{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:31:13Z","timestamp":1787776273816,"version":"build-2784847793"},"reference-count":120,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T00:00:00Z","timestamp":1685750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In heart failure with reduced ejection fraction, edema and congestion are related to reduced cardiac function. Edema and congestion are further aggravated by chronic kidney failure and pulmonary abnormalities. Furthermore, together with edema\/congestion, sodium\/water retention is an important sign of the progression of heart failure. Edema\/congestion often anticipates clinical symptoms, such as dyspnea and hospitalization; it is associated with a reduced quality of life and a major risk of mortality. It is very important for clinicians to predict the signs of congestion with biomarkers and, mainly, to understand the pathophysiological findings that underlie edema. Not all congestions are secondary to heart failure, as in nephrotic syndrome. This review summarizes the principal evidence on the possible roles of the old and new congestion biomarkers in HFrEF patients (diagnostic, prognostic, and therapeutic roles). Furthermore, we provide a description of conditions other than congestion with increased congestion biomarkers, in order to aid in reaching a differential diagnosis. To conclude, the review focuses on how congestion biomarkers may be affected by new HF drugs (gliflozins, vericiguat, etc.) approved for HFrEF.<\/jats:p>","DOI":"10.3390\/jcm12113834","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T02:18:29Z","timestamp":1685931509000},"page":"3834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Role of Congestion Biomarkers in Heart Failure with Reduced Ejection Fraction"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7863-253X","authenticated-orcid":false,"given":"Michele","family":"Correale","sequence":"first","affiliation":[{"name":"Cardiology Unit, Policlinico Riuniti University Hospital, 71100 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7174-8604","authenticated-orcid":false,"given":"Francesco","family":"Fioretti","sequence":"additional","affiliation":[{"name":"Cardiology Section, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-1885","authenticated-orcid":false,"given":"Lucia","family":"Tricarico","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Policlinico Riuniti University Hospital, 71100 Foggia, Italy"},{"name":"Department of Medical & Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Croella","sequence":"additional","affiliation":[{"name":"Department of Medical & Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natale Daniele","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Policlinico Riuniti University Hospital, 71100 Foggia, Italy"},{"name":"Department of Medical & Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4846-8529","authenticated-orcid":false,"given":"Riccardo M.","family":"Inciardi","sequence":"additional","affiliation":[{"name":"Cardiology Section, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-9530","authenticated-orcid":false,"given":"Anna Vittoria","family":"Mattioli","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical and Dental Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savina","family":"Nodari","sequence":"additional","affiliation":[{"name":"Cardiology Section, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"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":"75","DOI":"10.1007\/s00392-022-02036-9","article-title":"Lack of correlation between different congestion markers in acute decompensated heart failure","volume":"112","author":"Haag","year":"2022","journal-title":"Clin. Res. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/s41569-020-0379-7","article-title":"Congestion in heart failure: A contemporary look at physiology, diagnosis and treatment","volume":"17","author":"Boorsma","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","article-title":"The use of diuretics in heart failure with congestion\u2014A position statement from the Heart Failure Association of the European Society of Cardiology","volume":"21","author":"Mullens","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.amjmed.2006.09.011","article-title":"Congestion in Acute Heart Failure Syndromes: An Essential Target of Evaluation and Treatment","volume":"119","author":"Gheorghiade","year":"2006","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ijcard.2018.01.067","article-title":"Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure","volume":"258","author":"Demissei","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1161\/CIRCHEARTFAILURE.114.001957","article-title":"Goldsmith. Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights From Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart","volume":"8","author":"Lala","year":"2015","journal-title":"Circ. Heart Fail."