Mathew S Maurer1, Mazen Hanna2, Martha Grogan3, Angela Dispenzieri3, Ronald Witteles4, Brian Drachman5, Daniel P Judge6, Daniel J Lenihan7, Stephen S Gottlieb8, Sanjiv J Shah9, D Eric Steidley10, Hector Ventura11, Srinivas Murali12, Marc A Silver13, Daniel Jacoby14, Savitri Fedson15, Scott L Hummel16, Arnt V Kristen17, Thibaud Damy18, Violaine Planté-Bordeneuve18, Teresa Coelho19, Rajiv Mundayat20, Ole B Suhr21, Márcia Waddington Cruz22, Claudio Rapezzi23. 1. Columbia University College of Physicians and Surgeons, New York, New York. Electronic address: msm10@cumc.columbia.edu. 2. Cleveland Clinic, Cleveland, Ohio. 3. Mayo Clinic, Rochester, Minnesota. 4. Stanford University School of Medicine, Stanford, California. 5. Penn Philadelphia Heart Institute, Philadelphia, Pennsylvania. 6. Johns Hopkins University, Baltimore, Maryland. 7. Vanderbilt University School of Medicine, Nashville, Tennessee. 8. University of Maryland, Baltimore, Maryland. 9. Northwestern University Feinberg School of Medicine, Chicago, Illinois. 10. Mayo Clinic, Phoenix, Arizona. 11. Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School-University of Queensland School of Medicine New Orleans, Louisiana. 12. Allegheny General Hospital, Pittsburgh, Pennsylvania. 13. Advocate Christ Medical Center, Chicago, Illinois. 14. Yale-New Haven Hospital, New Haven, Connecticut. 15. University of Chicago Medical Center, Chicago, Illinois. 16. University of Michigan, Ann Arbor, Michigan; Ann Arbor Veterans Affairs Health System, Ann Arbor, Michigan. 17. Amyloidosis Center Medical University of Heidelberg, Heidelberg, Germany. 18. University Hospital Henri Mondor, Créteil, France. 19. Hospital de Santo António, Centro Hospitalar do Porto, Portugal. 20. Pfizer Inc, New York, New York. 21. Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 22. University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. 23. University of Bologna, Bologna, Italy.
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. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745).
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. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745).
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