{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:16:22Z","timestamp":1788977782978,"version":"build-2803163510"},"reference-count":115,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Right ventricular (RV) dysfunction is common and linked to poor outcomes across conditions such as heart failure (HF), acute coronary syndromes, pulmonary embolism, and pulmonary hypertension. While imaging, electrocardiogram (ECG), and invasive tests remain central to RV assessment, circulating biomarkers offer a rapid, non-invasive, and reliable alternative. These biomarkers reflect key pathophysiological processes, including myocardial injury, stress, fibrosis, inflammation, congestion, and multiorgan involvement. High-sensitivity troponins and natriuretic peptides (BNP, NT-proBNP) are already widely used, while emerging biomarkers\u2014such as CA125, copeptin, galectin-3, and others\u2014may enhance diagnostic accuracy and risk stratification. Some, like CA125 and NT-proBNP, have shown promise in guiding post-discharge therapy. However, challenges remain regarding the specificity of biomarkers for RV dysfunction and their role across different clinical contexts. This review provides an integrated overview of RV dysfunction, with a focus on the diagnostic and therapeutic potential of both established and novel biomarkers.<\/jats:p>","DOI":"10.3390\/ijms26189064","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T14:10:19Z","timestamp":1758118219000},"page":"9064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Right Approach: Power of Biomarkers in the Assessment and Management of Right Ventricular Dysfunction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-7990","authenticated-orcid":false,"given":"Mihajlo","family":"Viduljevi\u0107","sequence":"first","affiliation":[{"name":"Emergency Medicine and Center for Medical Biochemistry, Department of Cardiology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Polovina","sequence":"additional","affiliation":[{"name":"Emergency Medicine and Center for Medical Biochemistry, Department of Cardiology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-8413","authenticated-orcid":false,"given":"Oliviana","family":"Geavlete","sequence":"additional","affiliation":[{"name":"Emergency Institute for Cardiovascular Diseases Prof. C.C. Iliescu, University of Medicine Carol Davila, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Adamo","sequence":"additional","affiliation":[{"name":"Institute of Cardiology, 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\/0000-0003-4956-3093","authenticated-orcid":false,"given":"Adi","family":"Had\u017eibegovi\u0107","sequence":"additional","affiliation":[{"name":"Emergency Medicine and Center for Medical Biochemistry, Department of Cardiology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milika","family":"A\u0161anin","sequence":"additional","affiliation":[{"name":"Emergency Medicine and Center for Medical Biochemistry, Department of Cardiology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-535X","authenticated-orcid":false,"given":"Sanja","family":"Stankovi\u0107","sequence":"additional","affiliation":[{"name":"Emergency Medicine and Center for Medical Biochemistry, Department of Cardiology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, 34000 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuvia","family":"Ben Gal","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, Cardiology Department, Rabin Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv 4941492, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Abdelwahab","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine Kasr Al-Ainy, Cairo University, Cairo 4240310, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6701-7072","authenticated-orcid":false,"given":"Magdy","family":"Abdelhamid","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Faculty of Medicine Kasr Al-Ainy, Cairo University, Cairo 4240310, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Ambrosy","sequence":"additional","affiliation":[{"name":"Division of Research, Kaiser Permanente Northern California, California, CA 94588, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3197-3628","authenticated-orcid":false,"given":"Ovidiu","family":"Chioncel","sequence":"additional","affiliation":[{"name":"Emergency Institute for Cardiovascular Diseases Prof. C.C. Iliescu, University of Medicine Carol Davila, 022328 