Role of epicardial adipose tissue in cardiac remodeling.

Epicardial adipose tissue, or epicardial fat, is a type of visceral fat located between the heart and the pericardium. Due to its anatomical proximity to the heart, EAT plays a significant role in both cardiac physiology and pathologies, including cardiac remodeling and cardiovascular diseases (CVD). However, our understanding of how EAT pathology is influenced by risk factors such as obesity and type 2 diabetes mellitus and how altered EAT can drive cardiac remodeling and CVD, remains limited. Herein, we aimed to summarize and discuss the latest findings on EAT and its role in cardiac remodeling, highlighting the outcomes of clinical and observational studies, provide mechanistic insights, and finally introduce emerging therapeutic agents and nutritional guidelines aimed at preventing these conditions.

Characteristics of gene expression in epicardial adipose tissue and subcutaneous adipose tissue in patients at risk for heart failure undergoing coronary artery bypass grafting.

BACKGROUND: Epicardial adipose tissue (EAT) surrounds the heart and is hypothesised to play a role in the development of heart failure (HF). In this study, we first investigated the differences in gene expression between epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients undergoing elective coronary artery bypass graft (CABG) surgery (n = 21; 95% male). Secondly, we examined the association between EAT and SAT in patients at risk for HF stage A (n = 12) and in pre-HF patients, who show signs but not symptoms of HF, stage B (n = 9). RESULTS: The study confirmed a distinct separation between EAT and SAT. In EAT 17 clusters of genes were present, of which several novel gene modules are associated with characteristics of HF. Notably, seven gene modules showed significant correlation to measures of HF, such as end diastolic left ventricular posterior wall thickness, e'mean, deceleration time and BMI. One module was particularly distinct in EAT when compared to SAT, featuring key genes such as FLT4, SEMA3A, and PTX3, which are implicated in angiogenesis, inflammation regulation, and tissue repair, suggesting a unique role in EAT linked to left ventricular dysfunction. Genetic expression was compared in EAT across all pre-HF and normal phenotypes, revealing small genetic changes in the form of 18 differentially expressed genes in ACC/AHA Stage A vs. Stage B. CONCLUSIONS: The roles of subcutaneous and epicardial fat are clearly different. We highlight the gene expression difference in search of potential modifiers of HF progress. The true implications of our findings should be corroborated in other studies since HF ACC/AHA stage B patients are common and carry a considerable risk for progression to symptomatic HF.

Radiomics parameters of epicardial adipose tissue predict mortality in acute pulmonary embolism.

BACKGROUND: Accurate prediction of short-term mortality in acute pulmonary embolism (APE) is very important. The aim of the present study was to analyze the prognostic role of radiomics values of epicardial adipose tissue (EAT) in APE. METHODS: Overall, 508 patients were included into the study, 209 female (42.1%), mean age, 64.7 ± 14.8 years. 4.6%and 12.4% died (7- and 30-day mortality, respectively). For external validation, a cohort of 186 patients was further analysed. 20.2% and 27.7% died (7- and 30-day mortality, respectively). CTPA was performed at admission for every patient before any previous treatment on multi-slice CT scanners. A trained radiologist, blinded to patient outcomes, semiautomatically segmented the EAT on a dedicated workstation using ImageJ software. Extraction of radiomic features was applied using the pyradiomics library. After correction for correlation among features and feature cleansing by random forest and feature ranking, we implemented feature signatures using 247 features of each patient. In total, 26 feature combinations with different feature class combinations were identified. Patients were randomly assigned to a training and a validation cohort with a ratio of 7:3. We characterized two models (30-day and 7-day mortality). The models incorporate a combination of 13 features of seven different image feature classes. FINDINGS: We fitted the characterized models to a validation cohort (n = 169) in order to test accuracy of our models. We observed an AUC of 0.776 (CI 0.671-0.881) and an AUC of 0.724 (CI 0.628-0.820) for the prediction of 30-day mortality and 7-day mortality, respectively. The overall percentage of correct prediction in this regard was 88% and 79% in the validation cohorts. Lastly, the AUC in an independent external validation cohort was 0.721 (CI 0.633-0.808) and 0.750 (CI 0.657-0.842), respectively. INTERPRETATION: Radiomics parameters of EAT are strongly associated with mortality in patients with APE. CLINICAL TRIAL NUMBER: Not applicable.

