Iranian Heart Journal

Iranian Heart Journal

Evaluation of QTc-Interval Prolongation and Arrhythmogenic Indices and Associated Factors in Patients With COVID-19

Document Type : Original Article

Authors
Vahid Eslami 1
Mehrdad Jafari Fesharaki 1
Dorsa Shirini 1
Babak Gharaei 2
Laya Jalilian Khave 1
Taha Hassanzadeh 3
Saeed Abdi 4
Ali Pirsalehi 5
Ghazal Sanadgol 1
1 Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
2 Department of Anesthesia, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
3 Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
4 Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
5 Taleghani Hospital Research Development Committee, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran.
Abstract
Background: Patients with a prolonged corrected QT (QTc) interval are at risk of arrhythmias, including Torsade de pointes (TdP). This interval could be affected by demographic characteristics, ischemia, and most importantly drugs. Furthermore, hospitalized patients tend to experience arrhythmias, accompanied by electrolyte abnormalities and the inflammatory status of diseases.
 
Methods: The present retrospective study recruited 135 patients with COVID-19. We observed the QTc interval on the third post-administration day and laboratory findings for possible risk factors for QTc-interval prolongation.
 
Results: Ischemic heart disease was markedly more common among patients with prolonged and severely prolonged QTc intervals. Laboratory findings showed a significantly higher neutrophil-to-lymphocyte ratio (NLR) in patients with prolonged or severely prolonged QTc intervals compared with those with normal QTc intervals and QTc intervals exceeding 500 milliseconds (P<0.001) on admission and the third day. Ribavirin caused the most elevation in the QTc interval after 3 days of hospitalization compared with other drugs. Forty percent of the patients who took ribavirin experienced a QTc interval exceeding 500 milliseconds, which was significant compared with other therapeutic regimens.
 
Conclusions: In addition to the well-known predisposing factors for the prolongation of QTc interval, we suggest focusing on the history of ischemic heart disease and inflammatory status (eg, by NLR) in patients with COVID-19 before making decisions to commence drugs that greatly affect QTc intervals. Further studies are required to shed light on the cardiac side effects of medications applied for COVID-19, particularly ribavirin. (Iranian Heart Journal 2022; 23(3): 77-87)
Keywords
COVID-19
Torsade de pointes
Arrhythmia
Electrocardiogram
Prolonged QTc
  1. Monzani A, Genoni G, Scopinaro A, Pistis G, Kozel D, Secco QTc evaluation in COVID-19 patients treated with chloroquine/hydroxychloroquine. Eur J Clin Invest. 2020; 50(6):e13258. doi:10.1111/eci.13258
  2. Lazzerini PE, Capecchi PL, Laghi-Pasini F. Long QT syndrome: an emerging role for inflammation and immunity. Front Cardiovasc Med. 2015; 2:26
  3. Lazzerini PE, Capecchi PL, Laghi-Pasini F. Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis. Eur Heart J. 2017; 38(22):1717–27.
  4. Goldberger AL, Goldberger ZD, Shvilkin A. Clinical Electrocardiography: ASimplified Approach,Expert Consult: Online and Print, 8: ClinicalElectrocardiography: A Simplified Approach: Elsevier/Saunders; 2012.
  5. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395:507-13.
  6. Warren-Gash C, Blackburn R, Whitaker H, McMenamin J,Hayward AC. Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlledcase series analysis of national linked datasets from Scotland. EurRespir J. 2018; 51(3):1701794.
  7. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3):269-271. doi:10.1038/s41422-020-0282-0
  8. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial [published online ahead of print, 2020 Mar 20]. Int J Antimicrob Agents. 2020; 105949. doi:10.1016/j.ijantimicag.2020.105949
  9. Khalili JS, Zhu H, Mak NSA, Yan Y, Zhu Y. Novel coronavirus treatment with ribavirin: Groundwork for an evaluation concerning COVID-19. J Med Virol. 2020; 92(7):740-746. doi:10.1002/jmv.25798
  10. Choi Y, Lim HS, Chung D, Choi JG, Yoon D. Risk Evaluation of Azithromycin-Induced QT Prolongation in Real-World Practice. Biomed Res Int. 2018; 2018:1574806. Published 2018 Oct 14. doi:10.1155/2018/1574806
  11. Stas P, Faes D, Noyens P. Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine. Int J Cardiol. 2008; 127(2):e80-e82. doi:10.1016/j.ijcard.2007.04.055
  12. Saleh M, Gabriels J, Chang D, et al. Effect of Chloroquine, Hydroxychloroquine, and Azithromycin on the Corrected QT Interval in Patients With SARS-CoV-2 Infection. Circ Arrhythm Electrophysiol. 2020; 13(6):e008662. doi:10.1161/CIRCEP.120.008662
  13. Gibbs C, Thalamus J, Kristoffersen DT, et al. QT prolongation predicts short-term mortality independent of comorbidity. Europace. 2019; 21(8):1254-1260. doi:10.1093/europace/euz058
  14. Yu WL, Toh HS, Liao CT, Chang WT. A Double-Edged Sword-Cardiovascular Concerns of Potential Anti-COVID-19 Drugs. Cardiovascular Drugs and Therapy. 2020 Jun. DOI: 10.1007/s10557-020-07024-7
  15. Kochi, Adriano Nunes, et al. "Cardiac and arrhythmic complications in patients with COVID‐19." Journal of Cardiovascular Electrophysiology 31.5 (2020): 1003-1008.
  16. Szekely, Yishay, et al. "Chloroquine-induced torsade de pointes in a COVID-19 patient." Heart Rhythm (2020).
  17. Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020; 7(1):4.
  18. Product Information. Copegus (ribavirin)." Roche Laboratories, Nutley, NJ.
  19. Charbit, Beny, et al. "Relationship between HIV protease inhibitors and QTc interval duration in HIV‐infected patients: a cross‐sectional study." British journal of clinical pharmacology 67.1 (2009): 76-82.
  20. Chen YW, Yiu CB, Wong KY. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000Res. 2020; 9: –129.
  21. Schrezenmeier E, Dorner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020; 16(3):155–66.
  22. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005; 2:69.
  23. Capel RA, Herring N, Kalla M, Yavari A, Mirams GR, Douglas G, et al. Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential. Heart Rhythm. 2015; 12(10):2186–94.
  24. Liu, Yuwei, et al. "Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19." Journal of Infection (2020).
  25. Azab, Basem, et al. "Usefulness of neutrophil to lymphocyte ratio in predicting short-and long-term mortality after non–ST-elevation myocardial infarction." The American journal of cardiology 106.4 (2010): 470-476.
  26. Feng, Xudong, et al. "Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis." Frontiers in Medicine 7 (2020): 301.
  27. Numaguchi H, Johnson JP, Jr., Petersen CI, Balser JR. A sensitive mechanism for cation modulation of potassium current. Nature Neuroscience. 2000; 3(5):429–430.
  28. Tisdale, J. E., et al. "Development and validation of a risk score to predict QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes. 2013; 6: 479–87."
  29. Valera-Roman A, Gonzalez-Juanatey JR, Basante P, et al. Clinical characteristics and prognosis of hospitalised inpatients with heart failure and preserved or reduced left ventricular ejection fraction. Heart 2002; 88: 249–254.
  30. Li, Zhi-Dan, et al. "Association between ventricular repolarization variables and cardiac diastolic function: A cross-sectional study of a healthy Chinese population." World journal of clinical cases 7.8 (2019): 940.
Iranian Heart Journal
Volume 23, Issue 3
Summer 2022
Pages 77-87