Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)

on behalf of the THAOS investigators

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Aim: Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking. Methods and results: Patients (n = 1617) with any of the following cardiac biomarkers, BNP (n = 1079), NT-proBNP (n = 550), troponin T (n = 274), and troponin I (n = 108), available at baseline in the Transthyretin Amyloidosis Outcomes Survey (THAOS) were analyzed for differences between genotypes and phenotypes and their association with survival. Median level of BNP was 68.0 pg/ mL (IQR 30.5-194.9), NT-proBNP 337.9 pg/mL (IQR 73.0-2584.0), troponin T 0.03 μg/L (IQR 0.01-0.05), and troponin I 0.08 μg/L (IQR 0.04-0.13). NT-proBNP and BNP were higher in wild-type than mutant-type ATTR, troponin T and I did not differ, respectively. Non-Val30- Met patients had higher BNP, NT-proBNP and troponin T levels than Val30Met patients, but not troponin I. Late-onset Val30Met was associated with higher levels of troponin I and troponin T compared with early-onset. 115 patients died during a median follow-up of 1.2 years. Mortality increased with increasing quartiles (BNP/NT-proBNP Q1 = 1.7%, Q2 = 5.2%, Q3 = 21.7%, Q4 = 71.3%; troponin T/I Q1 = 6.5%, Q2 = 14.5%, Q3 = 33.9%, Q4 = 45.2%). Threeyear overall-survival estimates for BNP/NT-proBNP and troponin T/I quartiles differed significantly (p<0.001). Stepwise risk stratification was achieved by combining NT-proBNP/BNP and troponin T/I. From Cox proportional hazards model, age, modified body mass index, mutation (Val30Met vs. Non-Val30Met) and BNP/NT-proBNP (Q1-Q3 pooled vs. Q4) were identified as independent predictors of survival in patients with mutant-type ATTR. Conclusions In this ATTR patient cohort, cardiac biomarkers were abnormal in a substantial percentage of patients irrespective of genotype. Along with age, mBMI, and mutation (Val30Met vs. Non-Val30Met), cardiac biomarkers were associated with surrogates of disease severity with BNP/NT-proBNP identified as an independent predictor of survival in ATTR.

Original languageEnglish (US)
Article numbere0173086
JournalPLoS One
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2017

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troponin T
amyloidosis
prealbumin
Prealbumin
Biomarkers
Troponin T
Troponin I
biomarkers
Genotype
Phenotype
phenotype
genotype
Survival
mutation
natriuretic peptides
troponins
mutants
Surveys and Questionnaires
pro-brain natriuretic peptide (1-76)
Amyloidosis, Hereditary, Transthyretin-Related

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS). / on behalf of the THAOS investigators.

In: PLoS One, Vol. 12, No. 4, e0173086, 01.04.2017.

