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
Abstract
BACKGROUND 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. (C) 2016 by the American College of Cardiology Foundation.
