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

PLoS One. 2017 Apr 6;12(4):e0173086. doi: 10.1371/journal.pone.0173086. eCollection 2017.

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-Val30Met 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%). Three-year 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.

Trial registration: ClinicalTrials.gov NCT00628745.

MeSH terms

  • Amyloid Neuropathies, Familial / genetics*
  • Amyloid Neuropathies, Familial / physiopathology
  • Biomarkers / blood*
  • Genotype*
  • Humans
  • Natriuretic Peptide, Brain / blood
  • Phenotype*
  • Surveys and Questionnaires
  • Troponin I / blood
  • Troponin T / blood

Substances

  • Biomarkers
  • Troponin I
  • Troponin T
  • Natriuretic Peptide, Brain

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Associated data

  • ClinicalTrials.gov/NCT00628745

Grants and funding

THAOS registry is funded by Pfizer Inc. Data collection and analysis in THAOS were supported by Pfizer Inc. Pfizer Inc. provided financial support to enable the development and hosting of THAOS by a database vendor and provided compensation to survey sites for data reporting and quality of life assessment. A Scientific Board comprising participating physicians, clinical experts, and a medical representative of the sponsor gave advice on scientific and policy decisions and oversaw data review and analysis. The funder provided statistical support, and the statistician participated as an author, but other than this, the funder had no role in the decision to publish, in the interpretation of the findings, or in the writing of the manuscript. Assistance in preparing the manuscript for submission (editing and formatting of tables and text) was provided by Shuang Li, PhD, at Engage Scientific and was funded by Pfizer Inc. The authors take full responsibility for the content of the article.