bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4142087: Prevalence of Standard Modifiable Risk Factors in Patients with Ischemia and Nonobstructive Coronary Arteries
Authors: Kostantinis Spyridon , Garcia Castro Gabriel , Latif Nida , Nikolakopoulos Ilias , Cigarroa Natasha , Kunnirickal Steffne , Odanovic Natalija , Shah Samit
Published: November 2024

Introduction:
Ischemia with nonobstructive coronary arteries (INOCA) is an increasingly recognized clinical syndrome. Standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes, hypercholesterolemia, and smoking) are associated with the development of atherosclerotic coronary artery disease, but the prevalence in INOCA is not well described.

Methods:
From 2017 to 2024, 221 patients with INOCA underwent invasive coronary physiologic assessment including vasoreactivity testing with acetylcholine provocation, guidewire-based assessment of coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and fractional flow reserve (FFR). In our present study, we sought to examine the prevalence of SMuRFs in patients with INOCA.

Results:
In the entire cohort, the prevalence of SMuRFs were as follows: hypertension (63.3%), diabetes (23.1%), hypercholesterolemia (70.6%), and smoking (7.2%). 33 (14.9%) had no SMuRFs and the rest (85.1%) had at least one modifiable risk factor. SMuRF-less INOCA patients were younger (53.0 ± 11.8 years vs 58.5 ± 10.4 years; p=0.017) and were more commonly female (90.1% vs 68.1%; p=0.007). CFR, IMR and FFR were similar in both groups, but patients with SMuRFs had higher left ventricular end diastolic pressure (14.3 ± 4.7 mmHg vs 11.6 ± 3.4 mmHg; p=0.001) (Figure 1). Among patients with SMuRFs and no SMuRFs, the frequency of coronary microvascular dysfunction (CMD), vasospastic angina (VA), and mixed CMD/VA were similar, but patients with 0 SMuRFs had higher rates of myocardial bridging (21.2% vs 8.5%; p=0.044) (Figure 2).

Conclusion:
There was a high prevalence of SMuRFs in our study sample, with the majority of patients having hypertension and hyperlipidemia. The presence of SMuRFs was associated with left ventricular diastolic dysfunction. Among INOCA phenotypes, myocardial bridging was more common in patients without SMuRFs.
Abstract 4142090: Venous Access Alone
vs.
Arterial and Venous Access for Patent Arterial Duct Device Closure in Childhood
Authors: Hassan Ahmed , Chaturvedi Rajiv , Benson Lee
Published: November 2024

Background:
The persistently patent arterial duct accounts for ~12% of congenital heart lesions. Untreated, it may result in heart failure due to volume loading of the left heart, pulmonary hypertension, and infective endarteritis. Percutaneous device closure is the preferred occlusion technique, with the standard approach consisting of femoral artery access for angiography and venous access for device delivery (AA). A venous-only strategy (VA) for angiography and device delivery can also be employed.

Hypothesis:
We hypothesized that VA would eliminate arterial complications, and reduce procedure times and radiation exposure compared to standard AA.

Methods:
This retrospective cohort study reviewed isolated arterial duct device closures at the Hospital for Sick Children from January 1, 2011 through December 31, 2022. Exclusions included premature neonates, children requiring arterial access for monitoring and those who underwent other procedures. Children were categorized based upon initial access determined by operator preference, into VA or AA groups.

Results:
The cohort consisted of 405 children, 252 (62.2%) females, with a median age of 3.1 years (IQR1.30–5.84), median weight 13.2kg (IQR 9.0–19.5), and duct diameter of 2.9mm (IQR 2.0–3.5) with no significant differences between the groups. Type A ducts were more frequent in the AA group (90% vs. 72%). The VA group included 106 children, of which 14 (13.2%) required AA conversion for angiography due to complex anatomy, to assess device positon prior to release, but remained in the VA group for analysis.

Children in the VA group had lower dose area product (DAP) (p<0.001), fluoroscopy times (p=0.025), contrast volumes (p<0.001), procedure times (p<0.001), and recovery room lengths of stay (LOS) (p<0.001). Six (5.7%) VA children required admission compared to 44 (14.7%) in the AA group (p=0.015) with no difference in reintervention rates.

Weighted regression analysis showed VA was associated with reduced admission likelihood (OR: 0.354 [0.131,0.822], p=0.024), DAP (coef -126.4 [-213.3,-39.4], p=0.004) and contrast volumes (coef 31.2 [-36.6,-25.9], p<0.001) compared to AA.

Conclusions:
Venous only access was associated with lower DAP and recovery room LOS. Additionally, VA was associated with a lower likelihood of admission with no difference in reintervention rates, suggesting procedural safety. These findings support the consideration of VA as a preferred approach for appropriate cases.
Abstract 4142098: Clinical Link of Neutrophilia to Neovascularization and Fibrinolysis
Authors: Eton MD FACS DFSVS Darwin
Published: November 2024

The anti-angiogenic impact of neutrophil elastase clouded the understanding of the role of neutrophils in promoting neovascularization (NV) and fibrinolysis in patients with chronic limb-threatening ischemia (CLTI). The impact of significant neutrophilia was not studied during clinical trials using Granulocyte Colony Stimulating Factor (G-CSF) to boost the deficient circulating endothelial progenitor cell count. Only recently have activated human neutrophils been documented to release pro-angiogenic factors such as VEGFA, Hepatocyte Growth Factor (HGF), MMP-9, angiopoietin (Ang1). They also stimulate and modulate fibrinolysis through release of proteases, and by promoting endothelial cell release of plasmin.