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10741-019-09868-0","article-title":"Congestion occurrence and evaluation in acute heart failure scenario: Time to reconsider different pathways of volume overload","volume":"25","author":"Palazzuoli","year":"2019","journal-title":"Heart Fail. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0002-9343(91)90576-J","article-title":"Clinical, radiographic, and hemodynamic correlations in chronic congestive heart failure: Conflicting results may lead to inappropriate care","volume":"90","author":"Chakko","year":"1991","journal-title":"Am. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.annemergmed.2005.04.003","article-title":"Prevalence of Negative Chest Radiography Results in the Emergency Department Patient With Decompensated Heart Failure","volume":"47","author":"Collins","year":"2006","journal-title":"Ann. Emerg. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1161\/CIRCULATIONAHA.104.482570","article-title":"Biomarkers of Cardiovascular Disease Molecular Basis and Practical Considerations","volume":"113","author":"Vasan","year":"2006","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1602\/neurorx.1.2.181","article-title":"Biomarkers and Surrogates","volume":"1","author":"Fox","year":"2004","journal-title":"NeuroRx"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Biomarkers Definitions Working Group, Atkinson, A.J., Colburn, W.A., DeGruttola, V.G., DeMets, D.L., Downing, G.J., Hoth, D.F., Oates, J.A., Peck, C.C., and Spilker, B.A. (2001). Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin. Pharmacol. Ther., 69, 89\u201395.","DOI":"10.1067\/mcp.2001.113989"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2217\/nnm-2022-0269","article-title":"Nanoparticles in induced sputum\u2014A window to airway inflammation among active smokers","volume":"18","author":"Freund","year":"2023","journal-title":"Nanomedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s10741-018-9683-2","article-title":"Redefining biomarkers in heart failure","volume":"23","author":"Correale","year":"2018","journal-title":"Heart Fail Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s10741-019-09807-z","article-title":"Biomarkers in heart failure: The past, current and future","volume":"24","author":"Sarhene","year":"2019","journal-title":"Heart Fail. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/S0195-668X(03)00476-7","article-title":"Clinical applications of B-type natriuretic peptide (BNP) testing","volume":"24","author":"Cowie","year":"2003","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e12277","DOI":"10.1097\/MD.0000000000012277","article-title":"Midregional pro-atrial natriuretic peptide is a superior biomarker to N-terminal pro-B-type natriuretic peptide in the diagnosis of heart failure patients with preserved ejection fraction","volume":"97","author":"Cui","year":"2018","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Negi, S., Sawano, M., Kohsaka, S., Inohara, T., Shiraishi, Y., Kohno, T., Maekawa, Y., Sano, M., Yoshikawa, T., and Fukuda, K. (2014). Prognostic Implication of Physical Signs of Congestion in Acute Heart Failure Patients and Its Association with Steady-State Biomarker Levels. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096325"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa0706824","article-title":"Cardiac troponin and outcome in acute heart failure","volume":"358","author":"Peacock","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1093\/eurjhf\/hfs110","article-title":"Troponin I in acute decompensated heart failure: Insights from the ASCEND-HF study","volume":"14","author":"Felker","year":"2012","journal-title":"Eur. J. Heart Fail."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.ijcard.2010.04.081","article-title":"CA125 and immunoinflammatory activity in acute heart failure","volume":"145","author":"Sanchis","year":"2010","journal-title":"Int. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/j.1440-1843.2004.00602.x","article-title":"Mesothelial cell proliferation and apoptosis","volume":"9","author":"Leard","year":"2004","journal-title":"Respirology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.mehy.2012.05.042","article-title":"New mechanism of elevated CA125 in heart failure: The mechanical stress and inflammatory stimuli initiate CA125 synthesis","volume":"79","author":"Huang","year":"2012","journal-title":"Med. Hypotheses"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ejheart.2005.09.002","article-title":"Relationship between cytokines and tumour markers in patients with chronic heart failure","volume":"8","author":"Kosar","year":"2006","journal-title":"Eur. J. Heart Fail."