Skip to main content

Advertisement

SpringerLink
Log in

Tyrosine kinase inhibitor–associated ventricular arrhythmias: a case series and review of literature

  • Published:
Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Background

Tyrosine kinase inhibitors (TKIs) have been increasingly used as first-line therapy in hematologic and solid-organ malignancies. Multiple TKIs have been linked with the development of cardiovascular complications, especially atrial arrhythmias, but data on ventricular arrhythmias (VAs) is scarce.

Methods

Herein we describe five detailed cases of VAs related to TKI use in patients with varied baseline cardiovascular risk factors between 2019 and 2022 at three centers. Individual chart review was conducted retrospectively.

Results

Patient ages ranged from 43 to 83 years. Three patients were on Bruton’s TKI (2 ibrutinib and 1 zanubrutinib) at the time of VAs; other TKIs involved were afatinib and dasatinib. Three patients had a high burden of non-sustained ventricular tachycardia (NSVT) requiring interventions, whereas two patients had sustained VAs. While all patients in our case series had significant improvement in VA burden after TKI cessation, two patients required new long-term antiarrhythmic drug therapy, and one had an implantable defibrillator cardioverter (ICD) placed due to persistent VAs after cessation of TKI therapy. One patient reinitiated TKI therapy after control of arrhythmia was achieved with antiarrhythmic drug therapy.

Conclusions

Given the expanding long-term use of TKIs among a growing population of cancer patients, it is critical to acknowledge the association of TKIs with cardiovascular complications such as VAs, to characterize those at risk, and deploy preventive and therapeutic measures to avoid such complications and interference with oncologic therapy. Further efforts are warranted to develop monitoring protocols and optimal treatment strategies for TKI-induced VAs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Bohdan M, Kowalczys A, Mickiewicz A, Gruchała M, Lewicka E. Cancer therapy-related cardiovascular complications in clinical practice: current perspectives. J Clin Med Res [Internet]. 2021;10(8). https://doi.org/10.3390/jcm10081647.

  2. Ferguson FM, Gray NS. Kinase inhibitors: the road ahead. Nat Rev Drug Discov. 2018;17(5):353–77.

    Article  CAS  PubMed  Google Scholar 

  3. Wiczer TE, Levine LB, Brumbaugh J, Coggins J, Zhao Q, Ruppert AS, et al. Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib. Blood Adv. 2017;1(20):1739–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ganatra S, Sharma A, Shah S, Chaudhry GM, Martin DT, Neilan TG, et al. Ibrutinib-Associated Atrial Fibrillation. JACC Clin Electrophysiol. 2018;4(12):1491–500.

    Article  PubMed  Google Scholar 

  5. Guha A, Derbala MH, Zhao Q, Wiczer TE, Woyach JA, Byrd JC, et al. Ventricular Arrhythmias Following Ibrutinib Initiation for Lymphoid Malignancies. J Am Coll Cardiol. 2018;72(6):697–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lampson B, Yu L, Barrientos J, Jacobsen E, Banerji V, Jones J, et al. Ventricular arrhythmias and sudden death in patients taking ibrutinib [Internet]. Vol. 16, Clinical Lymphoma Myeloma and Leukemia. 2016. S52. https://doi.org/10.1016/j.clml.2016.07.075.

  7. Salem JE, Manouchehri A, Bretagne M, Lebrun-Vignes B, Groarke JD, Johnson DB, et al. Cardiovascular Toxicities associated with ibrutinib. J Am Coll Cardiol. 2019;74(13):1667–78.

    Article  CAS  PubMed  Google Scholar 

  8. Tam CS, Opat S, D’Sa S, Jurczak W, Lee HP, Cull G, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. 2020;136(18):2038–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. J Clin Oncol. 2021;39(31):3441–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bhat SA, Gambril JA, Azali L, Chen ST, Rosen L, Palettas M, et al. Ventricular arrhythmias and sudden death events following acalabrutinib initiation. Blood [Internet]. 2022; https://doi.org/10.1182/blood.2022016953.

  11. Beyer A, Ganti B, Majkrzak A, Theyyunni N. A Perfect Storm: Tyrosine kinase inhibitor-associated polymorphic ventricular tachycardia. J Emerg Med. 2017;52(4):e123–7.

    Article  PubMed  Google Scholar 

  12. Wallace N, Wong E, Cooper D, Chao H. A case of new-onset cardiomyopathy and ventricular tachycardia in a patient receiving ibrutinib for relapsed mantle cell lymphoma. Clin Case Rep. 2016;4(12):1120–1.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tomcsányi J, Nényei Z, Mátrai Z, Bózsik B. Ibrutinib, an approved tyrosine kinase inhibitor as a potential cause of recurrent polymorphic ventricular tachycardia. JACC: Clin Electrophysiol. 2016;2(7):847–9.

