Inflammatory biomarkers, angiogenesis and lymphangiogenesis in epicardial adipose tissue correlate with coronary artery disease.

In this study, we explored the relationship between inflammatory adipokine levels and coronary artery disease (CAD). We collected subcutaneous adipose tissues(SAT), pericardial adipose tissues(PAT), and epicardial adipose tissues (EAT) and serum samples from 26 inpatients with CAD undergone coronary artery bypass grafting and 20 control inpatients without CAD. Serum inflammatory adipokines were measured by ELISA. Quantitative real-time PCR and western blot were used to measure gene and protein expression. Adipocyte morphology was assessed by H&E staining. Immunohistochemistry and immunofluorescence were used to measure endothelial and inflammatory markers. Serum pro- and anti-inflammatory adipokine levels were higher and lower, respectively, in the CAD group than those in the control group (P < 0.05). In CAD, the pro-inflammatory adipokine levels via ELISA in EAT and PAT were elevated. Pro-inflammatory adipokine mRNA expression was increased, while anti-inflammatory adipokine mRNA expression decreased, in CAD relative to NCAD in EAT and PAT rather than SAT. In EAT, adipocyte area and macrophage-specific staining were lower, while lymphatic vessel marker expression was higher in CAD. Additionally, the endothelial marker expression in EAT was higher than PAT in CAD. The three tissue types had different blood vessel amounts in CAD. The regulation and imbalance expression of the novel biomarkers, including inflammatory adipokine, macrophage infiltration, angiogenesis, and lymphangiogenesis in EAT and PAT, may be related to the pathogenesis of CAD. The serum levels of inflammatory adipokines may correlate to CAD, which requires large sample size studies to get further validation before clinic practice.

COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.

PURPOSE OF REVIEW: To review myocarditis and pericarditis developing after COVID-19 vaccinations and identify the management strategies. RECENT FINDINGS: COVID-19 mRNA vaccines are safe and effective. Systemic side effects of the vaccines are usually mild and transient. The incidence of acute myocarditis/pericarditis following COVID-19 vaccination is extremely low and ranges 2-20 per 100,000. The absolute number of myocarditis events is 1-10 per million after COVID-19 vaccination as compared to 40 per million after a COVID-19 infection. Higher rates are reported for pericarditis and myocarditis in COVID-19 infection as compared to COVID-19 vaccines. COVID-19 vaccine-related inflammatory heart conditions are transient and self-limiting in most cases. Patients present with chest pain, shortness of breath, and fever. Most patients have elevated cardiac enzymes and diffuse ST-segment elevation on electrocardiogram. Presence of myocardial edema on T2 mapping and evidence of late gadolinium enhancement on cardiac magnetic resonance imaging are also helpful additional findings. Patients were treated with non-steroidal anti-inflammatory drugs and colchicine with corticosteroids reserved for refractory cases. At least 3-6 months of exercise abstinence is recommended in athletes diagnosed with vaccine-related myocarditis. COVID-19 vaccination is recommended in all age groups for the overall benefits of preventing hospitalizations and severe COVID-19 infection sequela.

Substrate Characterization and Outcome of Catheter Ablation of Ventricular Tachycardia in Patients With Nonischemic Cardiomyopathy and Isolated Epicardial Scar.

BACKGROUND: The substrate for ventricular tachycardia (VT) in left ventricular (LV) nonischemic cardiomyopathy may be epicardial. We assessed the prevalence, location, endocardial electrograms, and VT ablation outcomes in LV nonischemic cardiomyopathy with isolated epicardial substrate. METHODS: Forty-seven of 531 (9%) patients with LV nonischemic cardiomyopathy and VT demonstrated normal endocardial (>1.5 mV)/abnormal epicardial bipolar low-voltage area (LVA, <1.0 mV and signal abnormality). Abnormal endocardial unipolar LVA (≤8.3 mV) and endocardial bipolar split electrograms and predictors of ablation success were assessed. RESULTS: Epicardial bipolar LVA (27.3 cm2 [interquartile range, 15.8-50.0]) localized to basal (40), mid (8), and apical (3) LV with basal inferolateral LV most common (28/47, 60%). Of 44 endocardial maps available, 40 (91%) had endocardial unipolar LVA (24.5 cm2 [interquartile range, 9.4-68.5]) and 29 (67%) had characteristic normal amplitude endocardial split electrograms opposite the epicardial LVA. At mean of 34 months, the VT-free survival was 55% after one and 72% after multiple procedures. Greater endocardial unipolar LVA than epicardial bipolar LVA (hazard ratio, 10.66 [CI, 2.63-43.12], P=0.001) and number of inducible VTs (hazard ratio, 1.96 [CI, 1.27-3.00], P=0.002) were associated with VT recurrence. CONCLUSIONS: In patients with LV nonischemic cardiomyopathy and VT, the substrate may be confined to epicardial and commonly basal inferolateral. LV endocardial unipolar LVA and normal amplitude bipolar split electrograms identify epicardial LVA. Ablation targeting epicardial VT and substrate achieves good long-term VT-free survival. Greater endocardial unipolar than epicardial bipolar LVA and more inducible VTs predict VT recurrence.

