bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4141461: Zonal Coating Application System for Left Atrial Appendage Occlusion Devices: A Novel Approach to Reduce Peri-Device Leakage and Device Related Thrombus.
Authors: Houmsse Mustafa , Muskara Andrew , Pasca Damaris , Roy Arnab
Published: November 2024

Introduction:
Left atrial appendage occlusion (LAAO) is an effective method of stroke prevention in patients with atrial fibrillation (AF). However, peri-device leakage (PDL) and device related thrombus (DRT) are common limitations of LAAO. Notably, PDL is associated with an increased risk of thromboembolic events. In order to minimize DRT, the Watchman FLX Pro is coated with PVDF-HFP. We aim to minimize both DRT and PDL with our novel zonal coating application system (ZCAS). ZCAS integrates a two-part thromboresistant and endothelialization promoting coating onto LAAO devices (Figure 1). In order to determine the optimal coating for the endothelialization promoting zone of ZCAS, we validated coating candidates in an in vitro model of LAAO device endothelialization (Figure 2).

Hypothesis:
We hypothesized that polyethylene terephthalate (PET) mesh coated with collagen type IV, fibronectin + VEGF, or poly-L-lysine would improve endothelial cell viability and proliferation.

Methods:
Human umbilical vein endothelial cells (HUVEC) were cultured in DMEM/F12 supplemented with ATCC’s Endothelial Cell Growth Kit and antibiotics. For the cell viability and proliferation assay, HUVEC cells were cultured in DMEM/F12 supplemented with 2% FBS, 10 mM L-glutamine, and antibiotics. A 96 well plate with PET inserts was coated with three coating candidates. Each coating was applied in three concentrations ([1x], [10x], and [100x]) with triplicates for each concentration. The coatings included collagen type IV ([1x]: 1 ug/cm2), fibronectin ([1x]: 1 ug/cm2) + VEGF ([1x]: 10 ng/cm2), and poly-L-lysine ([1x]: 4 ug/cm2). An MTS assay was performed at 48 hours after plating to assess cell viability and proliferation.

Results:
MTS absorbance relative to the uncoated control (MTS absorbance coated well/MTS absorbance uncoated well) for collagen type IV at [1x], [10x], and [100x] was 0.81, 1.29, and 0.84 respectively (Table 1). Fibronectin + VEGF at [1x], [10x], and [100x] was 1.31, 1.62, and 0.96. Finally, poly-L-lysine at [1x], [10x], and [100x] was 0.69, 0.90, and 0.91 respectively.

Conclusion(s):
Among the coating candidates, fibronectin (1 ug/cm2) + VEGF (100 ng/cm2) had the greatest increase in cell viability and proliferation compared to the uncoated PET control. The significance of this finding lies in the potential for ZCAS to improve the endothelial seal between the LAAO device and LAA orifice, which may significantly reduce PDL post-implantation.
Abstract 4141469: Left Ventricular Septum Displacement Implications in the Limited Cardiac Reserve, RV to Pc Uncoupling and Oxygen Uptake During Exercise in Heart Failure
Authors: Serrantoni Violetta , CRISCI GIULIA , Losito Maurizio , Zagarra Tania , Ginelli Daniele , Bursi Francesca , Guazzi Marco
Published: November 2024

Background:
Dyspnea on exertion is cardinal symptom in heart failure (HF) and may be caused by an unfavorable dynamic of ventricular interaction. This concept has been poorly addressed over time and we hypothesized that a careful study of the interventricular septum adaptations during maximal exercise in HF might be implicated in the limited cardiac reserve and uncoupling of right ventricular (RV) to pulmonary circulation (Pc), both yielding to a limited O2 uptake.

Aim:
To study the pathophysiology behind biventricular interaction during exercise in HF, evaluating the role of septum displacement during exercise and how and whether it would affect peak exercise oxygen consumption (VO
2
peak) through a limited cardiac output (CO) increase and some degrees of RV to PC uncoupling assessed by TAPSE/PASP.

Methods:
22 HF performed a combined cardiopulmonary exercise testing imaging (CPET imaging) with RV 3D-imaging analysis and were compared with a control population.

3D imaging of the RV chamber was examined off-line using the 4D RV TomTec software and obtained 3D mesh of the RV model using custom software to obtain the mean curvature value of IVS in 4 regions of: inflow tract (RVIT), outflow tract (RVOT), apical and body. We acquired measurements of curvature during end-diastole (ED) and at end systole (ES) phases and obtained a parametric curvature map.

Results:
HF patients (mean age 72±12, 27% female) typically showed an abnormal septal curve, with a more leftward configuration either at rest and under exercise (rest =−0.01±0.007 at ED, and −0.01±0.009 at ES; peak exercise= −0.01±0.006 at ED, and −0.01±0.007 at ES) compared to controls (rest=−0.02±0.002 at ED, and −0.02±0.006 at ES; peak exercise −0.02±0.0.006 at ED, and −0.02±0.01 at ES, Figure). Notably, the degree of the IVS curvature showed a linear correlation with an impaired gas exchange performance as indicated by a lower peak VO
2
, a limited CO and impairment of TAPSE/PASP in HF (respectively, r=0.64, p<0.001, r=0.5, p<0.001, r=0.53, p<0.001 at ED during exercise; r=0.61, p<0.001 at ES during exercise; Figure).

Conclusions:
In HF, the evidence of right to left IVS displacement appears worth of investigation, by intervening strictly to a reduced CO response, and RV-PA uncoupling during exercise. These findings clearly point to the utility of assessing how new and current therapeutic strategies may modulate the negative septum displacement and overall cardiac mechanics.
Abstract 4141472: Birthweight is Associated with Left Ventricular Mass Index in Childhood
Authors: Sill Jordan , Woo Jessica , Urbina Elaine
Published: November 2024

Introduction/Background:
Increased left ventricular mass (LVM) is a risk factor for adult CV disease and is associated with cardiac development in utero. Associations of birthweight with LVM have been demonstrated in young children and adolescence, however, the association between birth weight and LVM in mid-childhood is not well described.

