Published: 2019-09-15

Proinflammatory phenotype of cardiac visceral fat in heart failure with preserved ejection fraction in the elderly

Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
Epicardial adipose tissue Heart failure, Elderly


Nearly half of all patients with heart failure (HF) symptoms have HF with preserved ejection fraction (HFpEF)
and the prevalence of this pathologic condition is rising being aging one of the most important risk factors.
HFpEF is a very challenging syndrome vulnerable and frail affecting, in the most of cases, patients, with high
health care costs due to high number of hospitalizations and medical cares.
More and more evidence are accumulating on the role of inflammation in the pathogenesis of HFpEF. The
presence of multiple comorbidities in HFpEF may significantly contribute to a systemic pro-inflammatory state
which negatively affects the myocardium.
Obesity promotes systemic inflammation and exacerbates the inflammatory burden imposed by many
chronic extracardiac comorbidities. Importantly, the chronic systemic inflammation related to obesity
is associated to a significant increase of the amount of epicardial adipose tissue (EAT), the cardiac visceral
fat. The increase of EAT volume is associated to a pro-inflammatory state of this fat depot. Several observations
support the hypothesis that the inflammation of EAT can act in a paracrine and vasocrine manner
to influence the structure and function of the heart, thus contributing to the pathohenesis of HFpEF.
Given the recognized role of EAT in the pathophysiology of HFpEF, it should be desirable to identify specific
therapies targeting the cardiac visceral fat and able to modulate its pro-inflammatory profile and the negative
effect of the inflammatory burden on the neighboring myocardium.


In the elders, heart failure (HF) shows clinical features that are substantially different to those observed in the adult population. In fact, in patients over 75 years, this syndrome predominantly affects women with isolated systolic hypertension, normal left ventricular ejection fraction, and several extracardiac comorbidities. In this regard, since 2000, Rich et al. identified the main characteristics of HF in the elderly population and paved the way for the nosographic identification of a new cardiovascular syndrome, to date known as heart failure with preserved ejection fraction (HFpEF) 1. Nearly half of all patients with HF symptoms have HFpEF and the prevalence of this pathologic condition is rising being aging one of the most important risk factors. The clinical outcomes of HFpEF are similar to those with HFrEF. In fact, 30-day to 1-year mortality post hospital discharge is similar between HFpEF and HFrEF and patients with either HF syndrome show similar functional limitations and poor quality of life 2-10. On the other hand, morbidity and cause of death are quite different between the two syndromes, being HFpEF predominantly associated with extracardiac comorbidities and deaths of non cardiac causes. The peculiarities of HFpEF imply many challenges for the researchers and the clinicians for several reasons: the population affected by HFpEF is very heterogeneous and its inclusion in clinical trials is particularly difficult, especially for the oldest-old; mechanistic hypothesis are still lacking due to limited access to biopsies from human heart tissues and the difficulties in obtaining adequate experimental models; the pathophysiological mechanisms accounting for this syndrome are often multifactorial, thus explaining why there is no evidence based therapy, to date, showing efficacy on the hard outcomes, such as morbidity and mortality 11-15.

Overall, HFpEF is a very challenging syndrome, affecting, in the most of cases, patients vulnerable and frail, with high health care costs due to high number of hospitalizations and medical cares. This review aims to report recent advances in the knowledge of the pathophysiology of HFpEF that can help for a better understanding of the mechanisms potentially involved in the onset and progression of such devastating cardiovascular disease.


More and more evidence are accumulating on the role of inflammation in the pathogenesis of HFpEF. Results from left ventricular (LV) endomyocardial biopsy 16 and analyses of inflammatory cell markers 17 indicate increased oxidative stress and depressed NO-signaling resulting in inflammation. Importantly, the presence of multiple comorbidities in HFpEF may significantly contribute to a systemic pro-inflammatory state which negatively affects the myocardium.

Chronic kidney disease (CKD) occurs in one third of HFpEF patients and is associated with poor prognosis 7 18 19. Albuminuria, occurring in almost 30% of HFpEF patients, leads to activation of the RAAS system, and systemic inflammation. It has been hypothesized a bidirectional continuum between renal dysfunction and HFpEF. CKD may lead by itself to myocardial inflammation, fibrosis, and resultant HFpEF. On the other hand, HFpEF may cause renal dysfunction by triggering RAAS pathway activation and venous congestion. In this regard, there are several pathways that may link renal and cardiac disease such as transient receptor potential channel-6, a Gq-receptor and ROS activated nonselective cation channel that plays an important role in proteinuria and glomerular dysfunction 20 but that can also induce cardiac hypertrophy 21 and fibrosis 22.

Chronic inflammation is obviously associated to chronic obstructive pulmonary disease (COPD), which is a crucial determinant of HFpEF mortality 23. Furthermore, sleep disordered breathing, often associated to COPD and HF, lead to systemic inflammation, other than adrenergic and oxidative activation 24.

Iron deficiency and anemia also contribute to immune responses, systemic inflammation and oxidative stress in HFpEF 25.

Diabetes mellitus (DM) is a common comorbidity in HFpEF and has a significant negative impact on prognosis. Insulin resistance in diabetes mellitus increases free fatty acid utilization by cardiomyocytes, thus leading to mitochondrial dysfunction, production of toxic lipid intermediates, and increased reactive oxygen species 26. Increased visceral fat, frequently seen in the DM population, also results in the release of proinflammatory cytokines. Hyperglycemia-induced advanced glycation end-products impair microvascular function and decrease nitric oxide availability 26.

Sarcopenia is another common condition in HFpEF. Frail patients with HFpEF are frequently affected by sarcopenia, which is a major component of the pathophysiology of frailty 27. Sarcopenia, given the impairment of limb and respiratory skeletal muscles leading to further functional decline, may contribute to cardiovascular remodelling and dysfunction and to the development of HFpEF through systemic inflammation and different metabolic and endocrine abnormalities 28.