The purpose of this abstract is to link clinical evidence* to these observations. Proteomic and cytometry data were obtained in 14 CLTI patients treated with Filgrastim 7-10 mcg/kg SQ every 72 h for up to a month. The absolute neutrophil count (ANC) increased a mean of 6-fold a day after each injection, returning to baseline within 72 hours. Significant (p < 0.05) increases in the concentration of VEGFA, HGF, MMP-9, Ang1 was measured by ELISA a day after both the 5th and the 10th Filgrastim doses as compared to baseline. The ANC peak was measured at the same time, as well as was the significant (p < 0.01) increases in the plasma concentration of plasmin (>10-fold) and Fibrin Degradation Products (FDP) (>5-fold). Since these patients also wore an infra-geniculate programmed compression pump (PCP) for 3 hours daily, these data were compared to 19 CLTI patients treated with PCP alone. PCP was used to improve the ischemic micro-environment and to provide endothelial shear stress as a strategy to induce arteriogenesis. PCP use did not influence the concentration of any of these proteins and did not induce neutrophilia. Resolution of ischemic rest pain and healing of ischemic ulcers contributed to limb salvage. Arterial hemodynamic improvement was supported by angiographic evidence of NV (enlarged corkscrew collaterals, improved contrast transit through the ischemic tissue). Segmental arterial recanalization indicated fibrinolysis. No hemorrhage occurred over the 30 day course. A prospective investigation of the uncovered link between neutrophilia, NV, and fibrinolysis is justified. * J Tissue Eng Regen Med. 2022 May;16(5):496-510. doi: 10.1002/term.3284
Abstract 4142099: Deep Learning Quantification of Aortic Compliance from Parasternal Long-Axis Echocardiograms
Authors: Rhee Justin , Lu Eileen , Nammalwar Shruthi , Duffy Grant , Vukadinovic Milos , Chou Elizabeth , Ouyang David
Published: November 2024

Introduction:
Aortic compliance is crucial for maintaining diastolic blood pressure and systemic perfusion throughout the cardiac cycle. Echocardiography is widely used for cardiovascular imaging but has limited precision in clinical phenotyping of aortic compliance.

Hypothesis:
We hypothesized that a deep learning approach can quantify aortic compliance by precision characterization of the aortic root in parasternal long-axis echocardiogram videos and that this deep learning measured aortic compliance would correlate with aspects of thoracic aortic repair.

Aims:
Develop a high precision deep learning model for quantifying aortic compliance from echocardiogram videos and explore associations with surgical repair.

Methods:
We used 51730 PLAX echocardiogram videos from Cedars-Sinai Medical Center, divided into training (46188), validation (5035), and test (507) cohorts. The DeepLabv3 architecture with a 50-layer residual network backbone was used for frame-level segmentation of the aortic root. Strain was obtained by dividing the change in root diameter by the minimum diameter during each cardiac cycle. Evaluation of measurements was performed on a separate cohort of 33 patients who underwent endovascular repair of the thoracic aorta.

Results:
The model accurately measured aortic root diameter with a mean absolute error (MAE) of 2.5mm comparing favorably with clinical inter-observer variability (MAE of 2.9mm, p=0.010). Exploratory data analysis showed increasing aortic root strain after endovascular repair (n=12, p=0.084) but no clear trends after combined endovascular and open repair (n=21, p=0.852). Aortic strain was lower in patients with prior abdominal surgery (n=12, p=0.001) and dissection that underwent repair (n=14, p=0.099), and postoperative aortic strains were lower in patients requiring surgery within 30 days (n=7, p=0.024).

Conclusion:
A deep learning workflow can measure aortic root diameter and identify changes in aortic compliance with higher precision than human assessment. Trends in preoperative and postoperative aortic strain in patients undergoing endovascular repair suggest utility of aortic strain phenotyping for prognosticating clinical outcomes.
Abstract 4142110: Coronary Artery Calcium Scans Powered by Artificial Intelligence (AI-CAC) Predicts Atrial Fibrillation and Stroke Comparably to Cardiac Magnetic Resonance Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Naghavi Morteza , Reeves Anthony , Atlas Kyle , Zhang Chenyu , Atlas Thomas , Henschke Claudia , Roy Sion , Budoff Matthew , Yankelevitz David , Wong Nathan
Published: November 2024

Background:
Coronary artery calcium (CAC) scans contain more actionable information than the Agatston CAC score. We have previously shown in the Multi-Ethnic Study of Atherosclerosis (MESA) that AI-enabled left atrial (LA) volumetry in CAC scans (AI-CAC) enabled prediction of atrial fibrillation (AF) as early as one year. Furthermore, we have recently shown adding AI-CAC LA volumetry to CHA
2
DS
2
-VASc risk score improved stroke prediction in MESA. In this study we evaluated the performance of AI-CAC LA volumetry versus LA measured by human experts using cardiac magnetic resonance imaging (CMRI) for predicting AF and stroke, and compared them with CHARGE-AF risk score, Agatston score, and NT-proBNP.

Methods:
We used 15-year outcomes data from 3552 asymptomatic individuals (52.2% women, age 61.7±10.2 years) who underwent both CAC scans and CMRI in the MESA baseline examination. We have applied the AutoChamber
TM
(HeartLung.AI, Houston, TX) component of AI-CAC to 3552 CAC scans. CMRI LA volume was previously measured by human experts. Data on NT-proBNP, CHARGE-AF risk score and the Agatston score were obtained from MESA. Discrimination was assessed using the time-dependent area under the curve (AUC).