Potential Mechanisms of Epicardial Adipose Tissue Influencing Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) is the predominant terminal stage and the leading cause of mortality in cardiac disease. Heart failure with preserved ejection fraction (HFpEF) affects roughly 50% of HF patients globally. Due to the global aging population, the prevalence, morbidity, and mortality of HFpEF have gradually increased. Epicardial adipose tissue (EAT), as a key visceral adipose tissue around the heart, affects cardiac diastolic function and exercise reserve capacity. EAT closely adheres to the myocardium and can produce inflammatory factors, neurotransmitters, and other factors through autocrine or paracrine mechanisms, affecting the heart function by inflammatory response, cardiac metabolism and energy supply, cardiomyocyte structure and electrical activity, and pericardial vascular function. Currently, research on the mechanism and treatment methods of HFpEF is constantly improving. EAT may play a multi-level impact on the occurrence and development of HFpEF. This review also summarizes the potential impact of EAT on the heart in HFpEF combined with other metabolism-related diseases such as obesity or diabetes over other obesity-related measures, such as body mass index (BMI) or other adipose tissue. Above all, this review comprehensively summarizes the potential mechanisms by which EAT may affect HFpEF. The objective is to enhance our comprehension and management of HFpEF. Future research should delve into the mechanistic relationship between EAT and HFpEF, and investigate interventions aimed at EAT to improve the prognosis of patients with HFpEF.

Artificial Intelligence Prediction of Cardiovascular Events Using Opportunistic Epicardial Adipose Tissue Assessments From Computed Tomography Calcium Score.

Background: Recent studies have used basic epicardial adipose tissue (EAT) assessments (eg, volume and mean Hounsfield unit [HU]) to predict risk of atherosclerosis-related, major adverse cardiovascular events (MACEs). Objectives: The purpose of this study was to create novel, hand-crafted EAT features, "fat-omics," to capture the pathophysiology of EAT and improve MACE prediction. Methods: We studied a cohort of 400 patients with low-dose cardiac computed tomography calcium score examinations. We purposefully used a MACE-enriched cohort (56% event rate) for feature engineering purposes. We divided the cohort into training/testing sets (80%/20%). We segmented EAT using a previously validated, deep-learning method with optional manual correction. We extracted 148 initial EAT features (eg, morphologic, spatial, and HU), dubbed fat-omics, and used Cox elastic-net for feature reduction and prediction of MACE. Bootstrap validation gave CIs. Results: Traditional EAT features gave marginal prediction (EAT-volume/EAT-mean-HU/BMI gave C-indices 0.53/0.55/0.57, respectively). Significant improvement was obtained with the 15-feature fat-omics model (C-index = 0.69, test set). High-risk features included the volume-of-voxels-having-elevated-HU-[-50,-30-HU] and HU-negative-skewness, both of which assess high HU values in EAT, a property implicated in fat inflammation. Other high-risk features include kurtosis-of-EAT-thickness, reflecting the heterogeneity of thicknesses, and EAT-volume-in-the-top-25%-of-the-heart, emphasizing adipose near the proximal coronary arteries. Kaplan-Meyer plots of Cox-identified, high- and low-risk patients were well separated with the median of the fat-omics risk, with the high-risk group having an HR 2.4 times that of the low-risk group (P < 0.001). Conclusions: Preliminary findings indicate an opportunity to use finely tuned, explainable assessments on EAT for improved cardiovascular risk prediction.

Pearls and Pitfalls of Epicardial Echocardiography for Implantation of Impella CP Devices in Ovine Models.

The Impella CP is a percutaneously inserted temporary left ventricular assist device used in clinical practice and in translational research into cardiogenic shock, perioperative cardiac surgery, acute cardiac failure and mechanical circulatory support. Fluoroscopic guidance is usually used for insertion of an Impella, thus limiting insertion to within catheterization laboratories. Transthoracic, transoesophageal and intracardiac echocardiography have been reported to guide Impella CP implantation with identified specific limitations stemming from the surgical, anatomical and equipment factors. We conducted translational prospective descriptive feasibility investigation as a part of two other hemodynamic Impella studies. It showed the successful application of epicardial echocardiographic scanning for implantation of Impella CP devices in ovine models, from which details of the technique and identified pitfalls are described with practical solutions for future investigators and clinicians. Many described findings are relevant to any other echocardiographic techniques when adequate imaging of the Impella and relevant anatomical structures is achievable.

