Clinical and Genotype Characteristics and Symptom Migration in Patients With Mixed Phenotype Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey

The THAOS investigators

doi:10.1007/s40119-023-00344-3

Clinical and Genotype Characteristics and Symptom Migration in Patients With Mixed Phenotype Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey

The THAOS investigators

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is primarily associated with a cardiac or neurologic phenotype, but a mixed phenotype is increasingly described. Methods: This study describes the mixed phenotype cohort in the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, longitudinal, observational survey of patients with ATTR amyloidosis, including both hereditary (ATTRv) and wild-type disease, and asymptomatic carriers of pathogenic transthyretin variants. Baseline characteristics of patients with a mixed phenotype (at enrollment or reclassified during follow-up) are described (data cutoff: January 4, 2022). Results: Approximately one-third of symptomatic patients (n = 1185/3542; 33.5%) were classified at enrollment or follow-up as mixed phenotype (median age, 66.5 years). Of those, 344 (29.0%) were reclassified to mixed phenotype within a median 1–2 years of follow-up. Most patients with mixed phenotype had ATTRv amyloidosis (75.7%). The most frequent genotypes were V30M (38.9%) and wild type (24.3%). Conclusions: These THAOS data represent the largest analysis of a real-world mixed phenotype ATTR amyloidosis population to date and suggest that a mixed phenotype may be more prevalent than previously thought. Patients may also migrate from a primarily neurologic or cardiologic presentation to a mixed phenotype over time. These data reinforce the need for multidisciplinary evaluation at initial assessment and follow-up of all patients with ATTR amyloidosis. Trial Registration: ClinicalTrials.gov: NCT00628745.

Original language	English (US)
Pages (from-to)	117-135
Number of pages	19
Journal	Cardiology and Therapy
Volume	13
Issue number	1
DOIs	https://doi.org/10.1007/s40119-023-00344-3
State	Published - Mar 2024

Funding

We thank all THAOS patients and investigators for their important contributions to this study. Additional THAOS investigators contributing to this analysis: Violaine Plante-Bordeneuve, CHU Henri Mondor, Cr\u00E9teil, France; Isabel Conceicao, Hospital Santa Maria, Lisboa, Portugal; Eun-Seok Jeon, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Mathew Maurer, Columbia University Medical Center, New York, NY, USA; Jose Gonzalez Costello, Hospital Universitari de Bellvitge, Barcelona, Spain; Olivier Lairez, CHU de Toulouse, Hopital Rangueil, Toulouse, France; Mitsuharu Ueda, Kumamoto University, Kumamoto, Japan; Arnt Kristen, Medical University of Heidelberg, Heidelberg, Germany; Yoshiki Sekijima, Shinshu University School of Medicine, Matsumoto, Japan; Brian Drachman, University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA, USA; David Slosky, Vanderbilt University School of Medicine, Nashville, TN, USA; Anna H\u00FCsing-Kabar, Universit\u00E4tsklinikum Muenster, Transplant Hepatology, Muenster, Germany; Maria Alejandra Gonzalez Duarte Briseno, Instituto Nacional de Ciencia Medicas y Nutricion Salvador Zubiran, Distrito Federal, Mexico; Miriam Freimer, The Ohio University College of Medicine, Columbus, OH, USA. Editorial support was provided by Emily Balevich, PhD, of Engage Scientific Solutions and was funded by Pfizer.

Keywords

Amyloidosis
Cardiomyopathy
Mixed phenotype
Polyneuropathy
THAOS
Transthyretin

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1007/s40119-023-00344-3

Cite this

@article{cd3ffcee4d5d432db06f7a17d22ba0d7,

title = "Clinical and Genotype Characteristics and Symptom Migration in Patients With Mixed Phenotype Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey",

