A study identified transthyretin cardiac amyloidosis (ATTR-CA) as a large cause of
“The principal findings of this study included the fact that ATTR-CA was the cause of HF in 7.8% of Black participants overall and 17.2% of Black participants older than 75 years of age, but in only 2.2% of Hispanic participants,” study investigator Frederick L. Ruberg, MD, from Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, and colleagues wrote.2
ATTR-CA is a treatable, but underdiagnosed, cause of heart failure in older adults, caused by normal wild-type (ATTRwt-CA) or an abnormal inherited (ATTRv-CA) TTR gene variant. V1421, the most common TTR variant, occurs in 3% to 4% of self-identified Black Americans and is associated with morbidity and mortality.1
Most V1421 carriers have an ancestry that originated in western Africa, and the allele has an increased frequency in Afro-Caribbean and Caribbean Hispanic individuals. Recent research has shown that carrying this allele increases the risk for HF hospitalization at age 50 years and death at 65 years old.2 However, despite this morbidity and mortality risk, the prevalence of ATTR-CA in Black individuals was unknown.
Investigators sought to assess the prevalence of ATTR-CA among older Black and Caribbean Hispanic individuals with HF.1 The team also aimed to assess the contribution of each gene variant to the prevalence of ATTR-CA.
Conducted in several major US cities, including Boston, New York, and New Haven, this prospective, multicenter, cross-sectional study enrolled 646 individuals between May 2019 and June 2024 who self-identified as Black or Caribbean Hispanic and were aged ≥ 60 years.1 The sample had a median age of 73 years (range, 66 – 80 years), with 50.6% women, 85.1% identified as Black, and 28.8% identified as Caribbean Hispanic. Median left ventricular wall thickness was 13 mm, and median left ventricular ejection fraction was 61%.
Investigators assessed ATTR-CA by radionuclide imaging. They also did blood testing to exclude light-chain amyloidosis and genotyping to determine the TTR gene variant. Investigators also assessed echocardiographic, biochemical, physical performance, and quality-of-life data.1
The overall prevalence of ATTR-CA was 6.66% (95% confidence interval [CI], 4.73 – 8.58%). Among these participants, 55.8% had ATTRw-CA and 44.2% had ATTRv-CA. Moreover, the overall prevalence of V1421 was 5.6%, and among those who had that gene variant, 52.8% had ATTRv-CA.1
The prevalence of ATTR-CA was greater in males (8.15%; 95% confidence interval [CI], 5.15 – 11.15) vs females (5.20%; 95% CI, 2.79% – 7.61%), although the difference was not significant (P =.13).1
When it came to race, the ATTR-CA prevalence 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). Black participants aged 75 years or younger had a greater ATTR-CA prevalence than participants over 75 years old (3.42 [95% CI, 1.43 – 5.40%] vs 14.04% [95% CI, 9.53 – 18.53%]; P <.001). However, Black male participants aged ≥ 75 years had an ATTR-CA prevalence of 17.17 (95% CI, 9.74% – 24.60).1
“In conclusion, the SCAN-MP cross-sectional study demonstrated that ATTR-CA is a commonly encountered cause of HF in older Black individuals with HF and is particularly common in men older than 75 years,” investigators wrote.1 “More than half of all cases had genetically normal TTR, indicating that a genotype-first approach would miss a large portion of affected individuals.”
References
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Ruberg FL, Teruya S, Helmke S, et al. Transthyretin Cardiac Amyloidosis in Older Black and Hispanic Individuals With Heart Failure. JAMA Cardiol. Published online September 10, 2025. doi:10.1001/jamacardio.2025.2948
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Selvaraj S, Claggett B, Shah SH, et al. Cardiovascular Burden of the V142I Transthyretin Variant. JAMA. 2024;331(21):1824-1833. doi:10.1001/jama.2024.4467