{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:49:51Z","timestamp":1768481391626,"version":"3.49.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is an under-recognized aetiology of heart failure (HF), necessitating early detection for timely treatment. Our study aimed to differentiate patients with ATTRwt-CM from ATTRwt-negative HFpEF\/HFmrEF patients by identifying and validating circulating protein biomarkers. In addition, we measured the same biomarkers in patients with cardiomyopathy due to light chain amyloidosis (AL)-CM to gain disease-specific insights.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>In this observational study, serum concentrations of 363 protein biomarkers were measured in a discovery cohort consisting of 73 ATTRwt-CM, 55 AL-CM, and 59 ATTRwt-negative HFpEF\/HFmrEF patients, using multiplex proximity extension assays. Sparse partial least squares analyses showed overlapping ATTRwt-CM and AL-CM biomarker profiles with clear visual differentiation from ATTRwt-negative patients. Pathway analyses with g:Profiler revealed significantly up-regulated proteoglycans (PG) and cell adhesion pathways in both ATTRwt-CM and AL-CM. Penalized regression analysis revealed that the proteoglycan decorin (DCN), lysosomal hydrolase alpha-L-iduronidase (IDUA) and glycosyl hydrolase galactosidase \u03b2-1 (GLB-1) most effectively distinguished ATTRwt-CM from ATTRwt-negative patients (R2 = 0.71). In a prospective validation cohort of 35 ATTRwt-CM patients and 25 ATTRwt-negative patients, DCN and IDUA significantly predicted ATTRwt-CM in the initial analysis (DCN: OR 3.3, IDUA: OR 0.4). While DCN remained significant after correcting for echocardiographic parameters, IDUA did not. DCN showed moderate discriminative ability (AUC, 0.74; 95% CI, 0.61\u20130.87; sensitivity, 0.91; specificity, 0.52) as did IDUA (AUC, 0.78; 95% CI, 0.65\u20130.91; sensitivity, 0.91; specificity, 0.61). A model combining clinical factors (AUC 0.92) outperformed DCN but not IDUA, a combination of the biomarkers was not significantly better. Neither DCN nor IDUA correlated with established disease markers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>ATTRwt-CM has a distinctly different biomarker profile compared with HFpEF\/HFmrEF, while ATTRwt-CM patients share a similar biomarker profile with AL-CM patients characterized by up-regulation of proteoglycans and cell-adhesion pathways. The biomarkers DCN and IDUA show the potential to serve as an initial screening tool for ATTTRwt-CM. Further research is needed to determine the clinical usefulness of these and other extracellular matrix components in identifying ATTRwt-CM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae189","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T16:30:26Z","timestamp":1726590626000},"page":"1727-1736","source":"Crossref","is-referenced-by-count":6,"title":["Circulating ECM proteins decorin and alpha-L-iduronidase differentiate ATTRwt-CM from ATTRwt-negative HFpEF\/HFmrEF"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-958X","authenticated-orcid":false,"given":"Alwin","family":"Tubben","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Medical Centre Groningen , 9713GZ Groningen ,","place":["The Netherlands"]},{"name":"Amyloidosis Centre of Expertise , 9713GZ Groningen ,","place":["The 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,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5860-7943","authenticated-orcid":false,"given":"Lukas","family":"Baumhove","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Groningen , 9713GZ Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1056-0482","authenticated-orcid":false,"given":"Milou","family":"Berends","sequence":"additional","affiliation":[{"name":"Amyloidosis Centre of Expertise , 9713GZ Groningen ,","place":["The Netherlands"]},{"name":"Department of Internal Medicine, University Medical Centre Groningen , 9713GZ Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8572-9428","authenticated-orcid":false,"given":"Hendrea S A","family":"Tingen","sequence":"additional","affiliation":[{"name":"Amyloidosis Centre of Expertise , 9713GZ Groningen ,","place":["The Netherlands"]},{"name":"Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen , 9713GZ Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0375-4460","authenticated-orcid":false,"given":"Johan","family":"Bijzet","sequence":"additional","affiliation":[{"name":"Amyloidosis Centre of Expertise , 9713GZ Groningen ,","place":["The Netherlands"]},{"name":"Department of Laboratory Medicine, University Medical Centre Groningen , 9713GZ Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1827-0482","authenticated-orcid":false,"given":"Bouke P C","family":"Hazenberg","sequence":"additional","affiliation":[{"name":"Amyloidosis Centre of Expertise , 9713GZ Groningen ,","place":["The Netherlands"]},{"name":"Department of Internal Medicine, University Medical Centre Groningen , 9713GZ Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-4415","authenticated-orcid":false,"given":"Adriaan A","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Groningen , 9713GZ Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1611-7935","authenticated-orcid":false,"given":"Dirk J","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Groningen , 9713GZ Groningen ,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5565-1164","authenticated-orcid":false,"given":"Riemer H J 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