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Electrophysiology Translational Considerations in Cardio-Oncology: QT and Beyond

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Abstract

With improved screening and the advent of many novel therapeutics, patients with cancer are living longer and often surviving their disease. Cardiovascular complications have significant impact on both short- and long-term morbidity and mortality in these patients. While a great deal of attention has been paid to cardiomyopathy and heart failure, many other cardiotoxicities can occur, often at higher rates. Arrhythmias are a particularly common cardiovascular complication of cancer therapeutics and can range from benign to life threatening. Moreover, management of these rhythm disturbances can be challenging in cancer patients for various reasons including drug interactions, as well as underlying hematologic and metabolic disturbances. In this review, we describe the most common therapeutics associated with arrhythmias in cancer patients and provide a discussion about the potential basic and translational mechanisms leading to the development of the various rhythm disturbances which may help to guide prevention and treatment decisions. Clinicaltrials.gov Identifier: NCT02928497

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References

  1. WHO. World health statistics 2018: monitoring health for the SDGs, sustainable development goals. World Health Organization; 2018. Licence: CC BY-NC-SA 3.0 IGO. 2018

  2. Society, A. C. (2014). Cancer treatment and survivorship facts & figures 2014–2015 (p. 2014). Atlanta: American Cancer Society.

    Google Scholar 

  3. Akhtar, S. S., Salim, K. P., & Bano, Z. A. (1993). Symptomatic cardiotoxicity with high-dose 5-fluorouracil infusion: a prospective study. Oncology., 50(6), 441–444.

    CAS  PubMed  Google Scholar 

  4. Sulpher, J., Dattilo, F., Dent, S., Turek, M., Reaume, M. N., & Johnson, C. (2014). Acute cardiogenic shock induced by infusional 5-fluorouracil. Case Rep Oncol Med, 2014, 819396.

    PubMed  PubMed Central  Google Scholar 

  5. Tamargo, J., Caballero, R., & Delpon, E. (2015). Cancer chemotherapy and cardiac arrhythmias: a review. Drug Saf, 38(2), 129–152.

    CAS  PubMed  Google Scholar 

  6. Fatema, K., Gertz, M. A., Barnes, M. E., et al. (2009). Acute weight gain and diastolic dysfunction as a potent risk complex for post stem cell transplant atrial fibrillation. Am J Hematol, 84(8), 499–503.

    PubMed  Google Scholar 

  7. Feliz, V., Saiyad, S., Ramarao, S. M., Khan, H., Leonelli, F., & Guglin, M. (2011). Melphalan-induced supraventricular tachycardia: incidence and risk factors. Clin Cardiol, 34(6), 356–359.

    PubMed  PubMed Central  Google Scholar 

  8. Hidalgo, J. D., Krone, R., Rich, M. W., et al. (2004). Supraventricular tachyarrhythmias after hematopoietic stem cell transplantation: incidence, risk factors and outcomes. Bone Marrow Transplant, 34(7), 615–619.

    CAS  PubMed  Google Scholar 

  9. Muchtar, E., Dingli, D., Kumar, S., et al. (2016). Autologous stem cell transplant for multiple myeloma patients 70 years or older. Bone Marrow Transplant, 51(11), 1449–1455.

    CAS  PubMed  Google Scholar 

  10. Peres, E., Levine, J. E., Khaled, Y. A., et al. (2010). Cardiac complications in patients undergoing a reduced-intensity conditioning hematopoietic stem cell transplantation. Bone Marrow Transplant, 45(1), 149–152.

    CAS  PubMed  Google Scholar 

  11. Singla, A., Hogan, W. J., Ansell, S. M., et al. (2013). Incidence of supraventricular arrhythmias during autologous peripheral blood stem cell transplantation. Biol Blood Marrow Transplant, 19(8), 1233–1237.

