Skip to main content

Advertisement

SpringerLink
Log in

Nuclear Imaging for the Assessment of Cardiotoxicity from Chemotherapeutic Agents in Oncologic Disease

  • Nuclear Cardiology (V Dilsizian, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

In this review, we summarize the major known cardiac toxicities of common chemotherapeutic agents and the role of nuclear cardiac imaging for the surveillance and assessment of cancer therapeutics–related cardiac dysfunction in routine clinical practice.

Recent Findings

Cardiotoxicity from chemotherapy causes a significant mortality and limits potentially life-saving treatment in cancer patients. Close monitoring of cardiac function during chemotherapy is an accepted method for reducing these adverse effects especially in patients with cancer therapeutics–related cardiac dysfunction. Nuclear imaging is a sensitive, specific, and highly reproducible modality for assessment of cardiac function.

Summary

Nuclear imaging techniques including equilibrium radio nucleotide angiography, myocardial perfusion imaging, and novel experimental molecular imaging are the various objective tools available in addition to conventional echocardiography and cardiac magnetic resonance imaging in the surveillance, assessment, and follow-up of cancer therapeutics–related cardiac dysfunction.

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

Similar content being viewed by others

References

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

  1. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69(5):363–85.

    Article  PubMed  Google Scholar 

  2. Abdel-Rahman O. Risk of cardiac death among cancer survivors in the United States: a SEER database analysis. Expert Rev Anticancer Ther. 2017;17(9):873–8.

    Article  CAS  PubMed  Google Scholar 

  3. •• Curigliano G, Lenihan D, Fradley M, Ganatra S, Barac A, Blaes A, et al. Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol. 2020;31(2):171–90 This document outlines the latest available guidelines for monitoring and treatment of cardiotoxicy from chemotherapy agents.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science (New York, NY). 1984;226(4673):466–8.

    Article  CAS  Google Scholar 

  5. Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015;131(22):1981–8.

    Article  CAS  Google Scholar 

  6. Von Hoff DD, Layard MW, Basa P, Davis HL Jr, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91(5):710–7.

    Article  Google Scholar 

  7. Avilés A, Neri N, Nambo JM, Huerta-Guzman J, Talavera A, Cleto S. Late cardiac toxicity secondary to treatment in Hodgkin's disease. A study comparing doxorubicin, epirubicin and mitoxantrone in combined therapy. Leuk Lymphoma. 2005;46(7):1023–8.

    Article  PubMed  Google Scholar 

  8. Yamaguchi N, Fujii T, Aoi S, Kozuch PS, Hortobagyi GN, Blum RH. Comparison of cardiac events associated with liposomal doxorubicin, epirubicin and doxorubicin in breast cancer: a Bayesian network meta-analysis. Eur J Cancer. 2015;51(16):2314–20.

    Article  CAS  PubMed  Google Scholar 

  9. Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers, Version 5.0, Section 33:40, Monrovia, CA: Children’s Oncology Group; October 2018; Available on-line: www.survivorshipguidelines.org.

  10. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.

    Article  CAS  Google Scholar 

  12. Guarneri V, Lenihan DJ, Valero V, Durand JB, Broglio K, Hess KR, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol. 2006;24(25):4107–15.

    Article  CAS  PubMed  Google Scholar 

  13. de Korte MA, de Vries EG, Lub-de Hooge MN, Jager PL, Gietema JA, van der Graaf WT, et al. 111Indium-trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: a clue to uncover the mechanisms of trastuzumab-related cardiotoxicity. Eur J Cancer. 2007;43(14):2046–51.

    Article  PubMed  Google Scholar 

  14. Anand AJ. Fluorouracil cardiotoxicity. Ann Pharmacother. 1994;28(3):374–8.

    Article  CAS  PubMed  Google Scholar 

  15. de Forni M, Malet-Martino MC, Jaillais P, Shubinski RE, Bachaud JM, Lemaire L, et al. Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J Clin Oncol. 1992;10(11):1795–801.

    Article  PubMed  Google Scholar 

  16. Labianca R, Beretta G, Clerici M, Fraschini P, Luporini G. Cardiac toxicity of 5-fluorouracil: a study on 1083 patients. Tumori. 1982;68(6):505–10.

