bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4142848: Apabetalone Protects Against Heart Failure with Preserved Ejection Fraction by Suppressing Myocardial Inflammation
Authors: costantino sarah , Gorica Era , Mohammed Shafeeq , Telesca Marialucia , Mongelli Alessia , Masciovecchio Valeria , Herwig Melissa , Ambrosini Samuele , RUSCHITZKA FRANK , Nazha Hamdani , Paneni Francesco
Published: November 2024

Background:
Post-translational histone modifications wield significant influence over cardiac hypertrophy and dysfunction. Apabetalone (APA), a selective inhibitor of BET proteins, effectively disrupts the interactions between bromodomain-containing protein 4 (BRD4) and chromatin, exerting modulation over transcriptional programs across various organs.

Aim:
We aim to investigate if APA could be beneficial in cardiometabolic heart failure with preserved ejection fraction (cHFpEF).

Methods:
Comprehensive assessments including histology, mouse echocardiography, and treadmill exhaustion tests were performed on mice subjected to high-fat diet and L-NAME for 15 weeks to induce cHFpEF. Unbiased gene expression profiling via PCR array and proteomics were conducted on left ventricular (LV) myocardial of HFpEF mice and control ones. Cultured cardiomyocytes (CMs) treated with palmitic acid (PA) served as an in vitro model of metabolic stress. cHFpEF mice received chronic treatment with APA (150mg/kg/day) or vehicle (DMSO). To bridge these findings to human relevance, passive stiffness of skinned CMs from cHFpEF patients was evaluated before and after APA treatment.

Results:
HFpEF mice exhibited notable characteristics including LV hypertrophy, diastolic dysfunction, myocardial fibrosis, lung congestion, and compromised exercise tolerance. APA treatment significantly ameliorated diastolic dysfunction, as evidenced by improvements in the E/A ratio and isovolumic relaxation time (IVRT), alongside a reduction in lung congestion, and enhancement in exercise tolerance. Transcriptomic analysis of PA-treated CMs and LV specimens of cHFpEF mice revealed a profound dysregulation of genes involved in inflammation, particularly IL-6, TNF-alpha, and IL-1beta. Chromatin immunoprecipitation assays demonstrated BRD4 occupancy on the promoters of various inflammatory genes, including IL6, with APA treatment resulting in the suppression of most inflammatory genes, notably impacting IL6 expression. APA led to a decrease in circulating levels of several inflammatory chemokines. The beneficial effects of APA were elucidated through the modulation of the IL-6/CaMKII/STAT3 pathway in both cHFpEF hearts and PA-treated CMs. Notably, in skinned CMs obtained from cHFpEF patients, both APA treatment and IL6 blockade exhibited a capacity to attenuate passive stiffness.

Conclusions:
Our findings set the stage for preclinical studies and exploratory clinical trials testing APA in patients with cHFpEF.
Abstract 4142865: Determining the Physiologic Effect of the Cavopulmonary Connection on Caval Flows Using 4D Flow MRI
Authors: Suresh Kumar Vasupradha , Kollar Sarah , Loke Yue-Hin , Vegulla Ravi
Published: November 2024

Background:
The single ventricular (SV) palliative strategy involves routing the caval blood flow into the pulmonary arterial circulation. The superior cavopulmonary connection (SCPC) and Fontan connection generally raises caval pressures, although the changes to caval flows in SV patients has not been investigated. In this study, we determined the effect of SCPC and Fontan operation by comparing caval flows in SV pediatric patients against patients with biventricular (BiV) circulation as determined by 4D flow cardiac MRI (CMR).

Methods:
Clinically indicated CMR of two hundred and thirty-eight pediatric patients (≤18 years of age) were retrospectively analyzed. All included studies had ferumoxytol-enhanced 4D flow (Seimens 1.5T). Patients with systemic/pulmonary venous abnormalities were excluded. Flow in the superior vena cava (SVC) was measured by an independent observer using cloud-based platform Arterys (
Figure 1A
). The SVC flow was indexed against body surface area or expressed as a ratio of total venous return. Unpaired T-test and correlation analysis was used to compare differences between BiV and SV patients.

Results:
The cohort consisted of 149 BiV and 89 SV patients (8.5±5.7 years, body surface area 1.1±0.5 m
2
, 99 female). The indexed SVC flow negatively correlated with age (r=-0.313, p<0.0001) and body surface area (r=-0.540, p <0.0001). SVC flow as a ratio of total venous return was also negatively correlated with age (r=-0.332, p<0.0001) and body surface area (r=-0.546, p<0.0001-
Figure 1B
). SV patients post-SCPC had associated lower SVC flow compared to BiV children (1.3±0.6 vs. 1.6±0.7 L/min/m
2
, p<0.0001-
Figure 1C
).

Conclusion:
The caval flow distribution in the pediatric population changes with age and body size. SV patients with an SCPC had associated lower SVC flow compared to BiV patients. Determining the general caval flow distribution provides insight into the evolving flow hemodynamics of the growing pediatric patient, which in turn could be used to optimize the cavopulmonary connection in SV patients.
Abstract 4142868: AI-enhanced Electrocardiographic Evaluation of Left Ventricular Ejection Fraction and Outflow Tract Gradient in Hypertrophic Cardiomyopathy
Authors: Sangha Veer , Aminorroaya Arya , Dhingra Lovedeep , Pedroso Camargos Aline , Oikonomou Evangelos , Khera Rohan
Published: November 2024

Background:
Longitudinal assessments of left ventricular ejection fraction (LVEF) and left ventricular outflow tract (LVOT) gradient have become critical in the management of HCM with the emergence of cardiac myosin inhibitors (CMI) but rely on repeated echocardiography. We developed AI-enhanced tools to evaluate these echocardiographic parameters using images/photos of 12-lead ECGs and 1-lead ECG signals captured by portable devices.

