bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143816: Effects of epicardial adipose tissue on cardiac function and exercise hemodynamics in patients with Heart Failure with Preserved Ejection Fraction
Authors: De Oliveira Gomes Diana , Brazile Tiffany , MacNamara James , Zamani Sauyeh , Hearon Christopher , Wakeham Denis , Nelson Michael , Levine Benjamin , Sarma Satyam
Published: November 2024

Background:
Obesity is a risk factor for developing Heart Failure with Preserved Ejection Fraction (HFpEF). Epicardial adipose tissue (EAT), an ectopic fat depot located between the epicardium and the pericardium, has emerged as a potential risk factor for various cardiovascular diseases, including HFpEF. Previous studies have linked increased EAT thickness, measured by echocardiography, to elevated cardiac filling pressures and systolic and diastolic dysfunction. Compared to echo, a volumetric assessment of EAT with MRI has greater accuracy, precision, and reproducibility. This study aimed to assess the relationship between EAT and cardiac function and exercise hemodynamics in patients with HFpEF.

Methods:
We studied 32 patients with HFpEF (19 women; BMI, 37±6kg/m
2
; age, 69±6years). Total and visceral fat were assessed with dual-energy x-ray absorptiometry. MRI was used to quantify EAT volume across short-axis slices and assess global longitudinal strain(GLS). We assessed ventricular filling pressures (right heart catheterization), oxygen uptake (VO
2
), cardiac output (Qc, Direct Fick), and diastolic function (echocardiography) on a seated upright cycle ergometer at rest, 20 Watts, and peak exercise (87±35 Watts). Correlation analyses were performed to examine the relationship between variables.

Results:
EAT was moderately correlated with visceral adiposity (r=0.57, P<0.001) but not with total body fat (Figure, Panel A). EAT was not associated with markers of diastolic function (early tissue Doppler relaxation velocity [e'], mitral inflow velocity ratio [E/A], early mitral inflow/e' ratio [E/e']), cardiac filling pressures (right atrial pressure and pulmonary capillary wedge pressure) or mean pulmonary artery pressure at rest or during exercise. In addition, there was no association between GLS and total EAT (r=-0.06, P=0.735) or EAT located over the left ventricle (r=-0.05, P=0.749). EAT was not associated with exercise capacity (Figure, Panel B).

Conclusions:
In patients with HFpEF, total EAT volume quantified with MRI did not correlate with measures of cardiac function at rest or during exercise. Our results suggest ventricular EAT does not impact cardiac function directly in patients with obesity and HFpEF.
Abstract 4143822: Trial emulation comparing percutaneous left atrial appendage occlusion to direct oral anticoagulants in Medicare beneficiaries
Authors: Jiao Tianze , Ruzieh Mohammed , Du Fanxing , Blotner Michael , Foy Andrew
Published: November 2024

Background:
Percutaneous left atrial appendage occlusion (pLAAO) is widely used procedure as an alternative to oral anticoagulants in patients with atrial fibrillation at increased risk of bleeding or prior bleeding events. The efficacy and safety of pLAAO in real-world Medicare patients remain uncertain.

Objectives:
To compare to pLAAO to DOACs in Medicare beneficiaries with atrial fibrillation.

Methods:
We used a 15% sample of Medicare claims data (2015-2019) to identify patients who received pLAAO and compared them to patients who received DOACs using trial emulation design. Relying on propensity score matching, we mimicked randomization and assigned patients to receive pLAAO or DOACs in a 1:3 ratio. Confounders in the propensity score model was selected by domain knowledge and machine learning approach (i.e., high dimensional propensity score). Patients were followed for up to 4 years. The primary efficacy outcome was a composite outcome of stroke, TIA or systemic thromboembolism leading to hospital admission. The primary safety outcome was any bleeding leading to hospital admission. We used a Cox proportional hazards regression model to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the outcomes between both treatment groups.

Results:
We identified 3,647 and 10,941, patients who underwent pLAAO and received DOACs, respectively. The primary composite endpoint was similar between pLAAO and DOACs (0.72%/ year vs 0.72%/ year, HR: 0.98, 95% CI: 0.72 – 1.34), figure 1A. The use of pLAAO was associated with significantly more bleeding (7.48%/ year vs 4.98%/ year, HR: 1.38, 95% CI: 1.24 – 1.54), figure 1B. Consistent with the clinical trials, all-cause mortality was not significantly different between both groups, (9.04%/ year with pLAAO vs 10.00%/ year with DOACs, HR: 0.98, 95% CI: 0.90 – 1.07).

Conclusion:
We successfully emulated the target trial using Medicare claims data. In Medicare beneficiaries with atrial fibrillation, pLAAO use compared to DOACs did not reduce the risk of stroke, TIA or systemic thromboembolism and was associated with more bleeding. The increase in bleeding events in the pLAAO arm is likely due to high upstream anticoagulant use after the procedure.
Abstract 4143830: Clonal hematopoiesis portends worse mortality among individuals with ATTR cardiac amyloidosis
Authors: Small Aeron , Vijayakumar Shilpa , Cuddy Sarah , Libby Peter , Natarajan Pradeep , Gaggin Hanna , Dorbala Sharmila , Honigberg Michael
Published: November 2024

Introduction:
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a restrictive cardiomyopathy characterized by deposition of misfolded transthyretin in the myocardium. Untreated individuals with ATTR-CM have a median survival of 2-4 years after diagnosis. Individuals with clonal hematopoiesis, including clonal hematopoiesis of indeterminate potential (CHIP), mosaic chromosomal alterations (mCAs), and loss of Y (LOY), have heightened risk of adverse cardiovascular outcomes. It is unknown whether the presence of clonal hematopoiesis is associated with mortality in ATTR-CM.

