Epicardial Adipose Tissue Research Articles

Tissue-resident memory T cells in epicardial adipose tissue comprise transcriptionally distinct subsets that are modulated in atrial fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia and carries an increased risk of stroke and heart failure. Here we investigated how the immune infiltrate of human epicardial adipose tissue (EAT), which directly overlies the myocardium, contributes to AF. Flow cytometry analysis revealed an enrichment of tissue-resident memory T (TRM) cells in patients with AF. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell T cell receptor (TCR) sequencing identified two transcriptionally distinct CD8+ TRM cells that are modulated in AF. Spatial transcriptomic analysis of EAT and atrial tissue identified the border region between the tissues to be a region of intense inflammatory and fibrotic activity, and the addition of TRM populations to atrial cardiomyocytes demonstrated their ability to differentially alter calcium flux as well as activate inflammatory and apoptotic signaling pathways. This study identified EAT as a reservoir of TRM cells that can directly modulate vulnerability to cardiac arrhythmia.

Epicardial and liver fat implications in albuminuria: a retrospective study

BackgroundAlbuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status.MethodsA retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome.ResultsAfter a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20–8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69–22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15–30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p < 0.001]).ConclusionsIdentification and management/decrease of excess adiposity must be a target in the primary and secondary prevention of chronic kidney disease development and progression. Visceral adiposity assessment may be an adequate target in the daily clinical setting. Moreover, epicardial adipose tissue and steatotic liver disease assessment may aid in the primary prevention of renal dysfunction.

Open-bore MRI Scanner Assessment of Epicardial Adipose Tissue after Bariatric Surgery: A Pilot Study.

The recognition of epicardial adipose tissue (EAT) as a cardiac risk factor has increased the interest in strategies that target cardiac adipose tissue. The effect of bariatric and metabolic surgery (BMS)-induced weight loss on EAT volume was evaluated in this study. Fifteen bariatric patients, with (MS) or without (wMS) Metabolic Syndrome, underwent magnetic resonance imaging (MRI) using an open-bore scanner to assess EAT volume, visceral adipose tissue (VAT) thickness, and other cardiac morpho-functional parameters at baseline and 12 months after BMS. Nine patients underwent laparoscopic sleeve gastrectomy (LSG), and 6 patients underwent Roux-en-Y Gastric Bypass (RYGBP). EAT volume significantly decreased in all the patients 12 months post-BMS from 91.6 cm3 to 67.1 cm3; p = 0.0002 in diastole and from 89.4 cm3 to 68.2 cm3; p = 0.0002 in systole. No significant difference was found between the LSG and RYGBP group. Moreover, EAT volume was significantly reduced among wMS compared with MS. In particular, EAT volume in diastole was significantly reduced from 80.9 cm3 to 54.4 cm3; p = 0.0156 in wMS and from 98.3 cm3 to 79.5 cm3; p = 0.031 in MS. The reduction was also confirmed in systole from 81.2 cm3 to 54.1 cm3; p = 0.0156 in wMS and from 105.7 cm3 to 75.1 cm3; p = 0.031 in MS. Finally, a positive correlation was found between EAT loss, BMI (r = 0.52; p = 0.0443) and VAT (r = 0.66; p = 0.008) reduction after BMS. These findings suggest that EAT reduction may be a fundamental element for improving the cardio-metabolic prognosis of bariatric patients. Moreover, this is the first study performed with an open-bore MRI scanner to measure EAT volume.

Feasibility of Epicardial Adipose Tissue Quantification Using Non-electrocardiogram-Gated Chest Computed Tomography Images.

Epicardial adipose tissue (EAT) is an important imaging indicator of cardiovascular risk. EAT volume is usually measured using electrocardiogram (ECG) gating. However, there are concerns regarding the influence of motion artifacts when measuring EAT volume on non-ECG-gated plain chest computed tomography (CT) images. Few studies have evaluated the EAT volume using non-ECG gating. This study aimed to validate the accuracy of EAT quantification using non-ECG-gated chest CT imaging. We included 100 patients (64 males, 36 females) who underwent simultaneous coronary artery calcification score imaging (ECG gated) and plain chest CT imaging (non-ECG gated). Images taken using non-ECG gating were reconstructed using the same field of view and slice thickness as those obtained with ECG gating. The EAT capacity of each image was measured and compared. An AZE Virtual Place (Canon) was used for the measurements. The Mann-Whitney U test and intraclass correlation coefficient were used for statistical analyses. P values <0.05 were considered statistically significant. Concordance was evaluated using Bland-Altman analysis. The mean EAT volume measured by ECG-gated imaging was 156.5 ± 66.9 mL and 155.4 ± 67.9 mL by non-ECG-gated imaging, with no significant difference between the two groups (P = 0.86). Furthermore, the EAT volumes measured using ECG-gated and non-ECG-gated imaging showed a strong correlation (r = 0.95, P < 0.05). Bland-Altman analysis revealed that the mean error of the EAT volume (non-ECG-gated imaging - ECG-gated imaging) was -1.02 ± 2.95 mL (95% confidence interval, -6.49 to 4.76). The EAT volume obtained using non-ECG-gated imaging was equivalent to that obtained using ECG-gated imaging.

