Detection of myocardial iron overload by two-dimensional speckle tracking in patients with beta-thalassaemia major: a combined echocardiographic and T2* segmental CMR study

  • Fausto Pizzino
  • Antonella Meloni
  • Anna Terrizzi
  • Tommaso Casini
  • Anna Spasiano
  • Carlo Cosmi
  • Massimo Allò
  • Concetta Zito
  • Scipione Carerj
  • Giovanni Donato Aquaro
  • Gianluca Di Bella
  • Alessia PepeEmail author
Original Paper


We aimed to evaluate the role of two-dimensional speckle tracking imaging (2DSTI) in detecting early changes of myocardial deformation in patients affected by thalassemia major (TM) and its relation with myocardial iron overload (MIO) detected by T2* cardiovascular magnetic resonance (CMR). We studied 28 TM patients (15 males, 37.4 ± 10 years). All patients underwent CMR and echocardiography in the same day. Segmental and global T2* values were measured. Values of global longitudinal strain (GLS) were derived from the three apical views, while radial and circumferential strain were obtained as average strain from the short axis views at basal, mid and apical level. Six patients (21.4%) showed significant MIO (global heart T2* < 20 ms). GLS showed a significant correlation with T2* values (R = −0.49; P = 0.001) and it was significantly lower in patients with a significant MIO than in those with no significant MIO (−18.3 ± 2 vs. −21.3 ± 2.7, P = 0.02). No significant difference was found for radial and circumferential strain in relation to the severity of MIO. Patients with impaired GLS (<−19.5%) had a significant higher risk of showing significant MIO (Odds-ratio-OR = 17; 95%). GLS is related with global T2* in TM patients. Moreover, GLS can identify TM patients with severe MIO detected by CMR.


Thalassemia major Myocardial deformation Myocardial iron overload 



We thank all patients for their cooperation. We also thank the technical radiologists, the nurses and the secretary for their support in this study.

Compliance with ethical standards

Conflict of interest

The authors do not have any conflict of interest to declare.


The MIOT project received ‘no-profit support’ from Chiesi Farmaceutici S.p.A., Apopharma Inc and Bayer S.P.A.


