BACKGROUND: Patients with myocardial ischemia without obstructive coronary artery disease often have coronary microvascular dysfunction (CMD) and associated increased risk of cardiovascular (CV) events and anginal hospitalizations. Epicardial adipose tissue (EAT) covers much of the myocardium and coronary arteries and when dysfunctional, secretes proinflammatory cytokines and is associated with CV events. While oxidative stress and systemic inflammation are associated with CMD, the relationship between EAT and CMD in women is not well known.
METHODS: Women diagnosed with CMD (n = 21) who underwent coronary computed tomography with coronary artery calcium (CAC) scoring were compared to a reference group (RG) of women referred for CAC screening for preventive risk assessment (n = 181). EAT attenuation (Hounsfield units (HU)) was measured adjacent to the proximal right coronary artery, along with subcutaneous adipose tissue (SCAT). Two-sample t-tests with unequal variances were utilized.
RESULTS: Mean age of the CMD group was 56 ± 8 years and body mass index (BMI) was 31.6 ± 6.8 kg/m2. CV risk factors in the CMD group were prevalent: 67 % hypertension, 44 % hyperlipidemia, and 33 % diabetes. Both CMD and RG had similar CAC score (25.86 ± 59.54 vs. 24.17 ± 104.6; p = 0.21. In the CMD group, 67 % had a CAC of 0. Minimal atherosclerosis (CAD-RADS 1) was present in 76 % of women with CMD. The CMD group had lower EAT attenuation than RG (-103.3 ± 6.33 HU vs. -97.9 ± 8.3 HU, p = 0.009, respectively). There were no differences in SCAT attenuation. Hypertension, smoking history, age, BMI, and CAC score did not correlate with EAT in either of the groups.
CONCLUSIONS: Women with CMD have decreased EAT attenuation compared to RG women. EAT-mediated inflammation and changes in vascular tone may be a mechanistic contributor to abnormal microvascular reactivity. Clinical trials testing therapeutic strategies to decrease EAT may be warranted in the management of CMD.

UNASSIGNED: Obesity cardiomyopathy (OCM) can be associated with sudden cardiac death (SCD) but its pathologic features are not well described.
UNASSIGNED: The objective of this study was to characterize the clinical and pathological features of OCM associated with SCD.
UNASSIGNED: This was a retrospective case control autopsy study. OCM was identified by an increased heart weight (>550 g in males; >450 g in females) in individuals with obesity (body mass index [BMI] ≥30 kg/m2) in the absence of other causes. Cases of OCM with SCD were compared to sex and age matched SCD controls with obesity or with normal weight (BMI 18.5-24.9 kg/m2) and morphologically normal hearts. Autopsy measures included: heart weight, atrial dimensions, ventricular wall thickness, and epicardial adipose tissue. Fibrosis was assessed microscopically.
UNASSIGNED: Of 6,457 SCD cases, 53 cases of OCM were identified and matched to 106 controls with obesity and 106 normal weight controls. The OCM mean age at death of individuals with OCM was 42 ± 12 with a male predominance (n = 34, 64%). Males died younger than females (40 ± 13 vs 45 ± 10, P = 0.036). BMI was increased in OCM cases compared to controls with obesity (42 ± 8 vs 35 ± 5). The average heart weight was 598 ± 93 g in OCM. There were increases in right and left ventricular wall thickness (all P < 0.05) in OCM cases compared to controls. Right ventricular epicardial fat was increased in OCM compared to normal weight controls only. Left ventricular fibrosis was identified in 7 (13%) cases.
UNASSIGNED: OCM may be a specific pathological entity associated with SCD. It is most commonly seen in young males with increased BMI.

Background: Modern treatments for transfusion-dependent β-thalassemia (TDβT) have allowed patients to reach high life expectancy with no iron overload. Despite survival improvement, atrial fibrillation (AF) has emerged as a relevant issue. AF pathophysiology and characteristics in TDβT are different than in the general population. Epicardial adipose tissue (EAT) may play a role but its relationship with AF in patients with TDβT has not been explored. Methods: A monocentric, cross-sectional study, enrolling consecutive patients with TDβT. Epicardial adipose tissue (EAT) was evaluated at magnetic resonance. Characteristics of patients with and without history of AF were investigated. Factors independently associated with AF prevalence were analyzed. Results: A total of 116 patients were enrolled. All patients were treated with regular chelation therapy. The prevalence of AF was 29.3% (34/116). Cardiac T2* and liver iron concentration were no different between patients with and without AF. EAT thickness was significantly higher in patients with AF at left atrium, right atrium and right ventricle (5.0 vs. 4.0 mm, p < 0.01, 4.4 vs. 4.0, p = 0.02 and 5.0 vs. 4.3, p = 0.04). Patients with AF presented with older age, (53 vs. 49 years, p < 0.01), more hypothyroidism (44.1 vs. 20.7%, p = 0.01), pulmonary hypertension (23.5 vs. 2.4% p < 0.01), splenectomy (88.2 vs. 64.6%, p = 0.01), higher right and left atrial volume (61 vs. 40 and 74 vs. 43 mL, both p < 0.01). At multivariable analysis, hypothyroidism, left atrial volume and left atrial EAT were independently associated with AF (odds ratio 9.95, 1.09 and 1.91, respectively). Conclusions: In a contemporary cohort of patients with TDβT, treated with regular chelation therapy, prevalence of AF was unrelated to iron overload. EAT was independently associated with AF.

