Jpn J Radiol (2014) 32:331–339 DOI 10.1007/s11604-014-0310-4
ORIGINAL ARTICLE
Evaluation of the relationship between epicardial fat volume and left ventricular diastolic dysfunction Murat Vural • Aslı Talu • Deniz Sahin • Ozgul Ucar Elalmis • Hasan Ali Durmaz Sadık Uyanık • Betul Akdal Dolek
•
Received: 20 November 2013 / Accepted: 16 March 2014 / Published online: 1 April 2014 Ó Japan Radiological Society 2014
Abstract Purpose The aim of the present study was to evaluate the relationship between epicardial fat tissue (EFT) volume and left ventricular diastolic function. Materials and methods A total of 63 patients (29 male, 34 female, mean age 57.8 ± 10.9 years) were enrolled in the study. Multidetector computed tomography (MDCT) and 2D transthoracic echocardiography were performed in 29 patients with left ventricular diastolic dysfunction and 34 patients with normal diastolic function. EFT volume and coronary calcium score were measured by MDCT. Results Mean EFT volume was 137.2 ± 56.2 cm3 for the whole study group. Mean EFT was 114.1 ± 46.6 cm3 in patients with normal left ventricular diastolic function and 164.4 ± 54.9 cm3 in those with left ventricular diastolic dysfunction (p = 0.0002). Diastolic dysfunction had no significant correlation with diabetes, hypertension, and M. Vural H. A. Durmaz S. Uyanık B. A. Dolek Department of Radiology, Ankara Numune Education and Research Hospital, Talatpasa Bulvarı, Sıhhiye, Ankara, Turkey e-mail: [email protected] S. Uyanık e-mail: [email protected] B. A. Dolek e-mail: [email protected] M. Vural (&) H. Rahmi Gurpinar sok. 5/15 06680, Cankaya, Ankara, Turkey e-mail: [email protected]
coronary calcium scoring (p [ 0.05). Also in our patient group EFT volume had no significant correlation with coronary calcium score (r = 0.148, p = 0.248). Conclusion Patients with left ventricular diastolic dysfunction had significantly increased EFT volume. Keywords Epicardial fat Tomography Echocardiography Diastole Dysfunction
Introduction In recent years, diastolic dysfunction has become a widely recognized clinical entity. Diastolic dysfunction is abnormal stiffening of the ventricles, resulting in abnormal ventricular filling during diastole. Many different conditions—such as aging, hypertension, obesity, aortic stenosis, O. U. Elalmis e-mail: [email protected] A. Talu Asan sok. No: 22/2, Yenimahalle, Ankara 06170, Turkey D. Sahin Ilkadım mah. No: 10/116, Dikmen 06450, Ankara, Turkey O. U. Elalmis Dikmen caddesi. 176/69, Cankaya 06460, Ankara, Turkey H. A. Durmaz Birlik mah. 474. sok. No: 2/5, Cankaya, Ankara, Turkey
A. Talu D. Sahin O. U. Elalmis Department of Cardiology, Ankara Numune Education and Research Hospital, Talatpasa Bulvarı, Sıhhiye, Ankara, Turkey e-mail: [email protected]
S. Uyanık 33 sok. No: 2 Bestepe konakları sitesi B blok D: 19, Bestepe 06500, Ankara, Turkey
D. Sahin e-mail: [email protected]
B. A. Dolek Hulya sok. No: 40/20B, Cankaya 06700, Ankara, Turkey
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hypertrophic cardiomyopathy, coronary artery disease, restrictive cardiomyopathy, and diabetes—can cause diastolic dysfunction [1–3]. In most cases, there is no other abnormality in patients who have diastolic dysfunction on echocardiography. The reported prevalence of diastolic dysfunction in the general population varies from 11.1 to 65.2 % [4, 5]. Many factors, for example the criteria applied to diagnose left ventricular diastolic dysfunction, or the choice of imaging modality, can cause this wide range of prevalence. Epicardial fat tissue (EFT) has received significant attention in recent years after studies demonstrated that it is correlated with cardiometabolic risk factors, coronary atherosclerosis, obesity, left ventricular mass, left atrial size, and impaired diastolic filling [6–8]. EFT is confined within the pericardial sac and is situated on the surface of the heart, covering 80 % of the cardiac surface and constituting 20 % of the total weight of the heart. EFT constitutes 1 % of the total fat mass in a healthy person, and the average volume of EFT ranges between 110 and 125 cm3 [9, 10]. Paracardial fat is situated on the external surface of the parietal pericardium. The term ‘‘pericardial fat’’ refers to both epicardial fat and paracardial fat. Epicardial fat tissue, myocardium, and coronary vessels have close anatomic relationships; there is no fibrous fascial layer that separates them. EFT is metabolically active in fatty acid metabolism, it secretes vasoactive products that regulate coronary artery tone, and it produces inflammatory cytokines [11, 12]. It stores triglycerides to supply free fatty acids for myocardial energy production, thus acting as a lipid storage depot. Acting as an endocrine organ, it secretes hormones; acting as an inflammatory tissue, it secretes cytokines. EFT obtained from coronary artery bypass surgery shows higher expression of interleukin-1, interleukin-6, tumor necrosis factor, and mRNA than leg subcutaneous fat tissue [13]. Finally, EFT buffers the mechanical forces arising from arterial pulse wave and cardiac contraction, and provides enough space for positive remodeling of the coronary arteries if necessary. Local effects of EFT may manifest as abnormalities of left ventricular function. Previous studies have shown that EFT volume is related to obesity [14], coronary artery disease [15–17], impaired diastolic function [18], left ventricular mass, left atrial size [19], amount of intraabdominal fat, and cardiometabolic risk factors [20, 21]. As EFT is in direct anatomic proximity to the myocardium, its paracrine and mechanical interactions may affect cardiac morphology and function. These local effects of EFT may have be more strongly correlated to cardiac structure and function than general measures of adiposity [22]. Therefore, in this study, we investigated the correlation between EFT and left ventricular diastolic dysfunction
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using multidetector computed tomography (MDCT) and 2D echocardiography (2DE).