Sex-Specific Associations of Aldosterone and Renin with Body Composition: A Population-Based Cohort Study.

Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood. To investigate the associations of aldosterone and renin with body composition according to sex in the general population. Population-based cohort study. Québec (Canada). Adults aged 40-69 years enrolled to CARTaGENE between 2009 and 2010 (N=3,687). Plasma aldosterone and renin concentrations. Body composition assessed via anthropometrics (waist circumference and waist-to-hip ratio), bioelectrical impedance (lean body mass, fat mass, and muscle mass), and cardiac magnetic resonance imaging (epicardial and pericardial adipose tissue volumes). The mean (SD) age and body mass index were 55 (8) years and 27.3 (4.8) kg/m2, respectively. Among males, higher aldosterone and renin were associated with increased waist circumference, increased waist-to-hip ratio, increased fat mass, decreased lean body mass, and decreased muscle mass (p<0.05). Aldosterone (p=0.02), but not renin (p=0.43), was associated with increased ectopic cardiac adiposity in males. In contrast, higher renin (p<0.05), but not aldosterone (p≥0.05), was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity in females. Among females, higher renin and aldosterone were associated with increased fat mass (p<0.05) but were not associated with lean body mass or muscle mass (p≥0.05). All aforementioned associations were independent of body weight. Independent of body weight, increased RAAS activity is associated with unfavorable differences in body composition; however, the strength and pattern of association varies by sex.

Lipoprotein(a) levels and epicardial adipose tissue in diabetes: Unraveling novel connections

Lipoprotein(a) levels and epicardial adipose tissue in diabetes: Unraveling novel connections

Expression level of ceramide synthase 5 (CERS5) gene in the epicardial adipose tissue of coronary artery disease patients

Expression level of ceramide synthase 5 (CERS5) gene in the epicardial adipose tissue of coronary artery disease patients

Circulating triglyceride-rich lipoproteins ceramides potential role in systemic and epicardial adipose tissue metabolic profile

Circulating triglyceride-rich lipoproteins ceramides potential role in systemic and epicardial adipose tissue metabolic profile

The influence of epicardial adipose tissue thickness on the risk of cardiovascular complications in patients with arterial hypertension and non-alcoholic fatty liver disease

The influence of epicardial adipose tissue thickness on the risk of cardiovascular complications in patients with arterial hypertension and non-alcoholic fatty liver disease

Secretome from epicardial adipose tissue of patients with obesity induces inflammation in human cardiomyocytes

Secretome from epicardial adipose tissue of patients with obesity induces inflammation in human cardiomyocytes

Epicardial Adipose Tissue and Psoriasis: A Systematic Review and Meta-Analysis.

Background: As a novel biomarker for cardiovascular diseases, epicardial adipose tissue (EAT) has been linked to psoriasis. We conducted an updated systematic review, building upon a previous report on the relationship between EAT and psoriasis. Methods: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials. The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. The pooled mean difference (MD) or standardized mean difference (SMD) and the corresponding confidence interval (CIs) were calculated. Results: We included 10 studies with 1287 participants. Five of the included studies were of high methodological quality, while the other five were of moderate quality. The pooled data indicated that psoriasis patients had significantly increased EAT compared to individuals in the control group (SMD 1.53, 95% CI 0.61 to 2.45, 9 studies, 1195 participants). The subgroup analysis showed that psoriasis patients had significantly increased EAT thickness compared with the controls (SMD 2.45, 95% CI 0.73 to 4.17, 5 studies, 657 participants). Similarly, EAT area in single-slice CT images was significantly higher in the psoriasis group than in the control group (SMD 0.45, 95% CI 0.14 to 0.76, 2 studies, 195 participants). The EAT volume based on CT images appeared to be higher in the psoriasis group than in the control group, but the difference was not statistically significant (SMD 0.32, 95% CI -0.06 to 0.70, 2 studies, 343 participants). Conclusions: EAT, especially echocardiographic EAT thickness and CT-determined EAT area, was significantly associated with psoriasis, but CT-determined EAT volume was not.

