Arrhythmias in Cancer Patients

  • Peter KimEmail author
  • Abdulrazzak Zarifa
  • Mohammed Salih
  • Kaveh Karimzad
Reference work entry


Cardiac dysrhythmias are common in cancer patients. Recognition and management of dysrhythmias requires an understanding of common etiologies seen in the cancer population. These may include cancer involvement of the myocardium or various cancer treatments including chemotherapy, radiation, and surgery. They can also be due to other underlying comorbidities such as preexisting cardiovascular disease, electrolyte derangements, or hormonal abnormalities.

Clinical recognition of dysrhythmias can be challenging as they can present incidentally in an asymptomatic patient. When symptomatic, patients may present with palpitations, dizziness, syncope, or cardiac arrest. The diagnosis is often made through rhythm interpretation on a 12-lead ECG, Holter monitor, or bedside cardiac monitor.

Acute management of cardiac rhythm disorders includes urgent patient stabilization and discontinuation of offending agents. Treatment for the arrhythmias and conduction abnormalities may require the use of antiarrhythmic medications, electrical cardioversion, pacemaker placement, and need for anticoagulation in high-risk patients. Cardiac interventions may often conflict with cancer treatment such as in the case of magnetic resonance imaging in patients with pacemakers and anticoagulation in patients with thrombocytopenia. Reconciliation of these complex decisions requires a multidisciplinary approach with understanding of both the cardiovascular and oncologic risks.


Arrhythmia Antiarrhythmic Atrial fibrillation Atrial flutter Bradyarrhythmias Defibrillator Pacemaker Supraventricular tachycardia Ventricular tachycardia QT prolongation 


  1. 1.
    Akl EA, Barba M, Rohilla S, Terrenato I, Sperati F, Muti P, Schünemann HJ. Low-molecular-weight heparins are superior to vitamin K antagonists for the long term treatment of venous thromboembolism in patients with cancer: a cochrane systematic review. J Exp Clin Cancer Res. 2008;27:21. Scholar
  2. 2.
    Al-Khatib SM, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2017;
  3. 3.
    Barbey JT, Pezzullo JC, Soignet SL. Effect of arsenic trioxide on QT interval in patients with advanced malignancies. J Clin Oncol. 2003;21:3609–15. Scholar
  4. 4.
    Barlogie B, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006;354:1021–30. Scholar
  5. 5.
    Barni S, Petrelli F, Cabiddu M. Cardiotoxicity of antiemetic drugs in oncology: an overview of the current state of the art. Crit Rev Oncol Hematol. 2016;102:125–34. Scholar
  6. 6.
    Behling J, Kaes J, Munzel T, Grabbe S, Loquai C. New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. Melanoma Res. 2017;27:155–8. Scholar
  7. 7.
    Benatar A, Decraene T. Comparison of formulae for heart rate correction of QT interval in exercise ECGs from healthy children. Heart. 2001;86:199–202. Scholar
  8. 8.
    Bodley A, et al. DNA topoisomerase II-mediated interaction of doxorubicin and daunorubicin congeners with DNA. Cancer Res. 1989;49:5969–78.PubMedGoogle Scholar
  9. 9.
    Cheng CW, Yang NI, Ng KK, Cherng WJ. Metastatic cardiac tumor presenting as atrial fibrillation in a previously healthy woman: a case report. Medicine. 2017;96:e7649. Scholar
  10. 10.
    Chung MK, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation. 2001;104:2886–91.CrossRefGoogle Scholar
  11. 11.
    Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51. Scholar
  12. 12.
    Darby SC, et al. Radiation-related heart disease: current knowledge and future prospects. Int J Radiat Oncol Biol Phys. 2010;76:656–65. Scholar
  13. 13.
    Drew BJ, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation. 2010;121:1047–60. Scholar
  14. 14.
    Emch GS, Hermann GE, Rogers RC. Tumor necrosis factor-α inhibits physiologically identified dorsal motor nucleus neurons in vivo. Brain Res. 2002;951:311–5. Scholar
  15. 15.
    Faderl S, et al. A randomized study of clofarabine versus clofarabine plus low-dose cytarabine as front-line therapy for patients aged 60 years and older with acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2008;112:1638–45. Scholar
  16. 16.
    Fahdi IE, et al. Bradycardia during therapy for multiple myeloma with thalidomide. Am J Cardiol. 2004;93:1052–5. Scholar
  17. 17.
    Fernando HC, Jaklitsch MT, Walsh GL, Tisdale JE, Bridges CD, Mitchell JD, Shrager JB. The Society of Thoracic Surgeons practice guideline on the prophylaxis and management of atrial fibrillation associated with general thoracic surgery: executive summary. Ann Thorac Surg. 2011;92:1144–52. Scholar
  18. 18.