Results:
Over 15 years follow-up, 562 cases of AF and 140 cases of stroke accrued. The AUC for 15-year
AF prediction
by AI-CAC LA volume (0.801) was comparable to CMRI LA volume (0.797) and significantly higher than Agatston CAC Score (0.687) and NT-proBNP (0.704). Similarly, the AUC for 15-year
stroke
prediction
for AI-CAC volumetry (0.761) was comparable to CMRI volumetry (0.751) and significantly higher than NT-proBNP (0.631) and Agatston CAC Score (0.646). AI-CAC LA volume outperformed CHARGE AF over 1-3 years for incident AF (p<0.02), but not for subsequent years. AI-CAC significantly improved the continuous Net Reclassification Index (NRI) for prediction of AF and stroke when added to CHARGE-AF risk score (0.28, 0.21), NT-proBNP (0.43, 0.37), and Agatston score (0.69, 0.41) respectively (p for all<0.0001).

Conclusion:
LA volumetry measured by the AutoChamber component of AI-CAC and CMRI LA volume measured by human experts similarly predicted incident AF and stroke over 15 years, and outperformed NT-proBNP and Agatston CAC Score. AI-CAC LA volumetry outperformed CHARGE-AF and NT-proBNP for short-term (1-3 years) AF prediction. Further studies to investigate the clinical utility of AI-CAC LA volumetry for AF and stroke prediction are warranted.
Abstract 4142116: The Association Between Urinary Sodium Concentration (UNa) and Outcomes of Acute Heart Failure in Patients Undergoing Diuretic Therapy: A Systematic Review and Meta-Analysis
Authors: Tabassum Shehroze , Khan Muhammad Khuzzaim , Khalil Namra , Al Hennawi Hussam , Bedi Angad , Shpilman Alexander
Published: November 2024

Introduction:
The measurement of Urinary Sodium Concentration (UNa) is a pivotal biomarker in managing Acute Heart Failure (AHF), offering a non-invasive and readily accessible means to evaluate diuretic response. This systematic review and meta-analysis is designed to investigate the correlation between UNa levels and patient-centric outcomes in AHF, aiming to validate the evidence base and refine clinical practice.

Methods:
This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. We systematically searched PubMed, Cochrane Central, Scopus, Google Scholar, and ClinicalTrials.gov from their inception to May 2024. Our search included randomized controlled trials (RCTs) and observational studies comparing outcomes between acute heart failure (AHF) patients with high urinary sodium concentration (UNa) and those with low UNa.

Results:
The analysis included 12 studies comprising 5 RCTs and 7 observational studies, incorporating a total of 8,743 AHF patients. In the high UNa group, pooled data demonstrated significantly higher urinary output (MD 534.49 ml, 95% CI 348.48 to 720.49; P < 0.00001) and increased weight loss (MD 1.15 kg, 95% CI 0.45 to 1.85; P < 0.001). Additionally, there was a lower risk of renal function decline (OR 0.48, 95% CI 0.24 to 0.97; P < 0.04). Patients with high urinary sodium had a shorter mean hospital stay of 7.6 days compared to 8.8 days for those with low UNa, with an overall reduction in length of stay (MD -1.38 days, 95% CI -2.44 to -0.32; P < 0.01). Mortality was also lower in the high UNa group, particularly over longer follow-up periods: at 1-month follow-up (OR 0.40, 95% CI 0.21 to 0.78; P = 0.007), at 6-month follow-up (OR 0.45, 95% CI 0.29 to 0.72; P = 0.0007), and at 12-month follow-up (OR 0.16, 95% CI 0.16 to 0.26; P < 0.00001). Furthermore, the high UNa group exhibited a lower risk of worsening heart failure requiring inotropes (OR 0.40, 95% CI 0.23 to 0.70; P = 0.002) and a reduced incidence of heart failure rehospitalization (OR 0.42, 95% CI 0.20 to 0.89; P = 0.02).

Conclusion:
High urinary sodium concentration is strongly associated with improved clinical outcomes in acute heart failure, including greater urinary output, increased weight loss, shorter hospital stays, and reduced risks of renal function decline, mortality, worsening heart failure, and rehospitalization.
Abstract 4142117: First Reported Case of Massive Gastrointestinal Bleeding Linked to Piperacillin-Tazobactam in a Patient on Rivaroxaban: A Comprehensive Case Review
Authors: Mohammadi Abbas , Alleyasin Sara , McDermott Nasim
Published: November 2024

Introduction:
The management of patients with Venous thromboembolism (VTE) receiving anticoagulant therapy is complicated by potential interactions with other medications, including antibiotics. Piperacillin-tazobactam (PTZ) has been implicated in unexpected disturbances in the coagulation cascade, which can be critical in patients concurrently using anticoagulants like rivaroxaban. This report explores the complexities of prescribing broad-spectrum antibiotics to patients with pre-existing cardiac conditions and the necessity of careful consideration of drug-drug interactions.

Case Report:
A 52-year-old white male with a history of deep vein thrombosis on rivaroxaban, presented with severe left leg cellulitis and subsequent gastrointestinal bleeding shortly after the initiation of piperacillin-tazobactam. His presentation was complicated by a rapid deterioration in his condition following a syncopal episode, characterized by hematochezia and hematemesis, necessitating urgent medical interventions including the cessation of all anticoagulation therapy, esophagogastroduodenoscopy and broad-spectrum antibiotics.

Discussion:
This case highlights the clinical challenges and potential risks of coagulopathies induced by PTZ or the interaction of PTZ with rivaroxaban, stressing the importance of multidisciplinary vigilance. The mechanisms by which PTZ may influence the coagulation pathways in patients already at risk due to their cardiac profiles underscore a significant area of concern for clinicians.
Abstract 4142124: Transcatheter mitral edge-to-edge repair in a patient with symptomatic SAM and LVOT obstruction following surgical robotic mitral valve repair
Authors: Chiou Andrew , Ibrahim Fady , Romero Steven , Price Matthew
Published: November 2024

Background:
Persistent systolic anterior motion (SAM) following robotic mitral valve repair can lead to symptomatic left ventricular outflow tract (LVOT) obstruction. Percutaneous mitral valve edge-to-edge repair using MitraClip to manage LVOT obstruction from SAM following mitral valve repair has been rarely reported.

