{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:48:27Z","timestamp":1790927307648,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014677","name":"University of Medicine, Pharmacy, Science and Technology \u201cGeorge Emil Palade\u201d of T\u00e2rgu Mure\u0219","doi-asserted-by":"publisher","award":["164\/9\/10.01.2023"],"award-info":[{"award-number":["164\/9\/10.01.2023"]}],"id":[{"id":"10.13039\/501100014677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aimed to investigate the impact of long-term survival on cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center, undergoing echocardiographic and invasive left cardiac catheterization for diastolic dysfunction assessment were prospectively included in this study. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, with a median follow-up of 1.66 (1.23\u20132.16) years during which 16 (14.5%) patients died. A total of 45.4% (50) of patients had diastolic dysfunction. In the univariate Cox regression, long-term survival was predicted by BNP (p &lt; 0.0001, HR = 0.39 [0.20\u20130.53]), NT-proBNP (p &lt; 0.0001, HR = 0.40 [0.22\u20130.55]), MR-proANP (p = 0.001, HR = 0.30 [0.11\u20130.46]), sST2 (p &lt; 0.0001, HR = 0.47 [0.30\u20130.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable Cox regression non-invasive and invasive models, NT-proBNP and sST2 remained independent predictors of survival. Natriuretic peptides (BNP and NT-proBNP) and sST2 were predictors of long-term survival, while MR-proANP, MR-proADM and galectin-3 did not have predictive values. NT-proBNP and sST2 improved survival prediction in both a non-invasive scenario (including clinical, serum and echocardiographic parameters) and an invasive clinical scenario (including left heart catheterization parameters). The sST2 pathway could provide a target for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms26083713","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T03:59:06Z","timestamp":1744689546000},"page":"3713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Natriuretic Peptides and Soluble ST2 Improve Echocardiographic and Invasive Long-Term Survival Prediction in Patients Evaluated for Diastolic Dysfunction"],"prefix":"10.3390","volume":"26","author":[{"given":"Hora\u021biu","family":"Suciu","sequence":"first","affiliation":[{"name":"Department of Surgery IV, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Department of Cardiovascular Surgery, Emergency Institute for Cardiovascular Diseases and Transplantation Targu Mures, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4948-2587","authenticated-orcid":false,"given":"Paul-Adrian","family":"C\u0103lburean","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Informatics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9798-1594","authenticated-orcid":false,"given":"Adina","family":"Hu\u021banu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Centre for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-3300","authenticated-orcid":false,"given":"M\u0103d\u0103lina","family":"Oprica","sequence":"additional","affiliation":[{"name":"Centre for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Roxana","family":"Opri\u0219","sequence":"additional","affiliation":[{"name":"Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda-Cristina","family":"Scurtu","sequence":"additional","affiliation":[{"name":"Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Stan","sequence":"additional","affiliation":[{"name":"Doctoral School, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Department of Interventional Cardiology, Emergency Institute for Cardiovascular Diseases and Transplantation Targu Mures, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9956-2312","authenticated-orcid":false,"given":"David","family":"Ani\u021bei","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Emergency Institute for Cardiovascular Diseases and Transplantation Targu Mures, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Br\u00eenzaniuc","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Hadadi","sequence":"additional","affiliation":[{"name":"Department of Interventional Cardiology, Emergency Institute for Cardiovascular Diseases and Transplantation Targu Mures, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9044-8866","authenticated-orcid":false,"given":"Marius","family":"Harpa","sequence":"additional","affiliation":[{"name":"Department of Surgery IV, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"},{"name":"Department of Cardiovascular Surgery, Emergency Institute for Cardiovascular Diseases and Transplantation Targu Mures, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s10741-014-9440-0","article-title":"A systematic review of BNP and NT-proBNP in the management of heart failure: Overview and methods","volume":"19","author":"Oremus","year":"2014","journal-title":"Heart Fail. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1056\/NEJMra0800239","article-title":"Biomarkers in Heart Failure","volume":"358","author":"Braunwald","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.hfc.2017.08.005","article-title":"Soluble ST2 in Heart Failure","volume":"14","author":"McCarthy","year":"2018","journal-title":"Heart Fail. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11897-010-0005-9","article-title":"ST2: A Novel Remodeling Biomarker in Acute and Chronic Heart Failure","volume":"7","author":"Shah","year":"2010","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1161\/CIRCRESAHA.118.312706","article-title":"Established and Emerging Roles of Biomarkers in Heart Failure","volume":"123","author":"Ibrahim","year":"2018","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"P\u00e1l, K., M\u0103nescu, I.