    PubMed  PubMed Central  Google Scholar 

  12. Buza, V., Rajagopalan, B., & Curtis, A. B. (2017). Cancer treatment-induced arrhythmias: focus on chemotherapy and targeted therapies. Circ Arrhythm Electrophysiol, 10(8), e005443. https://doi.org/10.1161/CIRCEP.117.005443.

    Article  PubMed  Google Scholar 

  13. Raja, W., Mir, M. H., Dar, I., Banday, M. A., & Ahmad, I. (2013). Cisplatin induced paroxysmal supraventricular tachycardia. Indian J Med Paediatr Oncol, 34(4), 330–332.

    PubMed  PubMed Central  Google Scholar 

  14. Yang, X., Li, X., Yuan, M., et al. (2018). Anticancer therapy-induced atrial fibrillation: electrophysiology and related mechanisms. Front Pharmacol, 9, 1058.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Zellos, L., Richards, W. G., Capalbo, L., et al. (2009). A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma. J Thorac Cardiovasc Surg, 137(2), 453–458.

    PubMed  Google Scholar 

  16. Kluza, J., Marchetti, P., Gallego, M. A., et al. (2004). Mitochondrial proliferation during apoptosis induced by anticancer agents: effects of doxorubicin and mitoxantrone on cancer and cardiac cells. Oncogene., 23(42), 7018–7030.

    CAS  PubMed  Google Scholar 

  17. Wessler, J. D., Grip, L. T., Mendell, J., & Giugliano, R. P. (2013). The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol, 61(25), 2495–2502.

    CAS  PubMed  Google Scholar 

  18. Zukkoor S, Thohan V. Drug-drug interactions of common cardiac medications and chemotherapeutic agents. 2018; https://www.acc.org/latest-in-cardiology/articles/2018/12/21/09/52/drug-drug-interactions-of-common-cardiac-medications-and-chemotherapeutic-agents. Accessed 30 Oct 2019

  19. Siegel, D., Martin, T., Nooka, A., et al. (2013). Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica., 98(11), 1753–1761.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. White Jr., R. L., Schwartzentruber, D. J., Guleria, A., et al. (1994). Cardiopulmonary toxicity of treatment with high dose interleukin-2 in 199 consecutive patients with metastatic melanoma or renal cell carcinoma. Cancer., 74(12), 3212–3222.

    PubMed  Google Scholar 

  21. Guo, Y., Lip, G. Y., & Apostolakis, S. (2012). Inflammation in atrial fibrillation. J Am Coll Cardiol, 60(22), 2263–2270.

    CAS  PubMed  Google Scholar 

  22. Heinzerling, L., Ott, P. A., Hodi, F. S., et al. (2016). Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy. J Immunother Cancer, 4, 50.

    PubMed  PubMed Central  Google Scholar 

  23. Yuan, M., Tse, G., Zhang, Z., et al. (2018). The incidence of atrial fibrillation with trastuzumab treatment: A systematic review and meta-analysis. Cardiovasc Ther, 36(6), e12475.

    PubMed  Google Scholar 

  24. McMullen, J. R., Boey, E. J., Ooi, J. Y., Seymour, J. F., Keating, M. J., & Tam, C. S. (2014). Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling. Blood., 124(25), 3829–3830.

    CAS  PubMed  Google Scholar 

  25. Jiang, L., Li, L., Ruan, Y., et al. (2019). Ibrutinib promotes atrial fibrillation by inducing structural remodeling and calcium dysregulation in the atrium. Heart Rhythm, 16(9), 1374–1382.

    PubMed  Google Scholar 

  26. Tuomi, J. M., Xenocostas, A., & Jones, D. L. (2018). Increased susceptibility for atrial and ventricular cardiac arrhythmias in mice treated with a single high dose of ibrutinib. Can J Cardiol, 34(3), 337–341.

    PubMed  Google Scholar 

  27. Ganatra, S., Sharma, A., Shah, S., et al. (2018). Ibrutinib-associated atrial fibrillation. JACC Clin Electrophysiol, 4(12), 1491–1500.

