Zhao et al. BMC Pediatrics(2024) 24:553
https://doi.org/10.1186/s12887-024-05022-4

BMC Pediatrics

RESEARCH

Open AccessA retrospective analysis of clinicalcharacteristics and outcomes of pediatricfulminant myocarditis
Yuhang Zhao1, Min Da1*, Xun Yang1, Yang Xu1 and Jirong Qi1*
Abstract
Background The study aimed to explore clinical indicators that can predict the prognosis of children with acutefulminant myocarditis (AFM) through a retrospective analysis.
Methods A retrospective analysis was conducted on the clinical indices of 79 children diagnosed with AFM andhospitalized from March 2013 to March 2023. Relevant demographic and clinical data, including symptoms at
admission, laboratory results, and outcomes were extracted to identify factors associated with in-hospital mortality.
Results A total of 79 children with AFM were analyzed. The survival group (n = 61) had a longer median hospital
stay and higher medical expenses compared to the death group (n = 18). Significant differences in the levels of left
ventricular ejection fraction (LVEF)(P < 0.001), myoglobin (MYO)(P < 0.001), aspartate aminotransferase (AST)(P < 0.001),
lactate dehydrogenase (LDH)(P = 0.004), B-type natriuretic peptide (BNP)(P = 0.005), arterial potential hydrogen(PH)(P < 0.001), bicarbonate (HCO3-)(P = 0.003), serum lactate (Lac)(P = 0.001), peripheral oxygen saturation (SpO2)(P = 0.008), and white blood cell count (WBC)(P = 0.007) were observed between the two groups. Additionally, there
were significant differences in the incidences of multi-organ failure (P = 0.003) and respiratory failure (P = 0.001)
between the two groups.
Conclusions Severe myocardial injury (AST > 194.00 U/L, LDH > 637.50 U/L, MYO > 265.75 µg/L, BNP > 1738.50 ng/L),
acidosis (PH < 7.29, HCO3− <18.45 mmol/L, Lac > 12.30 mmol/L), hypoxia (SpO2 < 97.50%), inflammatory response(WBC > 9.69*109/L), left ventricular systolic dysfunction (LVEF < 28.25%), multi-organ failure, and respiratory failure are
significantly associated with higher mortality rates. These factors can accurately identify AFM children at an increased
risk of death.
Keywords Children, Fulminant myocarditis, Extracorporeal membrane oxygenation, Risk factors, Pediatric*Correspondence:
Min Dadamingirlnanjing@126.com
Jirong Qi
ertongxinlianxin@163.com
1
Nanjing Medical University Affiliated Nanjing Children’s Hospital,
Nanjing 210008, China© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you
give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified thelicensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to thematerial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation
or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://
creativecommons.org/licenses/by-nc-nd/4.0/.

Zhao et al. BMC Pediatrics(2024) 24:553

Background
Acute myocarditis (AM), an inflammatory disease of the
myocardium, is often caused by viral infections or autoimmune diseases [1–3], and is clinically manifested by arange of subclinical symptoms that may deteriorate into
sudden death, which are more pronounced in children[4]. Currently, the diagnosis of AM is primarily based onclinical presentations, blood tests (elevated biomarkers of
myocardial necrosis), electrocardiography, and cardiac
magnetic resonance imaging (MRI) showing myocardial
dysfunction, edema, and fibrosis [5]. Endomyocardial
biopsy is the gold standard for diagnosis [6]. Acute fulminant myocarditis (AFM), a lethal form of AM with a low
incidence, can rapidly develop into refractory cardiogenic
shock, malignant arrhythmia, or even cardiac arrest [7].
Compared to patients with acute non-fulminant myocarditis, AFM patients have a higher mortality rate anda greater need for heart transplantation. Even longterm after treatment, AFM patients still present a poor
left ventricular systolic function [8]. The relationshipbetween clinical manifestations and outcomes in AFM
patients remains controversial [9–11]. Clinical criteria forpredicting AFM prognosis are conflicting, possibly due todifferences in diagnostic tests, methods, and timing [12,13]. Extracorporeal membrane oxygenation (ECMO) has
been proven effective in treating children with AFM, withyielding a better prognosis [14]. Therefore, it is imperative to explore reliable factors to predict the mortality
risk among children with AFM [15–17]. Based on a retrospective analysis, this study aimed to identify clinicalindicators that can predict the prognosis of children with
AFM. The study highlights the importance of vigilant
monitoring and timely interventions to improve survivalin these high-risk patients.
Methods
Data source