Epicardial adipose tissue radiodensity is associated with all-cause mortality in patients undergoing hemodialysis.

The radiodensity and volume of epicardial adipose tissue (EAT) on computed tomography angiography (CTA) may provide information regarding cardiovascular risk and long-term outcomes. EAT volume is associated with mortality in patients undergoing incident hemodialysis. However, the relationship between EAT radiodensity/volume and all-cause mortality in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis remains elusive. In this retrospective study, EAT radiodensity (in Hounsfield units) and volume (in cm3) on coronary CTA were quantified for patients with ESRD using automatic, quantitative measurement software between January 2012 and December 2018. All-cause mortality data (up to December 2019) were obtained from the Korean National Statistical Office. The prognostic values of EAT radiodensity and volume for predicting long-term mortality were assessed using multivariable Cox regression models, which were adjusted for potential confounders. A total of 221 patients (mean age: 64.88 ± 11.09 years; 114 women and 107 men) with ESRD were included. The median follow-up duration (interquartile range) after coronary CTA was 29.63 (range 16.67-44.7) months. During follow-up, 82 (37.1%) deaths occurred. In the multivariable analysis, EAT radiodensity (hazard ratio [HR] 1.055; 95% confidence interval [CI] 1.015-1.095; p = 0.006) was an independent predictor of all-cause mortality in patients with ESRD. However, EAT volume was not associated with mortality. Higher EAT radiodensity on CTA is associated with higher long-term all-cause mortality in patients undergoing prevalent hemodialysis, highlighting its potential as a prognostic imaging biomarker in patients undergoing hemodialysis.

Modulation of Cardiac Arrhythmogenesis by Epicardial Adipose Tissue: JACC State-of-the-Art Review.

Obesity is a significant risk factor for arrhythmic cardiovascular death. Interactions between epicardial adipose tissue (EAT) and myocytes are thought to play a key role in the development of arrhythmias. In this review, the authors investigate the influence of EAT on arrhythmogenesis. First, they summarize electrocardiographic evidence showing the association between increased EAT volume and atrial and ventricular conduction delay. Second, they detail the structural cross talk between EAT and the heart and its arrhythmogenicity. Adipose tissue infiltration within the myocardium constitutes an anatomical obstacle to cardiac excitation. It causes activation delay and increases the risk of arrhythmias. Intercellular electrical coupling between cardiomyocytes and EAT can further slow conduction and increase the risk of block, favoring re-entry and arrhythmias. Finally, EAT secretes multiple substances that influence cardiomyocyte electrophysiology either by modulating ion currents and electrical coupling or by stimulating fibrosis. Thus, structural and paracrine cross talk between EAT and cardiomyocytes facilitates arrhythmias.

Role of endocardial ablation in eliminating an epicardial arrhythmogenic substrate in patients with Brugada syndrome.

