Antiarrhythmic Effects of Vernakalant in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with Short QT Syndrome Type 1.

Abstract

(1) Background: Short QT syndrome (SQTS) may result in sudden cardiac death. So far, no drugs, except quinidine, have been demonstrated to be effective in some patients with SQTS type 1 (SQTS1). This study was designed to examine the potential effectiveness of vernakalant for treating SQTS1 patients, using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1. (2) Methods: Patch clamp and calcium imaging techniques were used to examine the drug effects. (3) Results: Vernakalant prolonged the action potential duration (APD) in hiPSC-CMs from a SQTS1-patient (SQTS1-hiPSC-CMs). In spontaneously beating SQTS1-hiPSC-CMs, vernakalant reduced the arrhythmia-like events induced by carbachol plus epinephrine. Vernakalant failed to suppress the hERG channel currents but reduced the outward small-conductance calcium-activated potassium channel current. In addition, it enhanced Na/Ca exchanger currents and late sodium currents, in agreement with its APD-prolonging effect. (4) Conclusions: The results demonstrated that vernakalant can prolong APD and reduce arrhythmia-like events in SQTS1-hiPSC-CMs and may be a candidate drug for treating arrhythmias in SQTS1-patients.

• Authors: Qiang Xu, Xuemei Huang, Zenghui Meng, Yingrui Li, Rujia Zhong, Xin Li, Lukas Cyganek, Ibrahim El-Battrawy, Ibrahim Akin, Xiaobo Zhou, Huan Lan
• Journal: Journal of cardiovascular development and disease (J Cardiovasc Dev Dis) Vol. 9 Issue 4 (Apr 09 2022) ISSN: 2308-3425 [Electronic] Switzerland
• PMID: 35448088 (Publication Type: Journal Article)