Research Questions/Hypothesis:
Utilizing an existing longitudinal data set of healthy children, we aimed to determine the association of birthweight to increased LVM at 6-8 years of age.

Methods/Approach:
A longitudinal cohort of 372 term-born children was enrolled at age 3 and followed until age 6-8 years. Anthropometrics, echocardiography, and maternal recall of birth weight were collected. LVM from echocardiography was indexed to height
2.7
. Multiple linear regression analysis was performed to assess the association of birthweight with LVM index at 6-8 years of age, adjusting for race, sex, body mass index (BMI) z-score, and systolic blood pressure (SBP) percentile collected at the time of echocardiography.

Results:
303 children were included in the analysis (21.5% Black and 88.5% White, mean age 7.4 ± 0.3 years at the time of echocardiography, mean birthweight 3.4 ± 0.6 kg, mean SBP percentile 42.7 ± 21.6 percentile). Greater birthweight significantly contributed to greater LVM index (1.2 ± 0.6, p = 0.03), along with Black race (1.9 ± 0.8, p = 0.02) and greater current BMI z-score (2.1 ± 0.3, p < 0.01). Sex and SBP percentile were included in the model but were not significantly related to LVM index (p = 0.23 and 0.51 respectively) in this analysis.

Conclusions:
Greater birthweight is significantly associated with greater left ventricular mass in childhood, independent of BMI z-score at the time of echocardiography. This suggests a critical period in fetal cardiac development that affects cardiac structure in mid-childhood.
Abstract 4141474: Impact of Serum 5-Hydroxytryptophan Levels on Coronary Artery Calcification Severity in Acute Coronary Syndrome Patients: Insights from the Microbiota-Gut-Brain Axis
Authors: Chen Ching Jung , Wang Chao-Yung
Published: November 2024

Background:
5-Hydroxytryptophan (5-HTP) has shown positive clinical effects on various neuropsychiatric and metabolic disorders, particularly depression. While it is known to increase serotonin levels in the brain and gastrointestinal tract, its pharmacology remains largely unexplored. Additionally, 5-HTP influences the mouse gut microbiome, which is closely linked to depression through the "microbiota-gut-brain axis." However, the role of 5-HTP in vascular disease is not well understood. This study aimed to investigate the potential correlation between serum 5-HTP levels and the severity of coronary artery calcification (CAC) in patients with acute coronary syndrome (ACS).

Methods and Results:
This study included 183 ACS patients who underwent coronary angiography. The severity of coronary calcification was recorded, and serum 5-HTP levels were measured after the coronary event. The study period was from February 4, 2009, to August 9, 2020. The primary exposure variable was 5-HTP levels, and the primary outcome was the severity of coronary calcification assessed through fluoroscopy. Logistic regression was used to determine the association between 5-HTP levels and calcification severity, adjusting for age, gender, smoking status, chronic kidney disease, hyperlipidemia, and diabetes. Odds ratios (OR) and 95% confidence intervals (CI) measured the strength of associations, with statistical significance set at p < 0.05.

High 5-HTP levels were significantly associated with more severe calcification (p = 0.04, OR = 3.3, 95% CI = 2.6 to 40686.5). For other factors, the OR for smokers was 0.97 (0.53 to 1.77); dyslipidemia 0.91 (0.5 to 1.63); hypertension 1.57 (0.87 to 2.82); male gender 1.35 (0.45 to 4.01); age 1.07 (1.03 to 1.10); diabetes 1.24 (0.67 to 2.31); chronic kidney disease 1.07 (0.33 to 3.50). After adjusting for conventional risk factors, the association between 5-HTP and calcification remained significant (p < 0.05).

Conclusion:
Higher 5-HTP levels are positively associated with greater severity of coronary artery calcification. This correlation persists even after adjusting for conventional risk factors.
Abstract 4141485: Liver Steatosis in Women with Coronary Microvascular Dysfunction
Authors: Paquin Amelie , Kwan Alan , Ranasinghe Sachini , Nelson Michael , Maughan Jenna , Lauzon Marie , Gulati Martha , Bairey Merz C Noel , Wei Janet
Published: November 2024

Introduction:
Metabolic dysfunction-associated steatotic liver disease (MASLD) has been previously associated with coronary microvascular dysfunction (CMD) and is closely related to metabolic syndrome among men and women. Data regarding the association of quantitative liver steatosis and CMD in women with ischemia and no obstructive coronary arteries (INOCA) are scarce.

Aim:
To evaluate the association of liver steatosis with myocardial perfusion in women with CMD and reference controls.

Methods:
Women with CMD and no obstructive coronary arteries (n=55) from 2 prospective cohort studies (R01HL146158, R01HL153500) and asymptomatic age- and sex-matched reference controls (n=10) underwent stress and rest cardiac magnetic resonance imaging (MRI), with a validated MRI quantification of liver fat by proton density fat fraction (PDFF), at a single center. CMD was confirmed by coronary function testing or prior diagnostic stress tests. Parameters of liver fat and LV structure, function and myocardial perfusion reserve index (MPRI, a measure of CMD) were compared between cases and controls. A threshold of PDFF ≥5.2% was used to define significant liver steatosis.

Results:
Other than higher prevalence of hypertension in the CMD group, age and cardiometabolic history were not significantly different between the groups, as were the PDFF and prevalence of liver steatosis (Table). PDFF directly correlated with body mass index (r=0.41, p<0.01). There was no correlation between PDFF and MPRI (Figure).

