Download Tissue Doppler Imaging and Early Myocardial Dysfunction In Poorly

Tissue Doppler Imaging and Early Myocardial Dysfunction In Poorly Treated
Pediatric Thalassaemia Patients
MANUSCRIPT TYPE: original research
AUTHORS:
Mohamed H. Ibrahim, MD, Department of cardiology, Benha Faculty of
Medicine, Benha University, Egypt.
Ahmed Azab, MD, Department of pediatrics, Benha Faculty of Medicine, Benha
University, Egypt.
Naglaa M Kamal, MD, Department of pediatrics, Faculty of Medicine, cairo
university, Egypt.
Mostafa Abdelazim, MD, Department of pediatrics, Benha Faculty of Medicine,
Benha University, Egypt.
Mohamed Samaha, MD.
FUNDING:
No funds were provided to the current work.
CONFLICTS OF INTEREST:
Authors declare no conflicts of interest.
ABSTRACT
Background: Cardiac disorders related to biventricular failure are the most
frequent cause of death in patients with beta-thalassemia-major (B-TM). Tissue
Doppler Imaging (TDI) has evolved as a new technique for detection of early
cardiac dysfunction.
Objective: to evaluate the value of TDI for early detection of myocardial
dysfunction in pediatric patients with B-TM before development of overt heart
failure or cardiomyopathy.
Patients and methods: This study was conducted on 100 thalassemic children 218 years and 100 healthy, age & sex matched controls. The patients were
subjected to echo-Doppler examination, through measuring left ventricular end
diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD),
ejection fraction (EF), fractional shortening (FS) and transmitral Doppler flow of
E & A waves. Patients have also undergone TDI for both the septal and lateral
walls of the basal mitral annulus and also the basal tricuspid annulus assessing
the systolic myocardial velocity (S wave), early diastolic myocardial velocity (Ea
wave) and late diastolic myocardial velocity (Aa wave ).
Results: Conventional Echo-Doppler techniques have failed to distinguish LV
systolic and diastolic function of patients with thalassaemia and that of normal
controls when global function was examined . Our data show that patients with
thalassaemia have RV and LV dysfunction on the basis of abnormal tissue
Doppler derived myocardial velocities. We found statistically significant
differences between the patients and the control subjects in (Aa) and (S) of the
septal wall of the basal mitral annulus and (Ea) of the lateral wall of the mitral
annulus . Also patients with thalassemia have significantly higher (S) of the basal
tricuspid annulus.
Conclusion: From our data we conclude that clinically asymptomatic patients
with thalassaemia have abnormal left ventricular and right ventricular
dysfunction detected by TDI in the absence of global dysfunction by
conventional echo-Doppler which may be a reflection of early myocardial
damage.
INTRODUCTION AND AIM OF THE WORK:
Beta thalassemia major is the most common chronic hemolytic anemia
among children and adolescents across the world.(1) In Egypt  thalassemia is the
most common hereditary hemolytic anemia. The rate of new births with
thalassemia is 1000 per year. (2)
The regular blood transfusion programs and chelation treatment have
considerably improved the survival of patients with thalassemia. However, a
consequence of chronic transfusion therapy is secondary iron overload, which
adversely affect function of the heart, liver and other organs, causing sever
morbidity and shorten the life expectancy.(1)
Despite the dramatic gains in survival after the use of desferrioxamine, the
cardiac complications are still the primary leading cause of death for young
adults with -thalassemia major. (3)
Heart failure is caused by anemic hypoxia, cardiac hemosiderosis,
arrhythmias and hyperdynamic circulatory overload.(3)
Chronic anemia and tissue hypoxia induce impaired free fatty acid
oxidation and ATP production in myocardial cell. Multiple pathologies have
been suggested in the development of cardiac dysfunction in thalassemic
patients including myocarditis and iron overload in the heart leading to LV
dysfunction and iron overload in the lungs leading to elevated pulmonary
arteriolar resistance, RV dilatation and dysfunction. However, congestive heart
failure develops late in the disease process of these patients. Because congestive
heart failure is the main cause of death in these patients, early recognition of
cardiac dysfunction may be useful in modifying therapy.(4)
Initial
cardiac
changes have been documented by conventional echocardiography, in
thalassemics without clinical manifestations.(5)
Several studies have demonstrated that pulsed Tissue Doppler Imaging
(TDI) has the ability to show additional information compare to conventional
echocardiography detecting early changes in cardiac function and thereby
predicting prognosis.(6)
The aim of this study was to evaluate the cardiac function of Thalassemia
patients using standard echocardiographic techniques and TDI .
