Sex differences in the clinical presentation of patients with transthyretin amyloid cardiomyopathy; results from a real-world study

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and life-threatening form of heart failure. Although ATTR-CM is more frequently diagnosed in men, evidence suggests that sex-related differences may exist but remain insufficiently characterised. Purpose To evaluate sex differences in clinical presentation and disease burden among patients with ATTR-CM in a real-world European setting. Methods Secondary data were drawn from a cross-sectional survey of ATTR-CM-treating physicians and their patients conducted in France, Germany, Italy, Spain, and the UK between August 2024 and February 2025. Physicians reported patient demographics, comorbidities, symptoms at first consultation, hospitalisations, mobility aid use, and caregiver support for up to 10 consecutive consulting patients with ATTR-CM. Sex differences were assessed using descriptive and bivariate analyses. Missing data were not imputed, and symptoms present in <5% of all patients are not reported. Results Overall, 124 physicians provided data for 630 patients with ATTR-CM, including 180 females (28.6%) and 450 males (71.4%). Mean (SD) age was 72.2 (12.1), with no significant sex differences. Significant differences in genotype data were observed (n=506, p<0.001); 32.8% of patients were wild type (males: 40.1%; females: 14.6%), 35.4% hereditary (males: 33.4%; females: 40.3%), and 31.8% had not been tested (males: 26.5%; females: 45.1%). Males more frequently presented with dyspnoea (males: 73.3%; females: 64.0%, p=0.029), while female patients more frequently presented with palpitations (males: 37.6%; females: 46.5%, p=0.044), constipation (males: 12.4%; females: 20.4%, p=0.016), loss of balance (males: 8.3%; females: 16.9%, p=0.003), and early satiety (males: 3.0%; females: 9.3%, p=0.002) (Figure 1). The number of diagnosed comorbidities at survey was greater (p=0.014) among female patients, with a mean (SD) of 2.8 (2.1) compared to 2.3 (1.9) in males. Females were more often diagnosed with anxiety (males: 14.7%; females: 23.9%, p=0.007), depression (males: 11.6%; females: 23.3%, p<0.001), and cerebrovascular disease (males: 4.4%; females: 8.9%, p=0.037). During the 12 months prior to survey, hospitalisation due to ATTR-CM occurred more frequently among females than males (males: 28.0%; females: 43.2%, p<0.001). Females more often required mobility aids (males: 34.9%; females: 49.9%, p=0.002) and caregiver support (males: 60.8%; females: 70.3%, p=0.036). Conclusion Our data found significant sex differences in the clinical presentation and disease burden of patients with ATTR-CM. These results highlight the importance of increasing the awareness of sex-specific manifestations of ATTR-CM, which may support earlier diagnosis and improved management of the condition in females.