Conclusions:
In this pilot study, our results suggest similar prevalence of liver steatosis between women with CMD and reference controls. Interestingly, MPRI did not correlate with PDFF, suggesting that mechanisms other than metabolic health may play a significant role in the pathophysiology of CMD among women with INOCA.
Abstract 4141486: Site-Specific Transcriptomic Patterns and Cell Types Associated with Hypertension
Authors: Milstone Zachary , Moreira Jesse , Smith Karan , Gower Adam , Alekseyev Yuiry , Cunha Jason , Fisher Nathaniel , Lepson Joshua , Lamason Ashlee , Tao Brian , Williams Christopher , Benjamin Emelia , Levy Daniel , Mitchell Richard , Padera Robert , Choi Seung Hoan , Gopal Deepa , Tucker Nathan , Fetterman Jessica
Published: November 2024

Introduction:
The biology of early human hypertensive heart disease (HHD) is largely unexplored due to limited cardiac tissue access. Site-specific transcriptomics of human cardiac tissue
before
development of overt HHD offers a unique vantage to understand the biology of HHD in human cardiac tissue.

Hypothesis:
We hypothesize that transcriptomic signatures and cell subtype proportions differ in human heart tissue from HTN donors compared to normotensive (NTN) donors in a site-specific manner.

Methods:
We performed bulk RNA-seq on rRNA-depleted libraries from left (LV) and right (RV) mid-ventricular-wall tissue (average depth 114 million reads/sample) collected postmortem from HTN (n=3, 67% Black/Latinx) and NTN (n=2, 50% Black/Latinx) donors. We performed single-nucleus RNA-seq (snRNA-Seq) on cardiac tissue from the same donors (average of 4,062 LV nuclei). Differential gene expression, lineage identification, and Gene Set Enrichment Analysis (GSEA) were performed with publicly available software.

Results:
All donors were female with matched postmortem intervals (time from death to tissue preservation; HTN 19±9 hours, NTN 18±6 hours). HTN donors were older (65±7 years) than NTN donors (36±16 years). A total of 416 genes were associated with HTN (Wald test, FDR
q
<0.05) across both ventricles (correcting for site). When tested separately, 72 (LV) or 83 (RV) genes were associated with HTN (FDR
q
<0.05), with 13 common genes, indicating site-specific differences. GSEA of genes ranked by Wald statistic computed across both ventricles showed that transcripts involved in single-stranded DNA helicase activity, branched-chain amino acid catabolism, and NAD-dependent deacetylase activity were coordinately associated with HTN (FDR
q
<0.05). snRNA-seq revealed 9 cell types in these samples, including immune cells and chamber-specific cardiomyocytes (CMs) with higher proportions of LV CMs and lymphocytes associated with HTN compared to NTN.
MYH6
and
MYL7
expression was unchanged with respect to HTN by RNA-seq but lower in LV HTN CMs compared to NTN by snRNA-seq, suggesting dysregulation of contractile programming in HTN LV CMs.

Conclusion:
HTN is associated with altered cardiomyocyte/lymphocyte ratios, and site-specific differential expression of cardiac contractile elements. Further study is required to validate these findings with additional samples and elucidate mechanisms driving transcriptional program differences in the hypertensive human heart.
Abstract 4141488: Initial Real-World Experience with a Novel Wearable Cardioverter Defibrillator
Authors: Syed Zain , Phukan Anisha , Gustavson Laura , Li Brian , Hazarika Surovi , Syed Qarab , Chung Roy , Sharma Navneet , Pattisapu Anish , Kanj Mohamed , Chung Mina , Tanaka Esposito Christine
Published: November 2024

Background:
The wearable cardioverter defibrillator (WCD) can reduce sudden cardiac death; effectiveness depends on adherence. A novel WCD designed for sex specific comfort and noise immunity has reported improved compliance.

Hypothesis:
Patient compliance with the WCD maximizes device utility in treating significant arrhythmia.

Aims:
Report WCD patient compliance and efficacy in a cohort with balanced gender representation. Evaluate WCD performance in minimizing noise artifact leading to false alarms and unnecessary shocks.

Methods:
Retrospective analysis of patients prescribed the ASSURE WCD at the Cleveland Clinic. Clinical data was collected via medical chart review. All device-detected arrhythmia episodes were manually adjudicated by a Board-certified Electrophysiologist. Detected rhythms that persist, result in an audible alarm notifying that a shock is imminent. A conscious patient can manually divert a shock. An alarm was deemed true and shock appropriate if the underlying rhythm was sustained VT/VF.

Results:
Fifty-five patients were fitted with a WCD. Median daily use 22 hr/day (IQR 13,24) and median duration of use 43 days (IQR 8,79). Female representation was 49%, significantly greater than prior reports of WCD experience. 4 episodes of sustained VT/VF were detected in 4 patients. A single shock terminated VT/VF in 2, while spontaneous termination of VT/VF occurred in the other 2 patients who diverted shocks. One shock for hemodynamically unstable atrial fibrillation with heart rate >200bpm was delivered and deemed necessary. No deaths occurred while wearing a WCD.

Of 163 recorded episodes, 62 (38%) persisted and triggered an alarm (Figure 1). 10 patients experienced a median of 1 (IQR 1,9.5) alarm during the WCD wear period. The majority (97%) of alarms were associated with a significant tachyarrhythmia, with only 3% due to noise artifact. No inappropriate, unnecessary shocks were delivered.