Methods:
Using ECGs and paired echocardiograms recorded within 30 days at Yale during 2015-2022, we developed convolutional neural networks to predict continuous LVEF and LVOT gradients from 12-lead ECG images and lead I ECGs. We plotted 12-lead ECGs in varying layouts to ensure the image model was agnostic of real-world variations and augmented ECG signals with random Gaussian noises to improve the 1-lead model’s resilience to noisy acquisition. We leveraged resampling and weighted loss functions to optimize our regression models. We tested our models for detecting EF<50%, and LVOT≥30 and ≥20 mmHg – clinically important thresholds for treatment with CMI – on ECGs from a subset of patients with cardiac-MRI confirmed HCM.

Results:
Models for LVEF and LVOT were developed in 98,778 and 11,135 unique patients, respectively. The LVEF models were tested on ECGs from 489 unique patients with HCM (age 61 [IQR:53-68] years, 182 [37.2%] women, 46 [9.4%] EF<50%) who were not in the development cohort. The image and 1-lead LVEF models had AUROCs of 0.865 and 0.803, sensitivities of 91.3% and 89.1%, and specificities of 63.7% and 44.0%, respectively. We tested the LVOT models in 426 patients with HCM (61[53-69] years, 163 [38.3%] women, 19 [4.5%] LVOT≥30, 28 [6.6%] LVOT≥20). The image and 1-lead LVOT models had AUROCs of 0.833 and 0.817, sensitivities of 89.5% and 90.0%, and specificities of 58.5% and 52.7%, respectively, for detecting LVOT≥30, and AUROCs of 0.784 and 0.722, sensitivities of 92.9% and 89.3%, and specificities of 58.5% and 35.5%, respectively for LVOT≥20.

Conclusion:
AI applied to accessible modalities such as ECG images and 1-lead ECGs from portable devices may mitigate the burden of therapeutic monitoring for CMI in HCM, but further development and refinement are needed to fully validate their clinical utility as an efficient alternative to echocardiography.
Abstract 4142878: Temporal and Regional Trends of Mortality Related to Heart Failure in Hypertensive Older Adults in the United States from 1999-2020
Authors: Raza Ahmed , Khan Ubaid , Bin Gulzar Abu Huraira , Arshad Mirza Ammar , Tanveer Rahman , Sohail Haroon , Hamza Ali
Published: November 2024

Background:
Hypertension is a leading cause of cardiovascular diseases (CVD) and is responsible for one-fourth of all cases of heart failure (HF). It affects approximately 75 million adults, or one in three US adults. Studies demonstrate an association between chronic hypertension and heart failure. Chronic hypertension causes pathological changes in the heart, increasing the risk of HF by twofold in men and by threefold in women. Treatment of high blood pressure prevents and reverses myocardial changes in patients at risk of HF.

Objective:
Our objective is to identify the mortality patterns related to HF due to hypertension in older adults in the United States, stratified by age, sex, region, and area, and to investigate any changes over time.

Methods:
We used the data from the CDC WONDER database to determine the crude death rates (CR) and age-adjusted mortality rates (AAMRs) per 100,000 individuals. Our study targeted individuals aged 65 and older. We examined the change in AAMR through annual percent change (APC) and the average annual percentage change (AAPC) using the Joinpoint regression.

Results:
From 1999 to 2020, HF caused 259,079 deaths in the hypertensive patient population in the US, demonstrating an increasing trend (AAPC = 5.5107). Females (28.57) had higher AAMRs than males (25.56). Non-Hispanic (NH) Black or African Americans had the highest AAMRs (43.99), while NH Asian or Pacific Islanders had the lowest (19.42). AAMRs also varied by region (West: 34.57, South: 27.74, Midwest: 26.78, Northeast: 21.44). Massachusetts and Tennessee had the highest percentage change in AAMRs, while the states with the lowest were New Hampshire and Colorado. Most deaths occurred at a hospice/nursing facility (57.9%). Non-metropolitan areas (30.69) had the highest AAMRs.

Conclusions:
We report concerning trends of heart failure in the hypertensive population in the US, with the highest mortality rates in females, NH Black/African Americans, and in the Western region. Future research should focus on targeted therapy for the vulnerable population and defining an optimal blood pressure target for HF patients, as the evidence is inconsistent and scarce on this topic.
Abstract 4142890: Risk of Life-Threatening Ventricular Arrhythmias in Newly Diagnosed Non-Ischemic Heart Disease – A Meta-Analysis
Authors: Marijon Eloi , Aidelsburger Pamela , elayi Claude , Providencia Rui , Narayanan Kumar , Piot Olivier , Casolo Giancarlo , Metra Marco , Boveda Serge , Duncker David
Published: November 2024

Background and Aims:
In patients with non-ischemic cardiomyopathy (NICM), conditions such as peripartum cardiomyopathy or myocarditis may resolve, and an increase in left ventricular ejection fraction (LVEF) may occur within the first months of initiating guideline-directed medical therapy before considering an implantable cardioverter defibrillator (ICD). However, patients are at increased risk for sudden cardiac death (SCD) during this period, and a wearable cardioverter defibrillator (WCD) may help mitigate this transient risk. In this meta-analysis, we sought to assess the risk for appropriate shocks delivered by the WCD in patients with NICM in this vulnerable period.

