Bedaquiline-related QTc Prolongation in Multidrug Resistant Tuberculosis Patients: A Prospective Study

Bedaquiline (BDQ) has revolutionized multidrug-resistant tuberculosis (MDR-TB) management in the Indian population with a high MDR-TB burden. However, its potential cardiotoxicity in the form of QTc prolongation warrants careful monitoring. This study aims to evaluate the prevalence, severity, and risk factors of BDQ-related QTc prolongation in MDR/rifampicin-resistant (RR)-TB patients. Given the genetic variability and diverse environmental factors, extrapolating foreign data to Indian patients is challenging; thus, local evidence is crucial.

A prospective analytical study was conducted over a period of 18 months on 55 adult patients with RR or MDR pulmonary or extrapulmonary TB initiated on BDQ-containing regimens. Electrocardiograms (ECGs) were performed at baseline, 1, 3, and 6 months. QTc intervals were calculated using Fridericia's formula at each time interval. Prevalence and severity of QTc prolongation were documented. Significant prolongation, defined as an absolute QTcF value ≥500 ms or a change from baseline of ≥60 ms, was also noted.

The overall prevalence of QTc prolongation was 37.25%, with 13.7% of patients experiencing significant prolongation. The highest proportion of moderate to severe cases occurred at 3 months. Male gender and body mass index (BMI) >18.5 kg/m² were identified as statistically significant risk factors. All patients with significant QTc prolongation were under 60 years old, contrasting with prior research. Temporary withdrawal of BDQ was required in 1.96% of patients due to severe QTc prolongation, but no serious cardiac events were observed, consistent with previous studies.

This prospective study highlights that while QTc prolongation is a frequent occurrence in MDR/RR-TB patients receiving BDQ, severe cases necessitating treatment modification remain uncommon. These findings reaffirm the critical role of BDQ in MDR-TB management while emphasizing the necessity of stringent cardiac monitoring, particularly during the initial 3 months of therapy.

The study's small sample size and concomitant use of other QTc-prolonging medications may have influenced the results. Further large-scale studies are needed to confirm these findings and explore additional risk factors.