Discussion:
Patient compliance with the ASSURE WCD was high in this real-world observational study with equal representation of both sexes. The WCD effectively terminated sustained hemodynamically significant tachyarrhythmias, emitted few false alarms due to noise and resulted in no unnecessary and inappropriate shocks.
Abstract 4141496: Methylation changes in monocytes of type 2 diabetes patients with cardiovascular disease are associated with apoptosis and inflammation pathways.
Authors: Bradic Martina , Halabi Najeeb , Shi Yuxin , Thomas Binitha , Abi Nahed Julien , Jayyousi Amin , Al suwaidi Jassim , Mezey Jason , Abi Khalil Charbel
Published: November 2024

Background:
Monocytes have been implicated in the initiation and progression of cardiovascular (CV) complications of type 2 diabetes (T2D).

Aim:
We investigated diabetes-induced methylation changes and enriched pathways in circulating monocytes of T2D patients. We compared T2D vs. non-T2D participants and analyzed T2D patients according to diabetes control. Further, we assessed methylation changes in a subset of patients with poor diabetes control and high CV risk following a 6-month treatment intensification.

Methods:
We recruited consecutively 200 participants, 160 with T2D and 40 non-diabetes controls. Circulating monocytes were sorted using the FACSAria2 ™ cell sorter. Samples were sequenced using enhanced reduced representation bisulfite sequencing. Methylation data was processed with Lumi and limma R packages to obtain batch and covariate corrected differential expression values for the indicated comparisons. Ingenuity Pathway Analysis (Qiagen) was used to identify enriched pathways for each tested condition. Differentially methylated genes used for pathway analysis were those with a p-value < 0.05 and an absolute logFC value ≥ 0.5.

Results:
There were 1122 differentially methylated genes when comparing T2D to non-T2D patients. Among the top five enriched canonical pathways, apoptosis signaling was predicted to be activated, while the RHO GTPase cycle and LPS-stimulated MAPK signaling pathways were predicted to be inhibited. Within patients with diabetes, there were 1670 differentially methylated genes comparing those with poor control (HbA1c ≥ 7%) vs. good control (HbA1c<7%). Among the top five enriched pathways, synthesis of DNA, DNA replication signaling, and cell cycle checkpoints were activated while inhibition of ARE-mediated mRNA degradation pathway was inhibited. In patients who responded to treatment intensification (Δ HbA1c = -1.5%, p= 0.02), 1377 differentially methylated genes and differentially inhibited pathways such as non-homologous end-joining and cellular response to heat stress were identified. In non-responders, we identified 1582 differentially methylated genes and activated pathways, including inhibition of mRNA degradation pathways and p14/p19 ARF signaling.

Conclusion:
Treatment intensification in T2D patients with CVD and poor control showed the presence of differentially methylated genes affecting pathways regulating cell proliferation and inflammation and are known to be associated with diabetic CVD complications.
Abstract 4142783: Association of Body Roundness Index and Cardiovascular Disease among US Adults
Authors: Wang Kang , Chen Pengfei , Tan Bohao , Wei Cheng , Tan Jianjun , Fang Zhen-fei , Liu Qiming , Zhou Shenghua , Chen Zhangling
Published: November 2024

Background:
Obesity is one of the major risk factors for cardiovascular disease (CVD), body roundness index (BRI) is more comprehensive in assessing fat distribution than traditional measurements. However, evidence regarding the association between BRI and the risk of CVD was limited, particularly in American people. This current study aimed to investigate the association between BRI and the risk of CVD among US adults.

Hypothesis:
We hypothesized that higher BRI was associated with a higher risk of CVD.

Methods:
A total of 21,852 participants were included in the National Health and Nutrition Examination Surveys from 6 survey cycles (2003-2004, 2005-2006, 2007-2008, 2009-2010, 2011-2012, 2013-2014, 2015-2016 and 2017-2018). Weighted multivariate logistic regression was carried out to examine the relationship between BRI and the risk of CVD. Restricted cubic spline (RCS) curves were employed to analyze nonlinear relationships.

Results:
Among 21,852 US adults, the mean (SD) age was 47.5 (17.3) years, 10,669 (48.8%) were female, and 1886 were diagnosed with CVD. In the weighted multi-variable logistic regression model with adjustment for demographics, lifestyle, economic status and dietary factors, higher BRI was significantly associated with a substantially higher risk of CVD. Compared with the participants in the lowest quartile of BRI, those in the highest quartile of BRI had a higher CVD, with OR and 95%CI of 2.47 (1.92-3.17). Furthermore, the RCS demonstrated a linear dose-response relationship between BRI and CVD (P
non-linearity
=0.29).

Conclusion:
This national cohort study found a higher BRI was associated with a higher risk of CVD among US adults. BRI may provide a new perspective for CVD prevention among adults.
Abstract 4142792: VA Lipid Optimization Reimagined Quality Improvement Project (VALOR-QI) at the Dallas VA
Authors: Bhatnagar Anupriya , Bryant Ananda , Shahin Daryoush , SOE KYAW
Published: November 2024

The Dallas VA is one of the 50 VA sites participating in a national quality improvement initiative called VALOR-QI: VA Lipid Optimization Reimagined Quality Improvement Project. VALOR-QI is a collaborative project between the U.S. Department of Veterans Affairs (VA) and the American Heart Association (AHA) with the goal of positively impacting veterans’ cardiovascular (CV) health. As part of the program, VA sites work with an AHA QI Consultant to develop and deploy a local quality improvement plan to help overcome site specific barriers preventing veterans from achieving optimal cholesterol levels.

We hypothesize that the QI strategies implemented will positively impact lipid levels and ultimately CV outcomes among high-risk patients. We aim to assess potential barriers to achieving LDL-C <70 mg/dL and develop efficient ways to maintain LDL-C goal.