Methods:
A systematic literature search was conducted in Medline, Embase, and Cochrane Library to identify studies reporting the use of WCD in patients with newly diagnosed NICM before April 2024. Two independent reviewers selected studies based on predefined inclusion and exclusion criteria. The study types considered included randomized and non-randomized controlled trials, prospective and retrospective cohort studies, registry data, and case series. Publications in languages other than English, German, or French were excluded. Studies with mixed populations (including patients with ischemic heart disease) were included if separate results were reported for each indication. Data on appropriate shocks, inappropriate shocks, WCD wear time, final device implantation, and deaths were extracted. Mean incidence rates for different outcomes were calculated for each subtype of NICM.

Results:
Forty-four studies were included. The mean incidence rate (per 1,000 patients) for appropriate shocks was 12 in dilated cardiomyopathy, 16 in myocarditis, 43 in peripartum cardiomyopathy, 19 in Takotsubo syndrome, and 13 in other genetic/congenital heart conditions. Inappropriate shocks were rare (<1% of patients). Finally, 1277 patients (35%) received an ICD across all studies.

Conclusion:
Patients with NICM face a significant risk of SCD during the waiting period before deciding if patient qualifies for an ICD implantation. Additional efforts are needed to refine identification methods and enhance strategies to manage at-risk patients during this critical period.
Abstract 4142894: Multimorbidity Trajectories Across the Lifespan in Patients with Congenital Heart Disease
Authors: Li Chao , Liu Aihua , Bendayan Solomon , Guo Liming , Therrien Judith , Yang Archer , Tamblyn Robyn , Brophy Jay , Li Yue , Marelli Ariane
Published: November 2024

Background:
Befitted from advances in medical care, patients with congenital heart disease (CHD) now survive to adulthood but face elevated risks of both cardiac and non-cardiac complications. Understanding the trajectories of comorbidity development over a patient's lifespan is cornerstone to optimize care expected to improve long-term health outcomes.

Research Aim:
This study aims to investigate the temporal sequences and evolution of comorbidities in CHD patients across their lifespan. We hypothesize that multimorbidity trajectories in CHD patients are linked to CHD lesion severity and age at onset of specific comorbidities.

Methods:
Using the Quebec CHD database which comprised data in outpatient visits, hospitalization records and vital status from 1983 to 2017, we designed a longitudinal cohort study evaluating the development of 39 comorbidities coded using ICD-9/10. Temporal sequences were mapped using median age of onset. Associations between disease pairs were quantified by hazard ratios from Cox proportional hazard models adjusting for age, sex, genetic syndrome, competing risks of death, and taking into account the time-varying nature of the predictor diseases.

Results:
The cohort included 9,764 individuals with severe and 127,729 with non-severe CHD lesions. In severe CHD patients, most comorbidities developed between ages 25 and 40. Comorbidity progression began with childhood cardiovascular diseases, followed by systemic diseases such as diabetes, liver and kidney diseases, and advanced to heart failure and dementia in middle adulthood. In addition, mental disorders emerged in early adulthood and were associated with subsequent development of kidney diseases and dementia. Different trajectories were observed in non-severe CHD patients with 2-3 decades later disease onsets and non-differential onsets between cardiovascular and systemic complications (Figure).

Conclusions:
Distinct multimorbidity trajectories were observed in CHD patients by CHD lesion severity. In patients with severe CHD lesions, early systemic diseases significantly influenced subsequent complications. These findings highlight the need for well-timed surveillance guidelines and interventions to improve health outcomes.
Abstract 4142897: The Burden of Adult Congenital Heart Disease in the United States
Authors: Suresh Kumar Vasupradha , Sable Craig , Nakiwala Dorothy , Kassebaum Nicholas
Published: November 2024

Introduction:
The Global Burden of Disease (GBD) study provides a unique opportunity to better understand fatal and nonfatal outcomes and their socioeconomic drivers in adults with congenital heart disease (ACHD). The aim of this study is to better understand trends in ACHD in the US and to analyze socioeconomic factors that may be correlated to geographic differences in patient outcomes.

Methods:
State specific data on mortality, prevalence, and disability adjusted life years (DALY) were acquired from GBD Database from 1990 to 2021 for ACHD patients aged 20 years and older in the USA. We subsequently correlated this data with median household income and percent uninsured in each state by using the US census bureau poverty and income data.

Results:
There are 292,625 (95% CI 258,956 – 342,906) adults > 20 years in the USA living with CHD in 2021 (compared to 212,366 in 1990). In 2021, ACHD was responsible for 1074 (CI 964 -1331) deaths and 62,244 (CI 51,820 – 76,301) DALYs (
FIGURE 1
). Between 1990 and 2021 there was a decrease in rates of mortality (0.79 to 0.43/100,000) and DALYs (44 to 25/100,000). There is considerable variation by state. The state with the highest mortality and DALYs (West Virginia) also has one of the lowest median household incomes ($51,122). States with lower ACHD mortality have higher median household incomes (r
2
=0.612, p<0.001) (
FIGURE 2
). The percent uninsured in each state also has a positive correlation with mortality (r
2
=0.142, p=0.006).

Conclusion:
The GBD study provides unique insight into ACHD mortality, prevalence, and disability and should be considered the gold standard for prevalence, disablity and mortality in the US. While mortality and disability rates have decreased from 1990 to 2021, ACHD patients living in states with lower median household income and higher percent uninsured have higher rates of mortality and disability. Investment into more equitable access to care is warranted for this population.
Abstract 4142901: Identification of ANGPTL4 and ITGAV as Therapeutic Targets for Calcific Aortic Valve Disease through Comprehensive Mendelian Randomization Using Human Plasma Proteome
Authors: Lu Jin , Xu Dilin , Hu Haochang , Qian Ningjing , Liu Xianbao , Wang Jianan
Published: November 2024

Background:
Calcific aortic valve disease (CAVD) is a degenerative disease characterized by aortic valve fibrosis and calcification with no medications available for treatment. Multi-omics research is highly beneficial for identifying disease targets. In this study, we aimed to identify potential therapeutic targets for CAVD through Mendelian randomization (MR) and summary data-based Mendelian randomization (SMR) combined with transcriptomic analysis.

