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Quantification of Epicardial Adipose Tissue

Objectives

Epicardial adipose tissue (EAT) is an important structure both as an active secretor of hormones and cytokines that play a role in the development of atherosclerosis, as well as its potential as a cardiac risk marker. The purpose of this article was to determine an easy but accurate quantification of EAT for routine clinical use.

Methods and Results

We randomly selected coronary computed tomography angiographies of 60 patients (20 lean, 20 overweight, and 20 obese) derived from a larger study. Systolic and diastolic surface areas (SAs) were measured at two axial levels: a) fat pocket (FP) between right atrium and right ventricular outflow tract at origin of right coronary artery (RCA-FP) and b) FP anterior to right ventricular free wall (RVFW-FP) at coronary sinus ostium level. Maximum RVFW-FP thickness and total diastolic EAT volume were measured. EAT SA and thickness measurements were correlated to EAT volume and compared. Both interobserver and intraobserver reliability were assessed for SA and thickness with the intraclass correlation coefficient (ICC) as well as mean relative difference ± standard deviation (SD). Differences between systolic and diastolic SA measurements were also evaluated. Diastolic RCA-FP showed the highest SA correlation with volume (ρ = 0.92) and compared to the correlation of EAT thickness with volume (ρ=0.59) demonstrated the largest difference in correlation (+ 0.33, P < .0001). Systolic RCA-FP, systolic RVFW-FP, and diastolic RVFW-FP correlations to volume were less than diastolic RCA-FP (ρ = 0.84, ρ = 0.82, ρ = 0.86 respectively), but all correlations were statistically significantly higher than EAT thickness with volume. Values of systolic SA were mildly higher than diastolic SA for the RCA-FP (relative difference ± SD = 1.8 ± 21%, P = .8), but significantly higher for the RVFW-FP (relative difference ± SD = 17 ± 35%, P < .0001). Both systolic and diastolic SA measurements showed excellent reproducibility (ICC >0.95). However, for EAT thickness, the inter-observer reliability was comparatively low (ICC = 0.66).

Conclusion

Diastolic RCA-FP SA is a quick, reproducible estimate of total EAT and compared to EAT thickness demonstrates a significantly better correlation with EAT volume.

There has been growing interest in the role of epicardial adipose tissue (EAT) in recent years, both as an active secretor of hormones and cytokines which play a role in the development of atherosclerosis, as well as its potential as a cardiac risk marker . Previous studies have shown a significant association between the amount of EAT and the incidence of obesity-related insulin resistance and coronary atherosclerosis . Moreover, because of a significant direct relationship between epicardial fat and visceral fat , EAT thickness has been suggested to be used as a therapeutic marker . Accordingly, serial measurements of EAT can potentially serve as a means to evaluate the effectiveness of pharmacological, physical, and surgical therapies specifically designed to target visceral adipose tissue .

Precise measurement of EAT, however, remains a challenge. To date, several imaging modalities, including echocardiography , magnetic resonance imaging (MRI) , and computed tomography (CT) , have been applied in attempts to quantify EAT. Assessment of EAT by echocardiography is limited to measurement of EAT thickness over the right ventricular free wall (RVFW). Consequently, contradictory results have been reported by various investigators, most likely attributable to the impracticality of standardizing the angle of the transducer and location of the measurements . Volumetric measurements using CT and MRI are largely accomplished by manually tracing fat in slices of a given thickness and then adding up the individual volume measurements . Unless fully automated, this method is obviously cumbersome and time-consuming, thereby precluding widespread clinical use.

Linear measurement of EAT thickness anterior to the RV is rather simple. However, this measurement has not been shown to be strongly correlated with EAT volume in linear regression models . It also measures the adipose tissue anterior to the RV, which is not the primary site of EAT deposition . Anatomic studies suggest that the atrioventricular and interventricular grooves, particularly over the RV free wall, are the most frequent location for fat accumulation . Given this fact, we hypothesized that the areas of fat pockets in these regions would likely correlate better to EAT volume compared with a simple linear measurement of EAT thickness. As a result of this method’s simplicity and speed in quantifying EAT, it can potentially be included in routine cardiac CT interpretation and follow-up studies for metabolic risk stratification of patients. To test our hypothesis, we correlated surface area (SA) measurements of two specific anatomic regions that, according to the literature, are most likely representative of total EAT and compared with EAT volume using multislice CT (MDCT): 1) fat surrounding the right coronary artery origin (RCA fat pocket, RCA-FP) and 2) pocket of fat anterior to the right ventricle free wall extending to the apex (RV free wall fat pocket, RVFW-FP).

Material and methods

Patient Selection

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Institutional Review Board Approval

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CT Scan Parameters and Image Interpretation

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Figure 1, Methods of measurement of epicardial adipose tissue (EAT) surface area and thickness. Surface area measurements for the right coronary artery fat pocket (RCA-FP) (a) and right ventricular free wall fat pocket (RVFW-FP) (b) are demarcated in red . Axial images are shown in diastole passing through designated anatomic landmarks used for slice selection including the origin of the RCA (a) and center of the coronary sinus (CS) ostium (b) . The slice passing through the CS was also used to measure the maximum EAT thickness overlying the RV free wall ( double-headed green arrow ).

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Results

Patient Characteristics

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Table 1

Patient Characteristics of the Study Population (n = 60)

Lean Overweight Fat Total Sex (male/female) 8/12 2/18 11/9 21/39 Age (y) 61 ± 13 61 ± 2 56 ± 9 59 ± 11 Body mass index 21 ± 2.3 27.4 ± 1.6 35 ± 6.0 28 ± 7.0

Data are mean values ± standard deviation.

