Cardiac Dysfunction in Hematology Oncology and Hematopoietic Cell Transplant Patients

  • Saad GhafoorEmail author
  • Marshay James
  • Jason Goldberg
  • Jennifer A. McArthur


Cardiac toxicity in cancer therapy and hematopoietic cell transplantation is increasingly appreciated. It is also well described in patients with chronic hemolytic anemias such as sickle cell disease. Traditional chemotherapeutic agents such as anthracyclines have a well-established history of causing cardiac complications. Newer chemotherapeutic agents have less established toxicities but likely place patients at risk for cardiac complications as well. The most frequently seen acute cardiac toxicities in the PICU include ventricular dysfunction, pulmonary hypertension, and pericardial effusions. Prompt recognition and management of these complications are imperative to achieve the best possible outcomes. The optimal screening regimen for cardiac complications has yet to be established, but there are promising new biomarkers and imaging modalities that may aid in more prompt diagnosis and intervention in the future.


Cardiomyopathy Systolic dysfunction Diastolic dysfunction Pulmonary hypertension Cardiac toxicity Pericardial effusion 


  1. 1.
    Ward E, et al. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin. 2014;64(2):83–103.CrossRefGoogle Scholar
  2. 2.
    Moller TR, et al. Decreasing late mortality among five-year survivors of cancer in childhood and adolescence: a population-based study in the Nordic countries. J Clin Oncol. 2001;19(13):3173–81.CrossRefGoogle Scholar
  3. 3.
    Lilje C, et al. A modified noninvasive screening protocol for pulmonary hypertension in children with sickle cell disease-Who should be sent for invasive evaluation? Pediatr Blood Cancer. 2017;64(11)CrossRefGoogle Scholar
  4. 4.
    Health, N.I.O. Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. 2018 2018]; Available from:
  5. 5.
    Yarnold J, Brotons MC. Pathogenetic mechanisms in radiation fibrosis. Radiother Oncol. 2010;97(1):149–61.CrossRefGoogle Scholar
  6. 6.
    Taunk NK, et al. Radiation-induced heart disease: pathologic abnormalities and putative mechanisms. Front Oncol. 2015;5:39.CrossRefGoogle Scholar
  7. 7.
    Nousiainen T, et al. Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction. J Intern Med. 2002;251(3):228–34.CrossRefGoogle Scholar
  8. 8.
    Lipshultz SE, et al. Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia. J Clin Oncol. 2005;23(12):2629–36.CrossRefGoogle Scholar
  9. 9.
    Kremer LC, et al. Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol. 2001;19(1):191–6.CrossRefGoogle Scholar
  10. 10.
    Lipshultz SE, Adams MJ. Cardiotoxicity after childhood cancer: beginning with the end in mind. J Clin Oncol. 2010;28(8):1276–81.CrossRefGoogle Scholar
  11. 11.
    Bagnes C, Panchuk PN, Recondo G. Antineoplastic chemotherapy induced QTc prolongation. Curr Drug Saf. 2010;5(1):93–6.CrossRefGoogle Scholar
  12. 12.
    Pansy J, et al. Add-on-therapy with bevacizumab in children and adolescents with poor prognosis non-CNS solid tumors. Anti-Cancer Drugs. 2013;24(2):198–203.CrossRefGoogle Scholar
  13. 13.
    Force T, Krause DS, Van Etten RA. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer. 2007;7(5):332–44.CrossRefGoogle Scholar
  14. 14.
    Quintas-Cardama A, et al. Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol. 2007;25(25):3908–14.CrossRefGoogle Scholar
  15. 15.
    Trachtenberg BH, et al. Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatr Cardiol. 2011;32(3):342–53.CrossRefGoogle Scholar
