Analysis of risk factors affecting prognosis of fulminant myocarditis in children: a ten-year single-center study

Abstract

Objective
The present study aimed to analyze the risk factors affecting the prognosis children with fulminant myocarditis.

Methods
The medical records of all patients (n = 40) who were diagnosed with fulminant myocarditis and admitted to the Cardiac Intensive Care Unit (CICU) and Pediatric Intensive Care Unit (PICU) at the Guanzhou Women and Children's Medical Center, Guangzhou Medical University between January 2014 and December 2023 were retrospectively analyzed. Patients were divided into two groups based on their in-hospital prognosis, namely, a survival group (n = 32) and an non-survival group (n = 8). Baseline demographics, laboratory findings, electrocardiograms, echocardiograms, and treatment regimens were compared between the two groups via multifactorial analysis.

Results
The median age of patients in the survival group was 7.8 years (M[5,11.5]), and the median age in the non-survival group was 9.0 years (M[6,11.5]). Compared with those in the survival group, patients in the non survival group had significantly higher levels of extracorporeal cardiopulmonary resuscitation (ECPR) use, ventricular tachycardia/ventricular fibrillation (VT/VF), peak creatine kinase isoenzyme (CK-MB), peak N-terminal B-type natriuretic peptide precursor (NT-proBNP), serum creatinine (Scr) on admission, peak serum Scr, peak aspartate aminotransferase (AST), peak alanine aminotransferase (ALT), peak cardiac troponin I (cTnI), lactate on admission, peak lactate, and extracorporeal membrane oxygenation (ECMO) use (all p < 0.05). Binary logistic regression analysis revealed that the peak lactate level was an independent risk factor for mortality in patients with fulminant myocarditis (OR = 0.661, 95% CI 0.488–0.897; p = 0.008).

Conclusions
The present study demonstrated that the peak lactate level is an independent risk factor for mortality in patients with fulminant myocarditis.

Full text

Yuanetal. BMC Pediatrics (2025) 25:209
https://doi.org/10.1186/s12887-025-05530-x
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BMC Pediatrics
Analysis ofrisk factors aecting prognosis
offulminant myocarditis inchildren: aten-year
single-center study
Jia Yuan1, Lijuan Li1, Fengxiang Li1, Jianbin Li1, Li Ma2, Ming Li1 and Na Zhou1*
Abstract
Objective The present study aimed to analyze the risk factors affecting the prognosis children with fulminant
myocarditis.
Methods The medical records of all patients (n = 40) who were diagnosed with fulminant myocarditis and admitted
to the Cardiac Intensive Care Unit (CICU) and Pediatric Intensive Care Unit (PICU) at the Guanzhou Women and Chil-
dren’s Medical Center, Guangzhou Medical University between January 2014 and December 2023 were retrospec-
tively analyzed. Patients were divided into two groups based on their in-hospital prognosis, namely, a survival group
(n = 32) and an non-survival group (n = 8). Baseline demographics, laboratory findings, electrocardiograms, echocar-
diograms, and treatment regimens were compared between the two groups via multifactorial analysis.
Results The median age of patients in the survival group was 7.8 years (M[5,11.5]), and the median age in the non-
survival group was 9.0 years (M[6,11.5]). Compared with those in the survival group, patients in the non survival group
had significantly higher levels of extracorporeal cardiopulmonary resuscitation (ECPR) use, ventricular tachycardia/
ventricular fibrillation (VT/VF), peak creatine kinase isoenzyme (CK-MB), peak N-terminal B-type natriuretic peptide
precursor (NT-proBNP), serum creatinine (Scr) on admission, peak serum Scr, peak aspartate aminotransferase (AST),
peak alanine aminotransferase (ALT), peak cardiac troponin I (cTnI), lactate on admission, peak lactate, and extracor-
poreal membrane oxygenation (ECMO) use (all p < 0.05). Binary logistic regression analysis revealed that the peak
lactate level was an independent risk factor for mortality in patients with fulminant myocarditis (OR = 0.661, 95% CI
0.488–0.897; p = 0.008).
Conclusions The present study demonstrated that the peak lactate level is an independent risk factor for mortality
in patients with fulminant myocarditis.
