---
title: "Emergency department warning indicators for pediatric fulminant myocarditis: clinical features and"
id: "plos-one-21-clinical-characteristics-and-emergency-department-based-warning-indicators-of"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-21-clinical-characteristics-and-emergency-department-based-warning-indicators-of"
content_type: "clinical_feed_article"
specialty: "Pediatrics"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0358335"
published_at: "2026-09-17T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Emergency department warning indicators for pediatric fulminant myocarditis: clinical features and
## Provenance & Clinical Metadata
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- **Specialty:** [Pediatrics](https://medichelpline.com/clinical-feed/pediatrics.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0358335)
- **Published At:** 2026-09-17T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Fulminant myocarditis (FM) in children carries high mortality and often begins with nonspecific symptoms, making early ED recognition critical. The study retrospectively analyzed 140 children with acute myocarditis admitted via the ED between 2015 and 2024; 54 had FM and 86 had acute non-fulminant myocarditis (ANFM). - The most common presenting feature among FM patients was **gastrointestinal symptoms** (88.9%). - At ED presentation, children who developed FM had lower **serum sodium** and higher **lactate** and myocardial injury markers compared with ANFM (all P < 0.05). - Variable selection used LASSO regression followed by multivariable logistic regression constrained by events-per-variable considerations. - Five ED-available early warning indicators were independently associated with FM: **gastrointestinal symptoms** (OR 11.468), **lactate** (OR 1.887 per unit), **cardiac troponin I (cTnI)** (OR 1.188 per unit), **third-degree atrioventricular block** (OR 32.211), and **serum sodium** (OR 0.785 per unit). - The study used ROC analysis, calibration curves, and internal bootstrap validation to evaluate discriminative performance; specifics of AUC and calibration metrics were reported in the full article. - Diagnostic confirmation relied on clinical criteria adapted from the 2013 ESC statement; CMR and endomyocardial biopsy were not routinely available. - The authors note the need for prospective multicenter validation of these ED-based indicators before broad clinical application. - Data were single-center and retrospective; exclusion criteria removed other cardiac or metabolic causes. - Funding: none declared. Ethics approval was obtained and requirement for informed consent was waived due to retrospective design.
## Clinical Analysis & Structured Key Points
Clinical characteristics and emergency department-based warning indicators of fulminant myocarditis in children | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Peer Review Reader Comments Figures Figures Abstract Background Fulminant myocarditis (FM) in children is associated with a high mortality rate, while its early clinical manifestations are often nonspecific. This study aimed to identify early warning indicators available at emergency department (ED) presentations to facilitate early recognition of children at high risk of FM. Methods A retrospective analysis was conducted on 140 children with acute myocarditis admitted through the ED between 01/01/2015 and 31/12/2024. Patients were classified into acute non-fulminant myocarditis (ANFM) (n = 86) and FM (n = 54) groups. The least absolute shrinkage and selection operator (LASSO) regression was utilized to optimize variable selection, followed by multivariable logistic regression analysis to identify early warning indicators of FM. Results Gastrointestinal symptoms were the most common clinical manifestation in children with FM (88.9%). Compared with the ANFM group, children with FM had lower serum sodium levels and higher lactate and myocardial injury marker levels (all P < 0.05). Multivariable logistic regression identified five early warning indicators of FM: gastrointestinal symptoms (OR = 11.468, 95% CI: 2.495–52.713), lactate (OR = 1.887, 95% CI: 1.155–3.082), cardiac troponin I (cTnI) (OR = 1.188, 95% CI: 1.055–1.337), third-degree atrioventricular block (OR = 32.211, 95% CI: 2.943–352.484), and serum sodium (OR = 0.785, 95% CI: 0.652–0.944). Conclusions Elevated lactate and cTnI, decreased