We conducted a retrospective observational study using
the inpatient information database of the Children’s Hospital Affiliated with Nanjing Medical University. The
database included the following information of eachchild: hospitalization ID number, times of hospitalizations, sex, date of birth, age, age unit, address of household registration, discharge date, discharge department,
length of hospital stay, primary diagnosis, primary diagnosis name, physician’s primary diagnosis and description, discharge status, etc. Diagnoses were establishedaccording to the International Classification of Diseases,
10th Revision (ICD-10). Due to the retrospective natureof the study and the anonymity of the data, the requirement for informed consent was waived.

Page 2 of 8

Patient selection

We included hospitalized children who were discharged
between March 2013 and March 2023, and had an ICD10-based diagnosis of AFM (I40.80 A). We excluded children who were suspected of having AFM at admission,
but not confirmed by laboratory and imaging examinations, or ultimately diagnosed with other diseases. To
avoid duplication, we manually merged records of AFM
for one child hospitalized multiple times. For all children,
the diagnosis of AFM was primarily based on clinical features and relevant auxiliary examinations. The diagnostic
criteria were as follows: (1) sudden onset, (2) hemodynamic instability caused by cardiogenic shock or arrhythmia, and (3) evidence of myocardial injury indicating
impaired cardiac function, such as changes in creatine
kinase isoenzyme (CK-MB), electrocardiogram (ECG),
and echocardiography.
Drug therapy and ECMOAll enrolled patients received routine glucocorticoid
therapy with a high dose of methylprednisolone, 10 mg/(kg ·d) to 30 mg/ (kg ·d), administered in a continuous
infusion for 3 days, followed by a gradual tapering withina short period [18, 19]. For cases suspected of viral AFM,
routine antiviral medication was administered. Oseltamivir was used for children with influenza virus infection, acyclovir for those with herpes virus infection, andinterferon for children with adenovirus and enterovirus
infections. Routine intravenous immunoglobulin was
administered at a dose of 200 mg/ (kg ·d)-400 mg/ (kg·d) for a duration of 3–5 days [20, 21]. ECMO was managed by a dedicated team under expert consensus on theentire ECMO process [22], including indications, timing,
establishment, management, weaning, and left ventricular decompression when necessary. Cannulation was performed through a cervical incision (via the right internal
jugular vein and carotid artery). In the case of cardiac
arrest, extracorporeal cardiopulmonary resuscitation was
initiated through a midline sternotomy, draining fromthe right atrium and infusing into the ascending aorta. A
centrifugal pump (MaquetRota flow, Germany), a membrane oxygenator (Medos Hillite, Beijing), and a heparincoated circuit were used to perform related procedures.
Variables

For statistical analysis, we extracted the following information from the electronic medical system in the hospital: sex, age, total hospitalization costs, chief complaints,
symptom onset time, presence of prodromal flu-like
symptoms, body mass index (BMI), blood pressure, temperature (T), peripheral oxygen saturation (SpO2), Vasoactive-inotropic score, white blood cell (WBC), c-reactive
protein (CRP), aspartate aminotransferase (AST), lactate
dehydrogenase (LDH), serum creatinine (Scr), sputum

Zhao et al. BMC Pediatrics(2024) 24:553

Page 3 of 8

Table 1 Baseline demographics and hospital admission information
Characteristics
Male
Age (month)
BMI (kg/m2)
Length of hospital stay (day)Medical expenses (RMB)