    PubMed  Google Scholar 

  28. Petrini, I., Lencioni, M., Ricasoli, M., et al. (2012). Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma. Cancer Chemother Pharmacol, 69(3), 773–780.

    CAS  PubMed  Google Scholar 

  29. Farmakis, D., Parissis, J., & Filippatos, G. (2014). Insights into onco-cardiology: atrial fibrillation in cancer. J Am Coll Cardiol, 63(10), 945–953.

    PubMed  Google Scholar 

  30. Iwasaki, Y. K., Nishida, K., Kato, T., & Nattel, S. (2011). Atrial fibrillation pathophysiology: implications for management. Circulation., 124(20), 2264–2274.

    CAS  PubMed  Google Scholar 

  31. Imperatori, A., Mariscalco, G., Riganti, G., Rotolo, N., Conti, V., & Dominioni, L. (2012). Atrial fibrillation after pulmonary lobectomy for lung cancer affects long-term survival in a prospective single-center study. J Cardiothorac Surg, 7, 4.

    PubMed  PubMed Central  Google Scholar 

  32. Kavurmaci, O., Akcam, T. I., Ergonul, A. G., Turhan, K., Cakan, A., & Cagirici, U. (2018). Is the risk of postoperative atrial fibrillation predictable in patients undergoing surgery due to primary lung cancer? Heart Lung Circ, 27(7), 835–841.

    PubMed  Google Scholar 

  33. Nattel, S., Burstein, B., & Dobrev, D. (2008). Atrial remodeling and atrial fibrillation: mechanisms and implications. Circ Arrhythm Electrophysiol, 1(1), 62–73.

    PubMed  Google Scholar 

  34. Hu, Y. F., Chen, Y. J., Lin, Y. J., & Chen, S. A. (2015). Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol, 12(4), 230–243.

    CAS  PubMed  Google Scholar 

  35. Mazur, M., Wang, F., Hodge, D. O., et al. (2017). Burden of cardiac arrhythmias in patients with anthracycline-related cardiomyopathy. JACC Clin Electrophysiol, 3(2), 139–150.

    PubMed  Google Scholar 

  36. Longhi, S., Quarta, C. C., Milandri, A., et al. (2015). Atrial fibrillation in amyloidotic cardiomyopathy: prevalence, incidence, risk factors and prognostic role. Amyloid., 22(3), 147–155.

    CAS  PubMed  Google Scholar 

  37. Chandrasekhar, S., & Fradley, M. G. (2019). QT interval prolongation associated with cytotoxic and targeted cancer therapeutics. Curr Treat Options in Oncol, 20(7), 55. https://doi.org/10.1007/s11864-019-0657-y.

    Article  Google Scholar 

  38. Fradley, M. G., Gliksman, M., Emole, J., et al. (2019). Rates and risk of atrial arrhythmias in patients treated with ibrutinib compared with cytotoxic chemotherapy. Am J Cardiol, 124(4), 539–544.

    PubMed  Google Scholar 

  39. Passalia, C., Minetto, P., Arboscello, E., et al. (2013). Cardiovascular adverse events complicating the administration of rituximab: report of two cases. Tumori, 99(6), 288e–292e.

    PubMed  Google Scholar 

  40. Dimopoulos, M. A., Tedeschi, A., Trotman, J., et al. (2018). Phase 3 trial of ibrutinib plus rituximab in Waldenstrom’s macroglobulinemia. N Engl J Med, 378(25), 2399–2410.

    CAS  PubMed  Google Scholar 

  41. Romond, E. H., Perez, E. A., Bryant, J., et al. (2005). Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med, 353(16), 1673–1684.

    CAS  PubMed  Google Scholar 

  42. Slamon, D. J., Leyland-Jones, B., Shak, S., et al. (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med, 344(11), 783–792.