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Epicardial Fat Volume and SA Measurement, Correlations and Reproducibility

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Table 2

Distribution of Measures for all Subjects and BMI Categories

Measurement All cases BMI Mean ± SD Median (Range) Category Mean ± SD Median (Range) RCA-FP (systole) (mm 2 ) 620 ± 225 627 (110–1353) Lean 462 ± 190 432 (110–966) Overweight 658 ± 161 683 (375–1027) Obese 740 ± 228 744 (250–1353) RCA-FP (diastole) (mm 2 ) 617 ± 219 619 (230–1116) Lean 477 ± 213 423 (230–1116) Overweight 680 ± 179 662 (399–995) Obese 693 ± 202 695 (246–1075) RVFW-FP (systole) (mm 2 ) 618 ± 353 507 (109–1518) Lean 450 ± 287 410 (109–1385) Overweight 618 ± 296 592 (130–1518) Obese 787 ± 397 757 (232–1381) RVFW-FP (diastole) (mm 2 ) 548 ± 297 457 (84–1214) Lean 390 ± 250 345 (84–1075) Overweight 583 ± 266 528 (104–1149) Obese 670 ± 313 586 (251–1214) EAT thickness (mm) 5.1 ± 2 4.7 (1.5–11.9) Lean 4.2 ± 2.0 3.9 (1.7–9.1) Overweight 4.8 ± 1.8 4.7 (1.5–8.9) Obese 6.2 ± 2.8 5.9 (1.7–11.9) EAT volume (cm3) 127 ± 51 123 (47–281) Lean 97 ± 46 91 (47–228) Overweight 141 ± 42 146 (61–215) Obese 144 ± 51 130 (61–281)

RCA-FP, right coronary fat pocket; RVFW-FP, right ventricle free wall fat pocket; EAT, epicardial fat.

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Table 3

Correlations of SA and EAT Thickness to Volume with Comparison Tests

Correlations to Eat Volume Correlation Comparison to Eat Thickness (All Subjects) BMI Categories All Subjects Difference to EAT Thickness Steiger Z-score_P_ < Z (2-sided) Lean Overweight Obese EAT thickness (mm) 0.53 ∗ 0.63 ∗ 0.51 ∗ 0.59 † — — — RVFW-FP area (systole) (mm 2 ) 0.82 † 0.66 ∗ 0.82 † 0.82 † 0.232 3.615 <.001 RVFW-FP area (diastole) (mm 2 ) 0.88 † 0.7 † 0.88 † 0.86 † 0.269 4.53 <.0001 RCA-FP area (systole) (mm 2 ) 0.56 ∗ 0.81 † 0.69 † 0.84 † 0.251 3.544 <.001 RCA FP area (diastole) (mm 2 ) 0.80 † 0.93 † 0.80 † 0.92 † 0.33 5.842 <.0001

RCA-FP, right coronary fat pocket; RVFW-FP, right ventricle free wall fat pocket; EAT, epicardial fat.

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Figure 2, Scatterplots of epicardial adipose tissue (EAT) thickness and surface areas plotted against EAT volume with 95% density ellipses. Right coronary artery fat pocket (RCA-FP) and right ventricular free wall fat pocket (RVFW-FP) surface areas are significantly correlated with the EAT volume both in systole and diastole. The strongest correlation is seen with RCA-FP during diastole (ρ = 0.92).

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Figure 3, Bland-Altman plots for assessing agreement/disagreement between the right ventricular free wall fat pocket (RVFW-FP) surface area measurements during systole and diastole and the right coronary artery (RCA)-FP surface area measurements during systole and diastole. Solid line indicates mean absolute difference (70 and 3.2 for RVFW-FP and RCA-FP, respectively). Dashed lines indicate 95% limits of agreement: (-181 to 321) for RVFW-FP and (-208, 214) for RCA-FP. It is evident that the RCA-FP systole and diastole measurements are in better agreement than RVFW-FP values.

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Table 4

Inter-observer and intra-observer variability for area and thickness measurements

Measurement Inter-observer Reliability Intra-observer Reliability Rel Diff ± SD (%) ICC ∗ ICC 95% CI Rel Diff ± SD (%) ICC ∗ ICC 95% CI RCA-FP area (systole) (mm 2 ) 1.1 ± 9.2 0.97 (0.96–0.98) 0.6 ± 6 0.99 (0.98–0.99) RCA FP area (diastole) (mm 2 ) 0.1 ± 6.6 0.97 (0.97–0.99) 1.9 ± 6 0.98 (0.97–0.99) RVFW-FP area (systole) (mm 2 ) 3.0 ± 18.0 0.96 (0.94–0.98) −1.0 ± 8 0.98 (0.98–0.99) RVFW-FP area (diastole) (mm 2 ) 2.4 ± 11.7 0.97 (0.95–0.98) −0.5 ± 6 0.98 (0.98–0.99) EAT thickness (diastole) (mm) −12.7 ± 36 0.66 (0.49–0.78) 0.4 ± 21 0.92 (0.87–0.95)

RCA-FP, right coronary fat pocket; RVFW-FP, right ventricle free wall fat pocket; rel diff ± SD%, relative difference ± standard deviation; ICC, intra-class correlation coefficient; CI, confidence interval.

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Discussion

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Limitations

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Conclusion

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