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@ARTICLE{Hein:306174,
      author       = {S. J. Hein and F. Aus dem Siepen and A. V. Kristen and S.
                      Schönland and U. Hegenbart and K. Rein$^*$ and H. A. Katus
                      and N. Frey and J. Furkel$^*$ and M. H. Konstandin and M.
                      Knoll$^*$},
      title        = {{P}rofibrotic {B}iomarkers {C}orrelate with {C}linical
                      {P}resentation and {O}utcome in {C}ardiac {T}ransthyretin
                      {A}myloidosis.},
      journal      = {International journal of molecular sciences},
      volume       = {26},
      number       = {21},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DKFZ-2025-02414},
      pages        = {10714},
      year         = {2025},
      note         = {#LA:E210#},
      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.},
      keywords     = {Humans / Biomarkers: metabolism / Biomarkers: blood / Male
                      / Female / Middle Aged / Amyloid Neuropathies, Familial:
                      metabolism / Amyloid Neuropathies, Familial: pathology /
                      Amyloid Neuropathies, Familial: diagnosis / Fibroblast
                      Growth Factor-23 / Aged / Fibrosis / Prealbumin: metabolism
                      / Prealbumin: genetics / Cardiomyopathies: metabolism /
                      Cardiomyopathies: pathology / Myocardium: pathology /
                      Myocardium: metabolism / Adult / Prognosis / cardiac
                      transthyretin amyloidosis (Other) / fibrosis (Other) /
                      outcome (Other) / remodeling (Other) / risk prediction
                      (Other) / Biomarkers (NLM Chemicals) / Fibroblast Growth
                      Factor-23 (NLM Chemicals) / FGF23 protein, human (NLM
                      Chemicals) / Prealbumin (NLM Chemicals)},
      cin          = {E210 / HD01},
      ddc          = {540},
      cid          = {I:(DE-He78)E210-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {315 - Bildgebung und Radioonkologie (POF4-315)},
      pid          = {G:(DE-HGF)POF4-315},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41226753},
      doi          = {10.3390/ijms262110714},
      url          = {https://inrepo02.dkfz.de/record/306174},
}