    CAS  PubMed  Google Scholar 

  43. Ozcelik, C., Erdmann, B., Pilz, B., et al. (2002). Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. Proc Natl Acad Sci U S A, 99(13), 8880–8885.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Byrd, J. C., Brown, J. R., O’Brien, S., et al. (2014). Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med, 371(3), 213–223.

    PubMed  PubMed Central  Google Scholar 

  45. Dreyling, M., Jurczak, W., Jerkeman, M., et al. (2016). Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet., 387(10020), 770–778.

    CAS  PubMed  Google Scholar 

  46. Miklos, D., Cutler, C. S., Arora, M., et al. (2017). Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood., 130(21), 2243–2250.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Treon, S. P., Tripsas, C. K., Meid, K., et al. (2015). Ibrutinib in previously treated Waldenstrom’s macroglobulinemia. N Engl J Med, 372(15), 1430–1440.

    CAS  PubMed  Google Scholar 

  48. O’Brien, S., Furman, R. R., Coutre, S., et al. (2018). Single-agent ibrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience. Blood., 131(17), 1910–1919.

    PubMed  PubMed Central  Google Scholar 

  49. Brown, J. R., Moslehi, J., O’Brien, S., et al. (2017). Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica., 102(10), 1796–1805.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Shanafelt, T. D., Parikh, S. A., Noseworthy, P. A., et al. (2017). Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL). Leuk Lymphoma, 58(7), 1630–1639.

    CAS  PubMed  Google Scholar 

  51. Byrd, J. C., Harrington, B., O’Brien, S., et al. (2016). Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med, 374(4), 323–332.

    CAS  PubMed  Google Scholar 

  52. Honigberg, L. A., Smith, A. M., Sirisawad, M., et al. (2010). The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A, 107(29), 13075–13080.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Figueroa, R., Alfonso, A., Lopez-Picazo, J., et al. (2018). Insights into venous thromboembolism prevention in hospitalized cancer patients: lessons from a prospective study. PLoS One, 13(8), e0200220.

    PubMed  PubMed Central  Google Scholar 

  54. Coppens, M., Eikelboom, J. W., Hart, R. G., et al. (2013). The CHA2DS2-VASc score identifies those patients with atrial fibrillation and a CHADS2 score of 1 who are unlikely to benefit from oral anticoagulant therapy. Eur Heart J, 34(3), 170–176.

    CAS  PubMed  Google Scholar 

  55. Patell, R., Gutierrez, A., Rybicki, L., & Khorana, A. A. (2017). Usefulness of CHADS2 and CHA2DS2-VASc scores for stroke prediction in patients with cancer and atrial fibrillation. Am J Cardiol, 120(12), 2182–2186.

    PubMed  Google Scholar 

  56. D’Souza, M., Carlson, N., Fosbol, E., et al. (2018). CHA2DS2-VASc score and risk of thromboembolism and bleeding in patients with atrial fibrillation and recent cancer. Eur J Prev Cardiol, 25(6), 651–658.

    PubMed  Google Scholar 

  57. Rhea, I. B., Lyon, A. R., & Fradley, M. G. (2019). Anticoagulation of cardiovascular conditions in the cancer patient: review of old and new therapies. Curr Oncol Rep, 21(5), 45.

    PubMed  Google Scholar 

  58. Connolly, S. J., Ezekowitz, M. D., Yusuf, S., et al. (2009). Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med, 361(12), 1139–1151.

    CAS  PubMed  Google Scholar 

  59. Granger, C. B., Alexander, J. H., McMurray, J. J., et al. (2011). Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med, 365(11), 981–992.

    CAS  PubMed  Google Scholar 

  60. Patel, M. R., Mahaffey, K. W., Garg, J., et al. (2011). Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med, 365(10), 883–891.

