bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146973: Surface Protein Profiling of Extracellular Vesicles: A Novel Biomarker Approach to detect heart allograft acute rejection
Authors: Ikeda Gentaro , Koike-Ieki Mariko , Inoue Hiroyuki , Tzng Eileen , Li Jiwen , Sierra Raymond , Wakatsuki Soichi , Valantine Hannah , Yang Phillip
Published: November 2024

Background:
After heart transplantation, endomyocardial biopsy is used to monitor for acute rejection (AR). However, endomyocardial biopsy is invasive, and its conventional histological interpretation has limitations. Extracellular vesicles (EVs) are lipid bilayer vesicles secreted by various cell types into the circulation. EVs express an array of biomolecules indicative of their parent cells and act as cargo vesicles capable of delivering nucleic acids, proteins, and organelles. Here, we investigated whether AR affects the surface markers and mitochondrial positivity of plasma EVs and explored their potential for detecting AR in cardiac transplant recipients.

Methods:
Plasma samples were collected from participants from the Genomic Research Alliance for Transplantation (GRAfT, sponsored by NIH). Histopathology data were collected to define AR. Patients with non-rejection (NR, N=6), acute cellular rejection (ACR, N=7), antibody-mediated rejection (AMR, N=5), and a combination of ACR and AMR (ACR/AMR, N=2) were employed. Plasma EVs were isolated from a total of 71 plasma samples using a size exclusion column (qEV, IZON Science). The size distribution and concentration of the plasma EVs were evaluated by nanoparticle tracking analysis. The positivity for surface markers was assessed by flow cytometry, including CD235a (erythrocytes), CD144 (endothelial cells), CD45 (leukocytes), CD3 (T cells), CD20 (B cells), CD14 (monocytes), and CD172a (cardiomyocytes). Additionally, the positivity for mitochondrial membrane potentials in each EV cluster was measured.

Results:
The concentrations and mean diameter of the plasma EVs were comparable among NR, AMR, and ACR groups (2.75 x 10
10
/mL, 9.61 x 10
9
/mL, and 2.70 x 10
10
/mL, and 192 nm and 211 nm, and 192 nm, respectively). The proportions of CD45 and CD172a-positive EVs were significantly increased in ACR/AMR compared to ACR or AMR alone. Additionally, mitochondrial markers within CD14-positive EVs exhibited a significant decrease in AMR. No significant trends were observed in the longitudinal EV profiles in each individual. Quantitative PCR confirmed that the expressions of mitochondrial DNA were decreased in the plasma EVs from AMR.

Conclusion:
CD172a, CD45, and mitochondrial positivity in CD14-positive EVs could serve as potential biomarkers for diagnosing AR in patients undergoing cardiac transplantation. These findings may offer insights into the pathogenesis of AMR.
Abstract 4146996: Trends in the Management and Outcomes of ST Elevation Myocardial Infarction with Cardiogenic Shock in Older Adults: Insights from US National Database
Authors: Kumar Manoj , Nso Nso , Ricciardi Mark , Arman Qamar
Published: November 2024

Background:
Due to increased life expectancy, there is increasingly high prevalence of myocardial infarction (MI) in older adults (age ≥75 years). Older adults tend to receive less guideline recommended treatment for MI due to associated frailty. We compare the management and outcomes in older adults with ST elevation myocardial infarction (STEMI) and cardiogenic shock (CS) as compared to adults age <75 years.

Methods:
Nationwide Readmissions Database (2016-2021) was analyzed to study patients with STEMI-CS. Cohort was stratified by age. Mahalanobis Distance Matching within the Propensity Score Caliper was used to match older adults (age ≥75 years) with patients age <75 years. Inverse Probability weighting (IPW) was utilized, and Pearson’s chi-squared test was applied to the PSM-2 matched cohorts to compare outcomes.

Results:
Among 177,874 hospitalizations of STEMI-CS, more than half (57.7%) were older adults (age ≥75). After propensity matching (N: 55,855 in each group), older adults were less likely to receive PCI (60.6% vs. 62.2%, aOR: 0.93 [95% CI], p <0.001) and had a higher mortality (45.2% vs. 33.9%, aOR:1.75 [95%CI], p <0.001) as compared to patients age <75 years. From the year 2016-2021, mortality of STEMI-CS has remained unchanged for older adults (mean: 43%) (p-trend >0.05). Moreover, an alarming decline for PCI for older adults was also noted (59.4% to 44%, p-trend<0.001).

Conclusion:
Older adults are less likely to receive PCI and have a higher mortality compared as to patients age <75 years when presenting with STEMI and cardiogenic shock. Focused initiatives are needed to improve STEMI care in older adults.
Abstract 4146997: S-nitrosylation of Aconitase-2 Facilitates Coronary Microembolization-induced Cardiac Injury by Suppressing Iron-sulfur Cluster Assembly
Authors: Chen Ao , Xia Yan , Che Xinyu , Chen Zhangwei , Qian Juying , Ge Junbo
Published: November 2024

Background:
Coronary microembolization (CME) is a common reason for periprocedural myocardial infarction after coronary interventions. S-nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in the pathogenesis of several cardiovascular diseases.

Purpose:
To explore the role of SNO of aconitase-2 (ACO2) in CME-induced cardiac injury, as well as the mechanism by which SNO-ACO2 modulates myocardial injury in response to CME.

Methods:
CME models were established in C57BL/6J mice by injecting 300,000 polyethylene microspheres (diameter 9 µm) into the left ventricle chamber with the occlusion of the ascending aorta. S-nitrosylated proteins and SNO sites of ACO2 were identified through LC-MS/MS analysis. De-nitrosylation of ACO2 was achieved by the mutation of SNO site or overexpression of the de-nitrosylation enzyme thioredoxin 1 (TRX1). Interacting effectors of SNO-ACO2 were screened through LC-MS/MS and confirmed by coimmunoprecipitation. Neonatal rat ventricular myocytes (NRVMs) were used for ACO2 enzyme activity analysis, mitochondrial morphology and function.