  16. 16.
    Mulrooney DA, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ. 2009;339:b4606.CrossRefGoogle Scholar
  17. 17.
    Lipshultz SE, 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.CrossRefGoogle Scholar
  18. 18.
    Lipshultz SE, et al. Cardiovascular status of childhood cancer survivors exposed and unexposed to cardiotoxic therapy. J Clin Oncol. 2012;30(10):1050–7.CrossRefGoogle Scholar
  19. 19.
    Lipshultz SE, et al. Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated survivors of childhood high-risk leukemia. Cancer. 2013;119(19):3555–62.CrossRefGoogle Scholar
  20. 20.
    Giantris A, et al. Anthracycline-induced cardiotoxicity in children and young adults. Crit Rev Oncol Hematol. 1998;27(1):53–68.CrossRefGoogle Scholar
  21. 21.
    Lipshultz SE, et al. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med. 1991;324(12):808–15.CrossRefGoogle Scholar
  22. 22.
    Maitland ML, et al. Initial assessment, surveillance, and management of blood pressure in patients receiving vascular endothelial growth factor signaling pathway inhibitors. J Natl Cancer Inst. 2010;102(9):596–604.CrossRefGoogle Scholar
  23. 23.
    Ay C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116(24):5377–82.CrossRefGoogle Scholar
  24. 24.
    Choueiri TK, et al. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. J Clin Oncol. 2010;28(13):2280–5.CrossRefGoogle Scholar
  25. 25.
    Nakamae H, et al. QT dispersion correlates with systolic rather than diastolic parameters in patients receiving anthracycline treatment. Intern Med. 2004;43(5):379–87.CrossRefGoogle Scholar
  26. 26.
    McArthur J, Duncan C, Rajapreyar P, Talano J, Tamburro R. Critical illness involving children undergoing hematopoietic cell transplantation. In: Care PC, Fuhrman BZJ, editors. Fuhrman and Zimmerman’s pediatric critical care. 5th ed. Philadelphia: Elsevier; 2017.Google Scholar
  27. 27.
    Kaestner M, et al. Pulmonary hypertension in the intensive care unit. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart. 2016;102(Suppl 2):ii57–66.CrossRefGoogle Scholar
  28. 28.
    Dandoy CE, et al. Abnormal echocardiography 7 days after stem cell transplantation may be an early indicator of thrombotic microangiopathy. Biol Blood Marrow Transplant. 2015;21(1):113–8.CrossRefGoogle Scholar
  29. 29.
    Desai AV, et al. Toxicities of busulfan/melphalan versus carboplatin/etoposide/melphalan for high-dose chemotherapy with stem cell rescue for high-risk neuroblastoma. Bone Marrow Transplant. 2016;51(9):1204–10.CrossRefGoogle Scholar
  30. 30.
    Ambrusko SJ, et al. Elevation of tricuspid regurgitant jet velocity, a marker for pulmonary hypertension in children with sickle cell disease. Pediatr Blood Cancer. 2006;47(7):907–13.CrossRefGoogle Scholar
  31. 31.
    Hebson C, et al. Elevated tricuspid regurgitant velocity as a marker for pulmonary hypertension in children with sickle cell disease: less prevalent and predictive than previously thought? J Pediatr Hematol Oncol. 2015;37(2):134–9.CrossRefGoogle Scholar
  32. 32.
    Liem RI, et al. Tricuspid regurgitant jet velocity elevation and its relationship to lung function in pediatric sickle cell disease. Pediatr Pulmonol. 2009;44(3):281–9.CrossRefGoogle Scholar
  33. 33.
    Das A, et al. Risk factors for thromboembolism and pulmonary artery hypertension following splenectomy in children with hereditary spherocytosis. Pediatr Blood Cancer. 2014;61(1):29–33.CrossRefGoogle Scholar
  34. 34.
