Advertisement

Cardiovascular Evaluation of Children With Malignancies

  • Jyothsna Akam-VenkataEmail author
  • James Galas
  • Sanjeev Aggarwal
Pediatric and Congenital Heart Disease (G Singh, Section Editor)
  • 76 Downloads
Part of the following topical collections:
  1. Topical Collection on Pediatric and Congenital Heart Disease

Abstract

Purpose of review

The anthracycline (AC) group of drugs is widely used for cancer chemotherapy and has improved outcomes in many childhood malignancies. However, cardiovascular complications are major causes of morbidity and mortality in AC recipients, with the greatest risk factor being a higher cumulative dosage. The purpose of this review is to describe the etio-pathogenesis and risk factors of AC induced cardiotoxicity, with emphasis on currently available and emerging modalities of non-invasive imaging in its surveillance, and to review guidelines on its prevention and treatment.

Recent findings

Presently, ejection fraction and shortening fraction derived from two-dimensional echocardiography are the most widely used parameter for monitoring of cardiac function in childhood cancer survivors. The newer speckle tracking echocardiography has shown potential to detect abnormalities in ventricular function prior to the conventional measures such as ejection fraction and shortening fraction. When available, three-dimensional echocardiography should be used as it allows for more accurate estimation of ejection fraction. Newer magnetic resonance imaging (MRI) techniques, such as delayed enhancement and T1 mapping, are useful adjuncts for cardiac evaluation in cancer survivors, especially in patients with poor echocardiographic windows.

Summary

Early detection and management of cardiovascular diseases is one of the major goals in the long-term follow-up of childhood cancer survivors. In addition to conventional two-dimensional echocardiography, newer techniques such as speckle tracking echocardiography and three-dimensional echocardiography should be incorporated due to its ability to detect early changes in anthracycline-induced cardiotoxicity. However further research are needed to guide changes in management due to abnormalities in speckle tracking echocardiography.

Keywords

Pediatric congenital heart disease anthracycline Ejection fraction 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Society AC. Cancer facts & figures 2018. Atlanta. 2018.Google Scholar
  2. 2.
    Institute NC. Childhood Cancer Survivor Study: an overview https://www.cancer.gov/types/childhood-cancers/ccss. 2018 Accessed December 19, 2018.
  3. 3.
    Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355(15):1572–82.  https://doi.org/10.1056/NEJMsa060185.CrossRefPubMedGoogle Scholar
  4. 4.
    Mertens AC, Liu Q, Neglia JP, Wasilewski K, Leisenring W, Armstrong GT, et al. Cause-specific late mortality among 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2008;100(19):1368–79.  https://doi.org/10.1093/jnci/djn310.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Adams MJ, Lipshultz SE. Pathophysiology of anthracycline- and radiation-associated cardiomyopathies: implications for screening and prevention. Pediatr Blood Cancer. 2005;44(7):600–6.  https://doi.org/10.1002/pbc.20352.CrossRefPubMedGoogle Scholar
  6. 6.
    Lipshultz SE, Lipsitz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, et al. Female sex and higher drug dose as risk factors for late cardiotoxic effects of doxorubicin therapy for childhood cancer. N Engl J Med. 1995;332(26):1738–43.  https://doi.org/10.1056/NEJM199506293322602.CrossRefPubMedGoogle Scholar
  7. 7.
    Orzan F, Brusca A, Conte MR, Presbitero P, Figliomeni MC. Severe coronary artery disease after radiation therapy of the chest and mediastinum: clinical presentation and treatment. Br Heart J. 1993;69(6):496–500.CrossRefGoogle Scholar
  8. 8.
    Adams MJ, Lipsitz SR, Colan SD, Tarbell NJ, Treves ST, Diller L, et al. Cardiovascular status in long-term survivors of Hodgkin’s disease treated with chest radiotherapy. J Clin Oncol. 2004;22(15):3139–48.  https://doi.org/10.1200/JCO.2004.09.109.CrossRefPubMedGoogle Scholar
  9. 9.