Results:
Cardiac injury was exacerbated by CME as demonstrated by impaired cardiac contractile function, increased fibrosis, microinfarct size. We identified 789 S-nitrosylated proteins in CME mouse hearts, and ACO2 is one of the highly S-nitrosylated proteins. The increased level of SNO-ACO2 was verified by immunoblot assay in CME mouse hearts and hypoxia-stimulated NRVMs. SNO site of ACO2 at cysteine 126 was identified by LC-MS/MS and confirmed in NRVMs. De-nitrosylation of ACO2 by the mutation of cysteine 126 or overexpression of TRX1 both greatly improved the activity of ACO2 by 39.7% and 31.4% respectively, further restored the mitochondrial function, and attenuated CME-induced cardiac injury. Mechanistically, SNO-ACO2 at cysteine 126 suppressed the interaction between ACO2 and NFU1, an iron-sulfur (Fe-S) cluster scaffold protein. The dissociation from NFU1 deprived ACO2 of the Fe-S cluster and the enzyme activity, thereby promoting the disruption of the mitochondrial tricarboxylic acid cycle and cardiac injury.

Conclusions:
Our data defined a previously unrecognized role of SNO-ACO2 in CME-induced cardiac injury. We demonstrated that SNO-ACO2 at cysteine 126 disrupted ACO2/NFU1 interaction to exacerbate myocardial injury after CME. Our results suggested that de-nitrosylation of ACO2 may provide a new therapeutic target for the treatment of CME.
Abstract 4147009: Advocacy in Cardiology: Healthcare lobbying and campaign finance activities of major cardiovascular professional societies, 2003 to 2023
Authors: Patel Prem , Milks Michael , Miller Andrew , Mehta Laxmi
Published: November 2024

Introduction:
Political advocacy is crucial for combating health inequities, improving population health, increasing funding of cardiovascular research, and promoting clinician wellbeing. The political activities of major cardiovascular organizations have not previously been characterized.

Methods:
Lobbying expenditures for six major cardiovascular professional societies were queried from OpenSecrets. Campaign finance data for three cardiovascular political action committees (PACs), ACC’s HeartPAC, SCAI-PAC, and STS-PAC, were obtained directly from the Federal Election Commission. Descriptive statistics of each organization’s lobbying expenditures and PAC donations from members were compared to other medical specialties. Data were aggregated per year to assess trends between 2003-2023.

Results:
From 2003-2023, the ACC and AHA spent $34,130,110 and $14,285,652 on lobbying, respectively. Other societies reported less robust and consistent lobbying expenditure over the study period: American Society of Echocardiography ($2,080,000), Heart Rhythm Society ($1,450,918), American Society of Nuclear Cardiology ($759,000), and Heart Failure Society of America ($140,000). Annually, the ACC and AHA spent more on lobbying compared to all other societies combined ($2,526,767 vs. $224,000). Temporal analysis revealed a meaningful increase for ACC, from $80,068 in 2003 to $1,890,000 by 2023 and a numerical decrease for AHA, from $570,000 in 2003 to $550,000 by 2023. Notably the American Society of Nuclear Cardiology and American Society of Echocardiography showed increases in annual lobbying expenditure over the study period ($10,000 to $90,000 and $40,000 to $200,000). HeartPAC and SCAI-PAC collected 19,326 donations from 2003-2023. HeartPAC received $7,015,821 from 6266 donors (median, $250) and SCAI PAC received $358,643 from 256 donors (median, $500). STS-PAC received $3,160,192 from 2231 donors (median, $500). Most donations to HeartPAC and SCAI-PAC came from cardiologists (95.5%), followed by administrators (1.0%) and executives (1.0%), and 2870 donations (14.9%) came from university-affiliated individuals.

Conclusion:
The ACC and AHA remain key stakeholders in cardiovascular lobbying efforts. Several other medical specialties raise >two-fold greater PAC contributions compared to cardiovascular medicine. With the rising importance of advocacy to affect issues facing clinicians, enhancing cardiovascular society engagement would be an important political strategy.
Abstract 4147021: Atorvastatin Therapy for Prevention of Anthracycline-Induced Cardiotoxicity in Cancer Patients: A Meta-Analysis
Authors: Bulhoes Elisio , Farias Carlos , Florindo Mayara , Fernandes da Silva Gustavo , Holmvard Oscar , Soares Silva Ana Laura , Carvalho Ferreira Andre , Sales Gabriel , Schneider Andre , Rayane Moura Roesch Heveline , Guida Camila
Published: November 2024

Introduction:
Cancer therapy-induced cardiac dysfunction is a significant adverse effect of chemotherapeutic agents, particularly anthracyclines (ANT). High-potency statin therapy, such as atorvastatin, appears to exert a protective effect against this condition.

Objective:
We aimed to perform a meta-analysis to evaluate the effect of atorvastatin therapy in preventing anthracycline-induced cardiotoxicity in cancer patients.

Methods:
We searched PubMed and Web of Science for randomized controlled trial (RCT) studies comparing atorvastatin prophylactic use to placebo in patients with cancer undergoing anthracycline-based chemotherapy. Outcomes were: mean change in left ventricular ejection fraction (LVEF), LVEF final, left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), LDL-c, cancer treatment related cardiac disease (CTRCD) and heart failure symptoms. A random effects model was used to calculate the risk ratios (RRs) and mean difference (MDs) with 95% confidence intervals. Statistical analysis was performed using the R program (version 4.3.2). Heterogeneity was assessed with I2 statistics.

