title: Electrophysiological Adverse Effects of Direct Acting Antivirals in Patients With Chronic Hepatitis C.
abstract: Recently, several cases of symptomatic, sometimes fatal bradycardia during the first days of direct-acting antiviral (DAA) (eg, sofosbuvir [SOF]) administration have been reported. We analyzed in detail electrocardiographic (ECG) changes during SOF- or non-SOF-based chronic hepatitis C (CHC) treatment, specifically focusing on bradyarrhythmias. All 39 consecutive patients treated at our center with any interferon-free regimen between June and December 2015 were included in this study (26 SOF-based therapy vs 13 no-SOF interferon-free regimens). ECG tracings were obtained from all patients the first day of treatment and after 7, 14, and 28 days. ECG parameters (P-wave, QRS, QT interval, JT interval, Tapex-Tendinterval duration) were compared between the 2 groups at baseline and at the 3 different time points during antiviral therapy. There were no cases of symptomatic bradycardia/syncope. In the SOF group, QTc duration rose after 1 week (from 424.3 to 431.2 milliseconds; P = .013) and returned to baseline during therapy. QT dispersion dropped since week 1 (from 85.6 to 67.2 milliseconds) and remained significantly reduced until the end of the observation period (72.9 msec) (P = .003). JT dispersion reduced up to week 2 (P = .010) and returned to baseline at week 4; in the no-SOF group, QRS dispersion transiently reduced (from 41 to 34.5 milliseconds, day 7). No other significant changes were observed in the remaining parameters. In CHC patients treated with SOF and other DAAs, ECG parameter changes were mild and/or transient and did not translate into clinically significant electrophysiological effects in the absence of amiodarone coadministration.
authors.affiliation: Internal Medicine, University of Campania 'Luigi Vanvitelli' and AORN dei Colli-Monaldi Hospital, Naples, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante-Mangoni
authors.affiliation: Internal Medicine, University of Campania 'Luigi Vanvitelli' and AORN dei Colli-Monaldi Hospital, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Parrella
authors.affiliation: Internal Medicine, University of Campania 'Luigi Vanvitelli' and AORN dei Colli-Monaldi Hospital, Naples, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Vitrone
authors.affiliation: Department of Cardiothoracic Sciences, Cardiology Section, University of Campania 'Luigi Vanvitelli' and AORN dei Colli-Monaldi Hospital, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rago
authors.affiliation: Internal Medicine, University of Campania 'Luigi Vanvitelli' and AORN dei Colli-Monaldi Hospital, Naples, Italy.
authors.forename: Pia Clara
authors.initials: PC
authors.lastname: Pafundi
authors.affiliation: Department of Cardiothoracic Sciences, Cardiology Section, University of Campania 'Luigi Vanvitelli' and AORN dei Colli-Monaldi Hospital, Naples, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Nigro
authors.affiliation: Internal Medicine, University of Campania 'Luigi Vanvitelli' and AORN dei Colli-Monaldi Hospital, Naples, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Utili
authors.affiliation: Department of Cardiothoracic Sciences, Cardiology Section, University of Campania 'Luigi Vanvitelli' and AORN dei Colli-Monaldi Hospital, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology*; D001919:Bradycardia / Q000139:chemically induced*; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000069474:Sofosbuvir / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000069474:Sofosbuvir
keywords: arrhythmia; direct antiviral agents; electrocardiography; hepatitis C; sofosbuvir