{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:42:00Z","timestamp":1788892920453,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Myocardial scarring is a primary pathogenetic process in nonischemic dilated cardiomyopathy (NIDCM) that is responsible for progressive cardiac remodeling and heart failure, severely impacting the survival of these patients. Although several collagen turnover biomarkers have been associated with myocardial fibrosis, their clinical utility is still limited. Late gadolinium enhancement (LGE) determined by cardiac magnetic resonance imaging (CMR) has become a feasible method to detect myocardial replacement fibrosis. We sought to evaluate the association between collagen turnover biomarkers and replacement myocardial scarring by CMR and, also, to test their ability to predict outcome in conjunction with LGE in patients with NIDCM. Method: We conducted a prospective study on 194 patients (48.7 \u00b1 14.3 years of age; 74% male gender) with NIDCM. The inclusion criteria were similar to those for the definition of NIDCM, performed exclusively by CMR: (1) LV dilation with an LV end-diastolic volume (LVEDV) of over 97 mL\/m2; (2) global LV dysfunction, expressed as a decreased LVEF of under 45%. CMR was used to determine the presence and extent of LGE. Several collagen turnover biomarkers were determined at diagnosis, comprising galectin-3 (Gal3), procollagen type I carboxy-terminal pro-peptide (PICP) and N-terminal pro-peptide of procollagen type III (PIIINP). A composite outcome (all-cause mortality, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. Results: Gal3, PICP and PIIINP were considerably increased in those with LGE+ (p &lt; 0.001), also being directly correlated with LGE mass (r2 = 0.42; r2 = 0.44; r2 = 0.31; all p &lt; 0.001). Receiver operating characteristic (ROC) analysis revealed a significant ability to diagnose LGE, with an area under the ROC of 0.816 for Gal3, 0.705 for PICP, and 0.757 for PIIINP (all p &lt; 0.0001). Kaplan\u2013Meier analysis showed that at a threshold of &gt;13.8 ng\/dL for Gal3 and &gt;97 ng\/dL for PICP, they were able to significantly predict outcome (HR = 2.66, p &lt; 0.001; HR = 1.93, p &lt; 0.002). Of all patients, 17% (n = 33) reached the outcome. In multivariate analysis, after adjustment for covariates, only LGE+ and Gal3+ remained independent predictors for outcome (p = 0.008; p = 0.04). Nonetheless, collagen turnover biomarkers were closely related to HF severity, providing incremental predictive value for severely decreased LVEF of under 30% in patients with NIDCM, beyond that with LGE alone. Conclusions: In patients with NIDCM, circulating collagen turnover biomarkers such as Gal3, PICP and PIIINP are closely related to the presence and extent of LGE and can significantly predict cardiovascular outcome. The joint use of LGE with Gal3 and PICP significantly improved outcome prediction.<\/jats:p>","DOI":"10.3390\/diagnostics12061435","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T10:25:12Z","timestamp":1654856712000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Role of Circulating Collagen Turnover Biomarkers and Late Gadolinium Enhancement in Patients with Non-Ischemic Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"12","author":[{"given":"Radu","family":"Revnic","sequence":"first","affiliation":[{"name":"Department of Family Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Olivia","family":"Cojan-Minzat","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1478-8156","authenticated-orcid":false,"given":"Alexandru","family":"Zlibut","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rares-Ilie","family":"Orzan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Agoston","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana Danuta","family":"Muresan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalma","family":"Horvat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Cionca","sequence":"additional","affiliation":[{"name":"Department of Radiology, Affidea Hiperdia Diagnostic Imaging Centre, 400487 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-2593","authenticated-orcid":false,"given":"Bogdan","family":"Chis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Department of Internal Medicine, Emergency County Hospital, 400347 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Agoston-Coldea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Department of Internal Medicine, Emergency County Hospital, 400347 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1001\/jama.2013.1363","article-title":"Association of Fibrosis with Mortality and Sudden Cardiac Death in Patients with Nonischemic Dilated Cardiomyopathy","volume":"309","author":"Gulati","year":"2013","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/eurheartj\/ehy713","article-title":"Prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in older adults","volume":"40","author":"Shanbhag","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1002\/ejhf.1406","article-title":"Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology","volume":"21","author":"Bauersachs","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1016\/j.jacc.2018.02.021","article-title":"Myocardial Interstitial Fibrosis in Heart Failure","volume":"71","author":"Schelbert","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1161\/CIRCHEARTFAILURE.112.000146","article-title":"Galectin-3 and Cardiac Function in Survivors of Acute Myocardial Infarction","volume":"6","author":"Weir","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3121","DOI":"10.1161\/01.CIR.0000147181.65298.4D","article-title":"Galectin-3 Marks Activated Macrophages in Failure-Prone Hypertrophied Hearts and Contributes to Cardiac Dysfunction","volume":"110","author":"Sharma","year":"2004","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s00392-010-0125-y","article-title":"Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: Data from the DEAL-HF study","volume":"99","author":"Lok","year":"2010","journal-title":"Clin. Res. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00392-012-0500-y","article-title":"Galectin-3 is an independent marker for ventricular remodeling and mortality in patients with chronic heart failure","volume":"102","author":"Lok","year":"2013","journal-title":"Clin. Res. