Medical Oncology

, 30:609

Arrhythmias during and after zoledronic acid infusion patients with bone metastasis

  • Ozan Yazici
  • Sercan Aksoy
  • Ozgul Ucar
  • Nuriye Ozdemir
  • Mevlut Demir
  • Mehmet Ali Nahit Sendur
  • Zafer Arik
  • Sebnem Yaman
  • Tulay Eren
  • Dogan Uncu
  • Nurullah Zengin
Original Paper

Abstract

Zoledronic acid (ZA) is one of the important bisphosphonates which is widely used in bone metastatic cancer and osteoporotic patients. In a few studies, it has been reported that treatment with bisphosphonates was associated with an increased risk of atrial fibrillation. We aimed to evaluate the arrhythmias that developed during and immediately after infusion of the ZA. Fifty-two bone metastatic patients were included in the study group. All patients had 24-h Holter monitorization during the first dose ZA infusion day. All of the patients had 4-h basal cardiac rhythm records before ZA infusion and about 19 h after infusion. A short survey including demographic data and past medical history has been completed. None of patients had clinically important arrhythmias before ZA infusion. We divided arrhythmias into two groups as supraventricular and ventricular. We evaluated arrhythmias in pre-infusion, during infusion, and post-infusion periods. ZA was administered 4 mg intravenously (IV) in 15 min. Thirty-three of patients (63.5 %) were male and 19 (36.5 %) patients were female. Mean age of the patients was 53.9 ± 11.8 years. Most frequent cancers were breast (25 %) and lung cancer (15.3 %). Twelve (23 %) patients had history of mediastinal radiotherapy. In basal records, we detected that twenty-four (46 %) of patients had supraventricular premature complexes (SVPC) or ventricular premature complexes (VPC). Fifteen (28.8 %) of patients had SVPC and fourteen (26.9 %) had VPC during infusion period. After infusion period, 48 (92.3 %) of patients had SVPC and 41 (78.8 %) had VPC. Only 3 patients had no arrhythmia after infusion. Three patients had sinus arrhythmia and two had Mobitz type 2 atrioventricular blocks after infusion. One patient, who had no history of comorbidities and had SVPC in the basal records, developed atrial fibrillation that was refractory to medical cardioversion after 10 days of seventh dose of ZA infusion. In this study, we found that both SVPC and VPC increased in cancer patients treated with ZA. Furthermore, ZA may induce clinically important arrhythmias.