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar M.","family":"Seferovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shaker, M.M., Taha, H.S., Kandil, H.I., Kamal, H.M., Mahrous, H.A., and Elamragy, A.A. (2024). Prognostic significance of right ventricular dysfunction in patients presenting with acute left-sided heart failure. Egypt. Heart J., 76.","DOI":"10.1186\/s43044-023-00432-8"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.3909\/ricm0602","article-title":"Contribution of right ventricular dysfunction to heart failure mortality: A meta-analysis","volume":"13","author":"Garrote","year":"2012","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2459\/JCM.0000000000001336","article-title":"Prognostic value of right ventricle to pulmonary artery coupling in transcatheter aortic valve implantation recipients","volume":"23","author":"Adamo","year":"2022","journal-title":"J. Cardiovasc. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Polovina, M., Chioncel, O., Savarese, G., Abdelhamid, M., Krljanac, G., Tsch\u00f6pe, C., and Seferovi\u0107, P. (2025). Predischarge and Postdischarge Heart Failure Management: Treatment Optimisation, Adherence, and Multidisciplinary Care. Med. Res. Arch., 13.","DOI":"10.18103\/mra.v13i5.6550"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/ejhf.478","article-title":"Contemporary management of acute right ventricular failure: A statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology","volume":"18","author":"Harjola","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.cca.2014.10.023","article-title":"Multiple biomarker strategies for risk stratifiction in heart failure","volume":"443","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/S0735-1097(03)00120-7","article-title":"Cardiogenic shock caused by right ventricular infarction: A report from the SHOCK registry","volume":"41","author":"Jacobs","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1001\/archinte.164.15.1685","article-title":"Prognostic Value of Echocardiographically Assessed Right Ventricular Dysfunction in Patients with Pulmonary Embolism","volume":"164","author":"Quak","year":"2004","journal-title":"Arch. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1093\/eurheartj\/ehu193","article-title":"Right heart dysfunction in heart failure with preserved ejection fraction","volume":"35","author":"Melenovsky","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1001\/jamacardio.2018.2454","article-title":"Right Ventricular Function, Right Ventricular\u2013Pulmonary Artery Coupling, and Heart Failure Risk in 4 US Communities: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"3","author":"Nochioka","year":"2018","journal-title":"JAMA Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e578","DOI":"10.1161\/CIR.0000000000000560","article-title":"Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association","volume":"137","author":"Konstam","year":"2018","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Noordegraaf, A.V., Chin, K.M., Haddad, F., Hassoun, P.M., Hemnes, A.R., Hopkins, S.R., Kawut, S.M., Langleben, D., Lumens, J., and Naeije, R. (2019). Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: An update. Eur. Respir. J., 53.","DOI":"10.1183\/13993003.01900-2018"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/clc.4960230721","article-title":"Right ventricular infarction--diagnosis and treatment","volume":"23","author":"Haji","year":"2000","journal-title":"Clin. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Copeland, V.J., Fardman, A., and Furer, A. (2023). Keep the Right in Mind-A Focused Approach to Right Ventricle-Predominant Cardiogenic Shock. Life, 13.","DOI":"10.3390\/life13020379"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.chest.2020.09.274","article-title":"Right Ventricular Dysfunction in Early Sepsis and Septic Shock","volume":"159","author":"Lanspa","year":"2021","journal-title":"Chest"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Agarwal, R., Yakkali, S., Shah, P., Vyas, R., Kushwaha, A., Krishnan, A., Nair, A.S., Hanumanthu, B.K.J., Faillace, R.T., and Gashi, E. (2025). Predictors and Outcomes of Right Ventricular Dysfunction in Patients Admitted to the Medical Intensive Care Unit for Sepsis\u2014A Retrospective Cohort Study. J. Clin. Med., 14.","DOI":"10.3390\/jcm14155423"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jaccas.2019.10.038","article-title":"An Exceptional Cause of Acute Right Heart Failure: Isolated Right Ventricular Takotsubo Syndrome","volume":"2","author":"Sionis","year":"2020","journal-title":"JACC Case Rep."