Materials and methods This study was approved by the ethics committee of our institution, and all patients gave written informed consent for participation in the study. The study conforms to the principles of the Helsinki Declaration 2008. Patients Patients presenting to the cardiology outpatient clinic with the complaint of chest pain with a moderate Diamond– Forrester risk score [23] who were referred to 2DE and MDCT for coronary calcium scoring were recruited. Patients with atrial fibrillation, valvular heart disease, cardiomyopathy, pericardial effusion, left ventricular systolic dysfunction, and known coronary artery disease were excluded. Blood pressure C140/90 mmHg, a self-reported history of hypertension, or the use of antihypertensive medications was defined as hypertension. Diabetes mellitus was defined as a fasting plasma glucose level of C126 mg/dl, a self-reported history of diabetes, or the use of diabetic medications. Hyperlipidemia was defined as total cholesterol C200 mg/dl, a self-reported history of hyperlipidemia, or the use of antihyperlipidemic medications. The flow diagram for the study is shown in Fig. 1. We prospectively studied 63 patients between April 2011 and January 2012. Each patient underwent MDCT on the same day as transthoracic echocardiography, or the day after, to perform coronary calcium scoring and assess EFT volume. On admission, blood sampling was performed to measure lipid levels in an overnight fasting state. Height and body weight were used to calculate body mass index. A noninvasive coronary evaluation was also performed by treadmill exercise test, dipyridamole nuclear myocardial perfusion imaging, or dobutamine stress echocardiography. The patients underwent invasive coronary angiography when necessary. Multidetector CT Multidetector computed tomography was performed using a 16-detector Toshiba Aquillion system (Toshiba Medical Systems, Otawara, Japan). Contiguous 3 mm slices with a prospectively ECG-triggered scanning protocol was used. The imaging and reconstruction parameters were as follows: voltage 120 kV, effective tube current 300 mA, and gantry rotation time 420 ms. All CT scans were obtained in the supine position and the craniocaudal direction. Image
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Fig. 1 Flow diagram of the study
acquisition was performed during an inspiratory breathhold. Transaxial images were reconstructed with an image matrix of 512 9 512 pixels using an ECG gated half-scan algorithm. Image reconstruction was performed in 75 % of the R–R interval. Calcium scoring and EFT calculations were done on a VitreaÒ post-processing workstation (Vital Images, Plymouth, MN, USA). Pericardial contours were manually traced for all axial images (Fig. 2). We chose the top boundary as the level of the right pulmonary artery (Fig. 2a). The other boundaries were the diaphragm, chest wall, and descending aorta (Fig. 2b). The slice thickness was 3 mm and the total EFT was calculated by evaluating more than 35 contiguous slices. We used predefined Hounsfield units (HU) of -30 to -190 to identify pixels that corresponded to fat tissue in the pericardial sac (Fig. 2).
Transthoracic echocardiography An experienced cardiologist blinded to the results of the cardiac MDCT acquired apical four- and two-chamber views using an echocardiography system (Vivid 7, GEVingmed Ultrasound AS, Horten, Norway) equipped with a 2.5-MHz phased array transducer. Left ventricular ejection fraction was measured by the Teichholz method from the parasternal long-axis view. All patients had normal left ventricular ejection fractions. Diastolic function was evaluated using the following Doppler echocardiographic parameters. Mitral inflow Doppler was measured in the standard fashion to determine the peak velocities of early (E-wave) and late diastolic filling (A-wave), the E/A ratio, the deceleration time of the transmitral E-wave (DT), and the isovolumic relaxation time (IVRT). IVRT was derived by placing the Doppler
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Statistical analysis
Fig. 2 a Axial MDCT image at the level of right pulmonary artery shows parietal pericardium (arrow) separating paracardial (P) and epicardial fat tissue (E). b Axial MDCT image at the midventricular level shows parietal pericardium (arrow) separating paracardial (P) and epicardial fat tissue (E)
cursor in the left ventricular outflow tract to simultaneously display the end of aortic ejection and the onset of mitral inflow. Using tissue Doppler imaging (TDI), the peak systolic (s) and the early (e0 ) and late (a0 ) diastolic myocardial velocities were recorded at the lateral mitral annulus, and the left ventricular filling index (E/e0 ) was calculated. The presence of diastolic dysfunction was determined according to the classification proposed by Alnabhan et al. [24], taking into consideration E/A, E/e0 , and E/A changes during rest and the Valsalva maneuver, which was performed to discriminate pseudonormal filling from a normal filling pattern. Diastolic dysfunction was classified as grade 0 for normal diastolic function, grade 1 for mild (impaired relaxation pattern), grade 2 for moderate (pseudonormal pattern), and grade 3 for severe (restrictive filling pattern) diastolic dysfunction, respectively. Patients were divided into two groups according to whether they had diastolic dysfunction (grade 1, 2, or 3) or not (grade 0).
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The SPSS software package (version 11.5; SPSS Inc., Chicago, IL, USA) was used for statistical evaluations. Continuous variables were expressed as the mean ± standard deviation (SD) and categorical variables were expressed as numbers and percentages. Body mass index (BMI) was calculated by the usual formula: BMI (kg/m2) = weight (kg)/height (m)2. Data were tested for normality using the Kolmogorov– Smirnov test. Continuous variables that showed normal distributions were compared using the independent-samples t test. The Mann–Whitney U test was applied to compare median values (coronary calcium score). Yates’s corrected chi-square test was used to assess categorical variables. Correlations between EFT volume and coronary calcium score, body mass index and e0 were assessed using the Pearson correlation test. ROC curve analysis was used to define the EFT volume cutoff value to discriminate patients with or without left ventricular diastolic dysfunction. Analysis was made by using the Youden’s index (J = max{sensitivityc ? specificityc - 1}, where c encompasses all possible criterion values). When the p value was less than 0.05, the difference was considered statistically significant. A multiple logistic regression analysis of diastolic dysfunction which included all possible confounding factors (age, systolic blood pressure, diastolic blood pressure, body mass index, waist circumference, total cholesterol, EFT volume) was performed. Odds ratios and 95 % confidence intervals (CI) for each independent variable were calculated.
Results A total of 63 patients (29 males, 34 females) with a mean age of 57.8 ± 10.9 years were enrolled in the study. All patients were in sinus rhythm. The demographic features of the study participants are given in Table 1. Twentynine patients (46 %) had left ventricular diastolic dysfunction and 34 patients (54 %) had normal diastolic function according to 2D echocardiographic criteria. Twenty-four patients had grade 1, four patients had grade 2, and one patient had grade 3 diastolic dysfunction. Patients with impaired diastolic function were older than those with normal diastolic function (63.7 ± 8.4 vs. 52.7 ± 10.3; p \ 0.001). Overall, 55.9 % of women and 34.5 % of men had diastolic dysfunction. 51.2 % of the hypertensive patients and 50 % of the diabetic patients had diastolic dysfunction. BMI was not statistically different between patients with and patients without diastolic dysfunction (29.1 ± 3.9 vs. 29.6 ± 4.5 kg/m2; p = 0.610) (Table 2).