Methods:
Protein quantitative trait locis (pQTLs) from two whole plasma protein databases deCODE and UK biobank pharma proteomics project (UKB-PPP) were utilized as the exposure. Three large CAVD cohorts from FinnGen (9,870 cases and 402,311 controls), the UK Biobank (3,552 cases and 425,855 controls) and France (3,123 cases and 6,531 controls) served as the outcome. MR and SMR was used to screen potential causal targets for CAVD. Colocalization analysis was performed to determine whether CAVD and target proteins shared common causal SNPs. Single-cell and bulk RNA sequencing was further used to detect the cell-type specific and differential expression of target proteins. Drug prediction and molecular docking was applied to discover potential medications.

Results:
15 plasma proteins were identified via MR and SMR analysis with 6 strongly supported via colocalization analysis. Among them, angiopoietin-related protein 4 (ANGPTL4) and integrin alpha-V (ITGAV) were validated in the replication CAVD cohorts from the UK Biobank or France as well as the bulk RNA sequencing data. Both of ANGPTL4 (OR = 1.963, 95% CI: 1.460-2.641,

P
FDR

= 7.30E-03) and ITGAV (OR = 1.579,95% CI: 1.257-1.985,

P
FDR

= 3.48E-02) were risk factors of CAVD and the protein levels of ANGPTL4 and ITGAV was upregulated in valvular interstitial cells as proved by Western blot. Molecular docking suggested a stable binding between the target proteins and medications.

Conclusions:
In a combination of proteome-wide MR and RNA sequencing analysis, ANGPTL4 and ITGAV were identified as the pivotal protein targets associated with the progression of CAVD.
Abstract 4142906: Efficacy and Safety of Aficamten in Patients Guideline-Eligible for Septal Reduction Therapy in the FOREST-HCM Trial
Authors: Masri Ahmad , Choudhury Lubna , Garcia-Pavia Pablo , Abraham Theodore , Barriales-Villa Roberto , bilen ozlem , Elliott Perry , Hagege Albert , Nagueh Sherif , Naidu Srihari , Nassif Michael , Olivotto Iacopo , Oreziak Artur , Owens Anjali , Wever-Pinzon Omar , Tower Rader Albree , Heitner Stephen , Kupfer Stuart , Malik Fady , Melloni Chiara , Meng Lixin , Wei Jenny , Saberi Sara
Published: November 2024

Background:
Patients (pts) with obstructive hypertrophic cardiomyopathy (oHCM) with severe symptoms despite medical therapy are offered septal reduction therapy (SRT) when available. We report the efficacy and safety of aficamten in SRT-eligible pts in the Phase 2 open-label extension trial FOREST-HCM (NCT04848506).

Methods:
Pts completing an aficamten parent study were offered participation in FOREST-HCM. Aficamten was initiated in all participants at 5 mg and escalated (10, 15, and 20 mg) at investigators’ discretion with protocol guidance according to left ventricular ejection fraction (LVEF) and left ventricular outflow obstruction (LVOT) criteria. SRT eligibility was defined per guidelines as both New York Heart Association (NYHA) class III/IV and any peak LVOT-G ≥50 mmHg.

Results:
Of 180 oHCM pts (mean age 60.8±13.1 years, 54% male) enrolled in FOREST-HCM from May 28, 2021 to March 15, 2024 with ≥24 weeks of follow-up, 57 (31.6%) were SRT-eligible at baseline. By week 24, only 2 (3.5%) pts remained SRT eligible (32 [56.1%] met neither criteria, 20 [35.1%] had LVOT-G ≥50 mmHg but were NYHA class I/II, and 2 (3.5%) had NYHA III/IV but LVOT-G <50 mmHg). NYHA improved ≥1 class in 52 (92.9%) SRT-eligible pts and in 80 (67.8%) pts of the remaining cohort. Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) improved more in SRT-eligible pts than remaining cohort (21.7±19.3 vs 13.5±13.9; p=0.003)
{Figure}.
Proportional reductions from baseline in NT-proBNP and high-sensitivity troponin were substantial in both groups. A modest reduction in LVEF occurred in both groups (-3.6% ±6.4 vs -3.4% ±6.2 in the SRT-eligible and remaining cohort respectively; between group p=0.34)
{Figure}.

Conclusions:
A third of pts enrolled in FOREST-HCM were guideline SRT-eligible at baseline despite optimized standard of care therapy, with almost all pts no longer meeting SRT-eligibility criteria by 24 weeks with aficamten treatment. Aficamten may provide an effective alternative to SRT in some patients with oHCM.
Abstract 4142932: Patients with Higher Stage of Cardiovascular-Kidney-Metabolic Syndrome Are More Likely to be Prescribed Antihypertensive Medication, Referred to Dietitians, and have an Echocardiogram among Youth Referred for Hypertension Disorders: A SUPERHERO Analysis
Authors: South Andrew , Baker-Smith Carissa , Campbell Jessica , Harry Giya , Laisure John , Murphy Margaret , Onugha Elizabeth , Pudupakkam Ashna , Riar Sandeep , Siddiqui Sahar , Vincent Carol , Walsh Michael
Published: November 2024

Background:
Presence of cardiovascular-kidney-metabolic (CKM) syndrome may help guide hypertension (HTN) management. However, whether initial management of youth with HTN disorders differs by CKM syndrome stage is unknown.

