{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T20:04:40Z","timestamp":1781813080678,"version":"3.54.5"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,8,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiac dysfunction is a prominent feature of multisystem inflammatory syndrome in children (MIS\u2010C), yet the etiology is poorly understood. We determined whether dysfunction is global or regional, and whether it is associated with the cytokine milieu, microangiopathy, or severity of shock.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We analyzed echocardiographic parameters of myocardial deformation and compared global and segmental left ventricular strain between 43 cases with MIS\u2010C \u226418\u00a0years old and 40 controls. Primary outcomes included left ventricular global longitudinal strain, right ventricular free wall strain), and left atrial strain. We evaluated relationships between strain and profiles of 10 proinflammatory cytokines, microangiopathic features (soluble C5b9), and vasoactive\u2010inotropic requirements. Compared with controls, cases with MIS\u2010C had significant impairments in all parameters of systolic and diastolic function. 65% of cases with MIS\u2010C had abnormal left ventricular function (\n              <jats:bold>|<\/jats:bold>\n              global longitudinal strain\n              <jats:bold>|<\/jats:bold>\n              &lt;17%), although elevations of cytokines were modest. All left ventricular segments were involved, without apical or basal dominance to suggest acute stress cardiomyopathy. Worse global longitudinal strain correlated with higher ratios of interleukin\u20106 (\u03c1 \u22120.43) and interleukin\u20108 (\u03c1 \u22120.43) to total hypercytokinemia, but not absolute levels of interleukin\u20106 or interleukin\u20108, or total hypercytokinemia. Similarly, worse right ventricular free wall strain correlated with higher relative interleukin\u20108 expression (\u03c1 \u22120.59). There were no significant associations between function and microangiopathy or vasoactive\u2010inotropic requirements.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Myocardial function is globally decreased in MIS\u2010C and not explained by acute stress cardiomyopathy. Cardiac dysfunction may be driven by the relative skew of the immune response toward interleukin\u20106 and interleukin\u20108 pathways, more so than degree of hyperinflammation, refining the current paradigm of myocardial involvement in MIS\u2010C.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.021428","type":"journal-article","created":{"date-parts":[[2021,8,7]],"date-time":"2021-08-07T09:01:33Z","timestamp":1628326893000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Skewed Cytokine Responses Rather Than the Magnitude of the Cytokine Storm May Drive Cardiac Dysfunction in Multisystem Inflammatory Syndrome in Children"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1691-4814","authenticated-orcid":false,"given":"Joyce C.","family":"Chang","sequence":"first","affiliation":[{"name":"Division of Rheumatology Children's Hospital of Philadelphia 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University of Pennsylvania Perelman School of Medicine Philadelphia PA"},{"name":"Division of Oncology Children's Hospital of Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumekala","family":"Nadaraj","sequence":"additional","affiliation":[{"name":"Division of Cardiology Children's Hospital of Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7373-8987","authenticated-orcid":false,"given":"David T.","family":"Teachey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Pennsylvania Perelman School of Medicine Philadelphia PA"},{"name":"Division of Oncology Children's Hospital of Philadelphia PA"},{"name":"Immune Dysregulation Frontier Program Department of Pediatrics Children's Hospital of Philadelphia 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Pediatrics Children's Hospital of Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-4802","authenticated-orcid":false,"given":"Anirban","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Pennsylvania Perelman School of Medicine Philadelphia PA"},{"name":"Division of Cardiology Children's Hospital of Philadelphia 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