The clinical presentation of acute myocarditis in children may range from asymptomatic to sudden cardiac arrest. This study analyzed the clinical spectrum of acute myocarditis in children to identify factors that could aid primary care physicians to predict the need for extracorporeal membrane oxygenation (ECMO) earlier and consult the pediatric cardiologist promptly. Between October 2011 and September 2016, we retrospectively analyzed 60 patients aged 18 years or younger who were admitted to our pediatric emergency department with a definite diagnosis of acute myocarditis. Data on demographics, presentation, laboratory tests, electrocardiogram and echocardiography findings, treatment modalities, complications, and long-term outcomes were obtained. During the study period, 60 patients (32 male, 28 female; mean age,
Acute myocarditis, which is an inflammatory condition of the myocardium due to infection, autoimmune disease, or toxins, possibly results in life-threatening events and is relatively uncommon in children [
The clinical presentation of acute myocarditis may range from mild and nonspecific symptoms to fulminant cardiovascular collapse [
It is difficult for emergency physicians to diagnose acute myocarditis early and prognosticate correctly in children with this condition based on the clinical presentation at the time of their emergency department (ED) visit. In this study, we aimed to analyze the clinical spectrum of acute myocarditis in patients, who presented at our pediatric ED, and attempted to discover the initial clinical characteristics that could help emergency physicians to predict the outcome of acute myocarditis earlier and consult the pediatric cardiologist in a timely fashion.
In this study, data were retrospectively collected on pediatric patients aged 18 years or younger who presented at our ED with a discharge diagnosis of acute myocarditis based on their medical histories. We reviewed the medical charts of all eligible patients between October 2011 and September 2016. The study was approved by the Institutional Review Board of Changhua Christian Hospital, and the necessity to obtain written consent from the participants was waived because of the retrospective nature of this study.
We identified potentially eligible patients by searching the Changhua Christian Hospital health records database. We selected the charts of all children whose International Classification of Diseases, Ninth or Tenth Revision hospitalization discharge diagnostic code was associated with myocarditis. These children had a final diagnosis of acute myocarditis at the time of discharge from the hospital or died during their hospital visit. The exclusion criteria included patients who (1) were older than 18 years, (2) did not present at the ED before admission, and (3) were not diagnosed with acute myocarditis by a pediatric cardiologist. Definite acute myocarditis is defined based on endomyocardial biopsy results according to the Dallas criteria [
The following information was obtained from the medical records of each patient: age, sex, clinical symptoms, and signs (such as fever, cough, rhinorrhea, chest pain, palpitation, diarrhea, anorexia or vomiting, tachypnea, weakness, and seizure), microbiology, electrocardiogram (ECG) and echocardiography findings, treatment modalities, complications, long-term outcomes, and laboratory tests such as white blood cell (WBC) counts, C-reactive protein (CRP), creatine phosphokinase (CK), creatine phosphokinase-MB (CK-MB), troponin-I (Trop-I), blood urea nitrogen (BUN), creatinine (Cr), alanine (ALT) and aspartate aminotransferase (AST), and serum electrolytes. We compared and analyzed the variables among the different age groups and management groups. In addition, we identified other factors that could predict acute myocarditis in children.
Data of the categorical variables were analyzed with the chi-square test or Fisher’s exact test, when appropriate. Continuous variables were analyzed with the Mann–Whitney
During the 5-year study period, 60 patients (32 male and 28 female; mean age,
Demographics and clinical presentation of the patients with acute myocarditis.
