Gender disparities in torsade de pointes ventricular tachycardia

Abstract

Background. Gender disparities in the incidence of torsade de pointes (TdP) ventricular tachycardia exist, but the mechanisms in humans are unresolved. We addressed this issue using a mathematical model of a human ventricular cell. Methods. We implemented gender differences in the Priebe-Beuckelmann model cell by modifying the amplitudes of the L-type Ca2+ current (I Ca,L), transient outward K+ current (Ito), and rapid component of the delayed rectifier K+ current (IKr), according to experimental data from animal male and female hearts. Gender disparities in electrical heterogeneity between transmural layers (subepicardium, midmyocardium, subendocardium) were implemented by modifying various ion currents according to experimental data. Results. Action potentials in female cells have longer durations and steeper duration versus frequency relationships than male cells. In the female cells, electrical heterogeneity between transmural layers is larger and the susceptibility to early afterdepolarisations is higher than in male cells. Conclusion. Gender-related differences in ICa,L, Ito, and IKr may explain the gender disparities in human cardiac electrophysiology. Female cells have an increased susceptibility to early afterdepolarisations following mild reductions in net repolarising forces. Combined with their greater electrical heterogeneity, this renders them more vulnerable to TdP.