Markers of Cardiac Injury and Dysfunction in Pediatric Hyperinflammatory States: From MIS-C to Sepsis and MAS/HLH

Cardiac dysfunction is a defining, prognostically significant complication across a spectrum of pediatric hyperinflammatory illnesses, including multisystem inflammatory syndrome in children (MIS-C), Kawasaki disease, sepsis and septic shock, macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH), cytokine release syndrome (CRS) after immunotherapy or cellular therapy, and cancer therapy-related cardiotoxicity. Despite differing triggers, these conditions converge on shared mechanisms of myocardial injury, including cytokine-mediated depression of contractility, endothelial dysfunction, microvascular thrombosis, and, in some cases, direct viral or immune-mediated myocarditis. The field still lacks a unified framework for detecting, stratifying, and monitoring cardiac involvement across this spectrum, and clinicians often extrapolate practice from one condition to another without strong supporting evidence, since each literature has developed largely in isolation.Recent work has advanced both the biomarker and imaging landscape. Meta-analyses have refined pooled estimates for NT-proBNP and troponin in MIS-C, while copeptin, CXCL9, angiopoietin-2, and IL-6 are emerging as candidate markers of endothelial and immune dysregulation. Speckle-tracking strain echocardiography has repeatedly detected subclinical myocardial dysfunction in children with preserved ejection fraction across MIS-C, Kawasaki disease, sepsis, and chemotherapy-related cardiotoxicity, suggesting strain parameters may generalize better than conventional ejection-fraction-based assessment. Comparative studies further show that MIS-C and Kawasaki disease follow distinct recovery trajectories, arguing for condition-specific rather than one-size-fits-all surveillance.Important gaps remain. Predictive models built from admission data perform well for myocardial dysfunction but poorly for coronary artery involvement, suggesting mechanistically distinct processes that current tools do not yet separate. A related blind spot is the child with pre-existing cardiac disease, such as congenital heart disease, cardiomyopathy, or prior cardiac surgery, who develops sepsis or another hyperinflammatory insult on top of that baseline, where thresholds derived from structurally normal hearts do not transfer cleanly. Pediatric-specific diagnostic criteria for MAS in the sepsis context remain under-validated, and adult- or oncology-derived tools risk misclassification in children. Cardiotoxicity surveillance in pediatric hematology-oncology and HSCT populations rarely features alongside the MIS-C or sepsis literature, and long-term follow-up after the acute episode remains inconsistent across centers.This Research Topic aims to bring these usually siloed literatures together, since the underlying injury pathways and the practical bedside questions, such as which biomarker, which imaging window, and which threshold triggers escalation, are strikingly similar across conditions. We welcome contributions from pediatric cardiologists, intensivists, rheumatologists, infectious disease specialists, hematologist-oncologists, and HSCT physicians, addressing cardiac involvement individually or comparatively, with the goal of building a genuinely cross-specialty reference collection. To gather further insights in this domain, we welcome articles addressing, but not limited to, the following themes:• Cardiac involvement in MIS-C, Kawasaki disease, and pediatric or neonatal sepsis• Cardiac injury in MAS/HLH and in CRS following CAR-T or HSCTHyperinflammation-associated cardiotoxicity, including anthracycline and immune-mediated injury•Hyperinflammatory insults superimposed on pre-existing cardiac disease•Biomarker discovery and validation (e.g., NT-proBNP, troponin, copeptin, CXCL9, angiopoietin-2, IL-6)•Strain and advanced imaging for detecting subclinical dysfunction•Myocardial-versus-coronary mechanistic distinctions•Pediatric-specific diagnostic criteria and validated predictive models•Longitudinal surveillance and long-term follow-up strategiesArticle types: Original Research, Systematic Review, Meta-Analysis, Mini Review, Perspective, Case Report, Brief Research Report Topic editors: Deepika Gandhi, Dr Indira Jayakumar, Shrishu Ravidas Kamath Source: https://www.frontiersin.org/research-topics/86531/markers-of-cardiac-injury-and-dysfunction-in-pediatric-hyperinflammatory-states-from-mis-c-to-sepsis-and-mashlh