Family screening and genetic testing in transthyretin cardiac amyloidosis

Abstract With increasing awareness of transthyretin amyloid cardiomyopathy (ATTR-CM) as a cause of heart failure and the availability of disease-modifying therapies, the importance of early diagnosis has grown. Consequently, greater emphasis has been placed on genetic testing and family screening to identify individuals with variant transthyretin amyloidosis (ATTRv) who are at risk of developing ATTRv cardiomyopathy (ATTRv-CM). To identify individuals with a genetic predisposition to the disease, all individuals with ATTR-CM should undergo genetic testing with subsequent cascade genetic testing in relatives when a genetic variant is identified. In asymptomatic pathogenic/likely pathogenic (P/LP) transthyretin ( TTR ) variant carriers, structured follow-up is recommended to enable early diagnosis, allowing timely initiation of treatment. Additionally, systematic family screening protocols may also help identify and detect ATTR-CM in general, including wild-type ATTR-CM. In conclusion, this narrative review provides clinicians with an overview of how to manage patients with ATTRv-CM and their families. Indeed, comprehensive genetic and cascade screening strategies are essential for early identification and optimal management of ATTR-CM. Future perspectives include refinement of risk stratification, optimization of diagnostic and screening pathways, improved timing of treatment initiation, and addressing health inequalities to ensure equitable access to care.