PREDIKTOR INDEPENDEN PERPANJANGAN INTERVAL QTc PADA PASIEN TUBERKULOSIS RESISTAN OBAT (TB-RO)

Authors

DOI:

https://doi.org/10.36387/jiis.v11i1.3002

Keywords:

Diabetes mellitus, Electrocardiography, Risk factors, QTc interval prolongation, Drug-resistant tuberculosis, Older adults

Abstract

Drug-resistant tuberculosis (DR-TB) remains a global health challenge with suboptimal treatment success rates. Long-term treatment regimens in DR-TB patients may lead to cardiotoxic adverse effects, including QTc interval prolongation, which increases the risk of fatal arrhythmias such as torsades de pointes. This study aimed to analyze the independent predictors of QTc interval prolongation in patients with DR-TB receiving long-term treatment regimens. A retrospective cohort study was conducted at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia, from January 2021 to December 2023. A total of 100 eligible DR-TB patients were included. QTc prolongation was defined as ≥ 450 ms in males and ≥ 470 ms in females using Bazett’s or Fridericia’s correction. Bivariate analysis was performed using the Mann–Whitney test and chi-square or Fisher’s exact. Multivariate logistic regression analysis was subsequently conducted to identify independent predictors of QTc interval prolongation. The results showed that 60% of patients experienced QTc interval prolongation. Multivariate analysis revealed that age ≥ 60 years (adjusted OR 6.94; 95% CI 1.34–35.98; p = 0.021) and diabetes mellitus (adjusted OR 8.76; 95% CI 2.99–25.68; p < 0.001) were independent predictors of QTc interval prolongation in patients with DR-TB receiving long-term treatment regimens. Diabetes mellitus was identified as the strongest independent risk factor in this study. These findings highlight the importance of cardiometabolic risk stratification and more intensive electrocardiography (ECG) monitoring in patients with these risk factors to improve treatment safety.

References

Aburisheh, K., AlKheraiji, M. F., Alwalan, S. I., Isnani, A. C., Rafiullah, M., Mujammami, M., & Alfadda, A. A. (2023). Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes. BMC Endocrine Disorders, 23(1), 50. https://doi.org/10.1186/s12902-022-01235-9

Baracaldo-Santamaría, D., Llinás-Caballero, K., Corso-Ramirez, J. M., Restrepo, C. M., Dominguez-Dominguez, C. A., Fonseca-Mendoza, D. J., & Calderon-Ospina, C. A. (2021). Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation. International Journal of Molecular Sciences, 22(15), 8090. https://doi.org/10.3390/ijms22158090

Cherub, J. (2020). Tinjauan atas Angiotensin Receptor Blocker Generasi Baru. Cdk-289, 47(8), 715–718. https://doi.org/10.55175/cdk.v47i8.583

Conradie, F., Bagdasaryan, T. R., Borisov, S., Howell, P., Mikiashvili, L., Ngubane, N., Samoilova, A., Skornykova, S., Tudor, E., Variava, E., Yablonskiy, P., Everitt, D., Wills, G. H., Sun, E., Olugbosi, M., Egizi, E., Li, M., Holsta, A., Timm, J., … Spigelman, M. (2022). Bedaquiline–Pretomanid–Linezolid Regimens for Drug-Resistant Tuberculosis. New England Journal of Medicine, 387(9), 810–823. https://doi.org/10.1056/NEJMoa2119430

Conradie, F., Diacon, A. H., Ngubane, N., Howell, P., Everitt, D., Crook, A. M., Mendel, C. M., Egizi, E., Moreira, J., Timm, J., McHugh, T. D., Wills, G. H., Bateson, A., Hunt, R., Van Niekerk, C., Li, M., Olugbosi, M., & Spigelman, M. (2020). Treatment of Highly Drug-Resistant Pulmonary Tuberculosis. New England Journal of Medicine, 382(10), 893–902. https://doi.org/10.1056/NEJMoa1901814

El-Sharkawy, A. M., Sahota, O., Maughan, R. J., & Lobo, D. N. (2014). The pathophysiology of fluid and electrolyte balance in the older adult surgical patient. Clinical Nutrition, 33(1), 6–13. https://doi.org/10.1016/j.clnu.2013.11.010

Gibbs, C., Thalamus, J., Kristoffersen, D. T., Svendsen, M. V., Holla, Ø. L., Heldal, K., Haugaa, K. H., & Hysing, J. (2019). QT prolongation predicts short-term mortality independent of comorbidity. EP Europace, 21(8), 1254–1260. https://doi.org/10.1093/europace/euz058

