bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4141574: LOSS OF ROR2 IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN PAH VIA INAPPROPRIATE INTEGRIN B1 ACTIVATION
Authors: Mitra Ankita , Chakraborty Ananya , Zhong Brian , Nair Ramesh , Heo Lyong , Agarwal Stuti , Dunn Alexander , Chelladurai Prakash , Dejesus Vinicio
Published: November 2024

Rationale:
Endothelial dysfunction is a major hallmark of PAH whose underlying mechanism remains unexplored. We recently showed the vital role of the Wnt7a ligand, promotes pulmonary angiogenesis via ROR2, a tyrosine kinase receptor. We sought to elucidate how ROR2 activation orchestrates angiogenic responses in endothelial barrier establishment in pulmonary microvascular endothelial cells (PMVEC), and its potential contribution to endothelial dysfunction in PAH.

Hypothesis:
ROR2 regulates lung angiogenesis, and its loss is associated with PAH.

Methods:
Healthy and PAH PMVECs and lung tissues were obtained from transplants and commercial sources. PMVECs were transfected with ROR2 siRNA/constructs for functional and molecular studies. Bulk RNA-seq of control and siROR2 PMVECs was followed by bioinformatic analysis. Focal adhesion (FA) activation and force generation were measured using FRET-based total internal reflection microscopy (TIRF). Endothelial-specific conditional ROR2 KO (ROR2 ECKO) mice exposed to normoxia and hypoxia were phenotyped using echocardiography, hemodynamics, and lung morphometry.

Results:
ROR2 expression was significantly reduced in PAH lesions versus healthy. ROR2 knockdown (siROR2) reduced vascular sprouting and VEGF response comparable to control PMVECs. siROR2 and ROR2-deficient PAH PMVECs shows increased adhesion to fibronectin and barrier permeability. Confocal and TIRF microscopy of siROR2 and ROR2-deficient PAH PMVECs showed increased FA number and force generated by individual FAs that inversely correlated with reduced VE-cadherin at cell-cell junctions. ROR2 overexpression in PAH PMVECs normalized ROR2 protein expression, FAs activity, and junctional integrity and promoted recovery. Proteomic studies showed, ROR2 interacts with Integrin b1 in focal adhesions, and its loss results in Integrin b1 activation, FA clustering, and high mechanical forces. RNA-seq of siROR2 PMVECs showed dysregulation of vesicular trafficking and adhesion genes and enriched vesicular trafficking and angiogenic pathways. In animal studies, ROR2 ECKO developed severe PH, right ventricular remodeling, microvascular reduction, and muscularization in hypoxia, correlating with increased integrin-b1 activation and decreased VE-cadherin expression.

Conclusions:
ROR2 promotes vessel sprouting and barrier formation, and its loss is associated with dysfunctional angiogenesis in PAH. Restoring ROR2 signaling activity could be a novel therapeutic strategy in PAH.
Abstract 4141620: Large-Scale Proteomics Identifies Novel Circulating Markers of Pulmonary Hypertension: the Atherosclerosis Risk in Communities Study
Authors: Giugni Fernando , Santos Mario , Yang Yimin , Lamberson Victoria , Claggett Brian , Hoogeveen Ron , Ballantyne Christie , Yu Bing , Shah Amil
Published: November 2024

Introduction:
Biomarkers for early-stage pulmonary hypertension (PH) are unavailable in clinical practice.

Aims:
We aimed to discover novel plasma biomarkers associated with pulmonary pressure and PH.

Methods:
Among participants in the community-based Atherosclerosis Risk in Communities (ARIC) cohort study who underwent protocol echocardiography at the 5
th
study visit (2011-2013), had assessable pulmonary artery systolic pressure (PASP), and were free of diagnosed heart failure (HF) or pulmonary disease, we measured 4,955 plasma proteins (SomaScan aptamer-affinity assay). Participants also performed spirometry at the same study visit. We assessed cross sectional associations of individual proteins with PASP using multivariable linear regression adjusted for demographic and clinical covariates. We further assessed the associations of candidate proteins with cardiac and pulmonary function to explore mechanisms of association with PASP. Additionally, we performed two-sample Mendelian Randomization (MR) analyses using
cis
-pQTLs to identify potential causal associations.

Results:
Among 2,015 participants included, mean age was 75±5 years, 64% were female, 17% reported Black race, and LVEF was 66±6%. Mean PASP was 28±6 mmHg. Twenty-five protein aptamers (21 unique proteins) were associated with PASP at Bonferroni significance (Figure A). Of these 21 candidate proteins, the 16 associated with higher PASP were also generally associated with greater LV mass, lower LVEF, and worse LV diastolic function (specially higher LA volume index and lower LA reservoir strain) and worse spirometric measures (Figure B). The 5 proteins associated with lower PASP were generally associated with better LV structure and function. Of these 21 proteins, two-sample MR identified one protein with potential causal effects on pulmonary arterial hypertension (PROC), one with effects on LV size (ENG), and 4 with effects on pulmonary function (ANGPT2, CLSTN2, ICAM5, SPON1).

Conclusion:
We identified novel protein markers of pulmonary pressure, with potential causal associations related to the pathological substrate for types 1, 2 and 3 PH.
Abstract 4141635: Reconstructing Invasive Aortic Pressure Waveforms from Non-Invasive Brachial Measurements Using a Machine Learning Approach
Authors: Tamborini Alessio , Aghilinejad Arian , Gharib Morteza
Published: November 2024

Background:
Pulse wave analysis (PWA) of aortic pressure waveforms carries valuable information about cardiovascular health. However, due to the invasiveness of direct measurement, peripheral pressure waveforms are commonly used as surrogates. Recent findings revealed that while algorithmic methods can preserve pressure dynamics in non-invasive measurements, significant waveform morphology changes disrupt the association between peripheral and central parameters
(PMID: 38591330, 2024
). There is a need for non-invasive methods to faithfully reconstruct the central pressure waveform.

