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Cardiovascular Magnetic Resonance Relaxometry in Early Detection of Anthracycline Cardiotoxicity

  • Cardio-Oncology (J Mitchell, Section Editor)
  • Published:
Current Cardiovascular Imaging Reports Aims and scope Submit manuscript

Abstract

Purpose of the Review

To provide an overview of the published data on the value of cardiovascular magnetic resonance (CMR) based T1 and T2 and extracellular volume (ECV) fraction quantification to identify myocardial abnormalities related to anthracycline treatment in patients with cancer.

Recent Findings

In animal models of anthracycline cardiotoxicity, elevations in myocardial T1 and T2 values appear to occur early during treatment followed by ventricular remodeling, persistent elevation in T1, and increase in ECV. These findings suggest early myocardial inflammation/edema followed by myocardial fibrosis and ventricular dysfunction. Similarly in patients receiving cancer therapy, T1 and ECV values increase early after anthracycline therapy. The value of T2 mapping in this setting has not been established. Likewise, adult cancer survivors with or without LV dysfunction have increased ECV values which may be associated with worse diastolic parameters. The value of ECV to identify subclinical cardiomyopathy in pediatric cancer survivors remains controversial.

Summary

Quantitative CMR tissue characterization techniques may have a unique role in identifying the pathophysiology of anthracycline-induced cardiomyopathy and for early detection of myocardial injury. In cancer survivors, these techniques have a potential role in identifying early and subclinical myocardial injury. However, the overall literature on quantitative CMR tissue characterization techniques to detect anthracycline cardiotoxicity is limited.

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References

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

  1. Hooning MJ, Botma A, Aleman BMP, Baaijens MHA, Bartelink H, Klijn JGM, et al. Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst. 2007;99(5):365–75.

    Article  PubMed  Google Scholar 

  2. Mulrooney DA, Yeazel MW, Mertens AC, Mitby P, Stovall M, Donaldson SS, 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):1–11.

    Google Scholar 

  3. Keegan THM, Kushi LH, Li Q, Brunson A, Chawla X, Chew HK, et al. Cardiovascular disease incidence in adolescent and young adult cancer survivors : a retrospective cohort study. J Cancer Surviv. 2018;12:388–97.

    Article  PubMed  Google Scholar 

  4. Chao C, Xu L, Bhatia S, Cooper R, Brar S, Wong FL, et al. Cardiovascular disease risk pro fi les in survivors of adolescent and young adult ( AYA ) cancer : the Kaiser Permanente AYA Cancer Survivors Study. J Clin Oncol. 2019;34(14).

    Article  CAS  PubMed  Google Scholar 

  5. Thavendiranathan P, Abdel-Qadir H, Fischer HD, Camacho X, Amir E, Austin PC, et al. Breast Cancer therapy-related cardiac dysfunction in adult women treated in routine clinical practice: a population-based cohort study. J Clin Oncol. 2016;34(19):2239–46.

    Article  PubMed  Google Scholar 

  6. 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. 2015;100(19):1368–79.

    Article  Google Scholar 

  7. Abdel-Qadir H, Austin PC, Lee DS, Amir E, Tu JV, Thavendiranathan P, et al. A population-based study of cardiovascular mortality following early-stage breast cancer. JAMA Cardiol. 2017;2(1):88–93. https://doi.org/10.1001/jamacardio.2016.3841.

    Article  PubMed  Google Scholar 

  8. Moslehi J. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med. 2016;375:1457–67.

    Article  CAS  PubMed  Google Scholar 

  9. Thavendiranathan P, Wintersperger BJ, Flamm SD, Marwick TH. Cardiac MRI in the assessment of cardiac injury and toxicity from cancer chemotherapy a systematic review. Circ Cardiovasc Imaging. 2013;6(6):1080–91.

    Article  PubMed  Google Scholar 

  10. Bernaba BN, Chan JB, Lai CK, Fishbein MC. Pathology of late-onset anthracycline cardiomyopathy. Cardiovasc Pathol. 2010;19(5):308–11. https://doi.org/10.1016/j.carpath.2009.07.004.