Case:
A 64-year-old male with history of mitral regurgitation from posterior leaflet prolapse who underwent robotic mitral valve repair with posterior leaflet butterfly resection and 38 mm Cosgrove annuloplasty band presented with progressive dyspnea with exertion and fatigue three years later. Transesophogeal echocardiogram (TEE) revealed 3+ mitral regurgitation (MR) (mean mitral valve pressure gradient 4.2 mmHg, heart rate 88 bpm) and SAM of the mitral valve with LVOT obstruction (resting gradient of 78 mmHg). He underwent a left heart catheterization to accurately measure the LVOT gradient with Dobutamine infusion. Baseline LVOT gradient was 20 mmHg that increased to 40 mmHg, 60 mmHg, and 140 mmHg with Stage 1 (5 mcg/kg/min), Stage 2 (10 mcg/kg/min), and Stage 3 (20 mcg/kg/min) of Dobutamine infusion, respectively.

Decision-Making:
Given his symptomatic LVOT obstruction from SAM, he was initially referred to CT Surgery for consideration of mitral valve replacement, however, given his desire to avoid long-term anticoagulation and risk of redo surgery, he was evaluated for percutaneous management. He underwent TEE guided transcatheter mitral edge-to-edge repair using a single XTW MitraClip with capture of the A2 and P2 leaflets. Post-procedural transthoracic echocardiogram (TTE) revealed trace MR and no SAM or LVOT obstruction with a resting LVOT gradient of 8 mmHg. At outpatient follow up, his shortness of breath and fatigue had significantly improved.

Conclusion:
Mitral valve edge-to-edge repair using MitraClip can be a safe and effective management option for patients who develop persistent SAM resulting in symptomatic LVOT obstruction following mitral valve repair.
Abstract 4142141: The Genetic and Phenotypic Determinants of Life-Threatening Arrhythmias in Pediatric Bileaflet Mitral Valve Prolapse Arrhythmia Syndrome
Authors: Mitchell Saige , Foote Henry , Sharaf Dabbagh Ghaith , McCrary Andrew , Chahal Anwar , Landstrom Andrew
Published: November 2024

Background:
Bileaflet mitral valve prolapse (BMVP) is a rare disease in the pediatric population. It may be a proarrhythmic substrate, particularly when present with mitral annular disjunction (MAD). There is less known about the genetic etiology and phenotypic spectrum of patients diagnosed with BMVP in childhood.

Objective:
To determine the genetic and phenotypic factors that influence arrhythmia

development and cardiac arrest in pediatric patients with BMVP.

Methods:
We established a cohort of pediatric probands with at least one clinical encounter at Duke University Hospitals. Patients were categorized by underlying cardiac condition leading to groups of idiopathic BMVP, aortopathies, cardiac channelopathies/cardiomyopathies, and congenital heart disease (CHD). We grouped patients by presence of MAD. Primary outcome was ventricular arrhythmias. Secondary outcomes were cardiac arrest, pacemaker or implantable cardioverter defibrillator (ICD) placement, and secondary cardiac surgery. Rates of arrhythmia and secondary outcomes were compared using Fisher’s exact test. Freedom from event curves were generated to track first arrhythmia episodes and age at diagnosis and compared using a log-rank test.

Results:
54 pediatric patients were included with 30 (55.6%) female and an average age at diagnosis of 8.2 years. Patients with concurrent CHD had earlier BMVP diagnosis compared to those with idiopathic BMVP and cardiac channelopathies/cardiomyopathies (p < 0.05). Yield of gene panel testing was 71.88% LP/P overall, 56.25% in isolated BMVP, and 12.5% in MAD. Among the pathogenic variants found in MAD, 60% were aortopathy genes, 20% cardiomyopathy/channelopathy genes, and 20% in sudden unexpected death in epilepsy genes. The most common arrhythmia was ventricular tachycardia found in 52% of arrhythmia episodes, followed by supraventricular tachycardia (19%), and ventricular fibrillation (15%) which only was seen in MAD. The rate of arrhythmia in MAD was higher (55%) compared to 14% in patients with isolated BMVP (p < 0.001), and rates of breakthrough arrhythmia were similar between groups. Patients with MAD had a rate of 27.27% for pacemaker or ICD placement compared to 2.33% in patients with isolated BMVP (p < 0.05).

Conclusions:
BMVP is likely a common phenotype with a variety of genetic and phenotypic subtypes. Presence of MAD increases risk of arrhythmia and need for a pacemaker or ICD in patients with BMVP independent of the underlying cardiac condition.
Abstract 4142146: Disparities in Health Literacy Are Present in Adult Congenital Heart Disease Patients in the Modern Era
Authors: Porter William , Dolgner Stephen , DiLeo Michael , Salciccioli Katherine , Flores Nicolas , Lopez Keila
Published: November 2024

Introduction:
Health literacy levels (HLL) in adults with chronic diseases correlate with health outcomes, especially in acquired cardiovascular disease. Data demonstrates that lower HLL correlate with lower education, and adult congenital heart disease (ACHD) patients have overall lower educational attainment. Currently, the HLL of ACHD patients is understudied and largely unknown. We hypothesized that adults with lower educational attainment would have a lower HLL.

Methods:
We conducted a cross-sectional study of health literacy between March and June 2024 in a large tertiary care ACHD outpatient clinic. We included patients ≥18 years old with simple, moderate, or great complexity CHD who spoke English or Spanish. We excluded patients with significant developmental delay and intellectual disability. The primary outcome was the Newest Vital Sign (NVS) Score, a validated 6-point adult health literacy assessment tool, where low HLL is a NVS score of 0-3. Our primary predictor variable was education level. Covariables included age, race/ethnicity, primary language, insurance type, and transition program participation. Analysis was performed using univariable logistic regression (Stata v.17).

