An interim analysis of a study reveals the depth of the challenges in screening for transthyretin cardiac amyloidosis (ATTR-CM), according to an article published in the Journal of the American Heart Association. 

Despite its classification as a rare disorder, there are indicators that it may perhaps not be as “rare” as previously imagined. In hereditary ATTR-CM, the most common genetic variant in the United States driving this disorder (V1221) is highly prevalent among the American Black population, with an estimated 1.5 million carriers, even if levels of penetrance remain unclear. This suggests that ATTR-CM may be underinvestigated in clinical practice. 

The authors of the study enrolled 278 individuals aged 60 years and above who self-identified as being of Black/Caribbean Hispanic descent with a history of heart failure, defined as having a left ventricular ejection fraction of less than 30% and increased wall thickness.

All participants were screened for the V1221 variant. In addition, various tests were conducted to characterize the differences between V1221 carriers with and without ATTR-CM, as well as control participants with heart failure but without a diagnosis of ATTR-CM. 

Read more about ATTR-CM etiology 

The research team reported that 6.8% of all participants had ATTR-CM, and 6.5% had V1221 carrier status. The clinical penetrance stood at 39%. Sixty-three percent had wild-type ATTR-CM; the rest had ATTR-CM associated with the V1221 variant. The researchers also reported that penetrance was observed in 63% of individuals over 75 years of age (compared with 20% in those under), making older age a risk factor for ATTR-CM. 

Leedy and colleagues believe that these findings make targeted, risk-tailored screening easier to be carried out. With an improved screening framework, clinicians can use tools such as echocardiographic features and cardiac biomarkers to further filter individuals with a higher propensity for ATTR-CM. This finally allows clinicians to choose the best candidates for further genetic testing. 


Leedy DJ, Cuddy SAM, Cheng RK. Transthyretin cardiac amyloidosis: underrecognized in the underrepresentedJ Am Heart Assoc. Published online July 24, 2023. doi:10.1161/JAHA.123.030802