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Drug Testing in Human‐Induced Pluripotent Stem Cell–Derived Cardiomyocytes From a Patient With Short QT Syndrome Type 1

Short QT syndrome (SQTS) predisposes afflicted patients to sudden cardiac death. Until now, only one drug—quinidine—has been shown to be effective in patients with SQTS type 1(SQTS1). The objective of this study was to use human‐induced pluripotent stem cell–derived cardiomyocytes (hiPSC‐CMs) from a patient with SQTS1 to search for potentially effective drugs for the treatment of SQTS1 patients. Patch clamp and single‐cell contraction measurements were employed to assess drug effects. Ivabradine, mexiletine, and ajmaline but not flecainide, ranolazine, or amiodarone prolonged the action potential duration (APD) in hiPSC‐CMs from an SQTS1 patient. Ivabradine, ajmaline, and mexiletine inhibited KCNH2 channel currents significantly, which may underlie their APD‐prolonging effects. Under proarrhythmic epinephrine stimulation in spontaneously beating SQTS1 hiPSC‐CMs, ivabradine, mexiletine, and ajmaline but not flecainide reduced the epinephrine‐induced arrhythmic events. The results demonstrate that ivabradine, ajmaline, and mexiletine may be candidate drugs for preventing tachyarrhythmias in SQTS1 patients.