Results:
Five RCTs with 831 participants were included. The median follow-up ranged from 1 to 24 months. The dose used in all studies was 40 mg. Breast cancer was present in 77% of the patients. In our analysis, atorvastatin prophylactic use was associated with a statistically significant lower LVEF final (MD 2.31 %; 95% IC [0,78; 3,84]; p<0.01; I2 =65%), LVESV (MD -4.50 mL; 95% IC [-7,57; -1,44]; p<0.01; I2 =0%), LVEDV (MD -6.08 mL; 95% IC [-11,27; -0,90]; p=0.02; I2 =0%), LDL-c (MD -38.11 mg/dL; 95% IC [-55,01; -21,20]; p<0.01; I2 =89%) and CTRCD (RR 0.42; 95% CI 0.28 - 0.65; p<0.001; I2 =0%). In addition, atorvastatin prophylactic use was associated with a statistically significant increased LVEF final (MD 2.31 %; 95% IC [0,78; 3,84]; p<0.01; I2 = 65%). There was no significant difference between groups in terms of mean change LVEF (MD 2.56 %; 95% IC [-0,20; 5,32]; p=0.07; I2 =89%) and heart failure symptoms (RR 0.40; 95% CI 0.14 - 1.18; p=0.097; I2 =0%).

Conclusion:
In conclusion, atorvastatin prophylactic use to placebo in patients with cancer undergoing anthracycline-based chemotherapy was associated with a reduction in LVESV, LVEDV, CTRCD and an increase in LVEF final. There was no difference between groups regarding mean change LVEF and heart failure symptoms.
Abstract 4147027: Apolipoprotein A-I Proteoforms, Cardiometabolic Status, and Coronary Heart Disease: Insights from the Dallas Heart Study
Authors: Gangwar Anamika , Soye Benjamin , Saldanha Suzanne , Jaiswal Shailesh , Patel Parthvi Bharatkumar , Shah Amil , Pandey Ambarish , Wilkins John , Rohatgi Anand
Published: November 2024

Background:
Coronary heart disease (CHD) is marked by dysfunctional high-density lipoproteins (HDL; impaired cholesterol efflux (CE), elevated oxidative stress, and inflammation). HDLs have a diverse proteome (>250 proteins), but simple protein abundances fail to fully capture its complexity and disease links. A proteoform is a specific molecular form of a protein that includes information of post-translational modifications (type, location, and combinations), which directly affect function. While HDL-associated apolipoproteins (apo), specially apoA-I, mediate HDL functions, it remains unknown whether apoA-I proteoforms are linked to CHD. Our prior work linking 15 apoA-I proteoforms to cardiometabolic traits supports uncovering proteoform-CHD relationships for mechanistic insight into CHD. This study aims to explore the spectrum of apoA-I proteoforms linked with incident CHD.

Method:
From Dallas Heart Study cohort (>2,000 participants without prevalent CVD at baseline), 33 incident myocardial infarction (MI) cases during follow-up and 32 matched controls (age, sex, and race/ethnicity) were selected. We analyzed plasma using top-down proteomics to quantify apoA-I proteoforms. Unadjusted associations of apoA-I proteoforms with cardiometabolic traits were stratified by CHD status and analyzed using correlation analysis.

Results:
Mean age was 56 years (45% women, 66% Black and 9% Hispanic). We identified 15 apoA-I proteoforms. Proteoform abundances were similar in cases vs. controls, the direction and magnitude of associations with cardiometabolic traits varied substantially. E.g., canonical (unmodified) apoA-I was positively correlated with oxidized LDL (Ox- LDL) in incident MI cases, but not in controls. Acylated apoA-I proteoforms showed different correlation directions with CE, TG and Ox-LDL in controls vs incident MI (Fig.1,
p
<0.05).

Conclusion:
We observed different patterns of association between apoA1 proteoforms and cardiometabolic traits in individuals who experienced CHD events compared to those who did not. These findings suggest that proteoform biology may vary and be involved in CHD pathogenesis. Further investigation in larger cohorts may unveil therapeutic targets for CHD, improving patient outcomes.
Abstract 4147030: Innovative Use of Large Language Models to Diagnose Pericarditis in Patients Referred to a Tertiary Center for Uncertain Diagnosis
Authors: El Hajjar Abdel Hadi , Motairek Issam , Rosenzveig Akiva , Syed Alveena , Kassab Joseph , Al-Dalakta Astefanos , Klein Allan
Published: November 2024

Background:
Accurate pericarditis diagnosis is challenging due to its subtle signs and wide differential diagnoses. Large language models such as Chat GPT-4 have been previously used to answer medical questions, but their efficacy in diagnosing medical conditions is unknown.

Research Question:
Can Chat GPT-4 accurately diagnose pericarditis in patients referred to a tertiary center for suspected pericarditis?

Aim:
We aim to evaluate the predictive capacity of a widely available AI tool (Chat GPT-4) for pericarditis diagnosis.

Methods:
Patients referred to the Cleveland Clinic Pericardial Center for suspected pericarditis were enrolled in a prospectively maintained registry between September 2022 and September 2023. Pericarditis diagnosis was confirmed by two physicians based on the 2015 ESC guidelines. The AI tool was provided with patient demographics, comorbidities, presenting symptoms, laboratory values and imaging findings. Chat GPT-4 was asked: “What is the probability that the patient has pericarditis?”. A probability >0.5 was considered a positive pericarditis diagnosis by Chat GPT-4. Predictions were compared to physician-based diagnosis to construct a contingency table.

Results:
The total number of patients enrolled in the study was 170, out of which 110 were diagnosed with pericarditis. Chat GPT-4 diagnosed pericarditis in 62 patients. Physician-based diagnoses and Chat GPT-4’s diagnoses are displayed in the contingency table attached. The AI tool was able to predict pericarditis diagnosis with a Sensitivity of 52% (95% CI: 43% to 61%) and a Specificity of 94% (95% CI: 87% to 98%). In the studied population, Chat GPT-4’s Positive Predictive Value was 93% (95% CI: 87% to 98%) and its Negative Predictive Value was 53% (95% CI: 44% to 62%). Overall, Chat GPT-4 demonstrated an AUC of 0.73, indicating a moderate level of diagnostic accuracy.