PATIENTS AND METHODS:
This study was carried out at pediatric department of Banha University
Hospital. It included 100 patients with β thalassemia major with ages 2 to 18
years. One hundred age and sex matched apparently healthy controls were
enrolled. The study was approved by the research and ethical committees of the
contributing hospital. Written informed consent was obtained from patients or
their parents. All cases and controls were subjected to full history taking (for
symptoms of heart failure,
co-morbid diseases, drug history and history of
transfusions), thorough clinical examination (for signs of heart failure such as
gallop rhythm, raised jugular venous pressure and delayed capillary refill),
laboratory investigations (CBC and serum ferritin) and imaging using EchoDoppler and TDI.
Echo-Doppler examination included:
(A) M-Mode and two dimensional echo to measure left ventricular end
systolic diameter (LVESD), left ventricular end diastolic diameter
LVEDD,
left
ventricular
mass
(LVM).,
ejection
fraction
(EF%),fractional shortening (FS% ) and tricuspid annular plane
systolic excursion (TAPSE).
(B)
Conventional Doppler.
(C) Tissue Doppler imaging.
Echo-Doppler technique
By using ATL 5000 echocardiography machine, tissue Doppler imaging
data were acquired transthoracically using a 2.5 or 3.5 MHZ transducer. The
mitral inflow velocity pattern was recorded in the apical 4-chamber view with
the pulsed wave Doppler sample volume positioned at the tip of mitral leaflets
during diastole. In Doppler tissue imaging, the sample volume was positioned at
the medial (septal) end of the mitral annulus, lateral end of the mitral annulus
and tricuspid annulus in apical four chamber view with proper alignment of the
examined area with the Doppler beam. The velocities of different waves then
determined (S, Ea, Aa). Isovolumic contraction time (IVCT) was calculated from
mitral valve closure to the aortic valve opening (end of Aa to onset of S wave).
Ejection time (ET) was calculated from onset of (S) to end of (S). Isovolumic
relaxation time (IVRT) was calculated from aortic valve closure to mitral valve
opening (end of S to onset of Ea). Then, myocardial performance index (MPI) or
(LV Tei index ) was calculated as the sum of IVCT and IVRT, dividing it by ET.
The same was applied on the tricuspid valve to assess the right ventricular MPI
(RV Tei index).
Pulmonary capillary wedge pressure (PCWP) was assessed using the mitral E
velocity to early diastolic myocardial velocity of the septal wall of the mitral
annulus (Ea) ratio, with the formula PCWP=1.9 + 1.24(E/Ea).
Measurements of the myocardial velocities were performed on three
consecutive heart beats and the average of the three measurements was
calculated. All patients were in sinus rhythm at the time of examination.
RESULTS :
Table (1): Demographic data of the study patients and control group
Parameter
β-TM
Control
P-value
Age (Years)
12.1 ± 4.1
11.5± 4
0.05
Male
70 (70%)
70 (70%)
0.05
Weight (kg)
35.7±12.7
40± 10.5
0.05
230
<0.05
Serum
Ferritin 1570 ± 50
22
(mg/L)
Hemoglobin
6.7±1.3
11.5±1.5
<0.05
(gm/dl)
Ten patients did not receive iron chelating drugs and ninety patients were
receiving it irregularly after blood transfusion by manual S.C. pump or through
I.V infusion. This makes all patients are poorly transfused and irregularly
chelated.
