Sex Differences in Presentation and Outcomes of Transthyretin Amyloid Cardiomyopathy

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM) is more often diagnosed in men than in women but sex-specific data remain limited. OBJECTIVES: The objective of the study was to characterize sex-related differences in presentation and outcomes in patients with ATTR-CM. METHODS: Consecutive prospective patients with confirmed ATTR-CM enrolled in the multicenter Swiss-CARE registry (February 2018-March 2025) were analyzed. Clinical data were obtained at diagnosis, 6 months postdiagnosis, and yearly thereafter. The primary endpoint was first major adverse cardiac event (MACE) (ie composite of heart failure hospitalization and all-cause mortality). Kaplan-Meier and Cox proportional hazards models were employed. RESULTS: Among 567 patients with ATTR-CM (age 77 ± 7 years, 52 [9%] women), women were older at diagnosis (80.3 ± 6.1 vs 76.9 ± 6.9 years; P < 0.001), had a higher NYHA functional class (P < 0.001), higher N-terminal pro-B-type natriuretic peptide (2,574 vs 1,632 pg/mL; P = 0.006), and shorter 6-minute walking distance (320 ± 111 vs 411 ± 114 m; P = 0.001). Tafamidis was less frequently prescribed in women (50.0% vs 69.7%; P = 0.004). Women had a higher incidence of MACE (HR: 1.86; 95% CI: 1.13-3.04; P = 0.014), driven by increased heart failure hospitalizations within the first 2 years (HR: 2.21; 95% CI: 1.17-4.19; P = 0.015) and a trend toward higher all-cause mortality (HR: 1.82; 95% CI: 0.97-3.43; P = 0.06). In multivariable analyses, sex was not independently associated with MACE (P = 0.23). CONCLUSIONS: Women exhibited a higher risk of MACE after diagnosis; however, sex was not an independent predictor of outcomes in multivariable analysis. This disadvantage in women may be partly explained by older age at diagnosis, higher NT-proBNP levels, greater symptom burden, and a higher prevalence of comorbidities, rather than intrinsic sex-specific differences in ATTR-CM progression.