased hsTnI. No significant differences were observed in myocardial perfusion reserve index (MPRI).

Conclusion:
Women with INOCA demonstrating objective evidence of handgrip exercise provoked myocardial injury exhibit evidence of myocardial dysfunction not related to myocardial perfusion. Further prospective research is needed to understand the sequence of relations between coronary microvascular dysfunction contribution to HFpEF progression.
Abstract 14161: Recreational Cannabis Use and the Risk of Atrial Arrhythmias: Evidence From a Meta-Analysis of Observational Studies
Authors: Garcia Quarto Levindo Jose , Sampaio Rodrigues Thalys , Young Naomie , Patel Suraj , Laband William , Lim Han S , Koshy Anoop N
Published: December 2023

Introduction:
Tetrahydrocannabinol is known to induce sympathetic stimulation and endothelial dysfunction, potentially increasing the susceptibility to arrhythmias. While a recent AHA consensus document outlined various cardiovascular risks associated with cannabis use, there was a paucity of data linking its use with arrhythmias. Therefore, we sought to investigate the association between recreational cannabis use and the risk of atrial arrhythmias.

Methods:
Electronic databases were searched for articles published up to April 2023 for studies that assessed the effect of the recreational use of cannabis on the risk of atrial arrhythmias (atrial fibrillation/flutter, supraventricular tachycardia). The study was prospectively registered (PROSPERO CRD42023428219). Three reviewers independently appraised the data, with summary odds ratios (OR) and 95% confidence intervals (CIs) pooled using a random-effects model.

Results:
Our analysis included seventeen cohort studies with a total of 81,269,314 participants from North America, Europe and Oceania. Four studies were prospective observational in design. Mean age was 46 years [41-72] and mean female participation was 45% [31-83] across studies. Recreational use of cannabis was associated with a significantly higher risk of atrial arrhythmias (OR 1.55, 95% CI 1.13-2.13) with high degree of heterogeneity (I2=99%). On meta-regression, mean age was not a contributing factor for the observed effect (p=0.58).

Conclusions:
Recreational use of cannabis was associated with 1.5-fold increased risk of atrial arrhythmias. Prospective studies are warranted to further explore this relationship and the public health implications of cannabis utilization.