The Current and Future Role of Echocardiography for the Detection of Cardiotoxicity Related to Cancer Therapy

  • Amita Singh
  • Jeanne M. DeCaraEmail author
Cardio-Oncology (J Mitchell, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cardio-Oncology


Purpose of the Review

The purpose of this review is to outline the role of echocardiography in identifying patients at increased cardiovascular risk for cancer treatment-associated cardiotoxicity.

Recent Findings

With a wide array of cancer therapeutics, a variety echocardiographic cardiotoxicity phenotypes have been identified. Recent consensus statements from several professional societies have provided a framework for risk assessment prior to cancer therapy that involves assessment and optimization of cardiac risk factors but also involves echocardiographic evaluation of left ventricular (LV) function at baseline, during, and after treatment. While newer echocardiographic techniques such as global longitudinal strain are key to detecting subclinical cardiotoxicity, it is as yet unclear if strain-directed initiation of cardioprotective medications will result in better outcomes. This is the subject of an ongoing clinical trial, the results of which are eagerly awaited. Given the serial nature of echocardiographic assessments in the cancer population, the application of automated techniques for ejection fraction and strain may have the potential to further reduce measurement variability and are also subjects of ongoing research.


Echocardiography is the preferred imaging modality for the detection of cardiotoxicity related to cancer therapy. Our expanded understanding of the cardiac side effects of cancer therapy and optimal surveillance strategies for those at risk is predicated on the ascertainment of cardiac outcomes in future clinical trials, for which echocardiography will undoubtedly play a pivotal role.


Cardiotoxicity Cardio-oncology Echocardiography Cancer Strain imaging 


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.