Survival group (n = 61)
23 (37.70%)
95.41 ± 38.21
17.03 ± 3.68
19.00 (15.00-35.50)
111867.14 (34053.08-273304.51)

t /χ2/Z
0.60
1.16
-0.15
-4.20
-2.99

Death group (n = 18)
5 (27.80%)
79.00 ± 56.17
17.21 ± 4.72
1.00 (1.00-13.50)
15638.33 (8195.63-106284.00)

P-value
0.439
0.257
0.884
< 0.001*
0.003*n, number of patients; BMI, body mass index; *Statistically significant difference between two groups

Table 2 Symptoms and complications
Characteristics
Symptoms
Vomiting
Fever
Abdominal pain
Chest distress
Low moodComplications
Cardiogenic shock
Abnormal electrocardiogram
Pneumonia
Heart failure
Multiple organ failure
Respiratory failure

Survival group (n = 61)

Death group (n = 18)

χ2/Fisher

P-value34 (55.70%)
29 (47.50%)
23 (37.70%)
23 (37.70%)
12 (19.70%)

7 (38.90%)
8 (44.40%)
4 (22.20%)
3 (16.70%)
5 (27.80%)

1.58
0.05
1.48
2.79
0.17

0.209
0.817
0.224
0.095
0.683

24 (39.30%)
23 (37.70%)
35 (57.40%)
16 (26.20%)
8 (13.10%)
3 (4.90%)

7 (38.90%)
7 (38.90%)
10 (55.60%)
3 (16.70%)
9 (50.00%)
7 (38.90%)

0.01
0.01
0.02
0.27
9.12
11.60

0.972
0.928
0.891
0.603
0.003*
0.001*n, number of patients; *Statistically significant difference between two groups

culture, blood culture, viral serological antibody test, viral
antigen test, cardiac troponin I (cTnI), myoglobin (MYO),
CK-MB, B-type natriuretic peptide (BNP), left ventricularejection fraction (LVEF), left ventricular fractional shortening (LVFS), pericardial effusion description, ECG diagnosis, arterial potential of hydrogen (PH), PaO2/ FiO2,
bicarbonate (HCO3−), lactate (Lac), treatment modalities,
renal replacement therapy, complications, and outcome.
Microbiological testing was conducted on the first dayof admission. Vasoactive-inotropic score was defined as
dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 10*milrinone dose (µg/kg/min) + 100*epinephrine
dose (µg/kg/min) + 100*norepinephrine dose (µg/kg/min) + 10,000* vasopressin dose (units/kg/min).
Statistical analysis

Qualitative variables were reported as frequencies andpercentages and analyzed using Chi-square (χ2) test.
Quantitative variables were reported as mean and standard deviation for parametric data, and median andinterquartile range for nonparametric data. Parametricdata were analyzed using the t-test, and nonparametricdata using the Mann-Whitney U test. We have performed
multiple imputations to address all missing data. Utilize
Receiver Operating Characteristic (ROC) curves wereplotted to determine the optimal cutoff values of quantitative variables that exhibit differences in single-factor
analysis. Based on whether they reach this cutoff value,

convert quantitative variables into qualitative variables.
Utilizing univariate logistic regression analyses to identify independent factors associated with in-hospital mortality. All statistical tests were two-sided, and a P-value ofless than 0.05 was considered statistically significant. All
statistical analyses were performed using SPSS software(version 26).

Results
Clinical symptoms and laboratory investigations

In this retrospective study, 79 children with AFM (28males and 51 females; aged 2 months to 13 years, average age 92 ± 43 months) were included. The hospital
stay in the survival group (median = 19, IQR = 15-35.5
days) was significantly longer than that in the deathgroup(median = 1,
IQR = 1-13.5days)(P < 0.001).
Additionally, medical expenses in the survival group(median = 111867.14, IQR = 34053.08 − 273304.51 RMB)
were significantly higher than those in the deceased
group (median = 15638.33, IQR = 8195.63 − 106284.00
RMB). Furthermore, there were no statistically significant differences between the two groups in terms of age,gender, or BMI (Table 1).
The top five symptoms were vomiting, fever, abdominal pain, chest tightness, and lethargy. These five symptoms appeared in more than 50% of the cases (Table 2).
The number of children with various symptoms showedno significant difference between the survival group andZhao et al. BMC Pediatrics(2024) 24:553

