Unravelling Sex Disparities in the Pathophysiology of Atrial Fibrillation: Review of the Current Evidence

Atrial fibrillation (AF) is the most common sustained arrhythmia associated with increased risks of stroke, heart failure, and mortality. Men experience AF more frequently than women, but women are more likely to suffer greater symptoms and reduced quality of life as a consequence of AF onset. Its pathophysiology is complex, influenced by hormonal, structural, electrophysiological, and genetic factors. Sex hormones, including oestrogen, progesterone, and testosterone, play critical roles in modulating cardiac electrophysiology, autonomic function, and atrial remodelling, contributing to sex-specific differences in AF prevalence and outcomes. Women experience increased AF risk post-menopause due to declining oestrogen levels, while testosterone fluctuations in men are associated with arrhythmogenesis. Thyroid hormones further complicate the hormonal landscape by influencing cardiac excitability and autonomic regulation. Electrophysiological and structural differences between sexes, such as longer P-wave durations and greater fibrosis in women, result in increased AF recurrence and complications, particularly after catheter ablation. Men, however, have a higher overall AF incidence, likely due to larger atrial sizes and different conduction properties. Lifestyle and psychological factors, including obesity, physical activity, and mental health, intersect with these sex-specific risks, further influencing AF susceptibility. Artificial intelligence (AI) offers transformative opportunities to integrate these factors into personalised prevention and treatment strategies, enhancing early detection and tailored interventions. This review highlights the critical role of hormonal and sex-specific factors in AF pathophysiology, emphasising the need for sex-specific approaches to optimise management. Understanding these mechanisms is essential for developing targeted, personalised strategies to improve outcomes for men and women with AF.