Epicardial adipose tissue in obesity with heart failure with preserved ejection fraction: Cardiovascular magnetic resonance biomarker study

BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evaluating HFpEF in obesity is crucial.Epicardial adipose tissue(EAT)has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets.Hence,assessing EAT is of paramount importance.Cardiovascular magnetic resonance(CMR)imaging is acknowledged as the gold standard for analyzing cardiac function and mor-phology.We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients.AIM To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction[HFpEF;left ventricular(LV)ejection fraction≥50%]by measuring the epicardial adipose tissue(EAT)volumes and EAT mass in obese patients.METHODS Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF.The two groups were defined as HFpEF+and HFpEF-.LV geometry,global systolic function,EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences.RESULTS Forty-five patients of HFpEF-group and seventeen patients of HFpEF+group were included.LV mass index(g/m2)of HFpEF+group was higher than HFpEF-group(P<0.05).In HFpEF+group,EAT volumes,EAT volume index,EAT mass,EAT mass index and the ratio of EAT/[left atrial(LA)left-right(LR)diameter]were higher compared to HFpEF-group(P<0.05).In multivariate analysis,Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF.CONCLUSION EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients.It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker.Further prospective studies,are needed to validate these proof-of-concept findings.

Targeting epicardial adipose tissue:A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus

Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.

Influence of increased epicardial adipose tissue volume on 1-year in-stent restenosis in patients who received coronary stent implantation

Background Epicardial adipose tissue （EAT） is significantly associated with the formation and composition of coronary atherosclerotic plaque, cardiac events and the clinical prognosis of coronary heart disease. But, whether increased EAT deposition may affect the incidence of in-stent restenosis （ISR） is currently unclear. This study used coronary computed tomography angiography （CCTA） as a mean to investigate whether increased EAT volume was associated with ISR. Methods A total of 364 patients who underwent 64-slice CCTA examination for the evaluation of suspected coronary artery disease, and subsequently underwent percutaneous coronary intervention （PCI） for the first time, and then accepted coronary angiography （CA） follow-up for ISR examination in one year, were retrospectively included in this study. EAT volume was measured by CCTA examination. CA follow-up was obtained between 9 and 15 months. ISR was defined as 〉 50% kuninal diameter narrowing of the stent segment or peri-stent segment. EAT volume was compared between patients with and without ISR and additional well-known predictors of ISR were compared. Results EAT volume was significantly increased in patients with ISR compared with those without ISR （154.5 ± 74.6 mL vs. 131.0 ± 52.2 mL, P 〈 0.001）. The relation between ISR and EAT volume remained significant after adjustment for conventional cardiovascular risk factors and angiographic parameters. Conclusions EAT volume was related with ISR and may provide additional information for future ISR.

Roles of Human Epicardial Adipose Tissue in Coronary Artery Atherosclerosis

This study examined the adipocytokine-vascular interactions and link between epicardial adipose tissue and coronary artery atherosclerosis.Thirty-four patients undergoing open heart surgery were chosen randomly, and divided into groupⅠ(non-coronary artery disease group) and group Ⅱ(coronary artery disease group).Blood samples were taken through peripheral vein prior to surgery.Plasma levels of a panel of proteins (adiponectin, IL-10, TNF-α) were detected by using ELISA.Epicardial adipose tissue was taken near the proximal tract of the right coronary artery and subcutaneous adipose was taken from the leg before cardiopulmonary bypassing, adiponectin and CD68+ were detected by using RT-PCR and immunohistochemistry.Our results showed that plasma adiponectin level was significantly lower in the group Ⅱ as compared with group Ⅰ(P【0.05).There were no differences in plasma concentration (IL-10, TNF-α, tatal-chol, HDL-chol, LDL-chol) between group Ⅰ and group Ⅱ.The number of CD68+ cells in epicardial adipose tissue of group Ⅱ was significantly higher than that in subcutaneous adipose tissue.Adiponectin mRNA expression was 6 fold higher in subcutaneous adipose tissue than in epicardial adipose tissue of group Ⅱ (P【0.01).Furthermore, the level of adiponectin mRNA in the epicardial adipose tissue in group Ⅱ was also significantly lower than in group Ⅰ (P【0.05).We are led to conclude that inflammation that occurs locally in epicardial adipose tissue of CAD contributes to the pathogenesis of coronary artery disease.