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

  1. 1.
    Agarwal MA, Aggarwal A, Rastogi S, Ventura HO, Lavie CJ. Cardiovascular disease burden in cancer patients from 2003 to 2014. Eur Heart J Qual Care Clin Outcomes. 2018;4(1):69–70.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Thavendiranathan P, Grant AD, Negishi T, Plana JC, Popovic ZB, Marwick TH. Reproducibility of echocardiographic techniques for sequential assessment of left ventricular ejection fraction and volumes: application to patients undergoing cancer chemotherapy. J Am Coll Cardiol. 2013;61(1):77–84.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Nolan MT, Plana JC, Thavendiranathan P, Shaw L, Si L, Marwick TH. Cost-effectiveness of strain-targeted cardioprotection for prevention of chemotherapy-induced cardiotoxicity. Int J Cardiol. 2016;212:336–45.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5•.
    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 This societal practice quideline reviews the available data upon which to base recommendations for monitoring of patients receiving cancer therapy and outlines areas wherein there is a paucity of data.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Hasan S, Dinh K, Lombardo F, Kark J. Doxorubicin cardiotoxicity in African Americans. J Natl Med Assoc. 2004;96(2):196–9.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Lotrionte M, Biondi-Zoccai G, Abbate A, Lanzetta G, D'Ascenzo F, Malavasi V, et al. Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity. Am J Cardiol. 2013;112(12):1980–4.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Sato A, Yoshihisa A, Miyata-Tatsumi M, Oikawa M, Kobayashi A, Ishida T, et al. Valvular heart disease as a possible predictor of trastuzumab-induced cardiotoxicity in patients with breast cancer. Mol Clin Oncol. 2019;10(1):37–42.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Nowsheen S, Aziz K, Park JY, Lerman A, Villarraga HR, Ruddy KJ, et al. Trastuzumab in female breast cancer patients with reduced left ventricular ejection fraction. J Am Heart Assoc. 2018;7(15):e008637.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Stanton SE, Ward MM, Christos P, Sanford R, Lam C, Cobham MV, et al. Pro1170 Ala polymorphism in HER2-neu is associated with risk of trastuzumab cardiotoxicity. BMC Cancer. 2015;15:267.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Furrer D, Jacob S, Michaud A, Provencher L, Lemieux J, Diorio C. Association of tobacco use, alcohol consumption and HER2 polymorphisms with response to trastuzumab in HER2-positive breast cancer patients. Clin Breast Cancer. 2018;18(4):e687–e94.PubMedCrossRefGoogle Scholar
  12. 12.
    Lemieux J, Diorio C, Cote MA, Provencher L, Barabe F, Jacob S, et al. Alcohol and HER2 polymorphisms as risk factor for cardiotoxicity in breast cancer treated with trastuzumab. Anticancer Res. 2013;33(6):2569–76.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Garcia-Pavia P, Kim Y, Alejandra Restrepo-Cordoba M, Lunde IG, Wakimoto H, Smith AM, et al. Genetic variants associated with cancer therapy-induced cardiomyopathy. Circulation. 2019.Google Scholar
  14. 14.
    Law W, Johnson C, Rushton M, Dent S. The Framingham risk score underestimates the risk of cardiovascular events in the HER2-positive breast cancer population. Curr Oncol. 2017;24(5):e348–e53.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Herceptin (trastuzumab)[package insert]. San Francisco, CA; Genentech, Inc; 2017.Google Scholar
  16. 16.
    Jones DN, Jordan JH, Melendez GC, Lamar Z, Thomas A, Kitzman DW, et al. Frequency of transition from stage a to stage B heart failure after initiating potentially cardiotoxic chemotherapy. JACC Heart Fail. 2018;6(12):1023–32.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Moslehi JJ. Cardiovascular toxic effects of targeted cancer therapies. N Engl J Med. 2016;375(15):1457–67.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Adriamycin (Doxorubicin HCl)[package insert]. Bedford, OH; Bedford Laboratories; 2012.Google Scholar
  19. 19.
    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015;16(3):233–70.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    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.PubMedCrossRefGoogle Scholar
  21. 21.
    Lorenzini C, Lamberti C, Aquilina M, Rocca A, Cortesi P, Corsi C. Reliability of left ventricular ejection fraction from three-dimensional echocardiography for cardiotoxicity onset detection in patients with breast cancer. J Am Soc Echocardiogr. 2017;30(11):1103–10.PubMedCrossRefGoogle Scholar