BACKGROUND: Epicardial ablation is occasionally limited by coronary artery (CA) injuries or epicardial fat (EF). OBJECTIVE: The purpose of this study was to evaluate the anatomic obstacles that prevent ablation of epicardial abnormal potentials (EAPs) in patients with Brugada syndrome (BrS) and to investigate the feasibility of EAP elimination by endocardial right ventricular (RV) ablation. METHODS: This study included 16 BrS patients with previous ventricular fibrillation (VF), including 10 with an electrical storm. Data from multidetector computed tomography were assessed, and the proximity of the CA and EF was correlated with EAPs. RESULTS: EAPs were present in the epicardial RV outflow tract and RV inferior wall in all patients and 12 patients (75%), respectively. These EAPs were present within 5 mm of the main body and branches of the right CA in 14 patients (87.5%). However, only 1.4% ± 2.9% of the EAP area was covered with thick EF (≥8 mm). Partial EAP elimination by endocardial RV ablation was feasible in all 10 patients, with 53.3% successful endocardial RV radiofrequency applications for eliminating EAPs. After the procedure, VF remained inducible in 37.5% of the patients. During the 25.1 ± 29.1 months of follow-up, no patients experienced an electrical storm, and VF burden significantly decreased (median VF episodes before and after ablation: 7 and 0, respectively). CONCLUSION: EAPs are near the CA in most BrS patients, thereby requiring caution during epicardial ablation, whereas EF is less of an issue. Endocardial ablation is feasible to eliminate some EAPs and may be combined with epicardial ablation.

Epicardial adipose tissue differentiates in patients with and without coronary microvascular dysfunction.

BACKGROUND/OBJECTIVES: Coronary microvascular dysfunction (CMD) is a common disorder, leading to symptoms similar to obstructive coronary artery disease and bears important prognostic implications. Local inflammation is suggested to promote development of CMD. Epicardial adipose tissue (EAT) is a local visceral fat depot surrounding the heart and the coronary arteries, modifying the inflammatory environment of the heart. We compared EAT in patients with and without CMD. METHODS: We retrospectively included consecutive patients undergoing diagnostic coronary angiography as well as transthoracic echocardiography between March and October 2016. EAT thickness was defined as space between the epicardial wall of the myocardium and the visceral layer of the pericardium and EAT index was calculated as EAT thickness/body surface area. Logistic regression analysis was used to determine the association of EAT index with the presence of CMD. RESULTS: Overall, 399 patients (mean age 60.2 ± 14.0 years, 46% male) were included. EAT thickness was significantly higher in patients with CMD compared to patients without CMD (EAT thickness 4.4 ± 1.8 vs. 4.9 ± 2.4 mm, p = 0,048 for patients without and with CMD, respectively). In univariate regression analysis, EAT index was associated with a 30% higher frequency of CMD (odds ratio [95% confidence interval]: 1.30 [1.001-1.69], p = 0.049). Effect sizes remained stable upon adjustment for body mass index (BMI, 1.30 [1.003-1.70], p = 0.048), but were attenuated when ancillary adjusting for age and gender (1.17 [0.90-1.54, p = 0.25). The effect was more pronounced in patients >65 years of age and independent of BMI and sex (1.85 [1.14-3.00], p = 0.013). CONCLUSION: EAT thickness is independently associated with CMD and can differentiate between patients with and without CMD especially in older age groups. Our results support the hypothesis that modulation of local inflammation by epicardial fat is involved in the development of CMD.

Association of epicardial fat thickness with left ventricular diastolic function parameters in a community population.

BACKGROUND: We examined the relationship between epicardial fat thickness (EFT) measured by echocardiography and left ventricular diastolic function parameters in a Beijing community population. METHODS: We included 1004 participants in this study. Echocardiographic parameters including E and A peak velocity, the early diastolic velocities (e') of the septal and lateral mitral annulus using tissue doppler imaging, E/e', and EFT were measured. EFT1 was measured perpendicularly on the right ventricular free wall at end diastole in the extension line of the aortic root. EFT2 was the maximum thickness measured perpendicularly on the right ventricular free wall at end diastole. Multivariable linear regression was used to analyze the relationship between EFT and the mean e' and E/e'. RESULTS: The mean age of the participants was 63.91 ± 9.02 years, and 51.4% were men. EFT1 and EFT2 were negatively correlated with lateral e', septal e', and mean e' (p < 0.05), and the correlation coefficient for EFT1 and EFT2 and mean e' was - 0.138 and - 0.180, respectively. EFT1 and EFT2 were positively correlated with lateral E/e', septal E/e', and mean E/e' (p < 0.05), and the correlation coefficient for EFT1 and EFT2 and mean e' was 0.100 and 0.090, respectively. Multivariable egression analysis showed that EFT2 was independently and negatively associated with e' mean (ß = - 0.078 [95% confidence interval = - 0.143, - 0.012, p = 0.020]). There were no interactions between EFT2 and any covariates, including age or heart groups, sex, BMI, or presence of hypertension, diabetes, or coronary heart disease, in relation to left ventricular diastolic dysfunction. CONCLUSIONS: EFT2 was negatively and independently associated with e' mean, which suggests that more attention to this type of adipose fat is required for cardiovascular disease therapy.

