Why the study?
AF risk varies across the female reproductive lifespan, rising after menopause but remaining low in pregnancy, suggesting female hormones modulate arrhythmia susceptibility.
Do oestrogen and progesterone modulate atrial electrophysiology and susceptibility to spiral wave activity across the menstrual cycle, pregnancy and menopause in female left atrial models?
Do oestrogen and progesterone modulate atrial electrophysiology and susceptibility to spiral wave activity across the menstrual cycle, pregnancy and menopause in female left atrial models?
Computational modeling demonstrates that estrogen exerts anti-arrhythmic effects primarily through non-genomic pathways, providing a mechanistic basis for the lower risk of atrial fibrillation during pregnancy compared to menopause.
Background and Aims Atrial fibrillation (AF) risk varies across the female reproductive lifespan, rising after menopause but remaining low in pregnancy despite left atrial dilation. This suggests a potential modulatory role for female hormones that if better understood could aid in risk stratification and guided therapy. We aimed to predict how oestrogen and progesterone modulate atrial electrophysiology and susceptibility to spiral wave activity across the menstrual cycle, pregnancy and menopause. Methods Human atrial cardiomyocyte electrophysiology and calcium dynamics were simulated using a biophysical cell model. A hormone regulation function incorporating non-genomic receptor independent and genomic ERα-mediated effects of oestrogen, and progesterone was added. Organ scale simulations were performed across nine reproductive phases in a cohort of reproductive-age female left atrial models derived from cardiovascular magnetic resonance imaging. Pregnancy-associated left atrial dilation was modelled, and atrial fibrillation was induced using spiral wave initiation protocols to assess arrhythmia sustenance. Results Relative to menopause, increasing hormone levels altered the action potential duration (oestrogen via both pathways: + 5-35%; progesterone: - 0.8-4%, combined: + 2-23 %) and spiral wave termination (oestrogen via both pathways: 51.4%; progesterone: 0%, combined: 38.9% of cases). Despite pregnancy-associated left atrial dilation, elevated oestrogen levels characteristic of pregnancy enabled spiral termination across all trimesters in all cases, driven primarily by the non-genomic pathway. In contrast, in menopause, low hormone levels permitted spiral sustenance in all simulations. Conclusion Oestrogen exerts anti-arrhythmic effects primarily through its non-genomic effects, overcoming pregnancy-associated structural remodelling, while progesterone promotes a pro-arrhythmic substrate. These findings suggest a mechanistic basis for reproductive phase-dependent differences in AF risk.
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Kulkarni et al. (2026) studied Atrial fibrillation. Oestrogen and progesterone vs. Menopause (low hormone levels) was evaluated on Action potential duration and spiral wave termination.
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