    Ficker E, et al. Mechanisms of arsenic-induced prolongation of cardiac repolarization. Mol Pharmacol. 2004;66:33–44. Scholar
  19. 19.
    Frendl G, et al. 2014 AATS guidelines for the prevention and management of perioperative atrial fibrillation and flutter for thoracic surgical procedures. J Thorac Cardiovasc Surg. 2014;148:e153–93. Scholar
  20. 20.
    Futatani T, Watanabe C, Baba Y, Tsukada S, Ochs HD. Bruton’s tyrosine kinase is present in normal platelets and its absence identifies patients with X-linked agammaglobulinaemia and carrier females. Br J Haematol. 2001;114:141–9.CrossRefGoogle Scholar
  21. 21.
    Ghatalia P, Je Y, Kaymakcalan MD, Sonpavde G, Choueiri TK. QTc interval prolongation with vascular endothelial growth factor receptor tyrosine kinase inhibitors. Br J Cancer. 2014;112:296. Scholar
  22. 22.
    Gomez DR, et al. Prospective exploratory analysis of cardiac biomarkers and electrocardiogram abnormalities in patients receiving thoracic radiation therapy with high-dose heart exposure. J Thorac Oncol: Off Publ Int Assoc Study Lung Cancer. 2014;9:1554–60. Scholar
  23. 23.
    Granger CB, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92. Scholar
  24. 24.
    Grant JD, et al. Radiotherapy-induced malfunction in contemporary cardiovascular implantable electronic devices: clinical incidence and predictors. JAMA Oncol. 2015;1:624–32. Scholar
  25. 25.
    Hong RA, Iimura T, Sumida KN, Eager RM. Cardio-oncology/onco-cardiology. Clin Cardiol. 2010;33:733–7. Scholar
  26. 26.
    Indik JH, Pearson EC, Fried K, Woosley RL. Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval. Heart Rhythm. 2006;3:1003–7. Scholar
  27. 27.
    Indik JH, et al. 2017 HRS expert consensus statement on magnetic resonance imaging and radiation exposure in patients with cardiovascular implantable electronic devices. Heart Rhythm. 2017;14:e97–e153. Scholar
  28. 28.
    Isbister GK, Page CB. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice. Br J Clin Pharmacol. 2013;76:48–57. Scholar
  29. 29.
    Iwata N, Karasawa M, Omine M, Maekawa T, Suzuki T, Kawai Y. Aclarubicin-associated QTc prolongation and ventricular fibrillation. Cancer Treat Rep. 1984;68:527–9.PubMedGoogle Scholar
  30. 30.
    January CT, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. 2014; 64:e1–e76
  31. 31.
    Johnson JN, Ackerman MJ. QTc: how long is too long? Br J Sports Med. 2009;43:657–62. Scholar
  32. 32.
    Kalin R, Stanton MS. Current clinical issues for MRI scanning of pacemaker and defibrillator patients. Pacing Clin Electrophysiol: PACE. 2005;28:326–8. Scholar
  33. 33.
    Kaur A, Yu SS, Lee AJ, Chiao TB. Thalidomide-induced sinus bradycardia. Ann Pharmacother. 2003;37:1040–3. Scholar
  34. 34.
    Khan MA, Masood N, Husain N, Ahmad B, Aziz T, Naeem A. A retrospective study of cardiotoxicities induced by 5-fluouracil (5-FU) and 5-FU based chemotherapy regimens in Pakistani adult cancer patients at Shaukat Khanum Memorial Cancer Hospital & Research Center JPMA. J Pak Med Assoc. 2012;62:430–4.PubMedGoogle Scholar
  35. 35.
    Khozin S, et al. FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2015;21:2436–9. Scholar
  36. 36.
    Kilickap S, Barista I, Akgul E, Aytemir K, Aksoy S, Tekuzman G. Early and late arrhythmogenic effects of doxorubicin. South Med J. 2007;100:262–5. Scholar
  37. 37.
    Kim PY, Ewer MS. Chemotherapy and QT prolongation: overview with clinical perspective. Curr Treat Options Cardiovasc Med. 2014;16:303. Scholar
  38. 38.
    Kupari M, Volin L, Suokas A, Timonen T, Hekali P, Ruutu T. Cardiac involvement in bone marrow transplantation: electrocardiographic changes, arrhythmias, heart failure and autopsy findings. Bone Marrow Transplant. 1990;5:91–8.PubMedGoogle Scholar
  39. 39.
    Kuryshev YA, Brown AM, Wang L, Benedict CR, Rampe D. Interactions of the 5-hydroxytryptamine 3 antagonist class of antiemetic drugs with human cardiac ion channels. J Pharmacol Exp Ther. 2000;295:614–20.PubMedGoogle Scholar
  40. 40.
    Larkin J, et al. Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open-label, multicentre, safety study. Lancet Oncol. 2014;15:436–44. Scholar
  41. 41.