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Table 1 Baseline demographic characteristics of the overall patient population (n = 63)
Table 2 Demographic and clinical characteristics of patients with and without left ventricular diastolic dysfunction (DD)
Characteristics (n = 63) Age (years)
57.8 ± 10.9
Gender (F/M)
34/29 (54 %/ 46 %)
Number of patients with hypertension
43 (68.3 %)
Hypertension duration (years)
10.5 ± 7.5
Number of patients with diabetes
38 (60.3 %)
Diabetes duration (years) Cigarette smoking
7.9 ± 6.8 22 (34.9 %)
Cigarette smoking (years)
19.8 ± 10.6
Body mass index (kg/m2)
29.4 ± 4.2
Waist circumference (cm)
100.9 ± 9.9
Systolic blood pressure (mmHg)
145.1 ± 13.9
Diastolic blood pressure (mmHg)
90.0 ± 10.1
Ejection fraction (%)
64.4 ± 4.3
Mitral E-wave (m/s)
0.73 ± 0.14
Mitral A-wave (m/s)
0.86 ± 0.19
Age (years)
DD (-) n = 34
DD (?) n = 29
p
52.7 ± 10.3
63.7 ± 8.4
\0.001
19 (55.9 %) 15 (44.1 %)
10 (34.5 %) 19 (65.5 %)
Gender Male Female
0.148
SBP (mmHg)
144.9 ± 13.4
145.3 ± 14.7
0.921
DBP (mmHg)
90.2 ± 10.5
89.9 ± 9.8
0.913
Diabetes
19 (55.9 %)
19 (65.5 %)
0.603
Current smoking
14 (41.2 %)
8 (27.6 %)
0.341
Total cholesterol (mg/dl)
201.6 ± 33.2
201.6 ± 42.5
0.992
LDL cholesterol (mg/dl)
129.0 ± 30.8
125.2 ± 41.7
0.685
Triglycerides (mg/dl)
180.5 ± 73.7
200.0 ± 141.4
0.497
e0 (cm/s)
12.1 ± 2.6
6.2 ± 1.2
IVRT (ms)
93.8 ± 11.3
109.9 ± 17.1
0.0002
Body mass index (kg/m2)
29.6 ± 4.5
29.1 ± 3.9
0.610 0.834
\0.001
E/A ratio
0.89 ± 0.27
Waist circumference (cm)
101.2 ± 10
100.6 ± 10.1
e0 (cm/s)
9.4 ± 3.6
Median CCS (HU)
2.5 (0–255)
9 (0–466)
0.427
Deceleration time of the transmitral E-wave (ms)
230.9 ± 51.2
EFT volume (cm3)
114.1 ± 46.6
164.4 ± 54.9
0.0002
Isovolumic relaxation time (IVRT) (ms)
101.7 ± 16.4
p \ 0.05 between groups was considered statistically significant
8.6 ± 4.3
e0 mitral annular early velocity, IVRT isovolumic relaxation time, CCS coronary calcium score, EFT epicardial fat tissue
E/e
0
Epicardial fat tissue volume (cm3)
137.2 ± 56.2
Coronary calcium score (HU)
4.0 (0–466)
Total cholesterol (mg/dl)
201.6 ± 37.3
Triglycerides (mg/dl)
189.1 ± 108.3
Low-density lipoprotein (mg/dl)
127.3 ± 35.7
High-density lipoprotein (mg/dl)
41.9 ± 10.4
Diastolic dysfunction Yes
29 (46 %)
No
34 (54 %)
Mean EFT volume was 137.2 ± 56.2 cm3 for the whole study group. Mean EFT was 114.1 ± 46.6 cm3 in patients with normal left ventricular diastolic function and 164.4 ± 54.9 cm3 in those with impaired left ventricular diastolic function (p = 0.0002). EFT volume was significantly higher in patients who had diastolic dysfunction compared to patients with normal diastolic function (Fig. 3). A ROC analysis revealed that the cutoff value for EFT volume to determine diastolic dysfunction was 129.60 cm3 (75.9 % sensitivity, 79.4 % specificity, 95 % CI 0.637–0.880, AUC 0.758) (Table 3; Fig. 4). After adjusting for the covariables, both age and EFT volume were significantly associated with diastolic dysfunction (OR 1.104; 95 % CI 1.003–1.214; p = 0.043 for age and OR 1.034; 95 % CI 1.010–1.060; p = 0.006 for EFT volume) (Table 4).
There was no significant correlation between EFT volume and coronary calcium score (r = 0.148, p = 0.248). Also, no significant correlation was found between EFT volume and body mass index (r = 0.054, p = 0.674). In the patients with diastolic dysfunction, there was a significant negative correlation between e0 and EFT volume (r = -0.437, p \ 0.0001). Out of 63 patients, 59 patients underwent noninvasive evaluation of coronary artery disease (the treadmill exercise test was performed in 40 patients, dipyridamole nuclear stress myocardial perfusion imaging in 10, and dobutamine stress echocardiography in 9). Thirty patients had abnormal results, and we decided to perform invasive coronary angiography on them. Three patients declined the coronary angiography. Finally, 27 patients underwent invasive coronary angiography. Coronary angiography was normal in 8 patients, 12 had minimal coronary artery disease (coronary artery plaques or \50 % stenosis in epicardial coronary arteries), and 7 had significant coronary artery disease ([50 % stenosis in at least one of the epicardial coronary arteries). When any (minimal or significant) coronary artery stenosis was included in the analysis, there was no significant difference between diastolic-dysfunction-positive and diastolicdysfunction-negative groups (11 patients vs. 8 patients; p = 0.3340).
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Fig. 3 Epicardial fat volume was significantly higher in patients with left ventricular diastolic dysfunction (EFTV epicardial fat tissue volume, DD diastolic dysfunction)
Table 3 Demographic and clinical characteristics according to epicardial fat tissue volume (EFTV)
EFTV \ 129.60 cm3 n = 34
EFTV C 129.60 cm3 n = 29
p value
54.3 ± 10.7
61.8 ± 10.0
0.006*
Male
14 (41.2 %)
15 (51.7 %)
0.559
Female
20 (58.8 %)
14 (48.3 %)
Age (years) Gender
* p \ 0.05 between groups was considered statistically significant
Hypertension
19 (55.9 %)
24 (82.8 %)
0.044*
Diabetes
19 (55.9 %)
19 (65.5 %)
0.603
Current smoking
13 (39.4 %)
9 (31.0 %)
0.674
Hyperlipidemia
23 (69.7 %)
24 (85.7 %)
0.239
Body mass index (kg/m2)
28.8 ± 4.8
30.0 ± 3.3
0.272
Median coronary calcium score (HU)
0.5 (0–255)
15 (0–466)
0.109
Discussion In this study, we found that EFT volume was associated with left ventricular diastolic dysfunction in a group of patients who presented with a complaint of chest pain. There are only a few studies in the literature that document the association between diastolic function and epicardial fat volume. Mean EFT volume was 137.2 ± 56.2 cm3 for the whole study group. In previous studies, the average volume of EFT was generally between 110 and 125 cm3 in the normal population [9, 10]. In this study, the mean EFT was 114 ± 46.5 cm3 in patients with normal left ventricular
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diastolic function and 164.4 ± 54.9 cm3 in those with impaired left ventricular diastolic function (p = 0.0002). Therefore, the mean EFT volume of patients with impaired diastolic dysfunction was higher than it was in patients with normal diastolic function in the present study. The mean EFT volume of patients with impaired diastolic dysfunction in this study is also higher than that of the normal population included in previous studies [9, 10]. Body mass index, which is an indicator of general adiposity, was not significantly different in patients with or without diastolic dysfunction. Therefore, local fat stores such as epicardial fat may be more important than general stores in terms of diastolic dysfunction.
