|Year : 2019 | Volume
| Issue : 2 | Page : 41-45
The relationship between the presence of fragmented QRS and iron overload determined by magnetic resonance imaging T2* in patients with beta-thalassemia major
Zahra Alizadeh Sani1, Majid Haghjoo1, Bordbar Armin2, Ghobadi Fard Ebrahim1
1 Rajaei Heart Center, Tehran, Iran
2 Department of Cardiology, Musavi Hospital, School of Medicine, Zanjan University Madical Sciences, Zanjan, Iran
|Date of Submission||25-Feb-2019|
|Date of Decision||06-Mar-2019|
|Date of Acceptance||27-May-2019|
|Date of Web Publication||03-Oct-2019|
Dr. Ghobadi Fard Ebrahim
Rajaei Heart Center, Valiasr Street, Tehran
Source of Support: None, Conflict of Interest: None
Background: Patients with beta-thalassemia major are categorized as high risk for cardiovascular complications due to myocardial iron overload that leads to reduce both systolic and diastolic function as well as cardiac arrhythmias. The present study aimed to assess the relationship between the presence of fragmented QRS and iron overload determined by magnetic resonance imaging (MRI) T2* in patients with beta-thalassemia major. Materials and Methods: This cross-sectional study was performed on 71 consecutive patients with beta-thalassemia major that referred to Shahid Rajaei Heart Center in 2014 for assessing myocardial T2* using cardiac MRI. The cardiac MR T2* values and electrocardiograms (ECGs) of the patients were evaluated. The patients' 12-lead surface ECGs were analyzed for the presence of fragmented QRS. Results: The presence of fragmented QRS was revealed in 19.7% of patients. The study showed the presence of a significant relationship between cardiac T2* value and fragmented QRS in ECG that the mean myocardial T2* in those with and without fragmented QRS was 11.46 ± 6.63 and 21.72 ± 9.49 (P < 0.001). Using the multivariable linear regression model, it was shown a significant association between the presence of fragmented QRS and myocardial T2* value (standardized beta = −0.318, P = 0.007). In those with fragmented QRS, a significant association was found between myocardial and liver T2* values [r = 0.677, P = 0.008. Conclusion: A notable number of patients with beta-thalassemia major have fragmented QRS pattern in ECGs that is accompanied with lowering myocardial T2* value in these patients.
Keywords: Beta-thalassemia major, fragmented QRS, iron overload, magnetic resonance imaging T2*
|How to cite this article:|
Sani ZA, Haghjoo M, Armin B, Ebrahim GF. The relationship between the presence of fragmented QRS and iron overload determined by magnetic resonance imaging T2* in patients with beta-thalassemia major. Res Cardiovasc Med 2019;8:41-5
|How to cite this URL:|
Sani ZA, Haghjoo M, Armin B, Ebrahim GF. The relationship between the presence of fragmented QRS and iron overload determined by magnetic resonance imaging T2* in patients with beta-thalassemia major. Res Cardiovasc Med [serial online] 2019 [cited 2019 Oct 18];8:41-5. Available from: http://www.rcvmonline.com/text.asp?2019/8/2/41/268478
| Introduction|| |
Myocardial ischemia, cardiac arrhythmias, and progressive heart failure are the common cardiovascular findings in untreated and uncontrolled beta-thalassemia that usually caused by hemolytic anemia and also myocardial iron overload., The cardiovascular complications related to iron overload have been revealed as the most common cause of mortality in these patients., In this regard, regular long-term blood transfusion and treatment by chelating can effectively prevent cardiovascular complications in these patients. Due to the high incidence of myocardial complications due to iron overload in beta-thalassemia, accurate determination of iron load in these patients is vital. Various methods have been employed to assess myocardial iron load in these patients. Although tissue biopsy is the most accurate method for assessing myocardial iron load because of its invasive and dangerous nature; the attempts have been recently focused on replacing noninvasive and sensitive modalities to assess iron overload in the patients. In this regard, the use of magnetic resonance imaging (MRI) T2* is now accepted as an accurate modality for assessing iron overload in beta-thalassemia patients.,
The patients with beta-thalassemia suffer different cardiac ischemic and arrhythmic complications that may lead to significantly lower their survival as well as increase risk for sudden cardiac death., The change in normal electrocardiographic pattern can effectively predict increased risk for cardiovascular complications. Fragmented QRS is now identified as a new tool for discriminate high-risk cardiovascular patients., It has been indicated that the presence of fragmented QRS is common in patients with the history of myocardial ischemia and also those with progressive heart failure., In fact, confirming fragmented QRS can predict the occurrence of further cardiac events in high-risk cardiovascular groups. It is now hypothesized that the presence of fragmented QRS may be related to iron overload and its cardiovascular complications in beta-thalassemia. Hence, the present study aimed to assess the relationship between the presence of fragmented QRS and iron overload determined by MRI T2* in patients with beta-thalassemia major.
