Sex differences and sex hormone effects in long-QT syndrome: what can we learn from rabbit models?

Abstract

Patients with inherited long-QT syndrome (LQTS) exhibit pronounced sex differences in cardiac repolarization and in the incidence of arrhythmias: Adult women have longer QT intervals and a higher risk to develop potentially lethal torsade-de-pointes (TdP) ventricular tachycardia and sudden cardiac death (SCD) than men. Rabbit models exhibit similar sex differences with longer QT intervals and a higher propensity to additional drug-induced QT prolongation and drug-induced TdP in females. Since rabbits also have similar cardiac repolarizing currents as human subjects, they provide a useful system to explore sex differences in cardiac repolarization and arrhythmogenesis in LQTS and to reveal the underlying molecular mechanisms. This review article summarizes clinical observations on sex differences and sex hormone effects on cardiac repolarization and arrhythmogenesis in patients with LQTS and recapitulates findings on underlying mechanisms (sex hormone effects on ion channels and Ca