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1,0
,8
Sensitivity
,6
,4
,2
0,0 0,0
,2
,4
,6
,8
1,0
1 - Specificity Fig. 4 ROC curve analysis for EFT volume to discriminate patients with or without left ventricular diastolic dysfunction revealed a cutoff value of 129.60 cm3 (AUC = 0.758, 95 % CI 0.637–0.880)
Table 4 Multiple logistic regression analysis showing parameters associated with diastolic dysfunction Odds ratio
95 % confidence interval Lower
p value
Upper
Age
1.104
1.003
1.214
0.043
SBP
1.054
0.925
1.202
0.428
DBP
0.844
0.692
1.030
0.094
BMI
0.952
0.660
1.372
0.791
Waist circumference
1.005
0.883
1.143
0.943
Total cholesterol EFT volume
1.056 1.034
0.989 1.010
1.127 1.060
0.106 0.006
SBP systolic blood pressure, DBP diastolic blood pressure, BMI body mass index, EFT epicardial fat tissue. Statistically significant results (p \ 0.05) are given in bold text
In our cohort of patients with normal left ventricular ejection fraction who were referred for echocardiographic testing, mild diastolic dysfunction was highly prevalent. Data on the natural history of diastolic dysfunction are limited, and further investigations are needed to understand the factors that affect myocardial stiffness. Long-term follow-up is required to identify the link between diastolic dysfunction and EFT volume. In some of the previous studies in this field, the quantity of EFT was evaluated by 2D echocardiography, by measuring its thickness. However, 2D echocardiography is highly dependent on acoustic windows and sometimes
cannot provide an adequate window on all cardiac segments, especially in obese patients and in patients with chronic obstructive lung disease [25]. In addition, there are different echocardiographic measurement techniques which yield different results (i.e., end-systolic vs. enddiastolic measurements, parasternal long-axis only vs. average of parasternal long and short axis measurements). In our study, we used MDCT in order to calculate EFT volume. Submillimeter collimation, high temporal and spatial resolution, and three-dimensional views of the heart and its epicardial surface are the advantages of MDCT. Another technique is cardiac magnetic resonance imaging (MRI). Although MRI has some limitations due to its low spatial resolution, specifically in the z-dimension, it does not involve any radiation and is considered a good modality for visceral fat measurement [26]. However, MRI may not be widely available for this purpose at every institution. Moderate or severe diastolic dysfunction is associated with increased mortality rates in patients with normal systolic function. Although mild diastolic dysfunction was prevalent in our study group, it does not affect survival rate, and less is known about factors involved in the progression of mild diastolic dysfunction to moderate and severe degrees [5]. Understanding the mechanisms of diastolic dysfunction is important from the perspectives of survival rate and prognosis. In our study, we found a significant correlation with diastolic dysfunction and EFT volume. Moderate and severe diastolic dysfunction and their association with EFT volume should be investigated in new studies, as they are associated with an increased mortality rate. In our study, patients with diastolic dysfunction were significantly older than patients without diastolic dysfunction. As shown in previous studies, diastolic dysfunction increases with age [27, 28]. Changes in myocardium occur even during the normal aging process, and they may alter the lusitropic function of the heart. These changes include remodeling of the myocardial interstitium and an increase in myocardial collagen content. Recently, a retrospective study of 14,298 patients revealed that echocardiographically assessed diastolic dysfunction increased with age [29]. Therefore, the fact that the diastolic dysfunction positive group was older in our study was expected. In previous studies, a relationship between EFT volume and coronary atherosclerosis was demonstrated [9, 10]. However, according to our knowledge, EFT volume, diastolic dysfunction, and coronary calcium score were not analyzed together for a single cohort of patients in those studies. In our study, we could not find any association with EFT volume and coronary calcium score. This result may be due to the small number of patients in our group, or there may be other mechanisms that should be investigated in future studies.
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Our study has several limitations. The number of patients included into the study was small, and most of the patients in this study had mild diastolic dysfunction. In addition, diastolic dysfunction was assessed by echo Doppler only, instead of direct catheter measurement of left ventricular end-diastolic pressure. Another limitation is that the presence of silent myocardial infarction in the patients could not be ruled out. In conclusion, epicardial fat tissue volume measured using multidetector computed tomography was found to be significantly associated with left ventricular diastolic function. This finding should enhance the utility of epicardial fat tissue volume measurement for understanding the mechanisms of left ventricular diastolic dysfunction. Further studies are required to identify the linkage between EFT volume and diastolic dysfunction. Conflict of interest of interest.
The authors declare that they have no conflict
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12. Kremen J, Dolinkova M, Krajickova J, Blaha J, Anderlova K, Lacinova Z, et al. Increased subcutaneous and epicardial adipose tissue production of proinflammatory cytokines in cardiac surgery patients: possible role in postoperative insulin resistance. J Clin Endocrinol Metab. 2006;91:4620–7. 13. Lacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G, et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29:251–5. 14. Wang TD, Lee WJ, Shih FY, Huang CH, Chang YC, Chen WJ, et al. Relations of epicardial adipose tissue measured by multidetector computed tomography to components of the metabolic syndrome are region specific and independent of anthropometric indexes and intraabdominal visceral fat. J Clin Endocrinol Metab. 2009;94:662–9. 15. De Vos AM, Prokop M, Roos CJ, Meijs MF, van der Schouw YT, Rutten A, et al. Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women. Eur Heart J. 2008;29:777–83. 16. Chaowalit N, Somers VK, Pellikka PA, Rihal CS, Lopez-Jimenez F. Subepicardial adipose tissue and the presence and severity of coronary artery disease. Atherosclerosis. 2006;186:354–9. 17. Ahn SG, Lim HS, Joe DY, Kang SJ, Choi BJ, Choi SY, et al. Relationship of epicardial adipose tissue by echocardiography to coronary artery disease. Heart. 2008;94:e7. 18. Iacobellis G, Willens HJ. Echocardiographic epicardial fat: a review of research and clinical applications. J Am Soc Echocardiogr. 2009;22:1311–9. 19. Fox CS, Gona P, Hoffmann U, Porter SA, Salton CJ, Massaro JM, et al. Pericardial fat, intrathoracic fat, and measures of left ventricular structure and function: the Framingham Heart Study. Circulation. 2009;119:1586–91. 20. Rosito GA, Massaro JM, Hoffman U, Ruberg FL, Mahabadi AA, Vasan RS, et al. Fox CS Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation. 2008;117:605–13. 21. Gorter PM, van Lindert AS, de Vos AM, Meijs MF, van der Graaf Y, Doevendans PA, et al. Quantification of epicardial and peri-coronary fat using cardiac computed tomography; reproducibility and relation with obesity and metabolic syndrome in patients suspected of coronary artery disease. Atherosclerosis. 2008;197:896–903. 22. Iacobellis G, Pond CM, Sharma AM. Different ‘‘weight’’ of cardiac and general adiposity in predicting left ventricle morphology. Obesity (Silver Spring). 2006;14:1679–84. 23. Forrester J, Diamond G, Chatterjie K, Swan HJ. Medical therapy of acute myocardial infarction by application of hemodynamic subsets (first of two parts). N Engl J Med. 1976;295: 1356–62. 24. Alnabhan N, Kerut EK, Geraci SA, McMullan MR, Fox E. An approach to analysis of left ventricular diastolic function and loading conditions in the echocardiography laboratory. Echocardiography. 2008;25:105–16. 25. Abbara S, Desai JC, Cury RC, Butler J, Nieman K, Reddy V. Mapping epicardial fat with multi-detector computed tomography to facilitate percutaneous transepicardial arrhythmia ablation. Eur J Radiol. 2006;57:417–22. 26. Iacobellis G. Imaging of visceral adipose tissue: an emerging diagnostic tool and therapeutic target. Curr Drug Targets Cardiovasc Hematol Dis. 2005;5:345–53. 27. Gardin JM, Arnold AM, Bild DE, Smith VE, Lima JA, Klopfenstein HS, Kitzman DW. Left ventricular diastolic filling in the elderly: the cardiovascular health study. Am J Cardiol. 1998;82:345–51.