    PubMed  Google Scholar 

  14. Prashar A, Ilsar R, Roncolato F, Hopkins A. Recurrent ventricular fibrillation with different tyrosine kinase inhibitors for chronic myeloid leukemia. HeartRhythm Case Rep. 2020;6(10):770–3.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Spechbach H, Morel P, IngLorenzini K, Besson M, Gétaz L, Sunthorn H, et al. Reversible ventricular arrythmia induced by dasatinib. Clin Case Rep. 2013;1(1):20–5.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Madgula AS, Singh M, Almnajam M, Pickett CC, Kim AS. Ventricular tachycardia storm in a patient treated with ibrutinib for Waldenstrom macroglobulinemia. Cardio Oncol. 2020;2(3):523–6.

    Google Scholar 

  17. Abu Rmilah AA, Lin G, Begna KH, Friedman PA, Herrmann J. Risk of QTc prolongation among cancer patients treated with tyrosine kinase inhibitors. Int J Cancer. 2020;147(11):3160–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Du B, Chakraborty P, Azam MA, Massé S, Lai PFH, Niri A, et al. Acute effects of ibrutinib on ventricular arrhythmia in spontaneously hypertensive rats. JACC: Cardio Oncol. 2020;2(4):614–29.

    Google Scholar 

  19. Tuomi JM, Xenocostas A, Jones DL. Increased susceptibility for atrial and ventricular cardiac arrhythmias in mice treated with a single high dose of ibrutinib. Can J Cardiol. 2018;34(3):337–41.

    Article  PubMed  Google Scholar 

  20. Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, et al. Absorption, metabolism, and excretion of oral 14c radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015;43(2):289–97.

    Article  PubMed  Google Scholar 

  21. Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36(41):2793–867.

    Article  PubMed  Google Scholar 

  22. Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2018;138(13):e272-391.

    PubMed  Google Scholar 

  23. Sapp JL, Wells GA, Parkash R, Stevenson WG, Blier L, Sarrazin JF, et al. Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs. N Engl J Med. 2016;375(2):111–21.

    Article  CAS  PubMed  Google Scholar 

  24. Madonna R, Pieragostino D, Cufaro MC, Del Boccio P, Pucci A, Mattii L, et al. Sex-related differential susceptibility to ponatinib cardiotoxicity and differential modulation of the Notch1 signalling pathway in a murine model. J Cell Mol Med. 2022;26(5):1380–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work is supported by National Institutes of Health grants K08 HL148540 (J.W.R), K08 HL153798 (P.C.) and K23 HL145017 (T.B.), R01 HL149134 and HL83359 (S.M.N.) and American Heart Association Career Development Awards (J.W.R. and P.C.).

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States

    Muhammad Fazal, Chen Wei, Sofia E. Gomez, Shayena Shah BA, Zaniar Ghazizadeh, Ridhima Kapoor, Ronald M. Witteles, Paul J. Wang, Roy M. John, Sanjiv M. Narayan, Paul Cheng & Tina Baykaner

  2. Division of Cardiology, Loma Linda University Medical Center, Loma Linda, CA, United States

    Katherine Lee Chuy

  3. Division of Cardiology, Cook County Health, Chicago, IL, United States

    Katherine Lee Chuy, Grzegorz Pietrasik & Neha Yadav

  4. Division of Cardiology, University of Chicago (Northshore University HealthSystem), Chicago, IL, United States

    Kifah Hussain

  5. Division of Cardiology, Rush Medical College, Chicago, IL, United States

    Grzegorz Pietrasik & Neha Yadav

  6. Department of Hematology, City of Hope Comprehensive Medical Center, Duarte, CA, United States

    Amanda Blackmon

  7. Department of Medicine, City of Hope Comprehensive Medical Center, Duarte, CA, United States

    June-Wha Rhee

Authors
  1. Muhammad Fazal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chen Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katherine Lee Chuy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kifah Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sofia E. Gomez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shayena Shah BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Grzegorz Pietrasik
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Neha Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zaniar Ghazizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ridhima Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ronald M. Witteles
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Amanda Blackmon
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Paul J. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Roy M. John
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sanjiv M. Narayan
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Paul Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. June-Wha Rhee
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Tina Baykaner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tina Baykaner.

Ethics declarations

Consent to participate

This retrospective article of case reports is not subject to Informed Consent by the participants.

Competing interests

​​The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fazal, M., Wei, C., Chuy, K.L. et al. Tyrosine kinase inhibitor–associated ventricular arrhythmias: a case series and review of literature. J Interv Card Electrophysiol 66, 1165–1175 (2023). https://doi.org/10.1007/s10840-022-01400-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10840-022-01400-z

Keywords

Search

Navigation