    Lipshultz SE, Cochran TR, Franco VI, Miller TL. Treatment-related cardiotoxicity in survivors of childhood cancer. Nat Rev Clin Oncol. 2013;10(12):697–710.  https://doi.org/10.1038/nrclinonc.2013.195.CrossRefPubMedGoogle Scholar
  10. 10.
    Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med. 1991;324(12):808–15.  https://doi.org/10.1056/NEJM199103213241205.CrossRefPubMedGoogle Scholar
  11. 11.
    Akam-Venkata J, Franco VI, Lipshultz SE. Late cardiotoxicity: issues for childhood cancer survivors. Curr Treat Options Cardiovasc Med. 2016;18(7):47.  https://doi.org/10.1007/s11936-016-0466-6.CrossRefPubMedGoogle Scholar
  12. 12.
    Canzoneri JC, Oyelere AK. Interaction of anthracyclines with iron responsive element mRNAs. Nucleic Acids Res. 2008;36(21):6825–34.  https://doi.org/10.1093/nar/gkn774.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18(11):1639–42.  https://doi.org/10.1038/nm.2919.CrossRefPubMedGoogle Scholar
  14. 14.
    Huang C, Zhang X, Ramil JM, Rikka S, Kim L, Lee Y, et al. Juvenile exposure to anthracyclines impairs cardiac progenitor cell function and vascularization resulting in greater susceptibility to stress-induced myocardial injury in adult mice. Circulation. 2010;121(5):675–83.  https://doi.org/10.1161/CIRCULATIONAHA.109.902221.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Borow KM, Neumann A, Marcus RH, Sareli P, Lang RM. Effects of simultaneous alterations in preload and afterload on measurements of left ventricular contractility in patients with dilated cardiomyopathy: comparisons of ejection phase, isovolumetric and end-systolic force-velocity indexes. J Am Coll Cardiol. 1992;20(4):787–95.CrossRefGoogle Scholar
  16. 16.
    Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440–63.  https://doi.org/10.1016/j.echo.2005.10.005.CrossRefPubMedGoogle Scholar
  17. 17.
    Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schwartz RG, Shaffer EM, et al. Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group. Pediatrics. 1992;89(5 Pt 1):942–9.PubMedGoogle Scholar
  18. 18.
    Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010;55(3):213–20.  https://doi.org/10.1016/j.jacc.2009.03.095.CrossRefPubMedGoogle Scholar
  19. 19.
    Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr. 2010;23(5):465–95; quiz 576-467.  https://doi.org/10.1016/j.echo.2010.03.019.CrossRefGoogle Scholar
  20. 20.
    Mirsky I, Parmley WW. Assessment of passive elastic stiffness for isolated heart muscle and the intact heart. Circ Res. 1973;33(2):233–43.CrossRefGoogle Scholar
  21. 21.
    Bansal M, Kasliwal RR. How do I do it? Speckle-tracking echocardiography. Indian Heart J. 2013;65(1):117–23.  https://doi.org/10.1016/j.ihj.2012.12.004.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E, et al. Noninvasive myocardial strain measurement by speckle tracking echocardiography: validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol. 2006;47(4):789–93.  https://doi.org/10.1016/j.jacc.2005.10.040.CrossRefPubMedGoogle Scholar
  23. 23.
    Lorch SM, Ludomirsky A, Singh GK. Maturational and growth-related changes in left ventricular longitudinal strain and strain rate measured by two-dimensional speckle tracking echocardiography in healthy pediatric population. J Am Soc Echocardiogr. 2008;21(11):1207–15.  https://doi.org/10.1016/j.echo.2008.08.011.CrossRefPubMedGoogle Scholar
  24. 24.
    •• Sengelov M, Jorgensen PG, Jensen JS, Bruun NE, Olsen FJ, Fritz-Hansen T, et al. Global longitudinal strain is a superior predictor of all-cause mortality in heart failure with reduced ejection fraction. JACC Cardiovasc Imaging. 2015;8(12):1351–9.  https://doi.org/10.1016/j.jcmg.2015.07.013 A study indicating that decreased global longitudinal strain is an independent predictor of all-cause mortality in 1065 heart failure patients with reduced ejection fraction.CrossRefPubMedGoogle Scholar
  25. 25.