Page 4 of 8

the deceased group. The most common complication
throughout the clinical course was cardiogenic shock(23.45%), followed by arrhythmia (10.34%), pneumonia (6.90%), heart failure (6.55%), multiple organ failure(5.86%), and respiratory failure (3.45%). The incidence ofmultiple organ failure and respiratory failure significantly
differed between the deceased group and the surviving
group (Table 2).
ECG abnormalities of cardiac excitation origin werethe most common, followed by abnormal cardiac conduction and myocardial ischemic changes. Among theabnormalities of cardiac excitation origin, that of supraventricular origin was the most common. Conduction
abnormalities were categorized into atrioventricular
block and intraventricular block, both having a similar
incidence. Among atrioventricular blocks, third-degree
block was predominant, while among intraventricular
blocks, right bundle branch block was the most common.
In this group, 12 patients were fitted with pacemakers,
and 11 of these patients survived, showing no significant
arrhythmia on the ECG before discharge. The numberof pediatric patients with abnormal electrocardiograms
showed no significant difference between the deceased
and surviving groups (Table 3).

We conducted an etiological analysis for all patientsand found that 60 children (75.9%) tested positive.
Among these, viruses were the most common pathogen, followed by mycoplasma pneumoniae, with bacterial infection being the least common. The presence ofany pathogenic infection did not have a predictive value
for mortality (Table 4). Based on the findings presented
in Tables 3 and 4, there are statistically significant differences observed between the deceased and surviving
groups across various indicators including LVEF, MYO,
AST, LDH, BNP, PH, HCO3−, Lac, SpO2, and WBC
indicators.
Table 5 presents the treatment protocols administered
to pediatric patients with fulminant myocarditis. Uponcomparing these protocols with patient outcomes, nostatistically significant differences were observed.
Correlation of clinical variables with mortality

We have performed ROC curve analysis for quantifiablevariables showing discrepancies in single-factor analysis, and used them to establish an optimal cutoff point.
The cutoff point aids in converting the quantifiable variables into qualitative ones based on whether they meet
the threshold. All ROC curve plots have been included

Table 3 Examination results
Characteristics
Electrocardiographic
Sinus tachycardia
Ventricular tachycardia
Ventricular premature beat
Degree I atrioventricular block
Degree II type 1 atrioventricular block
Degree II type 2 atrioventricular block
Degree III atrioventricular block
QT interval prolongation
Complete right bundle branch block
Incomplete right bundle branch block
Complete left bundle branch block
Left anterior branch block
Atrial tachycardia
Atrial flutter
Junctional escape
Ventricular escapeST changes
ST-T changes
T wave changes
Myocardial infarction
Supraventricular tachycardia
Low voltage in leads
Echocardiography
Left ventricular ejection fraction (%)
Left ventricular fractional shortening (%)
Pericardial effusion (mm)Survival group (n = 61)

Death group (n = 18)

t/χ2/Z/Fisher

P-value25 (41.00%)
4 (6.60%)
6 (9.80%)
5 (8.20%)
1 (1.60%)
1 (1.60%)
14 (23.00%)
1 (1.60%)
10 (16.40%)
1 (1.60%)
2 (3.30%)
7 (11.50%)
2 (3.30%)0 (0.00)
6 (9.80%)
1 (1.60%)
2 (3.30%)
7 (11.50%)
2 (3.30%)
6 (9.80%)
3 (4.90%)
3 (4.90%)

4 (22.20%)
2 (11.10%)
1 (5.60%)0 (0.00)0 (0.00)0 (0.00)
2 (11.10%)
0 (0.00)
3 (16.70%)
0 (0.00)0 (0.00)
2 (11.10%)
1 (5.60%)
1 (5.60%)0 (0.00)0 (0.00)0 (0.00)0 (0.00)0 (0.00)
1 (5.60%)0 (0.00)0 (0.00)

