Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update
Authors: Dispenzieri Angela , Coelho Teresa , Conceição Isabel , Waddington-Cruz Márcia , Wixner Jonas , Kristen Arnt V. , Rapezzi Claudio , Planté-Bordeneuve Violaine , Gonzalez-Moreno Juan , Maurer Mathew S. , Grogan Martha , Chapman Doug , Amass Leslie ,   the THAOS investigators, Pavia Pablo Garcia , Tarnev Ivaylo , Costello Jose Gonzalez , Briseno Maria Alejandra Gonzalez Duarte , Schmidt Hartmut , Drachman Brian , Barroso Fabio Adrian , Yamashita Taro , Lairez Olivier , Sekijima Yoshiki , Vita Giuseppe , Jeon Eun-Seok , Hanna Mazen , Slosky David , Luigetti Marco , LoRusso Samantha , Beamud Francisco Munoz , Adams David , Moelgaard Henning , Press Rayomand , Cirami Calogero Lino , Nienhuis Hans , Plana Josep Maria Campistol , Inamo Jocelyn , Jacoby Daniel , Emdin Michele , Quan Dianna , Hummel Scott , Witteles Ronald , Dori Amir , Shah Sanjiv , Lenihan Daniel , Azevedo Olga , Murali Srinivas , Zivkovic Sasa , Low Soon Chai , Nativi-Nicolau Jose , Fine Nowell , Tallaj Jose , Tschoepe Carsten , Torrón Roberto Fernandéz , Polydefkis Michael , Merlini Giampaolo , Badelita Sorina , Gottlieb Stephen , Tauras James , Correia Edileide Barros , Ventura Hector , Gess Burkhard , Darstein Felix , Oh Jeeyoung , Marburger Tessa , Van Cleemput Johan , Salutto Valeria Lujan , Parman Yesim , Chao Chi-Chao , Sarswat Nitasha , Mueller Christopher , Steidley David , Ralph Jeffrey , Warner Alberta , Cotts William , Hoffman James , Rugiero Marcelo , Misawa Sonoko , Blanco Jose Luis Munoz , Davila Lucia Galan , Sadeh Menachem , Luo Jin , Kyriakides Theodoros , Wang Annabel , Kaufmann Horacio , Zivkovic Sasa 
Published: June 2022

Background

Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs.

Methods

Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021).

Results

This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation.

Conclusions

This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease.

ClinicalTrials.gov Identifier: NCT00628745.