Methods:
Inferential cross-sectional analysis of baseline data from 7 sites in the Study of the Epidemiology of Pediatric Hypertension (SUPERHERO), a retrospective Registry of electronic health record data using standardized biomedical informatics scripts validated by manual record review. Inclusion criteria were youth <19 years old who received care from subspecialists for ICD-10 code-defined HTN disorders from 1/1/2016–12/31/2023. Exclusion criteria were ICD-10 code-defined kidney replacement therapy (dialysis or transplantation) or pregnancy. Exposure was CKM syndrome (Stage 0, Stage 1, Stage 2, or Unclassified) defined by ICD-10 codes and recorded blood pressure and BMI. Outcomes were orders for antihypertensive prescriptions (
n
=5,766) and for echocardiograms and dietitian referrals (
n
=9,356). We used directed acyclic graph-informed generalized linear models adjusted for acute kidney injury, cancer, growth restriction, lower birth weight, preterm birth, and social risk factors by ICD-10 codes and visit season.

Results:
Of 9,356 participants, 85% had CKM syndrome, 16% were prescribed a medication, 33% had an echocardiogram ordered, and 7% had a dietitian referral ordered. Participants with Stage 2 CKM syndrome were 34% more likely to have an echocardiogram ordered vs. Stage 0 (95% CL 1.16–1.55) and 25% more likely vs. Stage 1 (95% CL 1.14–1.38). Those with Stage 2 were 29% more likely to be prescribed medication vs. Stage 0 (95% CL 1.03–1.62) and 62% more likely vs. Stage 1 (95% CL 1.35–1.94). Compared to Stage 0, dietitian referrals were more common in those with Stage 2 CKM syndrome (RR 1.85, 95% CL 1.28–2.68), Stage 1 (RR 1.79, 95% CL 1.21–2.67), and Unclassified (RR 1.91, 95% CL 1.21–3.02).

Discussion:
At the first HTN disorder clinic visit, providers were more likely to order echocardiograms, prescribe antihypertensive medication, and refer to dietitians in youth with worse CKM syndrome stage. This supports current guideline recommendations for youth with HTN disorders. Ongoing steps in SUPERHERO are improving the definition of CKM syndrome and outcomes. Future analyses will investigate if presence of CKM syndrome can improve management and health outcomes.
Abstract 4142935: Circulating endothelial cells and microthrombosis as markers of vascular dysfunction in Long COVID
Authors: Dias Carolina , Condor Jose Manuel , Robleto Emely , Guevara Patricia , Bast Elizabeth , Palacio Ana , Tamariz Leonardo , Shehadeh Lina
Published: November 2024

Background.
Post-COVID syndrome is related to a multisystem disorder that affects in part the cardiovascular system. This disease involves symptoms, and conditions that continue or develop after acute COVID-19. SARS-CoV-2 infection of immune and endothelial cells are associated with NETosis, microthrombosis and endothelial dysfunction that could persist several weeks after acute phase of infection. Damaged endothelial cells can expose the vessel pro-coagulant area leading to platelet and neutrophil clumps. Increased levels of circulating endothelial cells (CECs) have been described as biomarkers for cardiovascular diseases. Therefore, we hypothesize that CECs and microthrombosis are potential biomarkers of vascular dysfunction in Long COVID.

Methods.
A cross-sectional study was conducted at the Miami VA long COVID clinic. Long COVID cases and controls were recruited according to WHO definition for long COVID. A total of 23 patients and 7 controls were included in this study. Blood samples were collected in Heparin and Sodium Citrate tubes. Cell immunophenotyping and NETosis markers (MPO) were quantified on a Cytek Aurora spectral flow cytometer system. Microclots (CD62P
+
PAC-1
+
) and platelet response were assessed by flow cytometry and response to Adenosine di-phosphate (ADP), respectively. A ttest was used for statistical analysis. Differences were considered significant when p < 0.05.

Results.
The age and gender were similar between cases and controls while their symptom score was significantly different. There was a significant increase in the number of CECs (CD31+CD309+CD45-CD133-) in Long COVID cases. MPO expression in neutrophils (CD11b
+
CD66b
+
CD15
+
) and classical monocytes (CD14
+
CD16
-
) was significantly higher in Long COVID. Microclots were significantly elevated, and the platelet aggregation response was dysregulated in Long COVID.

Conclusions.
CECs and microthrombosis including NETosis are present in Long COVID and may serve as potential biomarkers or causative mechanisms for vascular dysfunction.
Abstract 4142952: Feature Tracking Global Longitudinal Strain in Long-term Risk Stratification of Hypertrophic Cardiomyopathy without Septal Reduction Therapy
Authors: Ma Xuan , Tang Yun , Chen Xingrui , Yang Shujuan , Zhao Shihua
Published: November 2024

Background:
The significance of left ventricular global longitudinal strain (LV-GLS) for risk stratification of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) without septal reduction therapy remains to be investigated.

Aims:
To evaluate the prognostic utility of LV-GLS in a long-term follow-up HCM cohort without septal reduction therapy.

Methods:
We retrospectively enrolled 871 consecutive patients with HCM (mean age 49±13 years, 71% men) who underwent cardiac MRI in our center between January 2010 and December 2013. All study participants never received alcohol septal ablation or surgical myectomy during follow-up. LV-GLS were derived from cine cardiac MRI by using feature tracking method. The primary endpoint was SCD or SCD-equivalent events. The association between LV-GLS and SCD-related endpoints was evaluated by using time-dependent receiver operating characteristic (ROC) analysis, Kaplan-Meier analysis, and multivariable competing risk regression analysis.