The Role of Plain CT in Assessing and Estimating Normal Values of Pericardial Fat Pad Thickness and Their Correlation With Patient's Age, Gender, Body Weight, and Body Mass Index.

Introduction The pericardial fat pad, located anteriorly to the heart between the pericardium and myocardium, has garnered significant interest in cardiovascular research due to its potential role in the pathophysiology of various cardiac conditions. Despite its proximity to the myocardium, it is distinct from the epicardial fat depot found between the myocardium and the visceral layer of the pericardium. Studies have shown that excess pericardial fat is associated with an increased risk of heart failure and other cardiovascular diseases. Non-contrast computed tomography (CT) is a reliable, non-invasive method for assessing pericardial fat pad thickness, offering less radiation exposure compared to other imaging modalities. Establishing standardized measurements for pericardial fat pad thickness is essential, particularly for the South Indian population, which may exhibit unique genetic, dietary, and lifestyle influences on these measurements. Materials and methods A cross-sectional study was conducted on 300 participants from South India, stratified into three age groups: 18-35, 36-50, and 51-70 years, with body weights ranging from 45 kg to 120 kg. Participants were recruited from outpatient departments and community outreach programs, ensuring equal representation from each age group. Non-contrast CT imaging was performed using a Siemens Somatom goTop 128 Slice CT scanner to measure pericardial fat pad thickness and correlate it with age, gender, body weight, and body mass index. Exclusion criteria included diagnosed cardiac or pericardial diseases, prior chest surgery or trauma, pregnancy, and contraindications to CT scans. Ethical approval was obtained, and informed consent was collected from all participants. Data analysis was performed using SPSS software, employing descriptive statistics, ANOVA, t-tests, and Pearson's correlation. Results The study included 300 participants, with an equal gender distribution of 150 males and 150 females. Pericardial fat pad thickness increased with age, averaging 4.2 mm in the 18-35 age group, 5.1 mm in the 36-50 age group, and 6.4 mm in the 51-70 age group. Males exhibited a higher average thickness (5.6 mm) compared to females (5.0 mm). Body weight also showed a positive correlation with pericardial fat pad thickness, with mean values increasing from 4.5 mm in the 45-60 kg range to 6.7 mm in the 106-120 kg range. Statistical analysis confirmed significant differences in pericardial fat pad thickness across age groups, genders, and weight categories, emphasizing the importance of these factors in assessing cardiovascular risk. Conclusion This study provides a benchmark for pericardial fat pad thickness in the Kancheepuram Population of South India, highlighting its correlation with age, gender, body weight, and body mass index. The findings underscore the significance of non-invasive CT imaging in evaluating cardiovascular risk factors. Further research should focus on longitudinal studies and advanced imaging techniques to enhance the diagnostic accuracy and clinical relevance of pericardial fat pad measurements. The established reference values can aid clinicians in identifying individuals at higher risk for cardiovascular diseases, facilitating early intervention and management.

Negative association of apelin plasma levels with epicardial fat thickness in patients with stable angina and acute myocardial infarction: A case-control study.

Background: Apelin is one of the endogenous peptides that play a key role in the homeostasis of cardiovascular diseases. The purpose of the current study was to evaluate the correlation between apelin levels and epicardial fat thickness (EFT) in patients with stable angina and acute myocardial infarction (AMI). Materials and Methods: In a case-control study, 90 patients nominated for angiography were enrolled in the study and divided into three groups: healthy subjects without angiographic findings (Con), stable angina pectoris group (SAP), and acute AMI group. Data collected from all subjects included biochemical, echocardiographic, and angiographical parameters. The Gensini score analyzed the severity of coronary artery disease (CAD). Results: A decrease in adjusted apelin levels was evident in the AMI and SAP groups compared with healthy individuals (for both P < 0.001), especially in the AMI group. In addition, a detectable negative association was identified between apelin and Gensini score (r = -0.288, P = 0.006), Ck-MB (r = -0.300, P = 0.004), EFT (r = -0.300, P = 0.004), and troponin-T (r = -0.288, P = 0.006). Conclusion: Myocardial injury in patients with CAD appears to play a significant role in apelin concentration independent of the role of adipose tissue, which requires further studies.

