Cardiol Ther. 2026 May 27. doi: 10.1007/s40119-026-00450-y. Online ahead of print.
ABSTRACT
INTRODUCTION: Timely diagnosis and treatment are essential for improving outcomes and quality of life in patients with transthyretin (ATTR) amyloidosis. Early multisystem manifestations are often unrecognized, leading to diagnostic delays and misdiagnosis. Large-scale, multicountry, observational studies are needed to better characterize the real-world trajectory of these patients.
METHODS: OverTTuRe, an ANTHOLOGY study, is a retrospective, observational, descriptive, longitudinal, multicountry study using secondary data from claims databases, electronic health records, and healthcare registries. The primary aim of this analysis was to characterize baseline characteristics, early clinical manifestations, and outcomes in patients with hereditary transthyretin (ATTRv) amyloidosis from the United States (US), United Kingdom (UK), Japan, Denmark, and Sweden.
RESULTS: Of 1502 patients identified, the predominant phenotype across countries was ATTRv amyloidosis with polyneuropathy (ATTRv-PN 51.3-63.7%); however, many patients had ATTRv with mixed phenotype (ATTRv mixed 36.3-48.8%). Compared to patients with ATTRv mixed, patients with ATTRv-PN were younger, and a higher proportion were female (36.6-64.1% vs. 19.3-56.4%). Median (interquartile range) time from any initial cardiac or noncardiac manifestation to diagnosis varied across countries; time from any noncardiac manifestation to diagnosis was longest for both phenotypes in the US (ATTRv-PN 2.9 [1.0-4.0] years; ATTRv mixed 2.4 [0.8-3.7] years). Following diagnosis, treatment was not available for most patients. Mortality (ATTRv-PN 14.6-36.2%; ATTRv mixed 21.0-73.0%) and hospitalization (ATTRv-PN 23.5-66.2%; ATTRv mixed 20.8-70.5%) risk varied across countries in the 5 years following diagnosis. Pre- and post-diagnosis healthcare resource utilization was high for both phenotypes.
CONCLUSIONS: These findings highlight the heterogeneity of clinical manifestations and outcomes of ATTRv amyloidosis across phenotypes and countries. Patients frequently experience diagnostic delays and numerous healthcare interactions. Elevated clinical suspicion to facilitate earlier diagnosis, together with a multidisciplinary care approach and timely access to targeted therapies, is needed to improve outcomes.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06355934.
PMID:42201638 | DOI:10.1007/s40119-026-00450-y