serum sodium, gastrointestinal symptoms, and third-degree atrioventricular block at ED presentation may help identify children at high risk of FM. Prospective multicenter studies are needed to validate these findings. Citation: Huang L, Jiang J, Qi Y, Deng X, Ma W, Chen X, et al. (2026) Clinical characteristics and emergency department-based warning indicators of fulminant myocarditis in children. PLoS One 21(9): e0358335. https://doi.org/10.1371/journal.pone.0358335 Editor: Hany Mahmoud Abo-Haded, Mansoura University Faculty of Medicine, EGYPT Received: February 17, 2026; Accepted: August 31, 2026; Published: September 17, 2026 Copyright: © 2026 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the paper and its Supporting Information files. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Introduction Myocarditis is an inflammatory disease of the myocardium with clinical manifestations that vary widely, ranging from mild flu-like symptoms to syncope, seizures, heart failure, cardiogenic shock, and even sudden cardiac death [ 1 ]. Pediatric myocarditis may lead to severe long-term sequelae, such as chronic congestive heart failure, dilated cardiomyopathy (DCM), and even death [ 2 – 4 ]. Previous studies have estimated the annual incidence of pediatric myocarditis to range from 0.3 to 2 per 100,000 children [ 5 – 8 ]. According to the 2023 guidelines of the Japanese Circulation Society (JCS), approximately 30%–40% of pediatric myocarditis cases present as fulminant myocarditis (FM), while 40%–65% are classified as acute non-fulminant myocarditis (ANFM) [ 8 ]. FM is characterized by an insidious onset, rapid clinical deterioration, and an extremely high mortality risk. Early recognition and prompt initiation of aggressive circulatory support have been shown to improve clinical outcomes [ 9 ]. As the emergency department (ED) serves as the initial point of medical contact for most children, the early identification of those at high risk for FM from nonspecific symptoms and signs is critically important. Emergency physicians often need to make rapid clinical judgments based on limited information, including the initial clinical presentation, laboratory findings, and imaging results [ 10 ]. This study retrospectively analyzed the early clinical characteristics of children with ANFM and FM, aiming to identify associated indicators of FM based on parameters available at ED presentation, thereby providing evidence to support rapid clinical decision-making, including patient management, levels of care or referral. Materials and methods Study population This single-center retrospective study included children aged 28 days to 16 years who were admitted through the ED of Shenzhen Children’s Hospital between 01/01/2015 and 31/12/2024 with a primary discharge diagnosis of ANFM or FM. Patients were either directly admitted from the ED of our institution or transferred from other hospitals to the ED and subsequently hospitalized. Potential cases were initially identified through the hospital medical record database using International Classification of Diseases, 10th Revision (ICD-10) codes for myocarditis (I40 and I51.4). All candidate cases were independently reviewed by a pediatric emergency physician and a pediatric cardiologist, both blinded to study outcomes. Discrepancies were resolved by consensus after joint discussion. Patients were classified into the ANFM and FM groups according to the final discharge diagnosis. The study protocol was approved by the Ethics Committee of Shenzhen Children’s Hospital (Approval No. 2025049). Data were accessed for research purposes between 27/06/2025 and 30/08/2025. Identifiable information was removed prior to data analysis. Because this study involved retrospective data collection from existing medical records, the institutional review board waived the requirement for informed consent. Diagnostic criteria The diagnosis of ANFM was established by pediatric cardiology specialists, based on the 2013 European Society of Cardiology (ESC) position statement for clinically suspected myocarditis [ 11 ], with adaptations for pediatric patients. ANFM required at least one compatible clinical manifestation, which may include chest pain, dyspnea, palpitations, signs of heart failure, unexplained arrhythmia, or age-appropriate objective findings in young children such as feeding difficulties, lethargy or poor responsiveness, syncope