-B., Lupu, S., and Dobreanu, M. (2023). Emerging Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease. Life, 13.","DOI":"10.3390\/life13010230"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"C\u0103lburean, P.-A., Grebeni\u0219an, P., Nistor, I.-A., Pal, K., Vacariu, V., Drincal, R.-K., Ion, A.A., Adorj\u00e1n, I., Oltean, T., and Hadadi, L. (2024). Addition of eptifibatide and manual thrombus aspiration to ticagrelor does not improve long-term survival after STEMI treated with primary PCI. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1415025"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"C\u0103lburean, P.-A., Lupu, S., Hu\u021banu, A., Oprica, M., Opri\u0219, D.R., Stan, A., Scurtu, A.-C., Ani\u021bei, D., Harpa, M., and Br\u00eenzaniuc, K. (2024). Natriuretic peptides and soluble ST2 improves echocardiographic diagnosis of elevated left ventricular filling pressures. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-73349-0"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.hfc.2007.10.003","article-title":"Natriuretic Peptides and Filling Pressure at Rest and Stress","volume":"4","author":"Bansal","year":"2008","journal-title":"Heart Fail. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"64B","DOI":"10.1016\/j.jacc.2015.06.1267","article-title":"ST2 and patient prognosis in chronic heart failure","volume":"115","author":"Zhang","year":"2015","journal-title":"Am. J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin\u2013Neprilysin Inhibition versus Enalapril in Heart Failure","volume":"371","author":"McMurray","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"ehae666.1089","DOI":"10.1093\/eurheartj\/ehae666.1089","article-title":"The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: Real-world evidence from the CCA Database-HF Center","volume":"45","author":"Xie","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1159\/000509660","article-title":"Long-Term and Short-Term Prognostic Value of Circulating Soluble Suppression of Tumorigenicity-2 Concentration in Chronic Heart Failure: A Systematic Review and Meta-Analysis","volume":"146","author":"Dong","year":"2021","journal-title":"Cardiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1161\/CIRCHEARTFAILURE.110.958223","article-title":"High-Sensitivity ST2 for Prediction of Adverse Outcomes in Chronic Heart Failure","volume":"4","author":"Ky","year":"2011","journal-title":"Circ. Heart Fail."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.mayocp.2012.09.016","article-title":"Combined Use of the Novel Biomarkers High-Sensitivity Troponin T and ST2 for Heart Failure Risk Stratification vs Conventional Assessment","volume":"88","author":"Vila","year":"2013","journal-title":"Mayo Clin. Proc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1016\/j.jacc.2018.08.2165","article-title":"sST2 Predicts Outcome in Chronic Heart Failure Beyond NT\u2212proBNP and High-Sensitivity Troponin T","volume":"72","author":"Emdin","year":"2018","journal-title":"JACC"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cytogfr.2023.06.003","article-title":"Modulation of IL-33\/ST2 signaling as a potential new therapeutic target for cardiovascular diseases","volume":"71\u201372","author":"Thanikachalam","year":"2023","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"e99208","DOI":"10.1172\/jci.insight.99208","article-title":"From proteomics to discovery of first-in-class ST2 inhibitors active in vivo","volume":"3","author":"Ramadan","year":"2018","journal-title":"JCI Insight"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.jacc.2018.11.042","article-title":"Effects of Sacubitril\/Valsartan on Biomarkers of Extracellular Matrix Regulation in Patients with HFrEF","volume":"73","author":"Zile","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jacc.2013.07.087","article-title":"Head-to-Head Comparison of 2 Myocardial Fibrosis Biomarkers for Long-Term Heart Failure Risk Stratification","volume":"63","author":"Vila","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.ahj.2013.02.029","article-title":"Biological variation of galectin-3 and soluble ST2 for chronic heart failure: Implication on interpretation of test results","volume":"165","author":"Wu","year":"2013","journal-title":"Am. Heart J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10286-023-00922-4","article-title":"Heart rate variability and microvolt T wave alternans changes during ajmaline test may predict prognosis in Brugada syndrome","volume":"33","author":"Pannone","year":"2023","journal-title":"Clin. Auton. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jclinepi.2015.04.005","article-title":"Prediction models need appropriate internal, internal-external, and external validation","volume":"69","author":"Steyerberg","year":"2016","journal-title":"J. Clin. Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/bimj.201700067","article-title":"Variable selection\u2014A review and recommendations for the practicing statistician","volume":"60","author":"Heinze","year":"2018","journal-title":"Biom. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1001\/jama.2015.11082","article-title":"Evaluating Discrimination of Risk Prediction Models: The C Statistic","volume":"314","author":"Pencina","year":"2015","journal-title":"JAMA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3713\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:14:31Z","timestamp":1760030071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,14]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083713"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083713","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,14]]}}}