Results:
Seventy-three in-person HLL assessments were completed. One patient was excluded for developmental delays on assessment. The median age was 32 years (25-75% IQR 24.5-46). Most of the cohort was female (58%) and had great complexity CHD (72.2%). Patients were 59.7% non-Hispanic White, 25% Hispanic, and 12.5% Black. 89% primarily spoke English. 72% had private insurance, and 76% had at least a high school education. The median NVS score was 5, with a range of 0-6 (Figure). Logistic regression demonstrated ~4x higher odds of low HLL for Hispanics (OR 3.92, 95% CI 1.07-14.33) and 4.6x higher odds of low HLL for public insurance (OR 4.6, 95% CI 1.23-17.23). There was no HLL association with age, education level, CHD severity, primary language, or transition program participation.

Conclusion:
This is the largest study assessing the HLL of the ACHD population in the modern era. While education did not correlate with HLL, lower HLL in Hispanic and publicly insured patients underscores a need for further evaluation in these populations.
Abstract 4142147: Clinical Outcomes in Patients with Atrial Fibrillation and End-Stage Renal Disease Managed with Rivaroxaban versus Warfarin; A Propensity-Score Matched Analysis
Authors: Somerville Alexander , Anuforo Anderson , Rawlley Bharat , Ghosh Auyon
Published: November 2024

Introduction:
The utilization of direct oral anticoagulant (DOAC) agents for atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) has increased despite a lack of robust supportive data from randomized controlled trials. We planned to assess the outcomes associated with rivaroxaban versus warfarin in the ESRD population with AF.

Methods:
We utilized the TriNetX Global Collaborative Network, which includes 114 Healthcare organizations to perform a propensity-score matched retrospective cohort study. We used ICD-10 codes to identify individuals with ESRD and AF, over 18 years of age, excluding those with prosthetic valves and apixaban or edoxaban use. Data were collected from 2011 to 2024. We evaluated the incidence of ischemic stroke (I63), intracranial hemorrhage (I62.9), cardiac arrest (I46), mortality, gastrointestinal (GI) hemorrhage (K92.2), systemic embolism and thrombosis (I74.3, I74.2), and other cardiac arrythmias (I49). We performed propensity-score matching (PSM) on age, sex, race, BMI
,
hypertension, diabetes mellitus, tobacco use, heart failure, stroke, or acute myocardial infarction.

Results:
We identified 25,092 individuals in the warfarin group and 2,391 individuals in the rivaroxaban group. After PSM, 2,381 individuals remained in each group. The average age was 72.9, predominantly male (59.8%), with 62.9% white, 14.7% African American, and 6.5% Hispanic individuals. Compared to those treated with warfarin, individuals treated with rivaroxaban demonstrated a lower risk of a composite outcome (Infarct, intracranial hemorrhage, mortality) (RR 0.823, 95% CI 0.765-0.885), mortality (RR 0.830, 95% CI 0.775-0.888), GI hemorrhage (RR 0.566, 95% CI 0.439-0.730), and cardiac arrest (RR 0.696, 95% CI 0.531-0.911). We found no significant difference in the risk of ischemic stroke (RR 1.024, 95% CI 0.744-1.408), intracranial hemorrhage (RR 0.587, 95% CI 0.270-1.280), systemic embolism (RR 0.828 (95% CI 0.512-1.339), or other cardiac arrythmias (RR 0.973, 95% CI 0.804-1.179).

Conclusion:
In individuals with AF and ESRD the use of rivaroxaban, in comparison to warfarin, was associated with a reduction in the risk of mortality, gastrointestinal hemorrhage, and cardiac arrest. We found no difference in other clinically relevant outcomes, including ischemic stroke. These findings suggest an extension of the safety benefits previously observed with DOACs to the ESRD population, however further research is needed to guide management.
Abstract 4142152: Different Determinants of Thrombotic Events in Transthyretin Cardiac Amyloidosis versus Other Left Ventricular Hypertrophy Phenotypes
Authors: Ozbay Benay , Rearick Corey , Satyavolu Bharadwaj , Soman Prem , Wong Timothy , Azhar Abdullah , Katz William , Sade Leyla Elif
Published: November 2024

Background:
Thrombotic events (TE) are more frequent in cardiac amyloidosis (CA) as compared to other phenotypes of left ventricular hypertrophy (LVH) the absence of regional wall motion abnormalities.

Aim:
We sought to investigate the determinants of TE in patients with transthyretin cardiac amyloidosis (ATTR-CA).

Method:
Among subjects referred to our CA center those with LVH (interventricular septum thickness ≥ 1.2 cm) were included consecutively. Patients with hypertrophic obstructive cardiomyopathy, light chain CA or mitral valve disease were excluded. All subjects underwent echocardiography with speckle tracking imaging, Tc-99m pyrophosphate scintigraphy, serum and urine immune electrophoresis as per the registry protocol. Cardiac magnetic resonance imaging and endomyocardial biopsy were performed for diagnosis as needed. Control group consisted of subjects with non-amyloidosis LVH. Patients were followed-up over 5 years for TE (ischemic stroke, peripheral emboli, intracardiac thrombus).

