Incidence and Risk Factors of QT Prolongation and Torsades de Pointes following Intravenous Amiodarone Administration for Atrial Fibrillation: A Cohort Study
Archives of Academic Emergency Medicine,
Vol. 13 No. 1 (2025),
6 September 2025
,
Page e70
https://doi.org/10.22037/aaem.v13i1.2784
Abstract
Introduction: Amiodarone has been reported to be associated with QTc interval prolongation and Torsades de pointes (TdP). This study aimed to assess the incidence and identify the risk factors of QTc prolongation and TdP associated with intravenous amiodarone therapy in patients diagnosed with atrial fibrillation (AF).
Methods: A retrospective cohort study was conducted using electronic health records of Buddhachinaraj Hospital, a tertiary care center in Thailand, between January 2016 and September 2019. The study population comprised patients with AF who received intravenous amiodarone therapy. Incidence and associated risk factors for QTc interval prolongation and TdP were assessed using multivariable logistic regression analysis.
Results: A total of 2,944 patients were included in the analysis. Among these, 49 cases of intravenous amiodarone-associated QTc interval prolongation or TdP were identified (33 (1.12%) and 16 (0.54%) cases, respectively), corresponding to an overall incidence of 1.66% (95% confidence interval (CI): 1.23 - 2.19). Multivariable analysis revealed that diabetes mellitus (adjusted odds ratio (aOR): 1.85; 95% CI: 1.02 - 3.38; p-value = 0.045), history of stroke (aOR: 3.09; 95% CI: 1.26 - 7.57; p-value = 0.014), use of antipsychotic medications (aOR: 3.07; 95% CI: 1.64 - 5.74; p-value < 0.001), and use of anticholinergic medications (aOR: 3.89; 95% CI: 1.54 - 9.85; p-value = 0.004) were significantly associated with an increased risk of QTc interval prolongation and TdP following amiodarone therapy for AF patients.
Conclusion: Although the incidence of QTc interval prolongation and TdP related to intravenous amiodarone therapy in patients with AF was relatively low, the risk was significantly elevated in individuals with diabetes mellitus, a history of stroke, or concurrent use of antipsychotic or anticholinergic agents. These findings underscore the importance of vigilant risk assessment and monitoring in clinical practice to mitigate the potential for intravenous amiodarone-induced arrhythmic complications.
- amiodarone
- QT prolongation
- Torsades de pointes
- atrial fibrillation
How to Cite
References
Hamilton D, Sr., Nandkeolyar S, Lan H, Desai P, Evans J, Hauschild C, et al. Amiodarone: A Comprehensive Guide for Clinicians. Am J Cardiovasc Drugs. 2020;20(6):549-58.
Colunga Biancatelli RM, Congedo V, Calvosa L, Ciacciarelli M, Polidoro A, Iuliano L. Adverse reactions of Amiodarone. J Geriatr Cardiol. 2019;16(7):552-66.
Nachimuthu S, Assar MD, Schussler JM. Drug-induced QT interval prolongation: mechanisms and clinical management. Ther Adv Drug Saf. 2012;3(5):241-53.
Barnes BJ, Hollands JM. Drug-induced arrhythmias. Crit Care Med. 2010;38(6 Suppl):S188-97.
Joglar JA, Chung MK, Armbruster AL, Benjamin EJ, Chyou JY, Cronin EM, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2024;83(1):109-279.
Van Gelder IC, Rienstra M, Bunting KV, Casado-Arroyo R, Caso V, Crijns H, et al. 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2024;45(36):3314-414.
Gelman I, Sharma N, McKeeman O, Lee P, Campagna N, Tomei N, et al. The ion channel basis of pharmacological effects of amiodarone on myocardial electrophysiological properties, a comprehensive review. Biomed Pharmacother. 2024;174:116513.
Shenthar J, Rachaiah JM, Pillai V, Chakali SS, Balasubramanian V, Chollenhalli Nanjappa M. Incidence of drug-induced torsades de pointes with intravenous amiodarone. Indian Heart J. 2017;69(6):707-13.
Keller GA, Alvarez PA, Ponte ML, Belloso WH, Bagnes C, Sparanochia C, et al. Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice. Curr Drug Saf. 2016;11(1):86-98.
Yang J, You M, Wang J, Sun R, Han L, Liu X, et al. Adverse events in different administration routes of amiodarone: a pharmacovigilance study based on the FDA adverse event reporting system. Front Pharmacol. 2025;16:1517616.
Tisdale JE, Chung MK, Campbell KB, Hammadah M, Joglar JA, Leclerc J, et al. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. Circulation. 2020;142(15):e214-e33.
