{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:22:19Z","timestamp":1772817739313,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"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>Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome (PIMS), presents significant challenges in pediatric cardiology, due to its complex molecular pathophysiology. In this retrospective analysis of 15 cases that were managed at a single tertiary care center, we investigated the molecular contributors to myocardial dysfunction, including cytokine storms, hyperinflammation markers, and hypercoagulable states. Transient myocardial involvement was identified in 46.6% of patients, with complete recovery achieved within 2\u20134 weeks following treatment. Ferritin, NT-ProBNP, and troponin levels were significantly elevated in patients with ventricular dysfunction compared to those without. The neutrophil-to-lymphocyte ratio (NLR), which was previously identified as a severity marker in acute COVID-19, was also significantly higher in patients with ventricular dysfunction, suggesting its potential as a prognostic indicator in MIS-C. Notably, no coronary artery aneurysms were detected in the cohort. These findings underscore the importance of early, standardized therapeutic interventions in mitigating severe outcomes, and they provide valuable insights into the molecular mechanisms driving myocardial dysfunction in MIS-C. Incorporating NLR and ferritin into the initial diagnostic workup may improve the early triage and identification of high-risk MIS-C patients.<\/jats:p>","DOI":"10.3390\/ijms26083580","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T10:47:41Z","timestamp":1744282061000},"page":"3580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Mechanisms and Pathophysiology of Myocardial Disease: Insights from Pediatric Inflammatory Multisystem Syndrome (PIMS) Associated with SARS-CoV-2"],"prefix":"10.3390","volume":"26","author":[{"given":"Mar\u00eda Teresa","family":"Viadero","sequence":"first","affiliation":[{"name":"Pediatric Cardiology, Division of Pediatrics, University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, University of Cantabria, Avda. Valdecilla s\/n, 39008 Santander, Spain"},{"name":"Division of Pediatrics, University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, Avda. Valdecilla s\/n, 39008 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jes\u00fas","family":"Caldeiro","sequence":"additional","affiliation":[{"name":"Division of Pediatrics, University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, Avda. Valdecilla s\/n, 39008 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3146-8621","authenticated-orcid":false,"given":"Natalia","family":"Fern\u00e1ndez-Suarez","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Division of Pediatrics, University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, University of Cantabria, Avda. Valdecilla s\/n, 39008 Santander, Spain"},{"name":"Division of Pediatrics, University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, Avda. Valdecilla s\/n, 39008 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Garde","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology, Division of Pediatrics, University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, University of Cantabria, Avda. Valdecilla s\/n, 39008 Santander, Spain"},{"name":"Division of Pediatrics, University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, Avda. Valdecilla s\/n, 39008 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jes\u00fas","family":"Cabero","sequence":"additional","affiliation":[{"name":"Head of Pediatrics Division, University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, University of Cantabria, Avda. Valdecilla s\/n, 39008 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-241X","authenticated-orcid":false,"given":"Domingo","family":"Gonz\u00e1lez-Lamu\u00f1o","sequence":"additional","affiliation":[{"name":"Consultant of Nefrology, Rare Diseases and Clinical Genetics Department, Division of Pediatrics University Hospital \u201cMarqu\u00e9s de Valdecilla\u201d, University of Cantabria, Avda. Valdecilla s\/n, 39008 Santander, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.ccc.2022.01.005","article-title":"Severe COVID-19 and Multisystem Inflammatory Syndrome in Children in Children and Adolescents","volume":"38","author":"Blatz","year":"2022","journal-title":"Crit. Care Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cantarutti, N., Battista, V., Stagnaro, N., Labate, M.E., Cicenia, M., Campisi, M., Vitali, V., Secinaro, A., Campana, A., and Trocchio, G. (2022). Long-Term Cardiovascular Outcome in Children with MIS-C Linked to SARS-CoV-2 Infection\u2014An Italian Multicenter Experience. Biology, 11.","DOI":"10.3390\/biology11101474"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1001\/jama.2021.2091","article-title":"Characteristics and Outcomes of US Children and Adolescents with Multisystem Inflammatory Syndrome in Children (MIS-C) Compared with Severe Acute COVID-19","volume":"325","author":"Feldstein","year":"2021","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1161\/CIRCULATIONAHA.120.050065","article-title":"Acute Cardiovascular Manifestations in 286 Children with Multisystem