Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis – Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)
Copyright policy )Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis – Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)
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.
- Alma Mater Studiorum University of Bologna Italy
- Columbia University Libraries, Open Scholarship Services United States
- Umeå University Sweden
- Centre Hospitalier Universitaire Henri-Mondor France
- Columbia University Medical Center United States
Genotype, Science, 610, Medicine (all); Biochemistry; Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all), Medicine (all); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all), Kardiologi och kardiovaskulära sjukdomar, Troponin T, Surveys and Questionnaires, Natriuretic Peptide, Brain, Humans, Atrial natriuretic peptides, Amyloid Neuropathies, Familial, Q, Biochemical markers, Troponin I, R, 600, Amyloidosis, Phenotype, Medicine, Cardiology and Cardiovascular Disease, Biomarkers, Research Article
Genotype, Science, 610, Medicine (all); Biochemistry; Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all), Medicine (all); Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all), Kardiologi och kardiovaskulära sjukdomar, Troponin T, Surveys and Questionnaires, Natriuretic Peptide, Brain, Humans, Atrial natriuretic peptides, Amyloid Neuropathies, Familial, Q, Biochemical markers, Troponin I, R, 600, Amyloidosis, Phenotype, Medicine, Cardiology and Cardiovascular Disease, Biomarkers, Research Article
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).66 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!