Jpn J Radiol (2014) 32:331–339 28. Redfield MM, Jacobsen SJ, Borlaug BA, Rodeheffer RJ, Kass DA. Age- and gender-related ventricular-vascular stiffening: a community-based study. Circulation. 2005;112:2254–62. 29. Carvalho JC, Farand P, Do HD, Brochu MC, Bonenfant F, Lepage S. Effect of age and sex on echocardiographic left
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ORIGINAL ARTICLE
Evaluation of the relationship between epicardial fat volume and left ventricular diastolic dysfunction Murat Vural • Aslı Talu • Deniz Sahin • Ozgul Ucar Elalmis • Hasan Ali Durmaz Sadık Uyanık • Betul Akdal Dolek
•
Received: 20 November 2013 / Accepted: 16 March 2014 / Published online: 1 April 2014 Ó Japan Radiological Society 2014
Abstract Purpose The aim of the present study was to evaluate the relationship between epicardial fat tissue (EFT) volume and left ventricular diastolic function. Materials and methods A total of 63 patients (29 male, 34 female, mean age 57.8 ± 10.9 years) were enrolled in the study. Multidetector computed tomography (MDCT) and 2D transthoracic echocardiography were performed in 29 patients with left ventricular diastolic dysfunction and 34 patients with normal diastolic function. EFT volume and coronary calcium score were measured by MDCT. Results Mean EFT volume was 137.2 ± 56.2 cm3 for the whole study group. Mean EFT was 114.1 ± 46.6 cm3 in patients with normal left ventricular diastolic function and 164.4 ± 54.9 cm3 in those with left ventricular diastolic dysfunction (p = 0.0002). Diastolic dysfunction had no significant correlation with diabetes, hypertension, and M. Vural H. A. Durmaz S. Uyanık B. A. Dolek Department of Radiology, Ankara Numune Education and Research Hospital, Talatpasa Bulvarı, Sıhhiye, Ankara, Turkey e-mail: [email protected] S. Uyanık e-mail: [email protected] B. A. Dolek e-mail: [email protected] M. Vural (&) H. Rahmi Gurpinar sok. 5/15 06680, Cankaya, Ankara, Turkey e-mail: [email protected]
coronary calcium scoring (p [ 0.05). Also in our patient group EFT volume had no significant correlation with coronary calcium score (r = 0.148, p = 0.248). Conclusion Patients with left ventricular diastolic dysfunction had significantly increased EFT volume. Keywords Epicardial fat Tomography Echocardiography Diastole Dysfunction
Introduction In recent years, diastolic dysfunction has become a widely recognized clinical entity. Diastolic dysfunction is abnormal stiffening of the ventricles, resulting in abnormal ventricular filling during diastole. Many different conditions—such as aging, hypertension, obesity, aortic stenosis, O. U. Elalmis e-mail: [email protected] A. Talu Asan sok. No: 22/2, Yenimahalle, Ankara 06170, Turkey D. Sahin Ilkadım mah. No: 10/116, Dikmen 06450, Ankara, Turkey O. U. Elalmis Dikmen caddesi. 176/69, Cankaya 06460, Ankara, Turkey H. A. Durmaz Birlik mah. 474. sok. No: 2/5, Cankaya, Ankara, Turkey
A. Talu D. Sahin O. U. Elalmis Department of Cardiology, Ankara Numune Education and Research Hospital, Talatpasa Bulvarı, Sıhhiye, Ankara, Turkey e-mail: [email protected]
S. Uyanık 33 sok. No: 2 Bestepe konakları sitesi B blok D: 19, Bestepe 06500, Ankara, Turkey
D. Sahin e-mail: [email protected]
B. A. Dolek Hulya sok. No: 40/20B, Cankaya 06700, Ankara, Turkey
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hypertrophic cardiomyopathy, coronary artery disease, restrictive cardiomyopathy, and diabetes—can cause diastolic dysfunction [1–3]. In most cases, there is no other abnormality in patients who have diastolic dysfunction on echocardiography. The reported prevalence of diastolic dysfunction in the general population varies from 11.1 to 65.2 % [4, 5]. Many factors, for example the criteria applied to diagnose left ventricular diastolic dysfunction, or the choice of imaging modality, can cause this wide range of prevalence. Epicardial fat tissue (EFT) has received significant attention in recent years after studies demonstrated that it is correlated with cardiometabolic risk factors, coronary atherosclerosis, obesity, left ventricular mass, left atrial size, and impaired diastolic filling [6–8]. EFT is confined within the pericardial sac and is situated on the surface of the heart, covering 80 % of the cardiac surface and constituting 20 % of the total weight of the heart. EFT constitutes 1 % of the total fat mass in a healthy person, and the average volume of EFT ranges between 110 and 125 cm3 [9, 10]. Paracardial fat is situated on the external surface of the parietal pericardium. The term ‘‘pericardial fat’’ refers to both epicardial fat and paracardial fat. Epicardial fat tissue, myocardium, and coronary vessels have close anatomic relationships; there is no fibrous fascial layer that separates them. EFT is metabolically active in fatty acid metabolism, it secretes vasoactive products that regulate coronary artery tone, and it produces inflammatory cytokines [11, 12]. It stores triglycerides to supply free fatty acids for myocardial energy production, thus acting as a lipid storage depot. Acting as an endocrine organ, it secretes hormones; acting as an inflammatory tissue, it secretes cytokines. EFT obtained from coronary artery bypass surgery shows higher expression of interleukin-1, interleukin-6, tumor necrosis factor, and mRNA than leg subcutaneous fat tissue [13]. Finally, EFT buffers the mechanical forces arising from arterial pulse wave and cardiac contraction, and provides enough space for positive remodeling of the coronary arteries if necessary. Local effects of EFT may manifest as abnormalities of left ventricular function. Previous studies have shown that EFT volume is related to obesity [14], coronary artery disease [15–17], impaired diastolic function [18], left ventricular mass, left atrial size [19], amount of intraabdominal fat, and cardiometabolic risk factors [20, 21]. As EFT is in direct anatomic proximity to the myocardium, its paracrine and mechanical interactions may affect cardiac morphology and function. These local effects of EFT may have be more strongly correlated to cardiac structure and function than general measures of adiposity [22]. Therefore, in this study, we investigated the correlation between EFT and left ventricular diastolic dysfunction
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using multidetector computed tomography (MDCT) and 2D echocardiography (2DE).