Aim:
Evaluate the fidelity of reconstructed aortic waveforms using a machine learning method applied to non-invasive brachial measurements.

Methods:
This study analyzed concurrent aortic catheterization and brachial cuff waveform measurements in suprasystolic mode in subjects referred for non-emergent left heart catheterization (N=115; mean age 66, 63% male). Our machine learning method uses a non-linear mode mapping in the frequency domain between non-invasive calibrated brachial pressure waveforms and invasive aortic ones. PWA features captured waveform magnitude and shape: systolic blood pressure (SBP), diastolic blood pressure (DBP), systolic pressure-time integral (SPTI), diastolic pressure time integral (DPTI), peak timing (T
peak
), systole duration (T
sys
), maximum pressure derivative ((+)dP/dt), and form factor (FF). Percentage error ((true–predicted)/true) was used to assess parameter correspondence in the testing population (N=35; cardiac cycles=994).

Results:
The non-linear mapping technique successfully reconstructed central pressure waveforms with good agreement between measured and estimated (MEAN=0.5 mmHg; SD=7.3 mmHg) as shown in Fig. 1A. PWA features showed low mean percentage errors for pressure (SBP=-0.7 ±5.9%; DBP=-2.9±9.4%), area (SPTI=0.2±8.7%; DPTI=-2.8±9.3%), timing (T
peak
=1.0±12.3%; T
sys
=1.2±7.1%), and shape parameters ((+)dP/dt=11.5±24.3%; FF=1.4±4.7%) shown in Fig. 1B.

Conclusion:
Our results demonstrate that the machine learning method applied on brachial cuff measurements captures waveform morphological changes along the arterial system allowing for a faithful representation of the central pressure waveform.
Abstract 4141761: Safety and Efficacy of Radial Versus Femoral Access for Rotational Atherectomy: An Updated Systematic Review And Meta-Analysis
Authors: Ahmed Muhammad , Murtaza Muzna , Muzammil Muhammad , Sami Syeda Zuha , Nazir Ariba , Ahmed Muhammad , Asghar Muhammad Sohaib
Published: November 2024

Background:
Rotational atherectomy has been performed using both radial and femoral access over the years, but there is a lack of consensus on the safety and efficacy of these access sites.

Aim:
To assess the safety and efficacy of radial access and femoral access.

Methods:
MEDLINE, Scopus, and Cochrane Library were searched until May 2024 for studies comparing radial approach with femoral approach in patients undergoing rotational atherectomy. The primary outcome was major vascular site bleeding. Secondary outcomes included short-term mortality, long-term mortality, myocardial infarction, major adverse cardiovascular events (MACE), acute stent thrombosis, procedural success, procedural time, hospital stay and radiation exposure. Effect estimates were synthesized using a random-effects model and expressed as risk ratios (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with corresponding 95% confidence intervals (CIs).

Results:
13 studies including 13,581 patients with mean age of 60.76 years in the radial group and 66.86 years in the femoral group, who had undergone rotational atherectomy, were included in the analysis. For the outcome of major vascular site bleeding, there was significantly lower risk (RR: 0.25; 95% CI [0.15, 0.43]; p<0.00001) in the radial group as compared to the femoral group. From the secondary outcomes, MACE was found to be significantly lower (RR:0.80; 95% CI [0.68, 0.93]; p=0.004) in radial arm as compared to femoral arm. Radial group was also significantly associated with shorter procedural time (MD: -8.30 CI: 95% [-12.03, -4.56], p<0.00001) and hospital stay (MD: -2.30; 95% CI [-4.29, -0.30], p=0.02) as compared to femoral group. Whereas all the other secondary outcomes were found to be insignificant.

Conclusion:
Rotational atherectomy using the radial approach significantly shows a lower rate of major vascular site bleeding and MACE and is also associated with shorter procedural time and hospital stay.
Abstract 4141781: "Simple Arithmetic Representation to Classify of Right Ventricular Outflow Tract in Tetralogy of Fallot Patients "
Authors: casallas isabella , PEREZ CUALTAN CAMILO EDUARDO , Navarro Rueda Javier , Acosta-Izquierdo Laura , Forero Julian Francisco , perez Juan Manuel , Briceno Juan Carlos , Guerrero Carlos
Published: November 2024

In patients with tetralogy of Fallot (TOF) repaired with a transannular patch (TAP), right ventricular outflow tracts (RVOT) are classified by shape using complex 3D measurements. RVOT shape is crucial for evaluating transcatheter pulmonary valve replacement (TPVR).

Aim:
To evaluate if a simple graphical representation of the RVOT in TOF patients repaired with TAP can classify RVOTs than Level III imaging experts in a Latin American tertiary care center.

Methods:
This retrospective single-center study included TOF post-TAP patients who underwent cardiac magnetic resonance (CMR) between 2014 and 2023. Dynamic CMR angiography images were used to segment and create 3D reconstructions of the RVOT and pulmonary artery. Centerline-based measurements derived from perimeter were taken at six RVOT points (bifurcation, mid trunk, supravalvular, pulmonary valve annulus, subvalvular, and RVOT) following the TPVR planning protocol by Canan et al. to measure the area and create a graphical representation (Figure 1). The graphs and 3D reconstructions were categorized into five RVOT types based on Schievano et al.'s classification. Graphs were compared to the original classification by overlaying graph forms, and 3D files were classified by three Level III cardiac imagers. The correlation between evaluators and graphs was measured using the Kappa coefficient.

