Kamal M ^1*, Rao NK ¹, Vyas YS ¹

¹ Department of Pediatric Cardiology, Star Hospitals, Hyderabad, India.

 *Corresponding Author:Kamal M, Department of Pediatric Cardiology, Star Hospitals, C-203, Hivision Residency, Kompally-500014, Hyderabad, India, Tel: +91-9971259799, Fax: +91-9971259799.

Citation: Kamal M (2024) Tissue Doppler, Strain Imaging and Conventional 2- Dimensional Echocardiographic Assessments in Multi-Transfused Thalassemic Children with Iron Overload. Medcina Intern 6: 225.

Received: May 14, 2024; Accepted: May 21, 2024; Published: May 24, 2024.

Copyright: © 2024 Kamal M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Background: Ventricular dysfunction in thalassemia major is a known complication due to chronic iron overload. Global ventricular function often remains normal in these children till late. The present study was undertaken to assess the utility of tissue doppler imaging (TDI) and strain imaging in identifying this group of patients by assessment of regional myocardial involvement.

Methods: 2D echocardiography, Tissue doppler imaging and strain imaging in the basal and mid left ventricle (LV), right ventricle (RV) and septum were measured in 33 multi-transfused iron- overloaded thalassemic patients and 32 age and sex-matched healthy controls.

Results: 2D echocardiographic parameters showed no significant difference in the parameters except left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), Inter-ventricular septum thickness in diastole (IVSD) and left ventricular mass which was found to be significantly higher in the healthy controls in comparison to the thalassemic children (although indexed LV mass was not significantly different in the 2 groups). Left ventricular ejection fraction (LVEF) was found to be within the normal range in the 2 groups (60.94±4.038% vs 62.26±6.134%, p=0.12) with no significant difference; indicating preserved LV function in both

Conclusions: The present study demonstrates the ability of tissue doppler, strain and strain rate imaging to quantify regional myocardial involvement in asymptomatic iron-overloaded beta thalassemic children with preserved global ventricular function. The author suggests the use of these newer modalities of imaging for the detection of early regional myocardial involvement and its potential role in identifying early myocardial dysfunction.

Thalassemia Major, Tissue Doppler Imaging, Strain Imaging, Ferritin, Iron Overload.

Thalassemia is a disorder of haemoglobin chain synthesis, which results from mutations of genes encoding α or β chains of haemoglobin. These patients have extravascular haemolysis in addition to ineffective erythropoiesis, resulting in severe anaemia. The severity of anaemia depends on the type and amount of chain of haemoglobin involved. β Thalassemia major is a condition in which there is a defect in the synthesis of the β chain of haemoglobin leaving the child to be transfusion dependent for six months of life. These children require transfusion normally once each month, in turn leading to iron overload. These patients receive 0.3- 0.5 mg/kg/day of iron through transfusion [1]. These thalassemia children also absorb more iron than other normal persons. Overload of iron in these patients leads to deposition in different tissues including the heart, liver, gonads, pancreas etc.

Although cardiac involvement is often multifactorial secondary to iron deposition, myocarditis, immunogenic mechanisms and endothelial dysfunction, the main cause of death in patients with β thalassemia is congestive heart failure, mainly attributed to iron overload [2,3,4]. Aggressive chelation can prevent, delay or even revert myocardial dysfunction. But once heart failure occurs, only half of the patients survive [5]. Early recognition of the cardiac disease is useful in modifying the disease [6]. However, early recognition of these patients is difficult as global ventricular function and exercise capacity in chronically transfused patients remains normal until late in the process of the disease [5].

Echocardiography has remained the imaging modality of choice for the estimation of ventricular function, but they are often not adequate to detect subtle cardiac dysfunctions as the global ventricular dysfunction remains normal until late in the disease. It has been found that tissue velocity imaging (TVI), ventricular strain imaging (SI), and strain rate imaging (SRI) are superior to routine ECHO techniques for the assessment of regional and longitudinal myocardial function [7-9].

Previous studies of tissue Doppler and SI in patients with β-TM have yielded wide-ranging results [10-14]. The present prospective study was to assess conventional, TVI, SI, and SRI parameters in patients with β-TM and compare them with matched controls.