Results:
During median follow-up of 8.8 years, SCD-related endpoint occurred in 45 HCM patients (5.2%). Patients suffering from SCD had higher European Society of Cardiology (ESC) Risk-SCD score (2.2 ± 0.6 vs. 2.6 ± 0.6, P < .001) and absolute LV-GLS (11.4 ± 3.7% vs. 9.3 ± 3.4%, P < .001). According to time-dependent analysis, 9% is an optimal cut-off value for absolute LV-GLS in predicting the primary outcome after a 10-year follow-up. On competing risk regression analysis, absolute LV-GLS ≤ 9% was associated with a higher rate of primary endpoints (subhazard ratio: 2.66 [95% confidence interval: 1.96 to 3.36]) after adjustment for known risk factors. Finally, LV-GLS provided incremental prognostic value over 2020 American College of Cardiology (ACC)/American Heart Association (AHA) risk model (log-likelihood ratios, -262.2 vs -266.2; P = .003) and 2022 ESC risk model (log-likelihood ratios, -268.4 vs -264.9; P = .009), respectively. In the subgroup with Class 3 of recommendation for implantable cardioverter defibrillator, patients with absolute LV-GLS ≤ 9% showed significantly worse prognosis than those with absolute LV-GLS > 9% (p = .002 and .004 for 2020 AHA guideline and 2022 ESC guideline, respectively).

Conclusion:
Feature tracking LV-GLS derived by cardiac MRI may enable further risk stratification for the subgroup of HCM patients who never accept septal reduction therapy in their lifetime, especially for those recognized as low-risk for SCD based on current guidelines.
Abstract 4142958: Obesity Negatively Impacts Left Ventricular Mitochondrial Electron Transport Chain in End-Stage Heart Failure Patients
Authors: Vaka Ramana , Edwards Kristin , Hoang Ngoc , Lamarca Babbette
Published: November 2024

Introduction:
Obesity is an independent risk factor for heart failure (HF). Metabolic remodeling resulting from myocardial lipid accumulation is implicated in left ventricular (LV) dysfunction in HF patients with obesity. While obesity is shown to be inextricably linked to mitochondrial dysfunction in metabolic disease, its affect on LV mitochondrial function in failing hearts is unknown.
Hypothesis:
As such, we hypothesized that HF patients with obesity demonstrate reduced LV mitochondrial function in comparison to HF patients without obesity.

Methods:
In accordance with an approved IRB protocol, LV biopsies were sampled from end-stage HF patients undergoing left ventricular assist device (LVAD) surgery at the University of Mississippi Medical Center. Approximately 20 mg of LV tissue per patient was used to isolate mitochondria using differential centrifugation. The activities of individual electron transport chain (ETC) complexes (I-IV) and citrate synthase (CS; marker of mitochondrial content) were measured using Oxygraph-2K and spectrophotometer. Complex I-IV rates (nmol e
-
/min) were normalized to CS activity (nmol e
-
/min). Normality, statistical significance, correlations were tested using the Kolmogorov-Smirnov test, Welch’s t test, and Pearson correlation respectively. The data are presented as mean± standard error where appropriate. A p-value <0.05 was considered statistically significant.

Results:
The study included 16 HF patients (3 females; age=52±3 years; 58% black, 42% white; 6 obese, BMI=40.9±2.11 kg/m
2
; 10 non-obese, BMI=25.74±0.71 kg/m
2
). Obese HF patients showed significant reductions in Complex I (46% lower, n=6-10, p=0.0343), and Complex IV (47% lower, n=5-10, p=0.0162) activities vs. non-obese HF patients. However, Complex II and III activities were unaltered between the groups. Further, CS activity was not different between the groups suggesting that LV mitochondrial mass is preserved in obese HF patients. Further, our correlation analysis revealed that Complex I (R
2
=0.3090, p=0.0254) and Complex IV (R
2
=0.4418, p=0.0069) activities were inversely correlated with BMI of the patients.

Conclusions:
The ETC complex I and IV activities are reduced by nearly half in obese HF patients highlighting a pronounced impact of obesity on myocardial mitochondrial function in end-stage failing hearts. These preliminary findings encourage further exploration on obesity mediated mitochondrial perturbations in heart failure patients.
Abstract 4142959: Carotid 3D Plaque Composition after Carnitine Supplementation in Patients with Metabolic Syndrome
Authors: Chen Zejia , Hetu Marie-France , Collet-Billon Antoine , Rouet Laurence , Entrekin Robert , Johri Amer
Published: November 2024

Background:
L-Carnitine (L-C) is a widely used nutritional supplement, but its effect on cardiovascular disease (CVD) is controversial. L-C has been shown to have benefits for CVD but is also believed to be associated with pro-atherogenic mechanisms. We have previously shown that L-C does not cause plaque progression (no effect) in metabolic syndrome patients supplemented with L-C but indicated an increase in stenosis. Carotid plaque ultrasound pixel distribution analysis (PDA) can identify plaque tissue types (soft vs calcified) indicating if a plaque is prone to rupture and to cause cardiovascular events. Beyond plaque volume (quantity), a change in plaque composition may have a role in causing cardiovascular events (increased lipid core).

Research Questions/Hypothesis:
Is there a change in 3D plaque composition from baseline to 6-month when taking an L-C supplement in metabolic syndrome patients? If L-C is associated with pro-atherogenic mechanisms, perhaps plaque composition may change (increased fat), increasing risk for events.