Variables | Total |
Age |
| ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
<0 | 1–6 | 7–12 | 13–18 | ||||||||
( |
( |
( |
( |
||||||||
|
% |
|
% |
|
% |
|
% |
|
% | ||
Gender | |||||||||||
Female | 28 | 46.7 | 2 | 33.3 | 15 | 71.4 | 6 | 60.0 | 5 | 21.7 | 0.005 |
Male | 32 | 53.3 | 4 | 66.7 | 6 | 28.6 | 4 | 40.0 | 18 | 78.3 | |
Fever | |||||||||||
Yes | 41 | 68.3 | 4 | 66.7 | 16 | 76.2 | 4 | 40.0 | 17 | 73.9 | 0.211 |
Cough | |||||||||||
Yes | 34 | 56.7 | 3 | 50.0 | 16 | 76.2 | 3 | 30.0 | 12 | 52.2 | 0.086 |
Rhinorrhea | |||||||||||
Yes | 26 | 43.3 | 3 | 50.0 | 14 | 66.7 | 2 | 20.0 | 7 | 30.4 | 0.036 |
Vomiting | |||||||||||
Yes | 22 | 36.7 | 3 | 50.0 | 7 | 33.3 | 5 | 50.0 | 7 | 30.4 | 0.611 |
Diarrhea | |||||||||||
Yes | 7 | 11.7 | 0 | 0.0 | 1 | 4.8 | 2 | 20.0 | 4 | 17.4 | 0.420 |
Chest pain | |||||||||||
Yes | 32 | 53.3 | 0 | 0.0 | 6 | 28.6 | 6 | 60.0 | 20 | 87.0 | <0.001 |
Tachypnea | |||||||||||
Yes | 20 | 33.3 | 3 | 50.0 | 6 | 28.6 | 4 | 40.0 | 7 | 30.4 | 0.750 |
Palpitation | |||||||||||
Yes | 10 | 16.7 | 0 | 0.0 | 2 | 9.5 | 6 | 60.0 | 2 | 8.7 | 0.003 |
Weakness | |||||||||||
Yes | 19 | 31.7 | 3 | 50.0 | 6 | 28.6 | 3 | 30.0 | 7 | 30.4 | 0.788 |
Headache | |||||||||||
Yes | 5 | 8.3 | 0 | 0.0 | 1 | 4.8 | 0 | 0.0 | 4 | 17.4 | 0.355 |
Seizure | |||||||||||
Yes | 7 | 11.7 | 2 | 33.3 | 2 | 9.5 | 1 | 10.0 | 2 | 8.7 | 0.356 |
Family history of heart disease | |||||||||||
Yes | 1 | 1.7 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1 | 4.3 | 1.000 |
Age, years; ICU = intensive care unit.
In our study, nine (90%) of the 10 patients diagnosed with acute myocarditis in the ECMO group were female, with statistical significance (
Comparison of the clinical presentations of patients with acute myocarditis based on management with ECMO or not.
Variables | No ECMO support ( |
ECMO support ( |
| ||
---|---|---|---|---|---|
|
% |
|
% | ||
Gender | |||||
Female | 19 | 38.0 | 9 | 90.0 | 0.004 |
Male | 31 | 62.0 | 1 | 10.0 | |
Age | |||||
<0 | 5 | 10.0 | 1 | 10.0 | 0.916 |
1–6 | 17 | 34.0 | 4 | 40.0 | |
7–12 | 8 | 16.0 | 2 | 20.0 | |
13–18 | 20 | 40.0 | 3 | 30.0 | |
Fever | |||||
Yes | 33 | 66.0 | 8 | 80.0 | 0.480 |
Cough | |||||
Yes | 28 | 56.0 | 6 | 60.0 | 1.000 |
Rhinorrhea | |||||
Yes | 23 | 46.0 | 3 | 30.0 | 0.491 |
Vomiting | |||||
Yes | 14 | 28.0 | 8 | 80.0 | 0.003 |
Diarrhea | |||||
Yes | 6 | 12.0 | 1 | 10.0 | 1.000 |
Chest pain | |||||
Yes | 29 | 58.0 | 3 | 30.0 | 0.165 |
Tachypnea | |||||
Yes | 16 | 32.0 | 4 | 40.0 | 0.718 |
Palpitation | |||||
Yes | 9 | 18.0 | 1 | 10.0 | 1.000 |
Weakness | |||||
Yes | 11 | 22.0 | 8 | 80.0 | 0.001 |
Headache | |||||
Yes | 4 | 8.0 | 1 | 10.0 | 1.000 |
Seizure | |||||
Yes | 3 | 6.0 | 4 | 40.0 | 0.011 |
ECG | |||||
Normal | 14 | 29.8 | 0 | 0.0 | 0.093 |
Abnormal | 33 | 70.2 | 9 | 100.0 | |
Arrhythmia | |||||
ST | 18 | 36.0 | 5 | 50.0 | <0.001 |
PSVT | 6 | 12.0 | 1 | 10.0 | |
VT | 1 | 2.0 | 2 | 20.0 | |
VF | 0 | 0.0 | 1 | 10.0 | |
Heart block | 0 | 0.0 | 1 | 10.0 | |
LVEF (%) | |||||
<60 | 9 | 18.0 | 9 | 90.0 | <0.001 |
Age, years; ECMO = extracorporeal membrane oxygenation; ECG = electrocardiogram; ST = sinus tachycardia; PSVT = paroxysmal supraventricular tachycardia; VT = ventricular tachycardia; VF = ventricular fibrillation; LVEF = left ventricular ejection fraction.
