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, David Eric
AU - Hummel, Scott L.
N1 - Funding Information:
A. V. K. has received research support from and served on advisory boards for Pfizer Inc. including the THAOS scientific advisory board. M. S. M. has received support from FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010, as a clinical investigator and for scientific meeting expenses. His institution has received grant support from Pfizer Inc. He serves on the THAOS scientific advisory board. C. R. has received unrestricted research grants from Pfizer Inc. He serves on the THAOS scientific advisory board. R. M. is an employee of Pfizer Inc. and holds stock options in Pfizer Inc. O. B. S. served as an advisor for Alnylam Pharmaceuticals, Isis Pharmaceuticals, and Pfizer Inc. as well as having served as an advisor and receiving support as a clinical investigator from FoldRx Pharmaceuticals, which was acquired by Pfizer Inc. in October 2010. He currently serves on the THAOS (natural history disease registry) scientific advisory board. T. D. has received research support from and served on advisory boards for Pfizer Inc. including the THAOS scientific advisory board. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Publisher Copyright:
© 2017 Kristen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/4
Y1 - 2017/4
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.
UR - http://www.scopus.com/inward/record.url?scp=85017185365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017185365&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0173086
DO - 10.1371/journal.pone.0173086
M3 - Article
C2 - 28384285
AN - SCOPUS:85017185365
SN - 1932-6203
VL - 12
JO - PLoS One
JF - PLoS One
IS - 4
M1 - e0173086
ER -