Results:
The study population included 60 patients (55% male, mean age 17 ± 12 years at CMR). The RVOT type distribution, according to the graph representation, was 53.3% type 1, 13.3% type 2, 5% type 3, 10% type 4, and 15% type 5. Only 3% of the graphs did not fit the established classification. The initial agreement among the three evaluators regarding 3D classification was 28%. Compared with the graphs, evaluator 1 agreed fairly (Kappa=0.24, p=0.0006), evaluator 2 slightly (Kappa=0.197, p=0.0008), and evaluator 3 poorly (Kappa=0.07, p=0.15).

Conclusions:
Our approach reclassified RVOT shapes more effectively than imaging experts, showing a high fit in classification and low agreement among cardiac imagers. This method could be an additional tool to identify TOF patients suitable for TPVR post-TAP.
Abstract 4141790: Pre-Hospital Antiplatelet Therapy In Patients With Out-Of-Hospital Cardiac Arrest Suspected Of Acute Coronary Syndrome
Authors: CHARLEUX Pierre , Chommeloux Juliette , Elhadad Anthony , PROCOPI Niki , Guedeney Paul , Martinez Clelia , Rouanet Stephanie , VICAUT Eric , Kerneis Mathieu , Demoule Alexandre , COMBES Alain , Silvain Johanne , Montalescot Gilles , Zeitouni Michel
Published: November 2024

Background:
There are currently no specific guidelines regarding pre-hospital antiplatelet therapy in patients with out-of-hospital cardiac arrest (OHCA) suspected of acute coronary syndrome (ACS).

Purpose:
To evaluate efficacy and safety of pre-hospital administration of antiplatelet therapy in patients with OHCA directed to a cardiac catheterization laboratory (cath lab).

Method:
Using the cath lab database of a tertiary cardiovascular center, we included consecutive patients referred for coronary angiography within 24 hours of OHCA for suspected ACS from January 2012 to January 2024. Pre-hospital antiplatelet treatment was defined as prescribing any antiplatelet therapy before cath lab admission (aspirin alone or combined with a P2Y12 inhibitor). The outcomes of interest were: 1) all-cause death at 30 days, 2) intra-hospital major adverse cardiovascular events (MACE), defined by the composite of all-cause death, myocardial infarction, or stroke, and 3) intra-hospital major bleedings (BARC ≥ 3). To help account for the non-randomized pre-hospital antiplatelet administration, an Inverse Probability Weighting (IPW) approach was used to compare outcomes between the two groups.

Result:
Between January 2012 and January 2024, n = 411 patients with OHCA were referred to the cath lab, of whom 217 (52.8%) received a pre-treatment. Pre-hospital antiplatelet administration did not show a reduced risk of death from any cause at 30 days (56.7% [50.0%;63.1%] vs 59.8% [52.8%;66.4%], p=0.21) (

Figure 1

). The rates of intra-hospital MACE (57.1% [50.5%;63.5%] vs (61.3% [54.3%;67.9%]), p=0.38) and major bleedings (18.9% [14.2%;24.6%] vs (18.6% [13.7%;24.6%], p=0.51) did not differ significantly in pre-treated patients compared to non-pre-treated ones.

Conclusion:
In our cohort of patients with OHCA suspected of ACS, we did not observe an association between pre-hospital administration of an antiplatelet loading dose and outcomes.
Abstract 4141813: Assessing Short-Term Prognostic Value of eGFR Formulas in Patient with Acute Heart Failure: Comparison of Chronic Kidney Disease Epidemiology Collaboration 2021, 2009 Formula, and Modification of Diet in Renal Disease in Asian Population – A Study from Vietnam
Authors: TRAN DIEU HIEN , TRUYEN THIEN TAN TRI TAI , NGUYEN MINH NGHIEM , NGUYEN VAN KHOA , VO PHUC DAI , LE HOANG PHUC , Dinh Trí , Vu Loc , Kieu Doan Thi , DO CHAU , NGUYEN THI KIM CHUC , Pham Ngoc Anh Vu , PHAN HOANG SON , PHAN TRI CUONG , HAN NGUYEN LE MY , NGUYEN THI HUONG DUNG , Vo Le Y Nhi , CAO DOAN THI BICH HUYEN , TRAN THANH PHONG , TRAN VAN DUONG , NGUYEN NGOC HUYEN , PHAM THANH PHONG
Published: November 2024

Introduction:
In 2021, the American Society of Nephrology Task Force recommended using the new CKD-EPI 2021 formula to estimate the glomerular filtration rate (eGFR) and to classify CKD. Evidence to compare the efficacy of this new formula with the current utilized formula, including MDRD and CKD-EPI 2009, in predicting the short-term outcomes of Asian patients with acute heart failure (AHF) is lacking.

Hypothesis:
The eGFR calculated by the CKD-EPI 2021 formula predicts short-term outcomes of patients with AHF more accurately than those calculated by the MDRD and CKD-EPI 2009 formulas.

Methods:
We conducted a pilot retrospective cohort study from January 1, 2023, to December 31, 2023, at Can Tho Central General Hospital in Can Tho, Vietnam. Our study included patients aged ≥18 who were admitted with AHF, NT-pro BNP levels exceeding 300 pg/mL, and creatinine result within 24 hours of admission. eGFR was calculated using 3 different formulas such as CKD-EPI 2021, CKD-EPI 2009, and MDRD. The short-term outcome was determined by 3-months post-discharge all causes mortality.

