DOI: https://doi.org/10.22263/2312-4156.2022.3.35
L.V. Kalatsei, V.A. Snezhitskiy, A.V. Kapytski
Assessment of the risk of polymorphic ventricular tachycardia development in patients with drug-induced QT interval prolongation caused by class III antiarrhythmic drugs
Grodno State Medical University, Grodno, Republic of Belarus
Vestnik VGMU. 2022;21(3):35-45.
Abstract.
Objectives. To elaborate a risk assessment model for the development of polymorphic ventricular tachycardia (PVT) in patients with drug-induced long QT syndrome (LQTS) caused by class III antiarrhythmic drugs.
Material and methods. The study included 64 patients with drug-induced LQTS, 37 (57.8%) out of them were women and 27 (42.2%) men, their mean age made up 57.2±9.4 years. All patients underwent clinical, laboratory and instrumental studies, including 12-lead ECG recording, 24-hour Holter ECG monitoring while receiving antiarrhythmic therapy. Depending on the presence or absence of unsustainable PVT according to Holter monitoring, the patients were divided into 2 groups: “PVT” (n=17) and “Without PVT” (n=47). Based on the obtained data, a logistic regression equation with a binary response and a logit link function was constructed to predict the development of PVT.
Results. A logistic regression model has been elaborated, which includes the following indicators: patients’ gender, serum magnesium level, QT interval dispersion, and index of cardioelectrophysiological balance (QT/QRS). With a calculated threshold probability value of ≥0.599, the resultant model can identify patients at high risk of PVT development with drug-induced LQTS while taking class III antiarrhythmic drugs with a sensitivity of 88.24%, specificity of 90.00% and total accuracy of 89.55%.
Conclusions. The developed model will make it possible to predict the risk of ventricular arrhythmias in the sick with drug-induced LQTS, which will lead to a decrease in the number of cardiovascular complications and sudden cardiac death cases in this category of patients.
Keywords: class III antiarrhythmic drugs; drug-induced long QT syndrome; polymorphic ventricular tachycardia; magnesium; QT interval dispersion; logistic regression.
References
1. Nielsen JC, Lin Y-J, de Oliveira Figueiredo MJ, Shamloo AS, Alfie A, Boveda S, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus on risk assessment in cardiac arrhythmias: use the right tool for the right outcome, in the right population. J Arrhythm. 2020 Jun 15;36(4):553-607. doi: http://doi.org/10.1002/joa3.12338
2. Shliakhto EV, Arutiunov GP, Belenkov IuN, Boitcov SA. National guidelines for risk assessment and prevention of sudden cardiac death. 2nd ed. Moscow, RF: Medpraktika-M; 2018. 247 р. (In Russ.)
3. Kolotsey LV, Snezhitckii VA. Molecular genetic aspects of drug-induced long QT syndrome. Kardiologiya Belarusi. 2021;13(4):616-25. doi: http://doi.org/10.34883/PI.2021.13.4.010 (In Russ.)
4. Rohatgi RK, Sugrue A, Bos JM, Cannon BC, Asirvatham SJ, Moir C, et al. Contemporary outcomes in patients with Long QT Syndrome. J Am Coll Cardiol. 2017 Jul;70(4):453-462. doi: http://doi.org/10.1016/j.jacc.2017.05.046
5. Ostroumova OD, Goloborodova IV. Drug-Induced QT Prolongation: Prevalence, Risk Factors, Treatment and Prevention. Consilium Medicum. 2019;21(5):62-7. doi: http://doi.org/10.26442/20751753.2019.5.190415 (In Russ.)
6. Nakano Y, Shimizu W. Genetics of long-QT syndrome. J Hum Genet. 2016 Jan;61(1):51-5. doi: http://doi.org/10.1038/jhg.2015.74
7. Golovina GA, Zafiraki VK, Kosmacheva ED. Drug-induced long QT syndrome. Vestn Aritmologii. 2020;27(3):42-52. doi: http://doi.org/10.35336/VA-2020-3-42-52 (In Russ.)
8. Shenthar J, Rachaiah JM, Pillai V, Chakali SS, Balasubramanian V, Nanjappa MC. Incidence of drug-induced torsades de pointes with intravenous amiodarone. Indian Heart J. 2017 Nov-Dec;69(6):707-713. doi: http://doi.org/10.1016/j.ihj.2017.05.024 Epub 2017 Jun 3.
9. Poulsen CB, Damkjær M, Løfgren B, Schmidt M. Trends in Antiarrhythmic Drug Use in Denmark Over 19 Years. Am J Cardiol. 2020 Feb;125(4):562-9. doi: http://doi.org/10.1016/j.amjcard.2019.11.009
10. Molokhia M, Pathak A, Lapeyre-Mestre M, Caturla L, Montastruc JL, McKeigue P. Case ascertainment and estimated incidence of drug-induced long-QT syndrome: study in Southwest France. Br J Clin Pharmacol. 2008 Sep;66(3):386-95. doi: http://doi.org/10.1111/j.1365-2125.2008.03229.x
11. 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 Jan;16(1):101-8. doi: http://doi.org/10.1093/europace/eut214
12. Kopytckii AV. Information and Computing Technology Using the «R» Language in the Second Stage of Higher Education in Medical Universities. Vysh Shk. 2021;(3):18-22. (In Russ.)