 Methods

2-18 years old children with beta-thalassemia major who were attending different thalassemia clinics in the city were referred to our centre for cardiological evaluation during the period of January 2018 to March 2019, with iron overload (latest serum ferritin >1000 ng/dl) were included in the study after obtaining proper consent and confirmed to the institutional ethical guidelines.

Those children with congenital or rheumatic valvular heart disease, past or present history of heart failure, arrhythmias or on cardiac drugs were not included in the study. Age and gender-matched healthy-matched children were recruited as the control group. All the children underwent a detailed clinical examination and echocardiographic examination (Conventional 2D echo, TDI and strain imaging).

The study was performed using iE 33 Philips Echo Machine (Philips Health Care Imaging Systems, Bothell, WA, USA) by an operator blinded to clinical data. Images were obtained in the supine and left lateral decubitus positions with an S5-1 transducer with ECG gating. Standard 2D echocardiographic images were acquired. Depth was minimized to optimize the frame rate. At least 3 beats were digitally stored for offline analysis. Echo parameters including LV end-diastolic dimensions and LV end-diastolic volumes, LV end-systolic dimensions and LV end-systolic volumes, interventricular septal thickness (IVST), LV posterior wall thickness (LVPWT), LV fractional shortening (LVFS), LV stroke volume (LVSV), and LV ejection fraction (LVEF) were measured. The LV dimensions were obtained from M-mode parasternal long-axis views while LV volumes were obtained from the apical four and two-chamber views using standard transducer positions. The ejection fraction (EF) was automatically calculated. LV mass (g) and indexed LV mass were also obtained, and LV end-systolic stress and LV work were calculated. Diastolic Doppler parameters including early and late trans mitral diastolic velocities and their ratio and early deceleration time of the trans mitral diastolic flow were recorded.

The myocardial performance index (MPI) was also obtained. Tissue velocity imaging analysis of the mitral annulus was performed in the apical four-chamber view and sample volume was placed at the desired area of interest and Sm velocities at the basal segments of the lateral LV wall, septal wall, early and late diastolic myocardial velocities, and their ratio of the same basal segments of lateral LV wall and septal wall were recorded. For strain imaging, greyscale images for offline analysis were acquired in apical four-chamber, apical 3 chamber and 2-chamber views and used to record the cardiac cycle in tissue Doppler imaging modes at a frame rate of more than 100/s following which samples were placed at four segments of the LV and two segments of the RV in apical four-chamber view for strain analysis. The automatic tracking analysis was used for these views according to the vendor’s instructions.

The strain and SRI measures were obtained from the offline analysis of the stored loops by QLAB version 8.1. The endocardial border was manually traced at end-diastole. Tracking was automatically performed, and if tracking was suboptimal, the endocardial border was retraced. If satisfactory tracking was not accomplished within 5 minutes, the non-tracking segments were excluded from the analysis. Strain and SRI measures included longitudinal systolic strain and strain rate (SR) at the basal and mid-segment of the lateral LV wall, basal and mid-septum, and basal and mid-RV. Strain values were expressed as negative percentage values, and the SR was expressed as negative 1/s values.

 Statistical Analysis

Ventricular function-related parameters as assessed by different investigative modalities were considered outcome variables and the presence or absence of thalassemia was considered as the primary explanatory variable. Descriptive analysis was carried out by mean and standard deviation for quantitative variables where data followed a normal distribution, otherwise as median and ranges. Categorical variables were represented as frequencies and percentages. An Independent sample t-test was used to assess statistical significance. P value < 0.05 has been considered statistically significant. Data were analyzed using R studio.