    •• Levy PT, Machefsky A, Sanchez AA, Patel MD, Rogal S, Fowler S, et al. Reference ranges of left ventricular strain measures by two-dimensional speckle-tracking echocardiography in children: a systematic review and meta-analysis. J Am Soc Echocardiogr. 2016;29(3):209–225 e206.  https://doi.org/10.1016/j.echo.2015.11.016 Meta-analysis of 2325 healthy children providing reference range for left ventricular global longitudinal strain and global circumferential strain.CrossRefPubMedGoogle Scholar
  26. 26.
    Poterucha JT, Kutty S, Lindquist RK, Li L, Eidem BW. Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction. J Am Soc Echocardiogr. 2012;25(7):733–40.  https://doi.org/10.1016/j.echo.2012.04.007.CrossRefPubMedGoogle Scholar
  27. 27.
    Pignatelli RH, Ghazi P, Reddy SC, Thompson P, Cui Q, Castro J, et al. Abnormal myocardial strain indices in children receiving anthracycline chemotherapy. Pediatr Cardiol. 2015;36(8):1610–6.  https://doi.org/10.1007/s00246-015-1203-8.CrossRefPubMedGoogle Scholar
  28. 28.
    •• Armstrong GT, Joshi VM, Ness KK, Marwick TH, Zhang N, Srivastava D, et al. 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. 2015;65(23):2511–22.  https://doi.org/10.1016/j.jacc.2015.04.013 St. Jude lifetime cohort study evaluating 1820 adult survivors of childhood cancer exposed to chemotherapy and radiotherapy. One third of the survivors with normal left ventricular ejection fraction had either decraesed global longitudinal strain or decreased diastolic function.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    •• Tuzovic M, Wu PT, Kianmahd S, Nguyen KL. Natural history of myocardial deformation in children, adolescents, and young adults exposed to anthracyclines: systematic review and meta-analysis. Echocardiography. 2018;35(7):922–34.  https://doi.org/10.1111/echo.13871 A meta-analysis reviewing the natural history of myocardial deformation in childhood cancer survivors exposed to anthracycline. The global longitudinal strain was decreased before and immediately after chemotherapy, where as the global circumferential strain was decreased in the long-term follow-up.CrossRefPubMedGoogle Scholar
  30. 30.
    Leischik R, Dworrak B, Hensel K. Intraobserver and interobserver reproducibility for radial, circumferential and longitudinal strain echocardiography. Open Cardiovasc Med J. 2014;8:102–9.  https://doi.org/10.2174/1874192401408010102.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Singh GK, Cupps B, Pasque M, Woodard PK, Holland MR, Ludomirsky A. Accuracy and reproducibility of strain by speckle tracking in pediatric subjects with normal heart and single ventricular physiology: a two-dimensional speckle-tracking echocardiography and magnetic resonance imaging correlative study. J Am Soc Echocardiogr. 2010;23(11):1143–52.  https://doi.org/10.1016/j.echo.2010.08.010.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    •• Assuncao BMBL, Handschumacher MD, Brunner AM, Yucel E, Bartko PE, Cheng KH, et al. Acute leukemia is associated with cardiac alterations before chemotherapy. J Am Soc Echocardiogr. 2017;30(11):1111–8.  https://doi.org/10.1016/j.echo.2017.07.016 Retrospective study reporting abnormal left ventricular global longitudinal strain in adult acute leukemia patients even before exposure to chemotherapy.CrossRefGoogle Scholar
  33. 33.
    • Agha H, Shalaby L, Attia W, Abdelmohsen G, Aziz OA, Rahman MY. Early ventricular dysfunction after anthracycline chemotherapy in children. Pediatr Cardiol. 2016;37(3):537–44.  https://doi.org/10.1007/s00246-015-1311-5 A retrospective study evluating the conventoinal and speckle tracking echocardiography in pre- and post-chemotherapy evaluation of left and right ventricles. Study showed that compared to baseline, the post-chemotherapy left ventricular systolic function such as global longitudinal strain and right ventricular diastolic function were decreased.CrossRefPubMedGoogle Scholar
  34. 34.