  1. 1.
    Dubey AP, Parakh A, Dublish S (2008) Current trends in the management of beta thalassemia. Indian J Pediatr 75(7):739–743CrossRefPubMedGoogle Scholar
  2. 2.
    Hershko C (2010) Pathogenesis and management of iron toxicity in thalassemia. Ann NY Acad Sci 1202:1–9CrossRefPubMedGoogle Scholar
  3. 3.
    Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi R, Piga A, Cnaan A (2004) Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 89(10):1187–1193PubMedGoogle Scholar
  4. 4.
    Casale M, Meloni A, Filosa A, Cuccia L, Caruso V, Palazzi G, Gamberini MR, Pitrolo L, Putti MC, D’Ascola DG, Casini T, Quarta A, Maggio A, Neri MG, Positano V, Salvatori C, Toia P, Valeri G, Midiri M, Pepe A (2015) Multiparametric cardiac magnetic resonance survey in children with thalassemia major: a multicenter study. Circ Cardiovasc Imaging 8(8):e003230CrossRefPubMedGoogle Scholar
  5. 5.
    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(1):42CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kremastinos DT, Farmakis D (2011) Iron overload cardiomyopathy in clinical practice. Circulation 124(20):2253–2263CrossRefPubMedGoogle Scholar
  7. 7.
    Geyer H, Caracciolo G, Abe H, Wilansky S, Carerj S, Gentile F, Nesser HJ, Khandheria B, Narula J, Sengupta PP (2010) Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr 23(4):351–369 (quiz 453–355)CrossRefPubMedGoogle Scholar
  8. 8.
    Di Bella G, Pizzino F, Minutoli F, Zito C, Donato R, Dattilo G, Oreto G, Baldari S, Vita G, Khandheria BK, Carerj S (2014) The mosaic of the cardiac amyloidosis diagnosis: role of imaging in subtypes and stages of the disease. Eur Heart J Cardiovasc Imaging 15(12):1307–1315CrossRefPubMedGoogle Scholar
  9. 9.
    Carstensen HG, Larsen LH, Hassager C, Kofoed KF, Jensen JS, Mogelvang R (2015) Basal longitudinal strain predicts future aortic valve replacement in asymptomatic patients with aortic stenosis. Eur Heart J Cardiovasc Imaging 17(3):283–292CrossRefPubMedGoogle Scholar
  10. 10.
    Stampehl MR, Mann DL, Nguyen JS, Cota F, Colmenares C, Dokainish H (2015) Speckle strain echocardiography predicts outcome in patients with heart failure with both depressed and preserved left ventricular ejection fraction. Echocardiography 32(1):71–78CrossRefPubMedGoogle Scholar
  11. 11.
    Cusma Piccione M, Zito C, Bagnato G, Oreto G, Di Bella G, Bagnato G, Carerj S (2013) Role of 2D strain in the early identification of left ventricular dysfunction and in the risk stratification of systemic sclerosis patients. Cardiovasc Ultrasound 11:6CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Zito C, Sengupta PP, Di Bella G, Oreto G, Cusma-Piccione M, Longordo C, Caracciolo G, Lentini S, Carerj S (2011) Myocardial deformation and rotational mechanics in revascularized single vessel disease patients 2 years after ST-elevation myocardial infarction. J Cardiovasc Med 12(9):635–642CrossRefGoogle Scholar
  13. 13.
    Todaro MC, Khandheria BK, Longobardo L, Zito C, Cusma-Piccione M, Di Bella G, Oreto L, Mohammed M, Oreto G, Carerj S (2015) New diagnostic perspectives on heart failure with preserved ejection fraction: systolic function beyond ejection fraction. J Cardiovasc Med 16(8):527–537CrossRefGoogle Scholar
  14. 14.
    Zito C, Carerj S, Todaro MC, Cusma-Piccione M, Caprino A, Di Bella G, Oreto L, Oreto G, Khandheria BK (2013) Myocardial deformation and rotational profiles in mitral valve prolapse. Am J Cardiol 112(7):984–990CrossRefPubMedGoogle Scholar
  15. 15.
    Farsalinos K, Tsiapras D, Kyrzopoulos S, Voudris V (2013) Acute and chronic effects of smoking on myocardial function in healthy heavy smokers: a study of Doppler flow, Doppler tissue velocity, and two-dimensional speckle tracking echocardiography. Echocardiography 30(3):285–292. doi: 10.1111/echo.12052 CrossRefPubMedGoogle Scholar
  16. 16.
    Hung CL, Goncalves A, Lai YJ, Lai YH, Sung KT, Lo CI, Liu CC, Kuo JY, Hou CJ, Chao TF, Bulwer BE, Lin SJ, Yeh HI, Lam CS (2016) Light to moderate habitual alcohol consumption is associated with subclinical ventricular and left atrial mechanical dysfunction in an asymptomatic population: dose-response and propensity analysis. J Am Soc Echocardiogr 29(11):1043–1051. doi: 10.1016/j.echo.2016.07.014 CrossRefPubMedGoogle Scholar
  17. 17.
    Gokdeniz T, Kalaycioglu E, Aykan AC, Gul I, Boyaci F, Gursoy MO (2014) Effects of non-dipper blood pressure pattern on left ventricular rotational mechanics in hypertensive patients with type 2 diabetes mellitus: a speckle tracking study. Int J Cardiovasc Imaging 30(1):57–65. doi: 10.1007/s10554-013-0296-5 CrossRefPubMedGoogle Scholar