33 thalassemic major children and 32 age (median 11 vs 10; p=0.83) and sex (p=0.8) matched controls were included in the study. Almost all (32/33: 96.1%) of the thalassemic children were diagnosed in infancy and had a median blood transfusion number of 104 (range 43-289). Since all the children who were included in the study had iron overload, so chelation therapy (median duration: 9 years) was used in all either alone or in combination. Deferasirox (Asunra) either as individual therapy or in combination was the most common chelator being used (20/33: 60%). The mean haemoglobin (9.75±1.5 g/dl vs 11.65±1.99 g/dl; p<0.01) was lower significantly in the thalassic compared to the controls. Serum ferritin was higher in the thalassemic (2252.73±757.42ng/ml vs 128.25±51.22; p<0.01). With respect to anthropometric parameters both the groups had comparable height (126.82±18.52 cm vs 127.22±21.06; p=0.93) but the weight (26.27±7.49 kg vs 34.13±13.35cm; p<0.01) and BMI (15.76±4.02 kg/m2 vs 20.34±3.79 kg/m2;

p<0.01) of the thalassemic were significantly lower than that of the controls. The baseline characteristics are summarised in Table 1.

Table 1: Baseline and haematological characteristics of the thalassic and the healthy children.

 Table 2: 2 D Echocardiographic parameters of thalassemia children and controls.

LVESV(ML)          0.21

 Figure 1: LV tissue doppler imaging of lateral and septal tissue of thalassemia and controls.

Figure 2: Systolic strain imaging parameters of thalassemia and control groups.

The present study is an analytical cross-sectional study comparing the multi-transfused iron overloaded children with normal age and sex-matched healthy controls in terms of their ventricular function with 3 different echocardiographic modalities (2D echocardiography, tissue doppler imaging and strain and strain rate imaging). A total of 33 iron-overloaded thalassaemic children and 32 age and sex-matched healthy children were included in the study.

The 2 groups i.e. the thalassaemic and controls were compared with respect to descriptive parameters and ventricular functions with different echocardiographic parameters. In the present study, only children in the age group of 2-18 years were included. The median age of the thalassaemic group was 11 years and the control group was 10 years (Table 1). The two groups were age-matched (p=0.83). The 2 recent studies done in India by Narayana et al [15] (7.02±3 years) and Gupta et al [16] (12.4±5.2 years) too included children only. Vogel et al [5] (range 14.2-43.1years), Poorzand et al [17] (mean age: 23.51±6.2 years), Bilge et al [13] (mean age: 24.2±8 years), Rodrigues et al [18] (mean age: 18.1±7.27 years), and Parsaee et al (mean age: 27.5±8.8), included adult patients too in their studies. The male: female ratio of the thalassemic children in the present study is 1.5: 1 (20:13) which is comparable to the controls (p<0.8) (Fig 3). The ratios in the previous Indian studies by Narayana et al [15] (thalassemia (13:1); controls (12:1)) and Gupta et al [16] (thalassemia (23:7); controls (13:7)) showed a more amount of male dominance in comparison to the present study. This favorable sex ratio in the 2 groups of the present study can be attributed to the much more favorable sex ratio of Telangana state (985:1000) in comparison to the national average (943:1000).

Figure 3: Systolic strain rate imaging parameters of thalassemia and control groups.

The mean age of diagnosis of thalassemia in these children was 6.52±2.74 months and all the children were diagnosed in the infancy period only except one. This child was diagnosed at 14 months of age as he came to medical attention much later. 4 children were diagnosed as early as 3 months of age. Out of these 4 children, 2 were diagnosed in the antenatal period only and the rest 2 had an elder sibling with thalassemia, so they were tested for the condition before even the anaemia appeared. Thalassemia major is known to be diagnosed around 6 months of age as by this time the fetal haemoglobin reduces to <2% of the total haemoglobin level and hence severe anaemia is seen.

The total number of blood transfusions in these children of thalassemia ranged from 43 to 289 with a median value of 104 transfusions. The maximum number of transfusions were received by an 18 years girl who was diagnosed to have thalassemia at 3 months of age and had a severe iron overload. The number of transfusions in a thalassemic patient depends on the age of the patient and how well the condition is being managed.