Results:
The final cohort comprised 146 patients, with a mean age of 65.6 ± 14.2 years and male proportion of 46%. Significant correlations were observed among the three formulas, with the strongest correlation observed between the CKD-EPI 2021 and 2009 formulas. In predicting short-term outcomes, the CKD-EPI 2021 and CKD-EPI 2009 formulas demonstrated superior performance compared to the MDRD formula, with respective area under the curve values of 0.634, 0.635, and 0.607. After multivariable analysis, from 90mL/min/1.73m
2
, every 10 ml/min/1.73 m
2
decrease in eGFR calculated by CKD-EPI 2021, CKD-EPI 2009, and MDRD was associated with a 32% (95% CI: 9-49), 26% (95% CI: 4-47), and 30% (95% CI: 8-47) increase in the odds of all-cause mortality among patients with AHF. Only CKD-EPI 2021 formula showed significant predictive prognostic value (log-rank test, p=0.049) (Figure).

Conclusion:
The CKD-EPI 2021 formula showed superior prognostic efficacy for short-term outcomes in Asian patients with acute heart failure (AHF) compared to current formulas. Further research involving larger patient cohorts and longer-term outcomes is warranted.
Abstract 4141822: Factor VIII replacement therapy in patients with hemophilia undergoing pulsed-field or radiofrequency catheter ablation for atrial fibrillation
Authors: Mohanty Sanghamitra , Compagnucci Paolo , Torlapati PremGeeta , Della Rocca Domenico , La Fazia Vincenzo Mirco , Gianni Carola , MacDonald Bryan , QUINTERO MAYEDO ANGEL , Gallinghouse G , Burkhardt John , Horton Rodney , Al-Ahmad Amin , Di biase Luigi , Casella Michela , Dello Russo Antonio , Natale Andrea
Published: November 2024

Background:
Typically, hemophilia patients receive up to 6 weeks of intravenous Factor VIII replacement therapy while undergoing radiofrequency ablation (RFA) for atrial fibrillation (AF).

Objective:
We report the management of Factor-VIII replacement therapy in a series of hemophilia patients receiving either pulsed-field (PFA) or RFA.

Methods:
Consecutive hemophilia patients undergoing AF ablation were included in this series. All patients received pulmonary vein isolation (PVI) plus isolation of left atrial posterior wall using either RFA or PFA.

Results:
This series included 8 male patients of which 3 (37.5%) received PFA and 5 underwent RFA for drug-refractory AF. Mean CHA
2
DS
2
-VASc score were 2.67±1.15 and 2.80 ±1.48 (p=0.899) and the HAS-BLED score were 3.33± 1.53 and 2.80±1.10 (p=0.582) in the PFA and the RFA cohorts respectively. Details of pre- and post-procedural Factor VIII replacement therapy is provided in Table 1.

After the procedure, patients undergoing PFA received significantly less Factor VII replacement therapy compared to those receiving RFA (PFA: 78,866.67 ± 1,761.63 vs. RF: 152,260.00 ± 29,704.51 IU, P-value: <0.001). The duration of the replacement therapy was also significantly lower in the PFA patients compared to the RFA cohort (6.65±0.229 vs 31±3.316 days, p<0.001).

No peri-procedural bleeding or thromboembolic events were reported at 1-year follow-up.

Conclusion:
In hemophilia patients undergoing PFA for AF, factor-VIII replacement therapy and oral anticoagulants could be discontinued after one week of the procedure with no bleeding or thromboembolic complications at follow-up, whereas the duration of therapy was significantly longer following RFA.
Abstract 4141823: Deletion of Endothelial Neuropilin-1 Improves Cardiac Diastolic Function in Heart Failure with Preserved Ejection Fraction
Authors: Huo Yu , Chau Sarah , Wang Enfeng , Fayyaz Ahmed , Mukhopadhyay Debabrata , Redfield Margaret , Wang Ying
Published: November 2024

Heart failure with preserved ejection fraction (HFpEF), characterized by cardiac diastolic dysfunction, leads to premature mortality with limited effective treatments. A recent study in HFpEF patients suggested neuropilin 1 (NRP1), an endothelial cell (EC) originated prognostic marker, might contribute to the pathogenesis of HFpEF. However, the functional role of NRP1 in the pathogenesis of HFpEF remains unclear.

Purpose:
To determine the functional role of NRP1 in the pathogenesis of HFpEF.

Hypothesis:
NRP-1 contributes to the pathogenesis of HFpEF, potentially mediated through chronic inflammation.

Methods:
HFpEF was induced by hypertensive and metabolic stresses in control (n=14) and tamoxifen-induced, endothelial cell-specific NRP1 knockout (NRP1
iEC-KO
) mice (n=13). We assessed cardiac diastolic function via echocardiography and pressure-volume loop through invasive catheters. To determine the inflammation level, we tested leukocyte adhesion, inflammatory marker vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) mRNA level in control and NRP1 shRNA knockdown (NRP1 KD) human umbilical vein endothelial cells (HUVECs) with a stimulation of TNF-α. Student t-test (two tailed) was used and the criterion level of significance was set at p<0.05.

Results:
We found a significantly improved diastolic function in NRP1
iEC-KO
mice, evidenced by a significantly reduced end diastolic pressure in
NRP1
iEC-KO
mice (8±2mmHg; n=7) compared to the controls (17±2mmHg; n=9; p=0.01) after HFpEF induction. E/A ratio was also significantly lower in
NRP1
iEC-KO
mice (2.0±0.2; n=10) compared to controls (2.7±0.3; n=12; p=0.04). Moreover, the isovolumic relaxation time was also significantly reduced in NRP1
iEC-KO
mice (18±0.8ms; n=13) compared to controls (20±0.8ms; n=14; p=0.03). In addition, In HUVECs, NRP1 KD significantly reduced inflammatory marker VCAM-1 mRNA expression (95±16; n=5) compared to controls (293±36; n=5; p<0.01) upon TNF-α treatment. Similarly, NRP1 KD significantly reduced ICAM-1 mRNA expression (44±14; n=5) compared to controls (83±9; n=5; p=0.03) upon TNF-α treatment. Furthermore, leukocyte adhesion was significantly lower in the NRP1 KD group (57.0 ±8.6 cells/field) compared to the control group (90.8 ±9.1 cells/field; p=0.04).