Keywords Fulminant myocarditis, Pediatrics, Peak lactate
Introduction
Acute myocarditis typically presents as an inflamma-
tory heart disease arising from a combination of genetic,
infectious, and autoimmune factors. e clinical manifes-
tations vary considerably, with generally favorable prog-
noses in mild cases. However, fulminant myocarditis, a
particularly severe form of acute myocarditis, can lead to
cardiogenic shock, ventricular arrhythmias, heart block,
multiple organ failure, and even death [1]. Fulminant
myocarditis is estimated to account for approximately
*Correspondence:
Na Zhou
2023761102@gzhmu.edu.cn
1 Department of CICU, Guangzhou Women and Children’s Medical Center,
Guangzhou Medical University, Guangzhou, Guangdong 510623, China
2 Department of Cardiac Surgery, Guangzhou Women and Children’s
Medical Center, Guangzhou Medical University, Guangzhou, Guangdong
510623, China
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Page 2 of 8
Yuanetal. BMC Pediatrics (2025) 25:209
10% to 38% of all acute myocarditis cases [2]. Notably,
fulminant myocarditis may be responsible for approxi-
mately 10% to 20% of sudden and unexplained deaths in
the pediatric population [3].
e present retrospective analysis investigated the
clinical data of 40 pediatric patients diagnosed with ful-
minant myocarditis to identify risk factors affecting the
prognosis of fulminant myocarditis in children. e
present findings will inform clinical diagnosis and treat-
ment strategies for patients at high risk of fulminant
myocarditis.
Materials andmethods
Research subjects
e present retrospective study employed a grouped
case design to analyze patients with fulminant myocardi-
tis admitted to the Cardiac Intensive Care Unit (CICU)
and Pediatric Intensive Care Unit (PICU) of the Guang-
zhou Women and Children’s Medical Center, Guangzhou
Medical University between January 2014 and Decem-
ber 2023. e inclusion criteria were as follows: (1) age
less than 18years and (2) a diagnosis of fulminant myo-
carditis. e main clinical diagnoses of the cardiovascu-
lar myocarditis group (version 2018) [4] were as follows:
(1) cardiac insufficiency or cardiac shock; (2) cardiac
enlargement; (3) serum cardiac troponin T (cTnT),
serum cardiac troponin I (cTnI) or serum creatine kinase
isozyme (CK-MB) with dynamic changes; (4) significant
ECG changes (ECG or 24h Holter); or (5) typical myo-
carditis in cardiac magnetic resonance imaging. e sec-
ondary clinical diagnoses were as follows: (1) a history of
prodromal infection, such as a history of upper respira-
tory tract or gastrointestinal virus infection 1 to 3weeks
before onset; (2) chest tightness, chest pain, palpitations,
fatigue, dizziness, pale, or abdominal pain; (3) serum lac-
tate dehydrogenase (LDH), α-hydroxybutyrate dehydro-
genase (α-HBDH) or aspartate transaminotransferase
(AST); (4) mild abnormal electrocardiogram; or (5) posi-
tive anti-myocardial antibody. Myocarditis was clinically
diagnosed in accordance with 3 clinical diagnostic bases
for the main diagnosis of myocarditis or 2 main clini-
cal diagnostic bases plus 3 secondary clinical diagnostic
bases in addition to other diseases. Currently, there are
no clear diagnostic criteria for fulminant myocarditis in
children; these criteria were based on the Chinese Medi-
cal Association Cardiovascular Society guidelines for
adult fulminant myocarditis diagnosis and treatment,
created with Chinese expert consensus [5]. When acute
myocarditis suddenly and rapidly progresses, severe
heart failure, hypotension or cardiogenic shock soon
appear, and the use of positive inotropic drugs, vascular
active drugs or mechanical circulation adjuvant therapy
can lead to a diagnosis of fulminant myocarditis. Patients
were categorized into survival and non-survival groups
based on their in-hospital prognosis. Ethical approval for
the present study was granted by the Ethics Committee
of Guangzhou Women and Children’s Medical Center,
Guangzhou Medical University (Approval No. 257A01).
Informed consent was obtained from the parents or legal
guardians of participants under the age of 16.