As the study included all the children of the thalassemia group who were overloaded with iron, so all these 33 children received some form of chelation therapy. The duration of chelation therapy in the present study varied from 2 to 16 years. Three different types of chelation therapies were used in this group of thalassemic children for iron overload either alone or in combination. Deferasirox alone was being taken by the highest number of these children 9/33 (27.2%) followed by deferiprone 8/33 (24.2%). None of the children used deferoxamine alone. In the combination therapy, all the 3 chelating agents were being used by 7/33 (21.2%) of these children followed by each deferoxamine+ deferiprone (4/33) and deferoxamine+ deferasirox (4/33) combinations, each making 12.1% of the total. In contrast to our findings, the study by Narayana et al found Deferiprone (Kelfer) to be the most common drug in use: 24/25 thalassemic patients (96%) either alone or in combination with only a single patient (4%) who were not on deferiprone [15]. Much in contrast to what we are using in India, the study by Rageb et al from Egypt, which was also carried out in children, showed that none of their patients received deferiprone [20]. Out of their 25 thalassemic children deferoxamine alone was used in 16 (64%), whereas none of the children in the present study receive this drug alone. Deferasirox in their study was being used alone by 16% and in combination with deferoxamine in an additional 20% of children. This clearly depicts the contrast in the usage of types of chelation therapy in different parts of the globe.

The mean hemoglobin in the present study in the thalassemic and control group was 9.75±1.5g/dl and 11.65±1.99g/dl and the difference between the 2 groups has been found to be significant (p<0.01). Studies done by Rodrigues et al (thalassemia: 13±0.83, controls 14.5±1.75) [18], Narayana et al (thalassemia: 5.54±1.3, controls 10.96±1.36, p<0.001) [15] and Gupta et al. (thalassemia: 13.5±1.9, controls 14.9±0.94, p<0.00, p=0.002) [16] also found the difference between the 2 groups to be significant in their studies. The thalassemic have less hemoglobin attributable to the anemia which is produced in this condition due to the defective beta chain of hemoglobin. The lowest hemoglobin in the thalassemic group was 7.1 g/dl whereas in the control group was 8.6g/dl in present study. None of the groups had children who has severe anemia (Hb <7g/dl), which reflects that these children are under regular follow-up in the thalassemia clinic. The highest hemoglobin in the thalassemic group was 12.3g/dl whereas in the control group was 16.4g/ dl. None of the thalassemic children had hemoglobin >13g/dl. The present study included all the children of thalassemia who had an iron overload and hence the mean serum ferritin in this group was 2252.73±757.41ng/ ml. 21 (63.6%) out of these 33 children had ferritin in the range of 1000-2499bng/dl whereas 12/33 (36.3%) had ferritin ≥2500 ng/ml. In all the previous studies including the present study, none of the thalassemic had serum ferritin value <500ng/ml.

With respect to the anthropometric parameters in the present study, there was no statistically significant difference (p=0.93) in the mean height of the thalassemic (126.82±18.52 cm) and controls (127.22±21.06). The maximum number of thalassemic (84.8%) and healthy controls (84.3%) were in the height range of 101-150 cm. Only 7 children (4 in the thalassemia group and 3 in the control group) had a height > 150 cm. In contrast to the height the other anthropometric parameters i.e. weight (thalassemia: 26.27±7.49 kg; controls: 34.13±13.35cm; p<0.01) and BMI (thalassemia: 15.76±4.02 kg/m2; controls: 20.34±3.79 kg/m2; p<0.01) showed higher values for the healthy control group in comparison to the thalassemic group. Further 26/33 (78.7%) of the thalassemic children were undernourished (BMI <18.5 kg/m2) in comparison to just 11/31 (34.3%) of healthy control groups. This clearly demonstrates that thalassemic children have lower weights and BMI in comparison to similar age and sex-matched healthy children. This difference is attributable to the lifelong chronic condition of thalassemia which affects the growth of these children. Gupta et al [16] in their study on the other hand found the weight to be higher in the thalassemia group (30.96±9.36kg) than the healthy controls (28.08±9.9 kg), but the difference was not found to be significant statistically (p=0.377).

With respect to the vitals, the present study showed no statistically significant difference in the heart rates (thalassemia: 93.21±8.68/ min; controls: 89.38±9.35/ min; p=0.08) and BP (SBP thalassemia: 110±6.92 mm Hg; SBP controls: 110.88±6.11 mm Hg; p=0.59; DBP thalassemia: 70.85±5.91mm Hg; DBP controls: 79.69±6.63 mm Hg; p=0.91) of the 2 groups.