The differences in laboratory data between the patients with and without ECMO management are listed in Table
Comparison of the laboratory tests of patients with acute myocarditis based on management with ECMO or not.
Variables | No ECMO support | ECMO support |
| ||||
---|---|---|---|---|---|---|---|
|
Mean | SD |
|
Mean | SD | ||
WBC (×109/L) | 50 | 11481.80 | 4610.77 | 10 | 9210.00 | 3117.85 | 0.148 |
CRP (mg/L) | 35 | 2.62 | 3.60 | 10 | 6.26 | 11.42 | 0.246 |
Troponin-I (ng/mL) | 50 | 4.88 | 10.01 | 10 | 25.48 | 30.95 | 0.026 |
CK (U/L) | 34 | 812.87 | 1934.62 | 7 | 1327.14 | 1440.69 | 0.212 |
CK-MB (ng/mL) | 38 | 32.68 | 55.16 | 10 | 122.73 | 163.03 | 0.041 |
Sodium (mmol/L) | 43 | 137.84 | 3.93 | 10 | 139.20 | 10.65 | 0.599 |
Potassium (mmol/L) | 43 | 3.86 | 0.69 | 10 | 4.32 | 1.78 | 0.480 |
Calcium (mg/dL) | 24 | 8.98 | 0.78 | 9 | 7.17 | 1.42 | 0.001 |
AST (U/L) | 18 | 163.78 | 472.55 | 10 | 291.30 | 208.67 | 0.001 |
ALT (U/L) | 27 | 79.70 | 269.90 | 10 | 117.60 | 101.94 | 0.001 |
BUN (mg/dL) | 20 | 13.90 | 15.99 | 10 | 25.80 | 14.57 | 0.001 |
Creatinine (mg/dL) | 33 | 0.62 | 0.33 | 10 | 1.50 | 0.97 | <0.001 |
LVEF (%) | 49 | 66.90 | 9.04 | 10 | 46.10 | 18.61 | <0.001 |
Lactate (mmol/L) | 6 | 3.83 | 4.58 | 5 | 10.02 | 5.42 | 0.242 |
NT-proBNP (pg/mL) | 8 | 5938.88 | 11977.87 | 5 | 8560.60 | 9730.98 | 0.030 |
ECMO = extracorporeal membrane oxygenation; WBC = white blood count; CRP = C-reactive protein; CK = creatine phosphokinase; CK-MB = creatine phosphokinase-MB; AST = aspartate aminotransferase; ALT = alanine aminotransferase; BUN = blood urea nitrogen; LVEF = left ventricular ejection fraction; NT-proBNP = N-terminal prohormone of brain natriuretic peptide.
Analysis of factors influencing ECMO that was performed in patients with acute myocarditis.
Variables | Total | ECMO | Univariate analysis | |||
---|---|---|---|---|---|---|
|
% | Hazard ratio | 95% CI |
| ||
Gender | ||||||
Female | 28 | 9 | 32.1 | 11.805 | 1.495–93.242 | 0.019 |
Male | 32 | 1 | 3.1 | 1.000 | ||
CK-MB | ||||||
Median (IQR) | 16.5 (3.0–52.9) | 56.7 (10.9–161.7) | 1.006 | 1.002–1.011 | 0.004 |
|
LVEF (%) | ||||||
≥60 | 42 | 1 | 2.4 | 1.000 | ||
<60 | 18 | 9 | 50.0 | 27.237 | 3.442–215.532 | 0.002 |
IQR = interquartile range; ECMO = extracorporeal membrane oxygenation; CK-MB = creatine phosphokinase-MB; LVEF = left ventricular ejection fraction.