    CAS  PubMed  Google Scholar 

  61. Shah, S., Norby, F. L., Datta, Y. H., et al. (2018). Comparative effectiveness of direct oral anticoagulants and warfarin in patients with cancer and atrial fibrillation. Blood Adv, 2(3), 200–209.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kamel, S., Horton, L., Ysebaert, L., et al. (2015). Ibrutinib inhibits collagen-mediated but not ADP-mediated platelet aggregation. Leukemia., 29(4), 783–787.

    CAS  PubMed  Google Scholar 

  63. Levade, M., David, E., Garcia, C., et al. (2014). Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions. Blood., 124(26), 3991–3995.

    CAS  PubMed  Google Scholar 

  64. Wang, M. L., Rule, S., Martin, P., et al. (2013). Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med, 369(6), 507–516.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Lopez-Fernandez, T., Martin-Garcia, A., Roldan Rabadan, I., et al. (2019). Atrial fibrillation in active cancer patients: expert position paper and recommendations. Rev Esp Cardiol (Engl Ed), 72(9), 749–759.

    Google Scholar 

  66. Masoudi, F. A., Calkins, H., Kavinsky, C. J., et al. (2015). 2015 ACC/HRS/SCAI left atrial appendage occlusion device societal overview. J Am Coll Cardiol, 66(13), 1497–1513.

    PubMed  Google Scholar 

  67. Holmes Jr., D. R., Kar, S., Price, M. J., et al. (2014). Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol, 64(1), 1–12.

    PubMed  Google Scholar 

  68. January, C. T., Wann, L. S., Calkins, H., et al. (2019). 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol, 74(1), 104–132.

    PubMed  Google Scholar 

  69. Ibrutinib. Aust Prescr. 2015;38(5):178-180.

  70. Fradley, M. G., & Moslehi, J. (2015). QT prolongation and oncology drug development. Card Electrophysiol Clin, 7(2), 341–355.

    PubMed  Google Scholar 

  71. Tse, G., Chan, Y. W., Keung, W., & Yan, B. P. (2017). Electrophysiological mechanisms of long and short QT syndromes. Int J Cardiol Heart Vasc, 14, 8–13.

    PubMed  Google Scholar 

  72. Roden, D. M. (2004). Drug-induced prolongation of the QT interval. N Engl J Med, 350(10), 1013–1022.

    CAS  PubMed  Google Scholar 

  73. Drew, B. J., Ackerman, M. J., Funk, M., et al. (2010). Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol, 55(9), 934–947.

    PubMed  PubMed Central  Google Scholar 

  74. Zamorano, J. L., Lancellotti, P., Munoz, D. R., et al. (2016). 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Kardiol Pol, 74(11), 1193–1233.

    PubMed  Google Scholar 

  75. Chen, B., Peng, X., Pentassuglia, L., Lim, C. C., & Sawyer, D. B. (2007). Molecular and cellular mechanisms of anthracycline cardiotoxicity. Cardiovasc Toxicol, 7(2), 114–121.

    CAS  PubMed  Google Scholar 

  76. Thomas, D., Karle, C. A., & Kiehn, J. (2006). The cardiac hERG/IKr potassium channel as pharmacological target: structure, function, regulation, and clinical applications. Curr Pharm Des, 12(18), 2271–2283.

    CAS  PubMed  Google Scholar 

  77. Keating, M. T., & Sanguinetti, M. C. (2001). Molecular and cellular mechanisms of cardiac arrhythmias. Cell., 104(4), 569–580.

    CAS  PubMed  Google Scholar 

  78. Lu, Z., Wu, C. Y., Jiang, Y. P., et al. (2012). Suppression of phosphoinositide 3-kinase signaling and alteration of multiple ion currents in drug-induced long QT syndrome. Sci Transl Med, 4(131), 131ra150.

    Google Scholar 

  79. Ficker, E., Kuryshev, Y. A., Dennis, A. T., et al. (2004). Mechanisms of arsenic-induced prolongation of cardiac repolarization. Mol Pharmacol, 66(1), 33–44.

