The interplay of sex-specific electrophysiology and repolarization heterogeneity governs ventricular arrhythmia sustainability in women

Abstract

Background: The role of sex-specific electrophysiology in the development of lethal ventricular arrhythmia is poorly understood. Since female ventricles have a longer action potential duration (APD) than male ven-tricles, we hypothesized that female hearts are more vulnerable to sustained ventricular arrhythmia in the presence of known arrhythmogenic substrates. Purpose: To determine if prolonged APD in females leads to sustained ventricular arrhythmia in the presence of left ventricular (LV) hypertrophy, diffuse fibrosis, and repolarization heterogeneity. Methods: Magnetic resonance imaging (MRI) data were used to develop computational biventricular models of two aortic stenosis patients (male, 54 years; female, 64 years) before (LV hypertrophy) and 3 months after (re-gressed LV hypertrophy) aortic valve replacement (AVR). These patients were chosen since they exhibit reduced LV mass, less fibrosis, and no ven-tricular arrhythmias after AVR. The models were assigned sex-specific cellular electrophysiology and an apicobasal repolarization gradient derived from human data. Simulations of apical pacing with a cycle length (CL) of 750 ms were performed while APD at 90% repolarization (APD90) and repolarization time (activation time + APD90) were calculated. Reentrant arrhythmia was induced by rapidly pacing the LV with a 2 mm wide api-cobasal line electrode at CL≤265 ms. The simulations were repeated in the presence of diffuse myocardial fibrosis derived from the MRI patient