Epicardial adipose tissue deposition in patients with diabetes and renal impairment: Analysis of the literature

Diabetes mellitus(DM)is defined as a chronic disease of disordered metabolism with an ongoing increase in prevalence and incidence rates.Renal disease in patients with diabetes is associated with increased morbidity and premature mortality,particularly attributed to their very high cardiovascular risk.Since this group of patients frequently lacks specific symptomatology prior to the adverse events,a screening tool for the identification of high-risk patients is necessary.The epicardial adipose tissue(EAT)is a biologically active organ having properties similar to visceral adipose tissue and has been associated with metabolic diseases and coronary artery disease.Superior to conventional cardiovascular risk factors and anthropometric measures,including body mass index and waist circumference,the EAT can early predict the development of coronary artery disease.Assessment of EAT can be performed by twodimensional echocardiography,magnetic resonance imaging or computer tomography.However,its role and significance in patients with DM and nephropathy has not been thoroughly evaluated.The aim of the current editorial is to evaluate all available evidence regarding EAT in patients with DM and renal impairment.Systematic search of the literature revealed that patients with DM and nephropathy have increased EAT measurements,uncontrolled underlying disease,high body mass index and raised cardiovascular risk markers.Acknowledging the practical implications of this test,EAT assessment could serve as a novel and non-invasive biomarker to identify high-risk patients for cardiovascular adverse events.

Epicardial adipose tissue around the superior vena cava: A single center study of factors related to atrial fibrillation

The superior vena cava(SVC)is the main component of non-pulmonary vein(PV)ectopy in patients with atrial fibrillation(AF).Researchers have found that epicardial adipose tissue(EAT)volume is related to the AF substrate,which can be defined by the low voltage area(LVA).This study aimed to investigate the relationship between SVC-EAT and SVC-AF.Twenty-six patients with SVC-AF triggers were identified as the SVC-AF group.Other three groups were defined and included as the LVA-AF group(LVA>5%),non-LVA-AF group(LVA<5%),and physical examination(PE)group.EAT around left atrium(LA-EAT)and SVC-EAT volumes were obtained using a cardiac risk assessment module.According to the SVC/LA-EAT ratio,there are significant differences between the SVC-AF group and the three control groups(the SVC-AF group 0.092±0.041 vs.the LVA-AF group 0.054±0.026,the non-LVA-AF group 0.052±0.022,and the PE group 0.052±0.019,all P<0.001).Receiver operating characteristic curve analysis suggests the optimal cut-off point of SVC/LA-EAT ratio is 6.8%for detecting SVC-AF patients,with 81.1%sensitivity,73.1%specificity,and an area under the curve of 0.83(95%confidence interval,0.75-0.91).Those with SVC-AF have a higher SVC/LA-EAT ratio and empirical SVC isolation could be considered if the SVC/LA-EAT ratio was over 6.8%.

Role of Epicardial Adipose Tissue in Triggering and Maintaining Atrial Fibrillation

Atrial fibrillation is the most common arrhythmia leading to cardiogenic stroke.Without membranous sructure between epicardial adipose tissue and atrial myocardium,epicardial adipose tissue directly covers the surface of the atrial myocardium.The formation of an epicardial adipose tissue inflammatory microenvironment,fibrosis,infiltration by epicardial adipose tissue,autonomic dysfunction and oxidative stress are important mechanisms that trigger and maintain atrial fibrillation.Those mechanisms are reviewed herein.

Epicardial Adipose Tissue in Patients with Obstructive Sleep Apnea:A Systematic Review and Meta-analysis

Objective:Epicardial adipose tissue(EAT)is a potential risk factor for obstructive sleep apnea(OSA).We performed a meta-analysis to assess the association of EAT with OSA.Methods:The PubMed,EMBASE,Web of Science,Cochrane Library,and Wanfang databases were searched by two independent investigators for all observational studies assessing the association of EAT with OSA.Then we assessed the association of EAT thickness(EAT-t)and EAT volume(EAT-v)with OSA by a meta-analysis.Results:Ten studies were included in the fi nal analysis.Compared with that in controls,EAT-t in OSA patients was signifi cantly increased(standardized mean difference 0.88,95%confi dence interval 0.72-1.05,P=0.000).Furthermore,EAT-t was greater in OSA patients than in controls with similar BMIs.However,we did not fi nd signifi cant differences in EAT-v between OSA patients and controls(standardized mean difference 2.46,95%confi dence interval−0.36 to 5.29,P=0.088).EAT-t in the mild,moderate,and severe OSA subgroups was greater than in the controls.In addition,there were signifi cant differences in EAT-t among the mild,moderate,and severe OSA subgroups.Conclusions:EAT-t was greater in patients with OSA than in controls,and EAT-t was also associated with the severity of OSA.These fi ndings may provide a new clue for the pathogenesis and treatment of OSA.