| Materials and Methods|| |
This cross-sectional study was performed on 71 consecutive patients with beta-thalassemia major that referred to Shahid Rajaei Heart Center in 2014 for assessing myocardial T2* using cardiac MRI. Patients with diabetes mellitus, hypertension, ischemic heart disease, and smokers were excluded, beside individuals were excluded from the study, if they had a history of coronary artery disease or regional wall motion abnormalities under resting transthoracic echocardiography examination. The cardiac MR T2* values and electrocardiograms (ECGs) of the patients were evaluated. The patients' 12-lead surface ECGs were analyzed for the presence of fragmented QRS. The fragmented QRS pattern was identified by the presence of different RSR' patterns in the presence or absence of the Q wave in two adjacent derivations (QRS duration, <120 ms); additional R wave (R' wave) or notching in the nadir of the R or S wave or by the presence of ≥1 R wave in the absence of typical bundle branch block. The measurement of cardiac MR T2* was evaluated according to the description by Chen X et al. The cardiac T2* value <20 ms was accepted as cardiac iron overload. The relationship between the cardiac T2* value and fragmented QRS in ECG was investigated.
Data were analyzed with the SPSS software version 16.0 for Windows (IBM Company, Chicago). Categorical variables were presented as frequency and percentage and quantitative variables with mean ± standard deviation. The Chi-square test and Fisher's exact test were used to compare categorical variables. The Kolmogorov–Smirnov test was used to assess the distribution of continuous variables. Student's t-test was used for variables with normal distribution. Continuous variables without normal distribution were analyzed using Mann–Whitney U-test. The correlation between the variables was examined using the Pearson's or Spearman's test. Multivariate linear regression analysis was used to evaluate the association between the presence of fragmented QRS and cardiac T2* value with the presence of baseline variables. A two-tailed P < 0.05 was considered statistically significant.
| Results|| |
The study included 71 patients with beta-thalassemia major of whom 39 were male. The mean age of the patients was 19.84 ± 7.54 years. All patients were on regular blood transfusions and iron chelators. Patients had no cardiovascular risk factors. The presence of fragmented QRS was revealed in 19.7% of patients [Figure 1]. Between the groups with and without QRS fragmentation, there was no difference in baseline demographic characteristics including gender and age as well as mean pulse rate; however, those with fragmented QRS had significantly lower left ventricular ejection fraction (LVEF) as well as higher end-systolic and end-diastolic volumes and indices [Table 1]. The study showed the presence of a significant relationship between cardiac T2* value and fragmented QRS in ECG that the mean myocardial T2* in those with and without fragmented QRS was 11.46 ± 6.63 and 21.72 ± 9.49 (P < 0.001). Furthermore, those with fragmented QRS had lower liver T2* compared with those without fragmented QRS (2.10 ± 1.82 vs. 5.40 ± 5.50, P < 0.001). In those with fragmented QRS, a significant association was found between myocardial and liver T2* values (r = 0.677, P = 0.008) [Figure 2]. However, the value of myocardial T2* was not related to cardiovascular parameters including LVEF (r = 0.364, P = 0.201), end-diastolic volume (r = −0.185, P = 0.538), and end-systolic volume (r = −0.118, P = 0.689). Using the multivariable linear regression model [Table 2], it was shown a significant association between the presence of fragmented QRS and myocardial T2* value (standardized beta = −0.318, P = 0.007), however in a similar model, there was no association between the presence of fragmented QRS and liver T2* value (standardized beta = −1.651, P = 0.104) [Table 3].