Materials and methods This study was approved by the ethics committee of our institution, and all patients gave written informed consent for participation in the study. The study conforms to the principles of the Helsinki Declaration 2008. Patients Patients presenting to the cardiology outpatient clinic with the complaint of chest pain with a moderate Diamond– Forrester risk score [23] who were referred to 2DE and MDCT for coronary calcium scoring were recruited. Patients with atrial fibrillation, valvular heart disease, cardiomyopathy, pericardial effusion, left ventricular systolic dysfunction, and known coronary artery disease were excluded. Blood pressure C140/90 mmHg, a self-reported history of hypertension, or the use of antihypertensive medications was defined as hypertension. Diabetes mellitus was defined as a fasting plasma glucose level of C126 mg/dl, a self-reported history of diabetes, or the use of diabetic medications. Hyperlipidemia was defined as total cholesterol C200 mg/dl, a self-reported history of hyperlipidemia, or the use of antihyperlipidemic medications. The flow diagram for the study is shown in Fig. 1. We prospectively studied 63 patients between April 2011 and January 2012. Each patient underwent MDCT on the same day as transthoracic echocardiography, or the day after, to perform coronary calcium scoring and assess EFT volume. On admission, blood sampling was performed to measure lipid levels in an overnight fasting state. Height and body weight were used to calculate body mass index. A noninvasive coronary evaluation was also performed by treadmill exercise test, dipyridamole nuclear myocardial perfusion imaging, or dobutamine stress echocardiography. The patients underwent invasive coronary angiography when necessary. Multidetector CT Multidetector computed tomography was performed using a 16-detector Toshiba Aquillion system (Toshiba Medical Systems, Otawara, Japan). Contiguous 3 mm slices with a prospectively ECG-triggered scanning protocol was used. The imaging and reconstruction parameters were as follows: voltage 120 kV, effective tube current 300 mA, and gantry rotation time 420 ms. All CT scans were obtained in the supine position and the craniocaudal direction. Image
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Fig. 1 Flow diagram of the study
acquisition was performed during an inspiratory breathhold. Transaxial images were reconstructed with an image matrix of 512 9 512 pixels using an ECG gated half-scan algorithm. Image reconstruction was performed in 75 % of the R–R interval. Calcium scoring and EFT calculations were done on a VitreaÒ post-processing workstation (Vital Images, Plymouth, MN, USA). Pericardial contours were manually traced for all axial images (Fig. 2). We chose the top boundary as the level of the right pulmonary artery (Fig. 2a). The other boundaries were the diaphragm, chest wall, and descending aorta (Fig. 2b). The slice thickness was 3 mm and the total EFT was calculated by evaluating more than 35 contiguous slices. We used predefined Hounsfield units (HU) of -30 to -190 to identify pixels that corresponded to fat tissue in the pericardial sac (Fig. 2).
Transthoracic echocardiography An experienced cardiologist blinded to the results of the cardiac MDCT acquired apical four- and two-chamber views using an echocardiography system (Vivid 7, GEVingmed Ultrasound AS, Horten, Norway) equipped with a 2.5-MHz phased array transducer. Left ventricular ejection fraction was measured by the Teichholz method from the parasternal long-axis view. All patients had normal left ventricular ejection fractions. Diastolic function was evaluated using the following Doppler echocardiographic parameters. Mitral inflow Doppler was measured in the standard fashion to determine the peak velocities of early (E-wave) and late diastolic filling (A-wave), the E/A ratio, the deceleration time of the transmitral E-wave (DT), and the isovolumic relaxation time (IVRT). IVRT was derived by placing the Doppler
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Statistical analysis
Fig. 2 a Axial MDCT image at the level of right pulmonary artery shows parietal pericardium (arrow) separating paracardial (P) and epicardial fat tissue (E). b Axial MDCT image at the midventricular level shows parietal pericardium (arrow) separating paracardial (P) and epicardial fat tissue (E)
cursor in the left ventricular outflow tract to simultaneously display the end of aortic ejection and the onset of mitral inflow. Using tissue Doppler imaging (TDI), the peak systolic (s) and the early (e0 ) and late (a0 ) diastolic myocardial velocities were recorded at the lateral mitral annulus, and the left ventricular filling index (E/e0 ) was calculated. The presence of diastolic dysfunction was determined according to the classification proposed by Alnabhan et al. [24], taking into consideration E/A, E/e0 , and E/A changes during rest and the Valsalva maneuver, which was performed to discriminate pseudonormal filling from a normal filling pattern. Diastolic dysfunction was classified as grade 0 for normal diastolic function, grade 1 for mild (impaired relaxation pattern), grade 2 for moderate (pseudonormal pattern), and grade 3 for severe (restrictive filling pattern) diastolic dysfunction, respectively. Patients were divided into two groups according to whether they had diastolic dysfunction (grade 1, 2, or 3) or not (grade 0).
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The SPSS software package (version 11.5; SPSS Inc., Chicago, IL, USA) was used for statistical evaluations. Continuous variables were expressed as the mean ± standard deviation (SD) and categorical variables were expressed as numbers and percentages. Body mass index (BMI) was calculated by the usual formula: BMI (kg/m2) = weight (kg)/height (m)2. Data were tested for normality using the Kolmogorov– Smirnov test. Continuous variables that showed normal distributions were compared using the independent-samples t test. The Mann–Whitney U test was applied to compare median values (coronary calcium score). Yates’s corrected chi-square test was used to assess categorical variables. Correlations between EFT volume and coronary calcium score, body mass index and e0 were assessed using the Pearson correlation test. ROC curve analysis was used to define the EFT volume cutoff value to discriminate patients with or without left ventricular diastolic dysfunction. Analysis was made by using the Youden’s index (J = max{sensitivityc ? specificityc - 1}, where c encompasses all possible criterion values). When the p value was less than 0.05, the difference was considered statistically significant. A multiple logistic regression analysis of diastolic dysfunction which included all possible confounding factors (age, systolic blood pressure, diastolic blood pressure, body mass index, waist circumference, total cholesterol, EFT volume) was performed. Odds ratios and 95 % confidence intervals (CI) for each independent variable were calculated.
