DISCOVERY: prevalence of transthyretin () mutations in a US-centric patient population suspected of having cardiac amyloidosis.

BACKGROUND

Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a multisystem disease that presents with polyneuropathy and/or cardiomyopathy.

METHODS

DISCOVERY, a multicenter screening study, enrolled patients with clinically suspected cardiac amyloidosis to determine the frequency of transthyretin () mutations and assess disease characteristics.

RESULTS

Of 1007 patients, the majority were from the US (84%), Black/African American (56%), male (63%), and with a mean (standard deviation) age of 65 (13) years. Among 1001 patients with genotyping results, 74 (7%) had a pathogenic mutation (71/836 [8%] from the US). Val122Ile was the most common mutation, found in 11% of Black/African American patients overall; Black/African American ethnicity was an independent predictor of having a pathogenic mutation. Additional independent predictors of such mutations in the total population and Black/African American group were interventricular septum thickness, low electrocardiogram voltage, and age.

CONCLUSIONS

Pathogenic mutations occurred in 8% of US patients with suspected cardiac amyloidosis. Most mutations were Val122Ile, almost exclusively found in Black/African American patients. Disease often remains undetected until advanced and difficult to treat, therefore, clinicians should assess at-risk patients for hATTR amyloidosis as early as possible.