Methods:
Patients were selected from cardiology and stroke clinics who met the diagnostic criteria for metabolic syndrome. Participants (n=157) were randomized to 6-month L-C (2g/day, n=76) or placebo (n=81). Participants received a 3D carotid ultrasound at baseline and 6-months. Carotid plaques were analyzed using a novel 3D carotid arterial plaque composition analysis software (Carotid Model, Figure) that uses deep learning artery and plaque classifications with grayscale PDA (Philips Healthcare). 3D percent change in plaque volume, blood, fat, muscle, fibrous, and calcium due to L-C supplementation was assessed by pairwise t-test.

Results:
We found no difference in baseline characteristics between placebo and L-C arms. There was no change in percent total plaque volume (L-C=4.18% vs Placebo=17.0%; P=0.24). Each plaque composition component remained similar from baseline to 6-month within arms and between arms (Table). There was a slight increase in grayscale median value in the placebo arm.

Conclusion(s):
We did not observe a change in carotid 3D plaque volume or plaque composition following 6-month treatment with L-C. Our findings support the theory that L-C may not be directly involved in a pro-atherogenic mechanism. Although L-C supplementation did not influence plaque composition in this population, the software has great potential in determining changes in plaque vulnerability over time in response to drug therapy.
Abstract 4142963: Effects of high-intensity inspiratory muscle training as a pre-cardiac rehabilitation intervention on cardiovascular function in patients with heart disease: A pilot study
Authors: AKTAN RIDVAN , Severin Richard , Ozemek Cemal
Published: November 2024

Background:
Endothelial function is closely associated with cardiovascular health among individuals being treated for heart disease. Inspiratory muscle training (IMT) consists of repeated inspirations against a resistance on a handheld device. The effects of high-intensity IMT on endothelial function and arterial stiffness is not well known in this population.

Aim:
The aim of this study was to investigate whether high-intensity IMT, beyond usual clinical care, improves endothelial function, arterial stiffness, inspiratory muscle strength, functional capacity, and dyspnea perception in patients with heart disease.

Methods:
In this randomized controlled trial participants qualifying for phase two, outpatient cardiac rehabilitation were included. After baseline assessments, participants were randomized to 4 weeks of either high-intensity inspiratory muscle training (IMT) with a resistance set to 60% of baseline maximum inspiratory pressure (MIP) or sham-IMT without resistance (control group). Endothelial function was assessed using flow-mediated dilatation (FMD%), arterial stiffness by pulse wave velocity (PWV), 6-min walk distance (6MWD) was used to quantify functional capacity, dyspnea perception by modified medical research council dyspnea (mMRC) scale, and inspiratory muscle strength by maximal inspiratory pressure (MIP) were assessed. An ANOVA was applied using the intention-to-treat analysis. Data are expressed in mean±SD. Effect sizes presented based on between groups ANOVA.

Results:
There were no differences between groups for baseline age, BMI, sex, FMD%, PWV, mMRC, 6MWD and inspiratory muscle strength. No significant changes in the respective measures of interest were observed in the control group (n=6). The intervention group (n=5) experienced significant improvements in FMD% (pre = 5.41 ± 1.93, post = 7.53 ± 1.62, p< 0.05, η
2
effect size= 0.72), 6MWD (pre = 301.0 ± 39.8, post = 340.4 ± 36.6 meters, p< 0.05, η
2
effect size= 0.94), mMRC score (pre = 2.8 ± 0.5, post = 1.6 ± 0.6 points, p< 0.05, η
2
effect size= 0.76), and MIP (pre = 46.4 ± 13.4, post = 68.8 ± 13.6 cmH
2
O, p< 0.05, η
2
effect size= 0.82).There were no significant difference between group in PWV (p> 0.05).

Conclusion:
The findings of this study suggest that high-intensity IMT, as a pre-cardiac rehabilitation intervention, produced improvements in endothelial function, MIP, functional capacity, and dyspnea in patients with heart disease.
Abstract 4142988: Effectiveness of Additive Cardiac Computed Tomography Angiography for Pre-procedural Planning of Left Atrial Appendage Occlusion: A Systematic Review and Meta-Analysis
Authors: Pereira Vinicius , Fernandes Julia , Petri Santos Pinheiro Rafael , Andrade Naieli , Katsuyama Eric , Ezenna Chidubem , Murali Krishna Mrinal , Joseph Meghna , Gomes Wilton
Published: November 2024

Introduction:
The latest expert consensus on catheter-based Left Atrial Appendage Occlusion (LAAO) suggests considering either transesophageal echocardiography (TEE) alone or the addition of Cardiac Computed Tomography Angiography (CCTA) for pre-procedural planning. However, evidence comparing the effectiveness of adding CCTA to regular TEE planning on procedural success is limited.

Methods:
We aimed to perform a systematic review and meta-analysis to determine the impact of adding CCTA to regular TEE for pre-procedural planning in patients undergoing LAAO. We systematically searched Cochrane, Embase, and Medline for observational studies and randomized controlled trials (RCTs) comparing TEE alone to TEE with the addition of CCTA. The primary endpoint was procedural success. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled across studies using a random-effects model.

Results:
Four studies were included in our meta-analysis, three of which were RCTs and one observational study, comprising a total of 824 patients, of whom 496 (60.2%) underwent additional CCTA. In the pooled analysis, procedural success was higher in the group with added CCTA (RR 1.10; 95% CI 1.01 - 1.19; p=0.022; I2=52%). A subgroup analysis of RCTs alone confirmed these findings, with a slightly higher magnitude of effect in benefit of the addition of CCTA, and with lower heterogeneity (RR 1.15; 95% CI: 1.06 - 1.25; I2 = 0%).