Inflammatory Syndrome Associated with COVID-19 Infection in Europe","volume":"143","author":"Valverde","year":"2021","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1001\/jamapediatrics.2024.5466","article-title":"Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study","volume":"179","author":"Truong","year":"2025","journal-title":"JAMA Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1016\/j.jacc.2020.08.056","article-title":"Echocardiographic Findings in Pediatric Multisystem Inflammatory Syndrome Associated with COVID-19 in the United States","volume":"76","author":"Matsubara","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e927","DOI":"10.1161\/CIR.0000000000000484","article-title":"Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals from the American Heart Association","volume":"135","author":"McCrindle","year":"2017","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1001\/jama.2021.23262","article-title":"Multisystem Inflammatory Syndrome in Children by COVID-19 Vaccination Status of Adolescents in France","volume":"327","author":"Levy","year":"2022","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"52","DOI":"10.15585\/mmwr.mm7102e1","article-title":"Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA Vaccination Against Multisystem Inflammatory Syndrome in Children Among Persons Aged 12-18 Years\u2014United States, July-December 2021","volume":"71","author":"Zambrano","year":"2022","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S2352-4642(22)00100-6","article-title":"Incidence and clinical phenotype of multisystem inflammatory syndrome in children after infection with the SARS-CoV-2 delta variant by vaccination status: A Danish nationwide prospective cohort study","volume":"6","author":"Nygaard","year":"2022","journal-title":"Lancet Child. Adolesc. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.cjca.2023.01.002","article-title":"Emerging Insights Into the Pathophysiology of Multisystem Inflammatory Syndrome Associated with COVID-19 in Children","volume":"39","author":"Lin","year":"2023","journal-title":"Can. J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.cell.2020.09.016","article-title":"The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19","volume":"183","author":"Consiglio","year":"2020","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gelzo, M., Giannattasio, A., Maglione, M., Muzzica, S., D\u2019Anna, C., Scial\u00f2, F., Gagliardo, T., Grieco, M., Tipo, V., and Castaldo, G. (2022). Biomarkers of Endothelial Damage in Distinct Phases of Multisystem Inflammatory Syndrome in Children. Metabolites, 12.","DOI":"10.3390\/metabo12080680"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1111\/jth.15340","article-title":"Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort","volume":"19","author":"Vagrecha","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1007\/s00431-021-03993-5","article-title":"Multisystem inflammatory syndrome in children related to COVID-19: A systematic review","volume":"180","author":"Hoste","year":"2021","journal-title":"Eur. J. Pediatr."},{"key":"ref_16","first-page":"51","article-title":"Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation","volume":"38","author":"Radia","year":"2021","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Regolo, M., Vaccaro, M., Sorce, A., Stancanelli, B., Colaci, M., Natoli, G., Russo, M., Alessandria, I., Motta, M., and Santangelo, N. (2022). Neutrophil-to-Lymphocyte Ratio (NLR) Is a Promising Predictor of Mortality and Admission to Intensive Care Unit of COVID-19 Patients. J. Clin. Med., 11.","DOI":"10.3390\/jcm11082235"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Regolo, M., Sorce, A., Vaccaro, M., Colaci, M., Stancanelli, B., Natoli, G., Motta, M., Isaia, I., Castelletti, F., and Giangreco, F. (2023). Assessing Humoral Immuno-Inflammatory Pathways Associated with Respiratory Failure in COVID-19 Patients. J. Clin. Med., 12.","DOI":"10.20944\/preprints202305.0810.v1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41584-021-00709-9","article-title":"Multisystem inflammatory syndrome in children and Kawasaki disease: A critical comparison","volume":"17","author":"Sharma","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_20","unstructured":"Ministerio de Sanidad de Espa\u00f1a Aportaci\u00f3n al Pago de Medicamentos por Receta en el SNS (2025, January 02). Ministerio de Sanidad. Available online: https:\/\/www.sanidad.gob.es\/estadEstudios\/estadisticas\/sisInfSanSNS\/pdf\/aportacionRecetaSNS.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1161\/01.CIR.0000145143.19711.78","article-title":"Diagnosis, treatment, and long-term management of Kawasaki disease: A statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association","volume":"110","author":"Newburger","year":"2004","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1002\/art.41454","article-title":"American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 1","volume":"72","author":"Henderson","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1002\/art.41616","article-title":"American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 2","volume":"73","author":"Henderson","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1002\/art.42062","article-title":"American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 and Hyperinflammation in Pediatric COVID-19: Version 3","volume":"74","author":"Henderson","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_25","first-page":"e1","article-title":"Documento espa\u00f1ol de consenso sobre diagn\u00f3stico, estabilizaci\u00f3n y tratamiento del s\u00edndrome inflamatorio multisist\u00e9mico pedi\u00e1trico vinculado a SARS-CoV-2 (SIM-PedS) [Spanish consensus document on diagnosis, stabilisation and treatment of pediatric multisystem inflammatory syndrome related to SARS-CoV-2 (SIM-PedS)]","volume":"94","author":"Tagarro","year":"2021","journal-title":"An. Pediatr. (Engl. Ed.)"