Methods:
We tested the association between clonal hematopoiesis and all-cause mortality among individuals with ATTR-CM in the Mass General Brigham Biobank (MGBB). ATTR-CM status was determined by pyrophosphate scintigraphy (PYP) scan. CHIP was called from whole exome sequencing; mCAs and LOY were called from genotype array data. Key exposures were the presence of any CHIP (defined as a variant allele fraction [VAF] ≥2%), large CHIP (VAF ≥10%), CHIP driver mutations (DNMT3A, TET2, and non-DNMT3A), mCA, and LOY. Cox models were used to generate hazard ratios (HRs) for all-cause mortality with adjustment for age at scan, sex, type 2 diabetes, and coronary artery disease.

Results:
Among 54 genotyped individuals in the MGBB with a positive PYP scan (mean [SD] age 79.1 [6.7], 48 [89%] male), any CHIP was identified in 16 (29%) individuals, large CHIP in 9 (17%), LOY in 11 (23% of males), and mCAs in 10 (19%). The most common CHIP clones were
DNMT3A
(11 [20%] individuals),
TET2
(3 [6%] individuals), and
ASXL1
(2 [4%] individuals). Over a median [interquartile range] follow-up of 2.89 [1.48-4.37] years, non-DNMT3A CHIP was significantly associated with risk of all-cause mortality (HR 5.97 [95% CI 1.13-31.55], P =0.036). TET2 CHIP had a suggestive association with all-cause mortality (HR 5.94 [0.79-44.68], p = 0.08). Neither any CHIP, large CHIP, nor DNMT3A CHIP was significantly associated with all-cause mortality, though effect estimates were directionally consistent with increased risk (any CHIP: HR 2.06 [0.60-7.12], P=0.25; large CHIP HR 2.57 [0.53-12.60], P=0.24; DNMT3A CHIP HR 1.76 [0.47-6.57], P=0.40). In addition, mCAs, but not LOY, were associated with mortality (mCA HR 4.75 [1.33-16.96], P=0.017; LOY HR 2.79 [0.74-10.59], P=0.13).

Conclusions:
In a small observational study of individuals with ATTR-CM, non-DNMT3A CHIP and mCAs were associated with increased risk of all-cause mortality.
Abstract 4143841: Cardiomyocyte-specific PLCe1 knock-down attenuates Angiotensin II-induced cardiac hypertrophy.
Authors: Ni Kareemah , Rigaud Vagner , Vigneault Patrick , Xiao Chunyang , Klattenhoff Carla , Ellinor Patrick
Published: November 2024

Background:
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. We have recently identified Phospholipase C epsilon 1 (PLCe1) to be upregulated in cardiomyocytes (CMs) from HCM patients. PLCe1 has been reported to play a critical role in developing cardiac hypertrophy and PLCe1 heart-specific genetic ablation in mice prevents hypertrophic growth following transaortic constriction.

Aim:
To further assess the therapeutic potential of PLCe1 modulation, we assessed whether PLCe1 knockdown can rescue agonist-induced cardiac hypertrophy both in vitro and in vivo.

Methods:
Cardiomyocyte hypertrophy was induced by endothelin 1 (ET1) stimulation in iPSC-derived CMs and primary neonatal mouse ventricular myocytes (NMVMs) followed by PLCe1 knockdown using siRNAs. For in vivo assessment, cardiac hypertrophy was induced in C57BL/6J wild type mice by implanting angiotensin II (Ang II) osmotic minipumps for 4 weeks. Adeno-associated virus serotype 9 carrying GFP-tagged shRNAs against PLCe1 (AAV9-shPLCe1) or GFP alone (AAV9-GFP; control) were delivered retro-orbitally on the day of the surgeries and 1 week after Ang II infusion. M-mode echocardiography was performed at baseline and weekly for 4 weeks.

Results:
PLCe1 silencing in either human iPSC-CMs or NMVMs treated with ET1 resulted in 25% reduction in cell size, 46% reduction in total protein synthesis, and 72% and 81% reduced expression of the hypertrophic markers NPPA and NPPB, respectively. To evaluate whether PLCe1 therapy can promote left ventricle hypertrophy regression, mice were infused with Ang II and subsequent delivery of AAV9-shPLCe1. Approximately 65% of the CMs were transduced within 3 days after AAV9-shPLCe1 delivery while the maximal transduction levels of 74% were observed after 1 week. We observed significant attenuation of the cardiac hypertrophic response represented by decreased wall thickness and preserved cardiac structure and function 1 week after PLCe1 modulation. Ongoing analysis of the later time points will allow us to better evaluate the salutary effects of PLCe1 therapy.

Conclusion:
Cardiomyocyte-specific PLCe1 knockdown attenuates Ang II-induced cardiac hypertrophy, highlighting PLCe1 as a potential target for HCM.
Abstract 4143848: Trends in Ischemic Cardiomyopathy related mortality among older adults in US population: A CDC WONDER database analysis from 1999 to 2020
Authors: Ansari Huzaifa , Samad Muhammad Ammar , Mahboob Eman , Fatima Laveeza , Qazi Shurjeel , Ahmad Adeel , Rahman Asad , Jain Hritvik , Ahmed Mushood , Ahmed Raheel , Alraies M Chadi , alam mahboob
Published: November 2024

Introduction:
Ischemic cardiomyopathy (IC) is a significant contributor to cardiovascular mortality, especially among older adults in the United States. Understanding mortality trends related to IC can help identify at-risk populations and make informed targeted healthcare strategies. This study investigates IC-related mortality trends and disparities among older adults aged ≥75 years in the US population.

