Characteristics and prognosis of wild-type transthyretin cardiac amyloidosis patients diagnosed before 65 years old

Abstract Background Guidelines suggest screening patients for transthyretin amyloid cardiomyopathy (ATTR-CM) after the age of 65 years. However, in clinical practice a few but not insignificant number of patients are diagnosed younger than the 65-year age cut-off. To date, the characteristics and outcomes in these young patients have not been specifically studied. Purpose This study aimed to compare the prevalence, characteristics, and prognosis of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) diagnosed at or before 65 years old (ATTRwt-Yy) with those diagnosed after 65 (ATTRwt-O). Methods Data were obtained from the Healthcare European Amyloidosis Registry (HEAR), a multicenter, non-interventional, longitudinal registry for amyloidosis patients. Patients with confirmed ATTRwt-CM were included in study. ATTRwt-CM diagnosis could be established either invasively by a biopsy-proven diagnosis, or non-invasively based on the current guidelines. Patients were classified by age at diagnosis: ATTRwt-Yy (≤65 years) and ATTRwt-O (65 years) and by onset of first cardiac symptom ATTRwt-Oy (≤65 years) and ATTRwt-Oo (65years). Results Between July 2021 and May 2024, 3,980 ATTR patients were enrolled, with 1,417 diagnosed with ATTRwt-CM and documented first cardiac symptom onset. Among them, 67 (4.7%) were ATTRwt-Yy, 111 (7.8%) were ATTRwt-Oy (≤65 years), and 1,239 (87.4%) were ATTRwt-Oo (65 years). Median diagnostic delays from first symptoms were 0.65 years for ATTRwt-Yy, 0.77 years for ATTRwt-Oo, and 20.58 years for ATTRwt-Oy (p0.001). Heart failure signs were present initially in 34.9% of ATTRwt-Yy, 30.2% of ATTRwt-Oo, and 8.1% of ATTRwt-Oy (p0.001). ATTRwt-Yy patients exhibited more extracardiac manifestations, particularly osteoarticular disease, while rhythm disturbances were more common in ATTRwt-Oy. Morphological and functional echocardiographic data were similar between the groups. The analysis of survival in the study groups showed a significantly reduced life expectancy in ATTRwt-Yy patients. Conclusion Patients diagnosed with ATTRwt-CM before 65 years are not uncommon. They have a distinct phenotype with more severe osteo-tendinous disease and shorter survival, indicating a need for adapted diagnostic and care strategies.