Therapy-induced cardiotoxicity in drug-resistant tuberculosis patients: A systematic review and meta-analysis

Background: Drug-resistant tuberculosis remains a major public health challenge with substantial associated morbidity and mortality. Management requires complex, individualized treatment regimens. Emerging evidence suggests that contemporary antituberculosis agents for drug-resistant disease carry significant cardiotoxicity risk. This study aims to evaluate the cardiovascular toxicity of current therapeutic regimens in patients with multidrug-resistant, pre-extensively drug-resistant, and extensively drug-resistant tuberculosis. Methods: This systematic review and meta-analysis was conducted following the  PRISMA guidelines. A comprehensive literature search was performed across five databases (PubMed, Cochrane Library, Scopus, ProQuest, and Springer) through May 5, 2024. Methodological quality was assessed using NHLBU study quality assessment tools for controlled intervention studies. Statistical analyses were conducted using a random-effects model with the DerSimonian-Laird method, with results reported as pooled estimates with 95% confidence intervals. Results : Eight studies comprising 9,506 patients with multidrug-resistant, pre-extensively drug-resistant, and extensively drug-resistant tuberculosis were included. Bedaquiline without delamanid was associated with the greatest QTc prolongation [pooled mean difference: 21.9 ms (95% CI: 10.24–33.62)] and highest prevalence of clinically significant QTc prolongation [21.2% (95% CI: 8.6–22.8%)]. Treatment discontinuation rates were similar for bedaquiline monotherapy and bedaquiline-delamanid combination therapy [8% (95% CI: 2–18%) vs. 8% (95% CI: 0–21%)]. Conclusion: Drug resistant tuberculosis treatments were associated with cardiotoxicity concerns, evidenced by its QT prolongation, clinically significant arrhythmia, and treatment discontinuation.