ATTR-CA Variant Disproportionately Impacts Black Individuals With Heart Failure

Transthyretin cardiac amyloidosis (ATTR-CA) disproportionately impacts Black and Caribbean Hispanic individuals with heart failure (HF) due to the prevalence of genes more likely to be found in those with African ancestry, according to a recent study published in JAMA Cardiology.¹

ATTR-CA is caused by the misfolding of the TTR protein followed by aggregation and myocardial deposition of TTR amyloid fibrils. The most common variant, V142I, has been identified in 3% to 4% of self-identified Black individuals in the US, which equates to nearly 1.5 million Black individuals who carry this variant of the disease. However, prior studies aimed at increasing awareness and improvements in diagnostic testing enrolled very few Black individuals, leaving the true risk of ATTR-CA and the likelihood of inheriting the V142I variant unknown. ATTR-CA is treatable given multiple recent FDA-approved therapies; however, these therapies are most effective when started earlier, thus incentivizing a definitive risk assessment of older Black individuals with HF caused by ATTR-CA in the Screening for Cardiac Amyloidosis with Nuclear Imaging for Minority Populations (SCAN-MP; NCT03812172) clinical trial.

Black men over the age of 75 are disproportionately impacted by the ATTR-CA variant. | Image Credit: @Prostock-studio-AdobeStock.jpeg

“SCAN-MP was distinct from prior studies owing to its prospective design, rigorous genotyping and phenotyping methodology, and inclusion limited to older Black or Hispanic patients with HF,” the study authors wrote.

This multicenter, cross-sectional cohort study included sites in several major US cities: Boston, Massachusetts; New York, New York; and New Haven, Connecticut. The participants were individuals over the age of 60 years who self-identified as Black or Hispanic of Caribbean ethnicity, with a diagnosis of HF, left ventricular wall thickness of 1.2 cm or higher, and a left ventricular ejection fraction (LVEF) greater than 30%.

Of the 646 participants in the study, the mean age was 73 years. Among them, 329 (50.6%) were women, 550 (85.1%) self-identified as Black, and 186 (28.8%) identified as Caribbean Hispanic. The median left ventricular wall thickness was 13 mm, and the median LVEF was 61%. The study concluded that patients carrying this variant were also more likely to be older (> 75 years) and male.²

Perceptive Risk of ATTR-CA in Black and Hispanic Caribbean Individuals

The overall prevalence of ATTR-CA was 6.6% (95% CI, 4.7%-8.58%), of whom 24 (55.8%) had wild-type ATTR-CA and 19 (44.2%) had ATTR-CA by the V142I variant. ATTR-CA was more prevalent in individuals who self-identified as Black (7.82%; 95% CI, 5.57%-10.06%) than in those who identified as Hispanic (2.15%; 95% CI, 0.07%-4.24%; P = .004). It was also more prevalent among older individuals, specifically those older than 75 years old, with a prevalence of 11.72% (95% CI, 7.91%-15.54%) compared with 2.95% (95% CI, 1.23%-4.67%) of those aged 75 years or younger (P < .001).¹

While there was an observed difference in prevalence between men and women, it was not statistically significant.

“Our data suggests that ATTR-CA is underdiagnosed in women,” the study authors explained. “This may be potentially attributable to the different reference ranges for wall thickness and left ventricular mass index by sex, which are not accounted for in current guidelines that advise a singular wall thickness threshold irrespective of sex (>12 mm) to trigger suspicion of cardiac amyloidosis.”

The study’s limitations include reliance on administrative data, which may introduce coding errors and limit the ability to confirm diagnoses or assess disease severity. Important clinical details such as imaging, biomarkers, and outpatient outcomes were not available, restricting a full understanding of patient trajectories. Additionally, the cross-sectional design prevents assessment of long-term outcomes and causal relationships between ATTR-CA and disparities in HF care.

These findings underscore the disproportionate burden of ATTR-CA in older Black and Hispanic Caribbean individuals and highlight the urgent need for more inclusive diagnostic guidelines. Greater awareness, coupled with equitable access to effective therapies, will be essential to improving outcomes and reducing disparities in this underrecognized condition.

References

1. 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

2. Neale T. Transthyretin cardiac amyloidosis: a common cause of HF in older Black patients. TCTMD.com. September 12, 2025. Accessed September 12, 2025. https://www.tctmd.com/news/transthyretin-cardiac-amyloidosis-common-cause-hf-older-black-patients #:~:text=Among%20Black%20individuals%2C%20ATTR%2DCA,testing%20consistent%20with%20ATTR%2DCA