Clinical data collection
e following clinical data were collected: (1) demo-
graphic information; (2) hemodynamic parameters and
cardiac rhythm; (3) laboratory findings, including peak
levels of aspartate aminotransferase (AST), alanine ami-
notransferase (ALT), creatine kinase-MB isoenzyme (CK-
MB), cardiac troponin I (cTnI), serum creatinine (Scr),
N-terminal pro-B-type natriuretic peptide (NT-proBNP),
and lactate measured on admission; and (4) treatment
data, including immunomodulatory therapy and vaso-
active medications. A vasoactive-inotropic score (VIS)
was calculated using a previously published formula [6]
to quantify the degree of vasopressor support needed. A
VIS exceeding 20 points indicates severe cardiovascular
dysfunction, often necessitating interventions, such as
mechanical ventilation, temporary or permanent pace-
maker implantation, extracorporeal membrane oxygena-
tion (ECMO) for circulatory support, and continuous
renal replacement therapy (CRRT) [6].
3. Statistical methods. Data analysis was performed
using SPSS 29.0 statistical software. Categorical variables
are expressed as frequencies and percentages, and the
chi-square test was used to assess statistically significant
differences between groups. When the assumptions for
the chi-square test were not met, Fisher’s exact probabil-
ity test was employed. Nonnormally distributed continu-
ous variables are presented as medians with interquartile
ranges (M [Q1, Q3]), and the Mann‒Whitney U test was
used for comparisons between groups. Binary logistic
regression analysis was used to identify independent risk
factors associated with mortality in patients with fulmi-
nant myocarditis. A p value of less than 0.05 was consid-
ered statistically significant.
Results
Basic clinical data (Table1)
Forty patients diagnosed with fulminant myocarditis
were enrolled in the present study. Patients were cat-
egorized into the following two groups on the basis of
their in-hospital prognosis: a survival group (n = 32)
and an non-survival group (n = 8). e median age of
the survival group was 7.8 years (M[5,11.5]), whereas
the median age of the non-survival group was 9.0years
(M[6,11.5]). Fever was present upon admission in 29
patients. Fever and duration of fever at admission were
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Yuanetal. BMC Pediatrics (2025) 25:209
not significantly different between the two groups. e
clinical manifestations at admission varied and included
respiratory (cough and shortness of breath), digestive
(nausea, vomiting, and abdominal pain), and circula-
tory (chest tightness and chest pain) symptoms. ECPR
was performed prior to ECMO support in 5 patients in
the survival group and 4 patients in the non-survival
group; this difference in ECPR utilization between the
groups was statistically significant (p < 0.05).
Laboratory data
Table2 summarizes the results of initial laboratory tests
conducted upon admission, alongside the peak levels
measured for the same variables. Compared with the
survival group, the non-survival group presented signifi-
cantly greater peak levels of CK-MB, cTnI, NT-proBNP,
Scr (both at admission and peak), AST, and lactate (both
at admission and peak) (p < 0.05).
Etiological data
All patients underwent etiological testing, but etiological
data were available for only 9 patients (30%) as follows:
influenza B virus for 3 patients, Mycoplasma pneumoniae
for 3 patients, influenza A virus for 1 patient, enterovirus
for 1 patient, and adenovirus for 1 patient.
Electrocardiograms andechocardiograms (Table3)
Twelve-lead electrocardiogram (ECG) examinations were
performed on all patients, with most patients undergoing
multiple routine ECGs. Electrocardiographic abnormali-
ties were identified in 36 patients (90%), with 29 patients
in the survival group and 7 patients in the non-survival
group exhibiting these abnormalities. Notably, the preva-
lence of ventricular tachycardia/ventricular fibrillation
(VT/VF) was significantly greater in the non-survival
group than in the survival group (p < 0.05).