The mean hemoglobin level of the patients was 6.7 ± 1.3 gm/dl while the mean
level of the control group was 11.5±1.5 gm/dl (p-value <0.05 ). Serum Ferritin
level was significantly higher in the thalassemic patients compared to control
group (table 1)
Table (2): Conventional echocardiographic data
Parameter
β-TM
Control
P-value
LVEDD
4.4± 0.7
4±0.52
<0.05
2.8± 0.6
1.42± 0.42
<0.05
108.9±50.4
75± 20.5
<0.05
FS(%)
36.5 ± 6.03
35± 5.15
0.05
EF(%)
66±8.03
67±6.5
0.05
Mitral E/A ratio
2.2±0.8
2.3±0.7
0.05
LV Tei index
0.32±0.11
0.41±0.10
<0.05
RV Tei index
0.24±0.09
0.18±0.08
0.05
TAPSE (cm)
2.41±0.42
2.24±0.36
0.05
(in cm)
LVESD
(in cm)
LVM
(in gms)
The conventional echo-Doppler showed that the mean value of the LVEDD ,
LVESD and LVM for cases were significantly higher than the control group while
there was no significant difference between cases and control group regarding FS
and EF.
Also mean value of the transmitral E/A ratio for cases and control group was not
statistically significant ( table 2)
Table (3): Tissue Doppler imaging data
Parameter
β-TM
Control
P-value
Mitral valve, septal wall
Ea (cm/s)
12.7±2.10
13.2±2.41
0.05
Aa (cm/s)
7.70±2.50
5.72±1.41
<0.05
S (cm/s)
10.70±1.75
7.90±1.23
<0.05
Septal E/Ea ratio
8.10±1.31
6.55±1.60
<0.05
Mitral valve , lateral wall
Ea (cm/s)
18.2±2.41
15.8±1.82
<0.05
Aa (cm/s)
7.30±1.41
6.60±1.72
0.05
S (cm/s)
10.3±2.30
9.61±1.80
0.05
14.8±2.63
12.6±1.30
<0.05
Tricuspid valve
S (cm/s)
Ea (cm/s)
15.9±2.24
13.8±3.00
0.05
Aa (cm/s)
10.4±2.54
8.83±2.74
0.05
Discussion :
Beta-thalassemia is the most common hereditary hemolytic anemia in Egypt. The
rate of new births with thalassemia is 1000 per year. (2)
The regular blood transfusion programs and chelation treatment have
considerably improved the survival of patients with thalassemia. However, a
consequence of chronic transfusion therapy is secondary iron overload, which
adversely affect function of the heart, liver and other organs, causing sever
morbidity and shorten the life expectancy.(3) Chronic anemia and tissue hypoxia
induce impaired free fatty acid oxidation and ATP production in myocardial cell.
Multiple pathologies have been suggested in the development of cardiac
dysfunction in thalassemic patients including myocarditis and iron overload in
the heart leading to LV dysfunction and iron overload in the lungs leading to
elevated pulmonary arteriolar resistance, RV dilatation and dysfunction. (4)
In clinical practice, serum ferritin has been commonly used to assess the severity
of iron overload and the effectiveness of treatment.
(7)
Serum ferritin does not
correlate with myocardial iron load. However advantages of serum ferritin
measurement are that it is easy to assess, inexpensive, amenable to serial
measurements for monitoring chelation therapy, and correlates positively to
morbidity and mortality.
(8)
Also, systolic dysfunction was not correlated with
serum ferritin and occured in a late stage of the disease.
(9)
This is why we did
not correlate the echo-Doppler findings with serum ferritin levels. Congestive
heart failure develops late in the disease process of these patients. Because
congestive heart failure is the main cause of death in these patients, early
recognition of cardiac dysfunction may be useful in modifying therapy (4)
However conventional M-mode techniques have failed to distinguish LV
function of patients with thalassaemia from that of normal controls when global
function was examined.(6)
The present study aimed to investigate the value of
using
tissue Doppler
imaging in the evaluation of diastolic and systolic ventricular function in
addition to conventional echocardiography in patients with beta thalassemia.