Conclusion:
Chat GPT-4 can be used to support the diagnosis of pericarditis (rule in) in patients with suspected disease. However, it has poor sensitivity and cannot be used in the initial workup. Further studies are warranted to assess its application in clinical practice.
Abstract 4147050: Genetic Insights into Arrhythmogenic Mitral Valve Prolapse – A Case-Control Study from UK Biobank and NIH All of Us
Authors: Sharaf Dabbagh Ghaith , Hesse Kerrick , Agnihotri Ruchi , Kaur Gurpreet , Gurumoorthi Manasa , Shah Ravi , Asatryan Babken , Galanti Kristian , Wolfe Rachel , Mitchell Saige , Pargament Robert , Malik Adnan , Schuler Brian , Munroe Patricia , Obeng-Gyimah Edmond , Somers Virend , Ricci Fabrizio , Khanji Mohammed , Landstrom Andrew , Chahal Anwar
Published: November 2024

Background:
Mitral valve prolapse (MVP) is a common valvular abnormality. Observational studies demonstrate an association between MVP and increased risk of sudden cardiac death from ventricular arrhythmias, coined arrhythmogenic MVP. A genetic component has been postulated but remains under-investigated.

Hypothesis:
Predicted deleterious variants in Mendelian cardiomyopathy and arrhythmia genes are more frequent in arrhythmogenic MVP (aMVP) compared to non-arrhythmogenic MVP.

Aims:
To comprehensively phenotype and genotype a single-center
aMVP
cohort and compare to
non-aMVP
from two large population-based cohorts and investigate their clinical outcomes.

Methods:
The
aMVP
cohort included 46 prospectively enrolled patients from a regional referral center for inherited cardiovascular disease and had undergone multi-modality imaging and clinical gene panel testing.

The
non-aMVP
comparator cohorts included 453 participants from the UK Biobank (UKBB), a prospective cohort of 500,000 UK residents, and 1,418 participants from the National Institutes of Health (NIH) All of Us (AoU), a prospective cohort of 450,000 USA participants. Gene variants were annotated in ANNOVAR. Participants with and without pathogenic/likely pathogenic (P/LP) variants reported on ClinVar with ≥2-star level of evidence were considered genotype positive (G+) and negative (G-) respectively.

Results:
The demographics for
aMVP
(age 61.2 ± 12.8 years, 56.5% female) and
non-aMVP
(UKBB: age 59.8 ± 7.3 years, 50.7% female and AoU: age 65.3 ± 13.4 years, 76.2% female) were comparable.

G+ participants were more prevalent in the
aMVP
cohort 10/46 (21.7%) versus
non-aMVP
in the UKBB 8/453 (1.8%) and in the AoU 21/1418 (1.5%); p<0.001. The most frequently implicated gene in
aMVP
was
TTN
.

Of 46 in
aMVP
cohort, 33 (71%) underwent CMR. G+ participants had a higher frequency of late gadolinium enhancement [6/6 (100%) vs. 14/27 (51.8%), p<0.001] and wall motion abnormalities [3/6 (50%) vs. 1/27 (3.7%), p<0.001] compared to G- participants.

The
aMVP
cohort had significantly more implantable cardioverter defibrillator (ICD) implants compared to
non-aMVP
cohort [5/46 (10.9%) vs. 1/453 in UKBB (0.2%), p<0.001]. G+
aMVP
cohort showed a trend for developing heart failure and ICD implants compared to G-
aMVP
.

Conclusion:
P/LP variants in cardiomyopathy and arrhythmia genes are more prevalent in
aMVP
participants compared to
non-aMVP
participants. This could be a hitherto unrecognized effect modifier predicting
aMVP
.
Abstract 4147060: Artificial Intelligence-based improvement of smartwatch detection of AF
Authors: Wan Elaine , Glotzer Taya , Mittal Suneet , Senepart Oceane , Lefebvre Baptiste
Published: November 2024

Introduction:
Cardiac arrhythmias, such as atrial fibrillation (AF), are a common health problem. Standard 12-lead electrocardiograms (ECGs) and Holter monitors may not detect them due to their brief recording duration. There is increasing consumer use and demand for Smartwatch (SW), and herein we investigate the use of an AI algorithm (Philips Cardiologs) on the Apple Watch to improve detection of AF.

Hypothesis/Objective:
Evaluate the performance of the AI algorithm on a SW in detecting AF in comparison to physician interpretation on the 12-lead ECG among patients undergoing cardioversion.

Methods:
220 patients from 3 different US hospitals undergoing a cardioversion were included in the study. A SW single lead and a standard 12-lead ECGs were obtained before and after the procedure. 12-lead ECGs were annotated and adjudicated by three expert electrophysiologists as 91.3% AF before the procedure, 4.1% after the procedure and 49.3% of total ECGs were AF. The study design allowed us to reach a high AF:Sinus Rhythm (SR) ratio for the total ECGs dataset. The Apple ECG App 2.0 and the AI algorithm both processed the SW-ECGs to classify them as AF, SR or inconclusive and their performances were compared.

Results:
Among the 383 simultaneous combinations of single and 12-lead ECGs, the algorithm obtained a sensitivity of 91.21% (95% CI, 86.12%-94.89%) and a specificity of 91.48% (95% CI, 86.33%-95.15%) for AF detection. Among the same dataset, the ECG App 2.0 from Apple Watch yielded inconclusive diagnoses for 12.5% (48/383) of all SW-ECGs while the AI algorithm reduced that number to 6.5% (25/383) and reached a sensitivity and specificity of 82.9% (95% CI, 76.44%-88.12%) and 95.6% (95% CI, 91.19%-98.22%) for AF detection.

Conclusions:
The Philips Cardiologs AI algorithm has demonstrated strong performances in the detection of AF and SR. In comparison to the Apple Watch, the AI algorithm significantly reduced the number of inconclusive diagnoses by half (p=0.0023, Z-test), thereby significantly improving diagnostic outcomes. This AI driven ECG analysis could enhance detection of AF in SW. Further efforts are warranted to extend the achieved performance to encompass the detection of additional types of arrhythmias.
Abstract 4147061: Left Atrial Epicardial Adipose Tissue Is Associated with Worse Left Ventricular Strain in Atrial Fibrillation Patients
Authors: Kassar Ahmad , Chamoun Nadia , Chahine Yaacoub , Akoum Nazem
Published: November 2024

Background:
Atrial fibrillation (AF) is associated with abnormal left ventricular systolic and diastolic function. While left atrial epicardial adipose tissue (LA-EAT), a metabolically active visceral fat deposit has been associated with worse phasic left atrial strain, its effect on left ventricular (LV) function in AF patients is not well elucidated.