Echocardiographic evaluation revealed that all patients
exhibited cardiac enlargement. However, no statisti-
cally significant differences were observed between the
survival and non-survival groups regarding pericardial
Table 1 Comparison of basic clinical data of patients with
fulminant myocarditis
ECPR Extracorporeal cardiopulmonary resuscitation
survival (n = 32) non-survival (n = 8) p
Sex (female) 14 (43.8%) 3 (37.5%) 1.0
Age (years) 7.8 (5,11.5) 9 (6,11.5) 0.574
Fever 24 (75%) 5 (62.5%) 0.66
Fever days 2(2,3) 2(1.5,3.5) 0.674
Respiratory symptoms 8 (25%) 1 (12.5%) 0.655
Gastrointestinal
symptoms 19 (59.4%) 6 (75%) 0.686
Circulatory symptoms 5 (15.6%) 1 (12.5%) 1.0
Duration of symptoms
before admission
(days)
2(2, 4) 2(2,4.75) 0.792
ECPR 7 (21.9%) 5 (62.5%) 0.039
Table 2 Comparison of biochemical test indicators with fulminant myocarditis
CK-MB Creatine kinase isoenzyme, cTnI Cardiac troponin I, NT-proBNP N-terminal B-type natriuretic peptide precursor, Scr Serum creatinine, AST Aspartate
aminotransferase, ALT Alanine aminotransferase
survival (n = 32) non-survival (n = 8) p
On admission
CK-MB (U/L) 101 (49.3, 109.5) 226.8 (57, 290.3) 0.06
cTnI (ug/L) 1.1 (0.5, 1.3) 2.1 (0.9, 3.4) 0.052
Scr (umol/L) 70.2 (37, 70) 120.1 (56.8, 182.8) 0.016
AST(U/L) 287.3 (89, 424.5) 941.6 (102, 2006.8) 0.12
ALT(U/L) 150.7 (25, 210) 711.8 (59.5, 1330.8) 0.31
Lactate (mmol/L) 4.8 (2.5, 6.4) 7 (4.1, 9.1) 0.048
NT-proBNP (pg/mL) 24,553.2(4282.5, 27328.8) 18,375.3 (5156.5, 34480.3) 0.477
Peak levels
CK-MB (U/L) 178 (50, 160.3) 1004.8 (264.8, 902.8) < 0.001
cTnI (ug/L 1.8 (0.7, 2.3) 4.4 (2.0, 5.5) 0.006
Scr (umol/L) 93.8 (49, 86.5) 311.6 (122.8, 260.8) < 0.001
AST(U/L) 914.4 (116, 1122.5) 4124 (1144, 4526.5) 0.003
ALT(U/L) 764.4 (47.5, 909.8) 2448.8 (347, 3764.3) 0.015
Lactate (mmol/L) 7.8 (4.8, 11) 13.6 (11.3, 15) 0.002
NT-proBNP (pg/mL) 19,856.1(9297.5, 34378.3) 30,211 (23460.5, 35000) 0.014
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Yuanetal. BMC Pediatrics (2025) 25:209
effusion, ventricular wall motion abnormalities, or mitral
and tricuspid regurgitation (p > 0.05).
Treatment offulminant myocarditis (Table4)
All patients necessitated mechanical ventilation follow-
ing admission. Ten patients (25%) required temporary
pacemaker implantation due to high-grade atrioven-
tricular block. Unfortunately, one patient in this group
with a temporary pacemaker and ECMO support did
not survive. e remaining two patients with temporary
pacemakers did not experience a return to sinus rhythm
within two weeks, necessitating permanent pacemaker
placement. Following their diagnosis of fulminant myo-
carditis upon admission, 39 patients received treat-
ment with intravenous immunoglobulin (IVIG) and
corticosteroids.
ECMO was used for circulatory support in 19 patients
(47.5%), with a significant difference in utilization
between the survival and non-survival groups (p < 0.05).
Notably, six of these patients also received CRRT.
ECMO situation andoutcome (Table5)
Nineteen patients initiated ECMO, and there were no
statistically significant differences between the two
groups in terms of the time from shock to ECMO initia-
tion or the ECMO maintenance time.
ECMO was used in all 8 patients who died; the sur-
vival rate of patients with fulminant myocarditis treated
with ECMO was only 42.1% (4 patients died due to car-
diogenic shock, 3 patients died due to multiple organ
dysfunction syndrome, and 1 patient died due to septic
shock).
Analysis ofindependent risk factors fordeath inpatients
withfulminant myocarditis (Table6)
Variables identified in the univariate analysis to have sta-
tistically significant differences between the survival and
non-survival groups with fulminant myocarditis were
included in the subsequent multivariable logistic regres-
sion analysis. ese variables included ECPR use, VT/VF,
peak CK-MB levels, peak NT-proBNP levels, Scr levels
at admission, peak Scr levels, peak AST levels, peak ALT
levels, peak cTnI levels, lactate levels at admission, peak
lactate levels, and ECMO use. e peak lactate level was
an independent risk factor for mortality in patients with
fulminant myocarditis.
