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Left Ventricular Dysfunction and Chemotherapeutic Agents

  • Suparna C. Clasen
  • Joyce W. Wald
Heart Failure (H Eisen, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Heart Failure

Abstract

Purpose of Review

We aim to summarize the effect of cancer therapy-related cardiotoxicity on the development of left ventricular (LV) dysfunction.

Recent Findings

We discuss commonly used cancer therapeutics that have the potential for both acute and delayed cardiotoxicity. LV dysfunction from cancer therapies may be found by routine cardiac imaging prior to clinical manifestations of heart failure (HF) and we discuss the current multi-modality approaches for early detection of toxicity with the use of advanced echocardiographic parameters including strain techniques. Further, we discuss the role of biomarkers for detection of LV dysfunction from cancer therapies. Current approaches monitoring and treating LV dysfunction related to cancer therapy-related cardiotoxicity include addressing modifiable cardiovascular risk factors especially hypertension and early initiation of neurohormonal blockade (NHB) with disease-modifying beta-blockers and renin–angiotensin–aldosterone system (RAAS) inhibitors. Once LV dysfunction is identified, traditional ACC/AHA guideline-directed therapy is employed. Further, we highlight the use of advanced heart failure therapies including mechanical resynchronization devices, the use of durable ventricular assist devices, and cardiac transplantation as increasingly employed modalities for treatment of severe LV dysfunction and advanced heart failure in the cardio-oncology population.

Summary

This review seeks to highlight the importance of early detection, treatment, and prevention of LV dysfunction from cancer therapy-related cardiotoxicity.

Keywords

LV dysfunction Cardio-oncology Chemotherapy Cancer therapy-related cardiotoxicity Heart failure 

Abbreviations

ACC

American College of Cardiology

ACEi

angiotensin-converting enzyme inhibitors

AHA

American Heart Association

ARB

angiotensin receptor blockers

BB

beta-blockers

cMRI

cardiac magnetic resonance imaging

CVD

cardiovascular disease

CVRF

cardiovascular risk factors

GLS

global longitudinal strain

HF

heart failure

INTERMACS

Interagency Registry for Mechanically Assisted Circulatory Support

LV

left ventricle

LVEF

left ventricular ejection fraction

NHB

neurohormonal blockade

MUGA

multiple-gated acquisition

RAAS

renin–angiotensin–aldosterone system

TKI

tyrosine kinase inhibitors

Tn

troponin

Tn I

troponin I

Tn T

troponin T

UNOS

United Network for Organ Sharing

Notes

Funding Information

Suparna C. Clasen reports grants from NIH T32 funding.

Compliance with Ethical Standards

Conflict of Interest

Suparna C. Clasen and Joyce W. Wald 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