  18. 18.
    Meloni A, Ramazzotti A, Positano V, Salvatori C, Mangione M, Marcheschi P, Favilli B, De Marchi D, Prato S, Pepe A, Sallustio G, Centra M, Santarelli MF, Lombardi M, Landini L (2009) Evaluation of a web-based network for reproducible T2* MRI assessment of iron overload in thalassemia. Int J Med Inform 78(8):503–512CrossRefPubMedGoogle Scholar
  19. 19.
    Pepe A, Positano V, Santarelli F, Sorrentino F, Cracolici E, De Marchi D, Maggio A, Midiri M, Landini L, Lombardi M (2006) Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload. J Magn Reson Imaging 23(5):662–668CrossRefPubMedGoogle Scholar
  20. 20.
    Positano V, Pepe A, Santarelli MF, Ramazzotti A, Meloni A, De Marchi D, Favilli B, Cracolici E, Midiri M, Spasiano A, Lombardi M, Landini L (2009) Multislice multiecho T2* cardiac magnetic resonance for the detection of heterogeneous myocardial iron distribution in thalassaemia patients. NMR Biomed 22(7):707–715CrossRefPubMedGoogle Scholar
  21. 21.
    Cerqueira MD, Weissman NJ, Dilsizian V, Jacobs AK, Kaul S, Laskey WK, Pennell DJ, Rumberger JA, Ryan T, Verani MS (2002) Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 105(4):539–542CrossRefPubMedGoogle Scholar
  22. 22.
    Ramazzotti A, Pepe A, Positano V, Rossi G, De Marchi D, Brizi MG, Luciani A, Midiri M, Sallustio G, Valeri G, Caruso V, Centra M, Cianciulli P, De Sanctis V, Maggio A, Lombardi M (2009) Multicenter validation of the magnetic resonance T2* technique for segmental and global quantification of myocardial iron. J Magn Reson Imaging 30(1):62–68CrossRefPubMedGoogle Scholar
  23. 23.
    Anderson LJ, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell DJ (2001) Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J 22(23):2171–2179CrossRefPubMedGoogle Scholar
  24. 24.
    Carpenter JP, He T, Kirk P, Roughton M, Anderson LJ, de Noronha SV, Sheppard MN, Porter JB, Walker JM, Wood JC, Galanello R, Forni G, Catani G, Matta G, Fucharoen S, Fleming A, House MJ, Black G, Firmin DN, St Pierre TG, Pennell DJ (2011) On T2* magnetic resonance and cardiac iron. Circulation 123(14):1519–1528. doi: 10.1161/CIRCULATIONAHA.110.007641 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Positano V, Pepe A, Santarelli MF, Scattini B, De Marchi D, Ramazzotti A, Forni G, Borgna-Pignatti C, Lai ME, Midiri M, Maggio A, Lombardi M, Landini L (2007) Standardized T2* map of normal human heart in vivo to correct T2* segmental artefacts. NMR Biomed 20(6):578–590CrossRefPubMedGoogle Scholar
  26. 26.
    Marsella M, Borgna-Pignatti C, Meloni A, Caldarelli V, Dell’Amico MC, Spasiano A, Pitrolo L, Cracolici E, Valeri G, Positano V, Lombardi M, Pepe A (2011) Cardiac iron and cardiac disease in males and females with transfusion-dependent thalassemia major: a T2* magnetic resonance imaging study. Haematologica 96(4):515–520CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Meloni A, Favilli B, Positano V, Cianciulli P, Filosa A, Quarta A, D’Ascola D, Restaino G, Lombardi M, Pepe A (2009) Safety of cardiovascular magnetic resonance gadolinium chelates contrast agents in patients with hemoglobinopaties. Haematologica 94(11):1625–1627CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Pepe A, Positano V, Capra M, Maggio A, Lo Pinto C, Spasiano A, Forni G, Derchi G, Favilli B, Rossi G, Cracolici E, Midiri M, Lombardi M (2009) Myocardial scarring by delayed enhancement cardiovascular magnetic resonance in thalassaemia major. Heart 95:1688–1693CrossRefPubMedGoogle Scholar
  29. 29.
    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 16(3):233–270. doi: 10.1093/ehjci/jev014 CrossRefPubMedGoogle Scholar
  30. 30.
    Pepe A, Meloni A, Capra M, Cianciulli P, Prossomariti L, Malaventura C, Putti MC, Lippi A, Romeo MA, Bisconte MG, Filosa A, Caruso V, Quarta A, Pitrolo L, Missere M, Midiri M, Rossi G, Positano V, Lombardi M, Maggio A (2011) Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging. Haematologica 96(1):41–47CrossRefPubMedGoogle Scholar
  31. 31.
    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 beta-thalassemia major: a consensus statement from the American Heart Association. Circulation 128(3):281–308CrossRefPubMedGoogle Scholar
  32. 32.
