Viral myocarditis refers to inflammation of the myocardial interstitium caused by viral infection, accompanied by inflammatory cell infiltration and subsequent necrosis or degeneration of adjacent myocardial cells. It may also involve the pericardium or endocardium. The incidence rate during childhood in China is currently unknown. According to foreign data, the condition is not considered common.
Etiology
Common viruses associated with myocarditis in children include coxsackievirus (group B and group A), echovirus, adenovirus, influenza virus, parainfluenza virus, human parvovirus B19, herpes simplex virus, measles virus, and mumps virus. Of note, coxsackievirus group B infections during the neonatal period can lead to outbreaks in Neonatal Intensive Care Units, with a mortality rate exceeding 50%.
Pathogenesis
Although the precise mechanism of viral myocarditis remains unclear, advances in molecular virology and molecular immunology have revealed that the pathogenesis involves both direct myocardial damage caused by the virus and myocardial injury triggered by the host's immune response. Viruses like coxsackievirus and adenovirus invade myocardial cells by binding to specific receptors, replicate intracellularly, and directly damage the cells, leading to myocardial degeneration, necrosis, and lysis in the acute phase. Viral stimulation activates the host's cellular and humoral immune responses, resulting in the production of anti-myocardial antibodies, interleukin-1α, TNF-α, and interferon-γ. These, in turn, induce the production of cell adhesion molecules, promoting selective adhesion, infiltration, and attack on myocardial tissue by cytotoxic T cells (CD8+).
Clinical Manifestations
The clinical presentation varies in severity depending on factors such as age and whether the course is acute or chronic. Some patients exhibit subtle onset with symptoms such as fatigue, exercise intolerance, palpitations, or chest pain. Severe cases may involve heart failure, complications of severe arrhythmia, cardiogenic shock, and high mortality rates. A subset of patients may develop chronic disease and progress to dilated cardiomyopathy. In neonates, the condition progresses rapidly, often presenting with high fever, lethargy, respiratory distress, and cyanosis, along with complications affecting the nervous system, liver, and lungs.
The heart may show mild enlargement accompanied by tachycardia, muffled heart sounds, and a gallop rhythm. Recurrent heart failure can result in marked cardiac enlargement, pulmonary rales, hepatosplenomegaly, rapid breathing, and cyanosis. Severe cases may lead to sudden cardiogenic shock with weak pulse and hypotension.
Auxiliary Examinations
Laboratory Tests
Creatine Phosphokinase (CPK)
Levels are often elevated in the early stages, predominantly reflecting the myocardial isoenzyme CK-MB.
Cardiac Troponins (cTnI or cTnT)
Changes in these markers are highly specific for diagnosing myocarditis, though their sensitivity is relatively low.
Serum Lactate Dehydrogenase Isozymes (SLDH)
Elevated levels can aid in early diagnosis.
In the early stages, viruses may be isolated from nasopharyngeal swabs, lavage fluids, stool, or blood. A fourfold or greater increase in serum antibody titers during convalescence compared to the acute phase is considered diagnostic.
X-ray Examination
Cardiomegaly may be observed, though findings are nonspecific. Pulmonary congestion and signs of edema may appear during heart failure.
Electrocardiography (ECG)
While lacking specificity, dynamic and serial observations of ECG changes are considered crucial.
Echocardiography
Enlargement of the atria and ventricles, myocardial wall edema and thickening, impaired systolic function, presence of pericardial effusion, and valve function abnormalities can be assessed.
Cardiac Magnetic Resonance Imaging (CMR)
CMR offers valuable diagnostic insights, revealing characteristic inflammatory changes in myocarditis (as further detailed in the primary clinical diagnostic criteria for myocarditis).
Endomyocardial Biopsy
This procedure remains the gold standard for diagnosing myocarditis. However, its application is limited by sampling site constraints and low patient compliance.
Diagnosis
Clinical Indicators
Primary Clinical Diagnostic Criteria
These include:
- Signs of heart failure, cardiogenic shock, or cardio-cerebral syndrome.
- Cardiac enlargement.
- Elevated levels of cTnI, cTnT, or CK-MB with dynamic changes over time.
- Significant electrocardiographic (ECG) changes (on a standard ECG or 24-hour Holter monitoring), including any of the following: sustained ST-T changes in two or more major leads (I, II, aVF, V5) dominated by R waves for more than 4 days with dynamic evolution; newly identified sinoatrial or atrioventricular conduction block; complete right or left bundle branch block; sinus arrest; bigeminy, couplets, polymorphic, or multifocal premature contractions; ectopic tachycardia not caused by AV node or AV reentrant pathways; atrial flutter or fibrillation; ventricular flutter or fibrillation; low QRS voltage (excluding neonates); abnormal Q waves, among others.
