Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey)

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• 作者：Mathew S. Maurer ; MD^a ; ^{msm10@cumc.columbia.edu" class="auth_mail" title="E-mail the corresponding author} ; Mazen Hanna ; MD^b ; Martha Grogan ; MD^c ; Angela Dispenzieri ; MD^c ; Ronald Witteles ; MD^d ; Brian Drachman ; MD^e ; Daniel P. Judge ; MD^f ; Daniel J. Lenihan ; MD^g ; Stephen S. Gottlieb ; MD^h ; Sanjiv J. Shah ; MDⁱ ; D. Eric Steidley ; MD^j ; Hector Ventura ; MD^k ; Srinivas Murali ; MD^l ; Marc A. Silver ; MD^m ; Daniel Jacoby ; MDⁿ ; Savitri Fedson ; MD^o ; Scott L. Hummel ; MD^p ; ^q ; Arnt V. Kristen ; MD^r ; Thibaud Damy ; MD ; PhD^s ; Violaine Planté ; -Bordeneuve ; MD ; PhD^s ; Teresa Coelho ; MD^t ; Rajiv Mundayat ; MS^u ; Ole B. Suhr ; MD^v ; Má ; rcia Waddington Cruz ; MD^w ; Claudio Rapezzi ; MD^x ; on behalf of the THAOS Investigators
• 关键词：aging ; amyloid ; transthyretin
• 刊名：Journal of the American College of Cardiology
• 出版年：2016
• 出版时间：12 July 2016
• 年：2016
• 卷：68
• 期：2
• 页码：161-172
• 全文大小：1290 K

文摘

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

Objectives

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

Methods

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).

Results

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.

Conclusions

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)