Can We Decrease Epicardial and Pericardial Fat in Patients With Diabetes?

Diabetes mellitus (DM) is a chronic and complex metabolic disorder and also an important cause of cardiovascular (CV) disease (CVD). Patients with type 2 DM (T2DM) and obesity show a greater propensity for visceral fat deposition (and excessive fat deposits elsewhere) and the link between adiposity and CVD risk is greater for visceral than for subcutaneous (SC) adipose tissue (AT). There is growing evidence that epicardial AT (EAT) and pericardial AT (PAT) play a role in the development of DM-related atherosclerosis, atrial fibrillation (AF), myocardial dysfunction, and heart failure (HF). In this review, we will highlight the importance of PAT and EAT in patients with DM. We also consider therapeutic interventions that could have a beneficial effect in terms of reducing the amount of AT and thus CV risk. EAT is biologically active and a likely determinant of CV morbidity and mortality in patients with DM, given its anatomical characteristics and proinflammatory secretory pattern. Consequently, modification of EAT/PAT may become a therapeutic target to reduce the CV burden. In patients with DM, a low calorie diet, exercise, antidiabetics and statins may change the quantity of EAT, PAT or both, alter the secretory pattern of EAT, improve the metabolic profile, and reduce inflammation. However, well-designed studies are needed to clearly define CV benefits and a therapeutic approach to EAT/PAT in patients with DM.

Single-Cell RNA Sequencing Uncovers Paracrine Functions of the Epicardial-Derived Cells in Arrhythmogenic Cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) manifests with sudden death, arrhythmias, heart failure, apoptosis, and myocardial fibro-adipogenesis. The phenotype typically starts at the epicardium and advances transmurally. Mutations in genes encoding desmosome proteins, including DSP (desmoplakin), are major causes of ACM. METHODS: To delineate contributions of the epicardium to the pathogenesis of ACM, the Dsp allele was conditionally deleted in the epicardial cells in mice upon expression of tamoxifen-inducible Cre from the Wt1 locus. Wild type (WT) and Wt1-CreERT2:DspW/F were crossed to Rosa26mT/mG (R26mT/mG) dual reporter mice to tag the epicardial-derived cells with the EGFP (enhanced green fluorescent protein) reporter protein. Tagged epicardial-derived cells from adult Wt1-CreERT2:R26mT/mG and Wt1-CreERT2: R26mT/mG:DspW/F mouse hearts were isolated by fluorescence-activated cell staining and sequenced by single-cell RNA sequencing. RESULTS: WT1 (Wilms tumor 1) expression was progressively restricted postnatally and was exclusive to the epicardium by postnatal day 21. Expression of Dsp was reduced in the epicardial cells but not in cardiac myocytes in the Wt1-CreERT2:DspW/F mice. The Wt1-CreERT2:DspW/F mice exhibited premature death, cardiac dysfunction, arrhythmias, myocardial fibro-adipogenesis, and apoptosis. Single-cell RNA sequencing of ≈18 000 EGFP-tagged epicardial-derived cells identified genotype-independent clusters of endothelial cells, fibroblasts, epithelial cells, and a very small cluster of cardiac myocytes, which were confirmed on coimmunofluorescence staining of the myocardial sections. Differentially expressed genes between the paired clusters in the 2 genotypes predicted activation of the inflammatory and mitotic pathways-including the TGFß1 (transforming growth factor ß1) and fibroblast growth factors-in the epicardial-derived fibroblast and epithelial clusters, but predicted their suppression in the endothelial cell cluster. The findings were corroborated by analysis of gene expression in the pooled RNA-sequencing data, which identified predominant dysregulation of genes involved in epithelial-mesenchymal transition, and dysregulation of 146 genes encoding the secreted proteins (secretome), including genes in the TGFß1 pathway. Activation of the TGFß1 and its colocalization with fibrosis in the Wt1-CreERT2:R26mT/mG:DspW/F mouse heart was validated by complementary methods. CONCLUSIONS: Epicardial-derived cardiac fibroblasts and epithelial cells express paracrine factors, including TGFß1 and fibroblast growth factors, which mediate epithelial-mesenchymal transition, and contribute to the pathogenesis of myocardial fibrosis, apoptosis, arrhythmias, and cardiac dysfunction in a mouse model of ACM. The findings uncover contributions of the epicardial-derived cells to the pathogenesis of ACM.