The incidence of new-onset depression is high in HF (5.7-7.9%). The pathophysiology underlying the adverse effect of depression in HF patients has not been delineated. Potential factors linking depression with HF include activation of inflammatory cascades, dysregulation of neurohormonal axes, arrhythmias, and behavioural effects 29.

All these comorbidities induce a systemic proinflammatory state with elevated plasma levels of interleukin (IL)-6, tumor necrosis factor (TNF)-a, soluble ST2 (sST2), and pentraxin 3 30. Coronary microvascular endothelial cells reactively produce reactive oxygen species, vascular cell adhesion molecule (VCAM), and E-selectin. Production of ROS leads to formation of peroxynitrite and reduction of nitric oxide bioavailability with consequent lower soluble guanylate cyclase (sGC) activity in cardiomyocytes. Lower sGC activity decreases cyclic guanosine monophosphate concentration and protein kinase G (PKG) activity. This represents a prohypertrophic stimuli inducing cardiomyocyte hypertrophy. Endothelial expression of VCAM and E-selectin is associated to monocytes migration into the subendothelium which release transforming growth factor, thus stimulating conversion of fibroblasts to myofibroblasts, with consequent deposition of collagen in the interstitial space.


Obesity promotes systemic inflammation 31 32 and exacerbates the inflammatory burden imposed by many chronic extracardiac comorbidities. Importantly, the chronic systemic inflammation related to obesity is accompanied by a significant increase of epicardial adipose tissue (EAT) mass 33. It is known that inflammation may lead to adipogenesis. This represents an adaptive mechanism preventing the deposition of proinflammatory fatty acids in cells 34. Interestingly, EAT is more sensitive to lipogenesis than other types of visceral adipose tissue 35. In fact, it contains plastic mesenchymal cells that are the source of progenitor cardiomyocytes during fetal development but, in adulthood, differentiate into adipocytes 36). Systemic inflammation affects the biology of EAT 37-39, promoting its transition toward a proinflammatory phenotype 40. Several observations support the hypothesis that the inflammation of EAT can act in a paracrine manner to influence the structure and function of neighboring tissues 41 42. Furthermore, the release of proinflammatory adipocytokines from EAT into the general circulation may contribute to the systemic inflammatory state; systemic inflammation, in turn, can promote the accumulation of EAT, which induces local and systemic inflammation and end-organ dysfunction, thus creating a bidirectional continuum 43-48.

Therefore, obesity, such as other extracardiac comorbidities, promotes changes in the physiological characteristics of EAT which starts to produce and secrete proinflammatory factors. Of these, leptin, tumor necrosis factor-a, interleukin 1-β, interleukin-6, and resistin promote the infiltration of macrophages, destroy microvascular systems, and activate profibrotic pathways 49-52. As regard to leptin, it is known that obesity is characterized by high circulating levels of aldosterone, secreted by adipocytes or directly released from the adrenal gland in response to leptin 53. This is also exacerbated by a loss of the antialdosterone action of natriuretic peptides given the increased neprilysin activity in obesity. Visceral adiposity also leads to increased signaling through the leptin receptor, which causes sodium retention by a direct action on the renal tubules. EAT-derived leptin promotes cardiac inflammation, microcirculatory abnormalities, and fibrosis. The resulting interaction of aldosterone and leptin promotes plasma volume expansion and regional and systemic inflammation and fibrosis.

Another important mechanism by which EAT may exert an unfavourable activity for the myocardium and causes cardiac damage depends on the migration of EAT derived mesenchymal stem cells to the neighboring myocardium and differentiation of these cells into fibroblasts 54-56.

There are several experimental and clinical studies indicating a relationship between EAT volume and inflammatory profile and the degree of cardiac inflammation 43 50 57 58. It is widely recognized that EAT, especially the periatrial fat, may represent an inflammatory substrate acting as a trigger for the development of atrial arrhythmias 59-64. Interestingly, increased volume and proinflammatory abnormalities of EAT are close to myocardial areas of myocardium characterized by marked electrophysiological derangement 65 66. In obese individuals, increased EAT volume is significantly associated with an impaired myocardial microcirculation, abnormalities of cardiac diastolic properties and increased vascular stiffness, and left atrial dilatation 67-70. In these patients, structural and functional abnormalities of EAT often precedes clinical presentation of HFpEF 71-74. Another important evidence supporting the role of EAT as transducer of inflammatory signals derives from the observation of the structural abnormalities of cardiac visceral fat in patients affected by chronic systemic inflammatory disorders. In this regard, patients with rheumatoid arthritis, human immunodeficiency, virus infection, psoriasis, show increased EAT mass that is also associated to alterations of cardiac microcirculation, myocardial fibrosis, and cardiac diastolic abnormalities, that are all typical of HFpEF 75-79. This may explain the significant higher risk of developing HF in these clinical settings.

If it is true that extracardiac comorbidities contribute to the pathogenesis of HFpEF, it is also evident that EAT may play a role, through the release of proinflammatory adipocytokines, in exacerbating the dysfunction of visceral organs, other than the heart. In fact, increased EAT volume is associated to inflammation and fibrosis in the kidneys, lungs, liver, and brain, whose dysfunction participates to the clinical features of HFpEF 80-82.


Cardiac sympathetic nervous system (SNS) hyperactivity is associated to HF 1-6 and represents a compensatory mechanism to the loss of cardiac contractility aiming at increasing myocardial inotropism to preserve cardiac output. However, in the long term, this mechanism is associated to unfavourable cardiac remodeling and increased mortality 83-88. In the failing heart, a defect of neuronal norepinephrine reuptake caused by post-transcriptional downregulation of the cardiac norepinephrine transporter 89-93 leads to an increase in norepinephrine concentration in the sympathetic synapses. This is responsible for impaired myocardial β-adrenergic receptor system and functional and anatomic sympathetic denervation of the heart 94 95.

