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

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 QTc1,2, as do bedaquiline and delamanid3,4. A QTc u003e500 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 u003e70% 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.Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Guglielmetti has nothing to disclose.Conflict of interest: Dr. Tiberi has nothing to disclose.Conflict of interest: Dr. Burman has nothing to disclose.Conflict of interest: Dr. Kunst has nothing to disclose.Conflict of interest: Dr. Wejse has nothing to disclose.Conflict of interest: Dr. Togonidze has nothing to disclose.Conflict of interest: Prof. Dr. Bothamley has nothing to disclose.Conflict of interest: Dr. Lange reports personal fees from Chiesi, personal fees from Gilead, personal fees from Abbvie, personal fees from MSD, personal fees from Becton Dickinson, personal fees from Janssen, personal fees from Lucane, personal fees from Novartis, personal fees from Thermofisher, outside the submitted work.