Download Assessment of Left Ventricular Function in Juvenile Rheumatoid

Med. J. Cairo Univ., Vol. 81, No. 1, June: 431-435, 2013
www.medicaljournalofcairouniversity.net
Assessment of Left Ventricular Function in Juvenile
Rheumatoid Arthritis
GHADA 0. ELSEDFY, M.D.* and HISHAM M. HABIB, M.D.**
The Department of Pediatrics, Faculty of Medicine, Assiut University* and Rheumatology & Rehabilitation Department,
Mansoura University**, Egypt
Abstract
term disabilities [1,2]. It is comprised of a heterogeneous group of several disease subtypes that are
characterized by the onset of arthritis before the
age of 16 years and has symptoms lasting at least
6 weeks [3,4]. It is characterized by chronic synovitis
and associated with many extra-articular manifestations including cardiac involvement. Cardiac
involvement as pericarditis, myocarditis and valvular disease is common in JRA [5]. It is clinically
evident in 3-9% of JRA patients [6] and is known
to occur in children with JRA, as it does in adults
with rheumatoid arthritis [7]. There are, however,
few descriptions concerning systolic and diastolic
functions of the left ventricle (LV) in children with
JRA [8].
Background and Aims: Despite an asymptomatic cardiac
status, significant systolic and diastolic functional abnormalities
exist in patients with JRA. There is, however, paucityn of
data concerning systolic and diastolic functions of the left
ventricle (LV) in children with JIA. The aim of this study was
to identify cardiac involvement with concern to study the
systolic and diastolic function of left ventricle in a group of
children with JRA.
Methods: A total of 32 JRA children (24 females and 8
males) without any cardiac symptoms were included in this
study. The control group consisted of 32 age- and sex- matched
healthy children. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on both groups
to assess both systolic and diastolic functions of the left
ventricle.
Results: Patients with JRA had significantly higher LVESD
and LVEDD as well as higher LVEDV and LVESV than in
the control group (p=0.027, 0.004, 0.013, 0.001 respectively).
EF and FS were within the normal range but were lower
among patients with JRA as compared to controls (p=0.003,
0.082 respectively). Diastolic parameters like peak transmitral E velocity was lower and peak A velocity was higher
amongst the patients with JRA (p=0.015, 0.128 respectively).
This was also reflected by the E/A velocity ratio, which was
significantly lower among patients as compared to the control
group (p=0.001). PVS/PVD ratios was much lower in JRA
patient (p=0.008). Isovolumic relaxation time was found to
be higher in JRA patient as compared to the control group
(p=0.004).
Despite an asymptomatic cardiac status, significant systolic and diastolic functional abnormalities
exist in patients with JRA. The duration of the
illness, mode of presentation, patient's age and
gender have a significant impact on the left ventricular systolic and diastolic functions in patients
with JRA [9].
Pediatric echocardiography has clearly become
the primary tool for describing and characterizing
diastolic function in infants and children both with
and without heart disease. It is becoming an important noninvasive diastolic monitoring tool that
allows serial assessment of pathologic diastolic
disease in both primary myocardial and systemic
disease states [10].
Conclusion: In conclusion, children with JRA should be
assessed for systolic and diastolic functions with serial echocardiography. In this way it may be possible to reduce the
mortality and morbidity of the disease from cardiac causes.
Key Words: Left ventricular function — Juvenile rheumatoid
arthritis (JRA).
The aim of this study was to identify cardiac
involvement with concern to study the systolic and
diastolic function of left ventricle in a group of
children with JRA.
Introduction
JUVENILE rheumatoid arthritis (JRA) is the most
common chronic rheumatologic illness in children
and is a significant cause of both short- and long-
Patients and Methods
This study was conducted from August 2011
to February 2013, at the Departments of Pediatrics
Correspondence to: Dr. Ghada 0. Elsedfy, The Department
of Pediatrics, Faculty of Medicine, Assiut University
431
432
and Rheumatology in a University affiliated hospital in Alhofof, Alhasa, Eastern Province, Kingdom
of Saudi Arabia. Prior to subject recruitment, the
study protocol was reviewed and approved by the
local ethics committee and written informed consents were obtained from all the patients or their
guardians.
A total of 32 JRA children (24 females and 8
males) were included in this study. Patient's mean
age was 10.5 years (range of 3.5-15.5 years) with
disease duration of 44.3-19.5 months with a range
of 5-102 months. All the study group children did
not have any history of cardiac symptoms or any
clinically evident cardiac problem. None of the
patients had any symptoms related to cardiovascular
involvement, nor were there any abnormal auscultatory findings among them.