|Figure 1: Standard electrocardiogram from a 19-year-old male with major beta-thalassemia and cardiac T2* of 7.8 ms. RSR' pattern and notched R inferior leads are consistent with fragmented QRS|
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|Table 1: Comparing baseline characteristics between the patients with and without fragmented QRS|
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|Table 2: Multivariate linear regression analysis to assess relation between myocardial T2 value and presence of fragmented QRS|
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|Table 3: Multivariate linear regression analysis to assess relation between liver T2 value and presence of fragmented QRS|
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| Discussion|| |
As previously pointed, patients with beta-thalassemia major are categorized as high risk for cardiovascular complications due to myocardial iron overload that leads to reduce both systolic and diastolic function as well as cardiac arrhythmias. As shown in our survey, about one-fifth of the patients had fragmented QRS pattern in their ECGs. Due to the close relationship between the presence of fragmented QRS and adverse cardiac event, we thought that the myocardial iron overload might be associated with the presence of this ECG pattern in beta-thalassemia major [Figure 3]. In line with our hypothesis, we could show that the value of myocardial T2* was significantly lower in those patients with fragmented QRS in ECGs even adjusting gender and age variables as well as systolic and diastolic functional parameters that were comparable with the findings previously found in other studies. In a similar study by Bayar et al., in 48% of patients, fragmented QRS was detected, and in 74% of those, the T2* values were low. Furthermore, 86% of patients with cardiac involvement had fragmented QRS, but 22% of patients with noninvolvement had fragmented QRS (P < 0.001). In another study by Buyukkaya et al., when compared to those in control group, fragmented QRS was more frequent in beta-thalassemia major group, indicating statistical significance (P = 0.001). While E/Em and ferritin level exhibited statistically significant increase in thalassemia patients with fragmented QRS (P < 0.05), the mean Em and Sm values were found to be significantly low (P < 0.05).
|Figure 3: Different type of fragmented QRS from: Tarek M. QRS fragmentation as a prognostic test in acute cotonary syndrome. J Cardiovasc Surg 2013|
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Studies have shown that cardiac T2* is highly predictive over 1 year for the development of heart failure and arrhythmia. Low T2* values are associated with the occurrence of myocardial dysfunction. A study involving 652 patients with TM has reported that cardiac T2* values of <20 ms are significantly associated with the risk of arrhythmia and for patients with T2* values of <10 ms with risk of cardiac insufficiency. Cardiac iron overload first leads to delay or blockage in myocardial electrical conduction and later to disorders in myocardial contraction. In the early stage of the disorder, as criteria, bradycardia, changes in ST-T, seldom atrial and ventricular premature systoles, first-degree atrioventricular block, and left ventricular hypertrophy are observed., In the late stage of the disorder, frequent atrial and ventricular premature systoles, supraventricular tachycardia, second-degree atrioventricular block or complete cardiac block can occur. Despite confirmed association between iron overload and progression of myocardial functional impairment, we could not confirm the association between myocardial T2* value and myocardial parameters. This insignificant association may be explained by this fact that our patients might be in the early phases of myocardial iron overload before its potential effects on myocardial parameters.
| Conclusion|| |
A notable number of patients with beta-thalassemia major have fragmented QRS pattern in ECGs that is accompanied with lowering myocardial T2* value in these patients. However, our study could not demonstrate a significant association between myocardial T2* and myocardial systolic and diastolic function parameters may be due to the early phases of the effects of iron overload on myocardial functional status.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Hamed AA, Elguindy W, Elhenawy YI, Ibrahim RH. Early cardiac involvement and risk factors for the development of arrhythmia in patients with β-thalassemia major. J Pediatr Hematol Oncol 2016;38:5-11.
Meloni A, Restaino G, Borsellino Z, Caruso V, Spasiano A, Zuccarelli A, et al.
Different patterns of myocardial iron distribution by whole-heart T2* magnetic resonance as risk markers for heart complications in thalassemia major. Int J Cardiol 2014;177:1012-9.
Ozdogan O, Alp A, Turker M, Atabey B. Determination of early cardiac deterioration in beta-thalassaemia major by echocardiography. Acta Cardiol 2013;68:299-305.