Rapidly progressive coronary atherosclerosis in a young male: a retrospective advanced CCT phenotype analysis

We present a real-life case of a very young man with multiple risk factors who progressed rapidly from minimally obstructive non-calcified plaque on computed tomography angiography (CCTA) to severe three-vessel coronary disease presenting with STEMI. It questions the reliability of zero coronary calcium in high-risk subgroups like familial hypercholesterolemia, high Lp(a), and the young. While CCTA can accurately visualize non-calcified plaque, its interpretation requires expertise and clinical judgment should consider both imaging and clinical risk factors for management. Advanced plaque quantification, peri-coronary (PCAT), and epicardial (EAT) adipose tissue could help better-stratified patients but the evidence-based clinical application remains unknown.

Lymphocyte subsets in epicardial, thymic and subcutaneous adipose tissue during advanced coronary atherosclerosis in patients with coronary artery disease

The important role of epicardial (EAT) and thymic (TAT) adipose tissue in the development of atherosclerosis in patients with coronary artery disease (CAD) is widely discussed. The purpose of the study was to investigate the lymphocyte subsets and FoxP3+Treg lymphocytes in epicardial, thymic and subcutaneous adipose tissue depending on the severity of coronary atherosclerosis in patients with chronic CAD. We examined 24 patients with CAD (21 men; mean age 65.0 (58.0-68.0) years) scheduled for open-heart surgery. In samples of EAT, TAT and subcutaneous adipose tissue (SAT), the content of CD4+, CD8+, B lymphocytes, NK and NKT cells, CD4+CD25hiFoxP3+ and CD4+CD25lowFoxP3+T regulatory lymphocytes (Treg) and a proportion of Tregs with FoxP3 nuclear translocation was determined by imaging flow cytometry. Depending on the severity of atherosclerosis, assessed according to Gensini Score, patients were divided into groups: group 1 – patients with Gensini Score 65; group 2 – patients with Gensini Score ≥ 65. Patients in group 2 had higher frequency of EAT CD4+CD25lowTreg with FoxP3nuclear translocation, TAT CD8+T lymphocytes and NK cells, a lower content of TAT double positive CD4+CD8+T lymphocytes, and a tendency towards a decrease of frequency of TAT CD4+CD25hiTreg with FoxP3 nuclear translocation compared to patients in group 1. The level of nuclear translocation of FoxP3 in CD4+CD25hiTreg cells in TAT was inversely related to the proportion of CD8+T lymphocytes (rs = -0.653; p = 0.012) and NK cells (rs = -0.723; p = 0.003) in TAT, and directly – to the proportion of double positive CD4+CD8+T lymphocytes in TAT (rs = 0.567; p = 0.034) and the value of the waist-to-hip ratio (rs = -0.474; p = 0.041). Further research is required to study the molecular mechanisms of these relationships in patients with coronary atherosclerosis and chronic coronary artery disease.

Epicardial adipose tissue thickness associated with preeclampsia and birth weight in early pregnancy

ABSTRACT Objective Preeclampsia (PE) increases the risk of many adverse maternal and fetal outcomes. This study was to investigate the correlation between epicardial adipose tissue (EAT) thickness and PE and birth weight. Methods This was a single-center retrospective study, 221 patients with PE were selected, and 81 women without hypertension and proteinuria were selected as a comparison. Echocardiogram was performed in their first prenatal examinations at 11–13 gestational weeks, and the thickness of EAT was measured. At the subsequent follow-up, the birth weight was recorded. Results EAT thickness was significantly elevated (6.60 ± 1.34 vs. 5.71 ± 1.79 mm, p < 0.001) in severe PE compared to mild PE. In the multivariate analysis, EAT thickness (OR 5.671, 95% CI, 1.991–16.150, p = 0.001), and C reactive protein (OR 4.097, 95% CI, 2.323–7.224, p < 0.001) were found as significant independent predictors of severe PE after adjusting for other risk factors. Linear regression analysis showed that hs-CRP, EAT thickness, and severe PE significantly negatively affected birth weight. Conclusion EAT thickness can be used to identify pregnant women with severe PE risks and low birth weight. It is an independent risk factor for severe PE but is not a valuable sign of mild PE.

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing’s syndrome

Background Cushing’s syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. Methods A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. Results A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003–1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. Conclusion CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction

BackgroundHeart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear.MethodsA total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans.ResultsDuring a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology.ConclusionsThis study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.Graphical abstract

Exploring the interplay between epicardial fat, coronary artery calcium score, and nonalcoholic fatty liver disease through non-ECG-gated chest computed tomography: A cross-sectional study.

