Skip to main content
SpringerLink
Log in

Early detection of ventricular dysfunction by tissue Doppler echocardiography related to cardiac iron overload in patients with thalassemia

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Cardiac T2* MRI is used as a gold standard for cardiac iron quantification in patients with transfusion-dependent thalassemia (TDT). We hypothesized that left ventricular (LV) diastolic dysfunction would reflect the severity of iron overload and can serve as an early detection of cardiac iron deposits. A study was conducted on all patients with TDT. Hemoglobin, serum ferritin and non-transferrin bound iron, together with a complete echocardiography and cardiac T2* MRI, were performed on all patients. Seventy-seven patients with TDT were enrolled (median age 14 years). In the patient group with a mean serum ferritin of > 2500 ng/mL during the past 12 months, there were more patients with severe cardiac iron deposits than in the group with a mean serum ferritin of ≤ 2500 ng/mL. Diastolic dysfunction was absent in all patients with a serum ferritin of < 1000 ng/mL. All patients with cardiac T2* ≤ 20 ms had grade III LV diastolic dysfunction. However, twenty-one percent of patients with cardiac T2* > 20 ms had LV diastolic dysfunction. The differences observed in pulmonary vein atrial reversal duration and mitral A-wave (PVAR–MVA) duration ≥ − 1 ms and an E/E′ ratio ≥ 11 were proven to be the associated factors with the cardiac T2* ≤ 20 ms. Increased PVAR–MVA duration and increased E/E′ ratio reliably reflected a severe iron overload, according to a cardiac T2* in patients with TDT. LV diastolic dysfunction can occur prior to severe cardiac iron deposition. Tissue Doppler echocardiography has the potential for the early detection of cardiac involvement in patients with TDT .

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Origa R (2017) β-Thalassemia. Genet Med 19:609–619

    CAS  PubMed  Google Scholar 

  2. Martin A, Thompson AA (2013) Thalassemias. Pediatr Clin N Am 60:1383–1391

    Google Scholar 

  3. Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A et al (1994) Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 331:574–578

    CAS  PubMed  Google Scholar 

  4. Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC et al (2004) Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 89:1187–1193

    PubMed  Google Scholar 

  5. Poggiali E, Cassinerio E, Zanaboni L, Cappellini MD (2012) An update on iron chelation therapy. Blood Transfus 10:411–422

    PubMed  PubMed Central  Google Scholar 

  6. Fernandes JL (2012) Iron chelation therapy in the management of transfusion-related cardiac iron overload. Transfusion 52:2256–2268

    CAS  PubMed  Google Scholar 

  7. Ware HM, Kwiatkowski JL (2013) Evaluation and treatment of transfusional iron overload in children. Pediatr Clin N Am 60:1393–1406

    Google Scholar 

  8. Marsella M, Borgna-Pignatti C (2014) Transfusional iron overload and iron chelation therapy in thalassemia major and sickle cell disease. Hematol Oncol Clin N Am 28:703–727

    Google Scholar 

  9. Baksi AJ, Pennell DJ (2014)Randomized controlled trials of iron chelators for the treatment of cardiac siderosis in thalassaemia major. Front Pharmacol 5:217.

    PubMed  PubMed Central  Google Scholar 

  10. Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH et al (2001) Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 22:2171–9.

    CAS  PubMed  Google Scholar 

  11. Kirk P, Roughton M, Porter JB, Walker JM, Tanner MA, Patel J et al (2009) Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation 120:1961–1968

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wood JC, Noetzli L (2010) Cardiovascular MRI in thalassemia major. Ann N Y Acad Sci 1202:173–9.

    PubMed  Google Scholar 

  13. Anderson LJ (2011)Assessment of iron overload with T2* magnetic resonance imaging. Prog Cardiovasc Dis 54:287–94.

    CAS  PubMed  Google Scholar 

  14. Carpenter JP, He T, Kirk P, Roughton M, Anderson LJ, de Noronha SV et al (2011)On T2* magnetic resonance and cardiac iron. Circulation 123:1519–28.