Noori N, Mohamadi M, Keshavarz K, Alavi SM, Mahjoubifard M, Mirmesdagh Y. Comparison of right and left side heart functions in patients with thalassemia major, patients with thalassemia intermedia, and control group. J Tehran Heart Cent 2013;8:35-41.
Cassinerio E, Roghi A, Orofino N, Pedrotti P, Zanaboni L, Poggiali E, et al.
A 5-year follow-up in deferasirox treatment: Improvement of cardiac and hepatic iron overload and amelioration in cardiac function in thalassemia major patients. Ann Hematol 2015;94:939-45.
Bartoloni G, Italia F, Ferraro G, Lombardo T, Tamburino C, Cordaro S, et al.
Histopathology of thalassemic heart disease: An endomyocardial biopsy study. Cardiovasc Pathol 1997;6:205-11.
Hanneman K, Nguyen ET, Thavendiranathan P, Ward R, Greiser A, Jolly MP, et al.
Quantification of myocardial extracellular volume fraction with cardiac MR imaging in thalassemia major. Radiology 2016;279:720-30.
Chen X, Zhang Z, Zhong J, Yang Q, Yu T, Cheng Z, et al.
MRI assessment of excess cardiac iron in thalassemia major: When to initiate? J Magn Reson Imaging 2015;42:737-45.
Auger D, Pennell DJ. Cardiac complications in thalassemia major. Ann N
Y Acad Sci 2016;1368:56-64.
Cavallaro L, Meo A, Busà G, Coglitore A, Sergi G, Satullo G, et al.
Arrhythmia in thalassemia major: Evaluation of iron chelating therapy by dynamic ECG. Minerva Cardioangiol 1993;41:297-301.
Bozbeyoǧlu E, Yıldırımtürk Ö, Yazıcı S, Ceylan US, Erdem A, Kaya A, et al.
Fragmented QRS on admission electrocardiography predicts long-term mortality in patients with non-ST-segment elevation myocardial infarction. Ann Noninvasive Electrocardiol 2016;21:352-7.
Cetin MS, Ozcan Cetin EH, Canpolat U, Cay S, Topaloglu S, Temizhan A, et al.
Usefulness of fragmented QRS complex to predict arrhythmic events and cardiovascular mortality in patients with noncompaction cardiomyopathy. Am J Cardiol 2016;117:1516-23.
Sunbul M, Tigen K. Pathophysiological links, echocardiographic characteristics, and clinical implications of QRS morphology in patients with dilated cardiomyopathy. Ther Adv Cardiovasc Dis 2015;9:325-9.
Onoue Y, Izumiya Y, Hanatani S, Kimura Y, Araki S, Sakamoto K, et al.
Fragmented QRS complex is a diagnostic tool in patients with left ventricular diastolic dysfunction. Heart Vessels 2016;31:563-7.
Karakulak UN, Tutkun E, Yılmaz ÖH. Iron overload and fragmented QRS in patients with thalassemia major: Mechanisms, therapies, and new horizons. Anatol J Cardiol 2015;15:592.
Bayar N, Kurtoǧlu E, Arslan Ş, Erkal Z, Çay S, Çaǧırcı G, et al.
Assessment of the relationship between fragmented QRS and cardiac iron overload in patients with beta-thalassemia major. Anatol J Cardiol 2015;15:132-6.
Buyukkaya E, Karakas MF, Kurt M, Bilen P, Yalcın F, Celik M, et al.
The relation of fragmented QRS with tissue Doppler derived parameters in patients with b-thalassaemia major. Clin Invest Med 2012;35:E334.
Kirk P, Roughton M, Porter JB, Walker JM, Tanner MA, Patel J, et al.
Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation 2009;120:1961-8.
Veglio F, Melchio R, Rabbia F, Molino P, Genova GC, Martini G, et al.
Blood pressure and heart rate in young thalassemia major patients. Am J Hypertens 1998;11:539-47.
Kaye SB, Owen M. Cardiac arrhythmias in thalassaemia major: Evaluation of chelation treatment using ambulatory monitoring. Br Med J 1978;1:342.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]