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

Publication Details

Amyloid

May 2020

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Author(s)

Ola Akinboboye¹, Keyur Shah², Alberta L Warner³, Thibaud Damy⁴, Herman A Taylor⁵, Jared Gollob⁶, Christine Powell⁶, Verena Karsten⁶, John Vest⁶, Mathew S Maurer⁷

Affiliations

¹Laurelton Heart Specialists, Rosedale, NY, USA; ²Virginia Commonwealth University Medical Center, Richmond, VA, USA; ³VA Greater Los Angeles Health Care System, University of California, Los Angeles, CA, USA; ⁴Mondor Amyloidosis Network and GRC Amyloid Research Institute and Department of Cardiology at AP-HP Henri-Mondor Teaching Hospital and UPEC, Créteil, France; ⁵Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, GA, USA; ⁶Alnylam Pharmaceuticals, Cambridge, MA, USA; ⁷Cardiovascular Research Lab for the Elderly at New York-Presbyterian/Columbia Allen Hospital, Columbia University Medical Center, New York, NY, USA

Abstract

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 (TTR) 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 TTR 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 TTR 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 TTR 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.