2.10
0.02
0.01
0.50
0.30
0.30
0.59
0.30
0.01
0.30
0.60
0.01
0.20
3.39
0.77
0.30
0.60
1.07
0.60
0.01
0.91
0.91

0.147
0.893
0.929
0.481
0.587
0.587
0.445
0.587
0.978
0.587
0.439
0.966
0.659
0.066
0.380
0.587
0.439
0.301
0.439
0.929
0.341
0.341

47.76 ± 12.63
25.53 ± 7.20
0.00 (0.00-5.60)

37.41 ± 13.50
22.91 ± 5.72
1.61 (0.00-3.21)

3.01
1.42
-0.19

0.004*
0.161
0.853

n, number of patients; *Statistically significant difference between two groups

Zhao et al. BMC Pediatrics(2024) 24:553

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Table 4 Laboratory test results and others
Characteristics
Myocardial enzyme
Cardiac troponin I (µg/L)
Myoglobin (µg/L)
CK-MB (µg/L)
BNP (ng/L)
Aspartate aminotransferase (U/L)
Lactate dehydrogenase (U/L)
Arterial blood gas analysis
PaO2/ FiO2 (mmHg)
PH
HCO3− (mmol/L)
Serum lactate (mmol/L)
OthersSymptom onset time (day)Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Temperature (℃)
Peripheral oxygen saturation (%)
White blood cell (*109/L)
C-reactive protein (mg/L)
Serum creatinine (µmol/L)
Prodromal flu-like symptoms
Positive pathogen examination

Survival group (n = 61)

Death group (n = 18)

t/χ2/Z/Fisher

P-value

7.30 (3.18–22.40)
88.00 (34.40-225.25)
44.00 (24.20–85.00)
1338.00 (544.50-2371.50)
129.00 (58.00-292.50)
594.00 (427.50-981.87)

9.45 (0.45–23.02)
447.10 (153.43-2657.70)
94.00 (19.05–215.30)
2575.50 (1508.75-4375.25)
299.00 (214.50-682.66)
859.50 (666.00-1059.15)

-0.77
-3.76
-1.34
-2.11
-2.89
-2.32

0.444
< 0.001*
0.180
0.035*
0.004*
0.021*

440.40 (74.55-659.55)
7.39 ± 0.08
19.53 (19.53–20.25)
3.30 (1.60–5.23)

116.90 (69.95-389.08)
7.17 ± 0.28
19.53 (15.93–19.53)
5.23 (3.15–16.90)

-0.51
3.25
-2.69
-2.84

0.612
0.005*
0.007*
0.005*

3.00 (2.00–4.00)
101.88 ± 15.12
64.00 (57.00–70.00)
36.90 (36.90–37.30)
100.00 (97.00-100.00)
8.80 (5.86–11.07)
8.00 (6.40–9.19)
47.00 (35.00–71.00)
41 (67.20%)
50.00 (82.00%)

3.00 (2.00–4.00)
98.25 ± 23.84
63.50 (42.50–73.50)
37.00 (36.35–37.80)
97.00 (84.50–100.00)
10.95 (9.21–16.81)
8.00 (8.00-10.30)
85.95 (34.40-121.75)
14 (77.80%)
10.00 (55.60%)

-0.78
0.58
-0.70
-0.04
-2.75
-2.74
-0.86
-1.74
0.73
1.17

0.438
0.570
0.485
0.966
0.006*
0.006*
0.392
0.082
0.392
0.279

n, number of patients; CK-MB, creatine kinase isoenzyme; BNP, B-type natriuretic peptide; PH, arterial potential hydrogen; HCO3−, bicarbonate; *Statisticallysignificant difference between two groups

Table 5 Treatment and outcomes in all patients
Characteristics
Vasoactive-inotropic score
ECMO
Renal replacement therapy
Pacemaker
Antiviral medication