Results:
In all, 149 ATTR-CA and 133 LVH patients (24 non-obstructive hypertrophic cardiomyopathy, 18 aortic stenosis, 91 hypertensive cardiomyopathy) were studied. Maximal LA volume index (LAVImax) did not increase significantly with atrial fibrillation (AF) in the ATTR-CA group, unlike in the LVH group. In the ATTR-CA group left atrial reservoir strain (LASr) was significantly reduced (10.2±4.8 vs 16.1±8.1, p<0.001) and LA stiffness (LASr/E/e’) significantly increased (2.4±1.6 vs 1.3±1.0, p<0.001) as compared to the LVH group. CHA
2
DS
2
-VASc was similar in both groups. (p=0.376). The comparison of patients with and without TE is presented in the table (Figure 1). In the ATTR-CA group, a higher percentage of patients (74%) were in or developed new AF versus the LVH group (55%) (p<0.001). In the LVH group, AF (hazard ratio (HR): 10, 95% confidence interval (CI), 2.4-42.2, p=0.024) and CHA
2
DS
2
-VASc (HR: 3.6, 95% CI, 1.52-8.48, p=034) were the independent determinants of TE. Whereas, in the ATTR-CA group LASr (HR: 0.85, 95% CI, 0.74-0.97, p=0.021) and LA stiffness (HR: 1.54, 95% CI, 1.18-1.99, p=0.001) emerged as independent determinants of TE among relevant covariates (AF, CHA
2
DS
2
-VASc, LAVImax), (Figure 2).

Conclusion:
In ATTR-CA LA remodeling is associated with TE irrespective of AF or CHA
2
DS
2
-VASc. Whereas AF and CHA
2
DS
2
-VASc are the main determinants of TE in other LVH phenotypes. These findings have potential implications to develop empirical anticoagulation strategies.
Abstract 4142177: Structure-Function Alterations in Satellite Glial Cell-Neuronal Communication Underlie Sympathetic Hyperactivity after Myocardial Infarction
Authors: Lin Ruizhu , Zhao Yutian , Ang Kaitlyn , Sharma Sachin , Arreola Nigel , Ettipio Joseph , Ahn In Sook , Valenzuela Ripoll Carla , Javaheri Ali , Yang Xia , Ajijola Olujimi
Published: November 2024

Background:
Hyperactive cardiac sympathetic signaling characterizes chronic myocardial infarction. Although satellite glial cells (SGCs) regulate cardiac neuronal function, their role in mediating sympathetic hyperactivity following chronic myocardial injury remains poorly understood.

Research Questions:
The aim of the present study was to investigate the impact of cardiac injury on SGCs and SGC-neuronal communication in the stellate ganglion.

Methods:
Glial-specific reporter mice (7-9wks) with Cre-dependent tdTomato expression under the glial fibrillary acidic protein (GFAP)
+
promoter were randomized to sham or myocardial infarction (1, 2 or 4wks) verified by echocardiography. Stellate ganglions from mice received closed chest ischemia reperfusion (CCIR) were subjected to single nuclei RNA sequencing (snRNAseq) to glean transcriptomic profiles of glia and neurons, as well as ultrastructural imaging for high-resolution morphological analyses.

Results:
Following infarction, progressive LV dysfunction was confirmed by echocardiography at 1, 2, and 4wks in comparison with sham. High-resolution imaging of ganglia showed that SGCs exhibited a diminished cell structure with reduced process length at 4wk post-infarction. SnRNAseq in stellate ganglions of mice revealed two subpopulations of SGCs (GC1&GC2). GC1 exhibited greater expression of satellite glial markers (e.g. ApoE and Fabp7), while GC2 had enriched components related to myelination. In sham mice, GC1 accounted for the majority of SGCs (>75%), whereas CCIR shifted the main type from GC1 towards GC2 over time, with GC2 representing >80% glia 4wks post-CCIR. Pathway analysis of differentially expressed genes (4wk CCIR
vs
sham) showed enrichment of neural structure-related pathways, including synapses, axons and dendrites, in both GC1 and GC2 compared to sham. Moreover, cell-cell communication analysis indicated that compared to the change of GC1, GC2 became more interactive with sympathetic neurons, which used acetylcholine as the key neurotransmitter.

Conclusion(s)
In totality, these findings indicate that cardiac injury alters the morphology, distribution, and function of SGCs and their interaction with cardiac sympathetic neurons. These findings implicate a role of SGCs in post-injury sympathetic hyperactivity.
Abstract 4142182: Epicardial Adipose Tissue Association with Fibrotic Substrate Distribution and Rotor-attracting Locations: A Study Using Contrast Computed Tomography (CCT) Scans and Late Gadolinium Enhancement Magnetic Resonance Imaging (LGE-MRI)-based Digital Twins of Persistent Atrial Fibrillation
Authors: Sakata Kensuke , Prakosa Adityo , Yamamoto Alves Pinto Carolyna , Ali Syed Yusuf , Loeffler Shane , Kholmovski Eugene , Trayanova Natalia
Published: November 2024

Introduction:
Since pulmonary vein isolation (PVI) is often insufficient for persistent atrial fibrillation (PsAF) treatment, rotor ablation targeting AF drivers/substrates has been conducted as potential effective strategy. Recently, substrate location capable of attracting rotor (LR) has been reported to be associated with local fibrosis features. Meanwhile, epicardial adipose tissue (EAT) has been shown to be linked to developing fibrosis and arrhythmogenic substrates. Currently it is not well understood how EAT is related to the LR, and local fibrosis features. Personalized LGE-MRI-based digital twins (DTs) and cardiac CCT can be employed to investigate this.

Hypothesis:
EAT detected in CCT is correlated with LRs having specific local fibrosis features.

Aim:
To investigate the correlation between EAT, LRs, and the corresponding local fibrosis features using the merging of LGE-MRI-based DTs and CCT.