Although SNS hyperactivity in HF is mainly mediated by norepinephrine-releasing neurons and by circulating norepinephrine and epinephrine, other mechanisms may contribute to sympathetic derangement. For example, the adipose tissue, particularly the visceral fat depots, may stimulate central SNS activity through dysregulated adipokines production and secretion 96 97. In addition, experimental studies have recently demonstrated that adipocytes produce and secrete both norepinephrine and epinephrine 98, thus indicating that the sympathetic fibers within adipose tissue are not the only source of catecholamines. In a recent study, Parisi et al have demonstrated, in HF patients, that EAT represents an important source of norepinephrine, whose levels are 2-fold higher than those found in plasma 99. Because of the EAT proximity to the myocardium, the increase in catecholamine content in this tissue could result in a negative feedback on cardiac sympathetic nerves, which are associated with the ventricular myocardium, thus inducing a functional and anatomic denervation of the heart. Therefore, in the context of a widespread SNS hyperactivity in HF, EAT seems to play an additive role in generating the final net effect of cardiac sympathetic denervation. In this study, the EAT thickness, assessed by echocardiography, was an independent predictor of 123I-MIBG planar and SPECT scintigraphic parameters (indexes of cardiac sympathetic innervation) and provided additional predictive information on cardiac adrenergic nerve activity respect to important demographic, clinical, and left ventricular function parameters. Therefore, assessing EAT thickness in patients with HF may provide surrogate information on the status of cardiac adrenergic derangement that is strongly correlated with worse prognosis in HF.

In another study, Parisi et al. also explored the relationship between the presence of sleep disordered breathing and EAT thickness in patients with HF 100. They found a significant correlation between the EAT increase and the presence and the severity of sleep apneas and a significant increase of circulating norepinephrine in patients with central sleep apnea (CSAs). These data confirm the results of previous study exploring SNS activation in HF patients with prevalent obstructive or central sleep apneas (CSAs). According to results of Parisi et al, all these studies indicate that CSAs are associated with a greater SNS activation 101-103).

Overall these evidence indicate EAT as a possible contributor to SNS activation in HF, thus reinforcing the negative activity of cardiac visceral fat in the pathogenesis and progression of HF.


Given the recognized role of EAT in the pathophysiology of HFpEF, it should be desirable to identify specific therapies targeting the cardiac visceral fat and able to modulate its pro-inflammatory profile and the negative effect of the inflammatory burden on the neighboring myocardium. The discovery of new drugs for HFpEF is dramatically needed since the lack, to date, of evidence based therapy able to ameliorate the outcomes of this syndrome. In this rewiew, we report the results of recent studies focusing on this topic.

Statins have been shown to reduce both EAT accumulation and inflammatory status in HF patients 104 105. In a recent study, Parisi et al. 106-108 explored, in a population of elderly patients with calcific aortic stenosis, a clinical model of HFpEF, whether statin therapy might affect EAT accumulation and inflammatory profile. Major findings of this study was that statin therapy was significantly associated to a reduced EAT thickness. Furthermore, the association between statin therapy and reduction of EAT accumulation was paralleled by an attenuation of EAT inflammatory profile. Finally, in vitro studies conducted on the EAT secretomes, obtained from patients with aortic stenosis, indicated that statin had a direct and selective anti-inflammatory effect on EAT.

These evidence may explain why statins, independently from their antihyperlipidemic effect, reduce the development of ventricular diastolic abnormalities, myocardial microcirculatory alterations, and cardiac fibrosis 109-111. Furthermore, the use of statins in patients with HFpEF is associated with a reduced risk of death in several observational studies 112 113.

Patients with type 2 diabetes show a marked increase in the amount of EAT and a high incidence of HFpEF has been reported in this population 114. Importantly, many antidiabetic drugs cause weight gain, thus inducing a further increase of adipogenesis and of EAT. In this regard, insulin increases the volume of EAT 39 73; this may explain, at least in part, why its use is associated with an increased risk of heart failure 115. Sulfonylureas promote the insulin activity on adipocytes and enhance the secretion of proinflammatory adipokines 116-118. Thiazolidinediones reduce EAT volume and inflammation and the secretion of proinflammatory adipocytokines 119-122.

Newer antihyperglycemic medications, such as glucagon-like peptide 1 receptor antagonists are typically associated with weight loss and may reduce the accumulation of EAT 123, although they do not revert its pro-inflammatory phenotype 124 125. This may explain why these drugs do not affect the HF outcome in clinical trials 126 127. Although other antidiabetic drugs, such as dipeptidyl peptidase-4 inhibitors are able to reduce the volume of EAT 128, they may exacerbate its inflammatory state and lead to cardiac fibrosis 129-131. This finding explains why dipeptidyl peptidase-4 inhibitors negatively affect cardiac remodeling and increase the risk of HF in patients with type 2 diabetes 132.

It has been recently demonstrated that sodium-glucose cotransporter 2 inhibitors not only reduce the amount of EAT, but also ameliorate its inflammation and its secretion of pro-atherosclerotic and pro-fibrotic cytokines 133 134. This may explain why these drugs reduce myocardial fibrosis and improve ventricular diastolic properties 135-137 and reduce the risk of several HF outcomes in observational studies and randomized controlled trials 138-141.

Given the ability of mineralocorticoid receptor antagonists, such as eplerenone to revert inflammation in visceral adipose tissue of obese individuals 142, further studies are desiderable to confirm this effect also in EAT. Preliminary data on these drugs indicate a favourable activity to reduce cardiovascular events in patients with HFpEF 143.

Recent encouraging evidence indicate a positive activity of neprilysin inhibition in HFpEF 144. This drug could counteract the breakdown of natriuretic peptides that is known to be accelerated in HFpEF.

Finally, the prominent role of inflammation in HFpEF represents an important motivation for the current research to explore the efficacy of drugs targeting circulating and local inflammatory mediators. The results of the recent CANTOS trial have demonstrated that inhibition of Interleukin 1β has potent effect on cardiovascular morbidity and mortality in patients with previous myocardial infarction 145. Future studies are needed the potential role of immune therapy also in HFpEF.


