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

Clin Pharmacol Ther. 2019 Sep;106(3):642-651. doi: 10.1002/cpt.1449. Epub 2019 May 13.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Arrhythmias, Cardiac
  • Cardiovascular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • ERG1 Potassium Channel / metabolism*
  • Epinephrine / pharmacology
  • Heart Conduction System / abnormalities*
  • Heart Conduction System / drug effects
  • Heart Defects, Congenital
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Myocytes, Cardiac / drug effects*


  • Cardiovascular Agents
  • ERG1 Potassium Channel
  • KCNH2 protein, human
  • Epinephrine

Supplementary concepts

  • Short QT Syndrome 1