All patients met American College of Rheumatology criteria for JRA diagnosis 1111. Clinical
evaluation of the study population was done including thorough history taking and general and
systemic examination. Height and weight were
directly measured by using a standardized protocol
and accordingly body mass index (BMI) was calculated by the following equation:
BMI=Weight (Kg)/Square Height (squaremeter)
Collected data obtained included subtype of
JRA, disease duration. Laboratory investigations
of the JRA patients included erythrocyte sedimentation rate (ESR) by the Westergen method, Creactive protein (CRP), rheumatoid factor (RF),
antinuclear antibodies (ANA), anti-citrullinated
peptide/protein antibody (ACPA) and haemoglobin
(Hb) level. The severity of JRA was assessed using
the following: Disease activity score (DAS28) [12]
for polyarticular, oligoarticular JIA, and systemiconset subtypes; Bath AS Disease Activity Index
(BASDAI) for juvenile spondylarthropathy [13].
Medications used for JRA treatment were documented. Special attention was given to detailed
cardiovascular system examination including pulse
rate, blood pressure as well as complete cardiac
examination to find out any cardiac problem that
can be an exclusion criterion.
The control group consisted of children presenting to the Pediatric Outpatient Clinic for routine
vaccination or checkup and included 32 age- and
sex- matched healthy controls.
Echocardiography, was performed to all patients
and controls and included an M-mode, twodimensional, color and Doppler (continuous and
pulse wave) examination. Images were obtained
Assessment of Left Ventricular Function in Juvenile
on a Medison SA 9900 Prime with a 4 MH transducer. Recordings were performed with subjects
in the supine position. M-mode tracings were
obtained in parasternal short axis view. LV systolic
function was assessed by measuring the left ventricular end-systolic dimension (LVESD), LV enddiastolic dimension (LVEDD) using the "leading
edge to leading edge" according to the recommendations of the American Society of Echocardiography and averaged over three consecutive cardiac
cycle.
The left ventricular end-diastolic and endsystolic volumes (LVEDV, LVESV) were calculated
from the apical four-chamber view, using the ellipsoid single plane algorithm. Mean left ventricular
volume, fraction shortening (FS) and ejection
fraction (EF) were automatically calculated. Cardiac
output was measured by multiplying heart rate
with stroke volume.
LV diastolic function was assessed by measuring
the mitral flow velocity recorded in the apical fourchamber view using the pulse wave Doppler. Isovolumic relaxation time (IVRT) was measured in
the apical five-chamber view with the sample
volume placed between the aorta and mitral valve
where the recordings of both valves were taken
simultaneously. Pulmonary veins were then traced
from the subcostal view. Pulsed wave Doppler
patterns of pulmonary venous flow and mitral
inflow recorded to show the duration of flow during
atrial contraction. The various variables of diastolic
function were measured in both JRA children and
compared to those findings in normal controls.
Statistical analysis:
All statistical calculations were performed using
computer programs Microsoft Excel version 7
(Microsoft Corporation, NY, USA) and SPSS version 13 (Statistical Package for the Social Science;
SPSS Inc., Chicago, IL, USA) statistical program.
All data are expressed as mean and standard deviation. Student's t-test was used for inter-group
comparisons. Data were statistically described in
terms of number and percentage. Comparison of
the studied groups was done using the Chi square
test to compare categorical variables. A p-value
less than 0.05 was considered statistically significant.
Results
Demographic data for both groups were nearly
similar with no statistically significant differences
as shown in (Table 1). Athough the absolute values
were within the normal limits, the systolic and
433
Ghada 0. Elsedfy & Hisham M Habib
diastolic blood pressures were significantly higher
among patients with JRA as compared to the corresponding values found in controls (p=0.032 &
0.002 respectively). Resting heart rates were also
higher among the JRA patients as compared to
controls (p=0.005).
Table (1): Demographic and clinical characteristics of JRA
patients and controls.
Parameter
JRA group Control group P
(N=32)
(N=32)
value
Sex:
Female
Male
24 (75%)
8 (25%)
22 (68.8%)
10 (31.2%)
0.578
Age (years):
Mean±SD
Range
10.5±3.4
(3.5-15.5)
11.1±3.5
(4-16)
0.472
Body mass index (Kg/m 2) 21.8±3.6
(Mean±SD)
Heart Rate (Mean±SD)
86.4±13.3
22 .6±3. 5
0.367
77.7±10.6
0.005
107.9±10.2
67.8±11.8
0.032
0.002
Blood pressure (mmHg)
(Mean±SD):
Systolic
Diastolic
116.1±18.2
80.2±17.7
Table (2) showed data of JRA patients. The
most frequent subtype was rheumatoid factorpositive polyarthritis (28.1%) followed by oligoarticular and systemic subtypes; each of (25%) and
least frequency was enthesitis-related arthritis
subtype (9.4%). For laboratory data, RF was positive in 28.1%, mean CRP level was 12.6, ANA
was positive in 18.8%, ACPA Positive patients
were 15.6%, mean ESR was 39.5, mean CRP was
12.6 and mean Hb concentration in patients was
11.1gm%. For disease activity in JRA enrolled
patients except enthesitis-related arthritis subtype,
mean DAS 28 was 4.6 while mean BASDAI for
enthesitis-related arthritis subtype was 5.6. More
than fifth of the JRA children (21.9%) were receiving corticosteroid. Biological therapy was used in
9.4% of them, while disease-modifying antirheumatic drugs (DMARDs) were used in 93.7%.