BACKGROUND: Diastolic dysfunction and alterations in cardiac geometry are early indicators of diabetic cardiomyopathy. However, the association between cardiac changes across the glucose continuum and the contribution of epicardial adipose tissue (EAT) to these changes has not yet been investigated.
OBJECTIVE: In this study, we aim to investigated the EAT on cardiac diastolic function and structural alterations along the diabetic continuum using cardiac magnetic resonance imaging (CMRI).
METHODS: We enrolled individuals who were categorized into groups based on glucose tolerance status. Left ventricular structure and diastolic function were assessed using echocardiography and CMRI to determine the EAT, intramyocardial fat, and associated parameters. Multivariable logistic regression models were also used.
RESULTS: In a study of 370 patients (209 normal glucose tolerance, 82 prediabetes, 79 diabetes), those with prediabetes and diabetes showed increased heart dimensions and diastolic dysfunction, including E/E\' (the ratio of early mitral inflow velocity to mitral annular early diastolic velocity) (7.9±0.51 vs. 8.5±0.64 vs. 10.0±0.93, p=0.010), left atrial volume index (28.21±14.7 vs. 33.2±12.8 vs. 37.4±8.2 mL/m2, p<0.001), and left ventricular peak filling rate (4.46±1.75 vs. 3.61±1.55 vs. 3.20±1.30 mL/s, p<0.001). EAT significantly increased in prediabetes and diabetes (26.3±1.16 vs. 31.3±1.83 vs. 33.9±1.9 gm, p=0.001), while intramyocardial fat did not differ significantly. Prediabetes altered heart geometry, but not diastolic function (OR 1.22 [1.02-1.83], p=0.012; and 1.70 [0.79-3.68], p=0.135). Diabetes significantly affected both heart structure and diastolic function (OR 1.42 [1.11-1.97], p=0.032; and 2.56 [1.03-5.40], p=0.034) after adjusting for covariates.
CONCLUSIONS: Elevated EAT was observed in patients with prediabetes and is associated with adverse alterations in cardiac structure and diastolic function, potentially serving as an underlying mechanism for the early onset of diabetic cardiomyopathy.

Epicardial adipose tissue (EAT) deposition has been long associated with heart weight. However, recent research has failed to replicate this association. We aimed to determine the association of EAT volume with heart weight in post-mortem cases and identify potential confounding variables. EAT volume derived from post-mortem computed tomography (PMCT) and heart weight were measured in post-mortem cases (N = 87, age: 56 ± 16 years, 28% female). Cases with hypertrophied heart weights (N = 44) were determined from reference tables. Univariable associations were tested using Spearman correlation and simple linear regression. Independence was determined with stepwise regression. In the total cohort, EAT volume (median 66 ± 45 cm3) was positively associated with heart weight (median 435 ± 132 g) at the univariable level (r = 0.6, P < 0.0001) and after adjustment for age, female sex, and various body size metrics (R2 adjusted = 0.41-0.57). Median EAT volume was 1.9-fold greater in cases with hypertrophic hearts (P < 0.0001) but with considerably greater variability, especially in cases with extreme EAT volume or heart weight. As such, EAT volume was not associated with heart weight in hypertrophic cases, while a robust independent association was found in non-hypertrophic cases (R2 adjusted = 0.62-0.86). EAT mass estimated from EAT volume found that EAT comprised approximately 13% of overall heart mass in the total cases. This was significantly greater in cases with hypertrophy (median 15.5%; range, 3.6-36.6%) relative to non-hypertrophied cases (12.5%, 3.3-24.3%) (P = 0.04). EAT volume is independently and positively associated with heart weight in post-mortem cases. Excessive heart weight significantly confounded this association.