Our approach to the VALOR-QI program at Dallas VA is by enrolling patients with established ASCVD and LDL-C > 70 mg/dL from cardiology, vascular, diabetes, lipid, and independent PharmD clinics. These patients are followed by a health coach every 2- 6 months. Medical adherence is enforced by the health coach ensuring timely refills and reminders. Lifestyle modifications are encouraged via educational materials, referral to dieticians, recreation classes, and tobacco cessation. Patients are also encouraged to sign up for patient portal (my HealtheVet) to access electronic medical records and expedite communication with their healthcare team. The health coach provides individualized counseling regarding lipid lowering treatment and acts as liaison between patients and their providers.

VALOR-QI was launched at Dallas VA in Jan 2023. As of May 17
th
, 2024, an interim analysis showed that out of 132 veterans engaged, 49 (37.1%) achieved target LDL-C, 66 (50%) received educational material, 4 (3.03%) were referred to dieticians, 10 (7.58%) were referred to recreation programs, and 4 (17.4% of active smokers) were interested in quitting.

In conclusion, our VALOR-QI strategy at Dallas VA showed encouraging results, but it is premature to make final conclusions. The support of a health coach showed improved medication adherence, health literacy, and lifestyle modification, thus achieving LDL-C target. Major barriers to achieving target LDL-C were health literacy about high cholesterol, challenges in navigating the health care system, and treatment inertia among patients and providers.
Abstract 4142799: Central role of LIM domain binding 3 (LDB3) protein in Tetralogy of Fallot assessed by single-nuclei multiome profiling of paediatric right ventricular samples
Authors: Gyongyosi Mariann , Han Emilie , Lukovic Dominika , Hasimbegovic Ena , White Benjamen , Gynter Artur , Mancikova Veronika , Pavo Imre , Michel-Behnke Ina
Published: November 2024

Background and aims:
Tetralogy of Fallot (TOF; EC: 1565/2019) is the most common cyanotic congenital heart defect with a world-wide incidence of 0.02–0.04%. The pathophysiological mechanisms driven by variable genetic background are poorly understood. We applied the single-nuclei multiome profiling, composed of ATAC and RNA-seq from the same nuclei, of right ventricular samples of children with TOF. The final aim was to define cell types and characterize gene regulation states in different cell clusters including activation and maturation.

Methods:
Right ventricular samples were prospectively gathered during routinely performed cardiac surgery for TOF correction (EC: 1565/2019). In total, six paediatric patient samples were processed, and on average ~1,500 nuclei were sequenced per sample. Data was analysed using Scanpy to cluster and annotate cells, pycisTopic to identify cell stats and cis-regulatory topics, and SCENIC+ for enhancer-driven gene Regulatory network (eRegulon) construction.

Results:
Through manual annotation, using published markers, we identified cell types including cardiomyocyte, fibroblast, endothelial, pericyte, immune and neuronal cells. From this, we observed cell type specific expression, with overexpression of decorin in fibroblasts, PTPRC in immune cells, and neurexin genes in neuronal cells found. Differential expression analysis highlighted patient specific patterns of expression, of which gene set enrichment showed enrichment for genes associated with actomyosin structure organisation, dilated cardiomyopathy and cardiac muscle contraction. Integration of the gene expression data with the ATAC-seq data, across all patients, allowed for the construction of eRegulons networks. In detail, in the cardiomyocyte-annotated clusters, we identified enrichment of MEF2, MEIS2 and EPAS1 family enhancers with a central role of LIM domain binding 3 protein (LDB3, associated with cytoskeletal actin and muscle alpha-actin binding) (Fig. 1).

Conclusion:
Single nuclei multiome profiling of paediatric right ventricular TOF samples identified several patient specific patterns of expression and regulatory networks, related to the development of cyanotic congenital heart disease, and sheds light to the potential drivers of TOF.
Abstract 4143219: Pressure-Volume Analysis by Three-Dimensional Echocardiography: A Novel Method to Estimate Left Ventricular Efficiency
Authors: Hammersboen Lars-Egil , Boe Espen , Duchenne Jurgen , Aalen John , Odland Hans Henrik , Villegas-Martinez Manuel , Frostelid Vetle Christoffer , Khan Faraz , Sletten Ole Jakob , Witsoe Marit , Skulstad Helge , Rega Filip , Gheysens Olivier , Voigt Jens-Uwe , Smiseth Otto , Stugaard Marie , Remme Espen
Published: November 2024

Background:
Left ventricular (LV) efficiency is a key pathophysiological marker in heart failure (HF). LV pressure curve estimation and three-dimensional (3D) volumes via echocardiography allows for non-invasive pressure-volume (PV) analysis and calculation of an index of efficiency (Figure 1).

Aim:
Validate efficiency index by 3D echocardiography by comparing it to invasive measurements and efficiency derived from Positron Emission Tomography (PET) metabolism.

Methods:
Two experimental models were utilized - one with canines (n=21) and another with sheep (n=12). In canines, echocardiography provided 3D LV volumes and valve event timings. The pressure curve was estimated by adjusting the time axis of a reference pressure curve to the valve events and its amplitude to measured peak LV pressure, which in clinical practice would be approximated as systolic brachial cuff pressure. Invasive pressure was measured by micromanometer and volume by subendocardial piezoelectric crystals. Non-invasive and invasive efficiency indices, calculated as the ratio of stroke work to total mechanical energy (Figure 1), were compared during baseline, right ventricular pacing, aortic constriction and dobutamine infusion.

Twelve sheep implanted with a pacemaker underwent 8 weeks of rapid dyssynchronous DDD pacing to induce dilated HF. LV efficiency index was calculated as in Figure 1, using measurements from a PV-catheter calibrated to end-diastolic volume by cardiac MRI, and compared to efficiency calculated as stroke work divided by total LV glucose metabolism via PET/CT. Recordings were performed during AAI and DDD pacing, at baseline (n=3) and following 8 weeks pacing-induced HF (n=12).