    Moussavi F, Ghasabeh MA, Roodpeyma S, Alavi S, Shakiba M, Gheiratmand R, Omidghaemi M (2014) Optimal method for early detection of cardiac disorders in thalassemia major patients: magnetic resonance imaging or echocardiography? Blood Res 49(3):182–186CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Djer MM, Anggriawan SL, Gatot D, Amalia P, Sastroasmoro S, Widjaja P (2013) Correlation between T2* cardiovascular magnetic resonance with left ventricular function and mass in adolescent and adult major thalassemia patients with iron overload. Acta Med Indones 45(4):295–301PubMedGoogle Scholar
  34. 34.
    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(5):572–578CrossRefPubMedGoogle Scholar
  35. 35.
    Cusma Piccione M, Piraino B, Zito C, Khandheria BK, Di Bella G, De Gregorio C, Oreto L, Rigoli L, Ferrau V, Salpietro CD, Carerj S (2013) Early identification of cardiovascular involvement in patients with beta-thalassemia major. Am J Cardiol 112(8):1246–1251CrossRefPubMedGoogle Scholar
  36. 36.
    Garceau P, Nguyen ET, Carasso S, Ross H, Pendergrast J, Moravsky G, Bruchal-Garbicz B, Rakowski H (2011) Quantification of myocardial iron deposition by two-dimensional speckle tracking in patients with beta-thalassaemia major and Blackfan–Diamond anaemia. Heart 97(5):388–393CrossRefPubMedGoogle Scholar
  37. 37.
    Li SJ, Hwang YY, Ha SY, Chan GC, Mok AS, Wong SJ, Cheung YF (2016) Role of three-dimensional speckle tracking echocardiography in the quantification of myocardial iron overload in patients with beta-thalassemia major. Echocardiography 33(9):1361–1367. doi: 10.1111/echo.13266 CrossRefPubMedGoogle Scholar
  38. 38.
    Pepe A, Positano V, Santarelli MF, Sorrentino F, Cracolici E, De Marchi D, Maggio A, Midiri M, Landini L, Lombardi M (2006) Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload. J Magn Reson Imaging 23(5):662–668. doi: 10.1002/jmri.20566 CrossRefPubMedGoogle Scholar
  39. 39.
    Cheung YF, Liang XC, Chan GC, Wong SJ, Ha SY (2010) Myocardial deformation in patients with beta-thalassemia major: a speckle tracking echocardiographic study. Echocardiography 27(3):253–259CrossRefPubMedGoogle Scholar
  40. 40.
    Chen MR, Ko HS, Chao TF, Liu HC, Kuo JY, Bulwer BE, Yeh HI, Hung CL (2015) Relation of myocardial systolic mechanics to serum ferritin level as a prognosticator in thalassemia patients undergoing repeated transfusion. Echocardiography 32(1):79–88CrossRefPubMedGoogle Scholar
  41. 41.
    Malik V, Subramaniam A, Kapoor PM (2016) Strain and strain rate: an emerging technology in the perioperative period. Ann Card Anaesth 19(1):112–121. doi: 10.4103/0971-9784.173026 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Wood JC, Otto-Duessel M, Aguilar M, Nick H, Nelson MD, Coates TD, Pollack H, Moats R (2005) Cardiac iron determines cardiac T2*, T2, and T1 in the gerbil model of iron cardiomyopathy. Circulation 112(4):535–543. doi: 10.1161/CIRCULATIONAHA.104.504415 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Algranati D, Kassab GS, Lanir Y (2011) Why is the subendocardium more vulnerable to ischemia? A new paradigm. Am J Physiol Heart Circ Physiol 300(3):H1090–H1100. doi: 10.1152/ajpheart.00473.2010 CrossRefPubMedGoogle Scholar
  44. 44.
    Armstrong AC, Ricketts EP, Cox C, Adler P, Arynchyn A, Liu K, Stengel E, Sidney S, Lewis CE, Schreiner PJ, Shikany JM, Keck K, Merlo J, Gidding SS, Lima JA (2015) Quality control and reproducibility in M-mode, two-dimensional, and speckle tracking echocardiography acquisition and analysis: the CARDIA Study, Year 25 examination experience. Echocardiography 32(8):1233–1240. doi: 10.1111/echo.12832 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Fausto Pizzino
    • 1
    • 2
    • 3
  • Antonella Meloni
    • 2
  • Anna Terrizzi
    • 1
  • Tommaso Casini
    • 4
  • Anna Spasiano
    • 5
  • Carlo Cosmi
    • 6
  • Massimo Allò
    • 7
  • Concetta Zito
    • 1
  • Scipione Carerj
    • 1
  • Giovanni Donato Aquaro
    • 2
  • Gianluca Di Bella
    • 1
  • Alessia Pepe
    • 2
    Email author
  1. 1.Dipartimento di Medicina Clinica e SperimentaleUniversità di Messina, AOU “Policlinico G. Martino”MessinaItaly
  2. 2.Magnetic Resonance Imaging UnitFondazione G. Monasterio CNR-Regione ToscanaPisaItaly
  3. 3.Medical and Surgical Pathologies of the Heart UnitFondazione G. Monasterio CNR-Regione ToscanaMassaItaly
  4. 4.Centro Talassemie ed EmoglobinopatieOspedale “Meyer”FirenzeItaly
  5. 5.U.O.S.D. Centro per le MicrocitemieAORN CardarelliNapoliItaly
  6. 6.Clinica PediatricaAzienda Ospedaliero-Universitaria di SassariSassariItaly
  7. 7.Servizio MicrocitemiaPresidio Ospedaliero ASL 5CrotoneItaly

Personalised recommendations