The change of epicardial adipose tissue characteristics and vulnerability for atrial fibrillation upon drastic weight loss.

BACKGROUND: Obesity increases the risk of atrial fibrillation (AF). We hypothesize that 'obese' epicardial adipose tissue (EAT) is, regardless of comorbidities, associated with markers of AF vulnerability. METHODS: Patients >40y of age undergoing bariatric surgery and using <2 antihypertensive drugs and no insulin were prospectively included. Study investigations were conducted before and 1y after surgery. Heart rhythm and p-wave duration were measured through ECGs and 7-d-holters. EAT-volume and attenuation were determined on non-enhanced CT scans. Serum markers were quantified by ELISA. RESULTS: Thirty-seven patients underwent surgery (age: 52.1 ± 5.9y; 27 women; no AF). Increased p-wave duration correlated with higher BMI, larger EAT volumes, and lower EAT attenuations (p < 0.05). Post-surgery, p-wave duration decreased from 109 ± 11 to 102 ± 11ms. Concurrently, EAT volume decreased from 132 ± 49 to 87 ± 52ml, BMI from 43.2 ± 5.2 to 28.9 ± 4.6kg/m2, and EAT attenuation increased from -76.1 ± 4.0 to -71.7 ± 4.4HU (p <0.001). Adiponectin increased from 8.7 ± 0.8 to 14.2 ± 1.0 µg/ml (p <0.001). However, decreased p-wave durations were not related to changed EAT characteristics, BMI or adiponectin. CONCLUSION: In this explorative study, longer p-wave durations related to higher BMIs, larger EAT volume, and lower EAT attenuations. P-wave duration and EAT volume decreased, and EAT attenuation increased upon drastic weightloss. However, there was no relation between decreased p-wave duration and changed BMI or EAT characteristics.

Higher epicardial adipose tissue volume is associated with higher coronary fatty plaque volume and is regulated by waist circumference but not EPA+DHA supplementation.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation lower triglyceride levels. The impact on epicardial adipose tissue volume (EATV), which is associated with cardiovascular events, is unclear. OBJECTIVE: To determine if triglyceride reduction with EPA+DHA supplementation decreases EATV and whether EATV affects coronary plaque. METHODS: 139 subjects with coronary artery disease on statins were randomized to 3.36 g EPA+DHA daily or none (control) for 30 months. EATV, coronary plaque volumes and coronary artery calcium score were measured with coronary computed tomographic angiography. RESULTS: Change in triglyceride level correlated with change in EATV (r=0.236; p=0.006). Despite a 6.7% triglyceride reduction (p=0.021) with EPA+DHA supplementation compared to no change in control (between group p=0.034); both groups had similar reductions in EATV possibly due to statin treatment. EATV above the median (>115.6 cm3) was the only determinant of baseline coronary fatty plaque volume (ß=2.4, p=0.010). After multivariate adjustment, waist circumference, a surrogate of abdominal visceral adiposity, was the only determinant of baseline EATV (OR:1.093; 95% CI:1.003-1.192, p=0.042). Moreover, increase in waist circumference was the only predictor of an increase in EATV at 30 months (ß=0.320, p=0.018). CONCLUSIONS: EATV is associated with higher coronary fatty plaque volume and is regulated by waist circumference but not EPA+DHA supplementation at 30-month follow-up in CAD patients on statin treatment. The direct correlation between waist circumference and EATV suggests that maintaining a healthy weight may limit EATV and coronary fatty plaque volume, potentially leading to a decrease in cardiovascular events. Two sentence summary Subjects with clinical CAD on statin treatment randomized to EPA+DHA had similar reductions in epicardial adipose tissue volume (EATV) compared to control, despite a significant reduction in triglyceride level in the EPA+DHA group. Higher EATV was linked to greater fatty, rupture-prone plaques, boosting the risk of MI, and change in waist circumference was the only predictor of an increase in EATV at 30-month follow-up.