Results:
In canines, non-invasive and invasive efficiency indices showed excellent agreement (r=0.95, p<0.0001; mean difference 0.4%, SD 3.4%) (Figure 2). In sheep, the efficiency index showed similar decline compared to efficiency by PET/CT after induction of HF and after switching from AAI to DDD pacing (p<0.05 for all interventions). Overall correlation between the methods was moderate (r=0.67, p=0.0001) but excellent in animals with longitudinal data (r=0.89, p=0.0001) (Figure 3).

Conclusions:
Efficiency index by 3D echocardiography is accurate and reflects changes in efficiency measured by PET/CT. It may thus be of interest for clinical use.
Abstract 4143225: Carotid Artery Ultrasound Grayscale and Incident Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Tattersall Matthew , Mitchell Carol , Gangnon Ronald , Korcarz Claudia , Hansen Kristin , GEPNER ADAM , Rapp Stephen , Johnson Sterling , Stein James
Published: November 2024

Introduction:
Vascular contributions to cognitive impairment and dementia are potentially modifiable. Early detection of reversible arterial injury may improve dementia risk stratification and provide an opportunity for treatment monitoring. We hypothesized that carotid ultrasound grayscale-median (GSM), a novel imaging biomarker of early arterial injury, would predict incident all-cause dementia in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods:
The MESA enrolled adults aged 45-84 years old who were free of atherosclerotic cardiovascular disease at baseline. Common carotid artery GSM (grayscale units) was measured at baseline. Incident all-cause dementia events were identified by hospital and death records. Adjusted Cox proportional hazards models with natural cubic splines allowing for non-linear effects investigated the associations of baseline GSM and incident all-cause dementia.

Results:
The 1,788 participants were a mean (standard deviation) 63.1 (10.3) years old (53% female). Over a median of 13.7 years, 157 all-cause dementia events occurred. Lower (worse) carotid GSM independently predicted incident all-cause dementia (Hazard Ratio [HR] 1st to 3rd tertile, 1.39 [95% Confidence Intervals, 1.08-1.80], p =0.04). In models adjusting additionally for carotid IMT there was no attenuation of the association of GSM and incident all-cause dementia (HR 1.63 [95% CI 1.13-2.35], p=0.033) (Figure 1).

Conclusions:
Lower GSM predicts incident all-cause dementia independent of carotid intima-media thickness, suggesting it may serve as an early marker of dementia risk.
Abstract 4143239: Extracorporeal Shockwave Therapy Improves Physical Outcomes and Quality of Life In Patients With Symptomatic Peripheral Arterial Disease: Results from a Meta-analysis of Randomized Controlled Trials
Authors: Kashif Talha , Rahman Ummi , Qureshi Ali Akram , Mubashir Mohammad Maheer , Alvi Fatima , Qureshi Muhammad Ahmad
Published: November 2024

Introduction:
Extracorporeal shockwave therapy (ESWT) is a non-invasive procedure that may be useful to treat symptomatic peripheral arterial disease (PAD). Trials comparing ESWT with control groups have shown promising results.

Methods:
PubMed, Cochrane, EMBASE, and Google Scholar were searched for randomized controlled trials reporting the efficacy of extracorporeal shockwave therapy versus control in patients with symptomatic PAD. Data from eligible studies was analyzed using the Review Manager 5.4 software. Mean difference (MD) and 95% Confidence intervals (CI) were calculated for continuous outcomes. Inverse variance method and a random effects model were used for pooled estimates. A p-value < 0.05 (Z-test) was considered significant.

Results:
5 randomized controlled trials with 264 patients were included in our analysis. A significant increase in the mean walking distance (MD: 54.13, 95% CI 9.34 to 98.92, p=0.02), pain-free walking distance (MD: 54.13, 95% CI 14.19, 57.88, p= 0.001), SF-36 physical component summary (MD: 11.97, 95% CI 0.26 to 23.69, p=0.05), EQ-5D-3L index score (MD; 0.08, 95% CI: 0.00 to 0.15, p=0.05) and VascuQoL index ((MD: 0.48, 95% CI 0.03 to 0.92, p= 0.04) was seen with ESWT. A slightly higher ankle brachial pressure index was seen in the control group (MD: -0.01, 95% CI: -0.02 to -0.00, p=0.04). There was no difference in SF-36 physical functioning domain score (MD: 18.58, 95% CI: -0.29 to 37.45, p=0.05) and SF-36 bodily pain score (MD: 9.17, 95% CI: -2.885 to 21.19, p=0.13).

Conclusions:
There was significant improvement in walking distances, exertional symptoms, and quality of life with ESWT. However, ESWT did not translate to an increase in post-treatment ankle-brachial index which was slightly higher in the control group. There is a need for larger randomized controlled trials to substantiate the efficacy of ESWT in treating symptomatic PAD.
Abstract 4143256: Non-invasive, Radiation-free, Non-contrast Myocardial Volume Oxygen Consumption Quantification Using Free-breathing MR Blood Oximetry
Authors: Yang Chia Chi , Malagi Archana , Huang Li-Ting , Huang Yuheng , Yoosefian Ghazal , Zhang Xinheng , Guan Xingmin , Christodoulou Anthony , Li Debiao , Han Hui , Dharmakumar Rohan , Yang Hsin-jung
Published: November 2024

Background:
Myocardial oxygen consumption (MVO
2
) is a central marker in measuring cardiac energetics. Current methods to quantify MVO
2
are inaccessible due to the requirement of invasive procedures or PET agents that require onsite cyclotrons.

Hypothesis

A free-breathing, non-ECG-gated, motion-resolved Cardiac MR blood oximetry technique can noninvasively quantify MVO
2
in standard clinical MRI scanners without using ionizing radiation and contrast agents.