    Article  CAS  PubMed  Google Scholar 

  17. Arbuck SG, Strauss H, Rowinsky E, Christian M, Suffness M, Adams J, et al. A reassessment of cardiac toxicity associated with Taxol. J Natl Cancer Inst Monogr. 1993;15:117–30.

    Google Scholar 

  18. Gehl J, Boesgaard M, Paaske T, Vittrup Jensen B, Dombernowsky P. Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Ann Oncol. 1996;7(7):687–93.

    Article  CAS  PubMed  Google Scholar 

  19. Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol. 1995;13(11):2688–99.

    Article  CAS  PubMed  Google Scholar 

  20. Braverman AC, Antin JH, Plappert MT, Cook EF, Lee RT. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin Oncol. 1991;9(7):1215–23.

    Article  CAS  PubMed  Google Scholar 

  21. Gottdiener JS, Appelbaum FR, Ferrans VJ, Deisseroth A, Ziegler J. Cardiotoxicity associated with high-dose cyclophosphamide therapy. Arch Intern Med. 1981;141(6):758–63.

    Article  CAS  PubMed  Google Scholar 

  22. Sica DA. Angiogenesis inhibitors and hypertension: an emerging issue. J Clin Oncol. 2006;24(9):1329–31.

    Article  PubMed  Google Scholar 

  23. Zangari M, Fink LM, Elice F, Zhan F, Adcock DM, Tricot GJ. Thrombotic events in patients with cancer receiving antiangiogenesis agents. J Clin Oncol. 2009;27(29):4865–73.

    Article  CAS  PubMed  Google Scholar 

  24. Choueiri TK, Mayer EL, Je Y, Rosenberg JE, Nguyen PL, Azzi GR, et al. Congestive heart failure risk in patients with breast cancer treated with bevacizumab. J Clin Oncol. 2011;29(6):632–8.

    Article  CAS  PubMed  Google Scholar 

  25. Abdel-Qadir H, Ethier JL, Lee DS, Thavendiranathan P, Amir E. Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: a systematic review and meta-analysis. Cancer Treat Rev. 2017;53:120–7.

    Article  CAS  PubMed  Google Scholar 

  26. Ghatalia P, Morgan CJ, Je Y, Nguyen PL, Trinh QD, Choueiri TK, et al. Congestive heart failure with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Crit Rev Oncol Hematol. 2015;94(2):228–37.

    Article  PubMed  Google Scholar 

  27. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147–239.

    Article  PubMed  Google Scholar 

  28. Garcia-Alvarez A, Garcia-Albeniz X, Esteve J, Rovira M, Bosch X. Cardiotoxicity of tyrosine-kinase-targeting drugs. Cardiovasc Hematol Agents Med Chem. 2010;8(1):11–21.

    Article  CAS  PubMed  Google Scholar 

  29. Atallah E, Durand JB, Kantarjian H, Cortes J. Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood. 2007;110(4):1233–7.

    Article  CAS  PubMed  Google Scholar 

  30. Kim KB, Kefford R, Pavlick AC, Infante JR, Ribas A, Sosman JA, et al. Phase II study of the MEK1/MEK2 inhibitor trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J Clin Oncol. 2013;31(4):482–9.

    Article  CAS  PubMed  Google Scholar 

  31. Dickerson T, Wiczer T, Waller A, Philippon J, Porter K, Haddad D, et al. Hypertension and incident cardiovascular events following ibrutinib initiation. Blood. 2019;134(22):1919–28.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016;375(18):1749–55.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Hu JR, Florido R, Lipson EJ, Naidoo J, Ardehali R, Tocchetti CG, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors. Cardiovasc Res. 2019;115(5):854–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Earl HM, Hiller L, Vallier AL, Loi S, McAdam K, Hughes-Davies L, et al. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet. 2019;393(10191):2599–612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Conte P, Frassoldati A, Bisagni G, Brandes AA, Donadio M, Garrone O, et al. Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡. Ann Oncol. 2018;29(12):2328–33.

    Article  CAS  PubMed  Google Scholar 

  36. Armenian SH, Lacchetti C, Barac A, Carver J, Constine LS, Denduluri N, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2017;35(8):893–911.

    Article  PubMed  Google Scholar 

  37. Schwartz RG, McKenzie WB, Alexander J, Sager P, D'Souza A, Manatunga A, et al. Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography. Am J Med. 1987;82(6):1109–18.