  22. 22.
    • Santoro C, Arpino G, Esposito R, Lembo M, Paciolla I, Cardalesi C, et al. 2D and 3D strain for detection of subclinical anthracycline cardiotoxicity in breast cancer patients: a balance with feasibility. Eur Heart J Cardiovasc Imaging. 2017;18(8):930–6 This paper describes the opportunities and challenges associated with use of 3D echocardiography for early detection of cardiotoxicity.PubMedCrossRefGoogle Scholar
  23. 23.
    Ali MT, Yucel E, Bouras S, Wang L, Fei HW, Halpern EF, et al. Myocardial strain is associated with adverse clinical cardiac events in patients treated with anthracyclines. J Am Soc Echocardiogr. 2016;29(6):522–7 e3.PubMedCrossRefGoogle Scholar
  24. 24.
    Mousavi N, Tan TC, Ali M, Halpern EF, Wang L, Scherrer-Crosbie M. 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. 2015;16(9):977–84.PubMedGoogle Scholar
  25. 25.
    Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012;5(5):596–603.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Fallah-Rad N, Walker JR, Wassef A, Lytwyn M, Bohonis S, Fang T, et al. The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol. 2011;57(22):2263–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Narayan H, Finkelman BFB, Plappert T, Hyman D, Smith AM, Margulies KB, et al. Detailed echocardiographic phenotyping in breast cancer patients: associations with ejection fraction decline, recovery, and heart failure symptoms over 3 years of follow-up. Circulation. 2017;135(15):1397–412.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    • Demissei BG, Finkelman BS, Ra H, Zhang L, Smith AM, Sheline K, et al. Detailed phenotyping reveals distinct trajectories of cardiovascular function and symptoms with exposure to modern breast cancer therapy. Cancer. 2019; Epub ahead of print.Google Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    Medvedofsky D, Maffessanti F, Weinert L, Tehrani DM, Narang A, Addetia K, et al. 2D and 3D echocardiography-derived indices of left ventricular function and shape: relationship with mortality. JACC Cardiovasc Imaging. 2018;11(11):1569–79.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Thavendiranathan P, Poulin F, Lim KD, Plana JC, Woo A, Marwick TH. 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. 2014;63(25 Pt A):2751–68.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G, et al. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr. 2011;24(3):277–313.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33•.
    Negishi T, Thavendiranathan P, Negishi K, Marwick TH, the SUCCOUR investigators. Rationale and design of the strain surveillance of chemotherapy for improving cardiovascular outcomes: the SUCCOUR trial. JACC Cardiovasc Imaging. 2018;11(8):1098–105 This paper describes the design of the first randomized controlled clinical trial comparing strain-directed to LVEF directed cardioprotective therapy in patients receiving cardiotoxic chemotherapy. Results are eagerly awaited.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Thavendiranathan P, Negishi T, Cote MA, Penicka M, Massey R, Cho GY, et al. Single versus standard multiview assessment of global longitudinal strain for the diagnosis of cardiotoxicity during cancer therapy. JACC Cardiovasc Imaging. 2018;11(8):1109–18.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Negishi T, Negishi K, Thavendiranathan P, Cho GY, Popescu BA, Vinereanu D, et al. Effect of experience and training on the concordance and precision of strain measurements. JACC Cardiovasc Imaging. 2017;10(5):518–22.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Negishi T, Editor global longitudinal strain or ejection fraction as a marker of LV function in a multicentre trial: stability over time in the SUCCOUR trial. American Heart Association Scientific Sessions; 2018; Chicago, IL.Google Scholar
  37. 37.