Methods:
Both LGE-MRI and CCT were acquired in 19 consecutive PsAF patients. Bi-atrial DTs incorporating the fibrosis distribution were created, wherein, following virtual PVI, LRs were identified by rapid pacing from 40 bi-atrial sites near fibrosis. In silico ablation was repeated until non-inducibility of rotors (Fig). EAT segmented from CCT and DT were compared after merging them using the bi-atria and 4 PVs as reference points. The distance from each tissue type in DT to the closest EAT (DCE) was calculated. The correlation between local fibrosis density feature (FD) and the median DCE at LRs was analyzed. For each LR, both volumetric FD (vFD) and endo-epi surface FD (sFD), subtracting epicardial surface FD from the endocardial surface FD to measure the dissociation of Endo-Epi surface FDs, were calculated.

Results:
Among 17 DTs excluding 2 without qualified CCT images, 15 DTs had 95 extra-PVI LRs in total. The DCE of fibrotic tissues (16%) was significantly shorter than that of normal tissues (84%) (p<0.001). The DCE of tissues within LRs (2%) was also significantly shorter than outside LRs (98%) (p<0.001). The mean DCE among 95 LRs was 4.1 mm. The vFD of the LRs with DCE <4.1 mm (56 LRs) was comparable to that of LRs with DCE ≥4.1 mm (39 LRs) (p=0.543). However, the sFD was significantly higher for LRs with DCE ≤4.1 mm (p=0.010).

Conclusions:
EAT is associated with fibrotic tissue and LR. Higher sFD suggests shorter DCE is linked to higher FD on the endocardial surface at LRs. Detecting EAT with CCT could be useful for evaluation and ablation of PsAF substrate.
Abstract 4142197: Abbreviated Ticagrelor-Based Dual Antiplatelet Therapy in Acute Coronary Syndrome: A Systematic Review and Meta-Analysis
Authors: Harmouch Wissam , Thakker Ravi , Khalid Umair , Khalife Wissam , Kleiman Neal , Rangasetty Umamahesh , Kayani Waleed , Jneid Hani , Al Hemyari Bashar , Elbadawi Ayman
Published: November 2024

Introduction:
Few randomized clinical trials (RCTs) have evaluated the safety and efficacy of abbreviated Ticagrelor-based dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS); however, these RCTs were underpowered to detect differences in hard clinical outcomes.

Research Question:
What effect does abbreviated Ticagrelor-based DAPT have on risk of ischemic and bleeding events in ACS?

Methods:
A systematic search of MEDLINE, Cochrane, and Scopus databases was performed through 05/2024, for trials that compared abbreviated (≤ 3-months) versus standard 12-months Ticagrelor-based DAPT in ACS. The primary endpoint was all-cause mortality. Endpoints were measured at 12-months after DAPT initiation. Data were pooled using random-effects model. Heterogeneity was assessed via Chi-squared and Higgin’s I
2
test. RevMan 5.0 (Cochrane Collaboration, Oxford, United Kingdom) was utilized to perform statistical analysis.

Results:
Five trials were included in this analysis with 21,407 patients assessed. ULTIMATE-DAPT, T-PASS, and GLOBAL LEADERS-ACS assessed 1-month DAPT duration while TICO and TWILIGHT-ACS assessed 3-months DAPT duration. The average age was 62.7 years and 22.7% were women. Hypertension (61.7%), dyslipidemia (49.9%), diabetes (27.8%), and chronic kidney disease (12.7%) were the most common comorbidities. ACS presentations included NSTEMI (40.1%), unstable angina (35.2%), and STEMI (31.5%). Abbreviated Ticagrelor-based DAPT was associated with lower risk of all-cause mortality (RR 0.78; 95% CI 0.62-0.98, I
2
=0%) compared with standard duration DAPT. There was no differences between groups in cardiovascular death (RR 0.65; 95% CI 0.41-1.03, I
2
=0%), myocardial infarction (RR 1.04; 95% CI 0.85-1.27, I
2
=0%), stent thrombosis (RR 0.97; 95% CI 0.64-1.45, I
2
=0%), or ischemic stroke (RR 0.90; 95% CI 0.62-1.30, I
2
=0%). Abbreviated DAPT duration was associated with lower risk of major bleeding (RR 0.50; 95% CI 0.38-0.66, I
2
=46%).

Conclusion:
Our analysis includes the totality of randomized data evaluating the merits of abbreviated Ticagrelor-based DAPT after ACS. The salient study finding was the observed reduced risk of all-cause mortality with abbreviated DAPT approach, which was driven by reduced bleeding risk.
Abstract 4142198: The Fontan Circulation Demonstrates Premature Biologic Aging
Authors: Vincent Annabelle , Woo Jennifer , Reddy Sushma , Ichimura Shoko , Kushwaha Ankit
Published: November 2024

Background:
Patients with single ventricle congenital heart disease palliated to Fontan circulation have increased all-cause mortality compared to age-matched controls. The reason for this increased mortality is not clear and cannot be fully explained by the underlying cardiac disease alone. We hypothesize that premature biologic aging contributes to this increased mortality.

Methods:
We collected demographic, clinical data and blood from patients with Fontan circulation and controls with structurally normal hearts. We assessed biologic age using telomere length (TL) measured by quantitative PCR from buffy coat DNA. Telomeres are repeating nucleoprotein structures at the end of chromosomes which shorten with age. Between group differences were assessed using t-test. Data was presented as mean±SD and p<0.05 was considered significant.

Results:
Mean age was 15.6±8.1 years in the Fontan cohort (N=122) vs. 18±15.8 years in controls (N=30). 63% were males in the Fontan cohort vs. 73% in controls. The Fontan cohort had a trend toward shorter TL vs. controls (1.07±0.15 vs. 1.17±0.2; p=NS). The TL difference of 0.1 suggests that the Fontan cohort is 9 years biologically older than controls. In both groups, there was a trend towards shorter TL with increasing age but was most prominent in Fontan cohort (Fig a). Patients with single right ventricles had shorter TL vs. those with single left ventricles (1.04±0.17 vs. 1.10±0.2; p=0.03), with the single right ventricle patients being 5.4 years biologically older (Fig b). The hypoplastic left heart syndrome cohort had the shortest TL of 1.0±0.14 (15 years biologically older than control) and the most co-morbidities: protein losing enteropathy (20.4%), pulmonary hypertension (6%), endocarditis (2%), stroke (12%) and cirrhosis (2%) compared to the other groups. Interestingly, there was no association between TL and systolic ventricular function by echocardiogram.