},{"key":"ref_26","unstructured":"CDC Long COVID Basics (2025, January 02). Centers for Disease Control and Preventions (CDC), Available online: https:\/\/www.cdc.gov\/covid\/long-term-effects\/index.html."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Acevedo, L., Pi\u00f1eres-Olave, B.E., Ni\u00f1o-Serna, L.F., Vega, L.M., Gomez, I.J.A., Chac\u00f3n, S., Jaramillo-Bustamante, J.C., Mulett-Hoyos, H., Gonz\u00e1lez-Pardo, O., and Zemanate, E. (2021). Mortality and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 in critically ill patients: An observational multicenter study (MISCO study). BMC Pediatr., 21.","DOI":"10.1186\/s12887-021-02974-9"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev-med-042409-151944","article-title":"Kawasaki disease: Novel insights into etiology and genetic susceptibility","volume":"62","author":"Rowley","year":"2011","journal-title":"Annu. Rev. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2020009704","DOI":"10.1542\/peds.2020-009704","article-title":"Atrioventricular Block in Children with Multisystem Inflammatory Syndrome","volume":"146","author":"Dionne","year":"2020","journal-title":"Pediatrics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1001\/jama.2020.10370","article-title":"SARS-CoV-2-Related Inflammatory Multisystem Syndrome in Children: Different or Shared Etiology and Pathophysiology as Kawasaki Disease?","volume":"324","author":"McCrindle","year":"2020","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1002\/art.41103","article-title":"Benefit of Anakinra in Treating Pediatric Secondary Hemophagocytic Lymphohistiocytosis","volume":"72","author":"Eloseily","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S2352-4642(21)00050-X","article-title":"Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: A retrospective surveillance study","volume":"5","author":"Abrams","year":"2021","journal-title":"Lancet Child. Adolesc. Health"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1161\/CIRCULATIONAHA.120.048360","article-title":"Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic","volume":"142","author":"Belhadjer","year":"2020","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.jaci.2020.07.033","article-title":"Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1","volume":"146","author":"Lee","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e783","DOI":"10.1542\/peds.2008-1871","article-title":"Recognition of Kawasaki disease shock syndrome","volume":"123","author":"Kanegaye","year":"2009","journal-title":"Pediatrics"},{"key":"ref_36","unstructured":"World Health Organization (2020, May 17). Multisystem Inflammatory Syndrome in Children and Adolescents with COVID-19: Scientific Brief. Available online: https:\/\/www.who.int\/publications-detail\/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19."},{"key":"ref_37","unstructured":"(2023, January 27). CDC\/CSTE Standardized Case Definition for Surveillance of Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection. Available online: https:\/\/cdn.ymaws.com\/www.cste.org\/resource\/resmgr\/ps\/ps2022\/22-ID-02_MISC.pdf."},{"key":"ref_38","unstructured":"Centers for Disease Control and Prevention (2025, January 02). Child and Teen BMI Calculator, Available online: https:\/\/www.cdc.gov\/bmi\/child-teen-calculator\/index.html."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.echo.2023.11.015","article-title":"Guidelines for Performing a Comprehensive Pediatric Transthoracic Echocardiogram: Recommendations From the American Society of Echocardiography","volume":"37","author":"Lopez","year":"2024","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1161\/CIRCULATIONAHA.107.690875","article-title":"Pediatric Heart Network Investigators. Coronary artery involvement in children with Kawasaki disease: Risk factors from analysis of serial normalized measurements","volume":"116","author":"McCrindle","year":"2007","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.echo.2016.03.017","article-title":"A New Z-Score Curve of the Coronary Arterial Internal Diameter Using the Lambda-Mu-Sigma Method in a Pediatric Population","volume":"29","author":"Kobayashi","year":"2016","journal-title":"J. Am. Soc. Echocardiogr."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3580\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:12:22Z","timestamp":1760029942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,10]]},"references-count":41,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083580"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083580","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,10]]}}}