Survival group (n = 61)
23.34 ± 9.09
22 (36.07%)
10 (16.39%)
11 (18.03%)
27 (44.26%)

Death group (n = 18)
30.06 ± 17.64
5 (27.78%)
4 (22.22%)
1 (5.56%)
7 (38.89%)t/χ2/Z
-1.56
0.42
0.05
0.85
0.16

P-value
0.136
0.515
0.569
0.356
0.686

n, number of patients; ECMO, extracorporeal membrane oxygenationin the supplementary files. The findings indicated that an
AST level of 194.00 U/L, LDH level of 637.50 U/L, MYO
level of 265.75 µg/L, BNP level of 1738.50 ng/L, PH levelof 7.29, HCO3− level of 18.45 mmol/L, Lac level of 12.30
mmol/L, SpO2 level of 97.50%, WBC level of 9.69*109/L,
and LVEF level of 28.25% could serve as thresholds forpredicting mortality. Furthermore, we employed singlefactor logistic regression analyses to identify independent factors associated with inpatient mortality rates. A
higher in-hospital mortality rate was significantly associated with the following factors (Table 6): more severe
myocardial injury (AST > 194.00 U/L [OR 11.94; 95% CI
3.01–46.36; P < 0.001]; LDH > 637.50 U/L [OR 7.20; 95%
CI 1.88–27.51; P = 0.004]; MYO > 265.75 µg/L [OR 8.17;
95% CI 2.55–26.20; P < 0.001]; BNP > 1738.50 ng/L [OR
5.78; 95% CI 1.70–19.70; P = 0.005]); more severe acidosis (PH < 7.29 [OR 17.81; 95% CI 4.50-70.49; P < 0.001];
HCO3− <18.45 mmol/L [OR 7.13; 95% CI 1.91–26.61;

P = 0.003]; Lac > 12.30 mmol/L [OR 18.77; 95% CI 3.44102.58; P < 0.001]); worse left ventricular systolic function(LVEF < 28.25% [OR 11.40; 95% CI 2.88–45.11; P < 0.001).
Additionally, admission SpO2 < 97.50% (OR 4.42; 95% CI
1.46–13.36; P = 0.008) and WBC > 9.69*109/L (OR 5.40;
95% CI 1.59–18.35; P = 0.007) were also significantly associated with an increased in-hospital mortality rate.

Discussion
In our center, we found that AFM was more prevalent infemales than in males among children, which is inconsistent with the results of two previous studies [23, 24], butaligns with the results reported by Shanghai Children’s
Medical Center [25]. Pediatric AFM can be non-specific,
commonly presenting with symptoms such as vomiting,fever, abdominal pain, and chest tightness. Some children also present with syncope, poor appetite, coughing, dizziness, shortness of breath, headache, edema,Zhao et al. BMC Pediatrics(2024) 24:553

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Table 6 Results of univariate logistic regression analysis
Variables
Indicators of myocardial injury
AST > 194.00 U/L
LDH > 637.50 U/L
MYO > 265.75 µg/L
BNP > 1738.50 ng/L
Arterial blood gas analysis
PH < 7.29
HCO3− <18.45 mmol/L
Lac > 12.30 mmol/L
Complication
Multiple organ failure
Respiratory failure
OthersSpO2 < 97.50%
WBC > 9.69*109/L
LVEF < 28.25%

OR

95%CI

P-value

11.94
7.20
8.17
5.78

3.01–46.36
1.88–27.51
2.55–26.20
1.70–19.70< 0.001
0.004< 0.001
0.005

17.81
7.13
18.77

4.50-70.49
1.91–26.61
3.44-102.58< 0.001
0.003
0.001

6.63
12.30

2.02–21.69
2.75–55.04

0.003
0.001

4.42
5.40
11.40

1.46–13.36
1.59–18.35
2.88–45.11

0.008
0.007
< 0.001

OR, odds ratio; CI, confidence interval; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; MYO, myoglobin; BNP, B-type natriuretic peptide; PH, arterial
potential hydrogen; HCO3−, bicarbonate; Lac, lactate; SpO2, peripheral oxygen saturation; WBC, white blood cell; LVEF, left ventricular ejection fraction

