|Year : 2017 | Volume
| Issue : 4 | Page : 137-141
Assessment of regional and global myocardial systolic function by 2D longitudinal speckle tracking in children with beta thalassemia major
Ganesh Narayana MD, DM 1, Ganavi Ramagopal MD 2, Nita R Sutay MD 2, Bhanu Duggal MD, DM 1
1 Department of Cardiology, Chettinad Medical College Hospital and Research Institute, Grant Medical College, Chennai, Tamil Nadu, India
2 Department of Pediatrics, Chettinad Medical College Hospital and Research Institute, Grant Medical College, Chennai, Tamil Nadu, India
|Date of Web Publication||27-Oct-2017|
Department of Pediatrics, Chettinad Hospital and Research Institute, Kelambakkkam, Chennai - 603 103, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: Thalassemias constitute a group of chronic, inherited anemias that are transfusion dependent. Cardiac disease as a result of transfusional iron overload remains as the principal cause of death in these patients even though there have been lots of improvements in iron chelation therapy during the past 25 years. For this reason, it is recommended that regular cardiac evaluation should be done for all patients with thalassemia major. Objective: The present study was conducted with the primary objective to investigate the left ventricular (LV) myocardial function using conventional echocardiographic measures as well as two-dimensional (2D) speckle tracking in patients with beta-thalassemia major who received regular transfusions and chelation therapy. Methodology: This prospective observational study was conducted in the Department of Paediatrics, Sir Jamshedji Jeejeebhoy Group of Hospitals, Mumbai, over a period of 6 months from February 2012 to July 2012. The study comprised 25 consecutive cases of beta-thalassemia major who were diagnosed on the basis of hemoglobin electrophoresis and 25 controls with normal hemoglobin electrophoresis pattern. Patients with any congenital or acquired heart disease and also patients with heart disease of infectious, metabolic, autoimmune etiology were excluded from the study. 2D, M-mode, Doppler, and longitudinal speckle tracking echocardiographic assessment was performed in all the study cases and controls. Results: The mean age of beta-thalassemia group was 7.02 ± 3.00 years whereas the control group was 5.06 ± 3.62 years. The mean hemoglobin was 5.54 ± 1.30 g/dl in beta-thalassemia patients and 10.96 ± 1.36 g/dl in controls (P < 0.001). The thalassemia patients had lower LV ejection fraction (EF) (62.20 ± 7.93% vs. 66.40 ± 1.19%, P < 0.001) and lower global longitudinal strain (GLS) (−21.73 ± 3.68% vs. −26.80 ± 1.29%, P < 0.001) as compared to the controls. The age of the child, hemoglobin level, and serum ferritin level correlated with the LVEF and GLS. Conclusions: LV systolic dysfunction is common in patients with beta-thalassemia major. This is likely to be a consequence of chronic anemia as well as transfusional iron load, compounded by poor compliance to chelation therapy and sometimes nonavailability of proper cardiac monitoring. These findings suggest 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.
Keywords: Cardiac failure, echocardiography, left ventricular dysfunction, thalassemia major
|How to cite this article:|
Narayana G, Ramagopal G, Sutay NR, Duggal B. Assessment of regional and global myocardial systolic function by 2D longitudinal speckle tracking in children with beta thalassemia major. J Clin Prev Cardiol 2017;6:137-41
|How to cite this URL:|
Narayana G, Ramagopal G, Sutay NR, Duggal B. Assessment of regional and global myocardial systolic function by 2D longitudinal speckle tracking in children with beta thalassemia major. J Clin Prev Cardiol [serial online] 2017 [cited 2022 Jan 20];6:137-41. Available from: https://www.jcpconline.org/text.asp?2017/6/4/137/217391
| Introduction|| |
Beta-thalassemia major is one of the most common hemolytic anemias seen in young children and adolescents, particularly in countries where consanguinity is highly prevalent such as India.