    Al-Biltagi M, Abd Rab Elrasoul Tolba O, El-Shanshory MR, Abd El-Aziz El-Shitany N, El-Sayed El-Hawary E. Strain echocardiography in early detection of doxorubicin-induced left ventricular dysfunction in children with acute lymphoblastic leukemia. ISRN Pediatrics. 2012;2012:9.  https://doi.org/10.5402/2012/870549.CrossRefGoogle Scholar
  35. 35.
    Ganame J, Claus P, Eyskens B, Uyttebroeck A, Renard M, D’hooge J, et al. Acute cardiac functional and morphological changes after anthracycline infusions in children. Am J Cardiol. 2007;99:974–7.  https://doi.org/10.1016/j.amjcard.2006.10.063.CrossRefGoogle Scholar
  36. 36.
    Cheung YF, Hong WJ, Chan GC, Wong SJ, Ha SY. Left ventricular myocardial deformation and mechanical dyssynchrony in children with normal ventricular shortening fraction after anthracycline therapy. Heart. 2010;96(14):1137–41.  https://doi.org/10.1136/hrt.2010.194118.CrossRefPubMedGoogle Scholar
  37. 37.
    Mavinkurve-Groothuis AM, Groot-Loonen J, Marcus KA, Bellersen L, Feuth T, Bokkerink JP, et al. Myocardial strain and strain rate in monitoring subclinical heart failure in asymptomatic long-term survivors of childhood cancer. Ultrasound Med Biol. 2010;36(11):1783–91.  https://doi.org/10.1016/j.ultrasmedbio.2010.08.001.CrossRefPubMedGoogle Scholar
  38. 38.
    Yu AF, Raikhelkar J, Zabor EC, Tonorezos ES, Moskowitz CS, Adsuar R, et al. Two-dimensional speckle tracking echocardiography detects subclinical left ventricular systolic dysfunction among adult survivors of childhood, adolescent, and young adult cancer. Biomed Res Int. 2016;2016:9363951.  https://doi.org/10.1155/2016/9363951.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Venkata JA, Kadiu G, Aggarwal S Effect of presence of cancer in pre-chemotherapy stage in children on left ventricle function as assessed by speckle echocardiography. In: American Society of Echocardiography—annual scientific sessions, Baltimore, MD. 2017. Journal of the American Society of Echocardiography,Google Scholar
  40. 40.
    •• Harrington JK, Richmond ME, Fein AW, Kobsa S, Satwani P, Shah A. Two-dimensional speckle tracking echocardiography-derived strain measurements in survivors of childhood cancer on angiotensin converting enzyme inhibition or receptor blockade. Pediatr Cardiol. 2018;39(7):1404–12.  https://doi.org/10.1007/s00246-018-1910-z Study reporting improvement in the left ventricular global longitudinal strain and strain rate and improvement in global circumferential strain and strain rate in after treatment with angiotensin converting enzyme inhibitor/angiotensin receptor blockers in childhood cancer survivors.CrossRefPubMedGoogle Scholar
  41. 41.
    Kadiu G, Venkata JA, Aggarwal S. Speckle tracking abnormalities of global left ventricle strain in children following chemotherapy. J Am Soc Echocardiogr 2016;29.Google Scholar
  42. 42.
    Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, et al. 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. 2014;27(9):911–39.  https://doi.org/10.1016/j.echo.2014.07.012.CrossRefPubMedGoogle Scholar
  43. 43.
    Stapleton GE, Stapleton SL, Martinez A, Ayres NA, Kovalchin JP, Bezold LI, et al. Evaluation of longitudinal ventricular function with tissue Doppler echocardiography in children treated with anthracyclines. J Am Soc Echocardiogr. 2007;20(5):492–7.  https://doi.org/10.1016/j.echo.2006.10.011.CrossRefPubMedGoogle Scholar
  44. 44.