Epicardial adipose tissue and muscle distribution affect outcomes in very old patients after transcatheter aortic valve replacement.

Aims: To analyse the relevance of body composition and blood markers for long-term outcomes in very old patients after transcatheter aortic valve replacement (TAVR). Methods and results: A total of 403 very old patients were characterized with regard to subcutaneous, visceral, and epicardial fat, psoas muscle area, plasma growth differentiation factor 15 (GDF-15), and leptin. Cohorts grouped by body mass index (BMI) were analysed for long-term outcomes. Patients underwent transapical and transfemoral TAVR (similar 30-day/1-year survival). Body mass index >35 kg/m2 showed increased 2- and 3-year mortality compared with BMI 25-34.9 kg/m2 but not compared with BMI <25 kg/m2. Fat areas correlated positively to BMI (epicardial: R 2 = 0.05, P < 0.01; visceral: R 2 = 0.20, P < 0.001; subcutaneous: R 2 = 0.13, P < 0.001). Increased epicardial or visceral but not subcutaneous fat area resulted in higher long-term mortality. Patients with high BMI (1781.3 mm2 ± 75.8, P < 0.05) and lean patients (1729.4 ± 52.8, P < 0.01) showed lower psoas muscle area compared with those with mildly elevated BMI (2055.2 ± 91.7). Reduced psoas muscle area and increased visceral fat and epicardial fat areas were independent predictors of long-term mortality. The levels of serum GDF-15 were the highest in BMI >40 kg/m2 (2793.5 pg/mL ± 123.2) vs. BMI <25 kg/m2 (2017.6 pg/mL ±130.8), BMI 25-30 kg/m2 (1881.8 pg/mL ±127.4), or BMI 30-35 kg/m2 (2054.2 pg/mL ±124.1, all P < 0.05). Increased GDF-15 level predicted mortality (2587 pg/mL, area under the receiver operating characteristic curve 0.94). Serum leptin level increased with BMI without predictive value for long-term mortality. Conclusion: Morbidly visceral and epicardial fat accumulation, reduction in muscle area, and GDF-15 increase are strong predictors of adverse outcomes in very old patients post-TAVR.

Fully automated epicardial adipose tissue volume quantification with deep learning and relationship with CAC score and micro/macrovascular complications in people living with type 2 diabetes: the multicenter EPIDIAB study.

BACKGROUND: The aim of this study (EPIDIAB) was to assess the relationship between epicardial adipose tissue (EAT) and the micro and macrovascular complications (MVC) of type 2 diabetes (T2D). METHODS: EPIDIAB is a post hoc analysis from the AngioSafe T2D study, which is a multicentric study aimed at determining the safety of antihyperglycemic drugs on retina and including patients with T2D screened for diabetic retinopathy (DR) (n = 7200) and deeply phenotyped for MVC. Patients included who had undergone cardiac CT for CAC (Coronary Artery Calcium) scoring after inclusion (n = 1253) were tested with a validated deep learning segmentation pipeline for EAT volume quantification. RESULTS: Median age of the study population was 61 [54;67], with a majority of men (57%) a median duration of the disease 11 years [5;18] and a mean HbA1c of7.8 ± 1.4%. EAT was significantly associated with all traditional CV risk factors. EAT volume significantly increased with chronic kidney disease (CKD vs no CKD: 87.8 [63.5;118.6] vs 82.7 mL [58.8;110.8], p = 0.008), coronary artery disease (CAD vs no CAD: 112.2 [82.7;133.3] vs 83.8 mL [59.4;112.1], p = 0.0004, peripheral arterial disease (PAD vs no PAD: 107 [76.2;141] vs 84.6 mL[59.2; 114], p = 0.0005 and elevated CAC score (> 100 vs < 100 AU: 96.8 mL [69.1;130] vs 77.9 mL [53.8;107.7], p < 0.0001). By contrast, EAT volume was neither associated with DR, nor with peripheral neuropathy. We further evidenced a subgroup of patients with high EAT volume and a null CAC score. Interestingly, this group were more likely to be composed of young women with a high BMI, a lower duration of T2D, a lower prevalence of microvascular complications, and a higher inflammatory profile. CONCLUSIONS: Fully-automated EAT volume quantification could provide useful information about the risk of both renal and macrovascular complications in T2D patients.

