The International Journal of Cardiovascular Imaging

, Volume 34, Issue 9, pp 1373–1381 | Cite as

Use of speckle tracking in the evaluation of late subclinical myocardial damage in survivors of childhood acute leukaemia

  • Elena Guadalupe Corella Aznar
  • Ariadna Ayerza Casas
  • Lorenzo Jiménez Montañés
  • Maria Ángeles Carlota Calvo Escribano
  • José Ignacio Labarta Aizpún
  • Pilar Samper Villagrasa
Original Paper


Heart disease is the leading cause of non-cancer death in childhood cancer survivors. to determine the prevalence of subclinical cardiac dysfunction using speckle tracking and compare its results with those obtained by classical methods of assessing left ventricular function and its relationship with different factors to identify the population at higher risk. Echocardiographic assessment of left ventricular function included ejection fraction, tissue Doppler, longitudinal/circumferential strains and biochemical parameters (troponin-T and Pro-BNP) in a cohort of 57 survivors of childhood acute leukaemia with at least 10 years since diagnosis. Ventricular dysfunction was found in 5.2% of patients in M-mode (ejection fraction—EF < 53% with a reduction in the EF ≥ 10%) and in 7% of patients with Simpson’s method, compared with 21.05 and 8.8% with suboptimal global longitudinal strain (GLS) and global circumferential strain, respectively. The GLS alteration was significantly correlated with lower values of left ventricular systolic function and was associated with high tumour risk (odds ratio [OR] 13.8), cumulative doses of anthracyclines ≥ 250 mg/m2 (OR 7.6) and radiotherapy (OR 7.19). Biomarkers were not useful for the diagnosis of subclinical cardiomyopathy. Good reproducibility was obtained, with an intraobserver correlation of 93.6% and an interobserver correlation of 89.2% in the GLS. The alteration of the GLS was more prevalent than the alteration in the EF and was associated with the treatment received and high tumour risk. strain imaging seems to be a powerful tool to identify an increased number of survivor with an early myocardial injury.