This study examines the relationships between epicardial adipose tissue (EAT), nonalcoholic fatty liver disease (NAFLD), and coronary artery calcium score (CACS) using non-ECG-gated CT scans. It aims to determine the effectiveness of EAT measurements and NAFLD as predictors for coronary artery disease (CAD). This cross-sectional study was conducted at a specialized center, focusing on individuals who underwent non-ECG-gated chest CT scans without contrast. We evaluated EAT thickness and density in three areas: the right atrioventricular groove, the free wall of the right ventricle, and the central area of the right anterior interventricular groove. Additionally, we measured CACS and determined the presence of NAFLD by comparing liver-to-spleen density ratios. Statistical analyses, including regression models, were performed using SPSS (version 26). In this study, we enrolled 365 participants, including 203 males with an average age of 47 ± 17.93 years. EAT thickness was 6.28 ± 1.62 mm, and EAT density was -96.07 ± 12.47 Hounsfield units (HU). The mean CACS was 22.27 ± 79.01, and the mean liver density was 50.01 ± 10.76 HU. A significant positive correlation was observed between EAT thickness and CACS (r = 0.208, p < 0.001). EAT density showed a significant negative correlation with CACS (r = -0.155, p = 0.003). No correlation was found between NAFLD and CACS. Univariate logistic regression analysis identified significant predictors of increased CACS, including EAT thickness (OR: 1.803), EAT density (OR: 0.671), diabetes mellitus (DM) (OR: 5.921), and hypertension (HTN) (OR: 7.414). Multivariate analysis confirmed the significance of EAT thickness (OR: 0.682), DM (OR: 3.66), and HTN (OR: 2.79) as predictors of elevated CACS. Our findings demonstrate that increased EAT thickness and decreased density are associated with higher CACS. Also, both DM and HTN significantly contribute to increased CACS. These results support the inclusion of EAT measurements in cardiovascular risk assessment models to enhance diagnostic accuracy.

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

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. 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. 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. 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.

Epicardial adipose tissue defined by initial polytrauma CT of mechanically ventilated trauma patients: retrospective single-center cohort study to predict short-term outcomes.

Epicardial adipose tissue (EAT) detected by computed tomography (CT) is associated with morbidity and mortality in patients with COVID-19 and other critical care patient cohorts, whereas their prognostic relevance in trauma patients remains unclear. The present study explored associations with four potential short-term outcomes in trauma patients. All consecutive trauma patients requiring emergency tracheal intubation and mechanical ventilation before initial whole-body CT imaging at a level-1 trauma center over a 12-year period (2008-2019) were reanalyzed for this study. EAT was measured semiquantitatively in initial CT and analyzed regarding associations with 24-hour and 30-day mortality using Cox proportional hazard models. In survivors, associations of EAT with intensive care unit length of stay (ICU LOS) and mechanical ventilation duration were analyzed using linear regression analyses. Four hundred fifty-five patients (74.7% male) with a median age of 49 years, and a median injury severity score (ISS) of 26 points were analyzed. In univariable analysis, EAT index was significantly associated with 24-hour and 30-day mortality (p = 0.007, and p = 0.013, respectively). After adjustment for significant predictors age, body mass index, and ISS, no significant associations were confirmed (p = 0.622, and p = 0.903, respectively). In a subanalysis of 353 survivors, EAT index was significantly associated with ICU LOS and mechanical ventilation duration in univariable analyses (p = 0.031, and p = 0.014, respectively), but not in multivariable analyses (p = 0.81 and p = 0.46, respectively). EAT index was associated with short-term outcomes in severely injured trauma patients, which not remained significant in multivariable analysis, suggesting that its prognostic capability is limited.

KCa3.1 Promotes the Migration of Macrophages From Epicardial Adipose Tissue to Induce Vulnerability to Atrial Fibrillation During Rapid Pacing

BackgroundThe relationship between local epicardial adipose tissue (EAT) macrophages and atrial fibrillation (AF) remains unclear. The purpose of this study was to investigate the role of KCa3.1 in the migration of macrophages from EAT to adjacent atrial tissue during rapid pacing. MethodsPart 1: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + clodronate liposome (CL) group. Part 2: Eighteen beagles were randomly divided into the sham group, pacing group, and pacing + TRAM-34 group. HL-1 cells and RAW264.7 cells were co-cultured to explore the specific migratory mechanism of macrophages. ResultsDepleting EAT macrophages significantly reduced macrophage infiltration in the adjacent atrium and the induction of AF in canines with rapid atrial pacing. TRAM-34 significantly inhibited the migration of macrophages from EAT to the adjacent atrium and electrical remodelling in canines with rapid atrial pacing. Compared with those of the control HL-1 cells, the secretion of CCL2 and the number of migrating macrophages in pacing HL-1 cells was significantly increased, which could be reversed by TRAM-34. Further in vitro experiments showed that KCa3.1 regulated CCL2 secretion through the p65/STAT3 signalling pathway. ConclusionsInhibiting myocardial KCa3.1 reduced the migration of EAT macrophages to adjacent atrial muscles caused by rapid atrial pacing, thereby decreasing vulnerability to AF. The mechanism by which KCa3.1 regulates CCL2 may be related to the p65/STAT3 signalling pathway.