Accumulating evidence strongly support the role of structural and functional changes of EAT in the pathogenesis of HFpEF. Many inflammatory factors produced by cardiac visceral fat may penetrate the myocardium and coronary vessels in a paracrine and vasocrine manner and express their toxicity in the neighboring tissue. This promotes profound cardiac alterations such as fibrosis, alterations of left ventricular filling, derangement of electrophysiological properties, and sympathetic denervation that are all crucial factors for the development of HFpEF. Although it is widely recognized the multifactorial nature of HFpEF, EAT represents an intriguing target for future therapeutic strategies since its tight interconnection with the heart and its prominent role in enhance local and systemic inflammation. The epidemiological explosion of HFpEF and the lack of efficacious therapy strengthen the need to explore novel mechanisms and innovative therapeutic approaches to face the dramatic increase of cardiovascular deaths that are expected in the next decades.


  1. Rich MW, Kitzman DW, PRICE-III Organizing Committee; PRICE-III Investigators. Third pivotal research in cardiology in the elderly (PRICE-III) symposium: heart failure in the elderly: mechanisms and management. Am J Geriatr Cardiol. 2005; 14:250-61.
  2. Steinberg BA, Zhao X, Heidenreich PA. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012; 126:65-75.
  3. Owan TE, Hodge DO, Herges RM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006; 355:251-9.
  4. Bhatia RS, Tu JV, Lee DS. Outcome of heart failurewith preserved ejection fraction in a population-based study. N Engl J Med. 2006; 355:260-9.
  5. Liao L, Jollis JG, Anstrom KJ. Costs for heart failure with normal vs reduced ejection fraction. Arch Intern Med. 2006; 166:112-8.
  6. Fonarow GC, Stough WG, Abraham WT. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the optimize-hf registry. J Am Coll Cardiol. 2007; 50:768-77.
  7. Yancy CW, Lopatin M, Stevenson LW. Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the acute decompensated heart failure national registry (adhere) database. J Am Coll Cardiol. 2006; 47:76-84.
  8. Cacciatore F, Abete P, de Santis D. Mortality and blood pressure in elderly people with and without cognitive impairment. Gerontology. 2005; 51:53-61.
  9. Ungar A, Galizia G, Morrione A. Two-year morbidity and mortality in elderly patients with syncope. Age Ageing. 2011; 40:696-702.
  10. Cacciatore F, Abete P, Mazzella F. Six-minute walking test but not ejection fraction predicts mortality in elderly patients undergoing cardiac rehabilitation following coronary artery bypass grafting. Eur J Prev Cardiol. 2012; 19:1401-9.
  11. Ather S, Chan W, Bozkurt B. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012; 59:998-1005.
  12. Yusuf S, Pfeffer MA, Swedberg K. Effects of candesartan in patients with chronic heart failure and preserved left ventricular ejection fraction: the charm-preserved trial. Lancet. 2003; 362:777-81.
  13. Ahmed A, Rich MW, Fleg JL. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006; 114:397-403.
  14. Chan MM, Lam CS. How do patients with heart failure with preserved ejection fraction die?. Eur J Heart Fail. 2013; 15:604-13.
  15. Mangla A, Kane J, Beaty E. Comparison of predictors of heart failure-related hospitalization or death in patients with versus without preserved left ventricular ejection fraction. Am J Cardiol. 2013; 112:1907-12.
  16. van Heerebeek L, Hamdani N, Falcao-Pires I. Low myocardial protein kinase g activity in heart failure with preserved ejection fraction. Circulation. 2012; 126:830-9.
  17. Westermann D, Lindner D, Kasner M. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail. 2011; 4:44-52.
  18. Shah SJ, Heitner JF, Sweitzer NK. Baseline characteristics of patients in the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial. Circ Heart Fail. 2013; 6:184-92.
  19. Rusinaru D, Buiciuc O, Houpe D. Renal function and long-term survival after hospital discharge in heart failure with preserved ejection fraction. Int J Cardiol. 2011; 147:278-82.
  20. Dryer SE, Reiser J.. Trpc6 channels and their binding partners in podocytes: role in glomerular filtration and pathophysiology. Am J Physiol Renal Physiol. 2010; 299:F689-701.
  21. Eder P, Molkentin JD. Trpc channels as effectors of cardiac hypertrophy. Circ Res. 2011; 108:265-72.
  22. Davis J, Burr AR, Davis GF. A trpc6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo. Developmental cell. 2012; 23:705-15.
  23. Ather S, Chan W, Bozkurt B. Impact of noncardiac comorbidities on morbidity and mortality in a predominantly male population with heart failure and preserved versus reduced ejection fraction. J Am Coll Cardiol. 2012; 59:998-1005.
  24. Triposkiadis F, Giamouzis G, Parissis J. Reframing the association and significance of co-morbidities in heart failure. Eur J of Heart Failure. 2016; 18:744-58.
  25. Macdougall IC, Canaud B, de Francisco AL. Beyond the cardiorenal anaemia syndrome: recognizing the role of iron deficiency. Eur J Heart Fail. 2012; 14:882-6.
  26. McHugh K, DeVore AD, Wu J. Heart failure with preserved ejection fraction and diabetes. J Am Coll Cardiol. 2019; 73:602-11.
  27. Martone AM, Bianchi L, Abete P. The incidence of sarcopenia among hospitalized older patients: results from the Glisten study. J Cachexia Sarcopenia Muscle. 2017; 8:907-14.
  28. Kinugasa Y, Yamamoto K.. The challenge of frailty and sarcopenia in heart failure with preserved ejection fraction. Heart. 2017; 103:184-9.