Methods:
The CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) was used to analyze the National Vital Statistics System data from 1999 to 2020. Deaths with IC as the primary cause of mortality were identified, and results were presented as age-adjusted mortality rates (AAMR) per 100,000 population. Joinpoint regression was used to assess changes in trends and annual percentage change (APC).

Results:
A total of 186,136 deaths occurred in patients with IC from 1999 to 2020 (AAMR = 42.9, 95% CI: 42.7 - 43.2). Males had higher mortality rates (AAMR = 67.8) compared to females (AAMR = 27.7). Non-Hispanic Whites (NHW) had the highest AAMR (45.2, 95% CI: 45-45.4), followed by Hispanics (29.8, 95% CI: 29.1-30.5), non-Hispanic Blacks (NHB) (29.6, 95% CI: 29-30.1), non-Hispanic American Indian/Alaska Native (NH-AIAN) (29.1, 95% CI: 26.8-31.3). Non-Hispanic Asian/Pacific Islanders (NH-API) had the lowest AAMR (16.9, 95% CI: 16.2-17.6). Regionally, the South had the highest mortality rates (47.8, 95% CI: 47.5-48.2), followed by the Midwest (47.4, 95% CI: 46.9-47.8), the West (36.7, 95% CI: 36.3-37.1), and the Northeast (36.3, 95% CI: 35.9-36.7). Mortality rates were higher in rural areas (44.1, 95% CI: 43.5-44.7) compared to urban areas (36.5, 95% CI: 36.1-36.8). Overall, the AAMR increased from 51.3 in 1999 to 51.9 in 2005, followed by a decline to 31.5 in 2020 (APC: -2.0, 95% CI: -2.2, -1.7). Noteworthy declines in AAMR were observed in both men (APC: -2.0) and women (APC: -2.9) throughout the study (Figure, Panel A). Moreover, significant downward trends were evident in NH-AIAN (APC: -3.5), NHB (APC: -1.2), NHW (APC: -2.7 since 2004), Hispanics (APC: -5.5 since 2016), and NH-API (APC: -2.4) racial groups (Figure, Panel B).

Conclusion:
Our study reveals disparities in IC-related mortality, highlighting males, NHW, and the residents in the South and Midwest as well as those living in rural areas are at increased risk. Targeted interventions and resource allocation are essential to improve outcomes for vulnerable populations.
Abstract 4143855: Identifying the implementation potential for Mobile Integrated Health interventions for patients with heart failure
Authors: Reading Meghan , Puplampu Victoria , Shafran Topaz Leah , Nino de Rivera Stephanie , Ellison Melani , Blutinger Erik , Daniels Brock , Masterson Creber Ruth
Published: November 2024

Introduction:
Mobile Integrated Health (MIH) is a novel care delivery model utilizing community paramedics and telehealth to manage chronic illnesses such as heart failure (HF) outside hospital settings. Implementation of MIH is widely variable between institutions and stakeholder perspectives are poorly described in the literature.

Objective:
To identify stakeholder (e.g., MIH experts, HF clinicians, and caregivers of adults with HF) perspectives on predisposing, enabling, and reinforcing factors to the adoption, implementation, and maintenance of MIH.

Methods:
We used the RE-AIM (Reach Effectiveness Adoption Implementation Maintenance) framework to analyze MIH implementation. Stakeholders were recruited using a combination of convenience and snowball sampling nationally in the United States (U.S.). An interview guide based on the relevant domains of the RE-AIM framework was tailored to participant types. Interviews were conducted via phone or Zoom, with verbal consent obtained. Sessions were audio-recorded, transcribed verbatim, and qualitatively analyzed by four reviewers using directed content analysis.

Results:
Twenty-five stakeholders were recruited: six clinicians (four cardiologists, two nurses), eight MIH staff (four paramedics, one dispatcher, three nurse care coordinators), two caregivers, and nine MIH Program Directors. Predisposing factors included EMS skills and knowledge, the rising value of digital health, clinician beliefs about “phenotypes” of patients who benefit most from MIH, and alignment with the right outcome measures. Enabling factors included the comprehensiveness and quality of care provided during MIH visits, interdisciplinary team integration, patient trust in community paramedics, and telehealth functionality. Reinforcing factors included the ability of MIH programs to demonstrate value and financial sustainability, embrace future innovations and improvements, and show high patient satisfaction with MIH. Illustrative quotes are provided in
Table 1
.

Conclusions:
This study highlighted unifying predisposing, enabling, and reinforcing factors across MIH programs nationally, which may guide future efforts for those launching or scaling these programs for adults with HF.
Abstract 4143856: Aging Alone: Impact of Social Networks on Older Adults with Advanced Heart Failure
Authors: Godfrey Sarah , Jawaid Anas , Maini Mansi , Zhang Jingwen , Dutta Manasa , Wrobel Christopher , Thibodeau Jennifer , Grodin Justin , Morlend Robert , Drazner Mark , Farr Maryjane
Published: November 2024

Background:
Social health, including social isolation and kinlessness, has important implications for older adults. Social isolation and lack of traditional kin networks has been associated with adverse health outcomes including long-term facility placement, healthcare utilization, and all-cause mortality. Prior studies report 6-10% of older adults in the US are kinless. However, little is known about the prevalence and impact of kinlessness on older patients with advanced heart failure (HF), particularly given the psychosocial requirements for advanced therapies.

Aim

To describe the social support structures and their association with clinical outcomes in older adults with advanced HF at a large academic advanced HF center.

Methods:
We abstracted data from the electronic medical records of adults >70 referred for management of advanced HF from 2012-2022. Patients were excluded if they did not have clinical HF or were not seen by an advanced HF physician.

