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

Area of Science:

• Cardiology
• Infectious Diseases
• Pharmacology

Background:

• Bedaquiline (BDQ) is a vital drug for multidrug-resistant tuberculosis (MDR-TB), particularly in India.
• Potential cardiotoxicity, specifically QTc prolongation, necessitates careful monitoring in patients receiving BDQ.
• Local data on BDQ-induced QTc prolongation in Indian patients is crucial due to genetic and environmental variability.

Purpose of the Study:

• To assess the prevalence, severity, and risk factors of Bedaquiline-related QTc prolongation in Indian patients with MDR/rifampicin-resistant (RR)-TB.
• To provide local evidence to guide safe Bedaquiline use in a high MDR-TB burden population.

Main Methods:

• A prospective analytical study involving 55 adult patients with RR/MDR-TB initiated on BDQ-containing regimens.
• Electrocardiograms (ECGs) were performed at baseline, 1, 3, and 6 months, with QTc intervals calculated using Fridericia's formula.
• Significant QTc prolongation was defined as QTcF ≥500 ms or a change from baseline of ≥60 ms.

Main Results:

• The overall prevalence of QTc prolongation was 37.25%, with 13.7% experiencing significant prolongation.
• Moderate to severe QTc prolongation was most common at the 3-month mark.
• Male gender and BMI >18.5 kg/m² were identified as significant risk factors; patients with significant QTc prolongation were under 60 years old.

Conclusions:

• QTc prolongation is common in MDR/RR-TB patients on BDQ, but severe cases requiring treatment modification are infrequent.
• BDQ remains critical for MDR-TB management, underscoring the need for diligent cardiac monitoring, especially during the initial three months.
• Further large-scale studies are recommended to validate findings and identify additional risk factors, considering the study's limitations such as sample size and co-administered medications.