},{"key":"ref_19","first-page":"442","article-title":"Takotsubo Syndrome: An International Expert Consensus Report on Practical Challenges and Specific Conditions (Part-2: Specific Entities, Risk Stratification and Challenges After Recovery)","volume":"41","author":"Yalta","year":"2024","journal-title":"Balk. Med. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/ejhf.1461","article-title":"Heart failure in cardiomyopathies: A position paper from the Heart Failure Association of the European Society of Cardiology","volume":"21","author":"Polovina","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/ejhf.3106","article-title":"Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC","volume":"26","author":"Adamo","year":"2024","journal-title":"Eur. J. Heart Fail."},{"key":"ref_22","first-page":"584","article-title":"Epidemiology and management of right ventricular-predominant heart failure and shock in the cardiac intensive care unit","volume":"11","author":"Kanwar","year":"2022","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1093\/ehjci\/jeac022","article-title":"Right ventricular longitudinal strain in the clinical routine: A state-of-the-art review","volume":"23","author":"Muraru","year":"2022","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Negru, A., Tarc\u0103u, B.M., and Agoston-Coldea, L. (2024). Cardiac Magnetic Resonance Imaging in the Evaluation of Functional Impairments in the Right Heart. Diagnostics, 14.","DOI":"10.3390\/diagnostics14222581"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1159\/000486629","article-title":"High Right Ventricular Stroke Work Index Is Associated with Worse Kidney Function in Patients with Heart Failure with Preserved Ejection Fraction","volume":"8","author":"Kanjanahattakij","year":"2018","journal-title":"Cardiorenal Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e009085","DOI":"10.1161\/CIRCHEARTFAILURE.121.009085","article-title":"Association of Pulmonary Artery Pulsatility Index With Adverse Cardiovascular Events Across a Hospital-Based Sample","volume":"15","author":"Zern","year":"2022","journal-title":"Circ. Heart Fail."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1002\/ejhf.2190","article-title":"Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy","volume":"23","author":"Tsutsui","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Pitta, F.G., Leme, A.C., Gomes, S.R., Mota, T.P., Paladino, F.V., de Souza J\u00fanior, J.L., de Paula Braz, R., Lamounier, T., Ferreira, J.B.G., and Dos Santos Ferreira, C.E. (2024). Clinical Laboratory Validation Study of a High Sensitivity Troponin I Assay on a POCT (Point of Care Testing) Device. Glob. Heart, 19.","DOI":"10.5334\/gh.1377"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1093\/eurheartj\/ehad191","article-title":"2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC)","volume":"44","author":"Byrne","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_30","first-page":"480","article-title":"Early kinetics of cardiac troponin in suspected acute myocardial infarction","volume":"74","author":"Wildi","year":"2021","journal-title":"Rev. Espa\u00f1ola De Cardiol. (Engl. Ed.)"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1161\/01.CIR.94.6.1291","article-title":"Prognostic Significance of Admission Troponin T Concentrations in Patients With Myocardial Infarction","volume":"94","author":"Stubbs","year":"1996","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1183\/09031936.00088711","article-title":"Pulmonary embolism: CT signs and cardiac biomarkers for predicting right ventricular dysfunction","volume":"39","author":"Henzler","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.jjcc.2012.07.006","article-title":"Usefulness of cardiac biomarkers in the prediction of right ventricular dysfunction before echocardiography in acute pulmonary embolism","volume":"60","author":"Choi","year":"2012","journal-title":"J. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1161\/CIRCULATIONAHA.106.680421","article-title":"Prognostic value of troponins in acute pulmonary embolism: A meta-analysis","volume":"116","author":"Becattini","year":"2007","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ijcard.2011.07.107","article-title":"Cardiac troponin-T and the prediction of acute and long-term mortality after acute pulmonary embolism","volume":"165","author":"Ng","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/eurheartj\/ehz405","article-title":"2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC)","volume":"41","author":"Konstantinides","year":"2019","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1161\/CIRCULATIONAHA.111.051177","article-title":"Predictive Value of the High-Sensitivity Troponin T Assay and the Simplified Pulmonary Embolism Severity Index in Hemodynamically Stable Patients With Acute Pulmonary Embolism","volume":"124","author":"Lankeit","year":"2011","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1183\/09031936.00174514","article-title":"Age-adjusted high-sensitivity troponin T cut-off value for risk stratification of pulmonary embolism","volume":"45","author":"Kaeberich","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_39","first-page":"421","article-title":"Takotsubo Syndrome: An International Expert Consensus Report on Practical Challenges and Specific Conditions (Part-1: Diagnostic and Therapeutic Challenges)","volume":"41","author":"Yalta","year":"2024","journal-title":"Balk. Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ganipineni, V.D.P., Jitta, S.R., Gudiwada, M., Jasti, J.R., Janga, C., Merugu, B., Bandaru, R.R., Puli, S., Venkata, V.S., and Vasavada, A. (2024). High-Sensitivity Cardiac Troponin [hs-cTn] as a Valuable Biomarker for Pulmonary Hypertension Risk Stratification: A Contemporary Review of the Literature. Healthcare, 12.","DOI":"10.3390\/healthcare12202037"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/s11897-021-00532-z","article-title":"Insights Into Genetics and Pathophysiology of Arrhythmogenic Cardiomyopathy","volume":"18","author":"Gerull","year":"2021","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1080\/1354750X.2018.1490969","article-title":"Possible mechanisms behind cardiac troponin elevations","volume":"23","author":"Hammarsten","year":"2018","journal-title":"Biomarkers"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.amjmed.2015.12.009","article-title":"Prognostic Impact of Myocardial Injury Related to Various Cardiac and Noncardiac Conditions","volume":"129","author":"Sarkisian","year":"2016","journal-title":"Am. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1681\/ASN.2017030341","article-title":"Renal Dysfunction Influences the Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin I","volume":"29","author":"Gunsolus","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1080\/07853890.2020.1800075","article-title":"Heart-type fatty acid-binding protein: An overlooked cardiac biomarker","volume":"52","author":"Goel","year":"2020","journal-title":"Ann. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ahj.2010.05.010","article-title":"Correlation of heart-type fatty acid-binding protein with mortality and echocardiographic data in patients with pulmonary embolism at intermediate risk","volume":"160","author":"Boscheri","year":"2010","journal-title":"Am. Heart J."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wunderlich, C., Langer, M., Richter, U., Tausche, A.K., Sveric, K., Boscheri, A., Christoph, M., Strasser, R.H., and Ibrahim, K. (2013). Combined value of heart-type fatty acid-binding protein and myocardial creatine kinase in risk stratification of normotensive patients with pulmonary embolism. Eur. Heart J., 34.","DOI":"10.1093\/eurheartj\/eht308.761"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bajaj, A., Rathor, P., Sehgal, V., Shetty, A., Kabak, B., and Hosur, S. (2015). Risk stratification in acute pulmonary embolism with heart-type fatty acid-binding protein: A meta-analysis. J. Crit. Care, 30.","DOI":"10.1016\/j.jcrc.2015.05.026"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1253\/circj.69.922","article-title":"Combination of heart-type fatty acid binding protein and brain natriuretic peptide can reliably risk stratify patients hospitalized for chronic heart failure","volume":"69","author":"Niizeki","year":"2005","journal-title":"Circ. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1164\/rccm.200803-459OC","article-title":"Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: A systematic review and meta-analysis","volume":"178","author":"Klok","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00408-015-9752-4","article-title":"Prognostic Value of Biomarkers in Acute Non-massive Pulmonary Embolism: A Systematic Review and Meta-analysis","volume":"193","author":"Bajaj","year":"2015","journal-title":"Lung"},{"key":"ref_52","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","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"de la Espriella, R., N\u00fa\u00f1ez-Mar\u00edn, G., Codina, P., N\u00fa\u00f1ez, J., and Bay\u00e9s-Gen\u00eds, A. (2023). Biomarkers to Improve Decision-making in Acute Heart Failure. Card. Fail. Rev., 9.","DOI":"10.15420\/cfr.2023.08"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"E731","DOI":"10.1210\/jc.2011-2839","article-title":"Insulin Up-Regulates Natriuretic Peptide Clearance Receptor Expression in the Subcutaneous Fat Depot in Obese Subjects: A Missing Link between CVD Risk and Obesity?","volume":"97","author":"Pivovarova","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1161\/CIRCULATIONAHA.106.655142","article-title":"Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals","volume":"115","author":"Wang","year":"2007","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.ahj.2012.08.014","article-title":"Biomarkers in acutely decompensated heart failure with preserved or reduced ejection fraction","volume":"164","author":"Bishu","year":"2012","journal-title":"Am. Heart J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1161\/CIRCULATIONAHA.124.072156","article-title":"Evidence-Based Application of Natriuretic Peptides in the Evaluation of Chronic Heart Failure With Preserved Ejection Fraction in the Ambulatory Outpatient Setting","volume":"151","author":"Reddy","year":"2025","journal-title":"Circulation"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/j.semarthrit.2020.02.013","article-title":"An evidence-based strategy to screen for pulmonary arterial hypertension in systemic sclerosis","volume":"50","author":"Semalulu","year":"2020","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/ejhf.2848","article-title":"Natriuretic peptides: Role in the diagnosis and management of heart failure: A scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society","volume":"25","author":"Tsutsui","year":"2023","journal-title":"Eur. J. Heart Fail."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1177\/0004563221989364","article-title":"Copeptin reliably reflects longitudinal right ventricular function","volume":"58","author":"Natale","year":"2021","journal-title":"Ann. Clin. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1111\/crj.13230","article-title":"Relationship between right ventricular dilatation and blood copeptin levels in patients with acute pulmonary embolism","volume":"14","author":"Usul","year":"2020","journal-title":"Clin. Respir. J."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Schimmel, K., Ichimura, K., Reddy, S., Haddad, F., and Spiekerkoetter, E. (2022). Cardiac Fibrosis in the Pressure Overloaded Left and Right Ventricle as a Therapeutic Target. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.886553"},{"key":"ref_63","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_64","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_65","doi-asserted-by":"crossref","unstructured":"Riccardi, M., Myhre, P.L., Zelniker, T.A., Metra, M., Januzzi, J.L., and Inciardi, R.M. (2023). Soluble ST2 in Heart Failure: A Clinical Role beyond B-Type Natriuretic Peptide. J. Cardiovasc. Dev. Dis., 10.","DOI":"10.3390\/jcdd10110468"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.jchf.2024.10.023","article-title":"Growth Differentiation Factor\u201315 Is Associated With Congestion-Related Anorexia and Weight Loss in Advanced Heart Failure","volume":"13","author":"Monzo","year":"2025","journal-title":"JACC Heart Fail."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Zaborska, B., Sygitowicz, G., Smar\u017c, K., Pilichowska-Paszkiet, E., and Budaj, A. (2020). Galectin-3 is related to right ventricular dysfunction in heart failure patients with reduced ejection fraction and may affect exercise capacity. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-73634-8"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1086\/675981","article-title":"MicroRNAs in right ventricular (dys)function (2013 Grover Conference series)","volume":"4","author":"Thum","year":"2014","journal-title":"Pulm. Circ."