Results:
834 older adults were referred for management of advanced HF. Median age was 75 years (IQR 7), 68% were male, and 71% were white. Mean ejection fraction was 35 (SD 17.4), and most were NYHA class III-IV (62%) at time of referral. In terms of social support, 574 (69%) were married and 734 (88%) had living children, whereas only 28 (3.3%) had no documented living 1
st
degree relatives. One hundred twenty (14%) lived alone. Overall, 35 (4.2%) received a left ventricular assist device (LVAD) and 23 (2.8%) received a heart transplant (HT). LVAD recipients were more likely to be married (89%, p<0.001) and have living children (83%, p<0.001). All HT recipients had living children (100%, p=0.03), and they were more likely to be married (70%, p=0.01). No patients without a spouse or living child received an advanced therapy. Overall, 298 (36%) of patients died during the study period. While mortality did not vary by kin status, married adults were more likely to die on hospice (49% vs. 39%), and those with children were less likely to die in the hospital or ICU (38% vs. 43%).

Conclusion:
Very few (3.3%) older adults referred to an academic advanced HF center lack a living spouse or child, suggesting that kinless older adults are under-referred. Having a living spouse or child was associated with greater rates of LVAD and HT, as well as rates of hospice and out-of-hospital death. These data may identify important disparities in advanced therapies and end-of-life care for older adults with advanced HF who are kinless.
Abstract 4143857: Characterization of Arrhythmia Occurrence During Sleep and Activity in Patients Undergoing Long-Term Continuous Ambulatory ECG Monitoring
Authors: Yu Elaine , Pinkerton Relana , Kacorri Ardit , Battisti Anthony , Tamura Yuriko , Turakhia Mintu
Published: November 2024

Background:
Circadian patterns of arrhythmias based on time of occurrence have been described in small datasets, but there is little information on the relationship of arrhythmia occurrence to sleep and activity. We sought to quantify the occurrence of arrhythmias detected by long-term (≤14 days) continuous ambulatory ECG monitoring (LTCM) during sleep, wake, and activity.

Methods:
We performed a retrospective analysis of consecutive patients who underwent LTCM with an FDA cleared device that features an embedded accelerometer (Zio
®
Monitor, iRhythm Technologies, Inc.; San Francisco CA). This feasibility analysis included nationwide patients for whom LTCM ECG data were processed on a single day (Feb 1, 2024).

We applied an AI algorithm previously developed and validated as a wellness feature to classify periods of sleep, activity (≥2mph walking), and inactivity using LTCM accelerometry data. Rhythms were classified by an FDA-cleared deep learning algorithm, confirmed by a cardiographic technician and time-aligned to the algorithm-generated sleep/wake and activity/inactivity labels. Odds ratios (OR) associated with time in arrhythmia for sleep and activity periods were calculated by rhythm type.

Results:
Analysis included 3,840 patients (58.3% female, age 59.7±19.7 years) monitored for an average 10.5 days (Table 1); patients spent the most time in AF. Rhythms with the highest association with sleep (vs. wake) were pause (OR=2.06; 95% CI 2.00-2.12) and 3
rd
degree block, (OR=1.81; 95% CI 1.79-1.83). Notably, VT was among the arrhythmias least likely to occur during sleep (OR=0.31; 95% CI 0.30-0.31). Second degree (Mobitz type 2) and third degree block had the highest OR associated with activity.

Conclusion:
This is the largest study characterizing sleep, wake, and activity of ambulatory arrhythmias — and obtained from only a single day of data. Results demonstrate the feasibility of integrating sleep and activity labeling with LTCM findings and the potential to give context to arrhythmias, such onset or termination during sleep, wake, or exertion.
Abstract 4143872: Mode of Death in Heart Failure with Preserved Ejection across the Kidney Function Spectrum: Pooled Individual-Patient Level Analysis of 5 Trials
Authors: Bart Nicole , Ariss Robert , Claggett Brian , Vaduganathan Muthiah , Neuen Brendon , Beldhuis Iris , Desai Akshay , Jhund Pardeep , Mc Causland Finnian , Pfeffer Marc , Pitt Bertram , ZANNAD Faiez , Zile Michael , McMurray John , Solomon Scott , Cunningham Jonathan
Published: November 2024

Introduction:
Patients with comorbid heart failure (HF) and chronic kidney disease (CKD) face excess risks of mortality, but limited data are available examining specific modes of death across the spectrum of kidney function.

Methods:
We leveraged individual patient level data from 5 trials of HF with mildly reduced or preserved ejection (CHARM-Preserved, I Preserve, TOPCAT [Americas region], PARAGON-HF, and DELIVER). Causes of death (sudden, heart failure, other CV, and non-CV) were adjudicated by clinical events committees in each respective trial.

Results:
Among 17,947 patients across the 5 trials with available eGFR data, mean age was 71.6 ± 9.0 years, 51% were women, median NT-proBNP was 840 [25-75
th
percentile 424, 1566] pg/ml. Overall, 2084 (12%) had eGFR ≥90 mL/min/1.73m
2
, 7977 (44%) had eGFR 60 - < 90, 4701 (26%) had eGFR 45-60, 3185 (18%) had eGFR <45. During a mean of 2.9 years of follow-up, 3,140 patients died. All-cause death rate was greater in the lower eGFR groups, driven by greater rates of HF and non-CV death. Rates of CV and non-CV death were 5.7/100 patient years (py) and 4.4/100py in patients with eGFR <45 and 2.7/100py and 1.3/100py in patients with eGFR >90 (Table and Figure). HF-related death rate was markedly greater in participants with eGFR <45 (2.0/100py) compared to patients with eGFR>90 (0.3/100py)

Conclusions:
Among nearly 18,000 patients across contemporary HFmrEF/HFpEF clinical trials, mortality was markedly higher at lower ranges of kidney function, driven mostly by higher non-CV death and HF-related death.
Abstract 4143876: Endothelial Cell Gene Expression Profiling Demonstrates Inflammatory Activation In Young Adults Who Use Electronic Cigarettes Alone And In Combination With Combustible Cigarettes
Authors: Okazaki Ross , Zhou Yuxiang , Rizvi Syed Husain , Minetti Erika , Weisbrod Robert , Keith Rachel , Hamburg Naomi
Published: November 2024

Background:
Traditional combustible cigarette (combustible) use induces endothelial dysfunction accelerating cardiovascular disease progression. Young adults frequently use electronic cigarettes (e-cig) that is linked to impaired endothelial cell (EC) function. We aimed to use EC gene expression analysis to explore altered pathways across patterns of tobacco product use.

