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

Arnt V. Kristen, Mathew S. Maurer, Claudio Rapezzi, Rajiv Mundayat, Ole B. Suhr, Thibaud Damy, Fabio Adrian Barroso, Marcelo F. Rugiero, Johan J. Van Cleemput, Ivailo Tournev, Marcia Waddington Cruz, Nowell M. Fine, Arnt Volko Kristen, Hartmut H.J. Schmidt, Tim Zimmermann, Burkhard Gess, Henning Moelgaard, Josep Maria Campistol Plana, Juan Buades Reines, Jose Gonzalez CostelloPablo Garcia Pavia, Jose Luis Munoz Blanco, Violaine Plante-Bordeneuve, David Adams, Jocelyn Inamo, Giuseppe Vita, Giampaolo Merlini, Franco Bergesio, Yoshiki Sekijima, Yukio Ando, Sonoko Misawa, Ga Yeon Lee, Jeeyoung Oh, Maria Alejandra Gonzalez Duarte Briseno, Bouke P.C. Hazenberg, Teresa Coelho, Isabel M. Conceicao, Mathew Shane Maurer, Sanjiv Jayendra Shah, Dianna Quan, Daniel Philip Judge, Stephen Scott Gottlieb, Nitasha Sarswat, Srinivas C. Murali, Stanley Iyadurai, William Gerritt Cotts, Brian M. Drachman, Angela Dispenzieri, David Eric Steidley, Scott L. Hummel, on behalf of the THAOS investigators

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36 Scopus citations


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
Issue number4
StatePublished - Apr 1 2017
Externally publishedYes

ASJC Scopus subject areas

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


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