Conclusion:
Endothelial NRP1 contributes to cardiac diastolic dysfunction and the pathogenesis of HFpEF, potentially mediated through the activation of chronic low-grade inflammation.
Abstract 4141854: Paclitaxel Coated versus Uncoated Balloon for Coronary In-stent Restenosis: A Systematic Review and Meta-Analysis with Trial Sequential Analysis
Authors: Oliveira Vinicius , Alves Alencar Pedro Lucas , Oliveira Izadora , de Sousa Andre , Figueiredo Paro Piai Ricardo , Alves Alencar Joao Victor , Schmaltz Zalaf Felipe , Graner Moreira Humberto
Published: November 2024

Background:
Drug-coated balloons present a potentially advantageous therapeutic approach for managing coronary in-stent restenosis. However, the comparative benefits of paclitaxel-coated balloons (PCBs) over uncoated balloons (UCBs) in coronary interventions remain unclear. Therefore, we conducted a systematic review and meta-analysis with trial sequential analysis (TSA) to evaluate the clinical outcomes of patients treated with PCBs compared to those treated with UCBs for coronary in-stent restenosis.

Methods:
We searched PubMed, Embase and Cochrane databases for randomized clinical trials (RCTs) comparing the use of PCBs and UCBs in the treatment of coronary in-stent restenosis. A random-effects model was employed to pool odds ratios (ORs) and their 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager version 5.4.1. and TSA version 0.9.5.10 beta.

Results:
We included 7 RCTs with a total of 1,344 patients, of whom 834 underwent percutaneous coronary intervention (PCI) with PCBs. In our pooled analysis, patients treated with PCBs had lower odds of target lesion revascularization (OR 0.21; 95% CI 0.11 – 0.40; P<0.01; Figure 1A), target vessel revascularization (OR 0.43; 95% CI 0.32 – 0.59; P<0.01), major adverse cardiac events (MACE) (OR 0.15; 95% CI 0.09 – 0.27; P<0.01; Figure 1B), and myocardial infarction (OR 0.56; 95% CI 0.33 – 0.94; P=0.03). However, there were no significant differences between groups in the odds of all-cause mortality (OR 0.56; 95% CI 0.18–1.77; P=0.33), cardiac death (OR 0.81; 95% CI 0.12 – 5.27; P= 0.82) and stent thrombosis (OR 0.20; 95% CI 0.03 – 1.36; P=0.10). TSA indicates that the observed effect on the primary outcome of TLR can be deemed conclusive, with a low risk of type 1 error.

Conclusions:
These findings suggest that PCBs are superior to UCBs regarding the occurrence of target lesion revascularization, target vessel revascularization, MACE, and myocardial infarction. Nonetheless, there were no significant differences in the odds of all-cause mortality, cardiac death, and stent thrombosis.
Abstract 4141859: Impacts of the COVID-19 era Practice of Preventing Bypass of the Emergency Department for ST-Segment Elevation Myocardial Infarction Patients Identified in the Field by Emergency Medical Services on In-Hospital Mortality and Other Performance Metrics
Authors: Benziger Catherine , Mullvain Richard , Kaas Krysta , ARTANG RAMIN , Renier Colleen
Published: November 2024

Background:
Field activation of patients with ST-segment elevation myocardial infarction (STEMI) by Emergency Medical Services (EMS) during the COVID-19 (COVID) pandemic era involved a change in policy whereby patients underwent COVID-19 testing in the emergency department (ED) prior to Percutaneous Coronary Intervention (PCI) versus bypassing the ED to the Catheterization (Cath) Lab.

Research Question:
We aimed to compare In-Hospital Mortality and other performance metrics of field activated STEMI patients at a large rural health system during the COVID era to pre and post pandemic periods.

Methods:
Retrospective single-center (Essentia Health, Duluth, MN, USA) cohort study of consecutive patients with STEMI activation identified in the field by EMS prior to the COVID era (5/27/2018–3/26/2020), during the 22 months of the COVID testing policy (3/27/2020–1/25/2022), and post-COVID when ED bypass resumed (1/ 26/2022–11/26/2023). The main outcomes of this study were in-hospital mortality and common STEMI system performance metrics.

Results:
A total of 373 consecutive field activated STEMI cases were included (pre COVID [N =132], COVID [N = 104], post COVID [N = 137]). Pre COVID, 40.9% of EMS activated STEMI cases stopped in the ED prior to the Cath Lab, 97.1% during the COVID era, and 51.1% in the post-COVID era (p<0.0001 between pre COVID and COVID era).
The median door to device time
was increased from 32.5 (15-75 total range) 39 (18-122) min p= 0.042. The
time from symptom onset to device
placement was increased from 140 (63-806) to 170 (63-934) min p=0.0054. The

time from 1
st
positive EKG to device

time was increased from 80 (32-157) to 94 (43-197) min p=0.046. The first medical contact to device, 911 call to device, and symptoms onset to 911 call times during COVID era showed increasing trend as compared to pre-COVID times but were not statistically significant. The unadjusted In-hospital mortality rates for EMS identified STEMI during the pre-COVID era, COVID era, and post-COVID era were 6.1%, 8.7%, and 7.3%, respectively (p=ns). Most times metrics returned to the pre-COVID levels in the post-COVID phase.