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11897-010-0009-5","article-title":"Venous congestion and endothelial cell activation in acute decompensated heart failure","volume":"7","author":"Ganda","year":"2010","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrcardio.2016.163","article-title":"Neurohormonal activation in heart failure with reduced ejection fraction","volume":"14","author":"Hartupee","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e19","DOI":"10.15420\/cfr.2021.22","article-title":"Carbohydrate Antigen 125: A Biomarker at the Crossroads of Congestion and Inflammation in Heart Failure","volume":"7","author":"Kumric","year":"2021","journal-title":"Card. Fail. Rev."},{"key":"ref_29","first-page":"316","article-title":"Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure","volume":"75","author":"Santas","year":"2022","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_30","first-page":"475","article-title":"CA125 but not NT-proBNP predicts the presence of a congestive intrarenal venous flow in patients with acute heart failure","volume":"30","author":"Santas","year":"2021","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1002\/ejhf.2339","article-title":"Integration of imaging and circulating biomarkers in heart failure: A consensus document by the Biomarkers and Imaging Study Groups of the Heart Failure Association of the European Society of Cardi-ology","volume":"23","author":"Moura","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1016\/j.jacc.2019.08.1039","article-title":"Clinical and Prognostic Significance of sST2 in Heart Failure. JACC Rev Top Week","volume":"74","author":"Aimo","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_33","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_34","doi-asserted-by":"crossref","unstructured":"Blanda, V., Bracale, U.M., Di Taranto, M.D., and Fortunato, G. (2020). Galectin-3 in Cardiovascular Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239232"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16682","DOI":"10.1038\/s41598-020-73634-8","article-title":"Galectin-3 is related to right ventricular dysfunction in heart failure patients with reduced ejection fraction and may affect exercise capacity","volume":"10","author":"Zaborska","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejim.2017.10.016","article-title":"Liver disease and heart failure: Back and forth","volume":"48","author":"Correale","year":"2018","journal-title":"Eur. J. Intern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jchf.2017.09.023","article-title":"Integrative Assessment of Congestion in Heart Failure Throughout the Patient Journey","volume":"6","author":"Girerd","year":"2017","journal-title":"JACC Heart Fail."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/j.jacc.2013.03.042","article-title":"Cardiohepatic interactions in heart failure: An overview and clinical implications","volume":"61","author":"Samsky","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cardfail.2009.08.002","article-title":"Abnormal Liver Function in Relation to Hemodynamic Profile in Heart Failure Patients","volume":"16","author":"Damman","year":"2010","journal-title":"J. Card. Fail."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"26","DOI":"10.23736\/S0031-0808.19.03768-6","article-title":"Liver disease and heart failure","volume":"62","author":"Correale","year":"2020","journal-title":"Panminerva. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.jchf.2015.06.014","article-title":"Prognostic Value of Estimated Plasma Volume in Heart Failure","volume":"3","author":"Duarte","year":"2015","journal-title":"JACC Heart Fail."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/ejhf.74","article-title":"Decongestion in acute heart failure","volume":"16","author":"Mentz","year":"2014","journal-title":"Eur. J. Heart Fail."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/ejhf.414","article-title":"Circulating biomarkers of distinct pathophysiological pathways in heart failure with preserved vs. reduced left ventricular ejection fraction","volume":"17","author":"Wijk","year":"2015","journal-title":"Eur. J. Heart Fail."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1093\/eurjhf\/hfs130","article-title":"Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal pro brain na-triuretic peptide in heart failure with preserved vs. reduced ejection fraction","volume":"14","author":"Santhanakrishnan","year":"2012","journal-title":"Eur. J. Heart Fail."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.amjcard.2012.05.014","article-title":"Prevalence, Clinical Phenotype, and Outcomes Associated with Normal B-Type Natriuretic Peptide Levels in Heart Failure With Preserved Ejection Fraction","volume":"110","author":"Anjan","year":"2012","journal-title":"Am. J. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s12471-016-0817-7","article-title":"Biomarkers in heart failure with preserved ejection fraction","volume":"24","author":"Meijers","year":"2016","journal-title":"Neth. Heart J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1002\/ejhf.890","article-title":"Clinical phenotypes and outcome of patients hospitalized for acute heart failure: The ESC Heart Failure Long-Term Registry","volume":"19","author":"Chioncel","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s10741-021-10105-w","article-title":"Biomarkers for the diagnosis and management of heart failure","volume":"27","author":"Castiglione","year":"2021","journal-title":"Heart Fail. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.ejheart.2008.07.014","article-title":"State of the art: Using natriuretic peptide levels in clinical practice","volume":"10","author":"Maisel","year":"2008","journal-title":"Eur. J. Heart Fail."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1054","DOI":"10.1161\/CIR.0000000000000490","article-title":"Role of Biomarkers for the Prevention, Assessment, and Management of Heart Failure: A Scientific Statement From the American Heart Association","volume":"135","author":"Chow","year":"2017","journal-title":"Circulation"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.cardfail.2014.11.009","article-title":"The Potential Role of Natriuretic Peptide\u2013Guided Management for Patients Hospitalized for Heart Failure","volume":"21","author":"Maisel","year":"2014","journal-title":"J. Card. Fail."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1161\/01.CIR.0000144310.04433.BE","article-title":"N-Terminal\u2013Pro-Brain Natriuretic Peptide Predicts Outcome After Hospital Discharge in Heart Failure Patients","volume":"110","author":"Bettencourt","year":"2004","journal-title":"Circulation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jacc.2003.09.044","article-title":"Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure","volume":"43","author":"Logeart","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1002\/ejhf.749","article-title":"A multimarker multi-time point-based risk stratification strategy in acute heart failure: Results from the RELAX-AHF trial","volume":"19","author":"Demissei","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1016\/j.ijcard.2013.04.039","article-title":"Prealbumin improves death risk prediction of BNP-added Seattle Heart Failure Model: Results from a pilot study in elderly chronic heart failure patients","volume":"168","author":"Cabassi","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1161\/CIRCHEARTFAILURE.114.001185","article-title":"Clinical Risk Stratification Optimizes Value of Biomarkers to Predict New-Onset Heart Failure in a Community-Based Cohort","volume":"7","author":"Brouwers","year":"2014","journal-title":"Circ. Heart Fail."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1161\/CIRCULATIONAHA.109.929661","article-title":"Multimarker Approach for the Prediction of Heart Failure Incidence in the Community","volume":"122","author":"Velagaleti","year":"2010","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ijcard.2018.10.079","article-title":"High-sensitivity troponin T, NT-proBNP and glomerular filtration rate: A multimarker strategy for risk stratification in chronic heart failure","volume":"277","author":"Aimo","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.jacc.2019.12.069","article-title":"Multiple Plasma Biomarkers for Risk Stratification in Patients With Heart Failure and Preserved Ejection Fraction","volume":"75","author":"Chirinos","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1016\/j.jacc.2006.10.081","article-title":"Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: The STARS-BNP Multicenter Study","volume":"49","author":"Jourdain","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1093\/eurjhf\/hfs180","article-title":"Improvement in structural and functional echocardiographic parameters during chronic heart failure therapy guided by natriuretic peptides: Mechanistic insights from the ProBNP Outpatient Tailored Chronic Heart Failure (PROTECT) study","volume":"15","author":"Weiner","year":"2013","journal-title":"Eur. J. Heart Fail."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jacc.2009.02.095","article-title":"N-terminal pro-B-type natriuretic peptide-guided treatment for chronic heart failure: Results from the BATTLESCARRED (NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) trial","volume":"55","author":"Lainchbury","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.cardfail.2017.02.001","article-title":"N-Terminal Pro\u2013B-Type Natriuretic Peptide\u2013Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations\u2014Results From TIME-CHF","volume":"23","author":"Davarzani","year":"2017","journal-title":"J. Card. Fail."