Methods:
Healthy adults aged 18-45 who regularly use e-cig (sole or dual), combustible, and non-use controls were with forearm vein EC biopsy and magnetic bead purification. EC total RNA was isolated and profiled on a NextSeq sequencer. Samples with transcript integrity number (TIN) < 10 were removed, genes were filtered with edgeR::filterByExpr, and analyzed with DESeq2. Differentially expressed genes (DEGs) comparing each use group to the non-use group were defined as log
2
fold change >1 and FDR p<0.01. Pathway analysis was done via Gene Ontology database and analyzed using over-representation analysis with log
2
fold change >1 and p<0.05 and selected based on experimental observation.

Results:
64 adults were recruited with a mean age 26±7 years and 34% female. After exclusion of samples not meeting TIN-quality standards, 44 samples were available for analysis sole e-cig (N=13), dual use (N=7), combustible (N=10), non-use (N=14). Each use group revealed multiple DEG compared to non-use (Figure): sole e-cig (50 DEG), dual use (18 DEG), combustible (65 DEG) with 28 DEG shared between sole e-cig use and combustible use suggesting similar patterns of altered EC phenotype. Upregulation of 4 genes 1L1B, PTPRO RYR2, and CLEC4D was shared across all three use groups suggestive of inflammatory activation. Pathway analysis in e-cig alone use group showed multiple pathways related to inflammation and immunity enhanced compared to non-use.

Conclusions:
Young adults who use e-cig along display evidence of enhanced inflammatory gene expression in isolated EC suggestive of vascular inflammatory activation. Patterns of altered gene expression with e-cig use demonstrated both shared and distinct components compared to combustible cigarette use. Further work is needed to determine the components in e-cig that contribute to altered EC phenotype.
Abstract 4143899: cusp-overlap view versus three cusp coplanar view during transcatheter aortic valve replacement using self-expandable valves: A meta-analysis of 5947 patients.
Authors: K. Awad Ahmed , Khalefa Basma , R. Gonnah Ahmed , Negmeldin Aly Yassin Mazen , G.Hamam Nada , Ramadan Mohamed , Dway Ali , Alsalhi Karim , T. Osman Mohamed , Sicouri Serge , Basel Ramlawi
Published: November 2024

Background & Objectives:
Transcatheter aortic valve replacement (TAVR) is currently the treatment of choice for most patients with symptomatic severe aortic stenosis. We conducted this systematic review, and meta-analysis to compare the efficacy and procedural outcomes of using the cusp overlap technique (COT) versus the standard three-cusp technique during self-expandable valves implantation for the management of aortic stenosis.

Methodology:
We systematically searched PubMed, Scopus, Embase, Cochrane, and Web of Science (WOS) from inception to March 5, 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To estimate the effect size, dichotomous outcomes were pooled as risk ratio (RR), and continuous outcomes were pooled as mean difference (MD) with their respective 95% confidence interval (CI).

Results:
We included seventeen studies in our systematic review and meta-analysis with a total of 3129 patients in cusp-overlap technique (COT) arm and 2818 patients in standard technique (ST) arm. The rate of 30-day mortality was significantly decreased in COT compared with ST (RR = 0.61; 95% CI: [0.37–1.00], P = 0.05). Regarding conduction abnormalities, COT was related to lower risk of complete atrioventricular (AV) block (RR = 0.51; 95% CI: [0.37–0.69],
P
< 0.01), reduced likelihood of left bundle branch block (RR = 0.77; 95% CI: [0.61–0.97], P = 0.03) and permanent pacemaker implantation (PPI) (RR = 0.56; 95% CI: [0.46–0.70], P < 0.01). There was also lower likelihood of major and life-threatening bleeding with the COT compared to ST (RR = 0.60; 95% CI: [0.46–0.79],
P
< 0.01). Our analysis also showed that COT was associated with significantly lower implantation depth compared with ST (MD = -1.00; 95% Cl: [-1.83 to -0.17],
P
= 0.02). Procedural success was similar between COT and ST (RR = 1.01; 95% CI: [0.98–1.04],
P
= 0.42). Major vascular complications (RR = 0.90; 95% CI: [0.61–1.33], P = 0.61), and mild to severe paravalvular leak (RR = 1.00; 95% CI: [0.66–1.51], P = 1.00) were also comparable between COT and ST.

Conclusion:
Our study findings suggest that COT offers several advantages over ST, including reduced 30-day mortality and decreased bleeding complications, without compromising long-term outcomes or increasing procedural complications. The COT most importantly lower risk of conduction abnormalities, and hence permanent pacemaker implantation.
Abstract 4143923: Home-based Exercise Intervention for Children and Adolescents with Hypertrophic Cardiomyopathy: A Consensus of Experts on a Safe and Acceptable Exercise Protocol
Authors: Fortin-Moore Charles-Olivier , Jeewa Aamir , Power Alyssa , Khoury Michael , Lin Kimberly , Edelson Jonathan , Ball Geoff , Atallah Joseph , Cifra Barbara , Pidborochynski Tara , Conway Jennifer
Published: November 2024

Background:
Physical activity (PA) is a mainstay for cardiovascular health. However, those with hypertrophic cardiomyopathy (HCM) are often counselled to limit PA due to the potential risk of sudden cardiac death. The emphasis placed on restriction has put this population more susceptible for acquired cardiovascular (CV) risk factors, and poor long-term CV health from physical inactivity. To date, no consensus exists about what is appropriate and safe in terms of exercise for this population.