The results of the ROC analysis showed that the AUROC for the initial LVEF in predicting ECMO treatment was 0.86 (Figure
Receiver operating characteristic curve for initial left ventricular ejection fraction (LVEF) in predicting the need for extracorporeal membrane oxygenation treatment. The area under the curve was 0.86. The best cutoff value for LVEF was 57.5% (sensitivity, 0.9; specificity, 0.84).
Receiver operating characteristic curve for initial serum troponin-I in predicting the need for extracorporeal membrane oxygenation treatment. The area under the curve was 0.72. The best cutoff value for serum troponin-I was 14.21 ng/mL (sensitivity, 0.5; specificity, 0.9).
Acute myocarditis is a relatively uncommon clinical condition in children, but the prevalence in pediatric ED patients is still unknown. During the 5-year study period, about 140,000 children presented to our pediatric ED, 60 of whom were discharged with a final diagnosis of acute myocarditis. In the preschool-age group, acute myocarditis was diagnosed more frequently in girls than in boys, but in the adolescent age group, acute myocarditis was diagnosed more frequently in boys than in girls. However, the trend of sex was not well discussed in previous studies and we cannot make a conclusion about this trend. The clinical diagnosis of acute myocarditis is challenging because the symptoms and signs are often nonspecific, especially in younger children [
Delays in the diagnosis of acute myocarditis may result in increased morbidity and potential mortality. However, the diagnosis is not easy to make if the clinician is not experienced. Once acute myocarditis is suspected, further studies such as laboratory studies, chest radiography, ECG, echocardiography, cardiac magnetic resonance imaging, or endomyocardial biopsy may be clinically important to detect acute myocarditis. Acute myocarditis in children is commonly associated with severe, progressive heart failure, hospitalization, intensive care unit stays, and use of inotropic support [
Most of the literature lists arrhythmia, end-organ failure, and circulation failure as indications for the need for ECMO support [
In our study, we found a few factors that may predict the need for further ECMO support early in patients, including female sex, vomiting, weakness, seizure, arrhythmia, and LVEF < 60% seen on echocardiography. Moreover, elevated cardiac enzyme, abnormal liver, and renal function tests were important factors that helped us detect the need for ECMO support early in these patients. Finally, we performed a Cox proportional hazards regression analysis and found that female sex, elevated blood CK-MB level, and LVEF < 60% were important factors that predicted the need for ECMO management. Our study showed significant differences in initial LVEF detected by echocardiography between the patients with and without ECMO support, and the most appropriate cutoff value of the initial LVEF in predicting ECMO support was 57.5%. In addition, we found significant differences in serum Trop-I levels between the patients with and without ECMO support, and the most appropriate cutoff value of the initial serum Trop-I level in predicting ECMO support was 14.21 ng/mL. Therefore, primary care clinicians should be aware of these clinical factors in children with acute myocarditis to detect the need for ECMO support early. Early, aggressive treatment will be needed when children present with these risk factors.
The present study has some limitations. First, because it is a retrospective, single-center review of medical records, some details of the patients’ history and physical examination may not have been rigorously documented. Second, all patients in our study were considered to have probable myocarditis due to the absence of endomyocardial biopsy results. Another limitation is that we did not study treatment details such as inotropic agent therapy or intravenous immunoglobulin therapy. Finally, the laboratory data and echocardiography may be not checked at the same time, and the definite peak and low data were difficult to record. These limitations may lead to some bias in analyzing the factors that are associated with acute myocarditis and the need for ECMO management.
In conclusion, pediatric acute myocarditis is relatively uncommon, but it could lead to death. Female sex, vomiting, general weakness, seizure, arrhythmia, and LVEF < 60% on echocardiography may indicate that the patient has acute myocarditis and may also increase the risk of needing ECMO support. Most importantly, a cutoff value of the initial serum Trop-I > 14.21 ng/mL and initial LVEF < 57.5% on echocardiography should be considered in children with acute myocarditis to evaluate for the need for ECMO support.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Han-Ping Wu and Mao-Jen Lin contributed equally to this study. Chun-Yu Chen and Mao-Jen Lin analyzed and interpreted the data and drafted the manuscript. Kang-Hsi Wu interpreted the data and Wen-Chieh Yang reviewed the medical records. Han-Ping Wu and Chun-Yu Chen designed and oversaw the study and revised the manuscript. All authors have read and approved the final manuscript for publication.