Short QT syndrome is a rare inherited cardiac disorder associated with severe arrhythmias and sudden cardiac death. The researchers investigated two newly identified variants of the SLC4A3 gene using cardiomyocytes derived from induced pluripotent stem cells of affected patients.
They found that the genetic variants increased intracellular pH and altered the electrical properties of the cardiomyocytes, resulting in shortened action potentials and an increased occurrence of arrhythmic events. Correction of the genetic variants using CRISPR/Cas9 confirmed the causal relationship.
In the cellular models, the antiarrhythmic drugs quinidine and sotalol prolonged action potential duration and reduced arrhythmic events. The findings reveal a mechanism underlying SLC4A3-associated short QT syndrome and may contribute to the development of more targeted treatment strategies for affected patients.
Link to the publication:
Meng Z, Kovacs B, Yan C, et al. SLC4A3-related short QT syndrome assessed in human induced pluripotent stem cell-derived cardiomyocytes: mechanisms of ventricular arrhythmia and sudden cardiac death. Eur Heart J. 2026;47(23):2982–2998. doi: 10.1093/eurheartj/ehag068
