Sevenfold inter-center variation in female representation and its association with myocardial severity in ATTR-CM: data from the nationwide HEAR Registry

Background

Sex disparities are increasingly recognized in transthyretin amyloid cardiomyopathy (ATTR-CM), yet female representation varies substantially across centers.

Objectives

To determine whether inter-center variation in female prevalence is associated with differences in myocardial disease severity and to assess sex-specific center effects.

Methods

We analyzed 3,287 patients from the nationwide HEAR Registry (687 women [21%], 2,600 men). Female representation varied sevenfold across centers (5%–35%). Centers were categorized into tertiles according to female proportion (T1 lowest; T3 highest). Sex-stratified analyses assessed age, comorbidities, NYHA class, log(NT-proBNP), log(troponin), septal thickness, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). Multivariable models adjusted for age, hypertension, diabetes, and ATTR subtype were performed. Sex × tertile interactions were tested.

Results

Among women (T1:100; T2:352; T3:235) (Figure1), age, comorbidities, and NYHA class were similar across tertiles. However, higher-prevalence centers were associated with greater myocardial involvement:(22% higher NT-proBNP (adjusted β=+0.17; p-trend=0.018), 27% higher troponin (adjusted β=+0.19; p-trend=0.021), 1.2 mm septal thickness (p=0.015)and −1.5% absolute GLS impairment (adjusted β=−1.3%; p=0.041), LVEF was unchanged.

In men, tertiles were associated with broader severity gradients across age, functional class, biomarkers, LVEF, and GLS (all p<0.001). Significant sex × tertile interactions were observed for NT-proBNP (p=0.032) and GLS (p=0.041).

Conclusions

In this national cohort, female representation varied markedly across centers and was associated with differential myocardial severity among women independent of clinical profile. These findings suggest that structural characteristics of care delivery may influence sex representation and highlight the importance of equitable diagnostic strategies in ATTR-CM.Female prevalence by center