    Lepeschkin E, Surawicz B. The measurement of the Q-T interval of the electrocardiogram. Circulation. 1952;6:378–88.CrossRefGoogle Scholar
  42. 42.
    Luo S, Michler K, Johnston P, Macfarlane PW. A comparison of commonly used QT correction formulae: the effect of heart rate on the QTc of normal ECGs. J Electrocardiol. 2004;37(Suppl):81–90.CrossRefGoogle Scholar
  43. 43.
    Margolin KA, et al. Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines. J Clin Oncol. 1989;7:486–98. Scholar
  44. 44.
    Mazur M, et al. Burden of cardiac arrhythmias in patients with anthracycline-related cardiomyopathy. JACC: Clin Electrophysiol. 2017;3:139–50. Scholar
  45. 45.
    McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DK, Donehower RC. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med. 1989;111:273–9.CrossRefGoogle Scholar
  46. 46.
    Mikami Y, et al. Focal fibrosis in the left ventricle of subjects with cardiac amyloidosis evaluated by multislice computed tomography. Int J Cardiol. 2007;122:72–5. Scholar
  47. 47.
    Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins. 2010;2:2490–518. Scholar
  48. 48.
    Miyake CY, et al. Cardiac tumors and associated arrhythmias in pediatric patients, with observations on surgical therapy for ventricular tachycardia. J Am Coll Cardiol. 2011;58:1903–9. Scholar
  49. 49.
    Morcos PN, et al. Effect of alectinib on cardiac electrophysiology: results from intensive electrocardiogram monitoring from the pivotal phase II NP28761 and NP28673 studies. Cancer Chemother Pharmacol. 2017;79:559–68. Scholar
  50. 50.
    Narducci ML, et al. A challenging case of ventricular arrhythmia in a patient with myocarditis: ICD yes/no after ablation. J Atrial Fibrillation. 2014;7:1121. Scholar
  51. 51.
    Nazarian S, et al. Safety of magnetic resonance imaging in patients with cardiac devices. N Engl J Med. 2017;377:2555–64. Scholar
  52. 52.
    Obers S, et al. Multiple mechanisms of hERG liability: K+ current inhibition, disruption of protein trafficking, and apoptosis induced by amoxapine. Naunyn Schmiedeberg’s Arch Pharmacol. 2010;381:385–400. Scholar
  53. 53.
    Ohnishi K, Yoshida H, Shigeno K, et al. Prolongation of the qt interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia. Ann Intern Med. 2000;133:881–5. Scholar
  54. 54.
    Olivieri A, et al. Paroxysmal atrial fibrillation after high-dose melphalan in five patients autotransplanted with blood progenitor cells. Bone Marrow Transplant. 1998;21:1049–53. Scholar
  55. 55.
    Ou SH, Tang Y, Polli A, Wilner KD, Schnell P. Factors associated with sinus bradycardia during crizotinib treatment: a retrospective analysis of two large-scale multinational trials (PROFILE 1005 and 1007). Cancer Med. 2016;5:617–22. Scholar
  56. 56.
    Patel MR, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91. Scholar
  57. 57.
    Patell R, Gutierrez A, Rybicki L, Khorana AA. Usefulness of CHADS2 and CHA2DS2-VASc scores for stroke prediction in patients with cancer and atrial fibrillation. Am J Cardiol. 2017;120:2182–6. Scholar
  58. 58.
    Peres E, et al. Cardiac complications in patients undergoing a reduced-intensity conditioning hematopoietic stem cell transplantation. Bone Marrow Transplant. 2010;45:149–52. Scholar
  59. 59.
    Polk A, Vaage-Nilsen M, Vistisen K, Nielsen DL. Cardiotoxicity in cancer patients treated with 5-fluorouracil or capecitabine: a systematic review of incidence, manifestations and predisposing factors. Cancer Treat Rev. 2013;39:974–84. Scholar
  60. 60.
    Porta-Sanchez A, Gilbert C, Spears D, Amir E, Chan J, Nanthakumar K, Thavendiranathan P. Incidence, diagnosis, and management of QT prolongation induced by cancer therapies: a systematic review. J Am Heart Assoc. 2017;6.
  61. 61.
    Rajkumar SV, et al. Thalidomide as initial therapy for early-stage myeloma. Leukemia. 2003;17:775–9. Scholar
  62. 62.
    Rapp JH, Yuen M, Abraham T. Bradycardia after intravenous ondansetron with asystole on rechallenge: a case report. Hosp Pharm. 2015;50:918–21. Scholar
  63. 63.
    Russo RJ, et al. Assessing the risks associated with MRI in patients with a pacemaker or defibrillator. N Engl J Med. 2017;376:755–64. Scholar
  64. 64.
