title: Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS).
abstract: OBJECTIVE
  Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking.
  
  
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00628745.
authors.affiliation: Amyloidosis Center, Department of Cardiology, Heidelberg University, Heidelberg, Germany.
authors.forename: Arnt V
authors.initials: AV
authors.lastname: Kristen
authors.affiliation: Center for Advanced Cardiac Care, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
authors.affiliation: Institute of Cardiology, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Rapezzi
authors.affiliation: Pfizer Inc., New York, New York, United States of America.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Mundayat
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
authors.forename: Ole B
authors.initials: OB
authors.lastname: Suhr
authors.affiliation: Amyloidosis Network, Department of Cardiology, CHU Henri Mondor, Creteil, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Damy
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D005838:Genotype; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010641:Phenotype; D011795:Surveys and Questionnaires; D019210:Troponin I / Q000097:blood; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D019210:Troponin I; D020107:Troponin T; D020097:Natriuretic Peptide, Brain