Conclusions:
We show for the first time, premature biologic aging in the Fontan circulation, its association with increased comorbidities and with single right ventricles being most at risk. Premature aging may predispose to heightened all-cause mortality and predispose to early onset of age-related diseases.
Abstract 4142203: Reducing reperfusion injury in circulatory death hearts with calpain inhibitor
Authors: Chen Qun , Kiernan Zachary , Labate Gina Marie , Quader Mohammed
Published: November 2024

Background:
Donation after Circulatory Death (DCD) donor hearts are rarely utilized for transplantation following more than 30 minutes of ischemia. Calpains 1 and 2 (CPN1/2) are ubiquitous proteases known to exist in cytosol and mitochondria that significantly contribute to reperfusion injury by degrading the ND5 (NADH dehydrogenase subunit 5) and releasing apoptosis inducing factor (AIF). We elected to study the role of CPN1/2 activation in the mitochondria and their inhibition on DCD heart reperfusion injury.

Hypothesis: In the DCD hearts mitochondrial CPN1/2 are activated and administration of MDL-28170 (inhibitor of CPN1/2) during reperfusion will decrease cardiac injury.

Methods:
Male Sprague-Dawley rats were divided in three groups: control beating-heart donors (CBD n=6) without ischemia, DCD with 35 minutes of global ischemia (n=6), and DCD with 35 minutes of ischemia and 10 minutes of reperfusion (n=7). Hearts were procured and mitochondria isolated. Immunoblotting was used to measure CPN1/2 activation. In a separate group of DCD hearts, to assess the protective effect of MDL, hearts were reperfused for 90 minutes on Langendorff setup with MDL (10 μM n=8) while the control DCD hearts were reperfused without MDL (n=7). At the end hearts were collected to measure infarct size using triphenyl tetrazolium chloride staining.

Results:
There were no significant differences in either AIF or ND5 contents between CBD and DCD ischemia alone hearts (Panel A and B). However, a marked decrease in the contents of AIF and ND5 occurred in DCD hearts mitochondria following reperfusion (Panel A&B) indicating that CLP1/2 were mainly activated in DCD hearts during reperfusion. Although MDL treatment did not markedly improve cardiac function during reperfusion (Panel C), it did decrease infarct size in DCD hearts (Panel D), indicating that cardiac injury can be decreased by inhibiting CPN1/2 in DCD hearts even following 35 minutes of ischemia.

Conclusion:
Timely administration of selective CPN1/2 inhibitor is a practical approach to decrease cardiac injury in DCD hearts subjected to prolonged period of ischemia.
Abstract 4142206: Shear Stress-based Purification Method for Human Pluripotent Stem Cell-derived Endothelial Cells
Authors: Abulaiti Mosha , Maihemuti Wusiman , Murata Kozue , Gonzalez-Teshima Laura , Yalikun Yaxiaer , Masumoto Hidetoshi
Published: November 2024

Background:
To apply human pluripotent stem cell-derived endothelial cells (hPSC-ECs) in regenerative medicine, exploring methods for highly purified ECs is desirable. Cell sorting is a versatile technique for isolating and purifying specific cell types, yet mechanical cell loss persists. Previously, we established a differentiation method for human induced pluripotent stem cell-derived ECs (hiPSC-ECs) based on lineage control using vascular endothelial growth factor (VEGF) and 8-Bromo cyclic adenosine monophosphate (cAMP). However, achieving high hiPSC-ECs purity without cell sorting has not yet been possible.

Hypothesis:
We speculated that applying digital rocker-generated shear stress during a specific period of hiPSC-EC induction would yield highly purified hiPSC-ECs without cell sorting.

Methods:
We applied cyclic share stress to the cultured cells using a digital rocker. To optimize the frequency and duration of digital rocker application, ECs purity on day 13 of differentiation (d13) was analyzed by flow cytometry for vascular endothelial cadherin (VE-Cadherin). Shear stress was measured using a simulation model. The functionality of ECs was evaluated through reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) for endothelial nitric oxide synthase (eNOS) and angiogenesis assay.

Results:
The optimized protocol consisted of a rocking period from day 5 (representing the EC progenitor stage) to d13, at 30 cycles/min with 13° tilt (equivalent to 1.09 dyn/cm
2
), which significantly increased the purity of ECs (Control vs Rocking: VE-Cadherin; 69.25±17.43 vs 86.68±6.023 %, P = 0.0090). Examining the number of cells on d13 revealed rocking stimulation reduced both ECs and non-ECs. Non-ECs were nearly absent, suggesting EC purification occurs by removing non-ECs, indicating ECs are more resistant to being eliminated by the rocking stimulation. The rocking culture also led to increased eNOS mRNA expression on d13 (Control vs Rocking: 0.5574±0.4985 vs 1.056±0.1652, P = 0.0393). The angiogenesis assay showed a longer vascular structure length trend in the rocking group, indicating enhanced angiogenic capacity. (Control vs Rocking: 15407±2929 vs 18335±3568 Pixel, P= 0.4309).

Conclusion:
In this study, we developed a method where digital rocker-generated shear stress during a specific period of hiPSC-EC induction not only selectively purifies ECs without cell sorting, but also enhances endothelial function, demonstrating their therapeutic potential.