    Saccullo G, Malato A, Raso S, Santoro M, Zammit V, Casuccio A, Siragusa S. Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: the use of fixed sub-therapeutic doses of low-molecular weight heparin. Am J Hematol. 2012;87:388–91. Scholar
  65. 65.
    Salerno F, Girerd N, Chalabreysse L, Billaud G, Lina B, Chevalier P. Myocarditis and cardiac channelopathies: a deadly association? Int J Cardiol. 2011;147:468–70. Scholar
  66. 66.
    Sanguinetti MC, Mitcheson JS. Predicting drug–hERG channel interactions that cause acquired long QT syndrome. Trends Pharmacol Sci. 2005;26:119–24. Scholar
  67. 67.
    Sato Y, et al. Lipomatous hypertrophy of the interatrial septum presenting as sick sinus syndrome. Int J Cardiol. 2007;119:280–1. Scholar
  68. 68.
    Shah S, Norby FL, Datta YH, Lutsey PL, MacLehose RF, Chen LY, Alonso A. Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation. Blood Adv. 2018;2:200–9. Scholar
  69. 69.
    Sharabi Y, Dendi R, Holmes C, Goldstein DS. Baroreflex failure as a late sequela of neck irradiation. Hypertension (Dallas, Tex: 1979). 2003;42:110–6. Scholar
  70. 70.
    Shen S, Rizkallah J, Kirkpatrick ID, Khadem A, Jassal DS. Cardiac lipofibromatosis. Can J Cardiol. 2013;29:519.e511–2. Scholar
  71. 71.
    Shigeno K, et al. Arsenic trioxide therapy in relapsed or refractory Japanese patients with acute promyelocytic leukemia: updated outcomes of the phase II study and postremission therapies. Int J Hematol. 2005;82:224–9. Scholar
  72. 72.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. Scholar
  73. 73.
    Soignet SL, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852–60. Scholar
  74. 74.
    Stroeder J, Evans C, Mansell H. Corticosteroid-induced bradycardia: case report and review of the literature. Can Pharmacists J: CPJ = Rev Pharmaciens Can: RPC. 2015;148:235–40. Scholar
  75. 75.
    Subramanian R, Flygenring B. Mesothelioma of the atrioventricular node and congenital complete heart block. Clin Cardiol. 1989;12:469–72.CrossRefGoogle Scholar
  76. 76.
    Tötterman KJ, Pesonen E, Siltanen P. Radiation-related chronic heart disease. Chest. 1983;83:875–8. Scholar
  77. 77.
    Unnikrishnan D, et al. Torsades de pointes in 3 patients with leukemia treated with arsenic trioxide. Blood. 2001;97:1514–6.CrossRefGoogle Scholar
  78. 78.
    Vaduganathan M, Patel NK, Lubitz SA, Neilan TG, Dudzinski DM. A “Malignant” arrhythmia: cardiac metastasis and ventricular tachycardia. Tex Heart Inst J. 2016;43:558–9. Scholar
  79. 79.
    Vaporciyan AA, et al. Risk factors associated with atrial fibrillation after noncardiac thoracic surgery: analysis of 2588 patients. J Thorac Cardiovasc Surg. 2004;127:779–86. Scholar
  80. 80.
    Viskin S, et al. Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one. Heart Rhythm. 2005;2:569–74. Scholar
  81. 81.
    Xu MF, Tang PL, Qian ZM, Ashraf M. Effects by doxorubicin on the myocardium are mediated by oxygen free radicals. Life Sci. 2001;68:889–901. Scholar
  82. 82.
    Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53:2231–47. Scholar
  83. 83.
    Yilmaz U, et al. 5-fluorouracil increases the number and complexity of premature complexes in the heart: a prospective study using ambulatory ECG monitoring. Int J Clin Pract. 2007;61:795–801. Scholar
  84. 84.
    Yusuf SW, Razeghi P, Yeh ET. The diagnosis and management of cardiovascular disease in cancer patients. Curr Probl Cardiol. 2008;33:163–96. Scholar
  85. 85.
    Zaremba T, Jakobsen AR, Sogaard M, Thogersen AM, Johansen MB, Madsen LB, Riahi S. Risk of device malfunction in cancer patients with implantable cardiac device undergoing radiotherapy: a population-based cohort study. Pacing Clin Electrophysiol: PACE. 2015;38:343–56. Scholar
  86. 86.
    Zhang S, Liu X, Bawa-Khalfe T, Lu L-S, Lyu YL, Liu LF, Yeh ETH. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 2012;18:1639. Scholar
  87. 87.
    Zimmer L, et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy. Eur J Cancer (Oxford, England: 1990). 2016;60:210–25. Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Peter Kim
    • 1
    Email author
  • Abdulrazzak Zarifa
    • 1
  • Mohammed Salih
    • 1
  • Kaveh Karimzad
    • 1
  1. 1.Department of Cardiology, Division of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations