| disease | Infectious Myocarditis |
| alias | Cardiomyopathy |
Myocardial inflammation can be localized or diffuse, often as part of a systemic disease. Severe cases present obvious symptoms, while mild cases may be asymptomatic, making clinical recognition difficult.
bubble_chart Etiology
Myocarditis complicating infectious diseases includes myocarditis associated with viral, bacterial, spirochetal, fungal, rickettsial, and trypanosomal infections. Among these, myocarditis complicating viral and bacterial infections is relatively common, while the others are rare.
(1) Complicating viral infections: In 1952, neonatal Coxsackie viral myocarditis was first discovered in South Africa. With advances in virology research, viral myocarditis has become increasingly common, with Coxsackie B group viruses being the most frequent cause, accounting for about 50% of cases, and primarily manifesting as myocarditis. The pathogenesis of viral myocarditis is not yet fully understood. During viremia, the virus may directly invade the myocardium, causing lesions, or may induce myocardial injury through immune reactions. Animal experiments have shown that in mice, Coxsackie B3 viral myocarditis is primarily mediated by cellular immunity, with local viral injury playing a secondary role. Around six days after infection with cardiotropic Coxsackie B3 virus, mice develop pathological immune responses: ① Autoreactive cytotoxic T lymphocytes exert autoimmune effects on myocardial cell antigens, leading to extensive myocardial cell lysis and necrosis; ② Virus-specific cytotoxic T cells cause lysis of infected myocardial cells, resulting in milder inflammation.
Recent studies on generation and transformation mechanisms suggest that reactive oxygen species can cause cell injury, leading to certain diseases. Domestic reports indicate that superoxide dismutase levels are reduced in patients with acute myocarditis, which may increase intracellular reactive oxygen free radicals. This can cause myocardial cell nucleic acid断裂, polysaccharide depolymerization, and unsaturated fatty acid peroxidation, leading to myocardial cell membrane injury and altered mitochondrial oxidative phosphorylation, thereby damaging the myocardium.
(2) Complicating bacterial infections: Staphylococcal endocardial membrane inflammation, pericarditis, or sepsis can complicate myocarditis or myocardial abscesses. If not properly treated, bacteremia caused by streptococci, pneumococci, or meningococci can also lead to myocarditis. Other conditions, such as cold-damage disease and subcutaneous nodule disease, may occasionally complicate myocarditis, but the myocardial injury is usually mild. Although the incidence of diphtheria has significantly declined, myocarditis remains a major cause of death in diphtheria cases. Its clinical manifestations are distinctive, so it will be discussed separately later in this section.
(3) Complicating other infections: Rickettsial infections, particularly macula and papule cold-damage disease, often cause myocarditis. About 50% of fatal cases of macula and papule cold-damage disease show significant myocardial lesions. Leptospiral myocarditis. Chagas disease is a systemic illness caused by Trypanosoma cruzi infection, primarily occurring in South Africa and Brazil, especially in children. Death from myocarditis can occur during the acute phase. Most cases follow a latent course, with initial stage [first stage] symptoms being mild, and only becoming apparent during the chronic phase when cardiomyopathy develops. The heart becomes significantly enlarged, leading to heart failure, complications such as atrioventricular valve insufficiency, and severe arrhythmias, ultimately resulting in death. This section focuses on viral myocarditis.bubble_chart Pathological Changes
The heart shows varying degrees of enlargement. The myocardium appears very soft on gross examination. Microscopically, infiltration of mononuclear cells, lymphocytes, and neutrophils can be seen in the connective tissue between myocardial fibers and around blood vessels. The myocardial fibers exhibit varying degrees of degeneration, loss of striations, coagulation and/or dissolution of sarcoplasm, presenting as small focal, patchy, or extensive necrosis. Myocardial dissolution may occur, with both nuclei and cytoplasm disappearing, leaving only residual cell membranes. The distribution of cardiac lesions is typically most severe in the left ventricle and interventricular septum, followed by the right ventricle, with the left and right atria being the least affected. In chronic sexually transmitted disease cases, besides myocardial fiber degeneration, fibroblast proliferation and scar formation can be observed, along with endocardial membrane elastic fiber hyperplasia and ventricular mural thrombosis. Detachment of mural thrombi can lead to infarctions in the brain, kidneys, lungs, and other organs. Viral myocarditis is often accompanied by serofibrinous pericarditis, with minimal effusion. Some cases also exhibit endocardial membrane inflammation. Electron microscopy reveals myocardial cell fragmentation, loss of myofilaments, destruction of actin structure, and mitochondrial degeneration. Viruses can be isolated from the inner membrane, and specific viral antigens can be detected in the myocardium, pericardium, or endocardial membrane using fluorescent immunoassay. Viral particles can be observed under electron microscopy.
bubble_chart Clinical ManifestationsThe clinical manifestations of myocarditis vary greatly in severity, ranging from asymptomatic cases to extremely severe cases that present with fulminant cardiogenic shock or acute congestive heart failure, leading to death or sudden death within hours or days. Myocarditis symptoms can occur during the acute phase of viral infection or the {|###|}stage of convalescence. If they occur during the acute phase, the symptoms of myocarditis are often overshadowed by systemic symptoms.
1. Typical symptoms and signs: Cardiac symptoms may appear several days or up to 2 weeks after respiratory or gastrointestinal infections, accompanied by symptoms such as {|###|}grade II fever, sore throat, diarrhea, and rash, followed by cardiac symptoms. The main symptoms include fatigue, loss of appetite, nausea, vomiting, difficulty breathing, pale {|###|}complexion, fever, and in older children, complaints of precordial discomfort, palpitation, dizziness, abdominal pain, and myalgia. Physical examination often reveals a muffled first heart sound at the apex, gallop rhythm, tachycardia or bradycardia, or arrhythmias. Pericardial friction rub may be heard if pericarditis is present. The heart borders may be normal or enlarged, with decreased blood pressure and narrow pulse pressure. Based on severity, myocarditis can be classified into mild, moderate, and severe types. Mild cases may be asymptomatic or only show transient ST-T changes on ECG, or present with lethargy, weakness, loss of appetite, diminished first heart sound, gallop rhythm, or tachycardia. The heart borders are mostly normal, and the condition is relatively mild, often resolving within days or weeks with treatment or following a subclinical course. Moderate cases, in addition to the above symptoms, often exhibit congestive heart failure. The onset is usually acute, with refusal to eat, pale {|###|}complexion, vomiting, difficulty breathing, and dry cough. Children may complain of precordial pain, dizziness, and palpitation, and may experience acute abdominal pain, myalgia, dyspnea, orthopnea, dysphoria, cyanosis, enlarged heart borders, muffled heart sounds, gallop rhythm, or arrhythmias. Rales may be heard in both lungs, and the liver may be enlarged and tender, though edema is often not prominent. Neurological and renal {|###|}injury may occur. With timely treatment, most cases recover within months or years, but some patients may die from acute congestive heart failure during the acute phase or develop chronic myocardial damage. Severe cases may present with fulminant cardiogenic shock, characterized by dysphoria, difficulty breathing, pale {|###|}complexion, peripheral cyanosis, cold and clammy skin, profuse sweating, weak pulse, hypotension or unmeasurable blood pressure, tachycardia, and gallop rhythm. Some children may present with severe abdominal pain or myalgia, and the condition progresses rapidly. If treatment is deficient, death may occur within hours or days. Severe cases may also present as acute or chronic congestive heart failure, with symptoms similar to moderate cases. Some patients die due to uncontrolled acute heart failure, while a few transition from acute to chronic, experiencing recurrent heart failure due to infection or overexertion, leading to significant cardiac enlargement, dyspnea, hepatomegaly, and prominent edema, ultimately dying despite treatment. Chronic cases often present with thromboembolic phenomena or arrhythmias. Cerebral embolism may cause hemiplegia or aphasia, while renal embolism may present with hematuria. A few cases may develop myocardial infarction, and severe arrhythmias such as complete atrioventricular block, ventricular tachycardia, or ventricular fibrillation may lead to sudden death.
In neonates, myocarditis caused by coxsackievirus B group infection is severe and often accompanied by inflammation of other organs such as meningoencephalitis, pancreatitis, or hepatitis. Symptoms typically appear within 10 days after birth, with sudden onset of refusal to eat, vomiting, diarrhea, and drowsiness, along with significant dyspnea and tachycardia, rapidly progressing to acute heart failure.2. X-ray findings: The heart shadow may show {|###|}grade I to grade III generalized enlargement, predominantly in the left ventricle, with weakened cardiac pulsations, pulmonary congestion, pulmonary edema, and occasionally small pleural effusions.