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

  1. 1.
    Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66(4):271–89.CrossRefPubMedGoogle Scholar
  2. 2.
    Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS, et al. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol. 2007;25(25):3991–4008.CrossRefPubMedGoogle Scholar
  3. 3.
    Armenian SH, Xu L, Ky B, Sun C, Farol LT, Pal SK, et al. Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study. J Clin Oncol. 2016;34(10):1122–30.CrossRefPubMedGoogle Scholar
  4. 4.
    Bloom MW, Hamo CE, Cardinale D, Ky B, Nohria A, Baer L, et al. Cancer therapy-related cardiac dysfunction and heart failure: part 1: definitions, pathophysiology, risk factors, and imaging. Circ Heart Fail. 2016;9(1):e002661.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    • 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. Eur Heart J Cardiovasc Imaging. 2014;15(10):1063–93. This article provides an overarching view of imaging in the cardio-oncologic population. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 7.
    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.CrossRefPubMedGoogle Scholar
  8. 8.
    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.CrossRefPubMedGoogle Scholar
  9. 9.
    Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53(24):2231–47.CrossRefPubMedGoogle Scholar
  10. 10.
    Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004;109(25):3122–31.CrossRefPubMedGoogle Scholar
  11. 11.
    Langer SW. Dexrazoxane for the treatment of chemotherapy-related side effects. Cancer Manag Res. 2014;6:357–63.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Curigliano G, Cardinale D, Suter T, Plataniotis G, de Azambuja E, Sandri MT, et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012;23(Suppl 7):vii155–66.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130(25):2354–94.CrossRefPubMedGoogle Scholar
  15. 15.
    Ky B, Putt M, Sawaya H, French B, Januzzi JL Jr, Sebag IA, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2014;63(8):809–16.CrossRefPubMedGoogle Scholar
  16. 16.
    Juan Carlos Plana TLF, José Juan Gómez de Diego, y Miguel Ángel García Fernández. Cardio Oncology. 1st ed: CTO Editorial; 2014.Google Scholar
  17. 17.
    Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109(22):2749–54.CrossRefPubMedGoogle Scholar
  18. 18.
    Cardinale D, Sandri MT, Martinoni A, Borghini E, Civelli M, Lamantia G, et al. Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol. 2002;13(5):710–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Cardinale D, Sandri MT, Martinoni A, Tricca A, Civelli M, Lamantia G, et al. Left ventricular dysfunction predicted by early troponin I release after high-dose chemotherapy. J Am Coll Cardiol. 2000;36(2):517–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Sandri MT, Cardinale D, Zorzino L, Passerini R, Lentati P, Martinoni A, et al. Minor increases in plasma troponin I predict decreased left ventricular ejection fraction after high-dose chemotherapy. Clin Chem. 2003;49(2):248–52.CrossRefPubMedGoogle Scholar
  21. 21.
    Auner HW, Tinchon C, Linkesch W, Tiran A, Quehenberger F, Link H, et al. Prolonged monitoring of troponin T for the detection of anthracycline cardiotoxicity in adults with hematological malignancies. Ann Hematol. 2003;82(4):218–22.PubMedGoogle Scholar
  22. 22.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Morris PG, Chen C, Steingart R, Fleisher M, Lin N, Moy B, et al. Troponin I and C-reactive protein are commonly detected in patients with breast cancer treated with dose-dense chemotherapy incorporating trastuzumab and lapatinib. Clin Cancer Res. 2011;17(10):3490–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, et al. Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2008;26(32):5204–12.CrossRefPubMedGoogle Scholar
  25. 25.
    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.CrossRefPubMedGoogle Scholar
  26. 26.
    Writing Committee M, Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, 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. Circulation. 2013;128(16):e240–327.CrossRefGoogle Scholar
  27. 27.
    Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM. Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention. J Natl Cancer Inst. 2010;102(1):14–25.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Anju N. Prevention of cardiomyopathy in patients with cancer American College of Cardiology - Cardio-Oncology. 2016. [cited 2017 July 1]. Available from: http://www.acc.org/latest-in-cardiology/articles/2016/09/29/13/25/prevention-of-cardiomyopathy-in-patients-with-cancer.
  29. 29.
    Xing M, Yan F, Yu S, Shen P. Efficacy and cardiotoxicity of liposomal doxorubicin-based chemotherapy in advanced breast cancer: a meta-analysis of ten randomized controlled trials. PLoS One. 2015;10(7):e0133569.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Injectables P. Zinecard® (dexrazoxane for injection). 2012. [Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020212s013lbl.pdf.