    Article  CAS  PubMed  Google Scholar 

  38. Canclini S, Terzi A, Rossini P, Vignati A, La Canna G, Magri GC, et al. Gated blood pool tomography for the evaluation of global and regional left ventricular function in comparison to planar techniques and echocardiography. Ital Heart J. 2001;2(1):42–8.

    CAS  PubMed  Google Scholar 

  39. van Royen N, Jaffe CC, Krumholz HM, Johnson KM, Lynch PJ, Natale D, et al. Comparison and reproducibility of visual echocardiographic and quantitative radionuclide left ventricular ejection fractions. Am J Cardiol. 1996;77(10):843–50.

    Article  PubMed  Google Scholar 

  40. Lopez-Candales A, Hernandez-Suarez DF. Strain imaging echocardiography: what imaging cardiologists should know. Curr Cardiol Rev. 2017;13(2):118–29.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Inohara T, Endo A, Melloni C. Unmet needs in managing myocardial infarction in patients with malignancy. Front Cardiovasc Med. 2019;6:57.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Bharadwaj A, Potts J, Mohamed MO, Parwani P, Swamy P, Lopez-Mattei JC, et al. Acute myocardial infarction treatments and outcomes in 6.5 million patients with a current or historical diagnosis of cancer in the USA. Eur Heart J. 2020;41(23):2183–93.

    Article  CAS  PubMed  Google Scholar 

  43. Michel L, Rassaf T, Totzeck M. Cardiotoxicity from immune checkpoint inhibitors. Int J Cardiol Heart Vasculature. 2019;25:100420.

    Article  Google Scholar 

  44. • Nensa F, Kloth J, Tezgah E, Poeppel TD, Heusch P, Goebel J, et al. Feasibility of FDG-PET in myocarditis: Comparison to CMR using integrated PET/MRI. J Nucl Cardiol. 2018;25(3):785–94 This prospective study showed good agreement in findings from FDG-PET and CMR in patients with suspected myocarditis.

    Article  PubMed  Google Scholar 

  45. Kircher M, Lapa C. Novel noninvasive nuclear medicine imaging techniques for cardiac inflammation. Curr Cardiovasc Imaging Rep. 2017;10(2):6.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Harisankar CN, Mittal BR, Agrawal KL, Abrar ML, Bhattacharya A. Utility of high fat and low carbohydrate diet in suppressing myocardial FDG uptake. J Nucl Cardiol. 2011;18(5):926–36.

    Article  PubMed  Google Scholar 

  47. Maya Y, Werner RA, Schütz C, Wakabayashi H, Samnick S, Lapa C, et al. 11C-Methionine PET of myocardial inflammation in a rat model of experimental autoimmune myocarditis. J Nucl Med. 2016;57(12):1985–90.

    Article  CAS  PubMed  Google Scholar 

  48. Altena R, Perik PJ, van Veldhuisen DJ, de Vries EG, Gietema JA. Cardiovascular toxicity caused by cancer treatment: strategies for early detection. Lancet Oncol. 2009;10(4):391–9.

    Article  CAS  PubMed  Google Scholar 

  49. Lautamäki R, Tipre D, Bengel FM. Cardiac sympathetic neuronal imaging using PET. Eur J Nucl Med Mol Imaging. 2007;34(Suppl 1):S74–85.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Westchester Medical Center, Heart and Vascular Institute, New York Medical College, Valhalla, NY, USA

    Jayakumar Sreenivasan, Urvashi Hooda, Pragya Ranjan & Diwakar Jain

  2. Department of Cardiovascular Medicine, Westchester Medical Center, 100 Woods Road, Valhalla, NY, 10595, USA

    Diwakar Jain

Authors
  1. Jayakumar Sreenivasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Urvashi Hooda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pragya Ranjan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Diwakar Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Diwakar Jain.

Ethics declarations

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.

Additional information

Publisher’s Note

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

This article is part of the Topical Collection on Nuclear Cardiology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sreenivasan, J., Hooda, U., Ranjan, P. et al. Nuclear Imaging for the Assessment of Cardiotoxicity from Chemotherapeutic Agents in Oncologic Disease. Curr Cardiol Rep 23, 65 (2021). https://doi.org/10.1007/s11886-021-01493-4

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11886-021-01493-4

Keywords

Search

Navigation