Results A total of 63 patients (29 males, 34 females) with a mean age of 57.8 ± 10.9 years were enrolled in the study. All patients were in sinus rhythm. The demographic features of the study participants are given in Table 1. Twentynine patients (46 %) had left ventricular diastolic dysfunction and 34 patients (54 %) had normal diastolic function according to 2D echocardiographic criteria. Twenty-four patients had grade 1, four patients had grade 2, and one patient had grade 3 diastolic dysfunction. Patients with impaired diastolic function were older than those with normal diastolic function (63.7 ± 8.4 vs. 52.7 ± 10.3; p \ 0.001). Overall, 55.9 % of women and 34.5 % of men had diastolic dysfunction. 51.2 % of the hypertensive patients and 50 % of the diabetic patients had diastolic dysfunction. BMI was not statistically different between patients with and patients without diastolic dysfunction (29.1 ± 3.9 vs. 29.6 ± 4.5 kg/m2; p = 0.610) (Table 2).
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Table 1 Baseline demographic characteristics of the overall patient population (n = 63)
Table 2 Demographic and clinical characteristics of patients with and without left ventricular diastolic dysfunction (DD)
Characteristics (n = 63) Age (years)
57.8 ± 10.9
Gender (F/M)
34/29 (54 %/ 46 %)
Number of patients with hypertension
43 (68.3 %)
Hypertension duration (years)
10.5 ± 7.5
Number of patients with diabetes
38 (60.3 %)
Diabetes duration (years) Cigarette smoking
7.9 ± 6.8 22 (34.9 %)
Cigarette smoking (years)
19.8 ± 10.6
Body mass index (kg/m2)
29.4 ± 4.2
Waist circumference (cm)
100.9 ± 9.9
Systolic blood pressure (mmHg)
145.1 ± 13.9
Diastolic blood pressure (mmHg)
90.0 ± 10.1
Ejection fraction (%)
64.4 ± 4.3
Mitral E-wave (m/s)
0.73 ± 0.14
Mitral A-wave (m/s)
0.86 ± 0.19
Age (years)
DD (-) n = 34
DD (?) n = 29
p
52.7 ± 10.3
63.7 ± 8.4
\0.001
19 (55.9 %) 15 (44.1 %)
10 (34.5 %) 19 (65.5 %)
Gender Male Female
0.148
SBP (mmHg)
144.9 ± 13.4
145.3 ± 14.7
0.921
DBP (mmHg)
90.2 ± 10.5
89.9 ± 9.8
0.913
Diabetes
19 (55.9 %)
19 (65.5 %)
0.603
Current smoking
14 (41.2 %)
8 (27.6 %)
0.341
Total cholesterol (mg/dl)
201.6 ± 33.2
201.6 ± 42.5
0.992
LDL cholesterol (mg/dl)
129.0 ± 30.8
125.2 ± 41.7
0.685
Triglycerides (mg/dl)
180.5 ± 73.7
200.0 ± 141.4
0.497
e0 (cm/s)
12.1 ± 2.6
6.2 ± 1.2
IVRT (ms)
93.8 ± 11.3
109.9 ± 17.1
0.0002
Body mass index (kg/m2)
29.6 ± 4.5
29.1 ± 3.9
0.610 0.834
\0.001
E/A ratio
0.89 ± 0.27
Waist circumference (cm)
101.2 ± 10
100.6 ± 10.1
e0 (cm/s)
9.4 ± 3.6
Median CCS (HU)
2.5 (0–255)
9 (0–466)
0.427
Deceleration time of the transmitral E-wave (ms)
230.9 ± 51.2
EFT volume (cm3)
114.1 ± 46.6
164.4 ± 54.9
0.0002
Isovolumic relaxation time (IVRT) (ms)
101.7 ± 16.4
p \ 0.05 between groups was considered statistically significant
8.6 ± 4.3
e0 mitral annular early velocity, IVRT isovolumic relaxation time, CCS coronary calcium score, EFT epicardial fat tissue
E/e
0
Epicardial fat tissue volume (cm3)
137.2 ± 56.2
Coronary calcium score (HU)
4.0 (0–466)
Total cholesterol (mg/dl)
201.6 ± 37.3
Triglycerides (mg/dl)
189.1 ± 108.3
Low-density lipoprotein (mg/dl)
127.3 ± 35.7
High-density lipoprotein (mg/dl)
41.9 ± 10.4
Diastolic dysfunction Yes
29 (46 %)
No
34 (54 %)
Mean EFT volume was 137.2 ± 56.2 cm3 for the whole study group. Mean EFT was 114.1 ± 46.6 cm3 in patients with normal left ventricular diastolic function and 164.4 ± 54.9 cm3 in those with impaired left ventricular diastolic function (p = 0.0002). EFT volume was significantly higher in patients who had diastolic dysfunction compared to patients with normal diastolic function (Fig. 3). A ROC analysis revealed that the cutoff value for EFT volume to determine diastolic dysfunction was 129.60 cm3 (75.9 % sensitivity, 79.4 % specificity, 95 % CI 0.637–0.880, AUC 0.758) (Table 3; Fig. 4). After adjusting for the covariables, both age and EFT volume were significantly associated with diastolic dysfunction (OR 1.104; 95 % CI 1.003–1.214; p = 0.043 for age and OR 1.034; 95 % CI 1.010–1.060; p = 0.006 for EFT volume) (Table 4).
There was no significant correlation between EFT volume and coronary calcium score (r = 0.148, p = 0.248). Also, no significant correlation was found between EFT volume and body mass index (r = 0.054, p = 0.674). In the patients with diastolic dysfunction, there was a significant negative correlation between e0 and EFT volume (r = -0.437, p \ 0.0001). Out of 63 patients, 59 patients underwent noninvasive evaluation of coronary artery disease (the treadmill exercise test was performed in 40 patients, dipyridamole nuclear stress myocardial perfusion imaging in 10, and dobutamine stress echocardiography in 9). Thirty patients had abnormal results, and we decided to perform invasive coronary angiography on them. Three patients declined the coronary angiography. Finally, 27 patients underwent invasive coronary angiography. Coronary angiography was normal in 8 patients, 12 had minimal coronary artery disease (coronary artery plaques or \50 % stenosis in epicardial coronary arteries), and 7 had significant coronary artery disease ([50 % stenosis in at least one of the epicardial coronary arteries). When any (minimal or significant) coronary artery stenosis was included in the analysis, there was no significant difference between diastolic-dysfunction-positive and diastolicdysfunction-negative groups (11 patients vs. 8 patients; p = 0.3340).