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/ejhf.2295","article-title":"Antigen carbohydrate 125 as a biomarker in heart failure: A narrative review","volume":"23","author":"Santas","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_70","first-page":"437","article-title":"Factors associated with plasma antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide concentrations in acute heart failure","volume":"9","author":"Mollar","year":"2020","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1002\/clc.20868","article-title":"Role of CA-125 in identification of right ventricular failure in chronic obstructive pulmonary disease","volume":"34","author":"Yilmaz","year":"2011","journal-title":"Clin. Cardiol."},{"key":"ref_72","first-page":"685","article-title":"Long-term serial kinetics of N-terminal pro B-type natriuretic peptide and carbohydrate antigen 125 for mortality risk prediction following acute heart failure","volume":"6","author":"Fonarow","year":"2017","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/ejhf.1366","article-title":"Adrenomedullin in heart failure: Pathophysiology and therapeutic application","volume":"21","author":"Voors","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/ejhf.1437","article-title":"Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure","volume":"21","author":"Kremer","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1002\/ejhf.1245","article-title":"Bio-adrenomedullin as a potential quick, reliable, and objective marker of congestion in heart failure","volume":"20","author":"Kremer","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1002\/ejhf.1937","article-title":"Bioactive adrenomedullin in plasma is associated with biventricular filling pressures in patients with advanced heart failure","volume":"23","author":"Goetze","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Tromp, J., Khan, M.A., Klip, I.T., Meyer, S., de Boer, R.A., Jaarsma, T., Hillege, H., van Veldhuisen, D.J., van der Meer, P., and Voors, A.A. (2017). Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction. J. Am. Heart Assoc., 6.","DOI":"10.1161\/JAHA.116.003989"},{"key":"ref_78","first-page":"74","article-title":"Biomarkers and their involvement in the early diagnosis of right ventricular dysfunction in type 2 Diabetes Mellitus","volume":"5","author":"Vittos","year":"2012","journal-title":"J. Med. Life"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Sommariva, E., Stadiotti, I., Casella, M., Catto, V., Dello Russo, A., Carbucicchio, C., Arnaboldi, L., De Metrio, S., Milano, G., and Scopece, A. (2021). Oxidized LDL-dependent pathway as new pathogenic trigger in arrhythmogenic cardiomyopathy. EMBO Mol. Med., 13.","DOI":"10.15252\/emmm.202114365"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.jacc.2022.01.018","article-title":"SCAI SHOCK Stage Classification Expert Consensus Update: A Review and Incorporation of Validation Studies: This statement was endorsed by the American College of Cardiology (ACC), American College of Emergency Physicians (ACEP), American Heart Association (AHA), European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC), International Society for Heart and Lung Transplantation (ISHLT), Society of Critical Care Medicine (SCCM), and Society of Thoracic Surgeons (STS) in December 2021","volume":"79","author":"Naidu","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Kumar, A., Chidambaram, V., Geetha, H.S., Majella, M.G., Bavineni, M., Pona, P.K., Jain, N., Sharalaya, Z., Al\u2019Aref, S.J., and Asnani, A. (2024). Renal Biomarkers in Heart Failure: Systematic Review and Meta-Analysis. JACC Adv., 3.","DOI":"10.1016\/j.jacadv.2023.100765"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jacc.2004.09.061","article-title":"Cystatin-C and mortality in elderly persons with heart failure","volume":"45","author":"Shlipak","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Fenster, B., Smyser, J., Schroeder, J., Buckner, J.K., and Lasalvia, L. (2013). CYSTATIN C: A NOVEL BIOMARKER FOR PULMONARY ARTERIAL HYPERTENSION. JACC, 61.","DOI":"10.1016\/S0735-1097(13)61300-5"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Duan, A., Huang, Z., Zhao, Z., Zhao, Q., Jin, Q., Yan, L., Zhang, Y., Li, X., Zhang, S., and Hu, M. (2023). The potential of cystatin C as a predictive biomarker in pulmonary hypertension. BMC Pulm. Med., 23.","DOI":"10.1186\/s12890-023-02595-1"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0140-6736(09)61378-7","article-title":"Albuminuria in chronic heart failure: Prevalence and prognostic importance","volume":"374","author":"Jackson","year":"2009","journal-title":"Lancet"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Nickel, N.P., de Jesus Perez, V.A., Zamanian, R.T., Fessel, J.P., Cogan, J.D., Hamid, R., West, J.D., de Caestecker, M.P., Yang, H., and Austin, E.D. (2019). Low-grade albuminuria in pulmonary arterial hypertension. Pulm. Circ., 9.","DOI":"10.1177\/2045894018824564"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Phan Thai, H., Hoang Bui, B., Hoang Anh, T., and Huynh Van, M. (2020). Value of Plasma NGAL and Creatinine on First Day of Admission in the Diagnosis of Cardiorenal Syndrome Type 1. Cardiol. Res. Pract., 2020.","DOI":"10.1155\/2020\/2789410"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1365-2362.2011.02573.x","article-title":"Liver dysfunction in chronic heart failure: Prevalence, characteristics and prognostic significance","volume":"42","author":"Poelzl","year":"2012","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1007\/s00134-009-1508-2","article-title":"Hypoxic hepatitis: Underlying conditions and risk factors for mortality in critically ill patients","volume":"35","author":"Fuhrmann","year":"2009","journal-title":"Intensive Care Med."},{"key":"ref_90","first-page":"87","article-title":"Heart Failure and Liver Disease: Cardiohepatic Interactions","volume":"7","author":"Xanthopoulos","year":"2019","journal-title":"JACC: Heart Fail."},{"key":"ref_91","first-page":"99","article-title":"The predictive value of transaminases at admission in patients hospitalized for heart failure: Findings from the RO-AHFS registry","volume":"2","author":"Ambrosy","year":"2013","journal-title":"Eur. Heart J. Acute Cardiovasc. Care"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1016\/j.amjcard.2017.03.033","article-title":"Usefulness of the Direct and\/or Total Bilirubin to Predict Adverse Outcomes in Patients With Acute Decompensated Heart Failure","volume":"119","author":"Okada","year":"2017","journal-title":"Am. J. Cardiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1093\/eurjhf\/hfs007","article-title":"Clinical course and predictive value of liver function tests in patients hospitalized for worsening heart failure with reduced ejection fraction: An analysis of the EVEREST trial","volume":"14","author":"Ambrosy","year":"2012","journal-title":"Eur. J. Heart Fail."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/ejhf.440","article-title":"Liver function tests in patients with acute heart failure and associated outcomes: Insights from ASCEND-HF","volume":"18","author":"Samsky","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Myhre, P.L., Grupper, A., Mebazaa, A., Davison, B., Edwards, C., Takagi, K., Adamo, M., Arrigo, M., Barros, M., and Biegus, J. (2025). Changes in Liver Function Tests, Congestion, and Prognosis After Acute Heart Failure: The STRONG-HF Trial. JACC Adv., 4.","DOI":"10.1016\/j.jacadv.2025.101607"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/ejhf.532","article-title":"Abnormal liver function tests in acute heart failure: Relationship with clinical characteristics and outcome in the PROTECT study","volume":"18","author":"Biegus","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"B\u011bhounek, M., Lipcseyov\u00e1, D., V\u00edt, O., \u017d\u00e1\u010dek, P., Talacko, P., Huskov\u00e1, Z., Kikerlov\u00e1, S., Tykvartov\u00e1, T., Wohlfahrt, P., and Melenovsk\u00fd, V. (2025). Biomarkers of RV Dysfunction in HFrEF Identified by Direct Tissue Proteomics: Extracellular Proteins Fibromodulin and Fibulin-5. Circ. Heart Fail., 18.","DOI":"10.1161\/CIRCHEARTFAILURE.124.011984"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Benes, J., Kroupova, K., Kotrc, M., Petrak, J., Jarolim, P., Novosadova, V., Kautzner, J., and Melenovsky, V. (2023). FGF-23 is a biomarker of RV dysfunction and congestion in patients with HFrEF. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-42558-4"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1007\/s00392-023-02162-y","article-title":"Fibroblast growth factor 23 as a biomarker of right ventricular dysfunction in pulmonary hypertension","volume":"112","author":"Widmann","year":"2023","journal-title":"Clin. Res. Cardiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1080\/1354750X.2020.1745889","article-title":"SPARCL1 as a biomarker of maladaptive right ventricular remodelling in pulmonary hypertension","volume":"25","author":"Keranov","year":"2020","journal-title":"Biomarkers"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1002\/ejhf.2721","article-title":"Right ventricular dysfunction in patients with new-onset heart failure: Longitudinal follow-up during guideline-directed medical therapy","volume":"24","author":"Gorter","year":"2022","journal-title":"Eur. J. Heart Fail."