Method:
The developed free-breathing CMR imaging technique was prescribed in a 3T clinical scanner to the mid left ventricle (LV) and the cross-section of the coronary sinus(CS) slices of the heart to obtain the corresponding blood oxygenation (SbO
2
) and the hematocrit (Hct) in heart chambers. 2D phase contrast CMR was performed in the CS to quantify the myocardial blood flow (MBF). The MVO
2
was quantified with Fick’s law (MVO
2
=arterio-venous oxygen difference x MBF). We examined the developed method in healthy pigs (N=7) under rest and adenosine stress and validated it against invasive blood sampling. In addition, we tested the method’s clinical feasibility in healthy human volunteers (N=4).

Results:
Comparable blood oxygenation levels (SbO
2
) and MVO
2
were measured and compared between the non-invasive CMR and invasive ground truth (Fig. 1). Significantly increased coronary sinus SbO
2
is observed in both methods during adenosine infusion. It is accompanied by decreased MVO
2
and rate pressure product (RPP) (Rest: CMR=10.2±2.7ml/min, Inv.=10.8±6.9 ml/min, RPP=7956.9±620.9 mmHg/min; Stress: CMR=5.3±1.9 ml/min, Inv=6.3±3.6 ml/min, RPP=5338.2±618.3 mmHg/min). In Fig. 2, the healthy human volunteers' MVO
2
estimations(14.1±6.7ml/min) shows no statistical difference compared to the previous invasive measurements(16.5±4.8 ml/min, Ganz, et al. circulation 1971).

Conclusions:
The proposed noninvasive CMR technique can quantify MVO
2
in standard MRI scanners without using a needle. It has the potential to provide an accessible, risk-free assessment of myocardial metabolism for patients with potential metabolism impairments.
Abstract 4143262: Unlocking Value: Revealing the Hidden Cost of Outpatient Interstage Care
Authors: Stauber Catherine , Well Andrew , Stewart Eileen , Dillingham Christine , Schuman-McCoy Jeannine , Mahan Anne , Chinta Sindhu , Do Grace , Wang Chumeng , Isada Sher , Fraser Charles , Mery Carlos
Published: November 2024

Background:
Interstage programs decrease morbidity and mortality and are potentially resource intensive. The accurate cost of these programs is unknown. Understanding cost and outcomes of care is necessary to provide high-value care for this population. Time-driven activity-based costing(TDABC) provides an accurate way to understanding costs that occur at the level of the patient.

Research Question:
What is the outpatient cost of the interstage period to the health care system?

Methods:
Single-center study of outpatient interstage care. Direct observation (over 9 months) and retrospective review were utilized to develop process maps. Outpatient interstage and pediatric visits were timed by 5 observers. Cost of personnel was calculated in dollars per minute utilizing median national health system salary data.

Results:
Patients attended a median of 13 cardiology, 5 pediatric, 3 physical therapy(PT), 4 occupational therapy(OT), and 7 speech therapy(SLP) visits while interstage. Total cost of interstage visit personnel was $258.18[$208.59-$389.24] and equipment cost was $1457.79. Total cost of a pediatric visit was $123.55[$130.80-$167.12]. Total cost of outpatient PT, OT, and SLP was $70.58, $66.68 and $72.43, respectively. Total cost of the outpatient interstage period was $6417.38[$5808.94-$8338.96] per patient.(Table) In interstage clinic, patients spent 132[89-165] minutes with providers and 64[41-66] minutes waiting.(Figure) In pediatric clinic, patients spent 73[71-76] minutes with providers and 9[6-13] minutes waiting.

Conclusion:
This work demonstrates that while challenging, TDABC analysis can be applied to complex interstage care to understand costs and move to deliver high-value care for this population. While caring for a child during the interstage period is time and resource intensive, it carries a relatively low cost to the health care system with a total cost of $6417.38 per patient. Additional work is needed to understand costs of inpatient interstage care.
Abstract 4143289: Contemporary and Genomic Cardiovascular Risk Factors Have Explanatory Power Similar to Traditional Risk Factors for Incident Myocardial Infarction
Authors: Bhattacharya Romit , Marnell Christopher , Cho So Mi , Koyama Satoshi , Jowell Amanda , Trinder Mark , Haidermota Sara , Lannery Kim , Honigberg Michael , Zekavat Seyedeh , Surakka Ida , Peloso Gina , Natarajan Pradeep
Published: November 2024

Background:
Modifiable cardiovascular risk factors (CRF) have been proposed to be responsible for 80-90% of the risk for incident coronary artery disease (CAD). However, these studies were conducted prior to the era of preventive medications, novel biomarkers, and genetic risk scores. The relative contributions of traditional and contemporary CRF in light of secular trends in worsening cardiometabolic health globally have not been assessed.

Hypothesis:
Including genetic risk scores and contemporary biomarkers will enhance discrimination and explainability of myocardial infarction (MI) incidence prediction.

Methods:
The UKBiobank was used to identify traditional CRF (hypertension, diabetes, dyslipidemia, smoking, waist-to-hip ratio (WHR), diet, exercise, alcohol intake and socioeconomic deprivation), and contemporary/genetic CRF (lipoprotein(a), high-sensitivity C-reactive protein [hsCRP], familial hypercholesterolemia [FH] variants, and polygenic risk score for CAD [PRS
CAD
]). Incident MI was defined as first-time MI diagnosis or coronary revascularization. Base model discrimination was assessed using C-statistics from Cox proportional hazards models. Percent contribution of each risk factor was calculated by explanatory power lost via Nagelkerke R
2
after removal of the CRF from the full model. Population attributable risks (PAR) were additionally assessed for each model and CRF individually.

