New math could prevent heart damage in tuberculosis drug treatments
Researchers have developed a dynamic formula to safely monitor heart health in drug-resistant TB patients, whose elevated heart rates during illness interfere with standard cardiac tests. The breakthrough could help doctors better detect dangerous side effects from powerful TB medications without prematurely halting life-saving treatment.
Originaltitel: Development and validation of a time-varying correction factor for QT interval assessment in drug-resistant tuberculosis patients
<p>Background: Tachycardia associated with active tuberculosis (TB) often diminishes when patients recover from TB. Elevated heart rate (HR) may lead to suboptimal correction, complicating the assessment of QT prolongation when using standard correction factors (CFs), such as Fridericia's formula (QTcF). Olliaro has proposed a CF for QT interval correction in pretreatment TB patients. However, the QT-HR correlation changes as HR decreases during treatment, indicating the need for time-varying correction.</p><p>Methods: We developed an HR model to capture the HR normalisation during successful treatment. Subsequently, a time-varying CF was constructed using the estimated HR change rate. The performance of CFs to make corrected QT (QTc) independent from HR was evaluated by linear regression analyses of QTc versus HR within defined time bins.</p><p>Results: The final HR model included asymptotic change in HR attributed to time on treatment, circadian rhythm cycles, M2 (bedaquiline-metabolite) concentration, and patient covariates. The time-varying CF decreased from 0.4081 to 0.33, with a half-life of 7.74 weeks. The slope (QTc/HR vs. Time) derived from the time-varying correction was not significantly different from 0 (95% CI -0.003 to 0.002), and the intercept was not significantly different from 0 (95% CI -0.089 to 0.006), demonstrating successful QT correction from pretreatment to the end of treatment.</p><p>Conclusion: The time-varying CF effectively captures the dynamic QT-HR relationship during TB treatment, reducing the risk of misdiagnosing QT prolongation or unnecessary discontinuation of treatment. By addressing underestimation and overestimation issues in QT interval assessment, this method enhances drug evaluation in clinical trials and supports improved treatment decisions for TB patients. (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )</p>