    PubMed  PubMed Central  Google Scholar 

  15. Wood JC (2011) Impact of iron assessment by MRI. Hematol Am Soc Hematol Educ Program 2011:443–50

    Google Scholar 

  16. Wood JC (2014)Use of magnetic resonance imaging to monitor iron overload. Hematol Oncol Clin North Am 28:747–64.

    PubMed  PubMed Central  Google Scholar 

  17. Wood JC (2015) Estimating tissue iron burden: current status and future prospects. Br J Haematol 170:15–28

    PubMed  PubMed Central  Google Scholar 

  18. Modell B, Khan M, Darlison M, Westwood MA, Ingram D, Pennell DJ (2008) Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson 10:42

    PubMed  PubMed Central  Google Scholar 

  19. Carpenter JP, Roughton M, Pennell DJ, Myocardial Iron in Thalassemia (MINT) Investigators (2013) International survey of T2* cardiovascular magnetic resonance in β-thalassemia major. Haematologica 98:1368–1374

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R et al (2013) Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association. Circulation 128:281–308

    CAS  PubMed  Google Scholar 

  21. Auger D, Pennell DJ (2016) Cardiac complications in thalassemia major. Ann N Y Acad Sci 1368:56–64

    CAS  PubMed  Google Scholar 

  22. Lau KC, Li AM, Hui PW, Yeung CY (1989) Left ventricular function in beta-thalassemia major. Arch Dis Child 64:1046–1051

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Spirito P, Lupi G, Melevendi C, Vecchio C (1990) Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major. Circulation 82:88–94

    CAS  PubMed  Google Scholar 

  24. Kremastinos DT, Tsiapras DP, Tsetsos GA, Rentoukas EI, Vretou HP, Toutouzas PK (1993) Left ventricular diastolic Doppler characteristics in β-thalassemia major. Circulation 88:1127–1135

    CAS  PubMed  Google Scholar 

  25. Gharzuddine WS, Kazma HK, Nuwayhid IA, Bitar FF, Koussa SF, Moukarbel GV et al (2002) Doppler characterization of left ventricular diastolic function in beta-thalassaemia major. Evidence for an early stage of impaired relaxation. Eur J Echocardiogr 3:47–51

    CAS  PubMed  Google Scholar 

  26. Parale GP, Pawar SS, Tapare VS (2009) Assessment of LV diastolic function in patients with beta-thalassemia major with special reference to E/Eann ratio. J Pediatr Hematol Oncol 31:69–73

    PubMed  Google Scholar 

  27. Vogel M, Anderson LJ, Holden S, Deanfield JE, Pennell DJ, Walker JM (2003) Tissue Doppler echocardiography in patients with thalassaemia detects early myocardial dysfunction related to myocardial iron overload. Eur Heart J 24:113–119

    CAS  PubMed  Google Scholar 

  28. Silvilairat S, Sittiwangkul R, Pongprot Y, Charoenkwan P, Phornphutkul C (2008) Tissue Doppler echocardiography reliably reflects severity of iron overload in pediatric patients with beta thalassemia. Eur J Echocardiogr 9:368–372

    PubMed  Google Scholar 

  29. Magrì D, Sciomer S, Fedele F, Gualdi G, Casciani E, Pugliese P et al (2008) Early impairment of myocardial function in young patients with beta-thalassemia major. Eur J Haematol 80:515–522

    PubMed  Google Scholar 

  30. Uçar T, Ileri T, Atalay S, Uysal Z, Tutar E, Ertem M (2009) Early detection of myocardial dysfunction in children with beta-thalassaemia major. Int J Cardiovasc Imaging 25:379–386

    PubMed  Google Scholar 

  31. Leonardi B, Margossian R, Colan SD, Powell AJ (2008) Relationship of magnetic resonance imaging estimation of myocardial iron to left ventricular systolic and diastolic function in thalassemia. JACC Cardiovasc Imaging 1:572–578

    PubMed  Google Scholar 

  32. de Gregorio C, Piraino B, Morabito G, Salpietro CD, Coglitore S (2010) On the use of conventional and tissue Doppler echocardiography in patients with β-Thalassemia major and myocardial iron-overload: preliminary data by a single center study. Int J Cardiol 145:490–492

