Download Epicardial Fat Volume in Patients With COPD and Cor Pulmonale

Epicardial Fat Thickness in Patients with Cor Pulmonale
Dr Özgür Kaplan1* ([email protected]), Dr. Gökhan Gözübüyük1
([email protected]), Dr. Zeydin Acar2 ([email protected]), Dr. Hasan
Pekdemir3 ([email protected]), Dr.Ferhat Eyyüpkoca3 ([email protected])
*: Corresponding Author (Dr Özgür Kaplan1)
*1 : MALATYA STATE HOSPITAL, Department of Cardiology
*2: Ahi Evren Thorasic and Vascular Surgery Training and Research Hospital, Cardiology
Trabzon, Turkey
*3: İnönü University School of Medicine, CARDIOLOGY MALATYA, Turkey
ABSTRACT
The relation of epicardial-fat-tissue (EFT) with left-ventricular-dysfunction and
cardiovascular metabolism and coronary artery disease has been known. The objective of this
study is the evaluation of EFT in patients with cor-pulmonale (CP) who have an isolated right
heart failure.
36 patients with CP and 30 healthy controls were included in the study. The patients’
with CP right ventricular fractional area change is less than 17%, however that of control
group is between 32% and 60%. Patients with a history of CAD and left ventricular
dysfunction were not included in the study.
EFT was decreased (4,1 ±0,7 vs 6,1±1,2 p=0,001) in patients with CP compared to
control group. The difference between the two groups was independent of body-mass-index.
EFT is decreasing independently from BMI in the patients with right ventricular
dysfunction who do not have left ventricular dysfunction. Epicardial fat thickness would be
predictor for degree of right heart failure.
Key Words; Epicardial fat tissue,Epicardial fat thickness, Cor Pulmonale
Introduction
Pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD)
is a frequently seen cardiovascular complication. With the growth of the PAH secondary to
hypoxia, first right ventricular hypertrophy and / or dilatation or failure and then Chronic CP
develop over the time (1-2). In these patients, measurement of epicardial fat and evaluating
its relation with right heart functions by using echocardiography has great advantages in
practice because of echocardiography’s quick, repeatable and non-invasive nature. Epicardial
fat and its relation with coronary heart disease, metabolic syndrome and left ventricular
dysfunction has been shown in previous studies (3-8). However, the relation between EFT and
right heart functions has not been shown yet. In this study, we examined EFT in patients with
cor pulmonale with isolated right heart failure.
Methods and Procedures
Study Population
We have included 36 CP patients and 30 healthy subjects in our study, and those with CP
were selected from the subjects who were previously diagnosed and put under treatment. BMI
is calculated as weight in kilograms divided by the height in meters squared (kg/m2) and,
normal weight is defined as BMI ≤25 kg/m2 and obesity is defined as BMI ≥30 kg/m2.
Patients and controls with a history or clinical evidence of left ventricular (LV) wall motion
abnormality or coronary artery disease, LV ejection fraction (EF) less than 50%, primary
cardiomyopathy, valvular heart disease, congenital heart disease bundle branch block,
atrioventricular conduction abnormalities on electrocardiogram, pericarditis, liver disease,
chronic renal disease, thyroid dysfunction, anemia, electrolyte imbalance, systemic
inflammatory disease and inadequate transthoracic echocardiographic imaging were excluded
from study. All of the subjects have sinus rhythm. The study has been carried out according to
the principles of the Declaration of Helsinki and approved by Malatya State Hospital
investigational review board.
Echocardiography
In all subjects, echocardiographic examinations (Vivid 7pro,GE Vinmed ,Milwauke USA)
were performed by a cardiologist who was blinded to the clinical details and results of the
other investigations of each patient and control. During echocardiography examination, a 1lead ECG was recorded continuously. M-mode measurements were performed according to
the criteria of American Society of Echocardiography. Three consecutive cycles were
averaged for every parameter. Left atrial (LA) dimension, LV end-systolic and end-diastolic
diameters were measured. LVEF was estimated by Simpson’s rule. Transmitral pulsed-wave
Doppler velocities were recorded from the apical 4-chamber view with Doppler sample
placed between the tips of the mitral leaflets. Early (E) and late (A) wave velocities, E/A ratio,
E deceleration time (DT) and isovolumetric relaxation time (IVRT) were measured from the
mitral inflow profile. Right ventricular systolic function measured with right ventricular
fractional area change. EFT was measured according to the method previously described and
validated (9). The epicardial fat was identified as the echo-free space between the outer wall
of the myocardium and visseral layer of pericardium. EFT was measured perpendicularly on
the free wall of right ventricle at end diastole in 3 cardiac cycle. The maximum value at any
site was measured and the avarage value was calculated.