Discussion
Fulminant myocarditis represents a severe form of viral
myocarditis characterized by an abrupt onset and rapid
clinical deterioration. Patients swiftly develop hemo-
dynamic compromise (including pump failure and
circulatory insufficiency) alongside malignant arrhyth-
mias, resulting in an exceptionally high early mortal-
ity rate [7, 8]. Endomyocardial biopsy remains the gold
standard for definitive diagnosis. However, owing to its
Table 3 Comparison of electrocardiogram and echocardiogram
in fulminant myocarditis
A-V block Atrioventricular block, VT/VF Ventricular tachycardia/ventricular
brillation, SVT Supraventricular tachycardia, LVEF Left ventricular ejection
fraction, LVFS Left ventricular fractional shortening
survival (n = 32) non-survival (n = 8) p
A-V block 13 (40.6%) 1 (12.5%) 0.222
VT/VF 3 (9.4%) 4 (50%) 0.02
SVT 13 (40.6%) 2 (25%) 0.686
LVEF 38.7 (26.8, 47) 33 (23.3, 46.8) 0.426
LVFS 18.4 (12.5, 23) 15.8 (11, 23.5) 0.487
Pericardial effusion 10 (35%) 4 (50%) 0.416
Ventricular wall
motion abnormalities 8 (25%) 2 (25%) 1.0
Mitral regurgitation 16 (50%) 4 (50%) 1.0
tricuspid regurgitation 16 (50%) 4 (50%) 1.0
Table 4 Comparison of treatment in fulminant myocarditis
IVIG Intravenous immunoglobulin, VIS Vasoactive-inotropic score, CRRT
Continuous renal replacement therapy, ECMO Extracorporeal membrane
oxygenation
survival (n = 32) non-survival (n = 8) p
IVIG 32 (100%) 7 (87.5%) 0.2
Corticosteroids 32 (100%) 7 (87.5%) 0.2
VIS (scores) 18.8 (12.3,23.2) 23.3 (15.7,32) 0.37
Temporary pace-
maker 9 (28.1%) 1 (12.5%) 0.653
Permanent pacemak-
ers 2 (6.3%) 0 (0) 1.0
CRRT 3 (13.6%) 3 (50%) 0.091
Ventilator 32 (100%) 8 (100%) -
ECMO 11 (34.4%) 8 (100%) < 0.001
Table 5 ECMO situation
survival (n = 11) non-survival (n = 8) P
Shock to ECMO times(h) 10 (6.0,18) 8.5(6.5,30.25) 0.74
ECMO duration (days) 9.5(6.3, 13) 7.6(1.4, 24.3) 0.772
Table 6 Logistic regression analysis of mortality risk factors in
fulminant myocarditis
Risk factor B OR 95%CI P
Lactate peak −0.414 0.661 0.488, 0.897 0.008
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Yuanetal. BMC Pediatrics (2025) 25:209
inherent invasiveness, the diagnosis of fulminant myo-
carditis often relies on clinical features, biochemical
markers, electrocardiographic findings, and echocar-
diographic characteristics.
e present study revealed a diverse range of clinical
presentations upon admission, with predominant ext-
racardiac manifestations (gastrointestinal and respira-
tory) compared with circulatory symptoms. is aligns
with previous international studies reporting that ful-
minant myocarditis often manifests primarily through
extracardiac symptoms [2]. Owing to the nonspecific-
ity and symptoms of myocarditis, approximately 71%
of children are misdiagnosed with sepsis or pneumonia
[9, 10]. ese initial symptoms may delay the diagno-
sis of myocarditis and lead to delayed hospitalization,
thereby increasing mortality. e present analysis
compared duration of symptoms before admission
of the two groups of patients, but the difference was
not statistically significant, owing to the small sample
size. However, a high index of suspicion for fulminant
myocarditis should be carefully maintained in patients
with a history of infection after alternative explana-
tions for these extracardiac manifestations are ruled
out. ECPR, also known as venoarterial ECMO, has
demonstrated promising outcomes in fulminant myo-
carditis treatment. International studies have reported
a wider range of survival rates (33%−79%) for patients
with fulminant myocarditis who underwent ECPR and
were subsequently discharged [11–13]. However, the
observed survival rate of 21.9% following ECPR in the
present study is less than that reported internationally.