Conclusion:
In the rural setting, EMS activated STEMI patients had longer times to reperfusion during the COVID-19 era as compared to pre COVID due to the stop at the ED. The delayed reperfusion did not significantly reflect in in-hospital mortality, likely due to low number of events. Larger cohort multi-center studies on this issue is warranted.
Abstract 4141861: Detecting Acute Ischemia Prior to Troponin-I Rise Using Hyper-Acute Native T1 Mapping with Ultrastructural Tissue Validation: Implications for Rapid Diagnosis of Non-ST-Elevation Myocardial Infarction
Authors: Chan Shing Fai , Liu Ting , Singh Dhirendra , Huang Yuheng , Yang Hsin-jung , Yoosefian Ghazal , Tang Richard , Howarth Andrew , Vora Keyur , Dharmakumar Rohan
Published: November 2024

Background and Hypothesis:
Early detection of acute ischemia in non-ST-elevation MI (NSTEMI+) patients is crucial for timely treatment. Traditional biomarkers like high sensitivity cardiac troponin-I level [hs-cTnI] can take hours after myocardial injury to rise in NSTEMI+ patients and potentially delay diagnosis and treatment. We hypothesized that hyper-acute native T1 mapping with cardiac MRI (CMR) can rapidly identify ongoing ischemia. We studied this in canine models of ischemia and then in patients suspected of NSTEMI+.

Methods:
We performed LAD coronary artery ligation inside a CMR system to induce no-flow ischemia in a canine model (n=18) and performed repeat T1 and T2 mapping every 5 min. We also biopsied myocardial tissue at baseline and at defined time points from ischemic and remote areas. We used transmission electron microscopy (TEM) to analyze cardiac ultrastructure. Patients suspected of NSTEMI+ (n=16) underwent native cine, T1, and T2 CMR 3T.

Results:
T1 values increased significantly from 1182±51ms (baseline) to 1265±56ms (5 to 10 min after onset of ischemia), p<0.05; and continue to rise through 90 min (1327±56ms), while T2 values showed no significant changes over the first 90 min. TEM showed that the mitochondrial cristae density in ischemic zones was significantly decreased: 100±9.8%(baseline) vs 54±4.4% (5 min of ischemia), p<0.01, and decline to 40.6±9.8% by 90 min. After 5 min of ischemia, both mitochondrial width and circuity index showed no difference compared to baseline, but both paraments increased significantly: (a) mitochondrial width: 990.4±118.6nm (15 min of ischemia) vs 577±61nm (baseline), p<0.01; (b) circuity index: 0.87±0.04 (15 min of ischemia) vs 0.8±0.04 (baseline), p<0.01, and continued to rise and persist at high levels at 90 min: 1091±148 nm (mitochondrial width) and 0.94±0.01 (circuity index), respectively. Cristae number was significantly reduced 13.8±2.7 (baseline) vs 24.4±2.9 (5 min of ischemia), p<0.01, and remained low and reduced to 7.6±1.8 by 90 min. ΔT1 value in patients were significantly higher in NSTEMI+ than in NSTEMI- (11.51±3.7% vs 2.06±1.7%, p<0.0001), while [hs-cTnI] levels from NSTEMI+ gradually increased over time and were only significantly higher than NSTEMI-, several hours after CMR and peaked at 24 h (12.6±7.3% (24 h) vs 0.03±0.02% (baseline), p<0.05).

Conclusions:
Hyper-acute native T1 mapping has the potential to rapidly identify ongoing ischemia even in the absence of troponin-I rise.
Abstract 4141882: The importance of adenine in the formation of coronary artery calcification and development of ischemic cardiomyopathy
Authors: Tamayo Ian , Gruslova Aleksandra , Feldman Marc , Trevino Esmeralda , Bedi Kenneth , Margulies Kenneth , Lee Hak Joo , Bopassa Jean Chrisostome , Sharma Kumar
Published: November 2024

Introduction:
Adenine has been demonstrated to be involved in the development of diabetic kidney disease. We postulate that adenine may play a similar role in the progression of cardiovascular disease. The underlying metabolic changes in ischemic cardiomyopathy (ICM) progression are not fully understood and may present novel targets to mitigate ischemic heart injury. This study aims to identify common metabolic targets based on adenine metabolism in both coronary artery calcification and ICM.

Methods:
Coronary arteries from human donor hearts with and without calcification were analyzed by mass spectrometry imaging (MSI) and serial section von Kossa’s staining for image co-registration with identified metabolites. Bulk tissue LC-MS of the same artery samples were measured for adenine pathway metabolites. Another cohort of human heart tissues from healthy donors and those with a history of ICM were analyzed for bulk left ventricle tissue LC-MS measurement of adenine pathway metabolites. Further, to evaluate a mechanistic role for adenine in the development of ICM, a rat model of MI was studied with and without pharmacologic inhibition of MTAP, the enzyme responsible for adenine production. Infarct size was used as the readout of heart injury.

Results:
An untargeted analysis by MSI reveals an increase in adenine highly localized to arterial calcification as well as other metabolites such as glycolytic intermediates and C16 ceramide-derived lipids. Bulk tissue LC-MS showed calcified arteries have an overall increase in adenine, 5’-methylthioadenosine (MTA), S- adenosylmethionine (SAM). Left ventricle tissue from human donors with a history of ICM showed a significant increase in adenine by bulk LC-MS compared to controls (t-Test, **p<0.01). There was a negative correlation of heart adenine with LVEF (Pearson R = -0.6807, **p<0.01). In a rat model of MI, inhibition of MTAP resulted in significantly reduced infarct size (from 50% to 10%, t-Test, *p<0.05).