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1002\/ejhf.3452","article-title":"Burst steroid therapy for acute heart failure: The CORTAHF randomized, open-label, pilot trial","volume":"26","author":"Cotter","year":"2024","journal-title":"Eur. J. Heart Fail."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1002\/ejhf.2888","article-title":"Pre-discharge and early post-discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC","volume":"25","author":"Metra","year":"2023","journal-title":"Eur. J. Heart Fail."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1136\/heartjnl-2013-303632","article-title":"A novel discharge risk model for patients hospitalised for acute decompensated heart failure incorporating N-terminal pro-B-type natriuretic peptide levels: A European coLlaboration on Acute decompeNsated Heart Failure: ELAN-HF Score","volume":"100","author":"Salah","year":"2014","journal-title":"Heart"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jacc.2013.05.027","article-title":"Timing of hemoconcentration during treatment of acute decompensated heart failure and subsequent survival: Importance of sustained decongestion","volume":"62","author":"Testani","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1016\/j.jcin.2020.06.037","article-title":"Arterial Lactate in Cardiogenic Shock: Prognostic Value of Clearance Versus Single Values","volume":"13","author":"Fuernau","year":"2020","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s13613-024-01388-x","article-title":"Biomarkers in cardiogenic shock: Old pals, new friends","volume":"14","author":"Jozwiak","year":"2024","journal-title":"Ann. Intensive Care"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S2213-2600(21)00439-2","article-title":"Single-dose of adrecizumab versus placebo in acute cardiogenic shock (ACCOST-HH): An investigator-initiated, randomised, double-blinded, placebo-controlled, multicentre trial","volume":"10","author":"Karakas","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1007\/s00134-024-07618-x","article-title":"Management of cardiogenic shock: State-of-the-art","volume":"50","author":"Jung","year":"2024","journal-title":"Intensive Care Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1001\/jama.2017.10565","article-title":"Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial","volume":"318","author":"Felker","year":"2017","journal-title":"JAMA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.jchf.2016.06.007","article-title":"Carbohydrate Antigen-125-Guided Therapy in Acute Heart Failure: CHANCE-HF: A Randomized Study","volume":"4","author":"Bosch","year":"2016","journal-title":"JACC Heart Fail."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/eurheartj\/ehad335","article-title":"NT-proBNP and high intensity care for acute heart failure: The STRONG-HF trial","volume":"44","author":"Adamo","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1002\/ejhf.2327","article-title":"Guidance on the management of left ventricular assist device (LVAD) supported patients for the non-LVAD specialist healthcare provider: Executive summary","volume":"23","author":"Milicic","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_114","first-page":"43","article-title":"Advanced heart failure\u2014Current strategy of management","volume":"2","author":"Geavlete","year":"2024","journal-title":"Heart Fail. J. India"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/ejhf.2144","article-title":"Machine learning based on biomarker profiles identifies distinct subgroups of heart failure with preserved ejection fraction","volume":"23","author":"Woolley","year":"2021","journal-title":"Eur. J. Heart Fail."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9064\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:47:18Z","timestamp":1760035638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":115,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26189064"],"URL":"https:\/\/doi.org\/10.3390\/ijms26189064","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]}}}