Impact of Antiarrhythmic Drugs on the Outcome of Short QT Syndrome

Ibrahim El-Battrawy,Huan Lan,Siegfried Lang,Rainer Schimpf,Xiaobo Zhou,Martin Borggrefe,Volker Liebe,Christian Wolpert,Zhihan Zhao,Johanna Besler,Xin Li,Ibrahim Akin

doi:10.3389/fphar.2019.00771

Abstract

Short QT syndrome (SQTS) is associated with sudden cardiac arrest. There are limited data on the impact of antiarrhythmic drugs on the outcome of SQTS. Materials and Methods: We studied data that describe the clinical outcome of 62 SQTS patients treated with antiarrhythmic drugs, who were recruited from a pool of patients diagnosed in our institution and also from known databases after a systematic search of the published literature. Results: Sixty-two SQTS patients treated with antiarrhythmic drugs were followed up over a median timeframe of 5.6 years (interquartile range 1.6–7.7 years). Six patients, in particular, received multiple drugs as a combination. Of the 55 patients treated with hydroquinidine (HQ), long-term prophylaxis was documented in 41 patients. Fourteen patients stopped treatment due to the following reasons: gastrointestinal intolerance (n = 4), poor compliance (n = 8), and no QTc prolongation (n = 2). Of the 41 patients treated with HQ, the QTc interval increased from 313.5 ± 17.2 to 380.1 ± 21.2 ms. Thirteen of the 41 patients suffered from at least one or more ventricular tachyarrhythmias (VAs) before HQ initiation. VAs are reduced in incidence after HQ treatment (13/41: 31% versus 3/41: 7.3%, p < 0.001). Conclusion: HQ increases the corrected QT interval and prevents VAs in the majority of the patients in this cohort. HQ is safe for use in SQTS patients, particularly due to its low rate of side effects. Other antiarrhythmic drugs might be useful, but the data justifying their use are sparse.

Highlights

Short QT syndrome (SQTS) is a rare channelopathy, and patients affected with this disorder are predisposed to a higher risk of developing ventricular tachyarrhythmias (VAs; Giustetto et al, 2011; Mazzanti et al, 2014)
An arrhythmic event was defined as a documented ventricular fibrillation (VF)/ ventricular tachycardia (VT)
DNA sequencing using next-generation sequencing of affected genes (KCNH2, KCNQ1, KCNJ2, CACNA1C, CACNB2, and CACNA2D1) for SQTS1 to SQTS6 was performed for the purpose of genetic screening and analyzed for results

Summary

Introduction

Short QT syndrome (SQTS) is a rare channelopathy, and patients affected with this disorder are predisposed to a higher risk of developing ventricular tachyarrhythmias (VAs; Giustetto et al, 2011; Mazzanti et al, 2014). Since its first description in 2000 (Gussak et al, 2000), causative mutations have been identified in eight different genes: SQTS1 to SQTS3 are associated with gain-of-function mutations in potassium channels, whereas SQTS4 to SQTS6 are caused by loss-of-function of calcium channels, Antiarrhythmic Drugs in Short QT Syndrome demonstrating some overlap with Brugada syndrome. There are no conclusive data regarding the association of this variant with SQTS, it was described as SQTS7. A mutation in the cardiac Cl/HCO3 exchanger AE3 was found to cause SQTS and described as SQTS8 (Thorsen et al, 2017). Different antiarrhythmic drugs have been tested in a small series of SQTS patients (Schimpf et al, 2007; Zhao et al, 2019), there are few data describing the long-term outcome of treated patients

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