Conclusion:
Spatial metabolomics revealed increased adenine, several glycolytic intermediates, and C16 ceramide-derived lipids as highly co-localized to arterial calcification. Further, adenine was found to be increased in LV tissues with ICM and was negatively correlated with LVEF. Inhibition of adenine production reduced infarct size in a rat model of MI by >80%. Taken together, multimodal metabolomics reveals adenine to be mechanistically involved in cardiovascular disease and presents as a novel therapeutic target.
Abstract 4141884: Fully Automatic Quantification of the Aortic Root in 4D Transesophageal Echocardiography
Authors: Amin Silvani , Chan Trevor , Tran Nathanael , Al Ghofaily Lourdes , Cheung Albert , Yushkevich Natalie , Hao Jilei , Jolley Matthew , Woo Y Joseph , Bavaria Joseph , Desai Nimesh , Pouch Alison
Published: November 2024

Introduction:
Aortic root (AoR) morphology and dynamics are integral to understanding aortic valve function and planning patient-specific aortic interventions with transesophageal echocardiography (TEE). Modeling the AoR in time-varying 3D data is advantageous over conventional 2D cross-sectional analysis. However, manual segmentation of the AoR in 3D relies on a learning curve and takes up to 1.5 hours per volume. We hypothesize that the AoR can be rapidly and accurately segmented and quantified fully automatically with deep learning in pre-operative 4D TEE.

Methods:
Pre-operative TEE from both bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients were semi-automatically segmented and manually verified. A nnU-Net model was trained, validated, and tested with 74 TEE time-series images (46 BAV, 28 TAV) consisting of 1971 individual 3D volumes (60/40% training/testing split) from 2 institutions. The Dice similarity coefficient and average mesh-to-mesh distances were compared to interobserver variability between multiple manual tracers. AoR volume and diameters were automatically computed. Quantification agreement between model-generated and semi-automatic segmentations was analyzed with the intraclass correlation coefficient and Student’s t-test.

Results:
A representative automatic segmentation and quantification of the AoR is shown in Figure 1a-c. Quantification agreement between automatic and manual segmentations for all test data are shown in Figure 1d. Measurements on automatic segmentations have strong agreement with measurements on manual segmentations (ICC > 0.95). Automatic segmentation results are insignificantly different from interobserver tracings (p > 0.01), suggesting that a reliable AoR segmentation can be produced in inference time as little as 1-2 seconds per 3D volume (Figure 1e-g).

Conclusions:
The proposed deep learning method rapidly produces AoR segmentations and quantifications that are comparable to manual tracing. This framework can aid in population-based comparison of BAV and TAV roots and facilitate patient-specific AoR assessment for surgical planning. In the future, leaflet segmentations can be incorporated for analysis of the full aortic valve apparatus in TEE.
Abstract 4141889: Shifting trends and study characteristics associated with randomization, blinding, and data monitoring committee oversight of cardiovascular trials: analysis of ClinicalTrials.gov listings from 2000 to 2023
Authors: Chi Gerald , Bahit Maria , Castro Molina Alberto , Korjian Serge , Vitarello Clara , Nara Paul , Shaunik Alka , Gibson Charles
Published: November 2024

Background:
In response to concerns regarding insufficient transparency and selective reporting, the International Committee of Medical Journal Editors (ICMJE) issued a statement in 2004 mandating the registration of all clinical trials in a publicly accessible repository. Its impact on the trend of cardiovascular (CV) trial has not been comprehensively examined. The relationship between trial characteristics and designs aimed at enhancing methodological rigor and scientific validity, such as the implementation of randomization, blinding, and a data monitoring committee (DMC), remains unclear.

Methods:
The analysis included studies that: (1) were registered in ClinicalTrials.gov between 2000 and 2023; (2) involved ≥1 intervention; and (3) investigated ≥1 CV condition. Interrupted time-series analysis was performed to assess the impact of the ICMJE policy on the annual trend of trial registration. Multivariable logistic regression was conducted to assess the association between study characteristics and randomization, blinding, or DMC oversight.

Results:
A total of 38,262 CV trials were identified from 473,593 records. Prior to the implementation of ICMJE policy, the number of new CV trials increased by 10.9 (95% confidence interval [CI]: 1.5 to 20.3) every year. Following the implementation, the ascending trend intensified significantly (p<0.001), with a rate of 92.6 (95% CI: 60.6 to 124.5) new CV trials per year (Figure 1). Randomization and blinding were more commonly adopted in preventive trials, trials involving behavioral or dietary interventions, and phase 3 trials (Figure 2). In contrast, diagnostic trials and trials related to devices or procedures were less likely to include randomization or blinding in their design. More recent trials were less likely to implement randomization but more likely to implement blinding than earlier trials. DMC oversight was less prevalent in diagnostic trials, trials involving behavioral or dietary interventions, and non-phase 3 trials. Trials supported by the industry were less inclined to employ randomization, blinding, or DMC oversight. Study size was not correlated with any of these designs.

Conclusion:
The upward trend of CV trial registration augmented following the implementation of the ICMJE policy. Implementation of randomization, blinding, and DMC oversight was associated with study purpose, intervention, phase, funding source, and start year, with no discernible variation by study size.
Abstract 4141913: Feasibility and safety of ICE-guided electrical isolation of the superior vena cava using pulsed-field ablation in patients with atrial fibrillation
Authors: Mohanty Sanghamitra , Doty Brandon , Gabrah Kirollos , La Fazia Vincenzo Mirco , Schiavone Marco , Torlapati PremGeeta , Gianni Carola , allison John , Gallinghouse G , Burkhardt John , Horton Rodney , Al-Ahmad Amin , Tondo Claudio , Nair Devi , Natale Andrea
Published: November 2024

Background:
Earlier studies have documented the risk of sinoatrial node injury and phrenic nerve palsy as complications following radiofrequency catheter ablation for electrical isolation of superior vena cava (SVCI).

