Risk factors for cardiotoxic adverse reactions in the treatment of tuberculosis patients with MDR and XDR of the pathogen

Modern treatment regimens for tuberculosis with multiple and broad drug resistance (MDR/XDR) of the pathogen provide for the simultaneous administration of several drugs with a proven cardiotoxic effect in the form of prolongation of the QTc interval and provocation of life-threatening arrhythmias. In conditions of the spread of cardiovascular and other comorbid pathology, it is important to assess the risk of cardiotoxic reactions and ensure the safety of patients during the entire course of treatment. The aim of the study was to assess the degree and risk of prolongation of the QTc interval in tuberculosis patients with MDR/XDR pathogen, including concomitant cardiological pathology, against the background of treatment regimens with the inclusion of bedaquiline.

Materials and methods of research. The retrospective study included 185 tuberculosis patients with MDR/XDR of the causative agent: 70 people with cardiovascular pathology (except decompensation of heart failure, bradyarrhythmias, ventricular arrhythmias and QTc prolongation in the anamnesis) and 115 people. without it, who received chemotherapy with the inclusion of bedaquiline and fluoroquinolones. The dynamics of clinical symptoms and ECG were evaluated against the background of treatment. Risk factors for cardiotoxic reactions were determined using the method of multiple logistic regression.

The results of the study. Prolongation of the QTc interval was observed in 58 people (31.4%, 95% CI 25.1–38.4%), clinically significant (more than 500 ms, 60 ms or more from the baseline, with ventricular arrhythmia) – 4.3%; bradycardia – 3.8%, cardialgic syndrome – 8.1%. Risk factors for prolongation of the QTc interval were the presence of any cardiovascular disease (OR 2.33, 95% CI 1.23-4.41), simultaneous administration of three or more drugs that can lead to QTc prolongation (OR = 3.31, 95% CI 1.73–6.32), clarithromycin administration (OR = 4.01, 95%CI 1.4710.97), the number of points on the Tisdale scale is more than 6 (OR = 3.42, 95% CI 1.78–6.62).

Conclusion. Prolongation of the QTc interval is a common adverse reaction in the treatment of tuberculosis with MDR /XDR pathogen, clinically significant in 4.3% of cases. The use of a standard ECG monitoring scheme is justified; it is necessary to avoid prescribing three or more drugs that affect the QTc interval to patients with any cardiovascular pathology with a Tisdale score of more than 6 points.

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