Keywords

Zoledronic acid  Side effect  Arrhythmias  Supraventricular  Ventricular 

References

  1. 1.
    Ibrahim A, Scher N, Williams G, et al. Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clin Cancer Res. 2003;9:2394–9.PubMedGoogle Scholar
  2. 2.
    Abrahamsen B, Eiken P, Brixen K. Atrial fibrillation in fracture patients treated with oral bisphosphonates. J Intern Med. 2009;265:581–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Heckbert SR, Li G, Cummings SR, Smith NL, Psaty BM. Use of alendronate and risk of incident atrial fibrillation in women. Arch Intern Med. 2008;168:826–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356:1809–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Sorensen HT, Christensen S, Mehnert F, et al. Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study. BMJ. 2008;336:813–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Bunch TJ, Anderson JL, May HT, et al. Relation of bisphosphonate therapies and risk of developing atrial fibrillation. Am J Cardiol. 2009;103:824–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Erichsen R, Christiansen CF, Frøslev T, Jacobsen J, Sørensen HT. Intravenous bisphosphonate therapy and atrial fibrillation/flutter risk in cancer patients: a nationwide cohort study. Br J Cancer. 2011;105:881–3.PubMedCrossRefGoogle Scholar
  8. 8.
    Wilkinson GS, Baillargeon J, Kuo YF, Freeman JL, Goodwin JS. Atrial fibrillation and stroke associated with intravenous bisphosphonate therapy in older patients with cancer. J Clin Oncol. 2010;28:4898–905.PubMedCrossRefGoogle Scholar
  9. 9.
    Grosso A, Douglas I, Hingorani A, MacAllister R, Smeeth L. Oral bisphosphonates and risk of atrial fibrillation and flutter in women: a self controlled case-series safety analysis. PLoS ONE. 2009;4:e4720.PubMedCrossRefGoogle Scholar
  10. 10.
    McClung M, Harris ST, Miller PD, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med. 2013;126:13–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Lyles KW, Colón-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799–809.PubMedCrossRefGoogle Scholar
  12. 12.
    Arslan C, Aksoy S, Dizdar O, Dede DS, Harputluoglu H, Altundag K. Zoledronic acid and atrial fibrillation in cancer patients. Support Care Cancer. 2011;19:425–30.PubMedCrossRefGoogle Scholar
  13. 13.
    Loke YK, Jeevanantham V, Singh S. Bisphosphonates and atrial fibrillation: systematic review and meta-analysis. Drug Saf. 2009;32:219–28.PubMedCrossRefGoogle Scholar
  14. 14.
    Frame LH, Page RL, Hoffman BF. Atrial reentry around an anatomic barrier with a partially refractory excitable gap. a canine model of atrial flutter. Circ Res. 1986;58:495–511.PubMedCrossRefGoogle Scholar
  15. 15.
    Kamjoo K, Uchida T, Ikeda T, et al. Importance of location and timing of electrical stimuli in terminating sustained functional reentry in isolated swine ventricular tissues: evidence in support of a small reentrant circuit. Circulation. 1997;96:2048–60.PubMedCrossRefGoogle Scholar
  16. 16.
    Antzelevitch C, Burashnikov A. Overview of basic mechanisms of cardiac arrhythmia. Card Electrophysiol Clin. 2011;3:23–45.PubMedCrossRefGoogle Scholar
  17. 17.
    Messineo FC. Ventricular ectopic activity: prevalence and risk. Am J Cardiol. 1989;64:53J–6J.PubMedCrossRefGoogle Scholar
  18. 18.
    Bigger JT Jr, Dresdale FJ, Heissenbuttel RH, Weld FM, Wit AL. Ventricular arrhythmias in ischemic heart disease: mechanism, prevalence, significance, and management. Prog Cardiovasc Dis. 1977;19:255.PubMedCrossRefGoogle Scholar
  19. 19.
    Kantor RJ, Garson A. Arrhythmias in congenital heart disease. In: Podrid PJ, Kowey PR, editors. Cardiac arrhythmia: mechanisms, diagnosis, and management. Baltimore: Williams & Wilkins; 1995. p. 1131.Google Scholar
  20. 20.
    Benjamin EJ, Levy D, Vaziri SM, D’Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort the Framingham Heart Study. JAMA. 1994;271:840–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhuang J, Wang Y, Tang K, et al. Association between left atrial size and atrial fibrillation recurrence after single circumferential pulmonary vein isolation: a systematic review and meta-analysis of observational studies. Europace. 2012;14:638–45.PubMedCrossRefGoogle Scholar
  22. 22.
    Lainscak M, Dagres N, Filippatos GS, Anker SD, Kremastinos DT. Atrial fibrillation in chronic non-cardiac disease: where do we stand? Int J Cardiol. 2008;128:311–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Guo Y, Lip GY, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol. 2012;60:2263–70.PubMedCrossRefGoogle Scholar
  24. 24.
    Takahashi N, Kume O, Wakisaka O, et al. Novel strategy to prevent atrial fibrosis and fibrillation. Circ J. 2012;76:2318–26.PubMedCrossRefGoogle Scholar
  25. 25.
    Köroğlu S, Tuncer C, Acar G. Relation of inflammatory and oxidative markers to the occurrence and recurrence of persistent atrial fibrillation. Turk Kardiyol Dern Ars. 2012;40:499–504.PubMedCrossRefGoogle Scholar
  26. 26.
    Du RH, Yi HW, Dai DZ, Tang WH, Dai Y. Inflammatory factors that contribute to upregulation of ERG and cardiac arrhythmias are suppressed by CPU86017, a class III antiarrhythmic agent. J Pharm Pharmacol. 2008;60:1089–95.PubMedCrossRefGoogle Scholar
  27. 27.
    Corrado A, Santoro N, Cantatore FP. Extra-skeletal effects of bisphosphonates. Joint Bone Spine. 2007;74:32–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Wolf AM, Rumpold H, Tilg H, Gastl G, Gunsilius E, Wolf D. The effect of zoledronic acid on the function and differentiation of myeloid cells. Haematologica. 2006;91:1165–71.PubMedGoogle Scholar
  29. 29.
    Scheller EL, Hankenson KD, Reuben JS, Krebsbach PH. Zoledronic acid inhibits macrophage SOCS3 expression and enhances cytokine production. J Cell Biochem. 2011;112:3364–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ozan Yazici
    • 1
  • Sercan Aksoy
    • 2
  • Ozgul Ucar
    • 3
  • Nuriye Ozdemir
    • 1
  • Mevlut Demir
    • 3
  • Mehmet Ali Nahit Sendur
    • 1
  • Zafer Arik
    • 1
  • Sebnem Yaman
    • 1
  • Tulay Eren
    • 1
  • Dogan Uncu
    • 1
  • Nurullah Zengin
    • 1
  1. 1.Department of Medical OncologyAnkara Numune Education and Research HospitalSihhiye, AnkaraTurkey
  2. 2.Department of Medical OncologyHacettepe University Cancer InstituteAnkaraTurkey
  3. 3.Cardiology DepartmentAnkara Numune Research and Education HospitalAnkaraTurkey

Personalised recommendations