Myocarditis is an inflammatory disease of the myocardium caused by infectious and non-infectious factors. Infectious pathogens are often viral, with fewer cases caused by bacteria, fungi, rickettsiae, spirochetes, or protozoa. Non-infectious causes include physical and chemical factors, drugs, allergies, and immune-mediated mechanisms. Viral myocarditis (VM) is myocarditis caused by myocardial injury due to cardiotropic viral infections.
Etiology
Cardiotropic viruses primarily include:
- Enteroviruses: Coxsackievirus B3, echoviruses, poliovirus
- Respiratory viruses: Adenovirus, influenza virus (types A and B), parvovirus B19, and coronaviruses (e.g., SARS-CoV).
Pathogenesis
Viruses directly damage myocardial tissues, including myocardial cells, interstitial tissues, and microvasculature.
Viral infection triggers immune responses, primarily mediated by T lymphocytes, leading to myocardial tissue damage. Various cytokines and nitric oxide (NO) also contribute to myocardial injury.
Pathology
In the early stage, focal or diffuse infiltration of neutrophils into the myocardial interstitium and degeneration/necrosis of myocardial cells can be seen.
In the intermediate stage, lymphocytes, macrophages, and plasma cells infiltrate, with the formation of granulation tissue.
In the late stage, significant interstitial fibrosis is observed, accompanied by compensatory myocardial hypertrophy and cardiac chamber dilation.
Clinical Manifestations
Symptoms
Over half of patients experience symptoms of upper respiratory or gastrointestinal viral infections 1-3 weeks prior to onset, such as fever, body aches, sore throat, emesis, and diarrhea.
Mild cases may be asymptomatic or present with chest tightness, chest pain, palpitations, and tachypnea.
In severe cases, acute left heart failure, pulmonary edema, and cardiogenic shock may occur.
Signs
Mild cases may not exhibit cardiac enlargement, while moderate to severe cases may show mild to moderate enlargement.
Tachycardia may not correlate with body temperature. Bradycardia may occur if the conduction system is affected.
The first heart sound may be muffled. A third or fourth heart sound or a gallop rhythm may be heard, indicating severe myocardial damage. Pericardial friction rub may be heard in cases of concurrent pericarditis.
Various arrhythmias and varying degrees of atrioventricular conduction block may occur.
Signs of acute left heart failure, pulmonary edema, and cardiogenic shock may be present.
Auxiliary Examinations
Laboratory Tests
During the acute phase, leukocytosis, elevated erythrocyte sedimentation rate (ESR), and increased C-reactive protein (CRP) levels may be observed. Elevated levels of creatine kinase-MB (CK-MB) and cardiac troponins are typical, resembling myocardial infarction but persisting for a longer duration.
Chest X-ray
Cardiac silhouette enlargement may be observed. In cases with pericardial effusion, the heart may appear flask-shaped.
Electrocardiography (ECG)
Common findings include QRS or ST-T wave abnormalities, various arrhythmias (especially ventricular arrhythmias and atrioventricular conduction blocks), and occasionally abnormal Q waves. In cases of concurrent acute pericarditis, widespread ST-segment elevation may be observed in all leads except aVR.
Echocardiography
Mild cases may show normal findings. Severe cases may reveal left ventricular enlargement, globally reduced wall motion, and decreased left ventricular ejection fraction (LVEF). Pericardial effusion may be present in cases with concomitant pericarditis.
Cardiac Magnetic Resonance (CMR)
CMR has significant diagnostic value for myocarditis. Acute myocarditis is characterized by:
- Increased T2 signal intensity, indicating myocardial edema
- Early gadolinium enhancement, suggesting myocardial hyperemia
- Late gadolinium enhancement (patchy enhancement in the subepicardial or mid-myocardial layers), indicating myocardial fibrosis
Serological Testing
Viral serology can provide clues regarding the etiology but cannot be used as a definitive diagnostic criterion.
Endomyocardial Biopsy (EMB)
EMB is primarily indicated for patients with severe disease, poor response to treatment, or unexplained causes. A definitive diagnosis depends on the detection of viral particles, antigens, gene fragments, or proteins.
Diagnosis
The diagnosis of viral myocarditis (VM) is based on:
- Prodromal symptoms of viral infection
- Cardiac-related symptoms and signs
- Evidence from ECG, TTE, CMR, and elevated biomarkers of myocardial injury (a necessary criterion)
- Pathogen-related findings
- Exclusion of other diseases
EMB may be performed when necessary to confirm the diagnosis.
Acute Coronary Syndrome-like Myocarditis
ECG findings mimic acute myocardial infarction, but ischemic changes do not match coronary artery distribution. Troponin elevation persists longer than in myocardial infarction, and coronary angiography is negative.
Heart Failure-like Myocarditis
Newly diagnosed heart failure (HF) or worsening HF within 2 weeks to 3 months is present, without other identifiable causes. TTE or CMR shows impaired cardiac systolic function, with negative coronary angiography.
Fulminant Myocarditis
Rapid onset follows brief prodromal symptoms, progressing quickly to acute pump failure, cardiogenic shock, cardiac arrest, or death.
Differential Diagnosis
Special types of VM can be easily confused with acute coronary syndrome, ischemic cardiomyopathy, stress-induced cardiomyopathy, and other conditions, requiring urgent differentiation to guide treatment decisions.
Diseases that need to be differentiated from VM include:
- Beta-adrenergic receptor hyperactivity
- Autoimmune diseases involving the heart
- Other non-infectious myocarditis (e.g., thyroid hormone- or catecholamine-induced cardiomyopathy, allergic myocarditis)
Treatment
Currently, there is no specific treatment for VM. Management primarily involves symptomatic and supportive care.
General Measures
Patients should rest in bed and avoid physical exertion. The duration of rest should be individualized. Mild cases should avoid intense physical activity for 3 months. Severe cases should restrict activity for more than 3 months until heart failure improves.
Pharmacological Treatment
Intravenous immunoglobulin (IVIG) and interferon-alpha may suppress viral replication if used early, though their efficacy remains uncertain. Glucocorticoids can suppress excessive immune-mediated damage but are not recommended for early or routine use. However, they should be administered promptly in cases of severe arrhythmias or cardiogenic shock.
Vitamin C has antioxidant and myocardial protective effects. Coenzyme Q participates in oxidative phosphorylation and energy production, with antioxidant and membrane-stabilizing properties.
Various arrhythmias are common in VM. If necessary and without contraindications, amiodarone and beta-blockers are preferred treatment options. For bradyarrhythmias and atrioventricular conduction blocks, temporary pacing may be required.
Fulminant myocarditis progresses rapidly and has a high mortality rate. Aggressive cardiopulmonary mechanical support is critical for reducing mortality, including:
- Endotracheal intubation with mechanical ventilation
- Intra-aortic balloon pump (IABP)
- Extracorporeal membrane oxygenation (ECMO)