Bidimensional speckle tracking Strain Ejection fraction Tissue Doppler Asymptomatic cardiomyopathy Childhood acute leukemia survivors 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Bansal N, Franco VI, Lipshultz (2014) Anthracycline cardiotoxicity in survivors of childhood cancer: clinical course, protection and treatment. Progr Pediatr Cardiol 36:11–18CrossRefGoogle Scholar
  2. 2.
    Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M et al (2009) Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 339:b4606CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    van der Pal HJ, van Dalen EC, van Delden E, van Dijk IW, Kok WE, Geskus RB et al (2012) High risk of symptomatic cardiac events in childhood cancer survivors. J Clin Oncol 30(13):1429–1437CrossRefPubMedGoogle Scholar
  4. 4.
    Sadurska E (2015) Current views on anthracycline cardiotoxicity in childhood cancer survivors. Pediatr Cardiol 36(6):1112–1119CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Fulbright JM (2011) Review of cardiotoxicity in pediatric cancer patients: during and after therapy. Cardiol Res Pract 2011:942090CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M et al (2014) Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 27(9):911–939CrossRefPubMedGoogle Scholar
  7. 7.
    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernade L et al (2015) Recommendations for cardiac chamber quantification by echocardiography and the european Association of Cardiovasular Imaging. Eur Heart J Cardiovasc Imaging 16:233–271CrossRefPubMedGoogle Scholar
  8. 8.
    Tan TC, Scherrer-Crosbie M (2014) Cardiac complications of chemotherapy: role of imaging. Curr Treat Options Cardiovasc Med 16(4):296CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Mavinkurve-Groothuis AM, Groot-Loonen J, Marcus KA, Bellersen L, Feuth T, Bökkerink JP (2010) Myocardial strain and strain rate in monitoring subclinical heart failure in asymptomatic long-term survivors of childhood cancer. Ultrasound Med 36(11):1783–1791CrossRefGoogle Scholar
  10. 10.
    Children’s Oncology Group (2008) Long-term follow-up guidelines for survivors of childhood, adolescent and young adult cancers (Version 3.0). Children’s Oncology Group, Arcadia. Accessed 13 Nov 2017
  11. 11.
    Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, Dokainish H, Thor 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 29:277–314CrossRefPubMedGoogle Scholar
  12. 12.
    Voigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R et al (2015) Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. Eur Heart J Cardiovasc Imaging 16(1):1–11CrossRefPubMedGoogle Scholar
  13. 13.
    López-Fernández T, Thavendiranathan P (2017) Nuevas técnicas de imagen cardiaca en la detección precoz de cardiotoxicidad secundaria a tratamientos oncológicos. Rev Esp Cardiol 70(6):487–495CrossRefPubMedGoogle Scholar
  14. 14.
    Yingchoncharoen T, Agarwal S, Popović ZB, Marwick TH (2013) Normal ranges of left ventricular strain: a meta-analysis. J Am Soc Echocardiogr 26(2):185–191CrossRefPubMedGoogle Scholar
  15. 15.
    Yang H, Marwick TH, Fukuda N, Oe H, Saito M, Thomas JD (2015) Improvement in strain concordance between two major vendors after the strain standardization initiative. J Am Soc Echocardiogr 28(6):642–648CrossRefPubMedGoogle Scholar
  16. 16.
    Farsalinos KE, Daraban AM, Ünlü S, Thomas JD, Badano LP, Voigt JU et al (2015) Head-to-head comparison of global longitudinal strain measurements among nine different vendors: the EACVI/ASE Inter-Vendor Comparison Study. J Am Soc Echocardiogr 28(10):1171–1181CrossRefPubMedGoogle Scholar
  17. 17.
    Takigiku K, Takeuchi M, Izumi C, Yuda S, Sakata K, Ohte N et al (2012) Normal range of left ventricular 2-dimensional strain: Japanese Ultrasound Speckle Tracking of the Left Ventricle (JUSTICE) study. Circ J 76(11):2623–2632CrossRefPubMedGoogle Scholar
  18. 18.
    Kocabay G, Muraru D, Peluso D, Cucchini U, Mihaila S, Padayattil-Jose S et al (2014) Mecánica ventricular izquierda normal mediante ecocardiografía speckle tracking bidimensional. Valores de referencia para adultos sanos. Rev Esp Cardiol 67(8):651–658CrossRefPubMedGoogle Scholar
  19. 19.
    Christiansen JR, Massey R, Dalen H, Kanellopoulos A, Hamre H, Fosså SD et al (2016) Utility of global longitudinal strain by echocardiography to detect left ventricular dysfunction in long-term adult survivors of childhood lymphoma and acute lymphoblastic leukemia. Am J Cardiol 118(3):446–452CrossRefPubMedGoogle Scholar
  20. 20.
    Yu AF, Raikhelkar J, Zabor EC, Tonorezos ES, Moskowitz CS, Adsuar R (2016) Two-dimensional speckle tracking echocardiography dectects subclinical left ventricular systolic dysfunction among adult survivors of childhood, adolescent and young adult cancer. Biomed Res Int 2016:9363951PubMedPubMedCentralGoogle Scholar
  21. 21.
    Armstrong GT, Joshi VM, Ness KK, Marwick TH, Zhang N, Srivastava D et al (2015) Comprehensive echocardiographic detection of treatment-related cardiac dysfunction in adult survivors of childhood cancer: results from the St. Jude Lifetime Cohort Study. J Am Coll Cardiol 65(23):2511–2522CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Karakurt C, Koçak G, Ozgen U (2008) Evaluation of the left ventricular function with tissue tracking and tissue Doppler echocardiography in pediatric malignancy survivors after anthracycline therapy. Echocardiography 25(8):880–887CrossRefPubMedGoogle Scholar
  23. 23.
    Patel AA. LAbovitz AJ (2016) Advanced echocardiography techniques in detection of cardiotoxicity. Curr Treat Options Cardiovasc Med 18:28CrossRefPubMedGoogle Scholar
  24. 24.
    Lipshultz SE, Diamond MB, Franco VI, Aggarwal S, Leger K, g Santos MV et al (2014) Managing chemotherapy-related cardiotoxicity in survivors of childhood cancers. Paediatr Drugs 16(5):373–389CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ylänen K, Eerola A, Vettenranta K, Poutanen T (2016) Speckle tracking echocardiography detects decreased cardiac longitudinal function in anthracycline-exposed survivors of childhood cancer. Eur J Pediatr 175(10):1379–1386CrossRefPubMedGoogle Scholar