Table (3) shows the left ventricular systolic
function assessment in JRA and control groups.
Patients with JRA had significantly higher LVESD
and LVEDD as well as higher LVEDV and LVESV
than in the control group (p=0.027, 0.004, 0.013,
0.001 respectively). Although EF and FS were
within the normal range, the values were lower
among patients with JRA as compared to controls
(p=0.003, 0.082 respectively). The cardiac output
was comparable between the two groups (p=0.411).
Significant differences were observed in almost
all diastolic parameters in patients of JRA as com-
pared to controls as shown in (Table 4). Peak transmitral E velocity was lower and Peak A velocity
was higher amongst the patients with JRA (p=0.015,
0.128 respectively). This was also reflected by the
E/A velocity ratio, which was significantly lower
among patients as compared to the control group
(p=0.001).
Table (2): Data of JRA patients.
Variable
Data
JRA subtype:
RF-positive polyarthritis
RF-negative polyarthritis
Enthesitis-related arthritis
Oligoarticular
Systemic
9/32 (28.1%)
4/32 (12.5%)
3/32 (9.4%)
8/32 (25%)
8/32 (25%)
Laboratory findings:
RF- RF Positive
ANA positive
ACPA Positive
ESR (mm/h)
CRP Positive (mg/1)
Hb concentration mean (gm/dL)
9/32 (28.1%)
6/32 (18.8%)
5/32 (15.6%)
39.5±17.5
12. 6±4 .2
11.1±2.2
Disease activity findings:
DAS28
BASDAI
4.6±1.43
5.6±1.8
Medications:
Corticosteroid treated patients
Biologic treated patients
DMARD treated patients
7/32 (21.9%)
3/32 (9.4%)
30/32 (93.7%)
RF
= Rheumatoid factor.
ANA
= Antinuclear antibodies.
ACPA = Anti-citrullinated peptide/protein antibody.
ESR
= Erythrocytic sedimentation rate.
CRP
= C reactive protein.
Hb
= Hemoglobin.
DAS28 = Disease activity score 28.
BASDAI = Bath Ankylosing Spondylitis Disease Activity Index.
Table (3): Left ventricular systolic function assessment in
JRA and controls.
JRA
group
(N=32)
Control
group
(N=32)
P
value
Left Ventricular end
diastolic diameter (mm)
40.8±6.3
36.9±7.2
0.027
Left Ventricular end
systolic diameter (mm)
25.2±3.1
22.6±3.7
0.004
Left Ventricular end
diastolic volume (ml)
74.1±15.9
65.2±11.7
0.013
Left Ventricular end
systolic volume (ml)
25.9±3.8
23.1±2.5
0.001
Ejection fraction (%)
63.2±8.1
69. 8±9.1
0.003
Fractional shortening (%)
35.9±7.8
39.2±6.9
0.082
Cardiac output (L/min)
3.7±1.2
3 .4±1. 2
0.411
Parameter
434
Assessment of Left Ventricular Function in Juvenile
Though PVS velocities were comparable in the
two groups, PVD velocities were significantly
higher amongst patients, thus leading to much
lower PVS/PVD ratios in JRA patient (p=0.008).
Isovolumic relaxation time was found to be higher
in JRA patient as compared to the control group
(p=0.004).
Table (4): Left ventricular diastolic function assessment in
JRA and controls.