Research output: Contribution to journalArticle

@article{88f2a087827a4df4b33b6438a1f37cdb,
title = "Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)",
abstract = "Aim: Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking. Methods and results: Patients (n = 1617) with any of the following cardiac biomarkers, BNP (n = 1079), NT-proBNP (n = 550), troponin T (n = 274), and troponin I (n = 108), available at baseline in the Transthyretin Amyloidosis Outcomes Survey (THAOS) were analyzed for differences between genotypes and phenotypes and their association with survival. Median level of BNP was 68.0 pg/ mL (IQR 30.5-194.9), NT-proBNP 337.9 pg/mL (IQR 73.0-2584.0), troponin T 0.03 μg/L (IQR 0.01-0.05), and troponin I 0.08 μg/L (IQR 0.04-0.13). NT-proBNP and BNP were higher in wild-type than mutant-type ATTR, troponin T and I did not differ, respectively. Non-Val30- Met patients had higher BNP, NT-proBNP and troponin T levels than Val30Met patients, but not troponin I. Late-onset Val30Met was associated with higher levels of troponin I and troponin T compared with early-onset. 115 patients died during a median follow-up of 1.2 years. Mortality increased with increasing quartiles (BNP/NT-proBNP Q1 = 1.7{\%}, Q2 = 5.2{\%}, Q3 = 21.7{\%}, Q4 = 71.3{\%}; troponin T/I Q1 = 6.5{\%}, Q2 = 14.5{\%}, Q3 = 33.9{\%}, Q4 = 45.2{\%}). Threeyear overall-survival estimates for BNP/NT-proBNP and troponin T/I quartiles differed significantly (p<0.001). Stepwise risk stratification was achieved by combining NT-proBNP/BNP and troponin T/I. From Cox proportional hazards model, age, modified body mass index, mutation (Val30Met vs. Non-Val30Met) and BNP/NT-proBNP (Q1-Q3 pooled vs. Q4) were identified as independent predictors of survival in patients with mutant-type ATTR. Conclusions In this ATTR patient cohort, cardiac biomarkers were abnormal in a substantial percentage of patients irrespective of genotype. Along with age, mBMI, and mutation (Val30Met vs. Non-Val30Met), cardiac biomarkers were associated with surrogates of disease severity with BNP/NT-proBNP identified as an independent predictor of survival in ATTR.",
author = "{on behalf of the THAOS investigators} and Kristen, {Arnt V.} and Maurer, {Mathew S.} and Claudio Rapezzi and Rajiv Mundayat and Suhr, {Ole B.} and Thibaud Damy and Barroso, {Fabio Adrian} and Rugiero, {Marcelo F.} and {Van Cleemput}, {Johan J.} and Ivailo Tournev and Cruz, {Marcia Waddington} and Fine, {Nowell M.} and Kristen, {Arnt Volko} and Schmidt, {Hartmut H.J.} and Tim Zimmermann and Burkhard Gess and Henning Moelgaard and Plana, {Josep Maria Campistol} and Reines, {Juan Buades} and Costello, {Jose Gonzalez} and Pavia, {Pablo Garcia} and Blanco, {Jose Luis Munoz} and Violaine Plante-Bordeneuve and David Adams and Jocelyn Inamo and Giuseppe Vita and Giampaolo Merlini and Franco Bergesio and Yoshiki Sekijima and Yukio Ando and Sonoko Misawa and Lee, {Ga Yeon} and Jeeyoung Oh and Briseno, {Maria Alejandra Gonzalez Duarte} and Hazenberg, {Bouke P.C.} and Teresa Coelho and Conceicao, {Isabel M.} and Maurer, {Mathew Shane} and Shah, {Sanjiv Jayendra} and Dianna Quan and Judge, {Daniel Philip} and Gottlieb, {Stephen Scott} and Nitasha Sarswat and Murali, {Srinivas C.} and Stanley Iyadurai and Cotts, {William Gerritt} and Drachman, {Brian M.} and Angela Dispenzieri and Steidley, {D Eric} and Hummel, {Scott L.}",
year = "2017",
month = "4",
day = "1",
doi = "10.1371/journal.pone.0173086",
language = "English (US)",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

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TY - JOUR

T1 - Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)

AU - on behalf of the THAOS investigators

AU - Kristen, Arnt V.

AU - Maurer, Mathew S.

AU - Rapezzi, Claudio

AU - Mundayat, Rajiv

AU - Suhr, Ole B.

AU - Damy, Thibaud

AU - Barroso, Fabio Adrian

AU - Rugiero, Marcelo F.

AU - Van Cleemput, Johan J.

AU - Tournev, Ivailo

AU - Cruz, Marcia Waddington

AU - Fine, Nowell M.

AU - Kristen, Arnt Volko

AU - Schmidt, Hartmut H.J.

AU - Zimmermann, Tim

AU - Gess, Burkhard

AU - Moelgaard, Henning

AU - Plana, Josep Maria Campistol

AU - Reines, Juan Buades

AU - Costello, Jose Gonzalez

AU - Pavia, Pablo Garcia

AU - Blanco, Jose Luis Munoz

AU - Plante-Bordeneuve, Violaine

AU - Adams, David

AU - Inamo, Jocelyn

AU - Vita, Giuseppe

AU - Merlini, Giampaolo

AU - Bergesio, Franco

AU - Sekijima, Yoshiki

AU - Ando, Yukio

AU - Misawa, Sonoko

AU - Lee, Ga Yeon

AU - Oh, Jeeyoung

AU - Briseno, Maria Alejandra Gonzalez Duarte

AU - Hazenberg, Bouke P.C.

AU - Coelho, Teresa

AU - Conceicao, Isabel M.

AU - Maurer, Mathew Shane

AU - Shah, Sanjiv Jayendra

AU - Quan, Dianna

AU - Judge, Daniel Philip

AU - Gottlieb, Stephen Scott

AU - Sarswat, Nitasha

AU - Murali, Srinivas C.

AU - Iyadurai, Stanley

AU - Cotts, William Gerritt

AU - Drachman, Brian M.