Project Aim:
Use a modified Delphi method to gain consensus amongst subject matter experts on a proposed home-based exercise intervention for children 10 to 19 years of age with HCM.

Methods:
A panel of experts, including pediatric cardiologists, sports cardiologists, exercise physiolologists, obesity experts, and parent/patient representatives met a series of five times to develop a home-based exericse program. The proposed program was converted into a survey and sent out through the
Advanced Cardiac Therapies Improving Outcomes Network
(ACTION) from October 2023 to June 2024. Utilizing a modified Delphi method, each of the 11 components of the intervention were voted on regarding the degree of agreement by responders. For those who disagreed, they were prompted to provide feedback in order to modify that aspect of the exercise program. The participants were provided with feedback after each round. We aimed for 90% agreement on each component to declare consensus.

Results:
At total of 49 individuals completed the first round of the survey with 84% identified as a pediatric cardiologists, 75% working in a University center and two-thirds having more than five years of experience. After Round 1 consensus was reached on 3/11 and up to 8/11 after Round 2. The progression to the final home-based exercise protocol is outlined in Table 1.

Conclusion:
A home-based exercise program for children with HCM was developed, adapted from feedback, and the components were agreed to by experts in the field using a modified Delphi method. The next step in this process is to assess the safety and feasibility of this program in an in-hospital setting, prior to its evaluation through a multi-center, home-based exercise intervention.
Abstract 4143925: Cigar smoking and better quality of life positively impact cigarette smoking cessation in adults: Findings from the Population Assessment of Tobacco and Health Study, a national longitudinal cohort study
Authors: Majeed Ban , Kaplan Bekir , Ketchem Justin , Walsh David
Published: November 2024

The likelihood of smoking cessation success, sustained cigarette abstinence, varies by demographics, e.g. age, and other factors which shape quality of life, like stress and comorbidities. The recent emergence of newer tobacco products, like cigars and electronic nicotine delivery systems and in turn newer patterns of tobacco use, like exclusive smoking, dual, or poly use, complicates the picture of cessation process. To fill this gap and inform treatment, this study aimed to assess the role of patterns of tobacco use and perceived change in quality of life in cessation (abstinence ≥ 3 months) and examine the effect of age on those relationships in younger (18-44 years) and middle aged/older (45+) adults in the United States who smoke cigarettes.

Methods:
This study included (N=5,669) participants, in a longitudinal cohort study, Population Assessment of Tobacco and Health Study, with self-reported patterns of tobacco use (wave 4) and valid information on cessation at follow-up (wave 5). Patterns of use included exclusive smoking, dual cigarette/cigar, dual cigarette/ENDS, and poly use. Perceived change in quality of life—perception of quality of life now compared with 12 months ago—included worse, about the same, and better. Cessation at follow-up, included sustained abstinence of ≥3m and current smoking/short-term abstinence. Weighted descriptive analyses and logistic regressions were conducted with sustained abstinence as outcome and patterns of use and change in quality of life as predictors, adjusting for sex, race, education, income, BMI, and tobacco dependence. Analyses were stratified by age groups.

Results:
Overall, 25.7% reported sustained abstinence at follow-up. In both age groups, dual cigarette/cigar compared to exclusive smoking (45+ year adults OR 3.33, 95% CI: 1.26-8.79) and better quality of life (compared to about the same) were associated with higher odds of sustained abstinence. In both groups, lower odds were associated with being black and higher tobacco dependence. Of interest, only in 45+ year adults, worse change quality of life had OR 1.95 (95% CI: 1.02-3.74).

Conclusion:
Findings indicate that patterns of tobacco use, improved quality of life, race, and tobacco dependence influence likelihood of cessation in all ages, but worse change in life may produce cessation only in older adults. Improving quality of life may hold a great potential to achieve successful smoking cessation.
Abstract 4143931: Guideline Adherence in Severe Aortic Stenosis: Determinants of Timely Aortic Valve Replacement and Echocardiography Follow-up
Authors: Vakilpour Azin , Levin Michael , Anyanwu Emeka , Denduluri Srinivas , Lee Jennifer , Sharkoski Tiffany , Adusumalli Srinath , Lopez-Mattei Juan , Chittams Jesse , Jones David , Weiss Kathleen , hartwell carlton , Bolooki Michael , Bourque Jamieson , Scherrer-Crosbie Marielle
Published: November 2024

Background:
According to the 2020 ACC/AHA guidelines, patients with severe aortic stenosis (AS) should either undergo rapid AVR or be followed by an echocardiogram (echo) every 6-12 months to assess disease progression. Discrepancies have been reported in the care of severe AS.

Goal:
This study aims to evaluate adherence to guidelines, and identify factors associated with guidelines recommended care in patients with severe AS.

Methods:
All patients with a first echo report of severe AS diagnosis from January 2019 to December 2022 in a tertiary care academic health center were included. Adherence to guidelines was defined as undergoing AVR in 6 months or having a follow-up echo within 6-12 months of the index echo. Univariable and multivariable Cox proportional hazards models were performed to identify factors associated with guidelines recommended care. Patients who did not meet the endpoint and died before one year were censored at the time of death.

