Journal Article

DKFZ-2025-02414

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Profibrotic Biomarkers Correlate with Clinical Presentation and Outcome in Cardiac Transthyretin Amyloidosis.

Hein, S. J. ; Aus dem Siepen, F. ; Kristen, A. V. ; Schönland, S. ; Hegenbart, U. ; Rein, K.DKFZ* ; Katus, H. A. ; Frey, N. ; Furkel, J.DKFZ* ; Konstandin, M. H. ; Knoll, M. (Last author)DKFZ*

2025
Molecular Diversity Preservation International Basel

Abstract: In transthyretin cardiac amyloidosis (ATTR-CA), misfolded transthyretin accumulates in the myocardium, leading to wall thickening and interstitial fibrosis. Recently published in vitro studies revealed direct effects of transthyretin on the structure, function, and gene expression of cardiac fibroblasts. Therefore, we hypothesized that biomarkers known to modulate myocardial remodeling might be clinically valuable in ATTR-CA and may improve risk stratification in ATTR-CA. To analyze this hypothesis, we evaluated 14 fibrosis-related biomarkers (EN-RAGE, IGFBP-1, -2, -3, -4, -6, FGF-23, MMP-2, -7, -9, -13, TIMP-2, -4, and RAGE-AGE) in 125 patients using Luminex multiplex assays. The study cohort consists of 14 asymptomatic gene carriers (ATTRv-asymp), 47 symptomatic hereditary (ATTRv-CA), 43 wild-type Transthyretin amyloidosis (ATTRwt) patients, and 21 were healthy controls (ctrl). Associations of fibrotic biomarkers and clinical routine data with clinical outcomes-cardiac decompensation (DMP) and transplantation/death (HTX)-were assessed via hierarchical cluster analysis, regression, and prediction modeling. We found that ATTR-CA patients showed distinct biomarker profiles compared to controls. Several markers (e.g., MMP-7, RAGE-AGE, IGFBP-1, FGF-23, TIMP-2) were significantly associated with both endpoints. Cluster analysis identified a high-risk phenotype (Cluster 2) with worse renal function, greater myocardial thickening, and elevated NT-proBNP, hsTNT. Prediction modeling revealed IGFPB-1, -3, -4 and -6 as well as FGF-23, TIMP-2, and RAGE/AGE as the best predictive parameters for cluster assignment. Taken together, these findings confirm our hypothesis that fibrosis-related biomarkers are associated with adverse outcomes in ATTR-CM. Profibrotic mediators such as IGFBP-1, FGF-23, and TIMP-2 may, therefore, provide additional prognostic information beyond established cardiac biomarkers and may reflect underlying fibrotic remodeling pathways.

Keyword(s): Humans (MeSH) ; Biomarkers: metabolism (MeSH) ; Biomarkers: blood (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Amyloid Neuropathies, Familial: metabolism (MeSH) ; Amyloid Neuropathies, Familial: pathology (MeSH) ; Amyloid Neuropathies, Familial: diagnosis (MeSH) ; Fibroblast Growth Factor-23 (MeSH) ; Aged (MeSH) ; Fibrosis (MeSH) ; Prealbumin: metabolism (MeSH) ; Prealbumin: genetics (MeSH) ; Cardiomyopathies: metabolism (MeSH) ; Cardiomyopathies: pathology (MeSH) ; Myocardium: pathology (MeSH) ; Myocardium: metabolism (MeSH) ; Adult (MeSH) ; Prognosis (MeSH) ; cardiac transthyretin amyloidosis ; fibrosis ; outcome ; remodeling ; risk prediction ; Biomarkers ; Fibroblast Growth Factor-23 ; FGF23 protein, human ; Prealbumin

Note: #LA:E210#

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Contributing Institute(s):

1. E210 KKE Translationale Radioonkologie (E210)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2025

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Database coverage:
; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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