The exact processes underlying atrial fibrillation (AF) are still unclear. It has been suggested that epicardial adipose tissue (EAT) may contribute to arrhythmias and can release various bioactive molecules, including exosomes containing tRNA-derived small RNAs (tsRNAs). Numerous studies have indicated that these tsRNAs can significantly affect key cellular functions. However, there is currently no research investigating the relationship between tsRNAs from EAT and AF. In order to explore the regulatory mechanisms of tsRNAs from EAT associated with AF, we conducted RNA-sequencing analysis on EAT samples collected from 6 AF patients and 6 control subjects with sinus rhythm. Our analysis revealed an upregulation of 146 tsRNAs and a downregulation of 126 tsRNAs in AF. Furthermore, we randomly selected four tsRNAs (tRF-SeC-TCA-001, tiRNA-Gly-CCC-003, tRF-Gly-GCC-002, and tRF-Tyr-GTA-007) for validation using quantitative reverse transcription-polymerase chain reaction. Following this, bioinformatic analyses revealed that the target genes of these tsRNAs were prominently involved in the regulation of cell adhesion and various cellular processes mediated by plasma membrane adhesion molecules. Additionally, based on KEGG analysis, it was suggested that the majority of these target genes might contribute to the pathogenesis of AF through processes such as glycosaminoglycan biosynthesis, AMP-activated protein kinase activity, and the insulin signaling pathway. Our results elucidate changes in the expression profiles of tsRNAs within EAT samples obtained from AF patients, and they forecast potential target genes and interactions between tsRNAs and mRNA within EAT that could contribute to the pathogenesis of AF.

BACKGROUND: In patients with atrial fibrillation (AF), up to one third have recurrence after a first catheter ablation (CA). Epicardial adipose tissue (EAT) has been considered to be closely related to AF, with a potential role in its recurrence. We aimed to evaluate the association between the volume of EAT measured by cardiac computed tomography (CT) and AF recurrence after CA.
METHODS: Consecutive AF patients underwent a standardized cardiac CT protocol for quantification of EAT, thoracic adipose volume (TAV) and left atrium (LA) volume before CA. An appropriate cut-off of EAT was determined and risk recurrence was estimated.
RESULTS: 305 patients (63.6 % male, mean age 57.5 years, 28.2 % persistent AF) were followed for 24 months; 23 % had AF recurrence at 2-year mark, which was associated with higher EAT (p = 0.037) and LAV (p < 0.001). Persistent AF was associated with higher EAT volumes (p = 0.010), TAV (p = 0.003) and LA volumes (p < 0.001). EAT was predictive of AF recurrence (p = 0.044). After determining a cut-off of 92 cm3, survival analysis revealed that EAT volumes > 92 cm3 showed higher recurrence rates at earlier time points after the index ablation procedure (p = 0.006), with a HR of 1.95 (p = 0.008) of AF recurrence at 2-year. After multivariate adjustment, EAT > 92 cm3 remained predictive of AF recurrence (p = 0.028).
CONCLUSIONS: The volume of EAT measured by cardiac CT can predict recurrence of AF after ablation, with a volume above 92 cm3 yielding almost twice the risk of arrhythmia recurrence in the first two years following CA. Higher EAT and TAV are also associated with persistent AF.

BACKGROUND: Muscular strength and muscle mass are considered key factors for healthy ageing. Modification of body composition and redistribution of adipose tissue has been described in advanced age. Muscle strength has an important predictive role for health outcomes. However, little is known regarding the relationship between muscle strength and epicardial fat.
METHODS: In a cohort of healthy adults following physical capacity evaluations, anthropometric measurements, handgrip strength (HGS), echocardiography and bioimpedance analysis (BIA) were performed. Kruskal-Wallis test, Spearman\'s correlation and regression analysis adjusted for confounders were applied.
RESULTS: A total population of 226 adults, age range 18-83 years, were included. Epicardial fat thickness resulted significantly associated with age p < 0.001, HGS (p < 0.001). Regression analysis adjusted for confounders revealed an independent relationship between handgrip strength and epicardial fat thickness: regression coefficient: -1.34; R2 = 0.27 and p = 0.044.
CONCLUSIONS: The relationship between epicardial fat and muscle strength is inverse and independent. Implementation of HGS measurement may be useful for the identification of subjects with excessive epicardial fat and cardiovascular risk. Measurement of epicardial fat could be helpful in the early detection of physical decline associated to ageing.

OBJECTIVE: This study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging.
METHODS: 730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created.
RESULTS: In the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903-10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765-7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822-10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045-1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336-1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort.
CONCLUSIONS: In patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters.

OBJECTIVE: Preserved ejection fraction heart failure and obesity frequently coexist. Whether obesity plays a consistent role in the pathogenesis of preserved ejection fraction heart failure is unclear. Accumulation of visceral adiposity underlies the pathogenic aftermaths of obesity. However, visceral adiposity imaging is assessed by computed tomography or magnetic resonance and thus not routinely available. In contrast, epicardial adiposity thickness is assessed by echocardiography and thus routinely available. We review the rationale for assessing epicardial adiposity thickness in patients with preserved ejection fraction heart failure and elevated body mass index.
RESULTS: Body mass index correlates poorly with visceral, and epicardial adiposity. Visceral and epicardial adiposity enlarges as preserved ejection fraction heart failure progresses. Epicardial adiposity may hasten the progression of coronary artery disease and impairs left ventricular sub-endocardial perfusion and diastolic function. Epicardial adiposity thickness may help monitor the therapeutic response in patients with preserved ejection failure heart failure and elevated body mass index.