or near syncope, tachycardia, and tachypnea. Additionally, at least one diagnostic criterion from a different category must be met, including: (1) abnormalities on electrocardiography or Holter monitoring; (2) elevated biomarkers of myocardial injury (cardiac troponin I); or (3) structural and/or functional abnormalities detected by echocardiography or cardiac magnetic resonance (CMR), or tissue characterization on CMR demonstrating a typical myocarditis pattern, such as myocardial edema and/or late gadolinium enhancement (LGE). Based on published international and national guidelines and previous studies, FM was defined as acute myocarditis with rapid hemodynamic deterioration within 2 weeks of symptom onset, manifested as cardiogenic shock or life-threatening arrhythmias with hemodynamic instability, and requiring vasoactive agents and/or mechanical circulatory support [ 9 , 12 , 13 ]. As CMR was not routinely performed before discharge in most patients, and endomyocardial biopsy (EMB) was not available, the study population consisted of clinically suspected myocarditis cases diagnosed based on a comprehensive assessment of clinical presentation, laboratory findings, electrocardiography, echocardiography, and available CMR results. Exclusion criteria Patients were excluded from the study if they presented with congenital heart disease, cardiomyopathy, coronary or valvular disease, hyperthyroidism, inherited metabolic disorders, or other non-myocarditis causes of cardiac dysfunction; if symptom onset occurred more than 30 days prior to presentation; if they were transferred after more than 24 hours of treatment at another institution; or if myocarditis was listed as a secondary diagnosis. Data collection Candidate variables were selected based on clinical relevance, prior literature, and availability at initial medical contact. All variables were derived from data obtained at the first medical encounter. For patients presented directly to our ED, the earliest available clinical and laboratory data were recorded. For transferred patients, data obtained at the referring hospital prior to transfer were prioritized. For examinations not completed during the ED visit (e.g., echocardiography), the earliest available results on the day of admission were included. Baseline data included age, sex, duration of illness prior to admission, and clinical outcomes. Clinical manifestations were categorized as respiratory, gastrointestinal, cardiovascular, and neurological symptoms, as well as fever and hepatomegaly. Laboratory and imaging variables included white blood cell count (WBC), C-reactive protein (CRP), serum sodium (Na) and potassium (K), lactate (Lac), myocardial injury markers, electrocardiography, chest radiography, and echocardiography. Statistical analysis Continuous variables with a normal distribution were expressed as mean ± standard deviation and compared between groups using the independent-samples t -test. Non-normally distributed continuous variables were presented as median (interquartile range [IQR]) and compared using the Mann–Whitney U test. Categorical variables were expressed as counts (percentages) and compared using the chi-square test or Fisher’s exact test. Given the low proportion of missing data (<5%), missing values were imputed using the median for continuous variables and the mode for categorical variables. Univariable logistic regression analysis was performed to identify candidate variables ( P < 0.10). Echocardiography was not available for all patients at ED presentation, but LVEF was considered clinically important. Therefore, least absolute shrinkage and selection operator (LASSO) regression analyses were conducted both with and without LVEF. Variables were selected using LASSO regression with 10-fold cross-validation based on the λ.1se criterion. Given the limited number of events, the number of variables included in the final multivariable logistic regression was restricted according to the events-per-variable principle (EPV ≥ 10). Among variables selected by LASSO, indicators were prioritized based on their relative contribution (as reflected by the absolute magnitude of regression coefficients), and the final set of variables was determined within the EPV constraint. LASSO is a penalized regression method that performs variable selection by shrinking less informative coefficients toward zero, thereby reducing multicollinearity