    Article  CAS  PubMed  Google Scholar 

  11. Kajihara H, Yasui W, Nakagawa H, Maeda Y. Light and electron microscopic observations of the white pulp of the dog spleen during hemorrhagic shock. Pathol Res Pract. 1986;181(5):586–95 Available from: http://www.sciencedirect.com/science/article/pii/S0344033886801534.

    Article  CAS  PubMed  Google Scholar 

  12. Friedman MA, Bozdech MJ, Billingham ME, Rider AK. Doxorubicin cardiotoxicity: serial endomyocardial biopsies and systolic time intervals. JAMA. 1978;240(15):1603–6. https://doi.org/10.1001/jama.1978.03290150049023.

    Article  CAS  PubMed  Google Scholar 

  13. Bristow MR, Mason JW, Billingham ME, Daniels JR. Doxorubicin cardiomyopathy: evaluation by phonocardiography, endomyocardial biopsy, and cardiac catheterization. Ann Intern Med. 1978;88(2):168–75.

    Article  CAS  PubMed  Google Scholar 

  14. Schelbert EB, Messroghli DR. State of the art: clinical applications of cardiac T1 mapping. Radiology. 2016;278(3):658–76.

    Article  PubMed  Google Scholar 

  15. Neilan TG, Coelho-Filho OR, Shah RV, Feng JH, Pena-Herrera D, Mandry D, et al. Myocardial extracellular volume by cardiac magnetic resonance imaging in patients treated with anthracycline-based chemotherapy. Am J Cardiol. 2013;111(5):717–22. https://doi.org/10.1016/j.amjcard.2012.11.022.

    Article  CAS  PubMed  Google Scholar 

  16. Moon JC, Messroghli DR, Kellman P, Piechnik SK, Robson MD, Ugander M, et al. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson. 2013;15(1):1–12.

    Article  Google Scholar 

  17. Ugander M, Oki AJ, Hsu LY, Kellman P, Greiser A, Aletras AH, et al. Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology. Eur Heart J. 2012;33(10):1268–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Reiter G, Reiter C, Kräuter C, Fuchsjäger M, Reiter U. Cardiac magnetic resonance T1 mapping. Part 1: aspects of acquisition and evaluation. Eur J Radiol. 2018;109(October):223–34 Available from: https://linkinghub.elsevier.com/retrieve/pii/S0720048X18303565.

    Article  PubMed  Google Scholar 

  19. Reiter U, Reiter C, Kräuter C, Fuchsjäger M, Reiter G. Cardiac magnetic resonance T1 mapping. Part 2: diagnostic potential and applications. Eur J Radiol. 2018;109:235–47. https://doi.org/10.1016/j.ejrad.2018.10.013.

    Article  PubMed  Google Scholar 

  20. Mewton N, Liu CY, Croisille P, Bluemke D, Lima JAC. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol. 2011;57(8):891–903. https://doi.org/10.1016/j.jacc.2010.11.013.

    Article  PubMed  Google Scholar 

  21. Hamlin SA, Henry TS, Little BP, Lerakis S, Stillman AE. Mapping the future of cardiac MR imaging: case-based review of T1 and T2 mapping techniques. RadioGraphics. 2014;34(6):1594–611.

    Article  PubMed  Google Scholar 

  22. Roujol S, Weingartner S, Foppa M, Chow K, Kawaji K, Ngo LH, et al. Accuracy, precision, and reproducibility of four T1 mapping sequences: a head- to-head comparison of MOLLI, ShMOLLI, SASHA, and SAPPHIRE1. Radiology. 2014;272(3):683–9.

    Article  PubMed  Google Scholar 

  23. Messroghli DR, Moon JC, Ferreira VM, Grosse-wortmann L, He T, Kellman P, et al. Clinical recommendations for cardiovascular magnetic resonance mapping of T1 , T2 , T2 * and extracellular volume : a consensus statement by the Society for Cardiovascular Magnetic Resonance ( SCMR ) endorsed by the European Association for Cardiovascular. J Cardiovasc Magn Reson. 2017;19(75):1–24.

