title: Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey).
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).
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, New York. Electronic address: msm10@cumc.columbia.edu.
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: Mazen
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Martha
authors.initials: M
authors.lastname: Grogan
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Stanford University School of Medicine, Stanford, California.
authors.forename: Ronald
authors.initials: R
authors.lastname: Witteles
authors.affiliation: Penn Philadelphia Heart Institute, Philadelphia, Pennsylvania.
authors.forename: Brian
authors.initials: B
authors.lastname: Drachman
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lenihan
authors.affiliation: University of Maryland, Baltimore, Maryland.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gottlieb
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Sanjiv J
authors.initials: SJ
authors.lastname: Shah
authors.affiliation: Mayo Clinic, Phoenix, Arizona.
authors.forename: D Eric
authors.initials: DE
authors.lastname: Steidley
authors.affiliation: Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School-University of Queensland School of Medicine New Orleans, Louisiana.
authors.forename: Hector
authors.initials: H
authors.lastname: Ventura
authors.affiliation: Allegheny General Hospital, Pittsburgh, Pennsylvania.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Murali
authors.affiliation: Advocate Christ Medical Center, Chicago, Illinois.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Silver
authors.affiliation: Yale-New Haven Hospital, New Haven, Connecticut.
authors.forename: Daniel
authors.initials: D
authors.lastname: Jacoby
authors.affiliation: University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Savitri
authors.initials: S
authors.lastname: Fedson
authors.affiliation: University of Michigan, Ann Arbor, Michigan; Ann Arbor Veterans Affairs Health System, Ann Arbor, Michigan.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Hummel
authors.affiliation: Amyloidosis Center Medical University of Heidelberg, Heidelberg, Germany.
authors.forename: Arnt V
authors.initials: AV
authors.lastname: Kristen
authors.affiliation: University Hospital Henri Mondor, Créteil, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Damy
authors.affiliation: University Hospital Henri Mondor, Créteil, France.
authors.forename: Violaine
authors.initials: V
authors.lastname: Planté-Bordeneuve
authors.affiliation: Hospital de Santo António, Centro Hospitalar do Porto, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Coelho
authors.affiliation: Pfizer Inc, New York, New York.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Mundayat
authors.affiliation: Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Ole B
authors.initials: OB
authors.lastname: Suhr
authors.affiliation: University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Márcia
authors.initials: M
authors.lastname: Waddington Cruz
authors.affiliation: University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rapezzi
mesh_terms: D000368:Aged; D000682:Amyloid / Q000235:genetics* / Q000378:metabolism; D028227:Amyloid Neuropathies, Familial / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D009202:Cardiomyopathies / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012042:Registries; D011795:Surveys and Questionnaires; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology
chemical_list: D000682:Amyloid; D011228:Prealbumin; C041120:amyloid prealbumin
keywords: aging; amyloid; transthyretin