Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis

• Verfasst von: Kristen, Arnt [VerfasserIn]
• Titel: Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis
• Titelzusatz: report from the transthyretin amyloidosis outcome survey (THAOS)
• Verf.angabe: Arnt V. Kristen, Mathew S. Maurer, Claudio Rapezzi, Rajiv Mundayat, Ole B. Suhr, Thibaud Damy, on behalf of the THAOS investigators
• Jahr: 2017
• Umfang: 17 S.
• Fussnoten: Published: April 6, 2017 ; Gesehen am 27.06.2018
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2017
• Band/Heft Quelle: 12(2017), 4, Artikel-ID e0173086, Seite 1-17
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0173086
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Amyloid Neuropathies, Familial
• Sach-SW: Biomarkers
• Sach-SW: Genotype
• Sach-SW: Humans
• Sach-SW: Natriuretic Peptide, Brain
• Sach-SW: Phenotype
• Sach-SW: Surveys and Questionnaires
• Sach-SW: Troponin I
• Sach-SW: Troponin T
• K10plus-PPN: 157688578X

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.