abstract = "Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is primarily associated with a cardiac or neurologic phenotype, but a mixed phenotype is increasingly described. Methods: This study describes the mixed phenotype cohort in the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, longitudinal, observational survey of patients with ATTR amyloidosis, including both hereditary (ATTRv) and wild-type disease, and asymptomatic carriers of pathogenic transthyretin variants. Baseline characteristics of patients with a mixed phenotype (at enrollment or reclassified during follow-up) are described (data cutoff: January 4, 2022). Results: Approximately one-third of symptomatic patients (n = 1185/3542; 33.5%) were classified at enrollment or follow-up as mixed phenotype (median age, 66.5 years). Of those, 344 (29.0%) were reclassified to mixed phenotype within a median 1–2 years of follow-up. Most patients with mixed phenotype had ATTRv amyloidosis (75.7%). The most frequent genotypes were V30M (38.9%) and wild type (24.3%). Conclusions: These THAOS data represent the largest analysis of a real-world mixed phenotype ATTR amyloidosis population to date and suggest that a mixed phenotype may be more prevalent than previously thought. Patients may also migrate from a primarily neurologic or cardiologic presentation to a mixed phenotype over time. These data reinforce the need for multidisciplinary evaluation at initial assessment and follow-up of all patients with ATTR amyloidosis. Trial Registration: ClinicalTrials.gov: NCT00628745.",

keywords = "Amyloidosis, Cardiomyopathy, Mixed phenotype, Polyneuropathy, THAOS, Transthyretin",

author = "{The THAOS investigators} and Juan Gonz{\'a}lez-Moreno and Angela Dispenzieri and Martha Grogan and Teresa Coelho and Ivailo Tournev and M{\'a}rcia Waddington-Cruz and Jonas Wixner and Igor Diemberger and Pablo Garcia-Pavia and Doug Chapman and Pritam Gupta and Oliver Glass and Leslie Amass and Violaine Plante-Bordeneuve and Isabel Conceicao and Jeon, {Eun Seok} and Mathew Maurer and Costello, {Jose Gonzalez} and Olivier Lairez and Mitsuharu Ueda and Arnt Kristen and Yoshiki Sekijima and Brian Drachman and David Slosky and Anna H{\"u}sing-Kabar and Briseno, {Maria Alejandra Gonzalez Duarte} and Miriam Freimer and Marco Luigetti and Daniel Lenihan and Michael Polydefkis and Mazen Hanna and Hans Nienhuis and Stephen Gottlieb and Nicolau, {Jose Nativi} and Jocelyn Inamo and Michele Emdin and Olga Azevedo and Robert Brunkhorst and Edward Miller and Alberta Warner and Barroso, {Fabio Adrian} and Rayomand Press and Scott Hummel and Beamud, {Francisco Munoz} and Anna Mazzeo and Luca Gentile and Low, {Soon Chai} and Sorina Badelita and Dianna Quan and Sanjiv Shah",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2023.",

year = "2024",

month = mar,

doi = "10.1007/s40119-023-00344-3",

language = "English (US)",

volume = "13",

pages = "117--135",

journal = "Cardiology and Therapy",

issn = "2193-8261",

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TY - JOUR

T1 - Clinical and Genotype Characteristics and Symptom Migration in Patients With Mixed Phenotype Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey

AU - The THAOS investigators

AU - González-Moreno, Juan

AU - Dispenzieri, Angela

AU - Grogan, Martha

AU - Coelho, Teresa

AU - Tournev, Ivailo

AU - Waddington-Cruz, Márcia

AU - Wixner, Jonas

AU - Diemberger, Igor

AU - Garcia-Pavia, Pablo

AU - Chapman, Doug

AU - Gupta, Pritam

AU - Glass, Oliver

AU - Amass, Leslie

AU - Plante-Bordeneuve, Violaine

AU - Conceicao, Isabel

AU - Jeon, Eun Seok

AU - Maurer, Mathew

AU - Costello, Jose Gonzalez

AU - Lairez, Olivier

AU - Ueda, Mitsuharu

AU - Kristen, Arnt

AU - Sekijima, Yoshiki

AU - Drachman, Brian

AU - Slosky, David

AU - Hüsing-Kabar, Anna

AU - Briseno, Maria Alejandra Gonzalez Duarte

AU - Freimer, Miriam

AU - Luigetti, Marco

AU - Lenihan, Daniel

AU - Polydefkis, Michael

AU - Hanna, Mazen

AU - Nienhuis, Hans

AU - Gottlieb, Stephen

AU - Nicolau, Jose Nativi

AU - Inamo, Jocelyn

AU - Emdin, Michele

AU - Azevedo, Olga

AU - Brunkhorst, Robert

AU - Miller, Edward

AU - Warner, Alberta

AU - Barroso, Fabio Adrian

AU - Press, Rayomand

AU - Hummel, Scott

AU - Beamud, Francisco Munoz

AU - Mazzeo, Anna

AU - Gentile, Luca

AU - Low, Soon Chai

AU - Badelita, Sorina

AU - Quan, Dianna

AU - Shah, Sanjiv

PY - 2024/3

Y1 - 2024/3

N2 - Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is primarily associated with a cardiac or neurologic phenotype, but a mixed phenotype is increasingly described. Methods: This study describes the mixed phenotype cohort in the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, longitudinal, observational survey of patients with ATTR amyloidosis, including both hereditary (ATTRv) and wild-type disease, and asymptomatic carriers of pathogenic transthyretin variants. Baseline characteristics of patients with a mixed phenotype (at enrollment or reclassified during follow-up) are described (data cutoff: January 4, 2022). Results: Approximately one-third of symptomatic patients (n = 1185/3542; 33.5%) were classified at enrollment or follow-up as mixed phenotype (median age, 66.5 years). Of those, 344 (29.0%) were reclassified to mixed phenotype within a median 1–2 years of follow-up. Most patients with mixed phenotype had ATTRv amyloidosis (75.7%). The most frequent genotypes were V30M (38.9%) and wild type (24.3%). Conclusions: These THAOS data represent the largest analysis of a real-world mixed phenotype ATTR amyloidosis population to date and suggest that a mixed phenotype may be more prevalent than previously thought. Patients may also migrate from a primarily neurologic or cardiologic presentation to a mixed phenotype over time. These data reinforce the need for multidisciplinary evaluation at initial assessment and follow-up of all patients with ATTR amyloidosis. Trial Registration: ClinicalTrials.gov: NCT00628745.

AB - Introduction: Transthyretin amyloidosis (ATTR amyloidosis) is primarily associated with a cardiac or neurologic phenotype, but a mixed phenotype is increasingly described. Methods: This study describes the mixed phenotype cohort in the Transthyretin Amyloidosis Outcomes Survey (THAOS). THAOS is an ongoing, longitudinal, observational survey of patients with ATTR amyloidosis, including both hereditary (ATTRv) and wild-type disease, and asymptomatic carriers of pathogenic transthyretin variants. Baseline characteristics of patients with a mixed phenotype (at enrollment or reclassified during follow-up) are described (data cutoff: January 4, 2022). Results: Approximately one-third of symptomatic patients (n = 1185/3542; 33.5%) were classified at enrollment or follow-up as mixed phenotype (median age, 66.5 years). Of those, 344 (29.0%) were reclassified to mixed phenotype within a median 1–2 years of follow-up. Most patients with mixed phenotype had ATTRv amyloidosis (75.7%). The most frequent genotypes were V30M (38.9%) and wild type (24.3%). Conclusions: These THAOS data represent the largest analysis of a real-world mixed phenotype ATTR amyloidosis population to date and suggest that a mixed phenotype may be more prevalent than previously thought. Patients may also migrate from a primarily neurologic or cardiologic presentation to a mixed phenotype over time. These data reinforce the need for multidisciplinary evaluation at initial assessment and follow-up of all patients with ATTR amyloidosis. Trial Registration: ClinicalTrials.gov: NCT00628745.

KW - Amyloidosis

KW - Cardiomyopathy

KW - Mixed phenotype

KW - Polyneuropathy

KW - THAOS

KW - Transthyretin

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U2 - 10.1007/s40119-023-00344-3

DO - 10.1007/s40119-023-00344-3

M3 - Article

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AN - SCOPUS:85180174220

SN - 2193-8261

VL - 13

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JO - Cardiology and Therapy

JF - Cardiology and Therapy

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ER -

Clinical and Genotype Characteristics and Symptom Migration in Patients With Mixed Phenotype Transthyretin Amyloidosis from the Transthyretin Amyloidosis Outcomes Survey

Abstract

Funding

Keywords

ASJC Scopus subject areas

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