    El-Sheikh AA, et al. Congenital dyserythropoietic anemia type I presenting as persistent pulmonary hypertension with pigeon chest deformity. Pediatr Blood Cancer. 2014;61(8):1460–2.CrossRefGoogle Scholar
  35. 35.
    Murdych T, Weisdorf DJ. Serious cardiac complications during bone marrow transplantation at the University of Minnesota, 1977–1997. Bone Marrow Transplant. 2001;28(3):283–7.CrossRefGoogle Scholar
  36. 36.
    Dandoy CE, et al. Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2017;64(10)CrossRefGoogle Scholar
  37. 37.
    Steward CG, et al. Severe pulmonary hypertension: a frequent complication of stem cell transplantation for malignant infantile osteopetrosis. Br J Haematol. 2004;124(1):63–71.CrossRefGoogle Scholar
  38. 38.
    Kasow KA, et al. Malignant infantile osteopetrosis and primary pulmonary hypertension: a new combination? Pediatr Blood Cancer. 2004;42(2):190–4.CrossRefGoogle Scholar
  39. 39.
    Bunte MC, et al. Pulmonary veno-occlusive disease following hematopoietic stem cell transplantation: a rare model of endothelial dysfunction. Bone Marrow Transplant. 2008;41(8):677–86.CrossRefGoogle Scholar
  40. 40.
    Trobaugh-Lotrario AD, et al. Pulmonary veno-occlusive disease after autologous bone marrow transplant in a child with stage IV neuroblastoma: case report and literature review. J Pediatr Hematol Oncol. 2003;25(5):405–9.CrossRefGoogle Scholar
  41. 41.
    Mineo G, et al. Pulmonary veno-occlusive disease: the role of CT. Radiol Med. 2014;119(9):667–73.CrossRefGoogle Scholar
  42. 42.
    Rowan CB, O; McArthur J. Non-infectious pulmonary complications of hematopoietic stem cell transplant. J Pediatr Intensive Care. 2014;3:133–46.CrossRefGoogle Scholar
  43. 43.
    Ozyoruk D, et al. Pulmonary arterial hypertension in a child with stage-IV neuroblastoma after autologous hematopoietic stem cell transplantation and review of the literature. Pediatr Transplant. 2015;19(7):E185–8.CrossRefGoogle Scholar
  44. 44.
    Yildirim ZK, et al. Resolution of pulmonary hypertension with low-molecular-weight heparin, steroid, and prostacyclin analogue therapy: could it be early-phase pulmonary veno-occlusive disease? Pediatr Hematol Oncol. 2011;28(6):529–34.CrossRefGoogle Scholar
  45. 45.
    Alioglu B, et al. Pulmonary hypertension in a child with juvenile myelomonocytic leukemia secondary to pulmonary leukemic cell infiltration. Pediatr Hematol Oncol. 2006;23(8):667–75.CrossRefGoogle Scholar
  46. 46.
    Zeilhofer U, et al. Pulmonary hypertension following haematopoietic stem cell transplantation for primary haemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2013;60(3):521–3.CrossRefGoogle Scholar
  47. 47.
    Shankar S, et al. Pulmonary hypertension complicating bone marrow transplantation for idiopathic myelofibrosis. J Pediatr Hematol Oncol. 2004;26(6):393–7.CrossRefGoogle Scholar
  48. 48.
    Berger RM, et al. FUTURE-2: results from an open-label, long-term safety and tolerability extension study using the pediatric FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion. Int J Cardiol. 2016;202:52–8.CrossRefGoogle Scholar
  49. 49.
    Khandaker MH, et al. Pericardial disease: diagnosis and management. Mayo Clin Proc. 2010;85(6):572–93.CrossRefGoogle Scholar
  50. 50.
    Law MA, et al. Novel, long-axis in-plane ultrasound-guided pericardiocentesis for postoperative pericardial effusion drainage. Pediatr Cardiol. 2016;37(7):1328–33.CrossRefGoogle Scholar
  51. 51.
    Versluys AB, et al. Predictors and outcome of pericardial effusion after hematopoietic stem cell transplantation in children. Pediatr Cardiol. 2018;39(2):236–44.CrossRefGoogle Scholar
  52. 52.
