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M. Sadouni¹ ³, M. Durand¹ ² ³, A. Chin¹ ² ³, S. M. Le ², J. Chalaoui ², C. Tremblay¹ ² ³, C. Chartrand-Lefebvre¹ ² ³
1. Université de Montréal, Montréal, Québec, Canada.2. CHUM, Montréal, Québec, Canada.3. CRCHUM, Montréal, Québec, Canada.
World Congress of Thoracic Imaging (Boston)Society of Thoracic Radiology (STR)
June 18-21 (2017)
M. Sadouni : None.
M. Durand : None.
A. Chin : None.
S. M. Le : None.
J. Chalaoui : None.
C. Tremblay : None.
C. Chartrand-Lefebvre : ◦ Equipment loan : Philips, Bayer.◦ Research collaboration : Philips, Terarecon, Siemens
Objectives of this educational exhibit are to understand:
Anatomy and physiology of epicardial fat.
Method of measurement of epicardial fat.
Relationships of epicardial fat with coronary artery disease in general population and in HIV-infected patients.
Since the introduction of the highly activeantiretroviral therapy, life expectancy ofHIV individuals has dramatically improve,now, approaching that of generalpopulation(1).
Unfortunately, although HIV patients livelonger, they are subject to age-relateddiseases such as coronary artery disease (2).
Moreover, the risk for coronary arterydisease seems to be greater than of noninfected persons (3) .
Aids-related29 %
Liver-related13 %
Non-Aidscancer15 %
CVD11 %
Non natural10.5 %
Other / Unknown22.5%
Figure1 : Causes of death of HIV infectedpatients (adapted from the D:A:D study)
Risk stratification in the HIV patient population is of great importance.However, scores actually used underestimate cardiovascular disease risk,and probably do not take into account how specific is the HIV population(4,5).
Assessment of novel cardiovascular risk factors specific for this populationis needed.
More recently, epicardial fat has emerged as a potential risk biomarkerdue to the key localization of this fat depot, its metabolic properties andclinical measurability.
Epicardial fat is the visceral fat of the heart. It covers 80 % of its surface and represent 20 % of its weight (6).
Epicardial fat predominates in the atrioventricular and interventricular grooves around cardiac blood vessels. It can extend to cover the surface of the atria and/or ventricles and in extreme cases may cover the entire epicardial surface (7).
Epicardial fat is a dynamic fat depot. Its mass increases with age. It can also increase, or remodel, in conditions such as obesity and inflammation (6).
A BFigure 1 : Human epicardialfat. (A) anterior view of a normal heart. (B) anterior view of a hypertrophic heart. In the normal heart, the fat distribution is limited tothe atrioventricular and interventricular grooves. In the hypertrophic, the adipose tissue also fills the epicardial spaces between these sites. Iacobellis et al. Reprinted by permission from Macmillan Publishers Ltd: [Nature Clinical Practice Cardiovascular Medicine] (2, 536-543 doi:10.1038/ncpcardio0319), copyright (2005). http://www.nature.com/nrcardio/journal/v4/n9/full/ncpcardio0984.html
Epicardial fat is located between the visceral layerof pericardium and myocardium without astructure or fascia separating it from themyocardium and the epicardial vessels.
The coronary arteries are immersed in theepicardial fat allowing them to interact very closelywith it.
Figure 2 : Localization of epicardial fat. Iacobellis et al., 2015.Reprinted by permission from Macmillan Publishers Ltd: [Nature Reviews Endocrinology] (11, 363–371 (2015) doi:10.1038/nrendo.2015.58), copyright (2005). http://www.nature.com/nrcardio/journal/v4/n9/full/ncpcardio0984.html
Figure 3 : Macroscopic view of epicardial fat. Basel el Aloul et al. I ClinMed Res. 2015 Apr; 7(4): 270–273.doi:10.14740/jocmr1986w(open Access).
Epicardial fat has to be distinguished from the fat that is situated outside the visceral pericardium, the paracardial fat.
Both epicardial fat and paracardial fat form the pericardial fat (also called cardiac fat or mediastinal fat).