Hypothesis:
AF patients with increased LA-EAT have worse LV function.

Aims:
Assess the association between LV function in terms of global longitudinal strain (GLS) and global radial strain (GRS) and LA-EAT in AF patients.

Methods:
Patients were identified from the University of Washington Cardiac Arrhythmia Data Repository (CADRe). EAT volume was quantified using Dixon MRI sequences. The Cardiac Electro-Mechanic Research Group Application’s (CemrgApp) built-in tools were used to contour left atrial epicardial adipose tissue and total epicardial adipose tissue volume using Dixon sequences (panel A). Cardiac magnetic resonance cine images were used to extract GLS and GRS using image processing software (CVI42®) (panel B).

Results:
A total of 101 patients (average age 64 ±11 years; 72.3% male) were included. LA-EAT index was 18.22 ± 9.36 ml/m
2
. The median LV ejection fraction (LV-EF) was 57.6%±11.5. LV GLS and GRS were -14.86% ± 3.74% and 27.67%± 10.22% respectively. LA-EAT was significantly correlated with LV GLS (R=0.261; p=0.008) and GRS (R=0.283; p= 0.004); but not with LV-EF (R=0.134; p=0.181) (panel C). Multivariate linear regression also showed an independent association between LV GLS and GRS along with LA-EAT after adjusting for body mass index, left atrial volume, and congestive heart failure.

Conclusion:
LA-EAT is independently associated with worse LV global longitudinal strain and global radial strain. LA-EAT may negatively affect LV function in AF patients beyond the ejection fraction.
Abstract 4147077: Early Reported Events with the TriClip™ System for Transcatheter Tricuspid Valve Repair: Insights from FDA's MAUDE Database
Authors: Khanna Tejasvini , Futela Pragyat , Bansal Kannu , Chatterjee Arka
Published: November 2024

Background:
Tricuspid regurgitation (TR) worsens heart failure symptoms and perpetuates right ventricular failure (RVF). Given the limited efficacy of medicines and high risk of surgical mortality, percutaneous therapeutic options are gaining importance. The TRILUMINATE study reported an 86% reduction in TR severity and 4% mortality rate using Triclip G4 tricuspid transcatheter edge-to-edge repair (T-TEER) system with improvement in health status. Triclip subsequently gained FDA approval for TR on April 2, 2024.

Objective:
To evaluate reported device and patient related adverse events during early experience with Triclip system for T-TEER.

Methods:
The events reported for Triclip since it gained FDA approval were extracted from the FDA MAUDE database. Previously published reports, duplicates and events before FDA approval were excluded. Grades of TR at baseline and after T-TEER associated with single leaflet device attachment (SLDA) were compared using Wilcoxon rank sum test.

Results:
After excluding 14 reports, 45 were included, dating from 04/02/24 to 05/31/24. Of these, 31 (67.4%) featured patient complications, with SLDA being the most frequent (n=24, 53%).(Figure-1) Cause of SLDA was reported in 8 reports.(Figure-2) SLDA led to regression of TR to pre-procedure levels in 10 patients and Polymorphic VT in one patient. Other patient issues included damage to leaflets (n=7, 15.6%) which necessitated surgery in one case and prompted consideration of the same in another. There were 4 reports of clip entrapment in the chordae. Device-related issues included 3 cases of leaks in the steerable guide catheter affecting its ability to hold the column, knotting on the lock line, difficulties with positioning the second clip above the valve, clip reopening beyond the expected 5°, clip opening while locked but staying closed post-deployment, delays in clip delivery, and challengers in guiding catheter positioning. No acute deaths were reported in the MAUDE database within 2 months of device approval.

Conclusion:
Our research findings summarize the reported adverse events during the early period following FDA approval of Triclip G4 T-TEER system. This provides valuable insights into common failure modes and complications, offering guidance on their optimal utilization. Multiple adverse events can be noted soon after approval of the Triclip, underscoring the importance of good initial training and proctoring.
Abstract 4147079: Effects of Oral LT3 in Participants with Isolated Low T3 levels and Heart Failure: A Randomized, Placebo-controlled, Crossover Trial
Authors: Cappola Anne , Gallop Robert , Lin David , KOBALY KRISTEN , Chirinos Julio , Cappola Thomas
Published: November 2024

Introduction:
Observational studies in heart failure (HF) patients have shown that low levels of the thyroid hormone triiodothyronine (T3) with otherwise normal thyroid testing (‘low T3 syndrome’) is a risk factor for adverse clinical outcomes. Preclinical studies have shown beneficial effects from T3 therapy on myocardial contractility, myocardial relaxation, and vascular resistance, but human studies are lacking.

Research Question:
In patients with HF and low T3 syndrome, is oral liothyronine (LT3) safe, and does it impact cardiovascular clinical and physiologic phenotypes?

Aims:
Primary aim: To evaluate the safety of oral LT3 therapy in HFrEF and HFpEF. Secondary aim: To evaluate the feasibility and preliminary efficacy of oral LT3 therapy in HFrEF and HFpEF.

Methods:
A total of 28 participants with HFrEF and 28 with HFpEF aged 18+ years enrolled in a single-center, randomized, double-blind, placebo-controlled, crossover trial and were prescribed LT3 or placebo for 8 weeks with a 2-week washout period. Primary outcomes were safety as assessed by T3 level; arrhythmic events by EKG, 14-day adhesive patch monitoring, and ICD (HFrEF only); and adverse events. Secondary efficacy outcomes included Kansas City Cardiomyopathy Questionnaire, NT-proBNP level, peak O2 consumption during a cardiopulmonary exercise test, and actigraphy. Secondary mechanistic outcomes included non-invasive assessments of cardiac and arterial function measured via echocardiography and arterial tonometry.