    Neier M, et al. Pericardial effusion post-SCT in pediatric recipients with signs and/or symptoms of cardiac disease. Bone Marrow Transplant. 2011;46(4):529–38.CrossRefGoogle Scholar
  53. 53.
    Galderisi M, et al. Cancer therapy and cardiotoxicity: the need of serial Doppler echocardiography. Cardiovasc Ultrasound. 2007;5:4.CrossRefGoogle Scholar
  54. 54.
    Dhakal P, Bhatt VR. Is complement blockade an acceptable therapeutic strategy for hematopoietic cell transplant-associated thrombotic microangiopathy? Bone Marrow Transplant. 2017;52(3):352–6.CrossRefGoogle Scholar
  55. 55.
    Rawlinson E, Bagshaw O. Anesthesia for children with pericardial effusion: a case series. Paediatr Anaesth. 2012;22(11):1124–31.CrossRefGoogle Scholar
  56. 56.
    Markman TM, et al. Electrophysiological effects of anthracyclines in adult survivors of pediatric malignancy. Pediatr Blood Cancer. 2017;64(11)CrossRefGoogle Scholar
  57. 57.
    Nagueh SF, et al. 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. Eur Heart J Cardiovasc Imaging. 2016;17(12):1321–60.CrossRefGoogle Scholar
  58. 58.
    Nagiub M, Nixon JV, Kontos MC. Ability of nonstrain diastolic parameters to predict doxorubicin-induced cardiomyopathy: a systematic review with meta-analysis. Cardiol Rev. 2018;26(1):29–34.CrossRefGoogle Scholar
  59. 59.
    Hare JL, et al. Use of myocardial deformation imaging to detect preclinical myocardial dysfunction before conventional measures in patients undergoing breast cancer treatment with trastuzumab. Am Heart J. 2009;158(2):294–301.CrossRefGoogle Scholar
  60. 60.
    Thavendiranathan P, et al. Cardiac MRI in the assessment of cardiac injury and toxicity from cancer chemotherapy: a systematic review. Circ Cardiovasc Imaging. 2013;6(6):1080–91.CrossRefGoogle Scholar
  61. 61.
    Catana C, Guimaraes AR, Rosen BR. PET and MR imaging: the odd couple or a match made in heaven? J Nucl Med. 2013;54(5):815–24.CrossRefGoogle Scholar
  62. 62.
    Cardinale D, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109(22):2749–54.CrossRefGoogle Scholar
  63. 63.
    Mackay B, et al. Assessment of anthracycline cardiomyopathy by endomyocardial biopsy. Ultrastruct Pathol. 1994;18(1–2):203–11.CrossRefGoogle Scholar
  64. 64.
    Mitani I, et al. Doxorubicin cardiotoxicity: prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era. J Nucl Cardiol. 2003;10(2):132–9.CrossRefGoogle Scholar
  65. 65.
    Wassmuth 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
  66. 66.
    Lipshultz SE, 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.CrossRefGoogle Scholar
  67. 67.
    El-Shitany NA, et al. Protective effect of carvedilol on adriamycin-induced left ventricular dysfunction in children with acute lymphoblastic leukemia. J Card Fail. 2012;18(8):607–13.CrossRefGoogle Scholar
  68. 68.
    Hudson MM, et al. Long-term follow-up guidelines for survivors of childhood, adolescent and young adult cancers version 3.0. 2008. Available from:

Copyright information

© Springer International Publishing 2019

Authors and Affiliations

  • Saad Ghafoor
    • 1
    Email author
  • Marshay James
    • 2
    • 1
  • Jason Goldberg
    • 3
    • 1
  • Jennifer A. McArthur
    • 1
    • 4
  1. 1.Department of Pediatrics, Division of Critical Care MedicineSt. Jude Children’s Research HospitalMemphisUSA
  2. 2.Vanderbilt University School of NursingNashvilleUSA
  3. 3.Pediatric Cardiomyopathy and Heart TransplantationUniversity of Tennessee School of Health SciencesMemphisUSA
  4. 4.Medical College of WisconsinMilwaukeeUSA

Personalised recommendations