and overfitting when multiple candidate variables are analyzed. Selected variables were subsequently entered into multivariable logistic regression, and those with P < 0.05 were considered significantly associated with FM. The discriminative ability of the selected indicators was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration was assessed using calibration curves and the Hosmer–Lemeshow test. Internal validation was performed using bootstrap resampling (1,000 iterations) to obtain optimism-corrected AUC values. Univariable and multivariable logistic regression analyses were performed using SPSS (version 27.0), while LASSO regression, ROC analysis, and internal validation were conducted using R (version 4.5.1). Results Comparison of baseline and clinical characteristics between FM and ANFM Between 01/01/2015 and 31/12/2024, 178 children with acute myocarditis were admitted through the ED. After excluding children transferred from other hospitals after more than 24 hours of inpatient treatment (n = 14), those with myocarditis as a secondary diagnosis (n = 17), a previous history of myocarditis (n = 4), chronic myocarditis (n = 2), and congenital heart disease (n = 1), 140 children were included in the final analysis. Among these, 54 children were classified as FM and 86 as ANFM. Children with FM were younger than those with ANFM (6 years vs. 10 years, P < 0.001). The FM group had a median symptom duration of 2 days before admission, and all five deaths occurred within 72 hours of admission ( Table 1 ). Download: PNG larger image TIFF original image Table 1. Baseline and clinical characteristics of children with fulminant myocarditis and acute non-fulminant myocarditis. https://doi.org/10.1371/journal.pone.0358335.t001 FM occurred most frequently in preschool-aged (3–7 years) and school-aged (7–12 years) children ( Fig 1 ). The proportion of males was higher in the ANFM group than in the FM group, whereas the sex distribution in the FM group was relatively balanced. Gastrointestinal symptoms were more common in the FM group than in the ANFM group (88.9% vs. 40.7%, P < 0.001). Among children with FM, nausea and/or vomiting were the most common gastrointestinal manifestations, occurring in 79.6% (43/54) of cases, whereas chest pain was reported in only 9.3% (5/54). Compared with the ANFM group, children with FM had a longer hospital stay (15.5 days vs. 7 days, P < 0.001), a higher rate of ECMO use (35.2% vs. 0.0%, P < 0.001), and higher mortality (9.3% vs. 0.0%, P = 0.007) ( Table 1 ). Age-group distributions of clinical symptoms in children with FM and ANFM are shown in S1 Fig . Download: PNG larger image TIFF original image Fig 1. Age distribution of children with fulminant myocarditis and acute non-fulminant myocarditis. https://doi.org/10.1371/journal.pone.0358335.g001 Comparison of laboratory and imaging examinations between FM and ANFM Compared with the ANFM group, children with FM had significantly lower Na levels and higher Lac and myocardial injury marker levels, including cardiac troponin I (cTnI), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), and creatine kinase (CK) (all P < 0.05) ( Table 2 ). Download: PNG larger image TIFF original image Table 2. Laboratory, electrocardiographic, imaging, and echocardiographic findings in children with fulminant myocarditis and acute non-fulminant myocarditis. https://doi.org/10.1371/journal.pone.0358335.t002 Electrocardiographic abnormalities were observed in 92.6% of children with FM, with ST-segment changes (37.0%) and atrioventricular block (AVB) (37.0%) being the most common findings. Compared with the ANFM group, the FM group had a higher incidence of abnormal echocardiographic findings, including ventricular wall thickening, chamber dilation, wall motion abnormalities, and pericardial effusion. Furthermore, LVEF was significantly lower in the FM group (47.5% vs. 64.1%, P < 0.05). Cardiomegaly on chest radiography was also more frequent in the FM group ( P < 0.05) ( Table 2 ). CMR was performed in 46 patients, 29 of whom showed findings consistent with myocarditis. CMR was performed at a median of 7 (5–9) days after ED presentation, with a range of 2–22 days. Warning indicators for early identification of FM in the ED In the analysis excluding LVEF, variables were entered into LASSO regression with 10-fold cross-validation ( λ. 1se = 0.031). A total of 14 variables with non-zero