QT prolongation and cardiac toxicity of new tuberculosis drugs in Europe: A Tuberculosis Network European Trialsgroup (TBnet) study

Extract

There is concern that many second line drugs used to treat multidrug-resistant (MDR)- tuberculosis (TB) may cause fatal arrhythmias linked to QT interval prolongation. The QT interval, measured on an electrocardiogram (ECG), represents the duration of the ventricular electrical systole. In order to have a more reproducible value across time and heart rates, the QT interval is adjusted according to heart rate (QTc). Fluoroquinolones and, possibly, clofazimine can prolong the QTc^1,2, as do bedaquiline and delamanid^3,4. A QTc >500 ms is considered a risk factor for ventricular arrhythmias, such as torsades de pointes (TdP)⁵. Overall, 10–20% of patients with drug-induced TdP have genetic predisposition, and >70% have at least two other risk factors, like older age, female sex, and electrolyte disturbances⁶. In smaller cohorts, no cases of fatal arrhythmia have been reported in association with new TB drugs; deaths in bedaquiline/delamanid registration trials were not linked to prolonged QTc nor arrhythmias.^3,4,7 The objective of the study was to evaluate the clinical impact of QTc prolongation and the number of cardiac events in patients receiving bedaquiline/delamanid for MDR-TB treatment in TBnet treatment centres within the World Health Organization (WHO) Europe region.