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Fig. 3 Epicardial fat volume was significantly higher in patients with left ventricular diastolic dysfunction (EFTV epicardial fat tissue volume, DD diastolic dysfunction)
Table 3 Demographic and clinical characteristics according to epicardial fat tissue volume (EFTV)
EFTV \ 129.60 cm3 n = 34
EFTV C 129.60 cm3 n = 29
p value
54.3 ± 10.7
61.8 ± 10.0
0.006*
Male
14 (41.2 %)
15 (51.7 %)
0.559
Female
20 (58.8 %)
14 (48.3 %)
Age (years) Gender
* p \ 0.05 between groups was considered statistically significant
Hypertension
19 (55.9 %)
24 (82.8 %)
0.044*
Diabetes
19 (55.9 %)
19 (65.5 %)
0.603
Current smoking
13 (39.4 %)
9 (31.0 %)
0.674
Hyperlipidemia
23 (69.7 %)
24 (85.7 %)
0.239
Body mass index (kg/m2)
28.8 ± 4.8
30.0 ± 3.3
0.272
Median coronary calcium score (HU)
0.5 (0–255)
15 (0–466)
0.109
Discussion In this study, we found that EFT volume was associated with left ventricular diastolic dysfunction in a group of patients who presented with a complaint of chest pain. There are only a few studies in the literature that document the association between diastolic function and epicardial fat volume. Mean EFT volume was 137.2 ± 56.2 cm3 for the whole study group. In previous studies, the average volume of EFT was generally between 110 and 125 cm3 in the normal population [9, 10]. In this study, the mean EFT was 114 ± 46.5 cm3 in patients with normal left ventricular
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diastolic function and 164.4 ± 54.9 cm3 in those with impaired left ventricular diastolic function (p = 0.0002). Therefore, the mean EFT volume of patients with impaired diastolic dysfunction was higher than it was in patients with normal diastolic function in the present study. The mean EFT volume of patients with impaired diastolic dysfunction in this study is also higher than that of the normal population included in previous studies [9, 10]. Body mass index, which is an indicator of general adiposity, was not significantly different in patients with or without diastolic dysfunction. Therefore, local fat stores such as epicardial fat may be more important than general stores in terms of diastolic dysfunction.
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337
1,0
,8
Sensitivity
,6
,4
,2
0,0 0,0
,2
,4
,6
,8
1,0
1 - Specificity Fig. 4 ROC curve analysis for EFT volume to discriminate patients with or without left ventricular diastolic dysfunction revealed a cutoff value of 129.60 cm3 (AUC = 0.758, 95 % CI 0.637–0.880)
Table 4 Multiple logistic regression analysis showing parameters associated with diastolic dysfunction Odds ratio
95 % confidence interval Lower
p value
Upper
Age
1.104
1.003
1.214
0.043
SBP
1.054
0.925
1.202
0.428
DBP
0.844
0.692
1.030
0.094
BMI
0.952
0.660
1.372
0.791
Waist circumference
1.005
0.883
1.143
0.943
Total cholesterol EFT volume
1.056 1.034
0.989 1.010
1.127 1.060
0.106 0.006
SBP systolic blood pressure, DBP diastolic blood pressure, BMI body mass index, EFT epicardial fat tissue. Statistically significant results (p \ 0.05) are given in bold text
In our cohort of patients with normal left ventricular ejection fraction who were referred for echocardiographic testing, mild diastolic dysfunction was highly prevalent. Data on the natural history of diastolic dysfunction are limited, and further investigations are needed to understand the factors that affect myocardial stiffness. Long-term follow-up is required to identify the link between diastolic dysfunction and EFT volume. In some of the previous studies in this field, the quantity of EFT was evaluated by 2D echocardiography, by measuring its thickness. However, 2D echocardiography is highly dependent on acoustic windows and sometimes
cannot provide an adequate window on all cardiac segments, especially in obese patients and in patients with chronic obstructive lung disease [25]. In addition, there are different echocardiographic measurement techniques which yield different results (i.e., end-systolic vs. enddiastolic measurements, parasternal long-axis only vs. average of parasternal long and short axis measurements). In our study, we used MDCT in order to calculate EFT volume. Submillimeter collimation, high temporal and spatial resolution, and three-dimensional views of the heart and its epicardial surface are the advantages of MDCT. Another technique is cardiac magnetic resonance imaging (MRI). Although MRI has some limitations due to its low spatial resolution, specifically in the z-dimension, it does not involve any radiation and is considered a good modality for visceral fat measurement [26]. However, MRI may not be widely available for this purpose at every institution. Moderate or severe diastolic dysfunction is associated with increased mortality rates in patients with normal systolic function. Although mild diastolic dysfunction was prevalent in our study group, it does not affect survival rate, and less is known about factors involved in the progression of mild diastolic dysfunction to moderate and severe degrees [5]. Understanding the mechanisms of diastolic dysfunction is important from the perspectives of survival rate and prognosis. In our study, we found a significant correlation with diastolic dysfunction and EFT volume. Moderate and severe diastolic dysfunction and their association with EFT volume should be investigated in new studies, as they are associated with an increased mortality rate. In our study, patients with diastolic dysfunction were significantly older than patients without diastolic dysfunction. As shown in previous studies, diastolic dysfunction increases with age [27, 28]. Changes in myocardium occur even during the normal aging process, and they may alter the lusitropic function of the heart. These changes include remodeling of the myocardial interstitium and an increase in myocardial collagen content. Recently, a retrospective study of 14,298 patients revealed that echocardiographically assessed diastolic dysfunction increased with age [29]. Therefore, the fact that the diastolic dysfunction positive group was older in our study was expected. In previous studies, a relationship between EFT volume and coronary atherosclerosis was demonstrated [9, 10]. However, according to our knowledge, EFT volume, diastolic dysfunction, and coronary calcium score were not analyzed together for a single cohort of patients in those studies. In our study, we could not find any association with EFT volume and coronary calcium score. This result may be due to the small number of patients in our group, or there may be other mechanisms that should be investigated in future studies.
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Our study has several limitations. The number of patients included into the study was small, and most of the patients in this study had mild diastolic dysfunction. In addition, diastolic dysfunction was assessed by echo Doppler only, instead of direct catheter measurement of left ventricular end-diastolic pressure. Another limitation is that the presence of silent myocardial infarction in the patients could not be ruled out. In conclusion, epicardial fat tissue volume measured using multidetector computed tomography was found to be significantly associated with left ventricular diastolic function. This finding should enhance the utility of epicardial fat tissue volume measurement for understanding the mechanisms of left ventricular diastolic dysfunction. Further studies are required to identify the linkage between EFT volume and diastolic dysfunction. Conflict of interest of interest.
The authors declare that they have no conflict
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