pallor, discomfort in the precordial area, coma, drowsiness, sudden respiratory and cardiac arrest, diarrhea, andother symptoms. Additionally, AFM may simultaneously
involve multiple systems, such as the digestive, nervous,and respiratory systems [24]. Therefore, AFM may not
be timely identified promptly in a significant portion ofchildren, thus delaying the implementation of interventions. In our group, the most common symptoms werevomiting, fever, abdominal pain, chest tightness and poor
consciousness. These can easily lead to wrong or missed
diagnosis of AFM, necessitating vigilance on outpatientchildren with such symptoms.
The pathogenesis of AFM may involve direct viral damage or an excessive immune response to viruses [26].
Common viral pathogens include Parvovirus, Coxsackie
virus, and Cytomegalovirus [27, 28]. Our center has
found that viruses are the culprit of AFM, predominantly
Epstein-Barr virus (EB), herpes simplex virus (HSV),
cytomegalovirus (CMV), and rubella virus (RV). Previous
studies have indicated that 90% of patients present prodromal symptoms of viral infection [29], and our centerhas found that 70% of children exhibit flu-like symptoms.
Importantly, current detection methods are limited by a
low sensitivity and a high false-negative rate, as indicatedby a detection rate of just 38% for viral myocarditis [30].
In our study, the detection rate for viruses was 43.3%.
Literature shows that AFM predisposes children to cardiac conduction block [31]. While our study found thatthe most common ECG feature was sinus tachycardia.
Sinus tachycardia is a primary compensatory mechanism,and the most prevalent arrhythmia is atrioventricular
conduction block. For cases with third-degree atrioventricular block or a combination of atrioventricular andintraventricular blocks with a very low ventricular rate,

our center invariably opts for the placement of pacemakers. If circulation remains unstable after pacemakerplacement, ECMO treatment is initiated. A retrospective study of 18 children diagnosed with AFM has shown
encouraging outcomes achieved by ECMO in patientswith arrhythmia, with none requiring a permanent pacemaker or heart transplant [32]. Similarly, no children in
our study required a permanent pacemaker or a hearttransplant, and the survival rate was 87% for children
with arrhythmia treated with ECMO.
Currently, no consensus has reached regarding theindications of ECMO in patients with AFM. To identify
patients who may benefit from ECMO support, scholars
have evaluated clinical features before ECMO and identified those associated with survival. Lower PH, bloodpressure, cardiac arrest and necessity of cardiopulmonary
resuscitation before ECMO are associated with a highrisk of death, suggesting that clinicians should initiate
ECMO earlier to reduce organ damage and improve thesurvival [33]. Previous studies have found that ECMO isefficient in treating AFM patients, with a cure rate ranging from 64.3 to 83.3% [14, 34], which is consistent withthat observed in our center over the past decade.
AFM complications are complex, often resulting indeath due to cardiogenic shock, ventricular arrhythmia,
or multiple organ failure [35]. Similarly, the present study
found that multiple organ failure was predictive of death.
Additionally, respiratory failure is an important predictor
of in-hospital mortality in children with AFM. Managing the complications involving the cardiovascular andrespiratory systems in children with AFM is challenging. Yuji Tominaga et al. have proposed a biventricularassist device that has proven effective in AFM patientswith severe complications of cardiogenic shock andZhao et al. BMC Pediatrics(2024) 24:553

