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

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

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(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 Crew Neck Sweaters 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 Pour Over Stand 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.