These chronically transfused thalassemic patients, if not chelated early and adequately, are at high risk for cardiac dysfunction. In many patients, despite adequate and effective chelation, cardiac pathology continues to be present due to a complex combination of factors such as iron deposition, fibrosis, hypertrophy, and the structural effects due to chronic anemia. Cardiac disease contributes as the major cause of death in these patients and even in the best centers. It accounts for 70% of deaths in thalassemia major patients, and a third of thalassemic patients are known to die by the age of 35 years.
Early detection of cardiac involvement using echocardiography which is a simple, noninvasive technique can lead to the prompt initiation of aggressive chelation therapy during the early stages when the condition can still be reversed., In recent years, strain imaging by speckle tracking has emerged as a useful modality for the assessment of left ventricular (LV) myocardial function and has been shown to be more sensitive than the conventional echocardiography for this purpose.
Hence, this study was undertaken to investigate the myocardial function using two-dimensional (2D) speckle tracking in patients of beta-thalassemia major who had received regular transfusions and chelation therapy. The study also aims to find the relationship between cardiac dysfunction and age, serum hemoglobin and ferritin levels, and chelation therapy.
| Methodology|| |
This prospective study was conducted in the Department of Paediatrics, Sir JJ Group of Hospitals, Grant Medical College, Mumbai, for a period of 6 months from February 2012 to July 2012. The study population was 25 consecutive cases diagnosed as beta-thalassemia major by hemoglobin electrophoresis on blood transfusion and chelation therapy and 25 healthy controls with normal hemoglobin pattern.
Children who were diagnosed with beta-thalassemia major by hemoglobin electrophoresis, had received at least ten blood transfusions, and were on chelation therapy for 6 months or more were included in the study group. The control group consisted of age- and sex-matched 25 healthy children with normal hemoglobin pattern. Children with any congenital or acquired heart disease and also patients with heart disease due to infectious, metabolic, or autoimmune etiology were excluded from the study.
After obtaining a written informed consent from the parents, a detailed history was taken and clinical examination was done. The cases were then subjected to investigations such as hemoglobin estimation by automated analyzer, chest X-ray, electrocardiogram, and serum ferritin levels by chemiluminescence method. In both the groups, echocardiography was performed with a commercially available standard ultrasound scanner (Vivid 7, General Electric medical systems, Horten, Norway) with a 2.5 MHz transducer. The examination was conducted with the patient lying in supine position. Standard echocardiographic views were obtained. LV ejection fraction (EF) was calculated using the modified biplane Simpson's method. LV diastolic function was assessed by measuring mitral inflow early diastolic velocity (E), deceleration time of the E wave (dtE), intraventricular relaxation time (IVRT), ratio of the early diastolic to late diastolic mitral inflow velocity (E/A), and the ratio of the E velocity to early diastolic mitral annular velocity (E/Em). Speckle tracking echocardiography was performed offline using the proprietary automated software EchoPAC PC (Version 11.0.0, GE Medical Systems, GE- Healthcare, WI, USA). Apical four- and two-chamber views were used for the analysis. For each view, the LV endocardial border was manually traced in the end diastolic frame. The software then automatically created a region-of-interest, including the whole myocardial wall, and divided the entire circumference of the LV into six equal segments. The width of the region-of-interest was manually adjusted if required. The software then generated myocardial strain curves by frame-by-frame tracking of the natural acoustic markers throughout the cardiac cycle. From these curves, peak systolic strain was measured for each myocardial segment, and all the values were averaged to derive global longitudinal strain (GLS).