Results:
Of the 1655 patients included in the study (mean ± SD age: 77±12 years, 56% male, 80% white, 10% African-American, and 10% other race), 727 (43%) had AVR in 6 months, 184 (11%) had no AVR in 6 months but a follow-up echo within 6-12 months, and 744 (45%) did not achieve the guidelines recommended care. Two hundred and thirty-eight (14%) patients died within one year (178 patients did not meet guidelines). The multivariable Cox proportional hazards model (Table) revealed that younger age, lower LVEF, higher aortic valve mean gradient, cardiovascular history or risk factors, and having a cardiac specialty provider increased the rate of adherence to guidelines, while African-Americans and patients with renal failure were less likely to receive the guidelines recommended care.

Conclusions:
A substantial proportion of patients with severe AS does not receive the guidelines recommended care and follow-up. Factors including age, race, comorbidities such as renal failure, cardiovascular history and risk factors, provider specialty, and characteristics of the AS are associated with these discrepancies. These results call for urgent action to guide patient and provider behavior towards equitably implementing guideline-recommended valvular heart disease therapies.
Abstract 4143935: Clinical and Hemodynamic Correlates of Supranormal Ejection Fraction in Heart Failure with Preserved Ejection Fraction (HFpEF)
Authors: Dhruve Ritika , Patel Lajjaben , Subramanian Vinayak , Segar Matthew , Miller James , Lokesh Nidhish , Keshvani Neil , Tong Dan , Chandra Alvin , Koshy Thomas , Pandey Ambarish
Published: November 2024

Introduction:
Patients with heart failure with preserved ejection fraction (HFpEF) with EF≥65% may have a higher risk for adverse outcomes, however, the exercise, functional status, and hemodynamic correlates of this phenotype in a contemporary cohort is not well defined.

Methods:
This single-center study included patients with LVEF ≥50% with clinically indicated invasive right heart catheterization and echocardiogram enrolled in a prospective HFpEF registry at UT Southwestern between 4/2022-5/2024. Participants underwent peak oxygen uptake (VO
2
) assessment with maximal bicycle test (Lode ergometer), quality of life assessment (Kansas City Cardiomyopathy Questionnaire [KCCQ]), physical function testing with the Short Physical Performance Battery (SPPB), and 6-minute walk distance (6MWD). Participants were stratified by those with EF ≥ 65% and EF 50%-65%. Multivariable adjusted linear regression models were used to evaluate the association of EF ≥ 65% with peak VO
2
, quality of life, noninvasive and invasive cardiac filling pressures, and functional outcomes.

Results:
347 participants were included in the study. 112 (32.3%) participants had EF≥65%, and there were no differences in demographics across EF subgroups. Patients with EF≥65% had a higher burden of hypertension (94.6% vs. 86.8%, p = 0.04) and had higher E/e’ (14.0[95% CI 10.9-18.0] vs. 12.7[95% CI 9.5-16.7], p = 0.048) and PCWP with exercise (27[95% CI 20-30] vs 22[95% CI 18-28] mmHg, p=0.04) without differences in resting PCWP or PCWP/cardiac output slope at maximal exercise. After adjustment for age, sex, race, and BMI, EF≥65% was associated with higher KCCQ. However, these findings were attenuated after adjustment for comorbidities (Model 1: β 6.6, p=0.05 vs Model 2: β 6.0, p=0.08). EF≥65% was not associated with functional outcomes, peak exercise capacity, or elevated filling pressures in adjusted models. (Table)

Conclusions:
There were no significant differences in quality of life, functional status, exercise capacity, and filling pressures among patients with supranormal and normal ejection fraction. These findings suggest that extra-cardiac mechanisms may be more important contributors to functional status and peak exercise capacity in patients with EF≥65%.
Abstract 4143936: More Than a Portion of Probiotics a Day is Associated with a Decreased Likelihood of Having Hypertension
Authors: Thiravetyan Ben , Sodsri Tulaton , Prasitsumrit Vitchapong , Numwong Terasut , Wonghanchai Sireethorn , Xanthavanij Nutchapon , Pangkanon Watsachon , Vathesatogkit Prin
Published: November 2024

Background:
Probiotic consumption may have the potential to improve blood pressure in patients with hypertension. However, there is limited evidence regarding the specific daily dosage of probiotics that is directly associated with a reduced probability of hypertension occurrence in the general population.

Aim:
The study aims to evaluate the relationship between the amount of probiotics consumed per day and hypertension.

Methods:
A cross-sectional analysis of data from a survey of employees at the Electricity Generating Authority of Thailand (EGAT) was conducted. Baseline characteristics, hypertension status, and probiotic consumption were collected in 2017. Two tablespoons of kimchi or pickles, 200 mL of fermented milk, or 200 mL of yogurt constitute one portion. The mean portion per day was calculated by summing up all the probiotics consumed per day. Logistic regression models comparing participants among the non-probiotic group, the less than one portion of probiotics per day group (< 1 portion/day), and the more than one portion of probiotics per day group (≥ 1 portion/day) were analyzed to explore the association between the amount of probiotic consumption and hypertension.

Results:
The study included 1218 participants. The mean (SD) age was 73.3 (4.3) years, with 870 (71.4%) being male and 1014 (83.2%) having hypertension. Of all, 545 (44.7%) were non-probiotic users, 539 (44.3%) were using < 1 portion/day, and 134 (11.0%) were using ≥ 1 portion/day. For the ≥ 1 portion/day group, after univariate analysis, individuals were statistically 0.56 times less likely to have hypertension compared to those in the non-probiotic group, while those in the < 1 portion/day group did not meet statistical significance. Multiple logistic regression analysis also demonstrated that consuming ≥ 1 portion/day of probiotics was significantly associated with a decreased likelihood of having hypertension, with an odd ratio of 0.55 (95%CI 0.31-0.96).

