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Cardiac complications and iron overload in beta thalassemia major patients—a systematic review and meta-analysis

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Abstract

Despite the major improvement in therapeutic management of thalassemia major, iron overload is considered a challenging conundrum in these patients and heart disease still remains a major cause of morbidity and mortality in these patients. Therefore, this study aimed to investigate the prevalence of cardiac iron overload and cardiovascular complications in transfusion-dependent thalassemia patients in the worldwide. The following databases were searched: ISI/Web of Science, Embase, PubMed, Scopus, up to February 30, 2018. The quality of the studies was evaluated using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. The random model based on Metaprop was used. One hundred forty-two studies were included. The total number of patients included was 26,893. The mean age of patients was 22.6 (SD = 1.7) years. Based on Metaprop, the overall prevalence of cardiac iron overload/myocardial sidoresis (T2* < 20 ms) and cardiac complications in thalassemia major patients in the worldwide was 25% (95% CI 22–28%) and 42% (95% CI 37–46%), respectively. The results of this study show that the prevalence of cardiac iron overload and cardiovascular complications in patients with thalassemia major is almost high. Therefore, iron chelation and careful monitoring of serum ferritin level will prevent the cardiac iron overload, and interval monitoring of patients with transfusion-dependent thalassemia (TDT) by echocardiography and electrocardiography will help with early detection of cardiovascular complications.

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Abbreviations

β-TM :

β-Thalassemia major

TDT :

Transfusion-dependent thalassemia

CIO :

Cardiac iron overload

PH :

Pulmonary hypertension

TR :

Tricuspid regurgitation

MRI :

Magnetic resonance

References

  1. Higgs DR, Engel JD, Stamatoyannopoulos G (2012) Thalassaemia. Lancet 379:373–383

    Article  CAS  PubMed  Google Scholar 

  2. De Sanctis V, Kattamis C, Canatan D et al (2017) Beta-thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis 9:e2017018

    Article  PubMed  PubMed Central  Google Scholar 

  3. Williams TN, Weatherall DJ (2012) World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb Perspect Med 2:a011692

    Article  PubMed  PubMed Central  Google Scholar 

  4. Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R, Hoffman TM, Kiernan MS, Lerakis S, Piga A, Porter JB, Walker JM, Wood J (2013) Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association. Circulation 128:281–308

    Article  CAS  PubMed  Google Scholar 

  5. Krittayaphong R, Viprakasit V, Saiviroonporn P, Siritanaratkul N, Siripornpitak S, Meekaewkunchorn A, Kirawittaya T, Sripornsawan P, Jetsrisuparb A, Srinakarin J, Wong P, Phalakornkul N, Sinlapamongkolkul P, Wood J (2017) Prevalence and predictors of cardiac and liver iron overload in patients with thalassemia: a multicenter study based on real-world data. Blood Cell Mol Dis 66:24–30

    Article  CAS  Google Scholar 

  6. Wijarnpreecha K, Kumfu S, Chattipakorn SC, Chattipakorn N (2015) Cardiomyopathy associated with iron overload: how does iron enter myocytes and what are the implications for pharmacological therapy? Hemoglobin 39:9–17

    Article  CAS  PubMed  Google Scholar 

  7. Bonifazi F, Conte R, Baiardi P, Bonifazi D, Felisi M, Giordano P, Giannuzzi V, Iacono A, Padula R, Pepe A, Caterina Putti M, Ruggieri L, Carlo del Vecchio G, Filosa A, Maggio A, Ceci A, HTA-THAL Multiregional Registry (2017) Pattern of complications and burden of disease in patients affected by beta thalassemia major. Curr Med Res Opin 33:1525–1533

    Article  PubMed  Google Scholar 

  8. Kremastinos DT, Farmakis D, Aessopos A, Hahalis G, Hamodraka E, Tsiapras D, Keren A (2010) β-Thalassemia cardiomyopathy: history, present considerations, and future perspectives. Circ Heart Fail 3:451–458

    Article  PubMed  Google Scholar 

  9. Patel HV, Qari M, Mousa SA et al (2012) Iron balance in β-thalassemia: maintaining an antioxidant/oxidant ratio. J Appl Hematol 3:4

    Google Scholar 

  10. Carpenter J-P, Roughton M, Pennell DJ, Investigators MIiT (2013) International survey of T2* cardiovascular magnetic resonance in β-thalassemia major. Haematologica 98:1368–1374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Galanello R, Origa R (2010) Beta-thalassemia. Orphanet J Rare Dis 5:11

    Article  PubMed  PubMed Central  Google Scholar 

  12. Russo V, Rago A, Papa AA, Nigro G (2016) Electrocardiographic presentation, cardiac arrhythmias, and their management in β-thalassemia major patients. Ann Noninvasive Electrocardiol 21:335–342

    Article  PubMed  PubMed Central  Google Scholar 

  13. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097

    Article  PubMed  PubMed Central  Google Scholar 

  14. Munn Z, Moola S, Riitano D, Lisy K (2014) The development of a critical appraisal tool for use in systematic reviews addressing questions of prevalence. Int J Health Policy Manag 3:123–128

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nyaga VN, Arbyn M, Aerts M (2014) Metaprop: a Stata command to perform meta-analysis of binomial data. Arch Public Health 72:39

    Article  PubMed  PubMed Central  Google Scholar 

  16. Higgins J, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  17. Deeks JJ, Higgins JP, Altman DG (2008) Analysing data and undertaking meta-analyses. Cochrane handbook for systematic reviews of interventions: Cochrane book series 26:243–296

  18. Ades A, Lu G, Higgins J (2005) The interpretation of random-effects meta-analysis in decision models. Med Decis Mak 25:646–654