  29. Luijendijk HJ, Tiemeier H, van den Berg JF. Heart failure and incident late-life depression. J Am Geriatr Soc. 2010; 58:1441-8.
  30. Paulus WJ, Tschöpe C.. A novel paradigm for heart failure with preserved ejection fraction. J Am Coll Cardiol. 2013; 62:263-71.
  31. Ghigliotti G, Barisione C, Garibaldi S. Adipose tissue immune response: novel triggers and consequences for chronic inflammatory conditions. Inflammation. 2014; 37:1337-53.
  32. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005; 96:939-49.
  33. Packer M. Epicardial adipose tissue may mediate deleterious effects of obesity and inflammation on the myocardium. J Am Coll Cardiol. 2018; 71:2360-72.
  34. Wernstedt Asterholm I, Tao C, Morley TS. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab. 2014; 20:103-18.
  35. Marchington JM, Pond CM. Site-specific properties of pericardial and epicardial adipose tissue: the effects of insulin and high-fat feeding on lipogenesis and the incorporation of fatty acids in vitro. Int J Obes. 1990; 14:1013-22.
  36. von Gise A, Pu WT. Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease. Circ Res. 2012; 110:1628-45.
  37. Thalmann S, Meier CA. Local adipose tissue depots as cardiovascular risk factors. Cardiovasc Res. 2007; 75:690-701.
  38. Mach L, Bedanova H, Soucek M. Impact of cardiopulmonary bypass surgery on cytokines in epicardial adipose tissue: comparison with subcutaneous fat. Perfusion. 2017; 32:279-84.
  39. Hirata Y, Kurobe H, Akaike M. Enhanced inflammation in epicardial fat in patients with coronary artery disease. Int Heart J. 2011; 52:139-42.
  40. Shibasaki I, Nishikimi T, Mochizuki Y. Greater expression of inflammatory cytokines, adrenomedullin, and natriuretic peptide receptor-C in epicardial adipose tissue in coronary artery disease. Regul Pept. 2010; 165:210-7.
  41. Verhagen SN, Visseren FL. Perivascular adipose tissue as a cause of atherosclerosis. Atherosclerosis. 2011; 214:3-10.
  42. Aghamohammadzadeh R, Unwin RD, Greenstein AS. Effects of obesity on perivascular adipose tissue vasorelaxant function: nitric oxide, inflammation and elevated systemic blood pressure. J Vasc Res. 2015; 52:299-305.
  43. Lai YH, Yun CH, Yang FS. Epicardial adipose tissue relating to anthropometrics, metabolic derangements and fatty liver disease independently contributes to serum high-sensitivity C-reactive protein beyond body fat composition: a study validated with computed tomography. J Am Soc Echocardiogr. 2012; 25:234-41.
  44. Nakanishi K, Fukuda S, Tanaka A. Epicardial adipose tissue accumulation is associated with renal dysfunction and coronary plaque morphology on multidetector computed tomography. Circ J. 2016; 80:196-201.
  45. Cheng KH, Chu CS, Lee KT. Adipocytokines and proinflammatory mediators from abdominal and epicardial adipose tissue in patients with coronary artery disease. Int J Obes (Lond). 2008; 32:268-74.
  46. Kotulák T, Drápalová J, Kopecký P. Increased circulating and epicardial adipose tissue mRNA expression of fibroblast growth factor-21 after cardiac surgery: possible role in postoperative inflammatory response and insulin resistance. Physiol Res. 2011; 60:757-67.
  47. Aydin H, Toprak A, Deyneli O. Epicardial fat tissue thickness correlates with endothelial dysfunction and other cardiovascular risk factors in patients with metabolic syndrome. Metab Syndr Relat Disord. 2010; 8:229-34.
  48. Christensen RH, von Scholten BJ, Hansen CS. Epicardial, pericardial and total cardiac fat and cardiovascular disease in type 2 diabetic patients with elevated urinary albumin excretion rate. Eur J Prev Cardiol. 2017; 24:1517-24.
  49. Gruzdeva OV, Akbasheva OE, Dyleva YA. Adipokine and cytokine profiles of epicardial and subcutaneous adipose tissue in patients with coronary heart disease. Bull Exp Biol Med. 2017; 163:608-11.
  50. Patel VB, Basu R, Oudit GY. ACE2/Ang 1-7 axis: a critical regulator of epicardial adipose tissue inflammation and cardiac dysfunction in obesity. Adipocyte. 2016; 5:306-11.
  51. Company JM, Booth FW, Laughlin MH. Epicardial fat gene expression after aerobic exercise training in pigs with coronary atherosclerosis: relationship to visceral and subcutaneous fat. J Appl Physiol (1985). 2010; 109:1904-12.
  52. Bambace C, Sepe A, Zoico E. Inflammatory profile in subcutaneous and epicardial adipose tissue in men with and without diabetes. Heart Vessels. 2014; 29:42-8.
  53. Packer M. Leptin-aldosterone-neprilysin axis. Identification of its distinctive role in the pathogenesis of the three phenotypes of heart failure in people with obesity. Circulation. 2018; 137:1614-31.
  54. Naftali-Shani N, Itzhaki-Alfia A, Landa-Rouben N. The origin of human mesenchymal stromal cells dictates their reparative properties. J Am Heart Assoc. 2013; 2:e000253.
  55. Naftali-Shani N, Levin-Kotler LP, Palevski D. Left ventricular dysfunction switches mesenchymal stromal cells toward an inflammatory phenotype and impairs their reparative properties via toll-like receptor-4. Circulation. 2017; 135:2271-87.
  56. Ruiz-Villalba A, Simón AM, Pogontke C. Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar. J Am Coll Cardiol. 2015; 65:2057-66.
  57. Patel VB, Mori J, McLean BA. ACE2 deficiency worsens epicardial adipose tissue inflammation and cardiac dysfunction in response to diet-induced obesity. Diabetes. 2016; 65:85-95.
