Transthyretin Cardiac Amyloidosis in Older Black and Hispanic Individuals With Heart Failure

Importance Transthyretin cardiac amyloidosis (ATTR-CA) is an underdiagnosed but treatable cause of heart failure (HF) in older individuals that occurs in the context of normal wild-type (ATTRwt-CA) or an abnormal inherited (ATTRv-CA) TTR gene variant. While the most common inherited TTR variant, V142I, occurs in 3% to 4% of self-identified Black Americans and is associated with excess morbidity and mortality, the prevalence of ATTR-CA in this at-risk population is unknown. Objective To define the prevalence of ATTR-CA and proportions attributable to ATTRwt-CA or ATTRv-CA among older Black and Caribbean Hispanic individuals with HF. Design, Setting, and Participants This prospective, multicenter, cross-sectional study was conducted in several major US cities (Boston, Massachusetts; New York, New York; and New Haven, Connecticut) among individuals who self-identified as Black or Caribbean Hispanic older than 60 years with HF. Participants were enrolled between May 2019 and June 2024, and data analysis was conducted from June 2024 to May 2025. Main Outcomes and Measures ATTR-CA was determined by radionuclide imaging, with blood testing to exclude light-chain amyloidosis and genotyping to determine TTR gene variant. Echocardiographic, biochemical, physical performance, and quality-of-life data were collected. Results Among 646 participants, median (IQR) participant age was 73 (66-80) years, 329 (50.6%) were women, 550 (85.1%) identified as Black, and 186 (28.8%) identified as Caribbean Hispanic. Median (IQR) left ventricular wall thickness was 13 (12-14) mm, and median (IQR) left ventricular ejection fraction was 61% (55%-66%). Overall prevalence of ATTR-CA was 6.66% (95% CI, 4.73%-8.58%), of whom 24 (55.8%) had ATTRwt-CA and 19 (44.2%) had ATTRv-CA owing to V142I. Overall prevalence of V142I allele was 5.6%, and of those, 19 (52.8%) had ATTRv-CA. Prevalence of ATTR-CA was 8.15% (95% CI, 5.15%-11.15%) in men and 5.20% (95% CI, 2.79%-7.61%) in women ( P = .13). Prevalence of ATTR-CA was 7.82% (95% CI, 5.57%-10.06%) in Black participants and 2.15% (95% CI, 0.07%-4.24%) in Hispanic participants ( P = .004). Among Black participants aged 75 years or younger, ATTR-CA was observed in 3.42% of participants (95% CI, 1.43%-5.40%) compared to 14.04% (95% CI, 9.53%-18.54%) of those older than 75 years ( P < .001). Among Black male participants older than 75 years, prevalence of ATTR-CA was 17.17% (95% CI, 9.74%-24.60%). Conclusions and Relevance In this cross-sectional study, ATTR-CA was an important cause of HF in older Black individuals with HF, particularly in men older than 75 years. Approximately half of V142I carriers with HF had ATTR-CA, while 55.8% of all ATTR-CA cases had normal TTR genotype. Trial Registration ClinicalTrials.gov Identifier: NCT03812172