    CAS  PubMed  Google Scholar 

  80. Barbey, J. T., Pezzullo, J. C., & Soignet, S. L. (2003). Effect of arsenic trioxide on QT interval in patients with advanced malignancies. J Clin Oncol, 21(19), 3609–3615.

    CAS  PubMed  Google Scholar 

  81. Roboz, G. J., Ritchie, E. K., Carlin, R. F., et al. (2014). Prevalence, management, and clinical consequences of QT interval prolongation during treatment with arsenic trioxide. J Clin Oncol, 32(33), 3723–3728.

    CAS  PubMed  Google Scholar 

  82. Mumford, J. L., Wu, K., Xia, Y., et al. (2007). Chronic arsenic exposure and cardiac repolarization abnormalities with QT interval prolongation in a population-based study. Environ Health Perspect, 115(5), 690–694.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Siu, C. W., Au, W. Y., Yung, C., et al. (2006). Effects of oral arsenic trioxide therapy on QT intervals in patients with acute promyelocytic leukemia: implications for long-term cardiac safety. Blood., 108(1), 103–106.

    CAS  PubMed  Google Scholar 

  84. Sun, H., Oudit, G. Y., Ramirez, R. J., Costantini, D., & Backx, P. H. (2004). The phosphoinositide 3-kinase inhibitor LY294002 enhances cardiac myocyte contractility via a direct inhibition of Ik,slow currents. Cardiovasc Res, 62(3), 509–520.

    CAS  PubMed  Google Scholar 

  85. Morgan Jr., T. K., & Sullivan, M. E. (1992). An overview of class III electrophysiological agents: a new generation of antiarrhythmic therapy. Prog Med Chem, 29, 65–108.

    CAS  PubMed  Google Scholar 

  86. Porta-Sanchez, A., Gilbert, C., Spears, D., et al. (2017). Incidence, diagnosis, and management of QT prolongation induced by cancer therapies: a systematic review. J Am Heart Assoc, 6(12), e007724.

    PubMed  PubMed Central  Google Scholar 

  87. Blackhall, F. H., O’Brien, M., Schmid, P., et al. (2010). A phase I study of Vandetanib in combination with vinorelbine/cisplatin or gemcitabine/cisplatin as first-line treatment for advanced non-small cell lung cancer. J Thorac Oncol, 5(8), 1285–1288.

    PubMed  Google Scholar 

  88. Liu, Y., Liu, Y., Fan, Z. W., Li, J., & Xu, G. G. (2015). Meta-analysis of the risks of hypertension and QTc prolongation in patients with advanced non-small cell lung cancer who were receiving vandetanib. Eur J Clin Pharmacol, 71(5), 541–547.

    CAS  PubMed  Google Scholar 

  89. Malumbres, M., & Barbacid, M. (2001). To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer, 1(3), 222–231.

    CAS  PubMed  Google Scholar 

  90. Slamon, D. J., Neven, P., Chia, S., et al. (2018). Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol, 36(24), 2465–2472.

    CAS  Google Scholar 

  91. Holkova, B., Supko, J. G., Ames, M. M., et al. (2013). A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Clin Cancer Res, 19(7), 1873–1883.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. O’Connor, O. A., Horwitz, S., Masszi, T., et al. (2015). Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma: results of the pivotal phase II BELIEF (CLN-19) Study. J Clin Oncol, 33(23), 2492–2499.

    PubMed  PubMed Central  Google Scholar 

  93. Infante, J. R., Cassier, P. A., Gerecitano, J. F., et al. (2016). A phase I study of the cyclin-dependent kinase 4/6 inhibitor ribociclib (LEE011) in patients with advanced solid tumors and lymphomas. Clin Cancer Res, 22(23), 5696–5705.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Kuropkat, C., Griem, K., Clark, J., Rodriguez, E. R., Hutchinson, J., & Taylor, S. G. (1999). Severe cardiotoxicity during 5-fluorouracil chemotherapy: a case and literature report. Am J Clin Oncol, 22(5), 466–470.

