P174 - SEX-BASED DIFFERENCES IN CLINICAL PRESENTATION OF TRANSTHYRETIN CARDIAC AMYLOIDOSIS: A COMPARATIVE ANALYSIS OF REFERRED AND SCREENED POPULATIONS

Background: Diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) in women may be influenced by male-centric diagnostic criteria and referral patterns. Screening algorithms can capture patients regardless of sex-specific biases in clinical suspicion or echocardiographic presentation. However, the impact of these algorithms on eliminating sex bias in ATTR-CM diagnosis has not been reported.

METHODS AND RESULTS: We compared baseline characteristics among two populations with ATTR-CM: patients whose clinical presentation prompted their physician to refer for amyloidosis evaluation (Clinical) and those who were diagnosed based on a systematic screening algorithm applied to high-risk patient populations, predominantly in heart failure clinics (Algorithm). Within each cohort, we compared characteristics of men and women, and compared characteristics of women in the Clinical cohort to those of women in the Algorithm cohort.

The Clinical cohort included 272 patients, comprising 236 men (86.8%) and 36 women (13.2%), while the Algorithm cohort included 46 patients, with 37 men (80.4%) and 9 women (19.6%) (p = NS). In both cohorts, there were no significant differences between men and women in terms of age, NYHA class, or natriuretic peptide levels. Within the Clinical cohort, men had a higher mean septal wall thickness (15.6 ± 3.2 mm vs. 14.0 ± 3.4 mm, p = 0.024), lower mean LVEF (50.7 ± 11.3% vs. 57.8 ± 9.2%, p = 0.001), and more abnormal median GLS values (–11.8 [8.6, 13.9] vs. –13.5 [7.8, 11.5], p = 0.021) compared to women. In the Algorithm cohort, men demonstrated higher mean posterior wall thickness (15.1 ± 2.83 mm vs. 12.3 ± 3.6 mm, p = 0.017) and lower median LVEF (55.0 [49.0, 60.0] vs. 65.0 [58.0, 65.0], p = 0.02) than women. Among women, those in the Clinical cohort had lower mean BNP levels compared to those in the Algorithm cohort (437.8 ± 348.7 ng/L vs. 992.7 ± 818.4 ng/L, p = 0.023), though there were no significant differences between the two cohorts in terms of age, wall thickness, LV function, or NYHA class.

Conclusion: Among ATTR-CM patients diagnosed clinically or using a screening algorithm, men had greater wall thickness and lower LV function than women. Women diagnosed using an algorithm had biochemical evidence of more advanced heart failure than those clinically diagnosed. The consistent differences between male and female patients suggests the need to consider sex when interpreting ATTR-CM-related imaging. Together, these results suggest that to identify women at earlier stages of disease, sex-specific algorithms should be applied to lower-risk populations.