  58. Wu CK, Tsai HY, Su MM. Evolutional change in epicardial fat and its correlation with myocardial diffuse fibrosis in heart failure patients. J Clin Lipidol. 2017; 11:1421-31.
  59. Lin YK, Chen YC, Chang SL. Heart failure epicardial fat increases atrial arrhythmogenesis. Int J Cardiol. 2013; 167:1979-83.
  60. Hatem SN, Sanders P.. Epicardial adipose tissue and atrial fibrillation. Cardiovasc Res. 2014; 102:205-13.
  61. Yorgun H, Canpolat U, Aytemir K. Association of epicardial and peri-atrial adiposity with the presence and severity of non-valvular atrial fibrillation. Int J Cardiovasc Imaging. 2015; 31:649-57.
  62. Kusayama T, Furusho H, Kashiwagi H. Inflammation of left atrial epicardial adipose tissue is associated with paroxysmal atrial fibrillation. J Cardiol. 2016; 68:406-11.
  63. Mahajan R, Lau DH, Brooks AG. Electrophysiological electroanatomical, and structural remodeling of the atria as consequences of sustained obesity. J Am Coll Cardiol. 2015; 66:1-11.
  64. Venteclef N, Guglielmi V, Balse E. Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur Heart J. 2015; 36:795-805.
  65. Nagashima K, Okumura Y, Watanabe I. Does location of epicardial adipose tissue correspond to endocardial high dominant frequency or complex fractionated atrial electrogram sites during atrial fibrillation?. Circ Arrhythm Electrophysiol. 2012; 5:676-83.
  66. Zghaib T, Ipek EG, Zahid S. Association of left atrial epicardial adipose tissue with electrogram bipolar voltage and fractionation: electrophysiologic substrates for atrial fibrillation. Heart Rhythm. 2016; 13:2333-9.
  67. Nakanishi K, Fukuda S, Tanaka A. Relationships between periventricular epicardial adipose tissue accumulation, coronary microcirculation, and left ventricular diastolic dysfunction. Can J Cardiol. 2017; 33:1489-97.
  68. Natale F, Tedesco MA, Mocerino R. Visceral adiposity and arterial stiffness: echocardiographic epicardial fat thickness reflects, better than waist circumference, carotid arterial stiffness in a large population of hypertensives. Eur J Echocardiogr. 2009; 10:549-55.
  69. Iacobellis G, Leonetti F, Singh N. Relationship of epicardial adipose tissue with atrial dimensions and diastolic function in morbidly obese subjects. Int J Cardiol. 2007; 115:272-3.
  70. Ozturk C, Balta S, Demirkol S. Epicardial adipose tissue thickness may be related diastolic dysfunction in obese adolescents. Eur Rev Med Pharmacol Sci. 2014; 18:1109.
  71. Hage C, Michaëlsson E, Linde C. Inflammatory biomarkers predict heart failure severity and prognosis in patients with heart failure with preserved ejection fraction: a holistic proteomic approach. Circ Cardiovasc Genet. 2017; 10:e001633.
  72. Chan MM, Santhanakrishnan R, Chong JP. Growth differentiation factor 15 in heart failure with preserved vs reduced ejection fraction. Eur J Heart Fail. 2016; 18:81-8.
  73. Glezeva N, Voon V, Watson C. Exaggerated inflammation and monocytosis associate with diastolic dysfunction in heart failure with preserved ejection fraction: evidence of M2 macrophage activation in disease pathogenesis. J Card Fail. 2015; 21:167-77.
  74. Lam CS, Lyass A, Kraigher-Krainer E. Cardiac dysfunction and noncardiac dysfunction as precursors of heart failure with reduced and preserved ejection fraction in the community. Circulation. 2011; 124:24-30.
  75. Mavrogeni S, Karabela G, Stavropoulos E. Imaging patterns of heart failure in rheumatoid arthritis evaluated by cardiovascular magnetic resonance. Int J Cardiol. 2013; 168:4333-5.
  76. Holloway CJ, Ntusi N, Suttie J. Comprehensive cardiac magnetic resonance imaging and spectroscopy reveal a high burden of myocardial disease in HIV patients. Circulation. 2013; 128:814-22.
  77. Davis JM, Lin G, Oh JK. Five-year changes in cardiac structure and function in patients with rheumatoid arthritis compared with the general population. Int J Cardiol. 2017; 240:379-85.
  78. Fontes-Carvalho R, Mancio J, Marcos A. HIV patients have impaired diastolic function that is not aggravated by anti-retroviral treatment. Cardiovasc Drugs Ther. 2015; 29:31-9.
  79. Ozden HK, Polat M, Ozturk S. Assessment of subclinical cardiac damage in chronic plaque psoriasis patients: a case control study. Arch Med Sci Atheroscler Dis. 2016; 1:e126-32.
  80. Ozturk MT, Ebinç FA, Okyay GU. Epicardial adiposity is associated with microalbuminuria in patients with essential hypertension. Acta Cardiol Sin. 2017; 33:74-80.
  81. Kiraz K, Gökdeniz T, Kalaycıoglu E. Epicardial fat thickness is associated with severity of disease in patients with chronic obstructive pulmonary disease. Eur Rev Med Pharmacol Sci. 2016; 20:4508-15.
  82. Akıl E, Akıl MA, Varol S. Echocardiographic epicardial fat thickness and neutrophil to lymphocyte ratio are novel inflammatory predictors of cerebral ischemic stroke. J Stroke Cerebrovasc Dis. 2014; 23:2328-34.
  83. Lymperopoulos A, Rengo G, Koch WJ. Adrenergic nervous system iheart failure: pathophysiology and therapy. Circ Res. 2013; 113:739-53.
  84. Rengo G, Lymperopoulos A, Koch WJ. Future G protein-coupled receptor targets for treatment of heart failure. Curr Treat Options Cardiovasc Med. 2009; 11:328-38.
  85. Triposkiadis F, Karayannis G, Giamouzis G. The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications. J Am Coll Cardiol. 2009; 54:1747-62.
  86. Iaccarino G, Barbato E, Cipolletta E. Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure. Eur Heart J. 2005; 26:1752-8.