The Correlation between Epicardial Adipose Tissue Thickness Measured by Echocardiography and P-Wave Dispersion and Atrial Fibrillation.

Background: Recent studies have indicated a close relationship between the thickness of epicardial adipose tissue (EAT) and the occurrence as well as persistence of atrial fibrillation (AF). However, the pathogenesis of this association is still in the exploratory stage. The aim of this study is to explore the correlation EAT, as measured by echocardiography, and P-wave dispersion (Pd) in the context of atrial fibrillation. Additionally, the study seeks to analyze the utility of EAT at different anatomical sites in identifying individuals who are predisposed to atrial fibrillation. Methods: A total of 136 subjects were enrolled and categorized into groups based on the guidelines: paroxysmal atrial fibrillation group (PAF group), persistent atrial fibrillation group (AF group), and non-atrial fibrillation group. Comprehensive clinical data, including general information and medications that could impact the occurrence of atrial fibrillation, were gathered for all patients. Echocardiography was employed to measure the maximum EAT thickness near the apex of the heart on the anterior right ventricular wall and near the base of the right ventricle for each participant. Pd values were computed for each patient based on standard 12-lead synchronous electrocardiogram (ECG). The study involved comparing the disparity in EAT thickness between the two specified sites across the three groups. Additionally, correlation analyses were performed to assess the relationship between EAT thickness at the two sites and Pd. Regression analysis was applied to explore potential risk factors for atrial fibrillation. The diagnostic value of EAT at each site in predicting atrial fibrillation was evaluated using Receiver Operating Characteristic curve (ROC) analysis. Results: EAT thickness of the anterior wall near the apex of the heart and near the base of the right ventricle were significantly positively correlated with Pd (p < 0.05), EAT thickness near the base and left atrial diameter were independent risk factors for atrial fibrillation (OR = 13.673, 95% CI 2.819~66.316, p = 0.001; OR = 2.294, 95% CI 1.020~5.156, p = 0.045). ROC analysis showed that the area under the curve of EAT thickness near the heart base was 0.723, and the best threshold for predicting the occurrence of AF was 1.05 cm. Conclusions: The echocardiography-measured epicardial adipose tissue thickness, particularly in proximity to the heart base, exhibits a significant correlation with Pd. Notably, EAT thickness near the heart base demonstrates superior predictive capability for atrial fibrillation compared to thickness near the apex.

Segmental evaluation of predictive value of left atrial epicardial adipose tissue following catheter ablation for atrial fibrillation.

BACKGROUND: Left atrial epicardial adipose tissue (LA-EAT) is associated with the recurrence of atrial tachyarrhythmias (AF/AT) after catheter ablation for atrial fibrillation (AF). However, no previous studies have assessed the predictive value of segment-specific LA-EAT volumes for AF/AT recurrence. This study aimed to assess the relationship between segmental LA-EAT volume and AF/AT recurrence. METHODS: This study included 350 consecutive patients who underwent initial AF ablation (53.7 % paroxysmal AF (PAF)). Preoperative multidetector row computed tomography assessed LA-EAT, categorized into three segments: anterior-EAT, posterior-EAT, and interatrial septal adipose tissue (IAS-AT). RESULTS: During a mean follow-up period of 351 ± 109 days, 56 patients (16.0 %) experienced AF/AT recurrence. The mean LA-EAT volume was 20.7 ± 11.1 ml and LA-EAT ≥26.8 ml was an independent risk factor for AF/AT recurrence (HR 2.21, 95 % confidence interval (CI): 1.24-3.93, P = 0.007). Receiver operating characteristic analyses revealed the area under the curve for IAS-AT was 0.669 (95 % CI: 0.596-0.743) with an optimal cut-off point of 1.3 ml (sensitivity 76.8 %; specificity 50.0 %), significantly outperforming the anterior- and posterior-EAT in predicting recurrent AF/AT. Multivariate analysis indicated IAS-AT was an independent predictor of AF/AT recurrence in patients with persistent AF (PeAF) (HR 3.52, 95 % CI: 1.52-8.13, P = 0.003), but not in patients with PAF. CONCLUSIONS: LA-EAT predicts AF/AT recurrence after AF ablation, with IAS-AT proving significantly more effective than other LA-EAT segments in predicting recurrence. Notably, IAS-AT emerged as an independent predictor of AF/AT recurrence in patients with PeAF but not in those with PAF.