Thickness of epicardial and pericoronary adipose tissue measured using 128-slice MSCT as predictors for risk of significant coronary artery diseases.

AIM: Determination the relationship between the epicardial adipose tissue thickness (EATT) and pericoronary adipose tissue thickness (PATT) and the risk of significant coronary artery diseases (CAD) using the coronary artery calcium score (CACS). MATERIALS AND METHODS: The study group consisted of 80 patients. The risk of significant CAD was estimated based on CACS. Adipose tissue thickness was measured based on multiplanar reformation (MPR), left ventricle short axis and mid-chamber level. EATT in the middle of the length of the right ventricular free wall, PATT around the left anterior descending (LAD), around the left circumflex (LCX) and around the right coronary artery in the posterior interventricular sulcus (RCA). RESULTS: The median (IQR) values of CACS and EATT were 12.00 (97.90) and 8.65 (3.90) mm. It was found that in the subgroup CACS = 0 statistically significantly lower than in the subgroup CACS > 0 were mean values EATT and PATT RCA. Based on the regression analysis, it was demonstrated that higher CACS is associated with higher EATT, independent of older age and higher BMI. On the basis the ROC curve analysis, the highest prediction sensitivity of 98.4% was demonstrated for EATT ≥ 16.7 mm as a predictor of high risk of significant CAD and the highest specificity of 61.5% for the criterion EATT ≤ 8.7 mm as a predictor of practically no risk of significant CAD. CONCLUSION: There is a positive relationship between the risk of a significant CAD estimated based on the coronary artery calcium score and the epicardial adipose tissue thickness.

Blood SIRT1 Shows a Coherent Association with Leptin and Adiponectin in Relation to the Degree and Distribution of Adiposity: A Study in Obesity, Normal Weight and Anorexia Nervosa.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, and with leptin and adiponectin, it regulates metabolic homeostasis. Widely studied in tissues, SIRT1 is under evaluation as a plasmatic marker. We aimed at assessing whether circulating SIRT1 behaves consistently with leptin and adiponectin in conditions of deficiency, excess or normal fat content. Eighty subjects were evaluated: 27 with anorexia nervosa (AN), 26 normal-weight and 27 with obesity. Bloodstream SIRT1, leptin and adiponectin (ELISA), total and trunk fat mass (FM) %, abdominal visceral adipose tissue, liver steatosis and epicardial fat thickness (EFT) were assessed. For each fat store, the coefficient of determination (R2) was used to evaluate the prediction capability of SIRT1, leptin and adiponectin. Plasma SIRT1 and adiponectin coherently decreased with the increase of FM, while the opposite occurred with leptin. Mean levels of each analyte were different between groups (p < 0.005). A significant association between plasma variables and FM depots was observed. SIRT1 showed a good predictive strength for FM, particularly in the obesity group, where the best R2 was recorded for EFT (R2 = 0.7). Blood SIRT1, adiponectin and leptin behave coherently with FM and there is synchrony between them. The association of SIRT1 with FM is substantially superimposable to that of adiponectin and leptin. Given its homeostatic roles, SIRT1 may deserve to be considered as a plasma clinical/biochemical parameter of adiposity and metabolic health.

Epicardial Adipose Thickness and Neutrophil Lymphocyte Ratio in Acute Occlusive Cerebrovascular Diseases.

