Abstract
We carried out a cohort retrospective-prospective study in order to evaluate the impact of pathogenetic therapy of cardiovascular disorders (CVD) on bedaquiline (Bq) containing TB treatment in older children and adolescents with multi or extensively drug resistant (MDR/XDR) pulmonary TB. The study included 51 patients aged 13–17 years with pulmonary TB and established MDR/pre-XDR/XDR hospitalized in 2014–2023. The prospective study included 35 patients (main group), and the retrospective study included 16 patients (control group). The main group was administered correction of CVD due to QTc interval prolongation without Bq withdrawal; in the control group Bq was withdrawn (according to the current clinical recommendations). We established conduction disturbances in the form of QTc interval prolongation in both main and control groups, 45.7 and 18.7% respectively. In the control group QTc interval prolongation, which required Bq withdrawal, was observed in 3 out of 16 cases. The analysis of proarrhythmogenic factors and comprehensive ECG monitoring in the main group established functional nature of the changes (slow QTc interval adaptation to heart rate changes) in 16 out of 35 cases. Due to pathogenetic therapy (replacement, metabolic therapy, use of β-adrenoblockers) aimed to mitigate the impact of proarrhythmogenic factors we managed to neutralize signs of electrical instability of the heart and continue Bq containing treatment. The comparison of the frequency of Bq withdrawal between the groups associated with correction due to CVD established a significant correlation between the studied risk factor and the outcome (withdrawal of Bq) (χ2 = 3.997; p < 0.05). Thus, our study demonstrated that timely target correction of modifiable risk factors reduced the probability of drug-induced arrhythmia and allowed safe administration of TB drugs with potential cardiotoxic effect.
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