Giudicessi, J. R., Wilde, A. A. M., & Ackerman, M. J. (2018). The genetic architecture of long QT syndrome: A critical reappraisal. Trends in Cardiovascular Medicine, 28(7), 453–464. https://doi.org/10.1016/j.tcm.2018.03.003

Guo, X., Li, Z., Zhou, Y., Yu, S., Yang, H., Sun, G., Zheng, L., Lee, B. K., Pletcher, M. J., & Sun, Y. (2021). Corrected QT Interval Is Associated With Stroke but Not Coronary Heart Disease: Insights From a General Chinese Population. Frontiers in Cardiovascular Medicine, 8, 605774. https://doi.org/10.3389/fcvm.2021.605774

Gupta, A., Kumar, V., Natarajan, S., & Singla, R. (2020). Adverse drug reactions & drug interactions in MDR-TB patients. The Indian Journal of Tuberculosis, 67(4S), S69–S78. https://doi.org/10.1016/j.ijtb.2020.09.027

Heemskerk, C. P. M., Pereboom, M., van Stralen, K., Berger, F. A., van den Bemt, P. M. L. A., Kuijper, A. F. M., van der Hoeven, R. T. M., Mantel-Teeuwisse, A. K., & Becker, M. L. (2018). Risk factors for QTc interval prolongation. European Journal of Clinical Pharmacology, 74(2), 183–191. https://doi.org/10.1007/s00228-017-2381-5

Hu, M., Zheng, C., & Gao, F. (2016). Use of bedaquiline and delamanid in diabetes patients: clinical and pharmacological considerations. Drug Design, Development and Therapy, 10, 3983–3994. https://doi.org/10.2147/DDDT.S121630

Kementerian Kesehatan Republik Indonesia. (2023). Buku Pegangan Operasional Pengobatan Tuberkulosis Resistan Obat dengan Panduan BPaL/M. In Kementerian Kesehatan RI. https://repository.kemkes.go.id/book/884

Li, X., Ren, H., Xu, Z., Liu, Y., Yang, X., & Liu, J. (2012). Prevalence and risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes. Experimental Diabetes Research, 2012, 234084. https://doi.org/10.1155/2012/234084

Lin, N., Zhang, H., Li, X., Niu, Y., Gu, H., Lu, S., Yang, Z., Su, Q., & Qin, L. (2023). The influence of different glucose tolerance on QTc interval: a population-based study. BMC Cardiovascular Disorders, 23(1), 47. https://doi.org/10.1186/s12872-023-03081-6

Liu, P., Han, D., Sun, X., Tan, H., Wang, Z., Liu, C., Zhang, Y., Li, B., Sun, C., Shi, R., & Li, G. (2019). Prevalence and risk factors of acquired long QT syndrome in hospitalized patients with chronic kidney disease. Journal of Investigative Medicine, 67(2), 289–294. https://doi.org/10.1136/jim-2018-000798

Ma, Q., Li, Z., Guo, X., Guo, L., Yu, S., Yang, H., Zou, L., Zheng, L., Pan, G., Zhang, Y., & Sun, Y. (2019). Prevalence and risk factors of prolonged corrected QT interval in general Chinese population. BMC Cardiovascular Disorders, 19(1), 276. https://doi.org/10.1186/s12872-019-1244-7

Monedero-Recuero, I., Hernando-Marrupe, L., Sánchez-Montalvá, A., Cox, V., Tommasi, M., Furin, J., Chiang, C.-Y., Quelapio, M., Koura, K. G., Trébucq, A., Padanilam, X., Dravniece, G., & Piubello, A. (2018). QTc and anti-tuberculosis drugs: a perfect storm or a tempest in a teacup? Review of evidence and a risk assessment. The International Journal of Tuberculosis and Lung Disease, 22(12), 1411–1421. https://doi.org/10.5588/ijtld.18.0423

Munir, M. K., Saeed, M. S., Haider, S. Z., & Shamim, S. (2024). Comparison of short term and long term multidrug resistant tuberculosis treatment outcomes in tertiary care settings. Journal of King Saud University - Science, 36(4), 103133. https://doi.org/10.1016/j.jksus.2024.103133

Pasquier, M., Pantet, O., Hugli, O., Pruvot, E., Buclin, T., Waeber, G., & Aujesky, D. (2012). Prevalence and determinants of QT interval prolongation in medical inpatients. Internal Medicine Journal, 42(8), 933–940. https://doi.org/10.1111/j.1445-5994.2011.02447.x

Piccaro, G., Poce, G., Biava, M., Giannoni, F., & Fattorini, L. (2015). Activity of lipophilic and hydrophilic drugs against dormant and replicating Mycobacterium tuberculosis. The Journal of Antibiotics, 68(11), 711–714. https://doi.org/10.1038/ja.2015.52