    CAS  PubMed  Google Scholar 

  95. Guglin, M., Aljayeh, M., Saiyad, S., Ali, R., & Curtis, A. B. (2009). Introducing a new entity: chemotherapy-induced arrhythmia. Europace., 11(12), 1579–1586.

    PubMed  Google Scholar 

  96. Sarubbi, B., Orditura, M., Ducceschi, V., et al. (1997). Ventricular repolarization time indexes following anthracycline treatment. Heart Vessel, 12(6), 262–266.

    CAS  Google Scholar 

  97. Binah, O., Cohen, I. S., & Rosen, M. R. (1983). The effects of adriamycin on normal and ouabain-toxic canine Purkinje and ventricular muscle fibers. Circ Res, 53(5), 655–662.

    CAS  PubMed  Google Scholar 

  98. Duan, J., Tao, J., Zhai, M., et al. (2018). Anticancer drugs-related QTc prolongation, torsade de pointes and sudden death: current evidence and future research perspectives. Oncotarget., 9(39), 25738–25749.

    PubMed  PubMed Central  Google Scholar 

  99. Kosmas, C., Kallistratos, M. S., Kopterides, P., et al. (2008). Cardiotoxicity of fluoropyrimidines in different schedules of administration: a prospective study. J Cancer Res Clin Oncol, 134(1), 75–82.

    CAS  PubMed  Google Scholar 

  100. Sudhoff, T., Enderle, M. D., Pahlke, M., et al. (2004). 5-Fluorouracil induces arterial vasocontractions. Ann Oncol, 15(4), 661–664.

    CAS  PubMed  Google Scholar 

  101. Fradley, M. G., Viganego, F., Kip, K., et al. (2017). Rates and risk of arrhythmias in cancer survivors with chemotherapy-induced cardiomyopathy compared with patients with other cardiomyopathies. Open Heart, 4(2), e000701.

    PubMed  PubMed Central  Google Scholar 

  102. Raabe, N. K., & Storstein, L. (1991). Cardiac arrhythmias in patients with small cell lung cancer and cardiac disease before, during and after doxorubicin administration. An evaluation of acute cardiotoxicity by continuous 24-hour Holter monitoring. Acta Oncol, 30(7), 843–846.

    CAS  PubMed  Google Scholar 

  103. Aversano, R. C., & Boor, P. J. (1983). Acute doxorubicin-induced cardiac arrhythmias during ether anesthesia. Res Commun Chem Pathol Pharmacol, 41(2), 345–348.

    CAS  PubMed  Google Scholar 

  104. Gorelik, J., Vodyanoy, I., Shevchuk, A. I., Diakonov, I. A., Lab, M. J., & Korchev, Y. E. (2003). Esmolol is antiarrhythmic in doxorubicin-induced arrhythmia in cultured cardiomyocytes - determination by novel rapid cardiomyocyte assay. FEBS Lett, 548(1-3), 74–78.

    CAS  PubMed  Google Scholar 

  105. Bischiniotis, T. S., Lafaras, C. T., Platogiannis, D. N., Moldovan, L., Barbetakis, N. G., & Katseas, G. P. (2005). Intrapericardial cisplatin administration after pericardiocentesis in patients with lung adenocarcinoma and malignant cardiac tamponade. Hell J Cardiol, 46(5), 324–329.

    Google Scholar 

  106. Ganatra, S., & Neilan, T. G. (2018). Immune checkpoint inhibitor-associated myocarditis. Oncologist., 23(8), 879–886.

    PubMed  PubMed Central  Google Scholar 

  107. Arteaga, C. L., & Engelman, J. A. (2014). ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell, 25(3), 282–303.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Zhao, Y. Y., Sawyer, D. R., Baliga, R. R., et al. (1998). Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem, 273(17), 10261–10269.