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ahj.2014.04.008","article-title":"Rationale and design of PRIMA II: A multicenter, randomized clinical trial to study the impact of in-hospital guidance for acute decompensated heart failure treatment by a predefined NT-PRoBNP target on the reduction of readmIssion and Mortality rAtes","volume":"168","author":"Stienen","year":"2014","journal-title":"Am. Heart J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1002\/ejhf.1450","article-title":"Clinical factors related to morbidity and mortality in high-risk heart failure patients: The GUIDE-IT predictive model and risk score","volume":"21","author":"Fiuzat","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.ijcard.2014.08.007","article-title":"Obesity and natriuretic peptides, BNP and NT-proBNP: Mechanisms and diagnostic implications for heart failure","volume":"176","author":"Madamanchi","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1016\/j.bbadis.2012.12.014","article-title":"Biomarkers and diagnostics in heart failure","volume":"1832","author":"Gaggin","year":"2013","journal-title":"Biochim. Biophy. Acta"},{"key":"ref_68","first-page":"1893","article-title":"The role of BNP testing in heart failure","volume":"74","author":"Doust","year":"2006","journal-title":"Am. Fam. Physician"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/eurheartj\/ehaa575","article-title":"Corrigendum to: 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation","volume":"42","author":"Collet","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/jhm.13063","article-title":"Diag-nostic delays among COVID-19 patients with a second concurrent diagnosis","volume":"18","author":"Freund","year":"2023","journal-title":"J. Hosp. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00296-022-05106-3","article-title":"Concurrent myopathy and inflammatory cardiac disease in COVID-19 patients: A case series and literature review","volume":"42","author":"Freund","year":"2022","journal-title":"Rheumatol. Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"601","DOI":"10.2147\/VHRM.S327661","article-title":"The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis","volume":"17","author":"Chauin","year":"2021","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.chest.2017.05.018","article-title":"CA-125 in Disease Progression and Treatment of Lymphangioleio-myomatosis","volume":"153","author":"Glasgow","year":"2018","journal-title":"Chest"},{"key":"ref_74","first-page":"266","article-title":"Carbohydrate antigen 125 in heart failure. A New era in the monitoring and control of treatment","volume":"152","year":"2019","journal-title":"Med. Cl\u00ednica"},{"key":"ref_75","first-page":"599","article-title":"Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review)","volume":"41","author":"Dong","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.17219\/acem\/126049","article-title":"Clinical value of soluble ST2 in cardiology","volume":"29","author":"Dudek","year":"2020","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13613-017-0252-y","article-title":"Multi-marker approach using procalcitonin, presepsin, galectin-3, and soluble suppression of tumorigenicity 2 for the prediction of mortality in sepsis","volume":"7","author":"Kim","year":"2017","journal-title":"Ann. Intensiv. Care"},{"key":"ref_78","first-page":"29","article-title":"Clinical relevance of sST2 in cardiac diseases","volume":"54","author":"Lax","year":"2016","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"329","DOI":"10.21037\/atm.2016.08.65","article-title":"New role of biomarkers: Mid-regional pro-adrenomedullin, the biomarker of organ failure","volume":"4","year":"2016","journal-title":"Ann. Transl. Med."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Montrucchio, G., Sales, G., Rumbolo, F., Palmesino, F., Fanelli, V., Urbino, R., Filippini, C., Mengozzi, G., and Brazzi, L. (2021). Effectiveness of mid-regional pro-adrenomedullin (MR-proADM) as prognostic marker in COVID-19 critically ill patients: An observational prospective study. PLoS ONE, 8.","DOI":"10.21203\/rs.3.rs-56715\/v1"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"17","DOI":"10.33176\/AACB-20-00001","article-title":"The Emerging Role of Copeptin","volume":"42","author":"Jalleh","year":"2021","journal-title":"Clin. Biochem. Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fmed.2015.00019","article-title":"A Review of the Nonpressor and Nonantidiuretic Actions of the Hormone Vasopressin","volume":"2","author":"Mavani","year":"2015","journal-title":"Front. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"490842","DOI":"10.1155\/2015\/490842","article-title":"GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Pro-spective","volume":"2015","author":"Adela","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1002\/ehf2.13878","article-title":"Type III procollagen peptide level can indicate liver dysfunction associated with volume overload in acute heart failure","volume":"9","author":"Shirakabe","year":"2022","journal-title":"ESC Heart Fail."