In our study, conventional echocardiography showed LV dilatation and no
abnormalities in LV systolic function. There was significant difference between
cases and controls regarding LVEDD and LVESD. Kremastinos et al.(10) and
Favilli et al.
(11)
found also that the ventricles were dilated in thalassemic
patients than control subjects. Khalifa et al. (12) showed a significant increase of
all cardiac dimensions by echocardiography (LAD-AORD-LVEDD-LVESD).
They stated that these cardiac structural changes are due to chronic anemia more
than siderosis.
The mean LVM was increased in thalassemic patients than control group and
there was a highly significant difference between cases and control group . This
finding coincide with Favilli et al.
(11)
who found in a study included 25
thalassemic patients and 25 control subjects that the mean LVM index was
significantly increased in thalassemic patients versus controls.
Also Latanazi et al
(13)
found in a study included 38 thalassemic patients and 20
controls that the thalassemic patients showed higher values of LVM.
The LVEF% and fractional shortening were normal with no difference between
patients with beta thalassemia and the control group. (Table 2). Also right
ventricular function as assessed by RV Tei index and TAPSE showed no
difference between the cases of beta thalassemia and control group in our
patients.
These results are similar to other reports(5,9,14,15) which also demonstrated
preserved left ventricular systolic function in spite of cardiac dilatation.
Khalifa et al.
(12)
also found no significant difference between all the studied
cases and controls as regards the mean values of EF and FS.
Compared with controls, the diastolic indices of LV in beta thalassemia patients
(trans-mitral E/A ratio) showed no significant difference between cases and
controls which indicates preserved global diastolic function of the L.V. This is
consistent with Vogel et al. (6) in contrary to Rohimi et al.(9) who found diastolic
dysfunction of restrictive pattern in patients with beta- thalassemia compared to
normal E/A ratio in control group.
An interesting finding albeit not that accurate like cardiac catheterization is that
pulmonary capillary wedge pressure estimated by echo-Doppler was higher in
the thalassemia patients than in the control group which correlates with higher
left ventricular end-diastolic pressure and left ventricular dysfunction.
TDI is a relatively new and an easy method that permit early identification of
regional cardiac dysfunction even when left ventricular ejection fraction is still
preserved.
Assessment of the mitral valve with pulsed Doppler tissue imaging showed
statistically significant differences between the patients and the control subjects
in late diastolic myocardial velocities (Aa) and systolic myocardial velocities(S) at
the basal mitral annulus of the septal wall, also patients with thalassemia have
significantly higher early diastolic myocardial velocities (Ea) at the basal mitral
annulus of the lateral wall by tissue velocity imaging.
Assessment of the tricuspid valve showed significant difference for only systolic
myocardial velocity(S) at the basal tricuspid annulus by tissue Doppler imaging.
These alterations in myocardial velocities by TDI might indicate earlier left and
right ventricular dysfunction.
Iarussi et al.17
found that all Doppler tissue imaging systolic and diastolic
parameters of the mitral annulus were similar in patients with beta thalassemia
major before and after transfusion to those of healthy subjects and that only
lateral tricuspid annulus velocities in the patients before transfusion was
significantly reduced.
CONCLUSION :
This study showed that patients with beta-thalassemia have statistically
significant changes in pulsed tissue Doppler imaging giving an evidence of
systolic and diastolic myocardial dysfunction that was not
revealed by
conventional echocardiography.
TDI should be a routine part of the echocardiographic assessment of pediatric
patients with beta-thalassemia. Recent advances in echocardiography have
enabled this technique to be used for early identification of ventricular
dysfunction in asymptomatic patients with thalassemia major. TDI is simple, non
expensive, non-invasive and reproducible. Using this echocardiographic
technique, the effects of therapy, especially iron chelation, can be monitored and
modified according to the detection of myocardial involvement, thus potentially
improving the outlook of patients with thalassaemia.
The small number of patients and non availability of the more recent modalities
of TDI like strain, strain rate, and speckle tracking were the major limitations of
our study.
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