    PubMed  Google Scholar 

  33. Aypar E, Alehan D, Hazirolan T, Gümrük F (2010) 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 26:413–421

    PubMed  Google Scholar 

  34. Balci YI, Gurses D (2011) Detection of early cardiac dysfunction in patients with β-thalassemia major and thalassemia trait by tissue Doppler echocardiography. Pediatr Hematol Oncol 28:486–496

    PubMed  Google Scholar 

  35. Kostopoulou AG, Tsiapras DP, Chaidaroglou AS, De Giannis DE, Farmakis D, Kremastinos DT (2014) The pathophysiological relationship and clinical significance of left atrial function and left ventricular diastolic dysfunction in β-thalassemia major. Am J Hematol 89:13–18

    CAS  PubMed  Google Scholar 

  36. Agha HM, Beshlawy A, Hamdy M, Sobeih A, El Zahrae F, Abd El Satar IA et al (2015) Early detection of right ventricular diastolic dysfunction by pulsed tissue Doppler echocardiography in iron loaded beta thalassemia patients. Pediatr Cardiol 36:468–474

    PubMed  Google Scholar 

  37. Silvilairat S, Charoenkwan P, Saekho S, Tantiworawit A, Phrommintikul A, Srichairatanakool S et al (2016) Heart rate variability for early detection of cardiac iron deposition in patients with transfusion-dependent thalassemia. PLoS ONE 11:e0164300

    PubMed  PubMed Central  Google Scholar 

  38. O’Leary PW (1999) Pediatric diastology: use and limitations of Doppler echocardiography in the evaluation of ventricular diastolic function in children. Prog Pediatr Cardiol 10:83–93

    Google Scholar 

  39. Eidem BW, McMahon CJ, Cohen RR, Wu J, Finkelshteyn I, Kovalchin JP et al (2004) Impact of cardiac growth on Doppler tissue imaging velocities: a study in healthy children. J Am Soc Echocardiogr 17:212–221

    PubMed  Google Scholar 

  40. Frommelt PC (2016) Diastolic ventricular function assessment. Echocardiography in pediatric and congenital heart disease: from fetus to adult, 2nd edn. Wiley, New York, pp 132–153

    Google Scholar 

  41. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH et al (1997) Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 30:474–480

    CAS  PubMed  Google Scholar 

  42. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T et al (2016) Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 29:277–314

    PubMed  Google Scholar 

  43. Lekawanvijit S, Chattipakorn N (2009) Iron overload thalassemic cardiomyopathy: iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol 25:213–218

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Walker JM (2013) Thalassaemia major and the heart: a toxic cardiomyopathy tamed? Heart 99:827–834

    CAS  PubMed  Google Scholar 

  46. Moussavi F, Ghasabeh MA, Roodpeyma S, Alavi S, Shakiba M, Gheiratmand R et al (2014) Optimal method for early detection of cardiac disorders in thalassemia major patients: magnetic resonance imaging or echocardiography? Blood Res 49:182–186

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by grants from the Thailand Research Fund RSA5680014.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Suchaya Silvilairat & Pimlak Charoenkwan

  2. Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand

    Suwit Saekho

  3. Biomedical Engineering Center, Faculty of Engineering, Chiang Mai University, Chiang Mai, Thailand

    Suwit Saekho

  4. Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Adisak Tantiworawit

  5. Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Somdet Srichairatanakool

Authors
  1. Suchaya Silvilairat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pimlak Charoenkwan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suwit Saekho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adisak Tantiworawit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Somdet Srichairatanakool
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suchaya Silvilairat.

Ethics declarations

Conflict of interest

All authors have no conflict of interest.

Ethical approval

This study was approved by the Institutional Research Committee, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. All procedures performed in studies involving human participants were in accordance with the Ethical Standards of the 1964 Helsinki Declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Silvilairat, S., Charoenkwan, P., Saekho, S. et al. Early detection of ventricular dysfunction by tissue Doppler echocardiography related to cardiac iron overload in patients with thalassemia. Int J Cardiovasc Imaging 37, 91–98 (2021). https://doi.org/10.1007/s10554-020-01949-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-020-01949-8

Keywords

Search

Navigation