  87. Rengo G, Perrone-Filardi P, Femminella GD. Targeting the β-adrenergic receptor system through G-protein-coupled receptor kinase2: a new paradigm for therapy and prognostic evaluation in heart failure: from bench to bedside. Circ Heart Fail. 2012; 5:385-91.
  88. Rengo G., Lymperopoulos A, Leosco D. GRK2 as a novel gene therapy target in heart failure. J Mol Cell Cardiol. 2011; 50:785-92.
  89. Böhm M, La Rosée K, Schwinger RH. Evidence for reduction of norepinephrine uptake sites in the failing human heart. J Am Coll Cardiol. 1995; 25:146-53.
  90. Ungerer M, Hartmann F, Karoglan M. Regional in vivo and in vitro characterization of autonomic innervation in cardiomyopathic human heart. Circulation. 1998; 97:174-80.
  91. Backs J, Haunstetter A, Gerber SH. The neuronal norepinephrine transporter in experimental heart failure: evidence for a posttranscriptional downregulation. J Mol Cell Cardiol. 2001; 33:461-72.
  92. Paolillo S, Rengo G, Pagano G. Impact of diabetes on cardiac sympathetic innervation in patients with heart failure: a 123I metaiodobenzylguanidine (123I MIBG) scintigraphic study. Diabetes Care. 2013; 36:2395-401.
  93. Jacobson AF, Senior R, Cerqueira MD, ADMIRE-HF Investigators. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010; 55:2212-21.
  94. Mardon K, Montagne O, Elbaz N. Uptake-1 carrier downregulates in parallel with the beta-adrenergic receptor desensitization in rat hearts chronically exposed to high levels of circulating norepinephrine: implications for cardiac neuroimaging in human cardiomyopathies. J Nucl Med. 2003; 44:1459-66.
  95. Bristow MR, Ginsburg R, Minobe W. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med. 1982; 307:205-11.
  96. Maffei M, Halaas J, Ravussin E. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995; 1:1155-61.
  97. Considine RV, Sinha MK, Heiman ML. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996; 334:292-5.
  98. Vargovic P, Ukropec J, Laukova M. Adipocytes as a new source of catecholamine production. FEBS Lett. 2011; 585:2279-84.
  99. Parisi V, Rengo G, Perrone-Filardi P. Increased epicardial adipose tissue volume correlates with cardiac sympathetic denervation in patients with heart failure. Circ Res. 2016; 118:1244-53.
  100. Parisi V, Paolillo S, Rengo G. Sleep-disordered breathing and epicardial adipose tissue in patients with heart failure. Nutr Metab Cardiovasc Dis. 2018; 28:126-32.
  101. Naughton MT, Benard DC, Liu PP. Effects of nasal CPAP on sympathetic activity in patients with heart failure and central sleep apnea. Am J Respir Crit Care Med. 1995; 152:e473-9.
  102. Solin P, Kaye DM, Little PJ. Impact of sleep apnea on sympathetic nervous system activity in heart failure. Chest. 2003; 123:e1119-26.
  103. Mansfield D, Kaye DM, La Rocca BH. Raised sympathetic nerve activity in heart failure and central sleep apnea is due to heart failure severity. Circulation. 2003; 107:e1396-400.
  104. Soucek F, Covassin N, Singh P. Effects of atorvastatin (80 mg) therapy on quantity of epicardial adipose tissue in patients undergoing pulmonary vein isolation for atrial fibrillation. Am J Cardiol. 2015; 116:1443-6.
  105. Cho KI, Kim BJ, Cha TJ. Impact of duration and dosage of statin treatment and epicardial fat thickness on the recurrence of atrial fibrillation after electrical cardioversion. Heart Vessels. 2015; 30:490-7.
  106. Parisi V, Petraglia L, D’Esposito V. Statin therapy modulates thickness and inflammatory profile of human epicardial adipose tissue. Int J Cardiol. 2019; 274:326-30.
  107. Parisi V, Rengo G, Pagano G. Epicardial adipose tissue has an increased thickness and is a source of inflammatory mediators in patients with calcific aortic stenosis. Int J Cardiol. 2015; 186:167-9.
  108. Parisi V, Leosco D, Ferro G. The lipid theory in the pathogenesis of calcific aortic stenosis. Nutr Metabob Cardiovasc Dis. 2015; 25:519-25.
  109. Wu CK, Yeh CF, Chiang JY. Effects of atorvastatin treatment on left ventricular diastolic function in peritoneal dialysis patients-the ALEVENT clinical trial. J Clin Lipidol. 2017; 11:657-66.
  110. Beck AL, Otto ME, D’Avila LB. Diastolic function parameters are improved by the addition of simvastatin to enalapril-based treatment in hypertensive individuals. Atherosclerosis. 2012; 222:444-8.
  111. Akahori H, Tsujino T, Naito Y. Atorvastatin ameliorates cardiac fibrosis and improves left ventricular diastolic function in hypertensive diastolic heart failure model rats. J Hypertens. 2014; 32:1534-41.
  112. Fukuta H, Goto T, Wakami K. The effect of statins on mortality in heart failure with preserved ejection fraction: a meta-analysis of propensity score analyses. Int J Cardiol. 2016; 214:301-6.
  113. Liu G, Zheng XX, Xu YL. Meta-analysis of the effect of statins on mortality in patients with preserved ejection fraction. Am J Cardiol. 2014; 113:1198-204.
  114. Altara R, Giordano M, Nordén ES. Targeting obesity and diabetes to treat heart failure with preserved ejection fraction. Front Endocrinol (Lausanne). 2017; 8:160.
  115. Ferrara N, Abete P, Corbi G. Insulin-induced changes in beta-adrenergic response: an experimental study in the isolated rat papillary muscle. Am J Hypertens. 2005; 18:348-53.
  116. Nichols GA, Koro CE, Gullion CM. The incidence of congestive heart failure associated with antidiabetic therapies. Diabetes Metab Res Rev. 2005; 21:51-7.
  117. Shi H, Moustaid-Moussa N, Wilkison WO. Role of the sulfonylurea receptor in regulating human adipocyte metabolism. FASEB J. 1999; 13:1833-8.