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1161\/ATVBAHA.112.300569","article-title":"Galectin-3 Mediates Aldosterone-Induced Vascular Fibrosis","volume":"33","author":"Calvier","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1017\/S1462399408000719","article-title":"Galectins: Structure, function and therapeutic potential","volume":"10","author":"Yang","year":"2008","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1161\/CIRCHEARTFAILURE.113.000996","article-title":"Incremental Prognostic Value of Myocardial Fibrosis in Patients With Non\u2013Ischemic Cardiomyopathy Without Congestive Heart Failure","volume":"7","author":"Masci","year":"2014","journal-title":"Circ. Heart Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1161\/CIRCHEARTFAILURE.112.971168","article-title":"Genetic and Pharmacological Inhibition of Galectin-3 Prevents Cardiac Remodeling by Interfering With Myocardial Fibrogenesis","volume":"6","author":"Yu","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_13","first-page":"486","article-title":"Correlations between echocardiographic parameters of right ventricular dysfunction and Galectin-3 in patients with chronic obstructive pulmonary disease and pulmonary hypertension","volume":"17","author":"Lupu","year":"2015","journal-title":"Med. Ultrason."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3109\/07853890.2010.538080","article-title":"Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction","volume":"43","author":"Lok","year":"2011","journal-title":"Ann. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ijcard.2015.02.008","article-title":"Galectin-3 and myocardial fibrosis in nonischemic dilated cardiomyopathy","volume":"184","author":"Vergaro","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/ejhf.2201","article-title":"The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy\u2014A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy","volume":"23","author":"Raafs","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1093\/eurheartj\/ehv727","article-title":"Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: A position statement of the ESC working group on myocardial and pericardial diseases","volume":"37","author":"Pinto","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12968-021-00811-7","article-title":"Quantitative assessment of velocity and flow using compressed SENSE in children and young adults with adequate acquired temporal resolution","volume":"23","author":"Kocaoglu","year":"2021","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12968-019-0564-1","article-title":"Prognostic value of novel imaging parameters derived from standard cardiovascular magnetic resonance in high risk patients with systemic light chain amyloidosis","volume":"21","author":"Arenja","year":"2019","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.jcmg.2019.01.003","article-title":"Left Ventricular Spherical Index Is an Independent Predictor for Clinical Outcomes in Patients with Nonischemic Dilated Cardiomyopathy","volume":"12","author":"Liang","year":"2019","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1161\/hc0402.102975","article-title":"Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart","volume":"105","author":"Cerqueira","year":"2002","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1081\/JCMR-200053623","article-title":"Standardizing the Definition of Hyperenhancement in the Quantitative Assessment of Infarct Size and Myocardial Viability Using Delayed Contrast-Enhanced CMR","volume":"7","author":"Bondarenko","year":"2005","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1007\/s10741-020-09940-0","article-title":"Non-ischemic dilated cardiomyopathy and cardiac fibrosis","volume":"26","author":"Zlibut","year":"2021","journal-title":"Heart Fail. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/j.jcmg.2018.07.015","article-title":"Outcome in Dilated Cardiomyopathy Related to the Extent, Location, and Pattern of Late Gadolinium Enhancement","volume":"12","author":"Halliday","year":"2019","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/eurheartj\/ehr391","article-title":"Effects of myocardial fibrosis and ventricular dyssynchrony on response to therapy in new-presentation idiopathic dilated cardiomyopathy: Insights from cardiovascular magnetic resonance and echocardiography","volume":"33","author":"Leong","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"H45","DOI":"10.1152\/ajpheart.00609.2018","article-title":"Galectin-3 deficiency ameliorates fibrosis and remodeling in dilated cardiomyopathy mice with enhanced Mst1 signaling","volume":"316","author":"Nguyen","year":"2019","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/j.jacc.2015.04.026","article-title":"Circulating Biomarkers of Myocardial Fibrosis","volume":"65","author":"Ravassa","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1253\/circj.CJ-11-0568","article-title":"Prognostic Impact of Myocardial Interstitial Fibrosis in Non-Ischemic Heart Failure","volume":"75","author":"Aoki","year":"2011","journal-title":"Circ. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/j.jacc.2010.09.080","article-title":"Cardiomyocyte Hypertrophy, Oncosis, and Autophagic Vacuolization Predict Mortality in Idiopathic Dilated Cardiomyopathy With Advanced Heart Failure","volume":"57","author":"Vigliano","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1136\/heartjnl-2018-313182","article-title":"Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure","volume":"105","author":"Ferreira","year":"2019","journal-title":"Heart"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e007944","DOI":"10.1161\/CIRCHEARTFAILURE.120.007944","article-title":"Myocardial Tissue Reverse Remodeling After Guideline-Directed Medical Therapy in Idiopathic Dilated Cardiomyopathy","volume":"14","author":"Xu","year":"2021","journal-title":"Circ. Heart Fail."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/6\/1435\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:27:36Z","timestamp":1760138856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/6\/1435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["diagnostics12061435"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12061435","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,10]]}}}