    Harahsheh A, Aggarwal S, Pettersen MD, L’Ecuyer T. Diastolic function in anthracycline-treated children. Cardiol Young. 2015;25(6):1130–5.  https://doi.org/10.1017/S1047951114001760.CrossRefPubMedGoogle Scholar
  45. 45.
    • Christiansen JR, Kanellopoulos A, Lund MB, Massey R, Dalen H, Kiserud CE, et al. Impaired exercise capacity and left ventricular function in long-term adult survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2015;62(8):1437–43.  https://doi.org/10.1002/pbc.25492 A cross-sectional study of 138 survivors of childhood cancer survivors reporting LV diastolic dysfunction, impaired aerboic capacity, and their association with anthracycline exposure.CrossRefPubMedGoogle Scholar
  46. 46.
    Ryerson AB, Border WL, Wasilewski-Masker K, Goodman M, Meacham L, Austin H, et al. Assessing anthracycline-treated childhood cancer survivors with advanced stress echocardiography. Pediatr Blood Cancer. 2015;62(3):502–8.  https://doi.org/10.1002/pbc.25328.CrossRefPubMedGoogle Scholar
  47. 47.
    Armenian SH, Gelehrter SK, Vase T, Venkatramani R, Landier W, Wilson KD, et al. Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors. Clin Cancer Res. 2014;20(24):6314–23.  https://doi.org/10.1158/1078-0432.CCR-13-3490.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    • Christiansen JR, Massey R, Dalen H, Kanellopoulos A, Hamre H, Ruud E, et al. Right ventricular function in long-term adult survivors of childhood lymphoma and acute lymphoblastic leukaemia. Eur Heart J Cardiovasc Imaging. 2016;17(7):735–41.  https://doi.org/10.1093/ehjci/jew018 A study reporting decreased right ventricular function in 30% of 246 survivors of childhood cancer survivors. The RV dysfunction was three times more likely in survivors with LV dysfunction.CrossRefPubMedGoogle Scholar
  49. 49.
    • Murbraech K, Holte E, Broch K, Smeland KB, Holte H, Rosner A, et al. Impaired right ventricular function in long-term lymphoma survivors. J Am Soc Echocardiogr. 2016;29(6):528–36.  https://doi.org/10.1016/j.echo.2016.02.014 A study of 274 lymphoma survivors reporting impaired right ventriuclar systolic dysfunction compared to 222 controls. The RV function was associated with left ventricular systolic function indicating the interventricular dependence.CrossRefPubMedGoogle Scholar
  50. 50.
    Ganame J, Claus P, Uyttebroeck A, Renard M, D’Hooge J, Bijnens B, et al. Myocardial dysfunction late after low-dose anthracycline treatment in asymptomatic pediatric patients. J Am Soc Echocardiogr. 2007;20(12):1351–8.  https://doi.org/10.1016/j.echo.2007.04.007.CrossRefPubMedGoogle Scholar
  51. 51.
    Armstrong GT, Tolle JJ, Piana R, Santucci A, Leathers J, Ness KK, et al. Exercise right heart catheterization for pulmonary hypertension identified on screening echocardiography in adult survivors of childhood cancer: a report from the St. Jude Lifetime Cohort. Pediatr Blood Cancer. 2018;65(1).  https://doi.org/10.1002/pbc.26769.CrossRefGoogle Scholar
  52. 52.
    Jenkins C, Bricknell K, Hanekom L, Marwick TH. Reproducibility and accuracy of echocardiographic measurements of left ventricular parameters using real-time three-dimensional echocardiography. J Am Coll Cardiol. 2004;44(4):878–86.  https://doi.org/10.1016/j.jacc.2004.05.050.CrossRefPubMedGoogle Scholar
  53. 53.
    Kapetanakis S, Kearney MT, Siva A, Gall N, Cooklin M, Monaghan MJ. Real-time three-dimensional echocardiography: a novel technique to quantify global left ventricular mechanical dyssynchrony. Circulation. 2005;112(7):992–1000.  https://doi.org/10.1161/CIRCULATIONAHA.104.474445.CrossRefPubMedGoogle Scholar
  54. 54.
