{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:13:53Z","timestamp":1792030433822,"version":"4.4.0"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Introduction: Inflammatory cardiomyopathy (ICM) frequently leads to myocardial fibrosis, resulting in permanent deterioration of the left ventricular function and an unfavorable outcome. Soluble suppression of tumorigenicity 2 receptor (sST2) is a novel marker of inflammation and fibrosis in cardiovascular tissues. sST2 was found to be helpful in predicting adverse outcomes in heart failure patients with reduced ejection fraction. The aim of this study was to determine the association of sST2 plasma levels with cardiac magnetic resonance (CMR) and echocardiography imaging features of left ventricular impairment in ICM patients, as well as to evaluate the applicability of sST2 as a prognosticator of the clinical status in patients suffering from ICM. Methods: We used plasma samples of 89 patients presenting to the Heart Center Leipzig with clinically suspected myocardial inflammation. According to immunohistochemical findings in endomyocardial biopsies (EMB) conducted in the context of patients\u2019 diagnostic work-up, inflammatory cardiomyopathy was diagnosed in 60 patients (ICM group), and dilated cardiomyopathy in 29 patients (DCM group). All patients underwent cardiac catheterization for exclusion of coronary artery disease and CMR imaging on 1.5 or 3 Tesla. sST2 plasma concentration was determined using ELISA. Results: Mean plasma concentration of sST2 in the whole patient cohort was 45.8 \u00b1 26.4 ng\/mL (IQR 27.5 ng\/mL). In both study groups, patients within the highest quartile of sST2 plasma concentration had a significantly lower left ventricular ejection fraction (LV-EF) compared to patients within the lowest sST2 plasma concentration quartile (26 \u00b1 11% vs. 40 \u00b1 13%, p = 0.05 for ICM and 24 \u00b1 13% vs. 51 \u00b1 10%, p = 0.004 for DCM). sST2 predicted New York Heart Association (NYHA) class III\/IV at 12 months follow-up more efficiently in ICM compared to DCM patients (AUC 0.85 vs. 0.61, p = 0.02) and was in these terms superior to NT-proBNP and cardiac troponin T. ICM patients with sST2 plasma concentration higher than 44 ng\/mL at baseline had a significantly higher probability of being assigned to NYHA class III\/IV at 12 months follow-up (hazard ratio 2.8, 95% confidence interval 1.01\u20137.6, log rank p = 0.05). Conclusion: Plasma sST2 levels in ICM patients reflect the degree of LV functional impairment at hospital admission and predict functional NYHA class at mid-term follow-up. Hence, ST2 may be helpful in the evaluation of disease severity and in the prediction of the clinical status in ICM patients.<\/jats:p>","DOI":"10.3390\/cells11030414","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:44:33Z","timestamp":1643143473000},"page":"414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Soluble ST2 Receptor: Biomarker of Left Ventricular Impairment and Functional Status in Patients with Inflammatory Cardiomyopathy"],"prefix":"10.3390","volume":"11","author":[{"given":"Danilo Momira","family":"Obradovic","sequence":"first","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at the University of Leipzig, Str\u00fcmpellstra\u00dfe 39, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0799-4725","authenticated-orcid":false,"given":"Petra","family":"B\u00fcttner","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at the University of Leipzig, Str\u00fcmpellstra\u00dfe 39, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-8138","authenticated-orcid":false,"given":"Karl-Philipp","family":"Rommel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at the University of Leipzig, Str\u00fcmpellstra\u00dfe 39, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Blazek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at the University of Leipzig, Str\u00fcmpellstra\u00dfe 39, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goran","family":"Loncar","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Diseases \u201cDedinje\u201d, Faculty of Medicine, University of Belgrade, 11040 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"von Haehling","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, Heart Center, University of G\u00f6ttingen Medical Center, 37099 Gottingen, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site G\u00f6ttingen, 37099 Gottingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"von Roeder","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at the University of Leipzig, Str\u00fcmpellstra\u00dfe 39, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"L\u00fccke","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, Heart Center Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Gutberlet","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, Heart Center Leipzig, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-998X","authenticated-orcid":false,"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at the University of Leipzig, Str\u00fcmpellstra\u00dfe 39, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Lurz","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at the University of Leipzig, Str\u00fcmpellstra\u00dfe 39, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Besler","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Heart Center Leipzig at the University of Leipzig, Str\u00fcmpellstra\u00dfe 39, 04289 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.gheart.2014.01.007","article-title":"The global burden of myocarditis: Part 1: A systematic literature review for the Global Burden of Diseases, Injuries, and Risk Factors 2010 study","volume":"9","author":"Cooper","year":"2014","journal-title":"Glob. Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1161\/hc3401.095198","article-title":"Advances in the understanding of myocarditis","volume":"104","author":"Liu","year":"2001","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/ncpcardio1331","article-title":"Fulminant myocarditis","volume":"5","author":"Gupta","year":"2008","journal-title":"Nat. Clin. Pr. Cardiovasc. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0008-6363(03)00437-1","article-title":"Myocarditis and dilated cardiomyopathy: An inflammatory link","volume":"60","author":"Mason","year":"2003","journal-title":"Cardiovasc. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.jacc.2009.02.007","article-title":"Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper","volume":"53","author":"Friedrich","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jcmg.2013.10.011","article-title":"CMR sensitivity varies with clinical presentation and extent of cell necrosis in biopsy-proven acute myocarditis","volume":"7","author":"Francone","year":"2014","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1161\/CIRCULATIONAHA.117.026386","article-title":"Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis","volume":"136","author":"Ammirati","year":"2017","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1046\/j.1432-1327.1999.00615.x","article-title":"Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells","volume":"264","author":"Iwahana","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1172\/JCI30634","article-title":"IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system","volume":"117","author":"Sanada","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nrd2660","article-title":"The IL-33\/ST2 pathway: Therapeutic target and novel biomarker","volume":"7","author":"Kakkar","year":"2008","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1161\/CIRCULATIONAHA.105.606509","article-title":"Presentation, patterns of myocardial damage, and clinical course of viral myocarditis","volume":"114","author":"Mahrholdt","year":"2006","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1093\/eurheartj\/ehp328","article-title":"Diagnostic synergy of non-invasive cardiovascular magnetic resonance and invasive endomyocardial biopsy in troponin-positive patients without coronary artery disease","volume":"30","author":"Baccouche","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.jcmg.2011.11.022","article-title":"Diagnostic performance of CMR imaging compared with EMB in patients with suspected myocarditis","volume":"5","author":"Lurz","year":"2012","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1161\/01.CIR.0000118493.13323.81","article-title":"Cardiovascular magnetic resonance assessment of human myocarditis: A comparison to histology and molecular pathology","volume":"109","author":"Mahrholdt","year":"2004","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/3-540-30822-9_17","article-title":"Myocarditis and inflammatory cardiomyopathy: Histomorphological diagnosis","volume":"55","author":"Calabrese","year":"2006","journal-title":"Ernst Scher. Res. Found Workshop"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1161\/CIRCULATIONAHA.109.924167","article-title":"Comparative evaluation of left and right ventricular endomyocardial biopsy: Differences in complication rate and diagnostic performance","volume":"122","author":"Yilmaz","year":"2010","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.carpath.2011.10.001","article-title":"2011 consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology","volume":"21","author":"Leone","year":"2012","journal-title":"Cardiovasc. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1093\/clinchem\/43.3.458","article-title":"Improved troponin T ELISA specific for cardiac troponin T isoform: Assay development and analytical and clinical validation","volume":"43","author":"Hallermayer","year":"1997","journal-title":"Clin. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.jacc.2004.11.069","article-title":"Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: Comparison of different approaches","volume":"45","author":"Zagrosek","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1016\/j.jacc.2016.02.013","article-title":"Comprehensive Cardiac Magnetic Resonance Imaging in Patients with Suspected Myocarditis: The MyoRacer-Trial","volume":"67","author":"Lurz","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1161\/CIRCHEARTFAILURE.109.873240","article-title":"Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling","volume":"2","author":"Seki","year":"2009","journal-title":"Circ. Heart Fail."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1161\/01.CIR.0000038705.69871.D9","article-title":"Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction","volume":"106","author":"Weinberg","year":"2002","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jchf.2016.09.010","article-title":"Prognostic Value of Soluble Suppression of Tumorigenicity-2 in Chronic Heart Failure: A Meta-Analysis","volume":"5","author":"Aimo","year":"2017","journal-title":"JACC Heart Fail."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1161\/01.CIR.0000127958.21003.5A","article-title":"Serum levels of the interleukin-1 receptor family member ST2 predict mortality and clinical outcome in acute myocardial infarction","volume":"109","author":"Shimpo","year":"2004","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jacc.2007.05.014","article-title":"Measurement of the interleukin family member ST2 in patients with acute dyspnea: Results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study","volume":"50","author":"Januzzi","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/s41569-020-00435-x","article-title":"Myocarditis and inflammatory cardiomyopathy: Current evidence and future directions","volume":"18","author":"Ammirati","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/nrcardio.2015.108","article-title":"Viral myocarditis-diagnosis, treatment options, and current controversies","volume":"12","author":"Pollack","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s11886-017-0870-x","article-title":"Myocarditis: A Clinical Overview","volume":"19","author":"Caforio","year":"2017","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1164\/ajrccm.164.2.2008120","article-title":"Elevated soluble ST2 protein levels in sera of patients with asthma with an acute exacerbation","volume":"164","author":"Oshikawa","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1006\/bbrc.2001.5090","article-title":"Identification of human ST2 protein in the sera of patients with autoimmune diseases","volume":"284","author":"Kuroiwa","year":"2001","journal-title":"Biochem. Biophys Res. Commun."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/3\/414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:07:40Z","timestamp":1760134060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/3\/414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,25]]},"references-count":31,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cells11030414"],"URL":"https:\/\/doi.org\/10.3390\/cells11030414","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,25]]}}}