is statistically significant difference (p < 0.05) may
be attributed to the relatively recent development and
potentially limited experience with ECMO technology
in China.
e pathogenesis of fulminant myocarditis may be
related to direct damage from the virus or excessive
immunity to the virus [14] which is commonly observed
with Coxsackievirus. During the coronavirus disease
2019 (COVID-19) pandemic, multiple studies have
shown that COVID-19 is associated with a high inci-
dence of myocarditis. Amrei R etal. [15] reported that
SARS-CoV-2 causes vascular damage either directly or
indirectly by stimulating the immune response, which
leads to the overproduction of cytokines (cytokine
storms), ultimately causing blood vessel damage. Vascu-
lar damage caused by SARS-CoV-2, alone or in combina-
tion with preexisting endothelial dysfunction, can lead to
multisystem organ failure and death. In the present study,
all patients underwent etiological testing, but etiological
data were detected in only 9 patients (30%) as follows:
influenza B virus for 3 patients, mycoplasma pneumoniae
for 3 patients, influenza A virus for 1 patient, enterovirus
for 1 patient, and adenovirus for 1 patient. None of the
patients contracted SARS-CoV-2.
Myocardial enzymes are proteins located within
heart muscle cells. When these cells are damaged or die
(necrose or rupture), myocardial enzymes are released
into the bloodstream. e levels of these enzymes indi-
rectly reflect the extent of myocardial injury. CK-MB is a
dimeric enzyme found predominantly in myocardial tis-
sue, and the serum concentration of CK-MB significantly
increases 3–8h after myocardial injury. e severity of
the injury often correlates with the level of CK-MB, with
values potentially exceeding those of healthy individuals
by several-fold. Cardiac troponin I is a myocardial cell-
specific protein that binds calmodulin, and it exists in
both free and complex forms within human cardiomyo-
cytes. Myocardial injury triggers the release of cardiac
troponin I into the bloodstream, leading to significantly
higher serum levels than normal. While cTnI is highly
sensitive, its ability to return to normal levels can last
7–10 days. In the present study, the peak CK-MB and
cTnI levels in the survival group differed significantly
from those in the non-survival group. is finding sug-
gested that a continuous increase in myocardial injury
markers indicates disease deterioration, highlighting the
importance of early intervention [16]. Furthermore, ele-
vated AST and ALT levels were observed in most patients
in the present study. is elevation may be associated
with shock, congestive heart failure, or the viral triggers
responsible for myocarditis itself. A pediatric study sup-
porting this association has reported elevated AST levels
in children with myocarditis [9, 17].
NT-proBNP has gained widespread use in clinical
practice in recent years because of its high degree of car-
diac specificity and sensitivity; this biomarker reflects left
ventricular end-diastolic pressure, a measure of filling
pressure within the main pumping chamber of the heart.
When the ventricular volume or pressure load increases,
leading to elevated wall tension, the synthesis and secre-
tion of NT-proBNP increases accordingly. Consequently,
NT-proBNP serves as an accurate indicator of changes
in left ventricular function and is a key prognostic factor
for assessing disease severity and patient outcomes [16].
Notably, the present study revealed a significant differ-
ence (p < 0.05) in peak NT-proBNP levels between the
survival and non-survival groups.
End-organ perfusion, a marker of tissue oxygenation,
reflects the severity of hypoperfusion and aids in assess-
ing circulatory shock. e kidneys, which are highly
sensitive to ischemia and reperfusion injury, serve as
indicators of circulatory compromise. Scr is a well-estab-
lished clinical measure of renal function. In fulminant
myocarditis, reduced cardiac output, the use of vasoac-
tive medications, infection, hemolysis, and decreased
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Yuanetal. BMC Pediatrics (2025) 25:209
blood volume can all contribute to renal dysfunction.
Studies have demonstrated an association between Scr
changes and mortality in adult fulminant myocardi-
tis patients [18]. e present study revealed that some
patients received ECPR prior to ECMO, suggesting rapid
disease progression in the early stages, potentially lead-
ing to multiorgan dysfunction, particularly affecting the
kidneys. Hypotension and systemic hypoperfusion before
ECMO support in fulminant myocarditis patients can
cause acute renal ischemia‒reperfusion injury. Addition-
ally, virus-mediated immune responses following initial
viral infection can also contribute to acute kidney injury.
