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 tuberculosis (MDR-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 (as QTc). Fluoroquinolones and, possibly, clofazimine can prolong the QTc interval [1, 2], as do bedaquiline (Bdq) and delamanid (Dlm) [3, 4]. A QTc interval >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 a genetic predisposition and more than 70% have at least two other risk factors, like older age, female sex and electrolyte disturbances [6]. In smaller cohorts, no cases of fatal arrhythmia have been reported in association with new tuberculosis (TB) drugs and deaths in Bdq/Dlm 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 Bdq/Dlm treatment for MDR-TB in treatment centres of the Tuberculosis Network European Trialsgroup (TBnet), a clinical research collaboration of the European Respiratory Society, within the World Health Organization (WHO) Europe region. Few cardiac arrhythmias and no fatalities were observed in MDR-TB patients treated with bedaquiline and delamanid <http://ow.ly/2tC030koXJa> Additional members of the TBNET QTc survey collaboration: Hasan Hafizi (Albania), Ohanna Kirakosyan (Armenia), Rudolf Rumetshofer (Austria), Alena Skrahina (Belarus), Inge Muylle (Belgium), Hasan Zutic (Bosnia and Herzegovina), Roumiana Markova (Bulgaria), Mateja Jankovic (Croatia), Zsuzsanna Gyorfy (Czech Republic), Georgiades Georgios (Cyprus), Åse Bengård Andersen, Pernille Ravn and Shailesh Kolekar (Denmark), Manfred Danilovits (Estonia), Tuula Vasankari (Finland), Mathilde Fréchet-Jachym (France), Nana Kiria and Zaza Avaliani (Georgia), Nils Wetzstein and Korkut Avsar (Germany), George Dimopoulos (Greece), Ildiko Horvath (Hungary), Már Kristjánsson (Iceland), Anne Marie McLaughlin (Ireland), Elena Chiappini, Marco Confalonieri, Paola Del Bravo, Gina Gualano, Ilaria Motta, Emanuele Pontali and Simone Tunesi (Italy), Xhevat Kurhasani (Kosovo), Liga Kuksa (Latvia), Laimute Jacunskiene (Lithuania), Wirtz Gil (Luxembourg), Zorica Nanovikj (Macedonia), Dumitru Chesov (Moldova), Olivera Bojovic (Montenegro), Wiel De Lange, Cecile Magis-Escurra and Jakko Van Ingen (Netherlands), Mogens Jensenius (Norway), Katarzyna Kruczak (Poland), Raquel Duarte (Portugal), Traian Mihaescu and Elmira Ibraim (Romania), Anna Kaluzhenina and Grigory Volchenkov (Russian Federation), Dragica Pesut (Serbia), Ivan Solovic (Slovakia), José-María García-García, Rafael Luque-Márquez, Adrián Sánchez-Montalvá and M. Luiza de Souza Galvao (Spain), Maria Norrby (Sweden), Otto Schoch (Switzerland), Andrii Dudnyk (Ukraine), Moerida Belton and Martin Dedicoat (UK).