2d Echocardiographic Parameters

In the present study, the conventional 2D Echocardiographic parameters including LA size, aorta size, LVESD, PWD, LVESD, and LV mass index were not significantly different between the thalassemic and the controls (Table 2). The LVEF (60.94±4.038% vs 62.26±6.134%, p=0.12) was also similar in the 2 groups. None of the patients had LVEF<50% in the thalassemic group. LVEDD and LVEDV were found to be lower significantly in the thalassaemic (LVEDD: 35.03±6.522 mm; LVEDV: 53.64±24.426 ml) in comparison to the controls (LVEDD: 42.53±6.839mm; LVEDV: 83.97±30.810 ml). Children with thalassemia had lower LV mass (77.94±34.244g vs 96.56±33.796g; p=0.03) compared to the controls.

With respect to the mitral inflow velocities including E velocity (1.03±0.174m/s vs 1±0.254m/s; 0=0.57), A velocity (0.48±0.156m/s vs 0.50±0.187m/s; p=0.9), E/A ratio (1.97±0.467vs 1.88±0.336; p=0.35) and EDT (173.06±19.465s vs 176.78±22.051s; p=0.47), there was no statistically significant difference between the thalassemia group and the control group. This suggests that even the diastolic parameters in the 2 groups were not impaired and there was no significant difference between the groups. Even the difference in the myocardial performance index i.e. Tei index (0.35±0.03 and 0.34±0.03) was not found to be statistically significant (p=0.46). Analysis of the 2D echocardiographic parameters reveals that there was no significant difference in the parameters analyzed by this modality of echo except the LVEDD, LVEDV and LV mass (although the LV mass index is not significantly different between the 2 groups). This suggests that the ventricles are dilated significantly in the thalassaemic group in comparison to the controls.

Comparing the 2D echo parameters to the previous studies, Gupta et al also did not find any significant difference in these parameters with the exception of LV mass [16]. They in their study found the LV mass of the thalassaemic (177.05±52.51g) significantly higher than the controls (120.01±30.49g) (p=0.01). Similarly, in many previous other studies by Bay et al (80.92±39.49 g) [11], Bilge et al (228±94 g) [13] and Lang et al (113.8±38 g) [21], they have found the LV mass to be significantly higher than the control. The reason attributable to them this increased LV mass was chronic myocardial parenchymal iron overload.

A recent study by Narayana et al showed a significant difference in the EFs of the thalassemic (62.2±7.93%) and the controls (66.4±1.190%) [15]. Although the EF was lower among the thalassemic in their study, it was within the normal range (>55%). There was also a significant difference between the 2 groups in the diastolic functions which is in contrast to our study findings. In a study from Egypt by Ragab et al, even though they found the 2D parameters to be significantly different in the thalassemic and the control groups, the EF in the 2 groups (66.24±5.57% vs 69.50±3.34%) have been found to be similar (p=0.11) [20].

Seeing the trend of the 2D parameters in the present study and above quoted previous similar studies, it can be derived that the ventricular function as assessed by 2D Echocardiography remains preserved in the thalassemic with respect to controls. Even if in some studies if the EF is found to be lower significantly in the thalassemic groups, it remains within the normal range signifying non- depressed LV function.

LV Tissue Doppler Parameters

Assessment of the LV tissue doppler imaging parameters in the present study showed that Sm(10.18±1.685 cm/s vs 10.78±1.431cm/s; p=0.12), Em (13.58±1.803 cm/s vs 14.78±1.414cm/s; p=0.29)and Am (6.21±1.386 cm/s vs 6.84±1.439cm/s; p=0.07)velocities at the basal segments of the septal LV wall and their ratio i.e. septal Em/Am (2.15±0.364 cm/s vs 2.13±0.554 cm/s; p=0.82) although slightly lower in thalassemic, were not statistically different between the two groups (Fig 1). In contrast, velocities at the basal segments of the lateral LV wall (Sm: 9.45±1.970 cm/s vs 11.58±1.218 cm/s (p<0.01); Em: 10.24±1.838 cm/s vs 18.19±2.177 cm/s (p<0.01); Am 7.09±1.256 cm/s vs 7.59±1.365 cm/s (p<0.01); Em/Am ratio: 1.03±0.174 vs 2.34±0.483 (p<0.01)) revealed significant differences in thalassemic and controls. The velocities at the lateral LV were lower that the controls. This clearly demonstrates that despite an overall LVEF, there is a differential abnormality of TVI in the lateral versus septal regions in patients with beta-thalassemia.