Consequently, changes in Scr may reflect both the sever-
ity of hypoperfusion and the intensity of the immune
response, both of which can be confounding factors asso-
ciated with poor prognosis [18].
Lactate, a byproduct of anaerobic glycolysis, plays a
crucial role in metabolism and exercise. Lactate lev-
els not only reflect abnormalities in the respiratory and
circulatory systems but also reflect the severity of vari-
ous conditions [19]. In critical care medicine, lactate has
emerged as a risk factor for predicting patient mortal-
ity and a critical prognostic indicator [20, 21]. Elevated
lactate levels exacerbate heart failure and cardiogenic
shock, ultimately contributing to increased patient mor-
tality [22]. e literature on the prediction of the progno-
sis of patients with fulminant myocarditis is limited, and
the conclusions are controversial. Merkle-Storms et al.
[23] reported that pre-ECMO lactate levels in pediatric
patients are similar between survivors and non-survivors,
but Laimod et al. [24] reported that in adult patients
receiving ECMO, lactate levels are similar in patients
with fulminant myocarditis. e pre-ECMO lactate level
is significantly lower in survivors than in non-survivors.
A previous meta-analysis study [25] has reported no sta-
tistically significant difference in lactate levels between
survivors and non-survivors in adult and child popula-
tions, but the pooled analysis revealed that lactate levels
in survivors are significantly lower than those in non-sur-
vivors. e present study revealed a continuous increase
in lactate levels within the nonsurvival group, with
admission and peak levels exceeding those of the survival
group (p < 0.05). Furthermore, logistic regression analysis
identified the peak lactate level as an independent risk
factor for mortality in patients with fulminant myocardi-
tis. is finding is partially similar with previous findings
suggesting that peak lactate signifies severe myocardial
damage and adversely affects patient outcomes [26, 27].
ECG serves as a vital adjunct test in the diagnosis of
fulminant myocarditis. In the present study, approxi-
mately 90% of patients presented with abnormal ECG
findings. While previous studies have suggested that
a high degree of atrioventricular block on initial ECG
may correlate with improved survival [2], Miyake etal.
reported a poorer prognosis in patients with arrhythmias
[28]. Notably, the present study revealed a statistically
significant difference (p < 0.05) in the incidence of VT/VF
between the nonsurvival and survival groups, suggesting
a potential association with worse outcomes in patients
experiencing these arrhythmias. Echocardiography plays
a valuable role in the early detection of cardiac enlarge-
ment, aiding in the diagnosis of fulminant myocarditis.
is imaging modality allows for the evaluation of car-
diac function and the exclusion of alternative etiologies,
such as heart failure secondary to rheumatic or congeni-
tal heart disease, as well as valvular dysfunction. Interna-
tional studies have reported a poor long-term prognosis
for patients with a reduced left ventricular ejection frac-
tion (LVEF) [22, 29]. While the present data revealed a
lower LVEF and left ventricular fractional shortening
(LVFS) in the nonsurvival group than in the survival
group, these differences did not reach statistical signifi-
cance, which may be attributed to the relatively small
sample size of the present study.
Both domestic and international studies have demon-
strated the efficacy of mechanical circulatory support
therapy in reducing mortality rates for patients with
fulminant myocarditis [30]. ECMO remains the most
effective treatment option for fulminant myocarditis
in children due to limitations in the pediatric medical
device market and a paucity of relevant clinical research.
Survival rates for patients with fulminant myocardi-
tis treated with ECMO range from 64 to 83% [31–33].
