Key result
Higher center-level female representation in ATTR-CM is linked to ~22% higher NT-proBNP in women.
Why the study?
Sex disparities are increasingly recognized in transthyretin amyloid cardiomyopathy (ATTR-CM), yet female representation varies substantially across centers. It remained to be determined whether inter-center variation in female prevalence is associated with differences in myocardial disease severity and sex-specific center effects.
Is inter-center variation in female prevalence associated with differences in myocardial disease severity in patients with transthyretin amyloid cardiomyopathy (ATTR-CM)?
Cohort (n=3,287)
Yes
Is inter-center variation in female prevalence associated with differences in myocardial disease severity in patients with transthyretin amyloid cardiomyopathy (ATTR-CM)?
Female representation in ATTR-CM varied sevenfold across centers and was independently associated with greater myocardial severity among women at higher-prevalence centers, highlighting the need for equitable diagnostic strategies.
May indicate referral biases in ATTR-CM; hypothesis-generating for disparities and requires prospective validation before clinical use.
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.
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Zaroui et al. (2026) conducted a cohort in Transthyretin amyloid cardiomyopathy (ATTR-CM) (n=3,287). Higher center-level female prevalence (highest tertile, T3) vs. Lower center-level female prevalence (lowest tertile, T1) was evaluated on Myocardial disease severity (NT-proBNP, troponin, septal thickness, LVEF, and global longitudinal strain) (adjusted β=+0.17 for log(NT-proBNP), p=0.018). Higher center-level female representation in ATTR-CM was associated with greater myocardial severity in women, including 22% higher NT-proBNP (p=0.018) and 27% higher troponin (p=0.021).
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