    Sengupta PP, Tajik AJ, Chandrasekaran K, Khandheria BK. Twist mechanics of the left ventricle: principles and application. JACC Cardiovasc Imaging. 2008;1(3):366–76.  https://doi.org/10.1016/j.jcmg.2008.02.006.CrossRefPubMedGoogle Scholar
  55. 55.
    Nakatani S. Left ventricular rotation and twist: why should we learn? J Cardiovasc Ultrasound. 2011;19(1):1–6.  https://doi.org/10.4250/jcu.2011.19.1.1.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Geyer H, Caracciolo G, Abe H, Wilansky S, Carerj S, Gentile F, et al. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr. 2010;23(4):351–69; quiz 453-355.  https://doi.org/10.1016/j.echo.2010.02.015.CrossRefGoogle Scholar
  57. 57.
    Cheung YF, Lam WW, Ip JJ, Cheuk DK, Cheng FW, Yang JY, et al. Myocardial iron load and fibrosis in long term survivors of childhood leukemia. Pediatr Blood Cancer. 2015;62(4):698–703.  https://doi.org/10.1002/pbc.25369.CrossRefPubMedGoogle Scholar
  58. 58.
    • Okuma H, Noto N, Tanikawa S, Kanezawa K, Hirai M, Shimozawa K, et al. 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. 2017;70(4):396–401.  https://doi.org/10.1016/j.jjcc.2016.12.015 A case–control study reporting reduced left ventricular myocardial performance in patients with regional wall motion abnormalities compared to those without regional wall motion abnormalities.CrossRefPubMedGoogle Scholar
  59. 59.
    Sawyer DB, Peng X, Chen B, Pentassuglia L, Lim CC. Mechanisms of anthracycline cardiac injury: can we identify strategies for cardioprotection? Prog Cardiovasc Dis. 2010;53(2):105–13.  https://doi.org/10.1016/j.pcad.2010.06.007.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Wu E, Judd RM, Vargas JD, Klocke FJ, Bonow RO, Kim RJ. Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction. Lancet. 2001;357(9249):21–8.  https://doi.org/10.1016/S0140-6736(00)03567-4.CrossRefPubMedGoogle Scholar
  61. 61.
    Hunold P, Schlosser T, Vogt FM, Eggebrecht H, Schmermund A, Bruder O, et al. Myocardial late enhancement in contrast-enhanced cardiac MRI: distinction between infarction scar and non-infarction-related disease. AJR Am J Roentgenol. 2005;184(5):1420–6.  https://doi.org/10.2214/ajr.184.5.01841420.CrossRefPubMedGoogle Scholar
  62. 62.
    Ylanen K, Poutanen T, Savikurki-Heikkila P, Rinta-Kiikka I, Eerola A, Vettenranta K. Cardiac magnetic resonance imaging in the evaluation of the late effects of anthracyclines among long-term survivors of childhood cancer. J Am Coll Cardiol. 2013;61(14):1539–47.  https://doi.org/10.1016/j.jacc.2013.01.019.CrossRefPubMedGoogle Scholar
  63. 63.
    Lunning MA, Kutty S, Rome ET, Li L, Padiyath A, Loberiza F, et al. Cardiac magnetic resonance imaging for the assessment of the myocardium after doxorubicin-based chemotherapy. Am J Clin Oncol. 2013.Google Scholar
  64. 64.
    Wassmuth R, Lentzsch S, Erdbruegger U, Schulz-Menger J, Doerken B, Dietz R, et al. Subclinical cardiotoxic effects of anthracyclines as assessed by magnetic resonance imaging—a pilot study. Am Heart J. 2001;141(6):1007–13.CrossRefGoogle Scholar
  65. 65.
    Tham EB, Haykowsky MJ, Chow K, Spavor M, Kaneko S, Khoo NS, et al. Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling. J Cardiovasc Magn Reson. 2013;15:48.  https://doi.org/10.1186/1532-429X-15-48.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Nielsen KM, Offersen BV, Nielsen HM, Vaage-Nilsen M, Yusuf SW. Short and long term radiation induced cardiovascular disease in patients with cancer. Clin Cardiol. 2017;40(4):255–61.  https://doi.org/10.1002/clc.22634.CrossRefPubMedGoogle Scholar
  67. 67.