We have divided the patients into groups with respect to fractional area changes in order
to evaluate right ventricular functions. Right ventricular fractional area change was calculated
in apical four chamber view by the ratio of the difference between end-diastolic and endsystolic right ventricular areas to the end-diastolic right ventricular area. Normal range of
right ventricular fractional area change is between 32-60% , the values between 25-31%
were considered as mild and with values ≤ 17 were considered as severe right ventricular
systolic dysfunction (10). The patients with a right ventricular area change <17%
accompanied by a mean pulmonary artery pressure> 45 mmHg were considered as cor
pulmonale patients.
By placing pulsed-wave Doppler to right ventricular free wall and tricuspid annulus junction
in apical four-chamber view, isovolemic acceleration time (IVA) were measured by dividing
the baseline-peak velocity during isovolumic contraction to the peak myocardial velocity
during isovolumic contraction.In addition; by placing M-mode tracing at lateral free wall and
tricuspid annulus junction in apical four-chamber view, tricuspid annular plane systolic
excursion (TAPSE) were measured and right ventricular dysfunction was defined as TAPSE
value less than 2 cm (11). Myocardial performance index (MPI) were calculated by dividing
sum of right ventricle lateral wall interventricular contraction time (IVCT) and IVRT to total
ejection time (ET) with tissue wave Doppler and normal values accepted for right ventricule
were 0.28 ± 0.04 (12).
Statistical Analysis
Statistical analysis was performed using SPSS for Windows version 15.0 software (SPSS
Inc, Chicago, IL). All continuous variables were expressed as mean ± SD, and categorical
variables were defined as percentages. Categorical data was compared using the chi-square
test. Continuous variables were compared between the groups using the Student’s t-test or
Mann-Whitney U test, depending on whether they distributed normally or not, as tested by
the Shapiro-Wilk test. Pearson’s correlation analysis was used to estimate the relationship
between the test parameters. A P value <0.05 was considered to be statistically significant.
Results
Clinical characteristics and laboratory data of 36 CP patients (mean age 67 ± 9.9) and 30
normal healthy subjects (mean age 70± 5.7) are listed in Table 1. Obese subjects and the
controls were similar regarding to the age, gender, diabetes mellitus, hypertension,
dyslipidemia and BMI. However there exist only significant difference was in smoking habits
and it was higher in CP patients (p= 0.01).
The results of right ventricule echocardiographic parameters and EFT are shown in Table 2.
When right ventricle echocardiographic parameters of patients with CP were compared to
controls; IVA, TAPSE and MPI values were significantly lower (1.9 ± 0.3 vs 2.6± 0.4
p=0.001; 17 ± 2.4 vs 25 ± 2.2 p=0,001; 0,71 ± 0.12 vs 0.48±0.10 p=0.001; respectively) in
the patient group. When it is compared with controls, EFT were found to be thinner in
patients with CP (4.1 ± 0.7 vs 6.1±1.2 p=0.001) (Table 2, Figure 1).
A significant positive correlation was detected among EFT and both TAPSE and IVA
(r=0.653 p=0,001 and r=0.377 p=0.02, respectively) and also, there was a significant negative
correlation between EFT and MPI (r=-0.543 p=0.001) (Table 3). EFT / BMI ratio were
measured in each group by dividing EFT to BMI in order to show EFT in each group is
independently from BMI values. EFT / BMI was found 0.239 ± 0.417 in control group,
however its value in cor pulmonale group was found 0.173 ± 0.38. Difference between two
groups (p = 0.001) was significant (Fig. 2).
Table 1. Demographic and laboratory variables of the patients with CP and the
controls
Age
Cor Pulmonale (n=36)
67 ± 9,9
Control Group (n=30)
70± 5,7
P value
0,16
Gender (female/male)
10/26
12/18
0.3
BMI
23,9±3,3
25,3±3,3
0,08
Diabetes, n(%)
2(%5,6)
0
0,22
Dyslipidemia, n(%)
0
2(%6,7)
0,22
Hypertension, n(%)
11(%30,6)
16(%53,3)
0,06
Smoker, n(%)
20(%55,6)
8(%26,7)
0,01
BMI= Body mass index.
Table 2. Right ventricle parameters and epicardial fat tissue
TAPSE
MPI
IVA
EFT
Cor Pulmonale
(n=36)
17±2,4
0,71±12
1,9±0,3
4,1±0,7
Control Group
(n=30)
25±2,2
0,48±10
2,6±0,4
6,1±1,2
P value
0,001
0,001
0,001
0,001
MPI=Myocardial performance index, IVA=Isovolumic acceleration time,TAPSE= Tricuspid
annular plane systolic excursion, EFT= Epicardial fat tissue.