Results:
Low T3 syndrome was present in 20% of screened participants. After LT3 treatment, T3 levels markedly increased compared with placebo. Heart rate was higher on LT3 (mean difference 2.4 beats per minute, p <0.05), but otherwise, primary safety and secondary efficacy endpoints were not different between LT3 and placebo. In HFrEF participants, secondary mechanistic endpoints indicated an increase in LV ejection fraction and the intensity of forward compression and backward suction waves generated by the LV (p <0.05), despite GDMT and beta-blockade.

Conclusion:
In participants with HF and low T3 syndrome, oral LT3 titrated to T3 levels in the upper reference range was safe. LT3 increased heart rate, and, among HFrEF participants, increased LV ejection fraction and other parameters of LV inotropic and lusitropic function. A larger clinical trial of LT3 in HFrEF patients with low T3 syndrome is required to determine if these efficacy signals translate into clinical benefit.
Abstract 4147083: Incidental and progressive tobacco smoking from childhood through young adulthood with premature structural and functional cardiac damage in 1931 children: A 14-Year Longitudinal Study
Authors: Agbaje Andrew
Published: November 2024

Background:
Tobacco smoking in adolescence has been associated with increased risk of premature death in mid-forties. However, due to the scarcity of repeated measures of cardiac structure and function in a large cohort of children and adolescents, there is limited knowledge regarding the independent associations of initiating and progressive tobacco smoking with premature cardiac damage in apparently healthy youth. The earliest manifestation of the cardiovascular consequence of tobacco smoking is critical for public health intervention and preventive cardiology.

Purpose:
To investigate the incidence of tobacco smoking during growth from childhood through young adulthood and the longitudinal association of tobacco smoking with structural and functional cardiac damage.

Methods:
From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1931 children had questionnaire-based smoking status assessed at ages 10, 13, 15, 17 and 24 years clinic visits were included. Repeated echocardiography measured left ventricular mass indexed for height
2.7
(LVMI
2.7
), relative wall thickness (RWT), LV diastolic function from mitral E/A ratio (LVDF), and LV filling pressure from E/e ratio (LVFP) were available at ages 17 and 24 years. LVMI
2.7
≥51g/m
2.7
, RWT ≥0.44, LVDF<1.5, and LVFP ≥8 were categorised as LV hypertrophy, high RWT, LVD dysfunction, and high LVFP, respectively.

Results:
Among 1931 children (mean [SD] age at baseline was 10.6 [0.26] years; 1211 [62.7%] females]) the prevalence of smoking was 0.3%, 1.6%, 13.6%, 24%, and 26.4% at ages 10, 13, 15, 17, and 24 years, respectively. The prevalence of LV hypertrophy increased from 2.8% to 7.5% at age 24 years while LVD dysfunction prevalence increased from 10.4% to 16.9%. In a fully adjusted model, persistent smoking from childhood through young adulthood was significantly associated with higher odds of LV hypertrophy (odds ratio 1.52; [95% CI, 1.39 – 1.66], p<0.001), high RWT (1.38; [1.26 – 1.51], p<0.001), LVD dysfunction (1.33; [1.22 – 1.46], p<0.001), and high LVFP (1.35; [1.25 – 1.45], p<0.001) at age 24 years. Persistent smoking from childhood contributed 0.46g/m
2.7
(0.17 – 0.75) of 2.84g/m
2.7
increase in LVMI from ages 17 – 24 years.

Conclusion:
Tobacco smoking from childhood through young adulthood was prospectively associated with structural and functional cardiac damage and contributed 16% to cardiac mass increase between ages 17 to 24 years.
Abstract 4147087: Impact of fractional flow reserve measurement on outcomes in the invasive arm of the ISCHEMIA trial
Authors: Singh Ayesha , Rodman John , Brown David
Published: November 2024

Introduction:
Fractional flow reserve (FFR) is an invasive, lesion-specific surrogate for myocardial ischemia. The use of FFR to guide lesion selection for revascularization has been shown to improve outcomes compared to an angiographic approach because it allows revascularization of lesions based on hemodynamic significance.

Purpose:
To compare the outcomes of patients randomized to the invasive (INV) arm of the ISCHEMIA trial who underwent FFR during initial angiography with those whose treatment was guided by angiography alone.

Methods:
The ISCHEMIA data set was obtained from the NHLBI. Subjects randomized to the INV arm who underwent FFR were compared to those who underwent angiography alone. Unadjusted cumulative event probabilities were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analysis was used to estimate the independent impact of FFR on outcomes. Primary endpoint of interest was cardiovascular death (CV) death or MI.

Results:
Of the 5,179 patients with chronic coronary syndromes and at least moderate ischemia on stress testing, 2,588 were randomized to the INV strategy, 2,475 underwent angiography and 2,210 had baseline data available for analysis. Of these, 410 (19%) had FFR performed during diagnostic angiograms. Females comprised 24% of FFR patients and 24% of non-FFR patients (P=0.85). FFR patients were older than non-FFR patients (65.7 [8.7] years vs. 64.3 [9.6] years, P=0.006). The incidence of hypertension, diabetes, smoking, or prior MI at baseline did not differ between groups. Fewer FFR patients had severe ischemia at baseline (45% vs. 52%) and more had mild or moderate ischemia (54% vs. 48%) (P=0.009). FFR patients had less extensive disease as manifested by fewer native vessels with >70% stenosis than non-FFR patients (1.0 [0.9] vs. 1.5 [1.0], P<0.001) and less complex disease as assessed by the Duke jeopardy score (P<0.001). After 5 years of follow-up, individuals who underwent FFR had less CV death/MI (89% vs. 84%; log-rank P=0.046). However, on Cox proportional hazards analysis, FFR was not independently associated with CV death/MI (HR 0.89; 95% CI: 0.60-0.98; P=0.58).