Epicardial adipose tissue： the accomplice implicated in the genesis and maintenance of atrial fibrillation

Objective The purpose of this review was to delineate our current knowledge of the close relationship between the abundance of epicardial adipose tissue （EAT） and the risk of all major cardiovascular disease, especially atrial fibrillation （AF）. Data sources The data analyzed in this review were mainly from articles reported in PubMed published from 1972 to 2014. Study selection Original articles and critical reviews relevant to EAT and AF were selected. Results EAT, a particular form of metabolically active visceral fat deposited around the heart, is being regarded as an important independent predictor of cardio-metabolic diseases. EAT is composed of smaller adipocytes than other visceral fat depots and functioned like brown adipose tissue （BAT） to protect adjacent tissues. Improving the understanding of EAT in AF genesis and maintenance may contribute to prevent AF and reduce the complications associated with AF. Conclusion The findings suggest that EAT associates with AF severity and the recurrence of AF after catheter ablation even after adjustment forAF risk factors, but the precise mechanisms are not fully elucidated.

A new look at epicardial adipose tissue from the perspective of Iranian traditional medicine

The fact that distribution of body fat can have a major role in the development of metabolic derangement and cardiovascular diseases is supported by a considerable amount of evidence.Therefore it is no surprise that increased of metabolic syndrome. New evidence describing adipose tissue as an advanced endocrine unit, capable of producing substances with remarkable physiologic impacts, has led to increased research interest in this field. While many fatty tissues are similar in composition, some of them, notably subcutaneous and visceral adipose tissues, possess special properties.

Expression profile of circular RNAs in epicardial adipose tissue in heart failure

Background:Recent studies have reported circular RNA(circRNA)expression profiles in various tissue types;however,circRNA expression profile in human epicardial adipose tissue(EAT)remains undefined.This work aimed to compare circRNA expression patterns in EAT between the heart failure(HF)and non-HF groups.Methods:RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups.Quantitative real-time polymerase chain reaction was performed for validation.Comparisons of patient characteristics between the two groups were using t test,Mann-Whitney U test,and Chi-squared test.Results:A total of 141 circRNAs substantially different between the HF and non-HF groups(P<0.05;fold change>2)were detected,including 56 up-regulated and 85 down-regulated.Among them,hsa_circ_0005565 stood out,for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation.The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response,including GSE1,RHOBTB3,HIPK3,UBXN7,PCMTD1,N4BP2L2,CFLAR,EPB41L2,FCHO2,FNDC3B,and SPECC1.The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance,respectively.Conclusion:These data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.

Advances in research of epicardial adipose tissue and diastolic heart failure

Background Epicardial adipose tissue(EAT)is a unique visceral adipose tissue that is located between the myocardium and the visceral layer of the pericardium.Physiologically,EAT can produce heat and protect the heart.Under pathological conditions,EAT is involved in the development of diastolic heart failure(DHF)by secreting a variety of pro-inflammatory cytokines.More and more studies have shown that EAT plays an important role in the inflammatory mechanism and myocardial remodeling of DHF.Exercise,weight loss and drug therapy can significantly reduce the thickness/volume of EAT and its functional disorder.In recent years,research on EAT and DHF has made new progress.This article reviewed the mechanism and treatment of EAT in the development of DHF.

Cardiac adipose tissue and its relationship to diabetes mellitus and cardiovascular disease

Type-2 diabetes mellitus(T2DM) plays a central role in the development of cardiovascular disease(CVD). However, its relationship to epicardial adipose tissue(EAT) and pericardial adipose tissue(PAT) in particular is important in the pathophysiology of coronary artery disease. Owing to its close proximity to the heart and coronary vasculature, EAT exerts a direct metabolic impact by secreting proinflammatory adipokines and free fatty acids, which promote CVD locally. In this review, we have discussed the relationship between T2 DM and cardiac fat deposits, particularly EAT and PAT, which together exert a big impact on the cardiovascular health.