Key PointsQuestionsWhat is the association between amyloidogenic TTR gene variation (Val122Ile) and the risk of heart failure?FindingsIn this retrospective cohort study that included 7514 Black participants in the US with a median 11.1 years of follow-up, the incidence of heart failure was 15.6 per 1000 person-years among Val122Ile variant carriers compared with 7.2 per 1000 person-years among noncarriers, with an adjusted hazard ratio of 2.43.MeaningBeing a carrier of the Val122Ile variant was significantly associated with an increased risk of heart failure among Black individuals living in the US.