Factors influencing QT interval prolongation during rifampicin-resistant tuberculosis treatment: a multicenter real-world study from China

BACKGROUND: We sought to assess the factors influencing QTc interval prolongation in patients with multidrug- or rifampicin-resistant tuberculosis. METHODS: We conducted a retrospective cohort study of admissions with multidrug-resistant or rifampicin-resistant tuberculosis as the primary diagnosis from nine regions in China between May 2018 and June 2020. Guided by directed acyclic graphs, we developed two multivariable logistic regression models to account for identified confounders and examine their impact on outcomes across different aspects. Results were represented as odds ratios with 95% confidence intervals. Statistical analysis was performed using RStudio. RESULTS: Among the 1,421 patients included in the study, 1,293 (91.0%) had normal QTc intervals, while 128 (9.0%) exhibited prolonged QTc intervals. In treatment regimens-based adjusted models, treatment regimens containing bedaquiline and/or linezolid, baseline QTc prolongation (≥ 450 ms), hypertension, and pre-treatment anemia were significantly associated with an increased risk of QTc interval prolongation. Comorbidity-based adjusted models showed that baseline QTc interval prolongation, hypertension, pre-treatment anemia, and adverse events during treatment including gastrointestinal reactions, liver and kidney injury, and electrolyte imbalances were strongly correlated with QTc interval prolongation. CONCLUSIONS: Our study demonstrates that baseline QTc prolongation, hypertension and choice of treatment regimens significantly increase the risk of QTc interval prolongation in patients with multidrug- and rifampicin-resistant tuberculosis. Additionally, adverse events during treatment further elevate this risk and require careful monitoring.