    Article  CAS  Google Scholar 

  19. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  PubMed Central  Google Scholar 

  20. Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. Bmj 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kremastinos D, Farmakis D, Aessopos A et al (2010) Beta-thalassemia cardiomyopathy: history, present considerations, and future perspectives. Circ Heart Fail 3:451–458

    Article  PubMed  Google Scholar 

  22. Yang G, Liu R, Peng P, Long L, Zhang X, Yang W, Tan S, Pan H, Long X, He T, Anderson L, Lai Y (2014) How early can myocardial iron overload occur in beta thalassemia major? PLoS One 9:e85379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR, Thalassemia Clinical Research Network (2004) Complications of β-thalassemia major in North America. Blood 104:34–39

    Article  CAS  PubMed  Google Scholar 

  24. Richardson M, Matthews R, Alison J et al (1993) Prevention of heart disease by subcutaneous desferoxamine in patients with thalassaemia major. Intern Med J 23:656–661

    CAS  Google Scholar 

  25. Piga A, Gaglioti C, Fogliacco E, Tricta F (2003) Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. Haematologica 88:489–496

    CAS  PubMed  Google Scholar 

  26. Aessopos A, Farmakis D, Deftereos S, Tsironi M, Tassiopoulos S, Moyssakis I, Karagiorga M (2005) Thalassemia heart disease: a comparative evaluation of thalassemia major and thalassemia intermedia. Chest 127:1523–1530

    Article  PubMed  Google Scholar 

  27. Yaghobi M, Miri-Moghaddam E, Majid N et al (2017) Complications of transfusion-dependent β-thalassemia patients in Sistan and Baluchistan, south-east of Iran. Int J Hematol Oncol Stem Cell Res 11:268

    PubMed  PubMed Central  Google Scholar 

  28. Wood JC, Origa R, Agus A, Matta G, Coates TD, Galanello R (2008) Onset of cardiac iron loading in pediatric patients with thalassemia major. Haematologica 93:917–920

    Article  PubMed  Google Scholar 

  29. Farhangi H, Badiei Z, Moghaddam HM, Keramati MR (2017) Assessment of heart and liver iron overload in thalassemia major patients using T2* magnetic resonance imaging. Indian J Hematol Blood Transfus 33:228–234

    Article  PubMed  Google Scholar 

  30. Aydinok Y, Porter JB, Piga A, Elalfy M, el-Beshlawy A, Kilinç Y, Viprakasit V, Yesilipek A, Habr D, Quebe-Fehling E, Pennell DJ (2015) Prevalence and distribution of iron overload in patients with transfusion-dependent anemias differs across geographic regions: results from the CORDELIA study. Eur J Haematol 95:244–253

    Article  CAS  PubMed  Google Scholar 

  31. Davis BA, O’Sullivan C, Jarritt PH, Porter JB (2004) Value of sequential monitoring of left ventricular ejection fraction in the management of thalassemia major. Blood 104:263–269

    Article  CAS  PubMed  Google Scholar 

  32. Wood JC (2009) Cardiac complications in thalassemia major. Hemoglobin 33:S81–S86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Srihirun S, Tanjararak N, Chuncharunee S, Sritara P, Kaewvichit R, Fucharoen S, Pattanapanyasat K, Sibmooh N (2015) Platelet hyperactivity in thalassemia patients with elevated tricuspid regurgitant velocity and the association with hemolysis. Thromb Res 135:121–126

    Article  CAS  PubMed  Google Scholar 

  34. Chate SC (2016) Cardiac abnormalities in patients with beta thalassemia. Int J Contemp Pediatr 3:224–228

    Article  Google Scholar 

  35. Kirk P, Roughton M, Porter JB, Walker JM, Tanner MA, Patel J, Wu D, Taylor J, Westwood MA, Anderson LJ, Pennel DJ (2009) Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. J Cardiovasc Magn Reson 11:O2

    Article  PubMed Central  Google Scholar 

  36. Maggio A, Filosa A, Vitrano A, Aloj G, Kattamis A, Ceci A, Fucharoen S, Cianciulli P, Grady RW, Prossomariti L, Porter JB, Iacono A, Cappellini MD, Bonifazi F, Cassarà F, Harmatz P, Wood J, Gluud C (2011) Iron chelation therapy in thalassemia major: a systematic review with meta-analyses of 1520 patients included on randomized clinical trials. Blood Cell Mol Dis 47:166–175

    Article  CAS  Google Scholar 

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Funding

This study is financially supported by the Research Deputy of Birjand University of Medical Sciences.

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Authors and Affiliations

  1. Student Research Committee, Department of Epidemiology, School of Public Health and Safety, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    F. Koohi

  2. Cardiovascular Diseases Research Center & Department of Cardiology, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran

    T. Kazemi

  3. Cardiovascular Diseases Research Center & Dep. of Molecular Medicine, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran

    E. Miri-Moghaddam

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  1. F. Koohi
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  2. T. Kazemi
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  3. E. Miri-Moghaddam
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Contributions

F. Koohi was the main investigator and drafted the manuscript. E. Miri-Moghaddam and T. Kazemi were the study supervisors and contributed to all aspects of the study.

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Correspondence to E. Miri-Moghaddam.

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Koohi, F., Kazemi, T. & Miri-Moghaddam, E. Cardiac complications and iron overload in beta thalassemia major patients—a systematic review and meta-analysis. Ann Hematol 98, 1323–1331 (2019). https://doi.org/10.1007/s00277-019-03618-w

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  • DOI: https://doi.org/10.1007/s00277-019-03618-w

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