Parameter
Peak early diastolic flow
velocity (m/sec) E
Peak late diastolic flow
velocity (m/sec) A
E/A velocity ratio
Pulmonary vein systolic
peak velocity (m/sec)
Pulmonary vein diastolic
peak velocity (m/sec)
PVS/PVD
Isovolumic relaxation
time (msec)
JRA
group
(N=32)
Control
group
(N=32)
P
value
0.94±0.27
1.16±0.42
0.015
0.73±0.25
0.65±0.19
0.128
1.35±0.36
0.75±0.25
1.72±0.46
0.73±0.25
0.001
0.805
0.63±0.18
0.54±0.18
0.038
1.31±0.47
69.8±9.2
1.62±0.44
63.4±7.9
0.008
0.004
Discussion
This study was carried out to identify cardiac
involvement with concern to evaluate the systolic
and diastolic function of left ventricle in patients
with JRA. It is postulated that cardiac involvement
is common in JRA and it is the second major cause
of mortality in this disease [5,8] . Cardiac involvement as pericarditis, myocarditis and valvular
disease is known to occur in patients with JRA as
it does in adults with rheumatoid arthritis. There
are, however, few descriptions concerning systolic
and diastolic functions of the left ventricle (LV)
in children with JRA 1111.
The main purpose of the current study is the
early detection of cardiac involvement in JRA
patients without being clinically evident or presence
of any organic heart lesion. We relied upon Echocradigraphy to map out our results. Frommelt [10]
summarized that pediatric echocardiography has
clearly become the primary, non-invasive tool for
describing and characterizing diastolic function in
infants and children both with and without heart
disease.
The findings of the increased left ventricular
size and reduced systolic function indices as evident
by lower FS% and EF (inspite of being within the
normal range for both parameters) as compared to
normal controls. These early detectable significant
changes in the left ventricular systolic function
that could be detected by ECHO examination without any clinical manifestations of cardiac involvement could be considered as baseline information
for further follow-up of the cardiac function in
such group of JRA patients. These changes were
found to be in agreement with previous studies
checked JRA patients without cardiac involvement
[14] and those who had clinically evident cardiac
manifestations [15].
Almost all the left ventricular diastolic function
parameters in patients of JRA were found to be
impaired when compared to those of normal controls in the current study. Peak trans-mitral E
velocity was lower and Peak A velocity was higher
as well as significantly lower E/A velocity ratio
amongst the patients with JRA. This is the reverse
of the normal pattern which reflects an alteration
in left ventricular compliance and might reflect
left ventricular structural changes. These findings
are in consistence with that of Bharti et al., and
Oguz et al. [5,9].
We found that PVD velocities were significantly
higher amongst JRA patients and PVS/PVD ratio
was found to be significantly much lower in JRA
patient. Isovolumic relaxation time was found to
be significantly higher in JRA patient as compared
to the control group. These results were in agreement with that of Koka et al. [7].
It is reported that Inflammatory and cellular
myocardial fibrotic process happens in JRA 1151.
Moreover, Bergfeldt also concluded an increased
atrial filling phase due to increase interstitial fibers
in the myocardial tissue indicating post inflammatory changes [16]. As a result of that, there will be
a decrease in preload, an increase in afterload, or
impairment of relaxation of the left ventricle which
can explain these changes.
Our findings that detected left ventricular dysfunction in patients with JRA is consistent with
previous reports done in adult patients with RA.
Vizzardi et al., reported a high prevalence of left
ventricular systolic and diastolic dysfunction in a
population of outpatients affected by rheumatoid
arthritis [17]. This finding was also ascertained that RA patients were more likely to have abnormal
echocardiographic parameters of diastolic dysfunction -in the meta-analysis review for echocardiographic evaluation of asymptomatic patients affected by rheumatoid arthritis done by Aslam et al.
[1 8] . Silent myocarditis could be the underlying
mechanism of impaired ventricular functions in
Ghada 0. Elsedfy & Hisham M Habib
such JRA patients with implication of the humoral
component of bodily immunological reactivity.
This seems to have an important implication in
pathogenesis of carditis in JRA [19].
Finally, we observed some characteristics in
our cohort of patient depending on patients' data.
We do not know if these findings have implications
on cardiac status of JRA patients. The general
concept obtained was that those patients carry a
potential for disease activity. For example, those
patients were of moderate disease activity grading
depending on DAS 28 and BASDAI, more than
fifth of those patients are on corticosteroid therapy,
and about 10% of patients were on biological
therapy. Laboratory data was supporting this notice.
ESR, CRP were elevated, ACPA was elevated in
a sector of those patients and RF was present in
more than a quarter. Those observations need more
support through further wide-scale studies stressing
upon clinical characteristics of JRA patients and
correlations with their cardiac involvement. Bharti
et al noted that; the duration of the illness, mode
of presentation, patient's age and gender have a
significant impact on the left ventricular systolic
and diastolic functions in patients with JRA [9]. To
our knowledge, apart from that; no reports have
studied the correlation between clinical and cardiac
data in JRA patients.
Conclusion:
In conclusion, children with JRA should be
assessed for systolic and diastolic functions with
serial echocardiography. In this way it may be
possible to reduce the mortality and morbidity of
the disease from cardiac causes.
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