Presence or absence of beta-thalassemia was considered as a primary explanatory variable. LVEF and GLS were considered as the primary outcome variables. Other echocardiographic parameters were considered as the secondary outcome variables. Initial descriptive analysis of all the explanations and outcome variables was done using mean and standard deviation for quantitative variables and frequency and proportion for categorical variables. The association between beta-thalassemia and various parameters was assessed by comparing the mean and standard deviations across the groups. Independent sample t-test was used to test the statistical significance of the association. Separate descriptive analysis was presented for children with thalassemia. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY, IBM Corp was used for statistical analysis.
| Results|| |
The study included 25 children with beta-thalassemia as the study group and another 25 healthy children as controls. The mean age of children with beta-thalassemia was 7.02 ± 3.00 and 5.06 ± 3.62 of controls. The proportion of participants with male:female ratio was 13:1 and 12:1, respectively. The mean hemoglobin of beta-thalassemia children was 5.54 ± 1.30 and 10.96 ± 1.36 of the control group which was statistically significant with P < 0.001 as shown in [Table 1].
Various echo parameters across the two groups showed a significant difference among E velocity, declaration time, etc., as shown in [Table 2].
|Table 2: Comparison of echocardiographic parameters of left ventricular diastolic function across the study groups|
Click here to view
The mean LVEF of beta-thalassemia children was 62.20 ± 7.93% whereas it was 66.40 ± 1.19% in controls. The mean GLS of children with beta-thalassemia was 21.73 ± 3.68% and 26.80 ± 1.29% in the control group (P < 0.001) [Table 3].
|Table 3: Comparison of left ventricular ejection fraction and global longitudinal strain parameters across the study groups|
Click here to view
The number of participants on chelation with kelfer, Desirox (dsx), Kelfer + dsx, and kelfer + desferrioxamine, respectively, in the study population are given in [Table 4].
|Table 4: Descriptive analysis of chelation therapy in the study group (n=25)|
Click here to view
Of the 25 children with thalassemia, 1 (4.0%) had been receiving blood transfusion for the last 5 years, 3 (12.0%) for 4 years, 6 (24.0%) for 3 years, 2 (8%) for 2 years, and 13 (62.0%) for <1 year [Table 5].
[Table 6] shows the comparison of various echocardiographic parameters in the patients categorized according to the different clinical parameters. There was no statistical significance found in E velocity, E/A ratio, IVRT, and LVEF across the age groups studied. However, the differences in E/Em, dtE, and GLS were statistically significant with P < 0.05.
|Table 6: Comparison of echocardiographic parameters among thalassemic patients with different parameters|
Click here to view
The associations between hemoglobin level and E velocity, E/A, E/Em, dtE, LVEF, and GLS were also statistically significant with P < 0.05. However, there was no statistically significant difference in the IVRT.
There was no statistically significant difference found in E/A, IVRT, LVEF, and GLS as regards the serum ferritin levels across the study groups. However, the association between serum ferritin level and E velocity, E/Em, and dtE was statistically significant with P < 0.05.
Comparison of the groups based on the duration of chelation therapy did not reveal any significant difference in any of the echocardiographic parameters.
| Discussion|| |
In our study, the mean age of children with beta-thalassemia was 7.02 ± 3.00 years and the proportion of participants with male:female ratio was 13:1. The mean EF of children with beta-thalassemia was 62.20 ± 7.93. The mean GLS of beta-thalassemics was −21.73 ± 3.68.
It was also seen that the age of the child, hemoglobin percentage, and serum ferritin levels correlated well with the cardiac parameters such as LVEF, mitral E/A ratio, and GLS which was similar to other studies.
Standard echocardiographic measurements may still remain normal at late stages during the disease process in these patients. Various specific cardiological parameters that determine LV function have, therefore, been assessed to find out the efficacy in identifying early myocardial iron overload in thalassemics, to prevent heart failure. Techniques to assess diastolic function in thalassemia major are gaining importance.,
Echocardiographic strain and strain rate imaging (i.e., deformation imaging) is one of the new noninvasive methods for assessment of myocardial function. Strain imaging is identified as potentially superior to tissue velocity imaging in regional myocardial function assessment., Compared with tissue velocity imaging, strain imaging has several advantages such as the ability to differentiate between active and passive movement of myocardial segments and to evaluate different components of myocardial function (e.g., longitudinal, radial, and circumferential myocardial deformation) that are not visually assessable, thereby allowing a comprehensive assessment of myocardial contractile function.