Conclusion:
ISCHEMIA patients randomized to INV strategy who underwent FFR had less complex and extensive coronary disease and, on unadjusted analysis, less CV death/MI. However, after adjustment for differences in baseline characteristics, FFR was not independently associated with CV death/MI.
Abstract 4147096: Heart Transplantation Trends and Associated Costs: A 12-year Retrospective Analysis on Nationwide Readmission Database (2010-2021)
Authors: Mogga Phanidhar , Raol Karanrajsinh , Pinninty Dheeraj , Pillai Ashwin , Mudduluru prathyusha , Singh Kerry , Jedeon Zeina , Jaiswal Abhishek
Published: November 2024

Introduction:
Increased prevalence and incidence of heart failure have resulted in a significant rise in the number of patients progressing to advanced heart failure (AHF). Heart transplantation (HT) has been the gold standard treatment for AHF. However, there is limited long-term data on trends in HT procedures and associated costs.

Aim:
This study aims to perform a comprehensive analysis to ascertain the trends in the number of HTs and the corresponding costs incurred.

Methods:
Utilizing the National Readmission Database 2010 to 2021, the study population was identified as new recipients of HT, and their median index admission charges were evaluated. We excluded patients aged < 18 with HT and LVAD during the index hospitalization.

Results:
We identified 36,379 weighted index hospital admissions from January to December 2010 - 2021. The annual HTs increased from 2,905 to 4,046, and the HT numbers increased by 39.28% (Figure 1). From 2010 to 2017, the HT numbers increased by approximately 11.46%; from 2018 to 2021, the increase was about 19.81%. Concurrently, median index admission costs increased from $146,817 in 2010 to $243,079 in 2021 (Figure 2), with a 65.57% cost increase. Considering patient demographics, 47% had private insurance, and Medicare covered 34%. Most patients were discharged home (48%) or to home with health care services (42%).

Conclusion:
Over the past 12 years, the total number of HT procedures rose by 39.28%. However, associated costs have surged disproportionately by 65.57% since 2010. A significant increase in OHT procedures from 2018 may be linked to policy changes by the United Network for Organ Sharing(Maitra, Dugger et al., 2023). Escalating costs warrant in-depth evaluation and potential policy revisions to curb healthcare expenses for managing advanced end-stage heart failure.
Abstract 4147105: Risk Factors Associated with Non-Pulmonary Vein Triggers at First-Time Atrial Fibrillation Ablation
Authors: Oraii Alireza , Chaumont Corentin , Rodriguez-Queralto Oriol , Wasiak Michal , Peters Carli , Zado Erica , Hyman Matthew , Markman Timothy , Guandalini Gustavo , Supple Gregory , Lin David , Dixit Sanjay , Nazarian Saman , Frankel David , Callans David , Marchlinski Francis
Published: November 2024

Background:
The majority of non-pulmonary vein (PV) triggers of atrial fibrillation (AF) require provocative maneuvers for induction during catheter ablation. Identifying a subset of patients with higher likelihood of having non-PV triggers can guide more efficient use of these provocative maneuvers.

Objective:
This study aims to identify pre-procedural risk factors for the presence of non-PV triggers at first-time AF ablation.

Methods:
We included patients who underwent first-time AF ablation between 2019 and 2022 at the Hospital of the University of Pennsylvania. Non-PV trigger provocation maneuvers included cardioversion of AF if present at baseline, incremental isoproterenol (ISO) infusion (3-30mcg/min), and atrial burst pacing to induce focal atrial tachycardia (AT) or induce AF followed by cardioversion on 3-6mcg/min ISO or during high dose ISO washout. Non-PV triggers were defined as non-PV ectopic beats initiating AF or sustained focal AT. We used logistic regression analysis to identify pre-procedural risk factors associated with the presence of non-PV triggers. Risk factors with univariable p-value <0.2 were entered in a multivariable model.

Results:
Of 1805 patients with first-time AF ablation, 1701 (94.2%) patients that received non-PV trigger provocative maneuvers were included. A total of 146 (8.6%) patients were found to have non-PV triggers. The prevalence of non-PV triggers was numerically higher in patients with persistent AF than those with paroxysmal AF (9.7% vs 7.7%, p-value=0.163). In the multivariable model, female sex (OR=2.18, 95% CI: 1.49-3.17), cardiac sarcoidosis/amyloidosis (OR=7.29, 95% CI: 2.90-18.31), prior cardiac surgery (OR=2.30, 95% CI: 1.37-3.85), and moderate to severe left atrial enlargement on echocardiography (OR=2.66, 95% CI: 1.83-3.85) were independent predictors of non-PV triggers during first-time AF ablation.

Conclusion:
Non-PV triggers are present in approximately 10% of patients undergoing first-time AF ablation. A set of pre-procedural risk factors can risk stratify patients at high risk for non-PV triggers and guide choice of optimal ablation strategy at first procedure.
Abstract 4147108: Assessment of Myocardial Strain with Cardiac Magnetic Resonance Imaging in Patients at Genetic Risk of Dilated Cardiomyopathy
Authors: Pillutla Virimchi , Zheng Alice , Juhasz Vencel , Jurgens Sean , Challa Saketh , Ramo Joel , Kramarenko Daria , Daly Mark , Bezzina Connie , Ellinor Patrick , Neilan Tomas , Aragam Krishna
Published: November 2024

Background:
Genetic risk and myocardial strain have emerged as early indicators of susceptibility to dilated cardiomyopathy (DCM). However, it remains unclear whether these markers are associated with one another and enhance the prediction of incident disease.

Aim:
We evaluated the interplay between measures of myocardial strain by cardiac magnetic resonance imaging (CMR) and genetic (monogenic and polygenic) risk for DCM, and their capabilities for predicting incident disease.

Methods:
We performed a retrospective analysis of 39,217 participants in the UK Biobank without cardiomyopathy, heart failure, or valvular heart disease at enrollment. Genetic risk was determined by the presence of a high confidence rare variant across 12 ClinGen-prioritized DCM genes and/or a high DCM polygenic risk score (PRS). CMR-derived measures of left ventricular (LV) myocardial strain, size, and function were obtained. Myocardial strain assessments included LV global longitudinal (GLS), global circumferential (GCS) and global radial strain (GRS).