Davies RA, Ladouceur VB, Green MS, Joza J, Juurlink DN, Krahn AD, et al. The 2023 Canadian Cardiovascular Society Clinical Practice Update on Management of the Patient With a Prolonged QT Interval. Can J Cardiol. 2023;39(10):1285-301.
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Bmj. 2007;335(7624):806-8.
Bazett HC. An analysis of the time-relations of electrocardiograms. Heart. 1920;7:353-70.
Wang H, Peng J, Wang B, Lu X, Zheng JZ, Wang K, et al. Inconsistency Between Univariate and Multiple Logistic Regressions. Shanghai Arch Psychiatry. 2017;29(2):124-8.
Nattino G, Pennell ML, Lemeshow S. Assessing the goodness of fit of logistic regression models in large samples: A modification of the Hosmer-Lemeshow test. Biometrics. 2020;76(2):549-60.
Vatcheva KP, Lee M, McCormick JB, Rahbar MH. Multicollinearity in Regression Analyses Conducted in Epidemiologic Studies. Epidemiology (Sunnyvale). 2016;6(2):227.
Sarganas G, Garbe E, Klimpel A, Hering RC, Bronder E, Haverkamp W. Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany. Europace. 2014;16(1):101-8.
Geng DF, Jin DM, Wang JF, Luo YJ, Wu W. Clinical study of amiodarone-associated torsade de pointes in Chinese people. Pacing Clin Electrophysiol. 2006;29(7):712-8.
Tong KL, Lau YS, Teo WS. A case series of drug-induced long QT syndrome and Torsade de Pointes. Singapore Med J. 2001;42(12):566-70.
Hohnloser SH, Klingenheben T, Singh BN. Amiodarone-associated proarrhythmic effects. A review with special reference to torsade de pointes tachycardia. Ann Intern Med. 1994;121(7):529-35.
Lim HE, Pak HN, Ahn JC, Song WH, Kim YH. Torsade de pointes induced by short-term oral amiodarone therapy. Europace. 2006;8(12):1051-3.
van Erven L, Schalij MJ. Amiodarone: an effective antiarrhythmic drug with unusual side effects. Heart. 2010;96(19):1593-600.
Hii JT, Wyse DG, Gillis AM, Duff HJ, Solylo MA, Mitchell LB. Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone. Circulation. 1992;86(5):1376-82.
Lederman YS, Balucani C, Lazar J, Steinberg L, Gugger J, Levine SR. Relationship between QT interval dispersion in acute stroke and stroke prognosis: a systematic review. J Stroke Cerebrovasc Dis. 2014;23(10):2467-78.
Amin OSM, Al-Bajalan SJ, Mubarak A. QTc Interval Prolongation and Hemorrhagic Stroke: Any Difference Between Acute Spontaneous Intracerebral Hemorrhage and Acute Non-traumatic Subarachnoid Hemorrhage? Med Arch. 2017;71(3):193-7.
Tsivgoulis G, Palaiodimou L, Triantafyllou S, Köhrmann M, Dilaveris P, Tsioufis K, et al. Prolonged cardiac monitoring for stroke prevention: A systematic review and meta-analysis of randomized-controlled clinical trials. Eur Stroke J. 2023;8(1):106-16.
Li X, Ren H, Xu ZR, Liu YJ, Yang XP, Liu JQ. Prevalence and risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes. Exp Diabetes Res. 2012;2012:234084.
Bush SE, Hatton RC, Winterstein AG, Thomson MR, Woo GW. Effects of concomitant amiodarone and haloperidol on Q-Tc interval prolongation. Am J Health Syst Pharm. 2008;65(23):2232-6.
Girardin FR, Gex-Fabry M, Berney P, Shah D, Gaspoz JM, Dayer P. Drug-induced long QT in adult psychiatric inpatients: the 5-year cross-sectional ECG Screening Outcome in Psychiatry study. Am J Psychiatry. 2013;170(12):1468-76.
Annila P, Yli-Hankala A, Lindgren L. Effect of atropine on the QT interval and T-wave amplitude in healthy volunteers. Br J Anaesth. 1993;71(5):736-7.
Wolbrette DL. Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues. Am J Cardiol. 2003;91(6a):39d-44d.
Schrickel JW, Schwab JO, Yang A, Bielik H, Bitzen A, Lüderitz B, et al. Pro-arrhythmic effects of amiodarone and concomitant rate-control medication. Europace. 2006;8(6):403-7.
- Abstract Viewed: 369 times
- pdf Downloaded: 526 times
Download Statastics
Make a Submission
SJR
COPE