    •• Lancellotti P, Nkomo VT, Badano LP, Bergler-Klein J, Bogaert J, Davin L, et al. Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiogr. 2013;26(9):1013–32.  https://doi.org/10.1016/j.echo.2013.07.005 Expert opinion from the American Society of Echocardiography and European Society of Cardiovascular Imaging on multimodality imaging in evaluation of radiotherapy-related cardiovascular complications in adult cancer patients.CrossRefPubMedGoogle Scholar
  68. 68.
    Lipshultz SE, Miller TL, Scully RE, Lipsitz SR, Rifai N, Silverman LB, et al. Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes. J Clin Oncol. 2012;30(10):1042–9.  https://doi.org/10.1200/JCO.2010.30.3404.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    • Leerink JM, Verkleij SJ, Feijen EAM, Mavinkurve-Groothuis AMC, Pourier MS, Ylanen K, et al. Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: a systematic review. Heart. 2018.  https://doi.org/10.1136/heartjnl-2018-313634 A systematic review of eight studies evaluating the utility of biomarkers in asymptomatic childhood cancer survivors. It shows that NT-pro BNP and troponin T have limited utility in the detection of late cardiotoxicity.CrossRefGoogle Scholar
  70. 70.
    Aggarwal S, Pettersen MD, Bhambhani K, Gurczynski J, Thomas R, L’Ecuyer T. B-type natriuretic peptide as a marker for cardiac dysfunction in anthracycline-treated children. Pediatr Blood Cancer. 2007;49(6):812–6.  https://doi.org/10.1002/pbc.21100.CrossRefPubMedGoogle Scholar
  71. 71.
    Cifra B, Chen CK, Fan CS, Slorach C, Manlhiot C, McCrindle BW, et al. Dynamic myocardial response to exercise in childhood cancer survivors treated with anthracyclines. J Am Soc Echocardiogr. 2018;31(8):933–42.  https://doi.org/10.1016/j.echo.2018.02.003.CrossRefPubMedGoogle Scholar
  72. 72.
    Wouters KA, Kremer LC, Miller TL, Herman EH, Lipshultz SE. Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies. Br J Haematol. 2005;131(5):561–78.  https://doi.org/10.1111/j.1365-2141.2005.05759.x.CrossRefPubMedGoogle Scholar
  73. 73.
    Pai VB, Nahata MC. Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf. 2000;22(4):263–302.  https://doi.org/10.2165/00002018-200022040-00002.CrossRefPubMedGoogle Scholar
  74. 74.
    Schlitt A, Jordan K, Vordermark D, Schwamborn J, Langer T, Thomssen C. Cardiotoxicity and oncological treatments. Dtsch Arztebl Int. 2014;111(10):161–8.  https://doi.org/10.3238/arztebl.2014.0161.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol. 2014;64(9):938–45.  https://doi.org/10.1016/j.jacc.2014.06.1167.CrossRefPubMedGoogle Scholar
  76. 76.
    Lyu YL, Kerrigan JE, Lin CP, Azarova AM, Tsai YC, Ban Y, et al. Topoisomerase IIbeta mediated DNA double-strand breaks: implications in doxorubicin cardiotoxicity and prevention by dexrazoxane. Cancer Res. 2007;67(18):8839–46.  https://doi.org/10.1158/0008-5472.CAN-07-1649.CrossRefPubMedGoogle Scholar
  77. 77.
    •• Asselin BL, Devidas M, Chen L, Franco VI, Pullen J, Borowitz MJ, et al. Cardioprotection and safety of dexrazoxane in patients treated for newly diagnosed T-cell acute lymphoblastic leukemia or advanced-stage lymphoblastic non-Hodgkin lymphoma: a report of the Children’s Oncology Group Randomized Trial Pediatric Oncology Group 9404. J Clin Oncol. 2016;34(8):854–62.  https://doi.org/10.1200/JCO.2015.60.8851 Prospective study proving the cardioprotective effect of dexrazoxane without decreasing the antitumor efficacy and without increasing the frequency of secondary malignancies.CrossRefPubMedGoogle Scholar
  78. 78.
