QT prolongation and cardiac toxicity of new tuberculosis drugs in Europe: a Tuberculosis Network European Trialsgroup (TBnet) study. Issue 2 (16th August 2018)

• Record Type: Journal Article
• Authors: Guglielmetti, Lorenzo; Tiberi, Simon; Burman, Matthew; Kunst, Heinke; Wejse, Christian; Togonidze, Tamar; Bothamley, Graham; Lange, Christoph
• Other Names: author non-byline.; Hafizi Hasan author non-byline.; Kirakosyan Ohanna author non-byline.; Rumetshofer Rudolf author non-byline.; Skrahina Alena author non-byline.; Muylle Inge author non-byline.; Zutic Hasan author non-byline.; Markova Roumiana author non-byline.; Jankovic Mateja author non-byline.; Gyorfy Zsuzsanna author non-byline.; Georgios Georgiades author non-byline.; Andersen Åse Bengård author non-byline.; Ravn Pernille author non-byline.; Kolekar Shailesh author non-byline.; Danilovits Manfred author non-byline.; Vasankari Tuula author non-byline.; Fréchet-Jachym Mathilde author non-byline.; Kiria Nana author non-byline.; Avaliani Zaza author non-byline.; Wetzstein Nils author non-byline.; Avsar Korkut author non-byline.; Dimopoulos George author non-byline.; Horvath Ildiko author non-byline.; Kristjánsson Már author non-byline.; McLaughlin Anne Marie author non-byline.; Chiappini Elena author non-byline.; Confalonieri Marco author non-byline.; Del Bravo Paola author non-byline.; Gualano Gina author non-byline.; Motta Ilaria author non-byline.; Pontali Emanuele author non-byline.; Tunesi Simone author non-byline.; Kurhasani Xhevat author non-byline.; Kuksa Liga author non-byline.; Jacunskiene Laimute author non-byline.; Gil Wirtz author non-byline.; Nanovikj Zorica author non-byline.; Chesov Dumitru author non-byline.; Bojovic Olivera author non-byline.; De Lange Wiel author non-byline.; Magis-Escurra Cecile author non-byline.; Van Ingen Jakko author non-byline.; Jensenius Mogens author non-byline.; Kruczak Katarzyna author non-byline.; Duarte Raquel author non-byline.; Mihaescu Traian author non-byline.; Ibraim Elmira author non-byline.; Kaluzhenina Anna author non-byline.; Volchenkov Grigory author non-byline.; Pesut Dragica author non-byline.; Solovic Ivan author non-byline.; García-García José-María author non-byline.; Luque-Márquez Rafael author non-byline.; Sánchez-Montalvá Adrián author non-byline.; de Souza Galvao M. Luiza author non-byline.; Norrby Maria author non-byline.; Schoch Otto author non-byline.; Dudnyk Andrii author non-byline.; Belton Moerida author non-byline.; Dedicoat Martin author non-byline.;
• Is Part Of: European respiratory journal. Volume 52:Issue 2(2018)
• Publication Date: 2018-08-16
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.00537-2018
• Languages: English
• ISSNs: 0903-1936

Abstract

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