Unveiling sex dimorphism in the healthy cardiac anatomy: Fundamental differences between male and female heart shapes

Sex-based differences in cardiovascular disease are well documented, yet the precise nature and extent of these discrepancies in cardiac anatomy remain incompletely understood. Traditional scaling models often fail to capture the interplay of age, blood pressure and body size, prompting a more nuanced investigation. Here we use statistical shape modelling in a healthy subset (n = 456) of the UK Biobank to explore sex-specific variations in biventricular anatomy. We reconstruct 3D meshes and perform multivariate analyses of shape coefficients, controlling for age, blood pressure and various body size metrics. Our findings reveal that sex alone explains at least 25% of morphological variability, with strong discrimination between men and women (AUC = 0.96-0.71) persisting even after correction for confounders. Notably, the most discriminative modes highlight pronounced differences in cardiac chamber volumes, the anterior-posterior width of the right ventricle and the relative positioning of the cardiac chambers. These results underscore that sex has a fundamental influence on cardiac morphology, which may have important clinical implications for differing cardiac structural assessments in men and women. Future work should investigate how these anatomical differences manifest in various cardiovascular conditions, ultimately paving the way for more precise risk stratification and personalised therapeutic strategies for both men and women. KEY POINTS: Men's and women's hearts differ significantly in overall shape and size, but an in-depth quantification of these sex differences in healthy cardiac anatomy is lacking. We used a three-dimensional statistical shape modelling approach that goes beyond standard clinical measurements to capture subtle anatomical features. Our findings show that sex alone accounts for at least 25% of the natural variation in heart structure, even after correcting for age, blood pressure and various body size metric confounders. Female hearts consistently present smaller chambers and different inter-chamber positioning compared with male hearts. Our findings highlight the importance of sex-specific anatomical insights for better diagnosis, treatment and research on heart disease.