Results:
Both monogenic and polygenic risk for DCM were most strongly correlated with LV GCS as compared to LVGLS or LVGRS. Specifically, compared to non-carriers of DCM-rare variants, TTN rare variant carriers (n=139) demonstrated worse LVGCS (-19.79 vs. -22.40, p=1.51e-21). Participants with high DCM polygenic risk also had worse mean LVGCS (top 10% vs. middle 50% of the DCM PRS, -21.43 vs. -22.39, p = 8.06e-53) (Figure 1). In addition, those with a significant relative interval decline in LVGCS (≥ 12%, n=45) had a higher median PRS (0.43 vs. -0.05, p=0.0097) compared to those without (n=177); this relationship was not evident for LV GLS or GRS. Multivariable Cox regression models adjusted for baseline LVEF, age, sex and body mass index showed that both LVGCS (HR=1.56 [1.13–2.14] per standard deviation (SD) of LVGCS, p=0.0065) and DCM PRS (HR=1.52 per SD of PRS [1.19–1.95], p=0.00072) were associated with an increased risk of incident non-ischemic cardiomyopathy (n=67).

Conclusion:
High genetic risk for DCM is strongly associated with worse LVGCS, and both genetic risk and LVGCS may have value for incident disease prediction.
Abstract 4147111: Correlation between Plasma Adiponectin, Leptin Levels, and Adverse Outcomes in Hypertrophic Cardiomyopathy Patients
Authors: Younus Shifa , Cheema Muhammad Hassan , Cheema Muhammad Hussnain , Hussain Alamdar , Fatima Noor , Zafar Aeman , Ali Aamir , Saleem Hamza , Hussain Tauseef , Choudhary Humais
Published: November 2024

Introduction:
Hypertrophic cardiomyopathy (HCM) stands as a significant cause of sudden cardiac death in the younger population. Adipokines, originating from adipose tissue, regulate processes such as heart inflammation, fibrosis, and hypertrophy. Among these adipokines, adiponectin and leptin are particularly linked to cardiac remodeling in HCM. This study aimed to examine the association between plasma levels of adiponectin and leptin and the occurrence of all-cause mortality as well as ventricular tachycardia/fibrillation (VT/VF) in individuals with HCM.

Methods and Materials:
In a multicenter prospective cohort study involving individuals diagnosed with HCM, we assessed plasma adiponectin and leptin concentrations upon enrollment. We examined the combined occurrence of all-cause mortality and new-onset VT/VF. Subsequently, the cohort was stratified into four categories based on adiponectin and leptin levels. Using the Cox proportional hazards model, we compared the likelihood of experiencing the outcome event across these groups, adjusting for age, body mass index, left atrial diameter, and maximum left ventricular wall thickness, with the largest group serving as the reference.

Results:
The endpoint event occurred in 48 of 384 individuals throughout a 2.8-year median follow-up period. The four groups based on adiponectin and leptin levels exhibited varying risks of the outcome event (log-rank P < 0.001). The Cox proportional hazards model showed that the High-Adiponectin, Low-Leptin group had a considerably higher risk (adjusted HR 7.34, 95% CI 1.12-14.25, P < 0.005) than the reference (Low-Adiponectin, High-Leptin) group.

Conclusion:
High plasma adiponectin and low leptin levels are independently linked with mortality and new-onset VT/VF in HCM patients. These adipokines can potentially be novel biomarkers for risk stratification in HCM, improving current prediction models.
Abstract 4147118: Balloon-Expandable versus Self-Expandable Valve for the Management of Bicuspid Aortic Disease: An Updated Meta-Analysis of Clinical Outcomes
Authors: Oliveira Izadora , de Sousa Andre , Paiva Arthur , Ferreira Vitor , Neves de Sá Carlos Eduardo , Alves Alencar Joao Victor , Alves Alencar Pedro Lucas , Duarte Lima Ana Paula , Oliveira Vinicius , Graner Moreira Humberto
Published: November 2024

Background:
Transcatheter aortic valve implantation (TAVI) has been employed in the management of aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) disease. Nevertheless, the comparative clinical outcomes of different types of valves used in this procedure remain inconclusive. Therefore, we conducted an updated meta-analysis to evaluate the performance of balloon-expandable (BEV) vs self-expandable valves (SEV) in patients with BAV going through TAVI.

Methods:
We systematically searched PubMed, Embase and Cochrane for studies comparing BEV and SEV in the treatment of AS in patients with BAV undergoing TAVI. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was assessed with the Cochran Q test and I
2
statistics. Statistical analysis was performed utilizing Review Manager 5.4.1.

Results:
We included 9 observational studies with a total of 1,666 patients, of whom 974 (58,46%) received a BEV. The follow-up duration ranged from 30 days to 2 years. The pooled analysis revealed no significant differences between the BEV and SEV groups in terms of procedural death (OR 1.05; 95% CI 0.29 – 3.74; P=0.94), 30-day all-cause mortality (OR 0.98; 95% CI 0.55 – 1.72; P=0.93; Figure 1A), 30-day cardiovascular mortality (OR 1.02; 95% CI 0.47 – 2.23; P=0.96), 1 year all-cause mortality (OR 1.06; 95% CI 0.58 – 1.93; P=0.86), annulus rupture (OR 2.67; 95% CI 0.53 – 13.59; P=0.24), coronary obstruction (OR 1.29; 95% CI 0.31 – 5.43; P=0.72), new pacemaker implant (OR 0.76; 95% CI 0.48 – 1.20; P=0.23), moderate or severe aortic regurgitation (OR 0.34; 95% CI 0.11 – 1.00; P=0.05) and stroke (OR 1.18; 95% CI 0.58 – 2.40; P=0.64). However, the requirement of a second valve was significantly less common in patients with BEV compared to those with SEV (OR 0.36; 95% CI 0.17 – 0.76; P<0.01; Figure 1B).

Conclusions:
This meta-analysis suggests that both types of valves exhibit similar clinical outcomes in patients with BAV undergoing TAVI. Nonetheless, BEV was associated with lower odds of requiring a second valve compared to SEV. Further randomized controlled trials are necessary to confirm these findings.