Epicardial fat Paracardial fat
Anatomy
Between the myocardium and visceral layer of
pericardium
Outside the visceral pericardium
EmbryologySplanchnopleuric
mesoderm Primitive thoracic mesenchyme
Vascularization coronary arteries
Pericardiophrenicbranches of the
internalmammary artery
Table 1 : Differences between epicardial fat and paracardial fat
Visceral pericardium
Paracardial fat
Epicardial fat
Figure 4 : Removal of paracardial fat allowing to reveal epicardial fat. Nelson et al. Journal of Cardiovascular Magnetic Resonance 2009;11:15. DOI: 10.1186/1532-429X-11-15. (Open access)
Epicardial fat is considered as a “beige” or “brite” adipose tissue : it has the phenotype of white adipose tissue but produce “Uncoupling Protein 1” (UCP1), a marker of brown adipocytes.
Epicardial fat is composed of adipocytes and pre-adipocytes; It contains nervous and nodal tissue, as well as inflammatory, stromal and immune cells within it.
Figure 5 : Microscopic appearance of the epicardial fat in the right ventricle. Iacobellis et al. Reprinted by permission from Macmillan Publishers Ltd: [Nature ClinicalPractice Cardiovascular Medicine] (2, 536-543 doi:10.1038/ncpcardio0319), copyright (2005). http://www.nature.com/nrcardio/journal/v4/n9/full/ncpcardio0984.html
Epicardial fat
Myocardium
Epicardial fat, as a beige adipose tissue, combines secretory functions of white adipose tissue and thermogenic functions of brown adipose tissue.
Epicardial fat has the particularity to release and uptake free fatty acids greater than other fat depots and secrets a higher proportion of pro-inflammatory cytokines (8).
lipid and glucidmetabolism
Inflammation
Kidney function
Coagulation / fibrinolysis
AdipokinesAdiponectin
LeptinAdrenomodulin
OmentinIL6, IL8, TNFα…
Mechanical support
Absorb and release fatty acids at times of
high demand
BAT function Thermogenesis to
defend myocardium against hypothermia
WAT function
Hematopoiesis
Angiogenesis
How to evaluate epicardial fat?
During the last few years, there was a great interest in imaging epicardial fat as an indicator of the general adiposity or to predict incident cardiovascular events. Imaging epicardial fat has been used also to follow treatment (statins, weight loss….).
Epicardial fat can be measured by a variety of different imaging techniques including:
- Transthoracic echocardiography- Cardiac CT- Cardiac MRI
There is no consensus on what quantity of epicardial fat is considered to be “normal”.
Probably the easiest, cheapest and non invasive method for evaluating epicardial fat.
Epicardial fat is visible as an echo free space between the myocardium and the visceral layer of the pericardium.
The thickness is measured perpendicularly to the right ventricle free wall in the parasternal long and short axis views where EAT is thought to be thickest at the end of systole in 3 cardiac cycles. Systolic measurement is more accurate, and avoids chances of uneven fat compression which could occur in diastole.
Figure 6 : Transthoracic 2D echocardiographic of heart. AO, aortic root; LA, left atrium; LV, left ventricle; RV, right ventricle. Reprinted by permission from Macmillan Publishers Ltd: [Nature Reviews Endocrinology] (11, 363–371 (2015) doi:10.1038/nrendo.2015.58), copyright (2005). http://www.nature.com/nrcardio/journal/v4/n9/full/ncpcardio0984.html
RV
LV
LA
AO
Figure 7 :Epicardial fat measurement by echocardiography in the parasternal long and short axis views . Epicardial fat (indicated by arrows) with increased thickness (A and B) and minimum epicardial fat (C and D). Bertaso et al. ArgBras Cardiol 2013 Jul; 101(1): e18–e28.doi: 10.5935/abc.20130138. (Open access)
Most of clinical studies using echocardiography have reported excellentinterobserver and intraobserver agreement for epicardial fat thicknessmeasurement (9,10).
A main disadvantage of ultrasound is that it does not reflect the asymmetricdistribution of fat surrounding the heart, not does it enable to assess total fatvolume
It is possible to measure epicardial fat with CTscanners with 16 or more detectors.
Cardiac CT for both coronary calcium scoringand coronary CT angiography allows accuratemeasurement of epicardial fat.
Cardiac CT allows the measurement of thevolume, the area and the thickness ofepicardial fat.
Standard fat attenuation values are used todefine fat attenuation by CT; for non-contrastCT typically an attenuation range between -190and -30 Hounsfield units is used (as shown infigure A).
A
1. Epicardial fat volume quantification : A predefined threshold of -190 to -30 HU is
applied to identify voxels consisting of fat.
The pericardium is than traced of manually or via a semi-automated process to exclude any extra cardiac fat on 6 – 8 axial sections.