  118. Haffner SM, Hanefeld M, Fischer S. Glibenclamide, but not acarbose, increases leptin concentrations parallel to changes in insulin in subjects with NIDDM. Diabetes Care. 1997; 20:1430-4.
  119. Grosso AF, de Oliveira SF, Higuchi Mde L. Synergistic antiinflammatory effect: simvastatin and pioglitazone reduce inflammatory markers of plasma and epicardial adipose tissue of coronary patients with metabolic syndrome. Diabetol Metab Syndr. 2014; 6:47.
  120. Sacks HS, Fain JN, Cheema P. Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: changes associated with pioglitazone. Diabetes Care. 2011; 34:730-3.
  121. Distel E, Penot G, Cadoudal T. Early induction of a brown-like phenotype by rosiglitazone in the epicardial adipose tissue of fatty Zucker rats. Biochimie. 2012; 94:1660-7.
  122. Della-Morte D, Palmirotta R, Rehni AK. Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors. Pharmacogenomics. 2014; 15:2063-82.
  123. Dutour A, Abdesselam I, Ancel P. Exenatide decreases liver fat content and epicardial adipose tissue in patients with obesity and type 2 diabetes: a prospective randomized clinical trial using magnetic resonance imaging and spectroscopy. Diabetes Obes Metab. 2016; 18:882-91.
  124. Pastel E, McCulloch LJ, Ward R. GLP-1 analogue-induced weight loss does not improve obesity-induced AT dysfunction. Clin Sci (London). 2017; 131:343-53.
  125. Al-Barazanji KA, Arch JR, Buckingham RE. Central exendin-4 infusion reduces body weight without altering plasma leptin in (fa/fa) Zucker rats. Obes Res. 2000; 8:317-23.
  126. Marso SP, Daniels GH, Brown-Frandsen K. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375:311-22.
  127. Marso SP, Bain SC, Consoli A. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375:1834-44.
  128. Lima-Martínez MM, Paoli M, Rodney M. Effect of sitagliptin on epicardial fat thickness in subjects with type 2 diabetes and obesity: a pilot study. Endocrine. 2016; 51:448-55.
  129. Mulvihill EE, Varin EM, Ussher JR. Inhibition of dipeptidyl peptidase-4 impairs ventricular function and promotes cardiac fibrosis in high fat-fed diabetic mice. Diabetes. 2016; 65:742-54.
  130. Jackson EK, Zhang Y, Gillespie DD. SDF-1a (stromal cell-derived factor 1a) induces cardiac fibroblasts, renal microvascular smooth muscle cells, and glomerular mesangial cells to proliferate, cause hypertrophy, and produce collagen. J Am Heart Assoc. 2017; 6:e007253.
  131. Chu PY, Zatta A, Kiriazis H. CXCR4 antagonism attenuates the cardiorenal consequences of mineralocorticoid excess. Circ Heart Fail. 2011; 4:651-8.
  132. McMurray JJV, Ponikowski P, Bolli GB. Effects of vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure: a randomized placebo-controlled trial. J Am Coll Cardiol HF. 2018; 6:8-17.
  133. Bouchi R, Terashima M, Sasahara Y. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study. Cardiovasc Diabetol. 2017; 16:32.
  134. Fukuda T, Bouchi R, Terashima M. Ipragliflozin reduces epicardial fat accumulation in non-obese type 2 diabetic patients with visceral obesity: a pilot study. Diabetes Ther. 2017; 8:851-61.
  135. Hammoudi N, Jeong D, Singh R. Empagliflozin improves left ventricular diastolic dysfunction in a genetic model of type 2 diabetes. Cardiovasc Drugs Ther. 2017; 31:233-46.
  136. Habibi J, Aroor AR, Sowers JR. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes. Cardiovasc Diabetol. 2017; 16:9.
  137. Kusaka H, Koibuchi N, Hasegawa Y. Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome. Cardiovasc Diabetol. 2016; 15:157.
  138. Joubert M, Jagu B, Montaigne D. The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents cardiomyopathy in a diabetic lipodystrophic mouse model. Diabetes. 2017; 66:1030-40.
  139. Eurich DT, Weir DL, Majumdar SR. Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circ Heart Fail. 2013; 6:395-402.
  140. Zinman B, Wanner C, Lachin JM. Empagliflozin, cardiovascular out-comes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373:2117-28.
  141. Neal B, Perkovic V, Mahaffey KW. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377:644-57.
  142. Guo C, Ricchiuti V, Lian BQ. Mineralocorticoid receptor blockade reverses obesity related changes in expression of adiponectin, peroxisome proliferator-activated receptorgamma, and proinflammatory adipokines. Circulation. 2008; 117:2253-61.
  143. Anand IS, Claggett B, Liu J. Interaction between spironolactone and natriuretic peptides in patients with heart failure and preserved ejection fraction: from the TOPCAT trial. J Am Coll Cardiol HF. 2017; 5:241-52.
  144. Solomon SD, Zile M, Pieske B. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012; 380:1387-95.
  145. Ridker PM, Everett BM, Thuren T. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017; 377:1119-31.


D. Leosco

Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy

L. Petraglia

Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy

F.V. Grieco

Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy

M. Conte

Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy

N. Ferrara

Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy

V. Parisi

Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy


© Società Italiana di Gerontologia e Geriatria (SIGG) , 2019

How to Cite

Leosco, D., Petraglia, L., Grieco, F., Conte, M., Ferrara, N. and Parisi, V. 2019. Proinflammatory phenotype of cardiac visceral fat in heart failure with preserved ejection fraction in the elderly. JOURNAL OF GERONTOLOGY AND GERIATRICS. 67, 3 Suppl (Sep. 2019), 195-204.
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