Results:
Over a median [IQR] follow-up of 11.0 [9.6, 12.5] years, 17409/299707 (5.8%) of participants developed incident CAD. C-statistics sequentially increased from base model to traditional CRF to contemporary/genetic CRF model with PAR of 84.3% (95% CI 82.4%-86.5%) (
Table 1
). Among CRFs, hypertension (C 0.74, R
2
loss 15.2%, PAR 32.5%) and PRS
CAD
(C 0.72, R
2
loss 12.4%, PAR 38.4%) most strongly explained MI incidence by all 3 indices. Based on discriminability, ApoB:ApoA1 ratio (C 0.71, R
2
loss 3.4%), presence of diabetes (C 0.71, R
2
loss 2.2%), and log(hsCRP) (C 0.71, R
2
loss 1.82%) were subsequently prioritized. PAR analyses included prevalence in prioritization where WHR, presence of diabetes, and log(lipoprotein(a)) levels rose higher.

Conclusions:
The addition of genetic risk factors and contemporary biomarkers to explanatory models for CAD shows previously underappreciated importance of contemporary CRFs such as PRS, hsCRP, and lipoprotein(a) alongside traditional CRFs such as hypertension, dyslipidemia and presence of diabetes.
Abstract 4144512: Impact of Nutritional Status on Transcatheter Edge-to-Edge Repair Outcomes in Mitral Regurgitation: Insights from a National Database Analysis
Authors: Bolaji Olayiwola , Haider Mobeen , Upreti Prakash , Alsmairat Yousef , Hotwani Priya , Rajak Kripa , Basit Jawad , Goru Rohit , Ziaullah Abubakr , Alraies M Chadi
Published: November 2024

Introduction:
Transcatheter edge-to-edge repair of the mitral valve with the MitraClip has offered a less invasive percutaneous alternative to surgical repair in select candidates with mitral regurgitation. Various factors impact the outcomes of MitraClip. We investigated the impact of nutritional status on the outcomes of MitraClip.

Methods:
Utilizing the nationwide inpatient sample data for years from January 1, 2016, and December 31, 2021, patients who underwent MitraClip were identified. They were categorized based on obesity and protein energy malnutrition (PEM). Statistical significance was assigned at p<05.

Results:
Out of the 8115 patients undergoing MitraClip, 2215 had PEM, and 5900 had obesity—table 1. Patients in the PEM group were older, with a higher prevalence of comorbidities, including anemia, pneumonia, liver disease, and fluid and electrolyte disorders, compared to the obese group. Conversely, the obesity group had a higher prevalence of hypertension, diabetes, and hypertension with complications. Our analysis revealed that PEM subgroups had significantly higher in-hospital mortality, cardiogenic shock, mechanical circulatory support (MCS) requirement, post-procedural worsening heart failure, spontaneous cardiac arrest, and major adverse cardiovascular and cerebrovascular events (MACCE). After adjusting for potential confounders, PEM remained an independent predictor of increased odds of death, cardiac arrest, ECMO, MCS, and MACCE compared to obesity. The propensity score matching analysis confirmed that PEM was associated with significantly higher rates of in-hospital mortality, cardiac arrest, and MACCE compared to obesity. (Figure 1)

Conclusion:
Our results reveal that PEM is associated with significantly worse outcomes in patients undergoing MitraClip procedures compared to obesity. These findings are consistent across multivariate and propensity score matching analyses.
Abstract 4144525: An Observation Of Racial Disparities In Patients Admitted With St Segment Elevated Myocardial Elevation
Authors: Ajenaghughrure Godbless , Rahima Kenan , Shemisa Kamal , MISHRA AAVASH , Kishore Gehna
Published: November 2024

introduction:
This sudy explores the multifaceted nature of racial disparities among patients admitted with STEMI, shedding light on the complex interplay of social, economic, and healthcare factors that contribute to differential outcomes among diverse populations.

Methods:
we examined the national inpatient sample 2017-2020 for adult admitted with st segment myocardial infarction,we compared the clincal outcome based on racial distribution.STATA 18th edition was used for analyses. Age, gender, race, hypertension, diabetes, obesity, dyslipidemia, and Elixhauser comorbidity index were identified as confounders by univariate analyses and tested further with multivariate logistic regression models. The primary outcome was mortality. Secondary outcomes were the need for intubation, cardiac arrest, length of stay (LOS), and total hospital charges.

Results:
There were 826315 hospitalizations with STEMI. Mean age was 64 yrs and 62% were male. Among the admitted patients, Caucasians were 593575 (72%), Blacks were 75025(9.1%),Hispanics were 69605(8.4%), Asians were 23734(2.9%). All-cause mortality in patients admitted with STEMI was 88125 where subgroup Analysis with Caucasians, Blacks ,Hispanics and Asians had 60074(10.1%) vs 9135 (12.1%) vs 7645(10.9%) and 2999(12.6%) respectively.

Further subgroups analysis revealed that Blacks (13.9%, aOR 1.37 CI 1.28-1.47,P value<0.001) were more likely to require intubation,followed by Asians(13.5% aOR 1.59 CI 1.43--1.76, p value <0.001) ,then Hispanic (13% aOR 1.45,CI 1.35-1.56 P vale <0.001)and caucasians were least likely to require intubation(9.7% )

Finally, racial subgroup showed significant primary andsecondary outcomes that are presented in Table 1.

Conclusion:
All obtained results revealed statistical significance and we considered Caucasian population as baseline. Mortality waa highest amongst Asians,followed by Blacks then Hispanics and least in the caucasian subgroup. Understanding these disparities is essential for improving healthcare equity and ensuring that all patients receive appropriate and equitable care regardless of their racial or ethnic background.