    CAS  PubMed  Google Scholar 

  109. Rao, P., Liu, Z., Duan, H., et al. (2019). Pretreatment with neuregulin-1 improves cardiac electrophysiological properties in a rat model of myocardial infarction. Exp Ther Med, 17(4), 3141–3149.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Florido, R., Smith, K. L., Cuomo, K. K., & Russell, S. D. (2017). Cardiotoxicity from human epidermal growth factor receptor-2 (HER2) targeted therapies. J Am Heart Assoc, 6(9), e006915. https://doi.org/10.1161/JAHA.117.006915.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ou, S. H., Tang, Y., Polli, A., Wilner, K. D., & Schnell, P. (2016). Factors associated with sinus bradycardia during crizotinib treatment: a retrospective analysis of two large-scale multinational trials (PROFILE 1005 and 1007). Cancer Med, 5(4), 617–622.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhang, Z., Huang, T. Q., Nepliouev, I., et al. (2017). Crizotinib inhibits hyperpolarization-activated cyclic nucleotide-gated channel 4 activity. Cardiooncology., 3, 1.

    PubMed  PubMed Central  Google Scholar 

  113. Mostaghel, E. A., & Lin, D. W. (2014). Practical guide to the use of abiraterone in castration resistant prostate cancer. Can J Urol, 21(2 Supp 1), 57–63.

    PubMed  PubMed Central  Google Scholar 

  114. Bertilsson, L., Dahl, M. L., Dalen, P., & Al-Shurbaji, A. (2002). Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol, 53(2), 111–122.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Arbuck, S. G., Strauss, H., Rowinsky, E., et al. (1993). A reassessment of cardiac toxicity associated with Taxol. J Natl Cancer Inst Monogr, 15, 117–130.

    Google Scholar 

  116. Armanious, M. A., Mishra, S., & Fradley, M. G. (2018). Electrophysiologic toxicity of chemoradiation. Curr Oncol Rep, 20(6), 45. https://doi.org/10.1007/s11912-018-0691-0.

    Article  CAS  PubMed  Google Scholar 

  117. Khan, M. A., Masood, N., Husain, N., Ahmad, B., Aziz, T., & Naeem, A. (2012). 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. J Pak Med Assoc, 62(5), 430–434.

    PubMed  Google Scholar 

  118. McGuire, W. P., Rowinsky, E. K., Rosenshein, N. B., et al. (1989). Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med, 111(4), 273–279.

    CAS  PubMed  Google Scholar 

  119. Bovelli, D., Plataniotis, G., Roila, F., & Group EGW. (2010). Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. Ann Oncol, 21(Suppl 5), v277–v282.

    PubMed  Google Scholar 

  120. Alsaab, H. O., Sau, S., Alzhrani, R., et al. (2017). PD-1 and PD-L1 Checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol, 8, 561.

    PubMed  PubMed Central  Google Scholar 

  121. Mahmood, S. S., Fradley, M. G., Cohen, J. V., et al. (2018). Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol, 71(16), 1755–1764.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Katsume, Y., Isawa, T., Toi, Y., et al. (2018). Complete atrioventricular block associated with pembrolizumab-induced acute myocarditis: the need for close cardiac monitoring. Intern Med, 57(21), 3157–3162.

    PubMed  PubMed Central  Google Scholar 

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  1. Cardio-Oncology Program, Division of Cardiovascular Medicine, University of South Florida Morsani College of Medicine and H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr., MCB-CPT, Tampa, FL, 33612-9416, USA

    Mohammed Alomar & Michael G. Fradley

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Dr. Fradley has served as a consultant/advisor for Novartis.

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Alomar, M., Fradley, M.G. Electrophysiology Translational Considerations in Cardio-Oncology: QT and Beyond. J. of Cardiovasc. Trans. Res. 13, 390–401 (2020). https://doi.org/10.1007/s12265-019-09924-y

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