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

Abstract: 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 employ statistical shape modeling 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 percent 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 personalized therapeutic strategies for both men and women.