Genotype and phenotype of transthyretin cardiac amyloidosis THAOS (Transthyretin Amyloid Outcome Survey)

Maurer, Mathew S., Hanna, Mazen, Grogan, Martha, Dispenzieri, Angela, Witteles, Ronald, Drachman, Brian, Judge, Daniel P., Lenihan, Daniel J., Gottlieb, Stephen S., Shah, Sanjiv J., Steidley, D. Eric, Ventura, Hector, Murali, Srinivas, Silver, Marc A., Jacoby, Daniel, Fedson, Savitri, Hummel, Scott L., Kristen, Arnt V., Damy, Thibaud, Plante-Bordeneuve, Violaine, Coelho, Teresa, Mundayat, Rajiv, Suhr, Ole B., Cruz, Marcia Waddington and Rapezzi, Claudio (2016) Genotype and phenotype of transthyretin cardiac amyloidosis THAOS (Transthyretin Amyloid Outcome Survey). Journal of the American College of Cardiology, 68 2: 161-172. doi:10.1016/j.jacc.2016.03.596

Author Maurer, Mathew S.
Hanna, Mazen
Grogan, Martha
Dispenzieri, Angela
Witteles, Ronald
Drachman, Brian
Judge, Daniel P.
Lenihan, Daniel J.
Gottlieb, Stephen S.
Shah, Sanjiv J.
Steidley, D. Eric
Ventura, Hector
Murali, Srinivas
Silver, Marc A.
Jacoby, Daniel
Fedson, Savitri
Hummel, Scott L.
Kristen, Arnt V.
Damy, Thibaud
Plante-Bordeneuve, Violaine
Coelho, Teresa
Mundayat, Rajiv
Suhr, Ole B.
Cruz, Marcia Waddington
Rapezzi, Claudio
Title Genotype and phenotype of transthyretin cardiac amyloidosis THAOS (Transthyretin Amyloid Outcome Survey)
Journal name Journal of the American College of Cardiology   Check publisher's open access policy
ISSN 0735-1097
Publication date 2016-07-12
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.jacc.2016.03.596
Open Access Status Not yet assessed
Volume 68
Issue 2
Start page 161
End page 172
Total pages 12
Place of publication San Diego, CA United States
Publisher Elsevier
Language eng
Formatted abstract

Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis.


The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry.


Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189).


U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild-type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival.


In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745)
Keyword Aging
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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