Conclusions:
In this meta-analysis comparing TEE alone vs TEE with the addition of CCTA for preprocedural planning of LAAO, the addition of CCTA was associated with a higher procedural success rate, and this finding was confirmed in a subgroup analysis of randomized data.
Abstract 4142989: Myocardial Perfusion Reserve Index in Pediatric Heart Transplant Recipients
Authors: Lawson Andrew , Lee Simon , Popescu Andrada , Tannous Paul , Laternser Christina , Markl Michael , Rigsby Cynthia , Robinson Joshua , Magnetta Defne , Husain Nazia
Published: November 2024

Background:
Cardiovascular magnetic resonance (CMR) has an emerging role in graft surveillance for pediatric heart transplant recipients (PHTR). Transplanted grafts are susceptible to cardiac allograft vasculopathy, manifested as macrovascular narrowing on angiography, as well as micro-vessel disease. By CMR, myocardial perfusion abnormalities can be evaluated semi-quantitatively, by calculation of a myocardial perfusion reserve index (MPRI). However, normal MPRI values have not been well established in PHTR and prior investigation of associations between MPRI and graft pathology remain limited.

Research Aims:
The goals of this study were to describe the MPRI findings in a large cohort of PHTR and to evaluate clinical associations with low MPRI.

Methods:
We performed a retrospective chart review of consecutive, stress CMR studies at a single center from 2015-2024. Follow-up studies were excluded. Biventricular volume and function analyses were performed. A total dose of 0.15mg/kg gadobutrol was administered for rest and stress imaging. Regadenoson was the pharmacologic stressor at dose of 6-10mcg/kg, up to max 400mcg. Time signal intensity curves were obtained from perfusion datasets at stress and rest at the base, mid-ventricle, and apex. Segmental MPRI was calculated as a ratio of the maximal upslopes of the curves at stress versus rest. Global MPRI was computed as a mean of all segments.

Results:
128 PHTR were included. Mean age was 12.5±5.3y, with 5.9±3.8y since transplant. A clinical concern prompted CMR in 18% of studies; in 82% the indication was routine surveillance. History of CAV was present in 6% and moderate or severe rejection in 22%. In 11 studies, images were inadequate for MPRI analysis. In the 117 studies included for analysis, global MPRI was normally distributed with mean 1.38±5.3. Mean MPRI observed at the mid-ventricle (1.49±0.46) was higher than at the base (1.32±0.32) and apex (1.33±0.39), (p<0.001). PHTR with first tercile MPRI (<1.25), when compared to third tercile (>1.50), did not have significant differences in age, time since transplant, history of CAV, history of moderate or severe rejection, or LV or RV EF.

Conclusions:
Mean global MPRI values in this cohort of relatively healthy PHTR are significantly lower than reference values for healthy adults and similar to previously reported values in adult heart transplant patients. Future study should evaluate associations between MPRI and subsequent clinical outcomes.
Abstract 4142993: Myocardial Performance Score: A Novel Marker of Cardiac Power and Efficiency for Prognostication of Advanced Heart Failure
Authors: Randazzo Michael , Kanelidis Anthony , Kalantari Sara , Smith Bryan , Nguyen Ann , Chung Bow , Swat Stanley , Sarswat Nitasha , Salerno Christopher , Jeevanandam Valluvan , Kim Gene , Belkin Mark , Grinstein Jonathan
Published: November 2024

Introduction:
Assessment of invasive hemodynamics is a critical aspect of heart failure (HF) management influencing treatment decisions. However, standard metrics including intracardiac filling pressures and cardiac output do not consistently predict clinical outcomes. The myocardial performance score (MPS) is a novel hemodynamic parameter that combines myocardial power and efficiency into a single variable. We aimed to evaluate the prognostic significance of MPS and assess whether it can improve risk stratification compared to traditional measures.

Methods:
All patients who underwent isolated right heart catheterization for chronic, or acute on chronic HF between 2013-2019 at our institution were retrospectively analyzed. MPS is calculated as [aortic pulsatility index (API) x cardiac power output (CPO)]/2. The primary outcome was a composite endpoint of death or need for left ventricular assist device or heart transplant over a two-year period. MPS thresholds of 0.5 and 1.0 were selected from prior analyses showing declining efficiency less than 0.5 in addition to balanced power and efficiency greater than 1.0. Kaplan-Meier curves were calculated with statistical significance determined by log-rank tests.

Results:
A total of 709 patients (60±14 years; 54% male) were included, of which 102 (14%) had an MPS<0.5, 169 (24%) had an MPS between 0.5-1.0, and 438 (62%) had an MPS≥1.0. Of the 607 patients with an MPS≥0.5, 379 (62%) demonstrated freedom from the composite endpoint compared to 37 (36%) patients with an MPS<0.5 (p<0.0001). An intermediate MPS (0.5≤MPS<1.0) conveyed significantly greater freedom compared to patients with a low MPS<0.5 (57% vs 36%; p<0.001), yet lower freedom compared to those with a high MPS≥1.0 (57% vs. 66%, p<0.05). An MPS<0.5 demonstrated superior risk stratification with an odds ratio for the composite endpoint at two years of 3.1 compared to 1.8 for pulmonary capillary wedge pressure>15 mmHg and cardiac index<2.0 L/min/m
2
estimated by Fick equation or thermodilution (Figure).

Conclusions:
MPS is a novel, advanced hemodynamic measurement that outperforms current invasive hemodynamic parameters in accurately predicting long-term clinical outcomes in all patients with heart failure.