  31. 31.
    FDA. FDA Statement on Dexrazoxane. 2011. [Available from: https://www.fda.gov/Drugs/DrugSafety/ucm263729.htm.
  32. 32.
    Tebbi CK, London WB, Friedman D, Villaluna D, De Alarcon PA, Constine LS, et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin’s disease. J Clin Oncol. 2007;25(5):493–500.CrossRefPubMedGoogle Scholar
  33. 33.
    Salzer WL, Devidas M, Carroll WL, Winick N, Pullen J, Hunger SP, et al. Long-term results of the pediatric oncology group studies for childhood acute lymphoblastic leukemia 1984-2001: a report from the children's oncology group. Leukemia. 2010;24(2):355–70.CrossRefPubMedGoogle Scholar
  34. 34.
    Kalam K, Marwick TH. Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. Eur J Cancer. 2013;49(13):2900–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Hamo CE, Bloom MW, Cardinale D, Ky B, Nohria A, Baer L, et al. Cancer therapy-related cardiac dysfunction and heart failure: part 2: prevention, treatment, guidelines, and future directions. Circ Heart Fail. 2016;9(2):e002843.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Gulati G, Heck SL, Ree AH, Hoffmann P, Schulz-Menger J, Fagerland MW, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016;37(21):1671–80.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, et al. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006;48(11):2258–62.CrossRefPubMedGoogle Scholar
  38. 38.
    Nakamae H, Tsumura K, Terada Y, Nakane T, Nakamae M, Ohta K, et al. Notable effects of angiotensin II receptor blocker, valsartan, on acute cardiotoxic changes after standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone. Cancer. 2005;104(11):2492–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Cadeddu C, Piras A, Mantovani G, Deidda M, Dessi M, Madeddu C, et al. Protective effects of the angiotensin II receptor blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and early ventricular impairment. Am Heart J. 2010;160(3):487 e1–7.CrossRefGoogle Scholar
  40. 40.
    Bosch X, Rovira M, Sitges M, Domenech A, Ortiz-Perez JT, de Caralt TM, et al. Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies: the OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies). J Am Coll Cardiol. 2013;61(23):2355–62.CrossRefPubMedGoogle Scholar
  41. 41.
    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.CrossRefPubMedGoogle Scholar
  42. 42.
    • 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. This article is one of the seminal works in cardio-oncology which emphasizes the use of neurohormonal blockade in the treatment and ideal prevention of LV dysfunction. CrossRefPubMedGoogle Scholar
  43. 43.
    Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N, Civelli M, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006;114(23):2474–81.CrossRefPubMedGoogle Scholar
  44. 44.
    Rickard J, Kumbhani DJ, Baranowski B, Martin DO, Tang WH, Wilkoff BL. Usefulness of cardiac resynchronization therapy in patients with Adriamycin-induced cardiomyopathy. Am J Cardiol. 2010;105(4):522–6.CrossRefPubMedGoogle Scholar
  45. 45.
    Oliveira GH, Hardaway BW, Kucheryavaya AY, Stehlik J, Edwards LB, Taylor DO. Characteristics and survival of patients with chemotherapy-induced cardiomyopathy undergoing heart transplantation. J Heart Lung Transplant. 2012;31(8):805–10.CrossRefPubMedGoogle Scholar
  46. 46.
    Oliveira GH, Dupont M, Naftel D, Myers SL, Yuan Y, Tang WH, et al. Increased need for right ventricular support in patients with chemotherapy-induced cardiomyopathy undergoing mechanical circulatory support: outcomes from the INTERMACS Registry (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol. 2014;63(3):240–8.CrossRefPubMedGoogle Scholar
  47. 47.
    • Al-Kindi SG. OG. Advanced HF therapies in cancer survivors treated with anthracyclines and radiation American College of Cardiology - Cardio-Oncology 2017 [updated July 1 2017; cited 2017 July 1]. Available from: http://www.acc.org/latest-in-cardiology/articles/2017/05/18/08/27/advanced-hf-therapies-in-cancer-survivors-treated-with-anthracyclines-and-radiation?w_nav=LC. This online reference discusses the latest advanced heart failure therapies in patients with advanced LV dysfunction.
  48. 48.
    Oliveira GH, Qattan MY, Al-Kindi S, Park SJ. Advanced heart failure therapies for patients with chemotherapy-induced cardiomyopathy. Circ Heart Fail. 2014;7(6):1050–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Cardio-oncology in the Division of CardiologyHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Advanced Heart Failure in the Division of CardiologyHospital of the University of PennsylvaniaPhiladelphiaUSA

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