Exploring the mechanisms of sex-specific proarrhythmia in long QT syndrome through computational modeling

作者：Isabella Doherty, Roshni Shetty, Haibo Ni, Stefano Morotti, Eleonora Grandi · 发表于：American Journal of Physiology-Heart and Circulatory Physiology · 年份：2025 · DOI：10.1152/ajpheart.00792.2024 · 被引用次数：10 · 研究领域：Cardiac electrophysiology and arrhythmias、Ion channel regulation and function、ECG Monitoring and Analysis

We explored sex disparities in long QT syndrome (LQTS) using sex-specific human ventricular cardiomyocyte models. We showed that females exhibit greater susceptibility to early afterdepolarizations (EADs) than males, and identified key ionic predictors of EAD risk, including increases in the voltage-gated L-type Ca 2+ current and electrogenic Na + /Ca 2+ exchanger, and downregulation of the rapidly activating delayed rectifier K + current. These findings offer new insights into sex-specific mechanisms underlying arrhythmogenesis in LQTS, with potential implications for personalized treatments.