The superior extent for the epicardial fat measurements is defined as the bifurcation of the pulmonary artery and the inferior extent as the end of the pericardial sac.
The fat voxels were than summed to obtain the total epicardial fat volume with a dedicated software.
2. Epicardial fat area : measured on the slice where the epicardial fat is the most predominant.
3. Epicardial fat thickness :measured at the level of the right coronary artery and the left descending coronary artery.
4. Pericoronary epicardial fat volume: can also be measured.
CT disadvantages include exposure to ionizing radiation and a relatively high cost.
Interscan reproducibility for measurement of epicardial fat is high, with correlation coefficients ≥0.98 for the same multidetector CT scanner (11).
Figure 7 : Epicardial fat measurement by cardiac CT. Epicardial fat (indicated in green)with increased volume (A and B) and minimum epicardial fat (C and D).
A B C D
MRI is considered the gold standard for the evaluation of the adipose tissue.Itprovides the most specific and precise measurements of epicardial fat volume (12-14).
Quantification of epicardial fat volume is similar to cardiac CT, by tracing the pericardium and epicardial fat voxels are added in each slice.
While the image resolution and accuracy of CMR is greater than CT, it is also far more costly and less accessible.
Figure 8 : Quantification of epicardial fat with CMR. Nelson et al. Journal of Cardiovascular Magnetic Resonance 2009;11:15. DOI: 10.1186/1532-429X-11-15. Bertaso et al. . Arg Bras Cardiol 2013 Jul; 101(1): e18–e28. doi: 10.5935/abc.20130138. (Open access)
Epicardial fat and coronary artery disease (CAD)
A significant amount of research has investigated the link between increased Epicardial fat and CAD (15-18).
Overall, most observational studies identified a direct association between the amount of EF and the presence/severity of coronary artery disease (CAD) as well with MACE (Major adverse cardiac events).
Authors Imaging technique N Exposure Outcome Measure of
association
Mustelier et al. 2011
echocardiography 250 Thickness EF ≥ 5.2 mm
in systoleCAD(sténose ≥50%)
OR: 1.27 (95% IC: 1.1 - 1.5)
Yerramasu et al. 2012 CT 333 EF Volume CAC score OR: 1.13 (95%
IC: 1.04 - 1.22)
Cheng et al.2010 CT 223 EF Volume > 125cm3 MACE in 4
years
OR: 1.74 (95% CI:1.03 – 2.95)
Shmilovich et al.53, 2011 CT 232
EF volume indexed for total body surface > 68.1cm3/m2
MACE in 4 years
OR: 2.8 (95% CI: 1.3 - 6.4)*
Studies that evaluate epicardial fat in the HIV population are few. Most of them found that quantity of epicardial fat is higher than in the
non infected population (19,21). Epicardial fat seems to be associated to HIV related factors (HIV infection duration, HAART, CD4…)(19,20)
Epicardial fat is also associated to coronary artery disease (18-23).
Authors Imaging technique N Exposure
Clinicalvariables/out
come
Measure of association
Guaraldi et al., 2011 Cardiac CT 876 HIV + Epicardial fat
volume CAC > 100 OR = 1.10, p= 0.011
Zona et al., 2012 Cardiac CT 240 HIV +
Progression of epicardial fat
volume
Progression of CAC
OR= 1.04, p=0.03
Longenecker et al.,2013 Cardiac CT 100 HIV + Epicardial fat
volume CAC > 0 Spearman’s p = 0.228, p=0.024
Brener et al., 2014 Cardiac CT 706 HIV + Epicardial fat
volumePresence of
plaque
OR : 1,1,p=0.02
Epicardial quantification has been used in a multiples studies as a marker of the effectiveness of weight loss interventions, exercise and pharmaceutical treatments (24-27).
Epicardial fat can serve as target for pharmaceutical agents targeting the adipose tissue, such as statins or ant-diabetes medications.
Conclusion
Epicardial fat is a unique fat depot with anatomical and functionalcharacteristics different from other fat depots.
Epicardial fat can be quantified by different imaging techniques, and thismakes its assessment an appealing tool in both the clinical and researchsettings.
Despite the availability of different methods to assess epicardial fat, there iscurrently no clear guidelines for its use in clinical practice.
Future studies are needed to evaluate the prognostic value of quantitativeimaging techniques of epicardial fat assessment when included incardiovascular risk stratification approaches in various populations, such asin the population of HIV-infected patients.
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