Gupta et al also got similar results as the present study [16]. They also observed that the lateral tissue velocity parameters were significantly decreased in the thalassemic compared to the controls whereas the septal tissue doppler parameters were not significantly different from the controls.

Ragab et al measured the TVI parameters in the septal, lateral, anterior and inferior walls of LV and gave the mean values for them [20]. They also did not find any significant difference in the different tissue doppler parameters of the thalassic and the controls both at the septal wall and lateral walls except lateral LV Em velocity (12.90±1.85 cm/s vs. 16.84±3.32 cm/sec; p=0.001). Bilge et al also did not find any significant difference in the septal and lateral tissue doppler parameters except lateral Sm velocity (9.5±2.6 cm/s vs 11.1±2.1 cm/s; p=0.17) [13]. So, they did not find any significant difference even in the tissue doppler parameters of their patients and controls who had preserved LV function by 2D echocardiography. Bay et al in their study of TVI parameters of the 2 groups found lateral Em/Am (3.10±0.84 vs 2.42±0.55; p=0.001) velocity to be higher in the thalassemia group in comparison to the controls with a statistically significant difference [11].

The inference which can be taken out from this is that most of the studies have found some significant difference in the tissue doppler parameters in the thalassemic groups in comparison to the controls even when the LVEF was normal, suggesting that TVI is able to pick up regional changes in ventricular involvements too.

Strain and Strain Rate Imaging Parameters

Both strain and strain rate imaging parameters at basal (Strain: -19.39±4.351% vs -24.88±3.035%; SR: -1.73±0.626/s vs -2.03±0.647/s) and mid segments (Strain: -19.36±4.834% vs -24.47±3.529%; SR: -1.73±0.719/s vs -2.34±0.701/s) of the lateral LV wall, basal (Strain: -18.67±3.731% vs -25.38±3.087%;  SR:  -1.64±0.549/s  vs  -2.19±0.644/s  controls)  and  mid  septum  (Strain: -19.21±4.196% vs -25.81±2.879%; SR: -1.64±0.549/s vs -2.19±0.644/s) and basal (Strain: -18.30±4.482% vs -25.16±3.743%; SR: (-1.84±1.091/s vs -2.22±0.832/s) and mid RV (Strain: -19.55±4.251% vs 25.63±3.705%; SR: -1.83±0.992/s vs -2.34±0.653/s) were significantly lower in the thalassaemic children in comparison to the controls (Fig 2 and 3).

Hamdy et al in their study observed that the strain of LV free wall in thalassemic (-20.9±6.8%) was lower significantly than the controls (-27.2±4.3%) (p<0.001) similar to our study [12]. But they found the values to be reversed in the case of septal strain parameters (-31.1±8.3% vs -25.1±3.8%) which was also significant statistically (p<0.01). They did not obtain any significant difference in the RV strain parameters between the 2 groups (-33.2±10.1% vs -33.5±9.7). This selective involvement is attributed to the patchy and non-homogenous deposition of iron within cardiac myocytes. Bay et al in their study in contrast to the present study observed that the basal lateral wall’s strain and SRI measurements were higher in patients than controls (p=0.035 and p=0.008) respectively [11]. They found LV volume and mass index parameters more sensitive than other strain and SRI values during childhood. However, they concluded that the adulthood strain and SRI values may be lower than the controls, exceeding the critical level of iron overload. Parsaee et al found the global longitudinal strain in the thalassemic (-20.9±1.9%) to be significantly lower than the controls (-22.2±1.03%) (p=0.007) [19]. LV basal segments longitudinal strain was also found to be significantly lower in the thalassemic children than in the healthy controls (p=0.002). In contrast to this, the global circumferential strain was found to be higher in the thalassemia group in comparison to the controls but this difference was not found to be significant statistically (p=0.11). They also had MRI T2* in their study. But they did not find a correlation between the CMR T2* and global longitudinal strain. They recommended close follow-up in clinically silent thalassemia patients with reduced global longitudinal strain and normal CMR T2*.