  26. 26.
    Cheung YF, Hong WJ, Chan GC, Wong SJ, Ha SY (2010) Left ventricular myocardial deformation and mechanical dyssynchrony in children with normal ventricular shortening fraction after anthracycline therapy. Heart 96(14):1137–1141CrossRefPubMedGoogle Scholar
  27. 27.
    Okuma H, Noto N, Tanikawa S, Kanezawa K, Hirai M, Shimozawa K et al (2017) Impact of persistent left ventricular regional wall motion abnormalities in childhood cancer survivors after anthracycline therapy: assessment of global left ventricular myocardial performance by 3D speckle-tracking echocardiography. J Cardiol. PubMedGoogle Scholar
  28. 28.
    Lipshultz SE, Lipsitz SR, Sallan SE, Dalton VM, Mone SM, Gelber RD et al (2005) Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol 23:2629–2636CrossRefPubMedGoogle Scholar
  29. 29.
    Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M et al (2009) Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 8:339:b4606Google Scholar
  30. 30.
    Lipshultz SE, Adams MJ, Colan SD, Constine LS, Herman EH, Hsu DT et al (2013) Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, preven- tion, and research directions: a scientific statement from the American Heart Association. Circulation 128:1927–1995CrossRefPubMedGoogle Scholar
  31. 31.
    Landy DC, Miller TL, Lipsitz SR, Lopez-Mitnik G, Hinkle AS, Constine LS et al (2013) Cranial irradiation as an additional risk factor for anthracycline cardiotoxicity in childhood cancer survivors: an analysis from the cardiac risk factors in childhood cancer survivors study. Pediatr Cardiol 34(4):826–834CrossRefPubMedGoogle Scholar
  32. 32.
    Kalam K, Otahal P, Marwick TH (2014) Prognostic implications of global LV dysfunction: a systematic review and meta-analysis of global longitu- dinal strain and ejection fraction. Heart 100:1673–1680CrossRefPubMedGoogle Scholar
  33. 33.
    Tsai HR, Gjesdal O, Wethal T, Hermann H, Fossa A, Fossa SD et al (2011) Left ventricular function assessed by two-dimensional speckle tracking echocardiography in long-term survivors of hodgkin’s lymphoma treated by mediastinal radiotherapy with or without anthracycline therapy. Am J Cardiol 107(3):472–477CrossRefPubMedGoogle Scholar
  34. 34.
    Yoon JH, Kim HJ, Lee EJ, Moon S, Lee JY, Lee JW et al (2015) Early left ventricular dysfunction in children after hematopoietic stem cell transplantation for acute leukemia: a case control study using speckle tracking echocardiography. Korean Circ J 45(1):51–58CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Yu W, Li SN, Chan GC, Ha SY, Wong SJ, Cheung YF (2013) Transmural strain and rotation gradient in survivors of childhood cancers. Eur Heart J Cardiovasc Imaging 14(2):175–182CrossRefPubMedGoogle Scholar
  36. 36.
    Tamilselvan ST, Scott JX, Sneha L, Divyalakshmi J (2017) Metabolic syndrome in childhood cancer survivors. J Clin Oncol 35(5):145CrossRefGoogle Scholar
  37. 37.
    Moaref A, Faraji M, Tahamtan M (2016) Subclinical left ventricular systolic dysfunction in patients with metabolic syndrome: a case-control study using two-dimensional speckle tracking echocardiography. ARYA Atheroscler 12(6):254–258PubMedPubMedCentralGoogle Scholar
  38. 38.
    Armenian SH, Hudson MM, Mulder RL, Chen MH, Constine LS, Dwyer M et al (2015) Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 16(3):e123–e136CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Pourier MS, Kapusta L, van Gennip A, Bökkerink JP, Loonen J, Bellersen L, Mavinkurve-Groothuis AM (2015) Values of high sensitive troponin T in long-term survivors of childhood cancer treated with anthracyclines. Clin Chim Acta 441:29–32CrossRefPubMedGoogle Scholar
  40. 40.
    Zidan A, Sherief LM, El-sheikh A, Saleh SH, Shahbah DA, Kamal NM, Sherbiny HS, Ahmad H (2015). NT-proBNP as early marker of subclinical late cardiotoxicity after doxorubicin therapy and mediastinal irradiation in childhood cancer survivors. Dis Markers 2015:513219CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Mousavi N, Tan TC, Ali M, Halpern EF, Wang L, Scherrer-Crosbie M (2015) Echocardiographic parameters of left ventricular size and function as predictors of symptomatic heart failure in patients with a left ventricular ejection fraction of 50–59% treated with anthracyclines. Eur Heart J Cardiovasc Imaging 16(9):977–984PubMedGoogle Scholar
  42. 42.
    Thavendiranathan P, Poulin F, Lim KD, Plana JC, Woo A, Marwick TH (2014) Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy: a systematic review. J Am Coll Cardiol 63(25):2751–2768CrossRefPubMedGoogle Scholar
  43. 43.
    Cheng S, Larson MG, McCabe EL, Osypiuk E, Lehman BT, Stanchev P et al (2013) Reproducibility of speckle-tracking based strain measures of left ventricular function in a community-based study. J Am Soc Echocardiogr 26(11):10CrossRefPubMedCentralGoogle Scholar
  44. 44.
    Negishi T, Negishi K, Thavendiranathan P, Cho GY, Popescu BA, Vinereanu D et al (2016) Effect of experience and training on the concordance and precision of strain measurements. JACC Cardiovasc Imaging 10(5):518–522CrossRefPubMedGoogle Scholar
  45. 45.
    Mavinkurve-groothuis A, Weijers G, Groot-loonen J, Pourier M, Feuth T, Korte CL et al (2009) Interobserver, intraobserver and intrapatient reliability scores of myocardial strain imaging with 2D echocardiography in patients treated with anthracyclines. Ultrasound Med Biol 35:4:697–704CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Elena Guadalupe Corella Aznar
    • 1
  • Ariadna Ayerza Casas
    • 1
  • Lorenzo Jiménez Montañés
    • 1
  • Maria Ángeles Carlota Calvo Escribano
    • 1
  • José Ignacio Labarta Aizpún
    • 1
  • Pilar Samper Villagrasa
    • 2
  1. 1.Miguel Servet HospitalZaragozaSpain
  2. 2.Lozano Blesa HospitalZaragozaSpain

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