Page 7 of 8

respiratory failure [36]. Left ventricular systolic dysfunction is an important characteristic of AFM, emphasizing the importance of inotropic drug use and circulatory
support [37]. Therefore, providing immediate interventions for complications of AFM is crucial to improve thesurvival rate of children.
Here, we compared clinical data between survivors
and non-survivors, finding that prognostic factors forin-hospital survival in children with AFM included heartdamage, arterial PH, HCO3−, Lac, SpO2, WBC, and LVEF.
Consistent with prior research [38], non-survivors exhibited significantly lower LVEF. Research indicates that thepeaking time of troponin levels is a key predictive factor for myocardial recovery, along with cardiac enzyme,
arrhythmia, and thickness of the left ventricular posteriorwall (LVPWT) at admission [16]. Here, we found thatindicators of heart damage, such as AST, LDH, MYO,
and BNP, were significant determinants of survival. Ohki
et al. have reported that younger age (less than 5 years
old) is a high-risk factor for death [39]. Another metaanalysis has found that the efficacy of ECMO decreases
with age in adults [40]. Here, we found that any age above
or below cut-off point was not significantly associatedwith a high mortality. Additionally, previous studies haveidentified acidosis indicators, including serum bicarbonate level and lactate level, as predictors of in-hospital survival in ECMO patients [15, 41]. Their predictive values
were confirmed in this study, which revealed that PH andpeak lactate values, indicating the occurrence of poor tissue perfusion, were important predictors of in-hospitalmortality in children with AFM. In AFM, renal dysfunction can induce metabolic acidosis and electrolyte disturbances (hyperkalemia and hypocalcemia), which may berelated to ventricular tachycardia or fibrillation.

accurately identify AFM children at an increased risk ofdeath.

Limitations

Author contributions
The authors confirm contribution to the paper as follows: study conception
and design: YZ, MD; data collection: YZ; analysis and interpretation of results:
XY, YX, JQ; draft manuscript preparation: YZ, MD. All authors reviewed theresults and approved the final version of the manuscript.

This study has some limitations. First, being retrospective, it was not possible to autonomously select therequired clinical data, and some data were missing,which may have affected the results. The study was basedon the data from a single center, and the results may not
be generalizable. Second, due to various constraints, we
did not obtain post-discharge follow-up data, making it
impossible to determine the long-term prognosis of inhospital survivors. Third, although ECMO has been used
for AFM for a long time, there is still no consensus onwhen to use ECMO.

Conclusion
Severe myocardial injury, acidosis, hypoxia, inflammatory response, left ventricular systolic dysfunction, multiorgan failure, and respiratory failure are significantly
associated with higher mortality rates. These factors canAbbreviations
ECMO	Extracorporeal membrane oxygenation
AFM	Acute fulminant myocarditis
AST	Aspartate aminotransferase
LDH	Lactate dehydrogenase
MYO	Myoglobin
BNP	Brain natriuretic peptide
PH	Potential hydrogen
HCO3−	Bicarbonate
Lac	Lactate
SpO2	Peripheral oxygen saturationWBC	White blood cell
LVEF	Left ventricular ejection fraction
AM	Acute myocarditis
MRI	Magnetic resonance imaging
T	Temperature
CRP	C-reactive protein
Scr	Serum creatinine
cTnI	Cardiac troponin I
CK-MB	Creatine kinase isoenzyme
LVFS	Left ventricular fractional shortening
ECG	Electrocardiogram
ROC	Receiver operating characteristic
BMI	Body mass index
OR	Odds ratio
CI	Confidence intervalEB	Epstein-Barr virus
HSV	Herpes simplex virus
CMV	Cytomegalovirus
RV	Rubella virus
LVPWT	Thickness of the left ventricular posterior wall

Supplementary Information

The online version contains supplementary material available at https://doi.
org/10.1186/s12887-024-05022-4.
Supplementary Material 1
Acknowledgements
Not applicable.

Funding
The authors received no specific funding for this study.
Data availability
The data used in this manuscript are available upon reasonable request bycontacting the corresponding author via email.

Declarations
Ethics approval and consent to participate
This study had been approved by the hospital Ethics Committee of Children’s
Hospital of Nanjing Medical University to exempt patients’ informed consent.
(Ethical approval number: 202404029-1)
Consent for publication
Not applicable.

Zhao et al. BMC Pediatrics(2024) 24:553

Competing interests
The authors declare no competing interests.
Received: 9 April 2024 / Accepted: 19 August 2024

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