Genotype and Phenotype of Transthyretin Cardiac Amyloidosis

THAOS (Transthyretin Amyloid Outcome Survey)

Mathew S. Maurer, Mazen Hanna, Martha Grogan, Angela Dispenzieri, Ronald Witteles, Brian Drachman, Daniel P. Judge, Daniel J. Lenihan, Stephen S. Gottlieb, Sanjiv J. Shah, D. Eric Steidley, Hector Ventura, Srinivas Murali, Marc A. Silver, Daniel Jacoby, Savitri Fedson, Scott L. Hummel, Arnt V. Kristen, Thibaud Damy, Violaine Planté-Bordeneuve & 5 others Teresa Coelho, Rajiv Mundayat, Ole B. Suhr, Márcia Waddington Cruz, Claudio Rapezzi

Research output: Contribution to journalArticle

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)

Original languageEnglish (US)
Pages (from-to)161-172
Number of pages12
JournalJournal of the American College of Cardiology
Volume68
Issue number2
DOIs
StatePublished - Jul 12 2016

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Prealbumin
Amyloid
Genotype
Phenotype
Registries
Mutation
Survival
Hypesthesia
Isoleucine
Valine
Neurologic Manifestations
Cardiology
Nervous System
Walking
Arterial Pressure
Multivariate Analysis
Quality of Life
Demography
Surveys and Questionnaires
Amyloidosis, Hereditary, Transthyretin-Related

Keywords

  • aging
  • amyloid
  • transthyretin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Genotype and Phenotype of Transthyretin Cardiac Amyloidosis : THAOS (Transthyretin Amyloid Outcome Survey). / 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; Planté-Bordeneuve, Violaine; Coelho, Teresa; Mundayat, Rajiv; Suhr, Ole B.; Waddington Cruz, Márcia; Rapezzi, Claudio.

In: Journal of the American College of Cardiology, Vol. 68, No. 2, 12.07.2016, p. 161-172.

Research output: Contribution to journalArticle

Maurer, MS, Hanna, M, Grogan, M, Dispenzieri, A, Witteles, R, Drachman, B, Judge, DP, Lenihan, DJ, Gottlieb, SS, Shah, SJ, Steidley, DE, Ventura, H, Murali, S, Silver, MA, Jacoby, D, Fedson, S, Hummel, SL, Kristen, AV, Damy, T, Planté-Bordeneuve, V, Coelho, T, Mundayat, R, Suhr, OB, Waddington Cruz, M & Rapezzi, C 2016, 'Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey)', Journal of the American College of Cardiology, vol. 68, no. 2, pp. 161-172. https://doi.org/10.1016/j.jacc.2016.03.596
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 ; Planté-Bordeneuve, Violaine ; Coelho, Teresa ; Mundayat, Rajiv ; Suhr, Ole B. ; Waddington Cruz, Márcia ; Rapezzi, Claudio. / Genotype and Phenotype of Transthyretin Cardiac Amyloidosis : THAOS (Transthyretin Amyloid Outcome Survey). In: Journal of the American College of Cardiology. 2016 ; Vol. 68, No. 2. pp. 161-172.
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TY - JOUR

T1 - Genotype and Phenotype of Transthyretin Cardiac Amyloidosis

T2 - THAOS (Transthyretin Amyloid Outcome Survey)

AU - Maurer, Mathew S.

AU - Hanna, Mazen

AU - Grogan, Martha

AU - Dispenzieri, Angela

AU - Witteles, Ronald

AU - Drachman, Brian

AU - Judge, Daniel P.

AU - Lenihan, Daniel J.

AU - Gottlieb, Stephen S.

AU - Shah, Sanjiv J.

AU - Steidley, D. Eric

AU - Ventura, Hector

AU - Murali, Srinivas

AU - Silver, Marc A.

AU - Jacoby, Daniel

AU - Fedson, Savitri

AU - Hummel, Scott L.

AU - Kristen, Arnt V.

AU - Damy, Thibaud

AU - Planté-Bordeneuve, Violaine

AU - Coelho, Teresa

AU - Mundayat, Rajiv

AU - Suhr, Ole B.

AU - Waddington Cruz, Márcia

AU - Rapezzi, Claudio

PY - 2016/7/12

Y1 - 2016/7/12

N2 - 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)

AB - 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)

KW - aging

KW - amyloid

KW - transthyretin

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