    Google Scholar 

  24. Arheden H, Saeed M, Higgins CB, Gao DW, Bremerich J, Wyttenbach R, et al. Measurement of the distribution volume of gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction: comparison with 99mTc-DTPA autoradiography in rats. Radiology. 1999;211(3):698–708.

    Article  CAS  PubMed  Google Scholar 

  25. Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, et al. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010;122(2):138–44.

    Article  PubMed  Google Scholar 

  26. Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S. Cardiac T1 mapping and extracellular volume ( ECV ) in clinical practice : a comprehensive review. J Cardiovasc Magn Reson. 2016;18(89):1–12. https://doi.org/10.1186/s12968-016-0308-4.

    Article  Google Scholar 

  27. Farhad H, Staziaki PV, Addison D, Coelho-Filho OR, Shah RV, Mitchell RN, et al. Characterization of the changes in cardiac structure and function in mice treated with anthracyclines using serial cardiac magnetic resonance imaging. Circ Cardiovasc Imaging. 2016;9(12):1–8.

    Article  Google Scholar 

  28. Cottin Y, Ribugt C, Maupoil V, Godin D, Arnould L, Brunotte F, et al. Early incidence of adriamycin treatment on cardiac parameters in the rat. Can J Physiol Pharmacol. 2011;72(2):140–5.

    Article  Google Scholar 

  29. Lightfoot JC, D’Agostino RB, Hamilton CA, Jordan J, Torti FM, Kock ND, et al. Novel approach to early detection of doxorubicin cardiotoxicity by gadolinium-enhanced cardiovascular magnetic resonance imaging in an experimental model. Circ Cardiovasc Imaging. 2010;3(5):550–8.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hong YJ, Park HS, Park JK, Han K, Park CH, Kim TK, et al. Early detection and serial monitoring of anthracycline-induced cardiotoxicity using T1-mapping cardiac magnetic resonance imaging: an animal study. Sci Rep. 2017;7(1):1–10.

    Article  CAS  Google Scholar 

  31. Hong YJ, Kim TK, Hong D, Park CH, Yoo SJ, Wickum ME, et al. Myocardial characterization using dual-energy CT in doxorubicin-induced DCM: comparison with CMR T1-mapping and histology in a rabbit model. JACC Cardiovasc Imaging. 2016;9(7):836–45.

    Article  PubMed  Google Scholar 

  32. • Galán-Arriola C, Lobo M, Vílchez-Tschischke JP, López GJ, de Molina-Iracheta A, Pérez-Martínez C, et al. Serial magnetic resonance imaging to identify early stages of anthracycline-induced cardiotoxicity. J Am Coll Cardiol. 2019;73(7):779–91 Recent original research paper in an animal model that shows T2 mapping as the earliest marker of cardiotoxicity in doxorubicin-treated pigs, and in the absence of other altered CMR parameters, proposing a reversible disease stage.

    Article  PubMed  Google Scholar 

  33. Meléndez GC, Jordan JH, D’Agostino RB, Vasu S, Hamilton CA, Hundley WG. Progressive 3-month increase in LV myocardial ECV after anthracycline-based chemotherapy. JACC Cardiovasc Imaging. 2017;10(6):708–9. https://doi.org/10.1016/j.jcmg.2016.06.006.

    Article  PubMed  Google Scholar 

  34. Muehlberg F, Funk S, Zange L, von Knobelsdorff-Brenkenhoff F, Blaszczyk E, Schulz A, et al. Native myocardial T1 time can predict development of subsequent anthracycline-induced cardiomyopathy. ESC Hear Fail. 2018;5(4):620–9.