e present study revealed a slightly lower survival rate
(57.9%) following ECMO treatment for fulminant myo-
carditis than previously reported. Early identification of
prognostic risk factors associated with fulminant myo-
carditis in patients receiving ECMO support and subse-
quent interventions is critical for improving outcomes in
these at-risk patients. Currently, there is no consensus on
the ideal time to start ECMO. Various medical centers
have different time strategies, which are guided mainly by
the patient’s hemodynamic status and individual institu-
tional criteria to implement ECMO. A multicenter study
by Lee etal. [34] divided patients into early (< 0.9h), mid-
dle (1–2.2h), and late (> 2.2h) groups on the basis of the
time from the onset of shock to ECMO. e results high-
lighted that patients in the early group (0.6h) have signif-
icantly better outcomes than those in the middle (1.4h)
and late (5.1h) groups. Early initiation of ECMO does not
increase the rate of complications, such as hemorrhagic
or ischemic events, but delayed initiation of ECMO sup-
port (admission > 24h) is associated with poor prognosis,
with a mortality of up to 75% reported in patients with
delayed initiation of ECMO [2]. In our study, a total of
19 patients with fulminant myocarditis required ECMO
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Page 7 of 8
Yuanetal. BMC Pediatrics (2025) 25:209
support; the shock to ECMO durations were 10 (6, 18)
and 8.5 (6.5, 30.25) in the survival and non-survival
groups, respectively, but the differences were not statisti-
cally significant. It has been reported that the duration of
ECMO in the non-surviving patients is longer than that
in surviving patients, which may be due to these patients
having more severe disease and the myocardium being
not fully recovered, suggesting that the ECMO time
needs to be extended to ensure adequate tissue perfusion
[35]. In our study, there was no significant difference in
the duration of ECMO between the two groups, but the
duration of ECMO in the non-survival group was shorter
than that in the survival group, which may be attributed
to the patients being critically ill and parents stopping the
treatment.
Early and adequate administration of corticosteroids
effectively suppresses the immune response and poten-
tially limits further myocardial cell damage [36]. While
gamma globulin is currently used as an immunoregu-
latory support therapy for fulminant myocarditis in
children, existing evidence suggests that neither corti-
costeroids nor IVIG have a significant effect on mortality
rates [37, 38]. In the present study, one patient presented
with rapid disease progression upon admission. Despite
the implementation of ECMO circulatory support follow-
ing ECPR, the patient developed multiple organ failure,
precluding the use of corticosteroids therapy or IVIG.
Study limitations
Owing to the single-center, retrospective design and
limited sample size, the present study was susceptible to
missing data and selection bias, potentially limiting the
generalizability of the findings. Additionally, the absence
of follow-up data precluded an evaluation of long-term
outcomes in surviving patients after hospital discharge.
Conclusions
e present study identified peak lactate level as an inde-
pendent risk factor affecting the prognosis of fulminant
myocarditis in children. is finding underscores the
importance of early recognition, prompt diagnosis, and
timely intervention to improve overall patient outcomes.
Abbreviations
CICU Cardiac Intensive Care Unit
PICU Pediatric Intensive Care Unit
ECPR Extracorporeal cardiopulmonary resuscitation
VT Ventricular tachycardia
VF Ventricular fibrillation
CK-MB Creatine kinase isoenzyme
NT-proBNP N-terminal B-type natriuretic peptide precursor
Scr Serum creatinine
AST Aspartate aminotransferase
ALT Alanine aminotransferase
cTnI Cardiac troponin I
ECMO Extracorporeal membrane oxygenation
CRRT Continuous renal replacement therapy
A-V block Atrioventricular block
SVT Supraventricular tachycardia;
LVEF Left ventricular ejection fraction;
LVFS Left ventricular fractional shortening
IVIG Intravenous immunoglobulin
VIS Vasoactive-inotropic score
COVID-19 Coronavirus disease 2019
cTnT Cardiac troponin T
LDH Lactate dehydrogenase
α-HBDH α-Hydroxybutyrate dehydrogenase
Acknowledgements
We would like to thank the Guangzhou Women and Children’s Medical Center,
Guangzhou Medcial University for providing support and guidance. The above
opinions are those of the authors alone.
Author’s contributions
J Y was responsible for the writing of the article and analyzed the data. L-J L,
F-X Land M L performed the experiments and collected data. L M was respon-
sible for the placement of ECMO. N Z designed the research study. All authors
have read and approved the final version of this manuscript.
Funding
Guangzhou Major clinical technology project(2023C-ZD10). Guangzhou Sci-
ence and Technology Bureau Project(2024A03J1165). The Basic and Applied
Basic Research Project of Guangzhou Municiple Science and Technology
Bureau (2025A03J4265).
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethics approval and consent to participate
This study was performed with the ethics approval from the Institutional
Committee of Guangzhou Women and Children’s Medical Center, Guangzhou
Medcial University. The study obtained informed consent from parents or legal
guardians of participants under the age of 16.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Received: 9 August 2024 Accepted: 21 February 2025
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