coefficients were identified, including Lac, Na, third-degree AVB, cTnI, gastrointestinal symptoms, age, hepatomegaly, neurological symptoms, fever, CK-MB, male, glucose, cardiomegaly, and LDH ( Fig 2A and 2B ). Download: PNG larger image TIFF original image Fig 2. Least absolute shrinkage and selection operator variable selection for indicators of fulminant myocarditis. (A) Coefficient regularization paths of candidate variables. As the penalty parameter λ increases, coefficients shrink toward zero. The red dashed line indicates the value of λ. 1se = 0.031, at which 14 variables with non-zero coefficients were retained. (B) Ten-fold cross-validation curve for selection of the optimal penalty parameter λ. The red dashed line indicates λ. 1se = 0.031. https://doi.org/10.1371/journal.pone.0358335.g002 Based on the EPV ≥ 10 principle (EPV = 10.8) and variable contribution, the five variables with the largest absolute coefficients were included in the multivariable logistic regression analysis. Ultimately, five warning indicators of FM were identified ( Table 3 ): gastrointestinal symptoms (OR = 11.468, 95% CI: 2.495–52.713, P = 0.002), Lac (OR = 1.887, 95% CI: 1.155–3.082, P = 0.011), cTnI (OR = 1.188, 95% CI: 1.055–1.337, P = 0.004), third-degree AVB (OR = 32.211, 95% CI: 2.943–352.484, P = 0.004), and Na (OR = 0.785, 95% CI: 0.652–0.944, P = 0.010) ( Table 3 ). Download: PNG larger image TIFF original image Table 3. Multivariable logistic regression analysis of factors associated with fulminant myocarditis at emergency department presentation. https://doi.org/10.1371/journal.pone.0358335.t003 The combination of warning indicators showed good discriminatory ability, with an AUC of 0.935 ( Fig 3 ). The optimal cutoff value was 0.435, with a sensitivity of 0.777, specificity of 0.941, positive predictive value of 0.893, and negative predictive value of 0.871. After bootstrap internal validation (B = 1,000), the optimism-corrected AUC was 0.918. Calibration curves showed good agreement between predicted and observed probabilities ( Fig 4 ). The Hosmer–Lemeshow test indicated good fit (χ² = 2.469, P = 0.963). Download: PNG larger image TIFF original image Fig 3. Receiver operating characteristic curve of the selected early warning indicator combination for fulminant myocarditis. Abbreviation: ROC, receiver operating characteristic curve. https://doi.org/10.1371/journal.pone.0358335.g003 Download: PNG larger image TIFF original image Fig 4. Calibration curve of the combined early warning indicators for fulminant myocarditis. https://doi.org/10.1371/journal.pone.0358335.g004 In a supplementary analysis including LVEF when available ( S1 Table ), the AUC increased to 0.973, indicating improved discrimination ( S2 Fig ). Discussion Our institution is a tertiary pediatric referral center with an annual ED volume exceeding 200,000 visits, receiving critically ill children transferred from both the local city and surrounding regions. Using a combination of LASSO regression and multivariable logistic regression, this study explored warning indicators of FM at ED presentations. We identified elevated Lac and cTnI, decreased Na, gastrointestinal symptoms, and third-degree AVB as warning indicators associated with FM. Importantly, all the variables can be readily obtained during initial ED evaluation. These findings may assist pediatric emergency physicians in swiftly identifying children at high risk of progressing to FM and facilitate timely therapeutic interventions. Two nationwide epidemiological surveys conducted in Japan at a 10-year interval reported an overall survival rate of 75.6% among children with myocarditis, whereas the survival rate of FM remained substantially lower, ranging from 48.6% to 51.6% [ 1 , 14 ]. Some children with FM present to the ED with hemodynamic instability or overt shock, forcing emergency physicians to make urgent clinical decisions in the absence of sufficient diagnostic evidence. Furthermore, ANFM may rapidly progress to hemodynamic deterioration and refractory heart failure. Previous studies have demonstrated that early identification of FM, prompt initiation of mechanical circulatory support, and aggressive maintenance of organ function are associated with favorable outcomes in pediatric myocarditis [ 9 , 14 ]. When cardiac function deteriorates rapidly, resulting in a marked reduction
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