13. Linde C, Bongiorni MG, Birgersdotter-Green U, Curtis AB, Deisenhofer I, Furokawa T, et al. Sex differences in cardiac arrhythmia: a consensus document of the European Heart Rhythm Association, endorsed by the Heart Rhythm Society and Asia Pacific Heart Rhythm Society. Europace. 2018 Oct;20(10):1565-1565ao. doi: http://doi.org/10.1093/europace/euy067
14. Darpo B, Karnad DR, Badilini F, Florian J, Garnett CE, Kothari S, et al. Are women more susceptible than men to drug-induced QT prolongation? Concentration-QTc modelling in a phase 1 study with oral rac-sotalol. Br J Clin Pharmacol. 2014 Mar;77(3):522-31. doi: http://doi.org/10.1111/bcp.12201
15. Straus SMJM, Kors JA, De Bruin ML, van der Hooft CS, Hofman A, Heeringa J, et al. Prolonged QTc interval and risk of sudden cardiac death in a population of older adults. Am Coll Cardiol. 2006 Jan;47(2):362-7. doi: http://doi.org/10.1016/j.jacc.2005.08.067
16. Friedman A, Miles J, Liebelt J, Christia P, Engstrom K, Thachil R, et al. QT Dispersion and Drug-Induced Torsade de Pointes. Cureus. 2021 Jan;13(1):e12895. doi: http://doi.org/10.7759/cureus.12895
17. Lu HR, Yan G-X, Gallacher DJ. A new biomarker-index of cardiac electrophysiological balance (iCEB) – plays an important role in drug-induced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs). J Pharmacol Toxicol Methods. 2013 Sep-Oct;68(2):250-259. doi: http://doi.org/10.1016/j.vascn.2013.01.003
18. Robyns T, Lu HR, Gallacher DJ, Garweg C, Ector J, Willems R, et al. Evaluation of Index of Cardio-Electrophysiological Balance (iCEB) as a New Biomarker for the Identification of Patients at Increased Arrhythmic Risk. Ann Noninvasive Electrocardiol. 2016 May;21(3):294-304. doi: http://doi.org/10.1111/anec.12309
19. Ardahanlı İ, Akhan O, Aslan R, Çelik M, Akyüz O. A new index in the follow-up of arrhythmia of Coronavirus Disease-2019 (COVID-19) patients receiving Hydroxychloroquine and Azithromycin therapy; index of cardiac electrophysiological balance. Cumhuriyet Med J. 2021;43(1):1-7. doi: http://doi.org/org/10.7197/cmj.870158
20. Tangvoraphonkchai K, Davenport A. Magnesium and Cardiovascular Disease. Adv Chronic Kidney Dis. 2018 May;25(3):251-260. doi: http://doi.org/10.1053/j.ackd.2018.02.010
21. Zhang X, Xia J, Del Gobbo LC, Hruby A, Dai Q, Song Y. Serum magnesium concentrations and all-cause, cardiovascular, and cancer mortality among U.S. adults: Results from the NHANES I Epidemiologic Follow-up Study. Clin Nutr. 2018 Oct;37(5):1541-1549. doi: http://doi.org/10.1016/j.clnu.2017.08.021
22. Hoshino K, Ogawa K, Hishitani T, Kitazawa R. Studies of magnesium in congenital long QT syndrome. Pediatr Cardiol. 2002 Jan-Feb;23(1):41-8. doi: http://doi.org/10.1007/s00246-001-0011-5
23. Kolotsey LV, Snezhitckii VA. Genetic variability of the nitric oxide synthesis system in the cardiomyocyte - a new predictor of the development of drug-induced long QT syndrome during antiarrhythmic therapy. Kardiologiya Belarusi. 2021;13(6):998-1009. doi: http://doi.org/10.34883/PI.2021.13.6.013 (In Russ.)
Information about authors:
L.V. Kalatsei – postgraduate of the Chair of Internal Diseases No. 1, Grodno State Medical University, https://orcid.org/0000-0001-5211-709X
E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Lyudmila V. Kalatsei;
V.A. Snezhitskiy – Doctor of Medical Sciences, corresponding member of the National Academy of Sciences of Belarus, professor of the Chair of Internal Diseases No. 1, Grodno State Medical University, https://orcid.org/0000-0002-1706-1243
A.V. Kapytski – senior lecturer of the Chair of Medical & Biological Physics, Grodno State Medical University,
https://orcid.org/0000-0002-1862-4300