Table 3. Correlation between epicardial fat tissue and other measured variables
Correlation coefficient
P value
0,653
0,001
TAPSE
-0,543
0,001
MPI
0,377
0,02
IVA
MPI=Myocardial performance index, IVA=Isovolumic acceleration time,TAPSE= Tricuspid
annular plane systolic excursion.
Table 4. Correlation between epicardial fat tissue/body mass index ratio and other measured
variables.
Epikardial fat thickness (mm)
Correlation coefficient
P value
0,599
0,001
TAPSE
-0,587
0,001
MPI
0,379
0,02
IVA
MPI=Myocardial performance index, IVA=Isovolumic acceleration time,TAPSE= Tricuspid
annular plane systolic excursion.
7
6
p=0,001
5
4
3
2
1
0
CONTROL
COR PULMONALE
Figure 1: Analysis of epicardial fat thicknes in patients with cor pulmonale compared to
controls.
EFT/BMI(mm/kg/m2
0.3
0.25
p=0,001
0.2
0.15
0.1
0.05
0
CONTROL
COR PULMONALE
Figure 2: Epicardial fat thicknes corrected for body mass index in patients with cor pulmonale
compared to controls.
DISCUSSION
Epicardial adipose tissue has a smaller adipocyte size but higher rates of fatty acid uptake
and secretion than other visceral fat depots (13-14). Epicardial fat has some vital benefits such
as being a buffer, absorbing fatty acids and protecting the heart against high fatty acids levels.
In addition it is used as a local energy source at times of high demand, channeling fatty acids
to the myocardium (13). A body of evidence shows that epicardial fat is an extremely active
organ that produces several bioactive adipokines.
In earlier studies, it was shown that epicardial fat reduction in heart failure, coronary heart
disease and metabolic syndrome had a direct relation with the increase in cardiovascular
events(3-7). Also, many complex and diverse metabolic processes are known that plays role
in increase and decrease of EFT. However, we set our control groups that did not have a
difference with CP in terms of DM, hypertension, dyslipidemia, BMI, age and gender because
of the effect of direct metabolic events on EFT.
CP is known to have systemic effects like that of COPD. These are: systemic
inflammation, nutritional changes and effects on the cardiovascular system. Systemic
inflammation is discriminated by oxidative stress, activated inflammatory cells and cytokines
and an increase of plasma levels of acute phase proteins. In the meantime, an imbalance
between oxidant-antioxidant status could be observed (15). All of these metabolic processes
could be effective on EFT. Nutritional changes, especially weight loss, are seen in patients
with CP. However, herein weight loss is due to the loss of skeletal muscle mass rather than
the loss of fat mass (16). Decreament of EFT in CP group may indicate that EFT is different
from other fat tissues.
In an earlier studies, epicardial fat has been shown to be associated with left ventricular
volume and dysfunction independently from BMI. Left ventricular dysfunction has shown to
be significantly decreased in patients group(8). In our study, EFT and RV dysfunction showed
a similar relationship independent of BMI. That is, EFT has shown a similar change with a
dysfunction in any part of the heart. Because of its anatomical and functional proximity to the
myocardium and its intense metabolic activity, some interactions between the heart and its
visceral fat depot have been suggested. In another study, EFT was evaluated in patients with
obstructive sleep apnea. Thinning of EFT was seen with an increase in the degree of sleep
apnea, independent of BMI. Although EFT is associated with general adiposity, it was tought
that it was related with visceral adiposity (17, 18). These results support the results of our
study.
We suspect that this relation may represent a continuum in epicardial fat dynamics. As
the myocardium becomes more dysfunctional and develops abnormal metabolic needs, the
role for epicardial fat as a source of energy or cytokine hemeostasis would decrease,and as
such, less would be found.(19, 20).
One limitation of our study is that there was not any evaluation of patients for CAD and
the number of patients studied.
Conclusions
Echocardiographic determination of EFT is important because of its inexpensive,
reproducible and non-invasive nature. EFT evaluation is a very easy technigue and gives
valuable information in terms of its relation with cardiovascular events especially in
debilitated patients and those with chronic diseases. In this study we have showed that the
patients with CP have thinner EFT than healty persons. In addition, epicardial fat thickness
would be a predictor of the degree of right heart failure. This contribution was done by only
using echocardiography. One other important contribution of this study is reproducibiality of
it because of usage easily found devices during the diagnosis.
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