Sex-Based Differences in Mitral Annular Disjunction Severity and Arrhythmic Risk in Mitral Valve Prolapse

Arrhythmic mitral valve prolapse (AMVP), a condition with known female predominance, has been linked to mitral annular disjunction (MAD), yet the relationship between MAD, sex, body size, and arrhythmic events remains unclear.

To determine whether MAD exhibits sex-based differential effects on arrhythmic risk and explore the implications of indexing MAD measurements.

We examined 682 consecutive MVPs at the University of California San Francisco (2013-23) with detailed clinical, rhythmic, and echocardiographic data. Mitral annular disjunction was indexed to body surface area, resulting in the identification of 3 distinct groups: no MAD and indexed MAD (iMAD) below and iMAD above the median. Arrhythmic mitral valve prolapse was defined as MVP with frequent and/or complex ventricular ectopy, including severe arrhythmic events such as sustained ventricular tachycardia, ventricular fibrillation/sudden cardiac arrest, or death.

Among 682 MVP patients (48% women, mean age 58 ± 17 years), 35% had AMVP and 41% had MAD, with a median iMAD of 4 mm. Compared to women, men had greater absolute MAD length (9.0 ± 3.2 mm vs 7.3 ± 2.6, P < .001). Sex-based differences in MAD length were no longer appreciated after indexing for body surface area (P = .33). In multivariable analyses, iMAD >4 mm was significantly associated with arrhythmic events in men but not in women (P = .02 vs P = .63). Bileaflet MVP had a direct effect on severe arrhythmic events in women (P = .04 for MVP, P = .39 in mediation analysis), but in men this association was mediated by iMAD length (P = .03).

In a large MVP cohort, men exhibit greater MAD length and a stronger association between iMAD length and arrhythmic events. In contrast, iMAD length in women may be less important for arrhythmic risk stratification compared to other imaging parameters such as bileaflet involvement. Further studies are needed to confirm alternative mechanisms beyond localized MAD-related myocardial traction in women with MVP.