- Typical inflammatory manifestations of myocarditis on cardiac magnetic resonance imaging (CMR), meeting at least 2 of the following 3 criteria:
- Evidence of myocardial edema: localized or diffuse high-signal intensity on T2-weighted imaging.
- Indications of myocardial hyperemia and capillary leakage: early gadolinium enhancement on T1-weighted imaging.
- Signs of myocardial necrosis and fibrosis: at least one non-ischemic region showing localized late gadolinium enhancement (LGE) on T1-weighted imaging.
Secondary Clinical Diagnostic Criteria
These include:
- History of preceding infection.
- Symptoms such as chest tightness, chest pain, palpitations, fatigue, dizziness, pallor, grayish complexion, or abdominal pain (at least two symptoms); infants may exhibit signs such as feeding refusal, cyanosis, or cold extremities.
- Elevated levels of lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), or aspartate aminotransferase (AST).
- Mild ECG abnormalities that do not meet the criteria for "significant ECG changes" as defined in the primary diagnostic criteria (e.g., mild ST-T changes).
- Positive anti-myocardial antibodies.
Pathogenic Indicators
Definitive Criteria
Viral myocarditis can be confirmed by detecting any of the following findings in endocardium, myocardium, pericardium (via biopsy or pathology), or pericardial puncture fluid:
- Viral isolation.
- Viral nucleic acid detected using nucleic acid probes.
- Positive specific viral antibodies.
Reference Criteria
Viral myocarditis may be considered when clinical findings are coupled with any of the following:
- Isolation of a virus from stool, throat swabs, or blood, with convalescent serum showing a fourfold or greater increase in homologous antibody titers compared to acute-phase serum.
- Positive specific IgM antibodies detected in early-stage blood samples.
- Viral nucleic acid identified in the patient's blood using nucleic acid probes.
Diagnostic Basis
A clinical diagnosis of myocarditis may be established when at least 3 primary diagnostic criteria are met or when 2 primary criteria and at least 3 secondary criteria are fulfilled, provided that other diseases have been excluded.
Confirmed viral myocarditis requires meeting at least one of the definitive pathogenic criteria. A clinical diagnosis of viral myocarditis may be made if at least one reference pathogenic criterion is satisfied.
Patients who do not meet confirmation criteria should receive necessary treatment or follow-up. Diagnosis or exclusion of myocarditis should be reconsidered based on subsequent changes in their condition.
Other conditions must be ruled out, including coronary artery disease, toxic myocarditis, congenital heart disease, high-altitude heart disease, as well as myocardial damage caused by rheumatic diseases, metabolic disorders (e.g., hyperthyroidism), primary cardiomyopathy, primary endocardial fibroelastosis, congenital atrioventricular block, cardiac autonomic dysfunction, β-receptor hyperresponsiveness, and drug-induced ECG changes.
Treatment
Rest
Bed rest during the acute phase is necessary to alleviate cardiac workload.
Pharmacological Therapy
Antiviral therapy may be considered for early-stage patients still in the viremic phase, although its efficacy remains uncertain.
Myocardial nutrition improvement involves the use of agents such as fructose 1,6-diphosphate to enhance myocardial energy metabolism and facilitate the repair of damaged cells. High-dose vitamin C, coenzyme Q10 (CoQ10), vitamin E, and B-complex vitamins may also be used, alongside traditional Chinese medicines such as Shengmai Yin and Huangqi oral solution.
High-dose immunoglobulin helps mitigate myocardial cell damage through immunomodulatory effects.
Corticosteroids are generally not administered. In severe cases, including those with cardiogenic shock, life-threatening arrhythmias (e.g., third-degree atrioventricular block, ventricular tachycardia), or evidence of chronic autoimmune myocardial inflammation confirmed via myocardial biopsy, early and adequate corticosteroid use is warranted.
Arrhythmia management follows the specific guidelines for pediatric arrhythmias.
Treatment for heart failure involves restricting fluid intake and combining diuretics, digitalis, and vasoactive drugs as needed based on the patient's condition. Particular attention should be given to reducing the digitalis saturation dose compared to standard dosages and ensuring adequate potassium chloride supplementation to prevent digitalis toxicity.
Prognosis
Prognosis depends on factors such as patient age, disease severity, and the timeliness of treatment. Outcomes are generally poorer in neonates. Without timely intervention, severe cases have a high mortality rate. Patients presenting with significantly enlarged left ventricles and markedly impaired cardiac function tend to have worse prognoses.