A case report of a combined implantation technique of a cardioverter-defibrillator in an infant with long QT syndrome type 8 (Timothy's syndrome).

We present a case of successful implantation of a cardioverter-defibrillator (ICD) using combined technique in a child with Timothy's syndrome. Due to high risk of sudden cardiac death (SCD) such patients often need ICD for primary or secondary prevention but implantation technique in young children remains controversial. The subcutaneous cardioverter-defibrillators could be an option in some cases, however, reliable cardiac pacing should be implemented for patients with bradyarrhythmias. An ICD implantation technique with the epicardial pacing lead placement and subcutaneous tunnel formation for endocardial defibrillation lead seems to be promising in SCD prevention also providing the opportunity for permanent pacing.

The Role of Epicardial Adipose Tissue-Derived Proteins in Heart Failure with Preserved Ejection Fraction and Atrial Fibrillation: A Bioinformatics Analysis.

Background: The accumulation of epicardial adipose tissue (EAT) is associated with cardiometabolic risks and adverse outcomes in heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). This study aims to identify genes secreted by EAT that contribute to the shared pathogenesis of HFpEF and AF, potentially serving as biomarkers for diagnosis. Methods: Data sets from the GEO database for HFpEF-EAT, HFpEF-heart tissue, AF-EAT, AF-PBMC, and AF-heart tissue were analyzed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) identified key genes in EAT linked to HFpEF and AF. Functional enrichment and connectivity map analyses explored common pathways and therapeutic targets. Machine learning techniques, including LASSO regression, random forest, and support vector machine, identified shared biomarkers. CIBERSORT was used to assess immune cell infiltration, while gene set enrichment analysis identified pathways related to hub genes. Receiver operating characteristic (ROC) curve analysis and experimental validation assessed the bioinformatics findings. Results: In the HFpEF dataset, 200 key genes were identified by intersecting HFpEF-EAT, HFpEF-heart tissue, WGCNA analyses, and secretory proteins. For AF, 232 related genes were identified through similar methods. Thirteen genes were common between HFpEF and AF, with two central genes, ITPKA and WNT9B, selected as potential biomarkers through machine learning and ROC analysis. Immune cell infiltration and gene set enrichment analysis revealed pathways related to ITPKA/WNT9B. These patterns were confirmed in human samples. Conclusion: This study identified EAT-derived secretory proteins as potential biomarkers for HFpEF and AF, with ITPKA and WNT9B as central hub genes. These findings offer insights into potential diagnostic and therapeutic strategies for HFpEF and AF.

The relationship between rheumatoid arthritis and epicardial fat thickness, and serum levels of chemerin, adropin, and betatrophin.

BACKGROUND: Cardiovascular diseases (CVDs) are highly prevalent among patients with rheumatoid arthritis (RA). Epicardial adipose tissue, serum betatrophin, chemerin, and adropin levels are factors associated with atherosclerosis and cardiovascular involvement. OBJECTIVES: This study aimed to investigate the relationship between RA and epicardial fat thickness (EFT), as well as serum betatrophin, chemerin and adropin levels. MATERIAL AND METHODS: This cross-sectional study included 80 patients (62 women and 18 men) diagnosed with RA according to the American College of Rheumatology/The European Alliance of Associations for Rheumatology (ACR/EULAR) 2010 RA classification criteria and 80 healthy controls (64 women and 16 men). Exclusion criteria comprised other autoimmune diseases, CVDs, diabetes mellitus, other endocrine disorders, acute or chronic pancreatic disorders, malignancy, pregnancy, breastfeeding, or antihyperlipidemic drug usage. Serum betatrophin, chemerin and adropin concentrations were measured. Epicardial fat thickness was evaluated with transthoracic echocardiography. RESULTS: Adropin levels were significantly lower in the RA group compared to the control group (p < 0.001). Chemerin levels and EFT were significantly higher in the RA group than in the control group (p = 0.016, p < 0.001, respectively). When assessing the relationship between biomarkers and EFT in RA patients, a strong positive correlation was observed between chemerin and EFT (r = 0.73, p = 0.046) in patients with high disease activity. CONCLUSIONS: Epicardial fat thickness, as an indicator of cardiovascular involvement, is higher in patients with RA. Moreover, high chemerin levels and low adropin levels in these patients may be indicative of cardiovascular involvement.