    Song FY, Shi J, Guo Y, Zhang CJ, Xu YC, Zhang QL, et al. Assessment of biventricular systolic strain derived from the two-dimensional and three-dimensional speckle tracking echocardiography in lymphoma patients after anthracycline therapy. Int J Cardiovasc Imaging. 2017;33(6):857–68.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Zhang KW, Finkelman BS, Gulati G, Narayan HK, Upshaw J, Narayan V, et al. Abnormalities in 3-dimensional left ventricular mechanics with anthracycline chemotherapy are associated with systolic and diastolic dysfunction. JACC Cardiovasc Imaging. 2018;11(8):1059–68.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Xu Y, Shi J, Zhao R, Zhang C, He Y, Lin J, et al. Anthracycline induced inconsistent left ventricular segmental systolic function variation in patients with lymphoma detected by three-dimensional speckle tracking imaging. Int J Cardiovasc Imaging. 2019;35(5):771–9.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Arciniegas Calle MC, Sandhu NP, Xia H, Cha SS, Pellikka PA, Ye Z, et al. Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer. BMC Cancer. 2018;18(1):1037.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Moustafa S, Ho TH, Shah P, Murphy K, Nelluri BK, Lee H, et al. Predictors of incipient dysfunction of all cardiac chambers after treatment of metastatic renal cell carcinoma by tyrosine kinase inhibitors. J Clin Ultrasound. 2016;44(4):221–30.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Paraskevaidis IA, Makavos G, Tsirigotis P, Psarogiannakopoulos P, Parissis J, Gkirkas K, et al. Deformation analysis of myocardial layers detects early cardiac dysfunction after chemotherapy in bone marrow transplantation patients: a continuous and additive cardiotoxicity process. J Am Soc Echocardiogr. 2017;30(11):1091–102.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Saiki H, Petersen IA, Scott CG, Bailey KR, Dunlay SM, Finley RR, et al. Risk of heart failure with preserved ejection fraction in older women after contemporary radiotherapy for breast cancer. Circulation. 2017;135(15):1388–96.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Calabrese V, Menna P, Annibali O, Armento G, Carpino A, Cerchiara E, et al. Early diastolic dysfunction after cancer chemotherapy: primary endpoint results of a multicenter cardio-oncology study. Chemotherapy. 2018;63(2):55–63.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Kraigher-Krainer E, Shah AM, Gupta DK, Santos A, Claggett B, Pieske B, et al. Impaired systolic function by strain imaging in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2014;63(5):447–56.CrossRefGoogle Scholar
  46. 46.
    Boyd A, Stoodley P, Richards D, Hui R, Harnett P, Vo K, et al. Anthracyclines induce early changes in left ventricular systolic and diastolic function: a single centre study. PLoS One. 2017;12(4):e0175544.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Honda K, Takeshita K, Murotani K, Mitsuma A, Hayashi H, Tsunoda N, et al. Assessment of left ventricular diastolic function during trastuzumab treatment in patients with HER2-positive breast cancer. Breast Cancer. 2017;24(2):312–8.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Avila MS, Ayub-Ferreira SM, de Barros Wanderley MR Jr, das Dores Cruz F, Goncalves Brandao SM, VOC R, et al. Carvedilol for prevention of chemotherapy-related cardiotoxicity: the CECCY trial. J Am Coll Cardiol. 2018;71(20):2281–90.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Patel NR, Chyu CK, Satou GM, Halnon NJ, Nguyen KL. Left atrial function in children and young adult cancer survivors treated with anthracyclines. Echocardiography. 2018;35(10):1649–56.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Moustafa S, Murphy K, Nelluri BK, Northfelt D, Shah P, Lee H, et al. Temporal trends of cardiac chambers function with trastuzumab in human epidermal growth factor receptor II-positive breast cancer patients. Echocardiography. 2016;33(3):406–15.PubMedCrossRefGoogle Scholar
  51. 51.
    Singh A, Addetia K, Maffessanti F, Mor-Avi V, Lang RM. LA strain for categorization of LV diastolic dysfunction. JACC Cardiovasc Imaging. 2017;10(7):735–43.PubMedCrossRefGoogle Scholar
  52. 52.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Mason JW, Bristow MR, Billingham ME, Daniels JR. Invasive and noninvasive methods of assessing adriamycin cardiotoxic effects in man: superiority of histopathologic assessment using endomyocardial biopsy. Cancer Treat Rep. 1978;62(6):857–64.PubMedGoogle Scholar
  54. 54.
    Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869–79.PubMedCrossRefGoogle Scholar
  55. 55.
    Nysom K, Holm K, Lipsitz SR, Mone SM, Colan SD, Orav EJ, et al. Relationship between cumulative anthracycline dose and late cardiotoxicity in childhood acute lymphoblastic leukemia. J Clin Oncol. 1998;16(2):545–50.PubMedCrossRefGoogle Scholar
  56. 56.
    Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 2010;10:337.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Sara JD, Kaur J, Khodadadi R, Rehman M, Lobo R, Chakrabarti S, et al. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol. 2018;10:1758835918780140.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Polk A, Vistisen K, Vaage-Nilsen M, Nielsen DL. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharmacol Toxicol. 2014;15:47.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Grunwald MR, Howie L, Diaz LA Jr. Takotsubo cardiomyopathy and fluorouracil: case report and review of the literature. J Clin Oncol. 2012;30(2):e11–4.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Nishikawa T, Miyahara E, Kurauchi K, Watanabe E, Ikawa K, Asaba K, et al. Mechanisms of fatal cardiotoxicity following high-dose cyclophosphamide therapy and a method for its prevention. PLoS One. 2015;10(6):e0131394.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    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.PubMedCrossRefGoogle Scholar
  62. 62.
    Dugbartey GJ, Peppone LJ, de Graaf IA. An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures. Toxicology. 2016;371:58–66.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Chang HM, Moudgil R, Scarabelli T, Okwuosa TM, Yeh ETH. Cardiovascular complications of cancer therapy: best practices in diagnosis, prevention, and management: part 1. J Am Coll Cardiol. 2017;70(20):2536–51.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Polonsky TS, DeCara JM. Risk factors for chemotherapy-related cardiac toxicity. Curr Opin Cardiol. 2019;34(3):283–8.PubMedCrossRefGoogle Scholar
  65. 65.
    Cronin KA, Harlan LC, Dodd KW, Abrams JS, Ballard-Barbash R. Population-based estimate of the prevalence of HER-2 positive breast cancer tumors for early stage patients in the US. Cancer Investig. 2010;28(9):963–8.CrossRefGoogle Scholar
  66. 66.
    Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20(5):1215–21.PubMedCrossRefGoogle Scholar
  67. 67.
    Vermeulen Z, Segers VF, De Keulenaer GW. ErbB2 signaling at the crossing between heart failure and cancer. Basic Res Cardiol. 2016;111(6):60.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Lynce F, Barac A, Geng X, Dang C, Yu AF, Smith KL, et al. Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study. Breast Cancer Res Treat. 2019;175(3):595–603.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Joensuu H, Fraser J, Wildiers H, Huovinen R, Auvinen P, Utriainen M, et al. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018;4(9):1199–206.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    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.Google Scholar
  71. 71.
    Guglin M, Krischer J, Tamura R, Fink A, Bello-Matricaria L, McCaskill-Stevens W, et al. Randomized trial of lisinopril versus carvedilol to prevent trastuzumab cardiotoxicity in patients with breast cancer. J Am Coll Cardiol. 2019;73(22):2859–68.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Addetia K, DeCara JM. Cardiac complications of HER2-targeted therapies in breast cancer. Curr Treat Options Cardiovasc Med. 2016;18(6):36.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Jerusalem G, Lancellotti P, Kim SB. HER2+ breast cancer treatment and cardiotoxicity: monitoring and management. Breast Cancer Res Treat. 2019.Google Scholar
  74. 74.
    Hall PS, Harshman LC, Srinivas S, Witteles RM. The frequency and severity of cardiovascular toxicity from targeted therapy in advanced renal cell carcinoma patients. JACC Heart Fail. 2013;1(1):72–8.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Nhola LF, Abdelmoneim SS, Villarraga HR, Kohli M, Grothey A, Bordun KA, et al. Echocardiographic assessment for the detection of cardiotoxicity due to vascular endothelial growth factor inhibitor therapy in metastatic renal cell and colorectal cancers. J Am Soc Echocardiogr. 2019;32(2):267–76.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    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.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012;119(5):1123–9.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Weatherald J, Chaumais MC, Savale L, Jais X, Seferian A, Canuet M, et al. Long-term outcomes of dasatinib-induced pulmonary arterial hypertension: a population-based study. Eur Respir J. 2017;50(1).PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Ryan JJ. Tyrosine kinase inhibitors in pulmonary vascular disease. JACC Basic Transl Sci. 2016;1(7):684–6.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Montani D, Bergot E, Gunther S, Savale L, Bergeron A, Bourdin A, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation. 2012;125(17):2128–37.