OBJECTIVES: We investigate the relationship between the severity of vascular disease and epicardial adipose tissue thickness(EAT-t) and the neutrophil/lymphocyte (NEU/LY) ratio in acute stroke patients. METHODS: Seventy-six patients and 38 healthy controls were included in the study. Strokes were divided into three groups: lacunar infarction, middle cerebral artery infarction (MCA), and other arterial infarcts. Patients were assessed using the GCS (Glasgow coma scale) and NIHSS (National Institutes of Health Stroke Scale) scales. In addition to laboratory measurements, EAT-t was evaluated in all patients by using echocardiography. RESULTS: The EAT-t value and NEU/LY ratio were higher in the patient group than in the control group. The MCA group was found to have a significantly higher NEU/LY ratio than the lacuna group (p = 0.017) as well as the other patient (p = 0.025) group. There was a positive correlation of NIHSS score with EAT-t (r = 0.291; p = 0.013), and NEU/LY ratio (r = 0.289; p = 0.014). CONCLUSION: The EAT-t and NEU/LY ratio were high in patients with acute ischemic stroke patients. The higher ratio of NEU/LY compared to other infarcts in the MCA group. These findings support the relationship between acute ischemic stroke severity and inflammation .

Epicardial Adipose Tissue Accumulation Confers Atrial Conduction Abnormality.

BACKGROUND: Clinical studies have reported that epicardial adipose tissue (EpAT) accumulation associates with the progression of atrial fibrillation (AF) pathology and adversely affects AF management. The role of local cardiac EpAT deposition in disease progression is unclear, and the electrophysiological, cellular, and molecular mechanisms involved remain poorly defined. OBJECTIVES: The purpose of this study was to identify the underlying mechanisms by which EpAT influences the atrial substrate for AF. METHODS: Patients without AF undergoing coronary artery bypass surgery were recruited. Computed tomography and high-density epicardial electrophysiological mapping of the anterior right atrium were utilized to quantify EpAT volumes and to assess association with the electrophysiological substrate in situ. Excised right atrial appendages were analyzed histologically to characterize EpAT infiltration, fibrosis, and gap junction localization. Co-culture experiments were used to evaluate the paracrine effects of EpAT on cardiomyocyte electrophysiology. Proteomic analyses were applied to identify molecular mediators of cellular electrophysiological disturbance. RESULTS: Higher local EpAT volume clinically correlated with slowed conduction, greater electrogram fractionation, increased fibrosis, and lateralization of cardiomyocyte connexin-40. In addition, atrial conduction heterogeneity was increased with more extensive myocardial EpAT infiltration. Cardiomyocyte culture studies using multielectrode arrays showed that cardiac adipose tissue-secreted factors slowed conduction velocity and contained proteins with capacity to disrupt intermyocyte electromechanical integrity. CONCLUSIONS: These findings indicate that atrial pathophysiology is critically dependent on local EpAT accumulation and infiltration. In addition to myocardial architecture disruption, this effect can be attributed to an EpAT-cardiomyocyte paracrine axis. The focal adhesion group proteins are identified as new disease candidates potentially contributing to arrhythmogenic atrial substrate.

Simultaneous Endo-Epicardial Mapping of the Human Right Atrium: Unraveling Atrial Excitation.

Background The significance of endo-epicardial asynchrony (EEA) and atrial conduction block (CB), which play an important role in the pathophysiology of atrial fibrillation (AF) during sinus rhythm is poorly understood. The aim of our study was therefore to examine 3-dimensional activation of the human right atrium (RA). Methods and Results Eighty patients (79% men, 39% history of AF) underwent simultaneous endo-epicardial sinus rhythm mapping of the inferior, middle and superior RA. Areas of CB were defined as conduction delays of ≥12 ms, EEA as activation time differences of opposite electrodes of ≥15 ms and transmural CB as CB at similar endo-epicardial sites. CB was more pronounced at the endocardium (all locations P<0.025). Amount, extensiveness and severity of CB was higher at the superior RA. Transmural CB at the inferior RA was associated with a higher incidence of post-operative AF (P=0.03). EEA occurred up to 84 ms and was more pronounced at the superior RA (superior: 27 ms [interquartile range, 18.3-39.3], versus mid-RA: 20.3 ms [interquartile range, 0-29.9], and inferior RA: 0 ms [interquartile range, 0-21], P<0.001). Hypertension (P=0.009), diabetes mellitus (P=0.018), and hypercholesterolemia (P=0.015) were associated with a higher degree of EEA. CB (P=0.007) and EEA (P=0.037) were more pronounced in patients with a history of persistent AF compared with patients without AF history. Conclusions This study provides important insights into complex atrial endo-epicardial excitation. Significant differences in conduction disorders between the endo- and epicardium and a significant degree of EEA are already present during sinus rhythm and are more pronounced in patients with cardiovascular risk factors or a history of persistent AF.