    Article  Google Scholar 

  35. • Haslbauer JD, Lindner S, Valbuena-Lopez S, Zainal H, Zhou H, D’Angelo T, et al. CMR imaging biosignature of cardiac involvement due to cancer-related treatment by T1 and T2 mapping. Int J Cardiol. 2019;275:179–86 This paper found a positive correlation between native T1 and T2 values and high sensitive troponin, and between native T1 values, reduced strain and increased end-systolic volumes, proposing phenotypical signatures for early (inflammatory) and late (fibrotic) cardiac involvement.

    Article  PubMed  Google Scholar 

  36. • Ferreira de Souza T, Quinaglia AC, Silva T, Osorio Costa F, Shah R, Neilan TG, et al. Anthracycline therapy is associated with cardiomyocyte atrophy and preclinical manifestations of heart disease. JACC Cardiovasc Imaging. 2018;11(8):1045–55 This paper proposes total LV cardiomyocyte mass and intracellular water lifetime as new CMR parameters to evaluate for cardiomyocyte atrophy, suggesting that an increase in ECV can be explained by myocyte loss or by a decrease in myocyte size. The decrease in cardiomyocyte mass was higher in patients with elevated cardiac troponin T levels, suggesting a higher degree of cardiomyocyte injury.

    Article  PubMed  Google Scholar 

  37. Takagi H, Ota H, Umezawa R, Kimura T, Kadoya N, Higuchi S, et al. Left ventricular T1 mapping during chemotherapy – radiation therapy : serial assessment of participants with esophageal cancer. Radiology. 2018;289(2):347–54. https://doi.org/10.1148/radiol.2018172076.

    Article  PubMed  Google Scholar 

  38. Tong X, Li VW, Liu AP, So EK, Chan Q, Ho KK, et al. Cardiac magnetic resonance T1 mapping in adolescent and young adult survivors of childhood cancers. Circ Cardiovasc Imaging. 2019;12(4):1–3 Available from: https://www.ahajournals.org/doi/10.1161/CIRCIMAGING.118.008453.

    Article  Google Scholar 

  39. Kimball A, Patil S, Koczwara B, Raman KS, Perry R, Grover S, et al. Late characterisation of cardiac effects following anthracycline and trastuzumab treatment in breast cancer patients. Int J Cardiol. 2018;261:159–61. https://doi.org/10.1016/j.ijcard.2018.03.025.

    Article  PubMed  Google Scholar 

  40. • Jordan JH, Vasu S, Morgan TM, D’Agostino RB, Meléndez GC, Hamilton CA, et al. Anthracycline-associated T1 mapping characteristics are elevated independent of the presence of cardiovascular comorbidities in cancer survivors. Circ Cardiovasc Imaging. 2016;9(8):1–9 In this study with long-term follow-up of cancer survivors, ECV remained abnormally elevated in patients after 3 years of recieving anthracycline-based chemotherapy, and coincided with a decrease in left ventricular mass and function over time.

    Article  Google Scholar 

  41. 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(1):48 Available from: http://jcmr-online.biomedcentral.com/articles/10.1186/1532-429X-15-48.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Toro-Salazar OH, Gillan E, O’Loughlin MT, Burke GS, Ferranti J, Stainsby J, et al. Occult cardiotoxicity in childhood cancer survivors exposed to anthracycline therapy. Circ Cardiovasc Imaging. 2013;6(6):873–80.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiology, Peter Munk Cardiac Center, Ted Rogers Program in Cardiotoxicity Prevention and Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada

    Camila Urzua Fresno, Tamar Shalmon, Oscar Calvillo Argüelles & Paaladinesh Thavendiranathan

  2. Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Ontario, Canada

    Camila Urzua Fresno, Bernd J. Wintersperger & Paaladinesh Thavendiranathan

  3. Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada

    Bernd J. Wintersperger

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  1. Camila Urzua Fresno
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Correspondence to Paaladinesh Thavendiranathan.

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Urzua Fresno, C., Shalmon, T., Calvillo Argüelles, O. et al. Cardiovascular Magnetic Resonance Relaxometry in Early Detection of Anthracycline Cardiotoxicity. Curr Cardiovasc Imaging Rep 13, 2 (2020). https://doi.org/10.1007/s12410-019-9524-2

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