Conclusion:
Consuming ≥ 1 portion/day of probiotics is associated with a decreased likelihood of having hypertension. Further studies with larger sample sizes are required to determine the optimal amount of probiotic intake as a supplementary treatment for hypertension.
Abstract 4143937: Association Between Lipoprotein(a) Levels and Incident Complex Coronary Revascularization Procedures in the FOURIER Trial
Authors: Gaba Prakriti , O'Donoghue Michelle , Giugliano Robert , Bellavia Andrea , Monsalvo Maria Laura , Flores-Arredondo Jose , Kuder Julia , Atar Dan , Keech Anthony , Sabatine Marc , Bergmark Brian
Published: November 2024

Background:
Elevated Lp(a) levels are associated with a higher risk of major adverse CV events. Whether elevated Lp(a) levels are associated with a higher risk of complex coronary revascularization procedures or modify the benefit of evolocumab remains unknown.

Methods:
The FOURIER trial randomized 27,564 pts with stable ASCVD on optimized statin therapy to evolocumab vs placebo (median f/u 2.2 yrs). The association between Lp(a) (≥125 nmol/L) and complex coronary revascularization procedures (complex PCI or any CABG) was assessed in pts from the placebo arm with an adjusted Cox regression model. Complex PCI events were identified through blinded review of all revascularization events and defined as ≥1 of: multivessel PCI, ≥3 stents, ≥3 lesions treated, bifurcation PCI, or total stent length >60 mm. Effect modification between Lp(a), evolocumab and the risk of complex revascularization was assessed by including an interaction term in the model. Kaplan-Meier event rates are reported at 3 yrs.

Results:
In FOURIER, 4048 (32%) pts had a baseline Lp(a) concentration ≥125 nmol/L. A total of 332 complex coronary revascularization procedures occurred. Pts with higher baseline Lp(a) levels were more frequently female (29% vs 23%) and more likely to have multivessel disease (24% vs 21%), diabetes mellitus (38% vs 34%) or prior PCI (66% vs 60%). Higher baseline Lp(a) was associated with a 27% higher risk of complex coronary revascularization (3.7% vs 3.2%; HRadj 1.27, 95% CI: 1.01-1.59; P=0.04) (
Fig 1A
), including a 41% higher risk of complex PCI (2.3% vs 1.7%; HRadj 1.41, 95% CI: 1.05-1.90). Evolocumab significantly reduced the risk of complex coronary revascularization procedures by 22% (HR 0.78, 95%CI [0.63, 0.95]) in pts with Lp(a) <125 nmol/L and by 41% (HR 0.59, 95%CI [0.45, 0.78]) in pts with Lp(a) ≥125 nmol/L (
Fig 1B
).

Conclusion and Relevance:
Among pts with ASCVD in FOURIER, higher baseline Lp(a) levels helped identify those with an increased risk of complex PCI or CABG. These findings highlight the value of baseline Lp(a) levels in identifying pts at risk for future complex coronary revascularization and the potential for reducing such high-risk and costly procedures with evolocumab.

Clinical Trial Registration
. NCT01764633
Abstract 4143938: Transcription Factor EB (TFEB) Regulates Metabolic Exchange Between Cardiomyocytes and Epicardial Cells
Authors: Elena Astanina , Doronzo Gabriella , Riganti Chiara , Ghigo Alessandra , Cimino James , Parab Sushant , Ballabio Andrea , Bussolino Federico
Published: November 2024

Introduction:
Metabolic symbiosis has been discovered in several contexts between cells with a high energy demand and supporting cells. Recently, reports have highlighted the existing lactate shuttle between cardiomyocytes (CMs) and cardiac fibroblasts. Epicardium is the embryonic source of cardiac fibroblasts and an active player in ischemic heart repair, however, its contribution to heart metabolism is unstudied. TFEB is a known regulator of energy metabolism in different cell types. Previously, we demonstrated that in mouse embryonic epicardium TFEB modulates TGFβ-driven epithelial-to-mesenchymal transition.

Methods and Results:
In adult mice with epicardium-specific
Tfeb
knock-out, no morphological defects were observed in the hearts. However, echocardiography demonstrated impaired heart contractility, specifically, reduced fractional shortening. The analysis of lysates of mutant hearts revealed reduced activity of enzymes involved in glycolysis, oxidative phosphorylation, and ATP production. We developed in vitro co-cultures between CMs differentiated from H9C2 cells and mouse epicardial cells (MEC), silenced for
Tfeb
or control.
Tfeb
knockdown in MEC led to decreased glucose metabolism, as assessed by biochemical assays and Seahorse analysis, resulting in reduced lactate secretion. By measuring the activity of lactate dehydrogenase and C14 tracing, we showed that CMs consumed lactate produced by MEC utilizing it to fuel their metabolism. Knockdown of lactate transporters
Mct1
and
Mct4
in MEC led to the same inhibitory effect on the metabolism of CMs as
Tfeb
silencing, while the addition of lactate to the medium rescued CMs’ metabolic parameters. RNAseq and ChIPseq analyses in MEC pointed to TFEB targets, DUSP4 and DUSP6 phosphatases. They were upregulated in MEC si
Tfeb,
leading to dephosphorylation of AKT and ERK kinases, possibly deregulating glucose metabolism. To investigate whether the metabolic deficiency in CMs could cause functional impairment, we co-cultured primary rat CMs with MEC si
Tfeb
and analysed contraction dynamics in microscopy videos. CMs co-cultured with MEC siCtrl but not with MEC si
Tfeb
performed better in terms of contraction amplitude and frequency than CMs cultured alone, and the addition of lactate to the medium rescued the deficit.

Conclusions:
These data suggest a novel mechanism of lactate shuttle between epicardial cells and CMs with a potential role for TFEB in regulation of glucose metabolism in epicardial cells.