Monte et al. conducted a case–control study with 27 patients with thalassemia major and 27 healthy controls. The main aim of this study was to identify early markers of cardiac dysfunction using new parameters of cardiac rotational dynamics and to look for a relationship with iron overload. Standard echocardiography was done to assess LV rotation and longitudinal mechanics. Speckle tracking echocardiography was used. The study showed that LV rotational dynamics in patients with thalassemia major are negatively related to iron overload.
The study by Hyder et al. was done to evaluate the LV function in patients with thalassemia major using echocardiography. The study comprised fifty cases of beta-thalassemia major and thirty controls with normal hemoglobin and electrophoresis pattern. The age of the patients ranged from 1 year to 25 years. 2D, M-mode, and Doppler echocardiography were performed in all the cases and control participants. The results showed that 19 (38%) patients had LV dysfunction, of which isolated systolic dysfunction was seen in 2 (4%), isolated diastolic dysfunction in 15 (30%) and global dysfunction in 2 (4%) patients, and LV dimensions, stroke volume, and E/A ratio were considerably affected in the study group as evaluated by standard echocardiography.
Pal et al. conducted a study in 100 thalassemic children up to the age of 12. Echocardiography parameters such as the EF, LV posterior wall thickness, interventricular wall thickness, and E/A ratio showed a significant difference among high ferritin group and low ferritin group.
Similarly, the study by Chate in 32 children with thalassemia showed that LVEF on 2D echocardiography was ≥60% in all the 32 patients and diastolic dysfunction was present in 19 (59.37%) patients.
Observations similar to our study were also made by Hou et al., Hankins et al., and Spirito et al.,,
Eshaqhosseni et al. studied 140 cases of confirmed thalassemics and found that LV dimensions, stroke volume, and mitral E/A ratio were considerably affected, and a significant percentage of thalassemia patients has LV dysfunction which is mainly due to chronic anemia and iron overload.
The aim of the study by Bay et al. was to evaluate myocardial function in children with beta-thalassemia major using standard echocardiography technique and strain rate imaging. Using conventional echocardiographic analysis, tissue velocity imaging and strain/strain rate imaging of the left ventricle were determined in 48 children with beta-thalassemia major and 22 healthy children. They found that strain and strain rate imaging study of the basal lateral wall of the left ventricle was higher in patients than in controls.
Ibrahim et al. conducted a case–control study with 100 thalassemic patients below 18 years old and 100 healthy, age- and sex-matched controls. The aim was to evaluate the value of tissue velocity imaging for early detection of myocardial dysfunction in pediatric and adolescent patients with beta-thalassemia major before the development of overt heart failure or cardiomyopathy. Patients with thalassemia were found to have right and LV systolic dysfunction on the basis of abnormal myocardial velocities.
The study has some limitations, one of them being small sample size. Furthermore, the control group was not age matched with the study group as only those who gave consent were included in the study.
| Conclusions|| |
LV systolic dysfunction is common in patients with beta-thalassemia major. This is likely to be a consequence of chronic anemia as well as transfusional iron load, compounded by poor compliance to chelation therapy and sometimes nonavailability of proper cardiac monitoring. These findings suggest 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.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Verma IC, Choudhry VP, Jain PK. Prevention of thalassemia: A necessity in India. Indian J Pediatr 1992;59:649-54.
Aessopos A, Farmakis D, Hatziliami A, Fragodimitri C, Karabatsos F, Joussef J, et al.
Cardiac status in well-treated patients with thalassemia major. Eur J Haematol 2004;73:359-66.
