{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:41:39Z","timestamp":1790023299133,"version":"4.0.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/01469"],"award-info":[{"award-number":["PI18\/01469"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CB16\/11\/00483"],"award-info":[{"award-number":["CB16\/11\/00483"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We quantified fibrosis in 209 DCM patients at three levels: (i) non\u2010invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino\u2010terminal propeptide of procollagen type III (PIIINP) and carboxy\u2010terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life\u2010threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90\u20136.60;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001 and PICP 1.02, 95% CI 1.01\u20131.03;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.007) and reclassification (net reclassification index: 0.28,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.02; and integrated discrimination improvement index: 0.139,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+\/PICP+) had the worst prognosis (log\u2010rank\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). RNA\u2010sequencing and gene enrichment analysis of EMB showed an increased expression of pro\u2010fibrotic and pro\u2010inflammatory pathways in patients with high levels of fibrosis (LGE+\/PICP+) compared to patients with low levels of fibrosis (LGE\u2010\/PICP\u2010). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro\u2010fibrotic and pro\u2010inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2201","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T03:52:38Z","timestamp":1619754758000},"page":"933-944","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["The combination of carboxy\u2010terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy\u00a0\u2013\u00a0A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy"],"prefix":"10.1093","volume":"23","author":[{"given":"Anne G.","family":"Raafs","sequence":"first","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Job A.J.","family":"Verdonschot","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"},{"name":"Department of Clinical Genetics Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel T.H.M.","family":"Henkens","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bouke P.","family":"Adriaans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper","family":"Derks","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrurgia A.","family":"Abdul Hamid","sequence":"additional","affiliation":[{"name":"Department of Pathology Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Knackstedt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa P.M.","family":"van Empel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"D\u00edez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases CIMA Universidad de Navarra and IdiSNA  Pamplona Spain"},{"name":"CIBERCV Carlos III Institute of Health  Madrid Spain"},{"name":"Departments of Nephrology and of Cardiology and Cardiac Surgery University of Navarra Clinic  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Peter","family":"Brunner\u2010La Rocca","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han G.","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Centre  Maastricht The Netherlands"},{"name":"Department of Human Genetics, and Donders Centre for Neuroscience, Radboud UMC  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantxa","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases CIMA Universidad de Navarra and IdiSNA  Pamplona Spain"},{"name":"CIBERCV Carlos III Institute of Health  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan C.A.M.","family":"Bekkers","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane R.B.","family":"Heymans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The Netherlands"},{"name":"Department of Cardiovascular Research University of Leuven  Leuven Belgium"},{"name":"Netherlands Heart Institute (Nl\u2010HI)  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Hazebroek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Centre  Maastricht The 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