With respect to the 2 Indian studies, Narayana et al observed that the global longitudinal strain (GLS) was lower significantly in the beta thalassemic group (-21.73±3.68%) in comparison to the healthy control group (-26.8±1.29%) (p<0.001) [15]. They concluded that even in young children with beta-thalassemia major, who are asymptomatic, serial echocardiography is warranted to permit early recognition of LV systolic dysfunction and timely initiation of appropriate cardioprotective therapy. In the study by Gupta et al, they found that LV strain at the basal (-19.5±4.17% vs -24.196±1.81; p=0.002) and mid segments (-19.07±3.98% vs -25.56±262%; p=0.42) of lateral LV wall as well as the basal (-17.04±3.44 vs -25.43±2.53; p<0.001) and mid septum (-20.49±5.34 vs

-24.45±2.2; p=0.001) were significantly lower in beta-thalassemia major patients [16]. The SRI values at the basal and mid-segment of the lateral LV wall and at the basal and mid-septum were significantly lower in the thalassemic. Although in their study strain parameters of basal RV were also depressed in patients with beta-thalassemia, the strain at mid RV was not different in comparison to controls. Even the SRI at RV basal and mid RV segments though lesser in thalassemic children, they did not find the trend to be significant statistically.

LV systolic dysfunction is common in patients with thalassemia. Standard 2D echocardiographic measurements may still remain normal at late stages during the disease process in multi-transfused thalassemia patients. Various specific cardiological parameters that determine LV function, therefore, have been assessed in the present study to find out the efficacy in identifying early myocardial iron overload in thalassemic children, to prevent heart failure. Parameters to assess diastolic dysfunction have been also included in the present study.

Studies including the present study have found the usefulness of TDI in the early identification of ventricular involvement in these groups of children who have the normal ventricular function by conventional parameters. Echocardiographic strain and strain rate imaging are now gaining much importance as a non-invasive method of assessment of myocardial function. The present study has found both strain and SR imaging as potentially superior to the conventional 2D echocardiographic assessment of ventricular function. Strain imaging has the ability to differentiate between active and passive movement of myocardial segments and to evaluate different components of myocardial function that are not visually assessable, thereby allowing a comprehensive assessment of myocardial contractile function.

Limitations

The study is a single-center study done with a limited number of subjects. Studies done with large numbers will improve the power of the study. A larger number of subjects will also help further define the role of these newer echo parameters (Strain and strain rate imaging) in the assessment of the LV function of thalassemia patients. It is a single-point study which is an important limitation. Serial longitudinal studies with measurements of parameters in follow-up are necessary to clarify if these changes in SI, SRI and TDI will progress to ventricular dysfunction. Though multiple recordings were taken during echocardiographic evaluation, it was by a single observer. Analysis of each patient by more than one observer will improve the power of the study. CMR T2* is the imaging modality of choice for the assessment of iron overload, but in the present study, it has not been studied in all the patients.

Ventricular dysfunction is common in thalassemia children and it increases as the child grows. It is even reversible with appropriate and proper chelation therapy. Ejection fraction accessed by conventional 2D Echocardiography remains normal till the later stage of the ventricular impairment in these multi-transfused thalassemic patients. Other conventional 2D Echocardiographic parameters also remain normal till late in this group of patients. Tissue doppler imaging parameters are useful in picking up early and regional ventricular involvement which cannot be picked up by conventional 2D echocardiography in thalassemic patients. Echocardiographic strain and strain rate imaging (deformation imaging) is an emerging new non-invasive method of assessment of myocardial function. This modality is superior to EF estimation by conventional 2D Echocardiographic method and helpful in detecting early regional myocardial involvement in thalassemic children. Our study demonstrates the ability of these newer imaging modalities to quantify regional myocardial involvement in asymptomatic iron-overloaded thalassemia major children with normal ejection fraction.

Financial support and sponsorship

Nil

Conflictsofinterest

None

Acknowledgement

The authors thank Mr Satheesh K Pullokka, Senior Technician, Pediatric Echo Lab for his technical support during the study.

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