Chotivittayatarakorn P, Seksarn P, Pathmanand C, Thisyakorn C, Sueblinvong V. Cardiac dysfunction in beta-thalassemic children. J Med Assoc Thai 1993;76:591-6.
Ahmed S, Saleem M, Modell B, Petrou M. Screening extended families for genetic hemoglobin disorders in Pakistan. N Engl J Med 2002;347:1162-8.
Aessopos A, Kati M, Farmakis D. Heart disease in thalassemia intermedia: A review of the underlying pathophysiology. Haematologica 2007;92:658-65.
Aldouri MA, Wonke B, Hoffbrand AV, Flynn DM, Ward SE, Agnew JE, et al.
High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: Reversal by intensified chelation. Acta Haematol 1990;84:113-7.
Bay A, Başpinar O, Leblebisatan G, Yalçin AS, İrdem A. Detection of left ventricular regional function in asymptomatic children with beta-thalassemia major by longitudinal strain and strain rate imaging. Turk J Hematol 2013;30:283-9.
Aypar E, Alehan D, Hazirolan T, Gümrük F. The efficacy of tissue doppler imaging in predicting myocardial iron load in patients with beta-thalassemia major: Correlation with T2* cardiovascular magnetic resonance. Int J Cardiovasc Imaging 2010;26:413-21.
Balci YI, Gurses D. Detection of early cardiac dysfunction in patients with ß-thalassemia major and thalassemia trait by tissue doppler echocardiography. Pediatr Hematol Oncol 2011;28:486-96.
Nesbitt GC, Mankad S. Strain and strain rate imaging in cardiomyopathy. Echocardiography 2009;26:337-44.
Nesbitt GC, Mankad S, Oh JK. Strain imaging in echocardiography: Methods and clinical applications. Int J Cardiovasc Imaging 2009;25 Suppl 1:9-22.
Dandel M, Lehmkuhl H, Knosalla C, Suramelashvili N, Hetzer R. Strain and strain rate imaging by echocardiography - Basic concepts and clinical applicability. Curr Cardiol Rev 2009;5:133-48.
Monte I, Buccheri S, Bottari V, Blundo A, Licciardi S, Romeo MA. Left ventricular rotational dynamics in Beta thalassemia major: A speckle-tracking echocardiographic study. J Am Soc Echocardiogr 2012;25:1083-90.
Hyder SN, Kazmi U, Malik A. An echocardiographic evaluation of left ventricular function in patients with thalassemia major. J Pak Med Stud 2013;3:10-5.
Pal AC, Mukherjee R, Sinha P, Bandyopadhyay S. A study on thalassemic children to assess cardiovascular changes, in a rural medical college hospital; West Bengal; India. IOSR J Dent Med Sci (IOSR-JDMS) 2016;15:43-7.
Chate SC. Cardiac abnormalities in patients with beta thalassemia. Int J Contemp Pediatr 2016;3:224-8.
Hou JW, Wu MH, Lin KH, Lue HC. Prognostic significance of left ventricular diastolic indexes in beta-thalassemia major. Arch Pediatr Adolesc Med 1994;148:862-6.
Hankins J, Hillenbrand C, Joshi V, Loeffler R, Song R, Ware R, et al
. Cardiac T2* Magnetic Resonance Imaging (MRI) in iron overload and ventricular diastolic function blood. ASH Annu Meet Abstr 2007;110:2676.
Spirito P, Lupi G, Melevendi C, Vecchio C. Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major. Circulation 1990;82:88-94.
Eshaqhosseni K, Miri R, Arsang SH. Cardiac disorders in children with B-thalassemia major. Bull Environ Pharmacol Life Sci 2014;3:172-5.
Ibrahim MH, Azab AA, Kamal NM, Salama MA, Ebrahim SA, Shahin AM, et al.
Early detection of myocardial dysfunction in poorly treated pediatric thalassemia children and adolescents: Two Saudi centers experience. Ann Med Surg (Lond) 2016;9:6-11.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]