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 - 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.
AU - on behalf of the THAOS investigators
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
SN - 1932-6203
VL - 12
JO - PLoS One
JF - PLoS One
IS - 4
M1 - e0173086
ER -