Pickham, D., Flowers, E., & Drew, B. J. (2014). Hyperglycemia Is Associated With Corrected QT Prolongation and Mortality in Acutely Ill Patients. Journal of Cardiovascular Nursing, 29(3), 264–270. https://doi.org/10.1097/JCN.0b013e31827f174c

Pontali, E., Sotgiu, G., Tiberi, S., D’Ambrosio, L., Centis, R., & Migliori, G. B. (2017). Cardiac safety of bedaquiline: a systematic and critical analysis of the evidence. European Respiratory Journal, 50(5), 1701462. https://doi.org/10.1183/13993003.01462-2017

Rabkin, S. W. (2015). Impact of Age and Sex on QT Prolongation in Patients Receiving Psychotropics. The Canadian Journal of Psychiatry, 60(5), 206–214. https://doi.org/10.1177/070674371506000502

Rabkin, S. W., Cheng, X.-B. J., & Thompson, D. J. S. (2016). Detailed analysis of the impact of age on the QT interval. Journal of Geriatric Cardiology : JGC, 13(9), 740–748. https://doi.org/10.11909/j.issn.1671-5411.2016.09.013

Rautaharju, P. M., Surawicz, B., & Gettes, L. S. (2009). AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram. Journal of the American College of Cardiology, 53(11), 982–991. https://doi.org/10.1016/j.jacc.2008.12.014

Rossi, M., Marzi, F., Natale, M., Porceddu, A., Tuccori, M., Lazzerini, P. E., Laghi-Pasini, F., & Capecchi, P. L. (2021). Drug-Associated QTc Prolongation in Geriatric Hospitalized Patients: A Cross-Sectional Study in Internal Medicine. Drugs - Real World Outcomes, 8(3), 325–335. https://doi.org/10.1007/s40801-021-00234-x

Sandy, F. F., & Destiani, D. P. (2019). Review: Efek Merugikan Obat Antihipertensi Terhadap Perpanjangan Interval QT. Farmaka, 17(2), 390–398. https://doi.org/10.24198/jf.v17i2.23135

Sarkar, S., Srivastava, V., & Mohanty, M. (2017). Comparative assessment of effects of calcium channel antagonists, amlodipine, and cilnidipine, on QT interval in hypertensive patients - An observational study. National Journal of Physiology, Pharmacy and Pharmacology, 8(4), 1. https://doi.org/10.5455/njppp.2017.7.0937418112017

Schächtele, S., Tümena, T., Gaßmann, K.-G., Fromm, M. F., & Maas, R. (2016). Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients. PLOS ONE, 11(5), e0155649. https://doi.org/10.1371/journal.pone.0155649

Setiawan, E., Royland Marpaung, F., Sukandar, E., Lily Lukas, D., Wijono, H., Warindra, T., Kurniawan, R., Wibowo, T., Hendradi, W., Osbert Costa, M., Abdul-Aziz, M.-H., & Roberts, J. (2019). Kajian Narrative terhadap Profil Farmakokinetik Antibiotik pada Pasien Kritis: Implikasi terhadap Ketercapaian Target Farmakokinetik-Farmakodinamik. Pharmaceutical Sciences and Research, 6(1), 1–12. https://doi.org/10.7454/psr.v6i1.4274

Sherif, K. A., Abo‐Salem, E., Panikkath, R., Nusrat, M., & Tuncel, M. (2014). Cardiac Repolarization Abnormalities Among Patients With Various Stages of Chronic Kidney Disease. Clinical Cardiology, 37(7), 417–421. https://doi.org/10.1002/clc.22277

Triplitt, C. (2006). Drug Interactions of Medications Commonly Used in Diabetes. Diabetes Spectrum, 19(4), 202–211. https://doi.org/10.2337/diaspect.19.4.202

Vandael, E., Vandenberk, B., Vandenberghe, J., Willems, R., & Foulon, V. (2016). Risk factors for QTc-prolongation : systematic review of the evidence. International Journal of Clinical Pharmacy, 39(1), 16–25. https://doi.org/10.1007/s11096-016-0414-2

World Health Organization. (2023). Global Tuberculosis Report 2023. In World Health Organization. https://iris.who.int/handle/10665/373828

Published

2026-03-31

How to Cite

PREDIKTOR INDEPENDEN PERPANJANGAN INTERVAL QTc PADA PASIEN TUBERKULOSIS RESISTAN OBAT (TB-RO). (2026). JIIS (Jurnal Ilmiah Ibnu Sina): Ilmu Farmasi Dan Kesehatan, 11(1), 20-35. https://doi.org/10.36387/jiis.v11i1.3002

Similar Articles

1-10 of 243

You may also start an advanced similarity search for this article.