AU - Dispenzieri, Angela

AU - Steidley, D Eric

AU - Hummel, Scott L.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Aim: Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking. Methods and results: Patients (n = 1617) with any of the following cardiac biomarkers, BNP (n = 1079), NT-proBNP (n = 550), troponin T (n = 274), and troponin I (n = 108), available at baseline in the Transthyretin Amyloidosis Outcomes Survey (THAOS) were analyzed for differences between genotypes and phenotypes and their association with survival. Median level of BNP was 68.0 pg/ mL (IQR 30.5-194.9), NT-proBNP 337.9 pg/mL (IQR 73.0-2584.0), troponin T 0.03 μg/L (IQR 0.01-0.05), and troponin I 0.08 μg/L (IQR 0.04-0.13). NT-proBNP and BNP were higher in wild-type than mutant-type ATTR, troponin T and I did not differ, respectively. Non-Val30- Met patients had higher BNP, NT-proBNP and troponin T levels than Val30Met patients, but not troponin I. Late-onset Val30Met was associated with higher levels of troponin I and troponin T compared with early-onset. 115 patients died during a median follow-up of 1.2 years. Mortality increased with increasing quartiles (BNP/NT-proBNP Q1 = 1.7%, Q2 = 5.2%, Q3 = 21.7%, Q4 = 71.3%; troponin T/I Q1 = 6.5%, Q2 = 14.5%, Q3 = 33.9%, Q4 = 45.2%). Threeyear overall-survival estimates for BNP/NT-proBNP and troponin T/I quartiles differed significantly (p<0.001). Stepwise risk stratification was achieved by combining NT-proBNP/BNP and troponin T/I. From Cox proportional hazards model, age, modified body mass index, mutation (Val30Met vs. Non-Val30Met) and BNP/NT-proBNP (Q1-Q3 pooled vs. Q4) were identified as independent predictors of survival in patients with mutant-type ATTR. Conclusions In this ATTR patient cohort, cardiac biomarkers were abnormal in a substantial percentage of patients irrespective of genotype. Along with age, mBMI, and mutation (Val30Met vs. Non-Val30Met), cardiac biomarkers were associated with surrogates of disease severity with BNP/NT-proBNP identified as an independent predictor of survival in ATTR.

AB - Aim: Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking. Methods and results: Patients (n = 1617) with any of the following cardiac biomarkers, BNP (n = 1079), NT-proBNP (n = 550), troponin T (n = 274), and troponin I (n = 108), available at baseline in the Transthyretin Amyloidosis Outcomes Survey (THAOS) were analyzed for differences between genotypes and phenotypes and their association with survival. Median level of BNP was 68.0 pg/ mL (IQR 30.5-194.9), NT-proBNP 337.9 pg/mL (IQR 73.0-2584.0), troponin T 0.03 μg/L (IQR 0.01-0.05), and troponin I 0.08 μg/L (IQR 0.04-0.13). NT-proBNP and BNP were higher in wild-type than mutant-type ATTR, troponin T and I did not differ, respectively. Non-Val30- Met patients had higher BNP, NT-proBNP and troponin T levels than Val30Met patients, but not troponin I. Late-onset Val30Met was associated with higher levels of troponin I and troponin T compared with early-onset. 115 patients died during a median follow-up of 1.2 years. Mortality increased with increasing quartiles (BNP/NT-proBNP Q1 = 1.7%, Q2 = 5.2%, Q3 = 21.7%, Q4 = 71.3%; troponin T/I Q1 = 6.5%, Q2 = 14.5%, Q3 = 33.9%, Q4 = 45.2%). Threeyear overall-survival estimates for BNP/NT-proBNP and troponin T/I quartiles differed significantly (p<0.001). Stepwise risk stratification was achieved by combining NT-proBNP/BNP and troponin T/I. From Cox proportional hazards model, age, modified body mass index, mutation (Val30Met vs. Non-Val30Met) and BNP/NT-proBNP (Q1-Q3 pooled vs. Q4) were identified as independent predictors of survival in patients with mutant-type ATTR. Conclusions In this ATTR patient cohort, cardiac biomarkers were abnormal in a substantial percentage of patients irrespective of genotype. Along with age, mBMI, and mutation (Val30Met vs. Non-Val30Met), cardiac biomarkers were associated with surrogates of disease severity with BNP/NT-proBNP identified as an independent predictor of survival in ATTR.

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U2 - 10.1371/journal.pone.0173086

DO - 10.1371/journal.pone.0173086

M3 - Article

C2 - 28384285

AN - SCOPUS:85017185365

VL - 12

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e0173086

ER -