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Nikolov, A., and Popovski, N. (2022). Extracellular Matrix in Heart Disease: Focus on Circulating Collagen Type I and III Derived Peptides as Biomarkers of Myocardial Fibrosis and Their Potential in the Prognosis of Heart Failure: A Concise Review. Metabolites, 12.","DOI":"10.3390\/metabo12040297"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1093\/europace\/eus162","article-title":"Type III procollagen-N-peptide as a predictor of persistent atrial fibrillation recurrence after cardioversion","volume":"14","author":"Kawamura","year":"2012","journal-title":"Europace"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"565","DOI":"10.3109\/1354750X.2015.1123354","article-title":"The potential of lipocalin-2\/NGAL as biomarker for inflammatory and metabolic diseases","volume":"20","author":"Abella","year":"2015","journal-title":"Biomarkers"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jacc.2012.04.017","article-title":"Prognostic Utility of Neutrophil Gelatinase-Associated Lipocalin in Predicting Mortality and Cardiovascular Events in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention","volume":"60","author":"Lindberg","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1016\/j.cca.2012.07.010","article-title":"Natriuretic peptides and NGAL in heart failure: Does a link exist?","volume":"413","author":"Palazzuoli","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.clineuro.2012.01.031","article-title":"Elevated blood urea nitrogen\/creatinine ratio is associated with poor outcome in patients with ischemic stroke","volume":"114","author":"Schrock","year":"2012","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ajem.2021.03.081","article-title":"Comparison of IVC diameter ratio, BUN\/creatinine ratio and BUN\/albumin ratio for risk prediction in emergency department patients","volume":"47","author":"Bae","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"ref_92","first-page":"73","article-title":"Is it time for the practical application of biomarkers in chronic heart failure management?","volume":"50","author":"Zemleduch","year":"2022","journal-title":"Pol. Merkur. Lekarski."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1161\/CIRCULATIONAHA.109.928846","article-title":"Serial measurement of growth-differentiation factor-15 in heart failure: Relation to disease severity and prognosis in the Valsartan Heart Failure Trial","volume":"122","author":"Anand","year":"2010","journal-title":"Circulation"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1161\/ATVBAHA.110.213512","article-title":"Growth differen- tiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: Observations from PROVE IT-TIMI 22","volume":"31","author":"Bonaca","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s11897-012-0113-9","article-title":"Growth Differentiation Factor 15 in Heart Failure: An Update","volume":"9","author":"Wollert","year":"2012","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ijcard.2016.11.110","article-title":"Biomarkers for characterization of heart failure\u2014Distinction of heart failure with preserved and reduced ejection fraction","volume":"227","author":"Sinning","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s10741-022-10268-0","article-title":"Fibroblast growth factor 21 in heart failure","volume":"28","author":"Tucker","year":"2022","journal-title":"Heart Fail. Rev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"632260","DOI":"10.3389\/fphys.2021.632260","article-title":"An Overview of FGF-23 as a Novel Candidate Biomarker of Cardi-ovascular Risk","volume":"12","author":"Poveda","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ijcard.2017.10.010","article-title":"Fibroblast growth factor 23 is related to profiles indicating volume overload, poor therapy opti-mization and prognosis in patients with new-onset and worsening heart failure","volume":"253","author":"Maaten","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"841","DOI":"10.2217\/bmm.14.50","article-title":"Copeptin as a biomarker in heart failure","volume":"8","author":"Balling","year":"2014","journal-title":"Biomarkers Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cca.2017.10.001","article-title":"Copeptin in heart failure: Review and meta-analysis","volume":"475","author":"Zhong","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1530\/EC-14-0017","article-title":"Plasma chromogranin A is a marker of death in elderly patients presenting with symptoms of heart failure","volume":"3","author":"Goetze","year":"2014","journal-title":"Endocr. Connect."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"337","DOI":"10.12701\/yujm.2020.00843","article-title":"Prognostic impact of chromogranin A in patients with acute heart failure","volume":"38","author":"Kim","year":"2021","journal-title":"Yeungnam Univ. J. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"R173","DOI":"10.1530\/JOE-17-0031","article-title":"Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease","volume":"233","author":"Girona","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.jchf.2022.05.013","article-title":"Pathophysiologic Processes and Novel Biomarkers Associated With Congestion in Heart Failure","volume":"10","author":"Pandhi","year":"2022","journal-title":"JACC Heart Fail."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0168-8278(91)90929-6","article-title":"Serum type I collagen and N-terminal peptide of type III procollagen in chronic hepatitis: Relationship to liver histology and conventional liver tests","volume":"12","author":"Trinchet","year":"1991","journal-title":"J. Hepatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1111\/j.1530-0277.2008.00664.x","article-title":"Value of fibrosis markers for staging liver fibrosis in patients with precirrhotic alcoholic liver disease","volume":"32","author":"Lieber","year":"2008","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4149\/BLL_2021_002","article-title":"Altered serum levels of neprilysin in heart failure patients with reduced ejection fraction","volume":"122","author":"Nemcekova","year":"2021","journal-title":"Bratisl. Med. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8671","DOI":"10.3934\/mbe.2022402","article-title":"Predicting potential biomarkers and immune infiltration characteristics in heart failure","volume":"19","author":"Chen","year":"2022","journal-title":"Math. Biosci. Eng."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.amjcard.2022.07.019","article-title":"GlycA and GlycB as Inflammatory Markers in Chronic Heart Failure","volume":"181","author":"Cediel","year":"2022","journal-title":"Am. J. Cardiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"569","DOI":"10.2459\/JCM.0000000000000152","article-title":"Insufficienza del cuore destro e sinistro group, a research group of the Italian Society of Cardiology. Management of heart failure in the new era: The role of scores","volume":"17","author":"Mantegazza","year":"2016","journal-title":"J. Cardiovasc. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"665797","DOI":"10.3389\/fcvm.2021.665797","article-title":"New Targets in Heart Failure Drug Therapy","volume":"8","author":"Correale","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"96","DOI":"10.15420\/cfr.2015.1.2.96","article-title":"Biomarker Guided Therapy in Chronic Heart Failure","volume":"1","author":"Bektas","year":"2015","journal-title":"Card. Fail. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s11886-020-01288-z","article-title":"Soluble ST2 and Soluble Markers of Fibrosis: Emerging Roles for Prognosis and Guiding Therapy","volume":"22","author":"Sharim","year":"2020","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/S0140-6736(22)02076-1","article-title":"Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): A multinational, open-label, randomised, trial","volume":"400","author":"Mebazaa","year":"2022","journal-title":"Lancet"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1007\/s10741-021-10107-8","article-title":"Paradigm shift in heart failure treatment: Are cardiologists ready to use gliflozins?","volume":"27","author":"Correale","year":"2022","journal-title":"Heart Fail. Rev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ijcard.2021.06.045","article-title":"Effects of empagliflozin on CA125 trajectory in patients with chronic congestive heart failure","volume":"339","author":"Santas","year":"2021","journal-title":"Int. J. Cardiol."},{"key":"ref_118","first-page":"e007048","article-title":"4330 Effect of empagliflozin as add-on therapy on decongestion and renal function in diabetic patients hospitalized for acute decompensated heart failure: A prospective randomized controlled study","volume":"14","author":"Tamaki","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.jchf.2022.04.015","article-title":"Sequential Evaluation of NT-proBNP in Heart Failure: Insights Into Clinical Outcomes and Efficacy of Vericiguat","volume":"10","author":"Armstrong","year":"2022","journal-title":"JACC Heart Fail."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1016\/S0735-1097(19)33679-4","article-title":"B-type natriuretic peptide during treatment with sacubitril\/valsartan: The paradigm-HF trial","volume":"73","author":"Vaduganathan","year":"2019","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/11\/3834\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:48:25Z","timestamp":1760125705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/11\/3834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,3]]},"references-count":120,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["jcm12113834"],"URL":"https:\/\/doi.org\/10.3390\/jcm12113834","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,3]]}}}