Objective:
We evaluated the safety and feasibility of SVCI in patients with atrial fibrillation (AF) undergoing pulsed-field ablation (PFA)

Methods:
Consecutive patients undergoing PFA procedure for SVCI were included in this multicenter analysis. SVC ablation was performed with the ablation catheter placed at the level of the pulmonary artery under the guidance of intracardiac echocardiography (ICE). A total of 4 applications were given; two in the flower and 2 in the basket configuration of the PFA catheter. In all patients, the procedure was performed under imaging with ICE; endpoint was complete electrical isolation of the vein. Mapping was done before and after ablation to verify the effect of PFA. Patients were asked to report symptoms compatible with phrenic nerve injury (cough, shortness of breath) at follow-up. They also underwent periodic clinical and 7-day holter monitoring to assess sinus node injury.

Results:
A total of 67 patients (age: 62.92±9.44 year, male: 20 (66.6%), BMI: 26.43±4.33) receiving SVCI were included in the analysis. Acute SVCI was achieved in all 67 (100%) patients (fig 1 and 2). After ablation, the PFA catheter placed in the SVC did not record any electrical activity (figure 2).

No phrenic nerve palsy (normal diaphragmatic motion with fluoroscopy) or sinus node injury (no acceleration of the sinus rate) was observed during the procedure. Additionally, during the 3-month follow-up period, patients neither reported symptoms pertaining to phrenic nerve injury nor the Holter monitoring revealed sinus node dysfunction.

Conclusion:
ICE-guided PFA can effectively isolate SVC without causing phrenic nerve palsy or sinus node injury.
Abstract 4141917: Incidence of Autoimmune Disease in Hospitalized Patients with Congenital Heart Disease
Authors: Caryl Natalie , Macaraeg Marci , Bose Cameron , Meziab Omar , Guerrero Claudia , Andrews Jennifer , barber brent , Seckeler Michael
Published: November 2024

Introduction:
Individuals with congenital heart disease (CHD) have increased risk of immune suppression and elevated inflammatory markers in response to abnormal cardiac physiology. This pathologic milieu may put them at risk for developing autoimmune disease (AID).

Hypothesis:
We hypothesized a higher incidence of AID in patients with CHD.

Methods:
We conducted a retrospective review of the Vizient® Clinical Data Base (a national, administrative database) from 10/2019–12/2023 for admissions aged 1-25 years with ICD-10 codes for AID, with and without ICD-10 codes for CHD. ICD-10 codes for 22q11 deletion were also included in the query due to its potential confounding immunologic effects. Data included: demographics, length of stay (LOS), complication and in-hospital mortality rates, and costs. Comparisons were made between the groups with CHD and AID and those without AID (NO-AID).

Results:
There were 4,680,247 admissions without 22q11 deletion. Of these admissions, there was a lower incidence of AID in the CHD group compared to those without CHD [1,771 (0.7%) vs 59319 (1.3%),
p
<0.001]. There was no difference in 22q11 deletion in CHD admissions with AID and those without (2.1 vs 2.2%,
p
=0.643); only the population without 22q11 deletion was analyzed further. Of 61,090 admissions with CHD, there were 1,771 with AID and 59,319 with NO-AID. Details are in Table 1. CHD patients with AID were older (18 vs 6 years), more likely female (54.9% vs 47.6%), more commonly White individuals (63% vs 58.9%) and had longer LOS (
p
<0.001 for all). There were no differences in complication and mortality rates or costs.

Conclusions:
This national database review suggests a lower incidence of AID in patients with CHD compared to those without CHD. However, patients with CHD and AID were older and had a longer LOS. These findings highlight a possible time-dependent component in AID development, as well the potential negative effects on hospital outcomes in the setting of multiple, complex comorbid conditions.
Abstract 4141919: Differential Association of Atrial Myopathy Subtypes with Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities Study (ARIC)
Authors: Moser Ethan , He Ruoyu , Wang Wendy , Van't Hof Jeremy , Sun Daokun , Zhang Chunxiao , Zhang Michael , Chan Lap Sum , Solomon Scott , Shah Amil , Pan Wei , Chen Lin
Published: November 2024

Background:
Atrial myopathy—characterized by abnormal left atrial (LA) function or size— is independently associated with cardiovascular outcomes such as atrial fibrillation (AF) and stroke. One obstacle to the discovery of strategies to prevent atrial myopathy-related outcomes is its heterogeneity.

Objective:
Resolve heterogeneity of atrial myopathy by identifying distinct subtypes of atrial myopathy with differential risk of AF using an unsupervised machine learning clustering analysis.

Methods:
We included ARIC participants at visit 5 (2011-13) with atrial myopathy—defined using LA reservoir strain (Female: <28.6%, Male: <26.4%)—and no prevalent AF. We considered 52 clinical, demographic, ECG, and echocardiographic candidate variables for the clustering analysis. Random forest imputation was used for missing data. LASSO regression of atrial myopathy was used to select pertinent variables. Selected variables were standardized, and clusters were identified using model-based clustering with
mClust
, based on the Bayesian Information Criterion. Multivariable Cox regression model was used to evaluate the association between final clusters and incident AF.

Results:
In total, 1,415 (mean age ± SD, 77 ± 5 years, 70% Female, 26% Black) participants with atrial myopathy were included in the clustering analysis, and 5,209 participants in the Cox regression analysis. There were 22 variables selected, and 3 clusters identified (
Table 1
). Over a mean follow-up of 6.3 years, 712 incident AF cases occurred. Compared to those with no atrial myopathy, all three clusters had differentially increased risk of incident AF (
Table 2
).

Conclusion:
Clustering analysis of individuals with atrial myopathy identified 3 unique clusters that were differentially associated with incident AF providing evidence of the heterogeneity of atrial myopathy. The clustering scheme may be used to select high-risk patients for clinical trials aimed at preventing outcomes related to atrial myopathy.