    Lipshultz SE, Franco VI, Sallan SE, Adamson PC, Steiner RK, Swain SM, et al. Dexrazoxane for reducing anthracycline-related cardiotoxicity in children with cancer: an update of the evidence. Prog Pediatr Cardiol. 2014;36(1–2):10.Google Scholar
  79. 79.
    Lipshultz SE, Adams MJ, Colan SD, Constine LS, Herman EH, Hsu DT, et al. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association. Circulation. 2013;128(17):1927–95.  https://doi.org/10.1161/CIR.0b013e3182a88099.CrossRefPubMedGoogle Scholar
  80. 80.
    O’Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15(3):440–9.CrossRefGoogle Scholar
  81. 81.
    Danesi F, Malaguti M, Di Nunzio M, Maranesi M, Biagi PL, Bordoni A. Counteraction of adriamycin-induced oxidative damage in rat heart by selenium dietary supplementation. J Agric Food Chem. 2006;54(4):1203–8.  https://doi.org/10.1021/jf0518002.CrossRefPubMedGoogle Scholar
  82. 82.
    Shimpo K, Nagatsu T, Yamada K, Sato T, Niimi H, Shamoto M, et al. Ascorbic acid and adriamycin toxicity. Am J Clin Nutr. 1991;54(6 Suppl):1298S–301S.  https://doi.org/10.1093/ajcn/54.6.1298s.CrossRefPubMedGoogle Scholar
  83. 83.
    Wang YM, Madanat FF, Kimball JC, Gleiser CA, Ali MK, Kaufman MW, et al. Effect of vitamin E against adriamycin-induced toxicity in rabbits. Cancer Res. 1980;40(4):1022–7.PubMedGoogle Scholar
  84. 84.
    Silber JH, Cnaan A, Clark BJ, Paridon SM, Chin AJ, Rychik J, et al. Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J Clin Oncol. 2004;22(5):820–8.  https://doi.org/10.1200/JCO.2004.06.022.CrossRefPubMedGoogle Scholar
  85. 85.
    Lipshultz SE, Lipsitz SR, Sallan SE, Simbre VC 2nd, Shaikh SL, Mone SM, et al. Long-term enalapril therapy for left ventricular dysfunction in doxorubicin-treated survivors of childhood cancer. J Clin Oncol. 2002;20(23):4517–22.  https://doi.org/10.1200/JCO.2002.12.102.CrossRefPubMedGoogle Scholar
  86. 86.
    Shaddy RE, Boucek MM, Hsu DT, Boucek RJ, Canter CE, Mahony L, et al. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA. 2007;298(10):1171–9.  https://doi.org/10.1001/jama.298.10.1171.CrossRefPubMedGoogle Scholar
  87. 87.
    Dipchand AI, Naftel DC, Feingold B, Spicer R, Yung D, Kaufman B, et al. Outcomes of children with cardiomyopathy listed for transplant: a multi-institutional study. J Heart Lung Transplant. 2009;28(12):1312–21.  https://doi.org/10.1016/j.healun.2009.05.019.CrossRefPubMedGoogle Scholar
  88. 88.
    Brancaccio G, Filippelli S, Michielon G, Iacobelli R, Alfieri S, Gandolfo F, et al. Ventricular assist devices as a bridge to heart transplantation or as destination therapy in pediatric patients. Transplant Proc. 2012;44(7):2007–12.  https://doi.org/10.1016/j.transproceed.2012.06.034.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jyothsna Akam-Venkata
    • 1
    Email author
  • James Galas
    • 1
  • Sanjeev Aggarwal
    • 1
  1. 1.Division of Cardiology, The Carman and Ann Adams Department of Pediatrics, Children’s Hospital of MichiganWayne State University School of MedicineDetroitUSA

Personalised recommendations