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Minami M, Arita T, Iwasaki H, Muta T, Aoki T, Aoki K, et al. Comparative analysis of pulmonary hypertension in patients treated with imatinib, nilotinib and dasatinib. Br J Haematol. 2017;177(4):578–87.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Jain P, Kantarjian H, Boddu PC, Nogueras-Gonzalez GM, Verstovsek S, Garcia-Manero G, et al. Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs. Blood Adv. 2019;3(6):851–61.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Li W, Garcia D, Cornell RF, Gailani D, Laubach J, Maglio ME, et al. Cardiovascular and thrombotic complications of novel multiple myeloma therapies: a review. JAMA Oncol. 2017;3(7):980–8.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Grandin EW, Ky B, Cornell RF, Carver J, Lenihan DJ. Patterns of cardiac toxicity associated with irreversible proteasome inhibition in the treatment of multiple myeloma. J Card Fail. 2015;21(2):138–44.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Cole DC, Frishman WH. Cardiovascular complications of proteasome inhibitors used in multiple myeloma. Cardiol Rev. 2018;26(3):122–9.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Iannaccone A, Bruno G, Ravera A, Gay F, Salvini M, Bringhen S, et al. Evaluation of cardiovascular toxicity associated with treatments containing proteasome inhibitors in multiple myeloma therapy. High Blood Press Cardiovasc Prev. 2018;25(2):209–18.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Jakubowiak AJ, DeCara JM, Mezzi K. Cardiovascular events during carfilzomib therapy for relapsed myeloma: practical management aspects from two case studies. Hematology. 2017;22(10):585–91.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Kyprolis (carfilzomib). Thousand Oaks, CA; Amgen; 2019.Google Scholar
  89. 89.
    Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018;71(16):1755–64.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Atallah-Yunes SA, Kadado AJ, Kaufman GP, Hernandez-Montfort J. Immune checkpoint inhibitor therapy and myocarditis: a systematic review of reported cases. J Cancer Res Clin Oncol. 2019;145(6):1527–57.PubMedCrossRefGoogle Scholar
  91. 91.
    Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018;391(10124):933.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Ardehali R, Tocchetti CG, Lyon AR, Padera RF, Johnson DB, Moslehi J. Cardiovascular toxicities associated with immune checkpoint inhibitors. Cardiovasc Res. 2019;115(5):854–68.PubMedCrossRefGoogle Scholar
  93. 93.
    Galper SL, Yu JB, Mauch PM, Strasser JF, Silver B, Lacasce A, et al. Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation. Blood. 2011;117(2):412–8.PubMedCrossRefGoogle Scholar
  94. 94.
    Cutter DJ, Schaapveld M, Darby SC, Hauptmann M, van Nimwegen FA, Krol AD, et al. Risk of valvular heart disease after treatment for Hodgkin lymphoma. J Natl Cancer Inst. 2015;107(4).Google Scholar
  95. 95.
    Wu W, Masri A, Popovic ZB, Smedira NG, Lytle BW, Marwick TH, et al. Long-term survival of patients with radiation heart disease undergoing cardiac surgery: a cohort study. Circulation. 2013;127(14):1476–85.PubMedCrossRefGoogle Scholar
  96. 96.
    Donnellan E, Krishnaswamy A, Hutt-Centeno E, Johnston DR, Aguilera J, Kapadia SR, et al. Outcomes of patients with mediastinal radiation-associated severe aortic stenosis undergoing transcatheter aortic valve replacement. Circulation. 2018;138(16):1752–4.PubMedCrossRefGoogle Scholar
  97. 97.
    Paven E, Cimadevilla C, Urena M, Dilly MP, Nataf P, Raffoul R, et al. Management of radiation-induced valvular heart disease due to Hodgkin’s lymphoma in the modern era. EuroIntervention. 2018;13(15):e1771–e3.PubMedCrossRefGoogle Scholar
  98. 98.
    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.PubMedCrossRefGoogle Scholar
  99. 99.
    Denlinger CS, Sanft T, Baker KS, Broderick G, Demark-Wahnefried W, Friedman DL, et al. Survivorship, version 2.2018, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2018;16(10):1216–47.CrossRefGoogle Scholar
  100. 100.
    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.PubMedCrossRefGoogle Scholar
  101. 101.
    Zhang J, Gajjala S, Agrawal P, Tison GH, Hallock LA, Beussink-Nelson L, et al. Fully automated echocardiogram interpretation in clinical practice. Circulation. 2018;138(16):1623–35.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Medicine Section of CardiologyUniversity of ChicagoChicagoUSA

Personalised recommendations