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