Association of epicardial adipose tissue density with postoperative atrial fibrillation after isolated aortic valve replacement.

Backgrounds: It is well known that epicardial adipose tissue (EAT) is associated with the development of atrial fibrillation (AF). The aim of this study was to investigate whether EAT density (EAT-d) is associated with the development of new-onset atrial fibrillation (POAF) after aortic valve replacement (AVR). Methods: We retrospectively studied 143 patients who underwent simple AVR at Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command between June 2020 to August 2023. All patients received cardiac coronary artery computed tomography (CT) before surgery. EAT-d, EAT volume and EAT volume index (EATVI) were quantitatively measured and analysed using EAT analysis software (TIMESlicePro). POAF was detected by 7-day Holter monitoring. Results: Of 143 patients undergoing AVR, 55 patients (38.46 %) developed POAF after surgery. Male patients and patients who had elder age or smoking history were more likely to develop POAF. On univariable analysis, patients developed POAF had significantly more EAT-d (-79.19(-83.91, -74.69) vs. -81.54(-87.16, -76.76); P = 0.043) and EATVI (4.14(3.32,5.03) vs. 3.90(2.70,4.51); P = 0.043) than patients without POAF. On multivariable analysis, EAT-d and age were independent risk factors for POAF (odds ratio (OR): 1.186, 95 % confidence interval (CI): 1.062-1.324, P = 0.002; OR: 1.119, 95 %CI: 1.055-1.187, P < 0.001). Furthermore, EAT-d was significantly associated with age. Furthermore, EAT-d was associated with cardiac structure changes, such as cardiac left ventricular end-diastolic, left ventricular end-systolic volumes and NT-proBNP before surgery. Conclusion: EAT-d and age are independent predictors of POAF after simple AVR. EAT-d was related with age.

Liraglutide effects on epicardial adipose tissue micro-RNAs and intra-operative glucose control.

BACKGROUND AND AIM: Epicardial adipose tissue (EAT) plays a role in coronary artery disease (CAD). EAT has regional distribution throughout the heart and each location may have a different genetic profile and function. Glucagon like peptide-1 receptor analogs (GLP-1RAs) reduce cardiovascular risk. However, the short-term effects of GLP-1RA on microRNA (miRNA) profile of each EAT location is unknown. Objective was to evaluate if EAT miRNAs were different between coronary (CORO-EAT), left atrial EAT (LA-EAT) and subcutaneous fat (SAT), and liraglutide can modulate EAT miRNAs expression. METHODS AND RESULTS: This was a 12-week randomized, double-blind, placebo-controlled study in 38 patients with type 2 diabetes (T2DM) and coronary artery disease (CAD) who were started on either liraglutide or placebo for a minimum of 4 up to 12 weeks prior to coronary artery by-pass grafting (CABG). Fat samples were collected during CABG. miR16, miR155 and miR181a were significantly higher in CORO-EAT and in LA-EAT than SAT (p < 0.01 and p < 0.05) in overall patients. miR16 and miR181-a were significantly higher in CORO-EAT than SAT (p < 0.01), and miR155 and miR181a were higher in LA-EAT than SAT (p < 0.05) in the liraglutide group. Liraglutide-treated patients had better intra-op glucose control than placebo (146 ± 21 vs 160 ± 21 mg/dl, p < 0.01). CONCLUSIONS: Our study shows that CORO- and LA-miRNAs profiles were significantly different than SAT miRNAs in overall patients and miRNAs were significantly higher in CORO-EAT and LA-EAT than SAT in the liraglutide group. Pre-op liraglutide was also associated with better intra operative glucose control than placebo independently of weight loss.