3. Prolonged ECG examination often shows low QRS wave voltage, ST segment deviation, inverted, flat, or low T waves, with some ST-T forming a monophasic curve resembling acute myocardial infarction. Prolonged QT interval is also observed, along with various arrhythmias such as atrioventricular block, intraventricular block, paroxysmal tachycardia, premature beats, atrial flutter, atrial fibrillation, and ventricular fibrillation. Chronic sexually transmitted disease cases may exhibit left ventricular hypertrophy.
4. Echocardiography Approximately one-third of cases show left ventricular enlargement, reduced motion amplitude of the interventricular septum and left ventricular posterior wall, but these findings are nonspecific.
5. Radionuclide Imaging 67Ga myocardial imaging positivity suggests myocarditis. 111In monoclonal antimyosin antibody myocardial imaging can detect myocardial necrosis, aiding in the diagnosis of myocarditis.
6. Other Laboratory Tests Mild leukocytosis (grade I), neutrophilia, and slightly increased erythrocyte sedimentation rate (ESR). Serum aspartate aminotransferase (GOT), creatine phosphokinase (CPK), creatine phosphokinase isoenzyme (CPK-MB), and lactate dehydrogenase (LDH) may be elevated during the acute phase, but the rise in CPK and CPK-MB is diagnostically significant for myocardial injury. CPK-MB is a myocardium-specific plasma isoenzyme, normally present in trace amounts in serum, so its elevated levels can serve as an early diagnostic marker for myocarditis. LDH is widely distributed in the body and has poor specificity, but LDH isoenzyme serum enzyme pattern analysis is more valuable. The normal pattern is LDH1 > LDH1 > LDH3 > LDH4 > LDH5. If LDH1 > LDH2 or LDH1 > 40%, it is more diagnostically significant for myocarditis. Since enzyme activity elevation can be influenced by non-cardiac factors, comprehensive clinical analysis is necessary.
Virological tests may isolate specific viruses from pericardial effusion, throat swabs, or stool in the early stage. Viral RNA can also be detected using polymerase chain reaction (PCR). During the convalescence stage, a fourfold increase or decrease in serum intermediate virus-neutralizing antibodies or hemagglutination inhibition antibodies compared to the first serum sample, or specific IgM positivity, is observed. In fatal cases, viruses may be isolated from the pericardium, myocardium, or endocardial membrane, or specific fluorescent antibody tests may be positive. Electron microscopy may reveal viral particles near myocardial necrotic lesions.
A small number of pediatric patients may test positive for serum anti-myocardial antibodies.
During the course of viral infection or at the stage of convalescence, if cardiac enlargement, heart failure, cardiogenic shock, or arrhythmia occurs, observation should be conducted based on X-ray findings and electrocardiogram (ECG) manifestations. After excluding other cardiac diseases, the diagnosis of viral myocarditis should be considered. The diagnostic criteria for pediatric viral myocarditis formulated by the Pediatric Viral Myocarditis Collaborative Group of Nine Provinces and Cities can serve as a reference for diagnosis.
1. Etiological diagnostic basis
(1) Isolation of the virus from the patient's feces or throat swab, with a fourfold or greater increase or decrease in the neutralizing antibody (or hemagglutination inhibition antibody) titer of the same virus in the serum during the stage of convalescence compared to the first serum sample, or positive specific IgM; or the isolated virus strain can induce myocarditis in experimental animals.
(2) Isolation of the virus from the patient's pericardial puncture fluid or blood.
(3) Isolation of the virus from endocardial membrane or myocardial biopsy specimens, or from the pericardium, myocardium, or endocardial membrane postmortem, or positive specific fluorescent antibody test. Viral particles can be observed under electron microscopy.
2. Clinical diagnostic basis
(1) Major criteria: ① Acute or chronic cardiac insufficiency or cardiocerebral syndrome; ② Presence of gallop rhythm or pericardial friction rub; ③ Cardiac enlargement; ④ ECG showing severe arrhythmias, including ectopic rhythms other than frequent or occasional premature beats, second-degree type II or higher atrioventricular block, sinoatrial or bifascicular/trifascicular block, or significant ST-T changes or low voltage.
(2) Minor criteria: ① History of upper respiratory tract infection, diarrhea, or other viral infections either concurrently or 1–3 weeks before onset; ② Presence of at least two of the following symptoms: marked lack of strength, pallor, profuse sweating, palpitation, shortness of breath, chest tightness, dizziness, precordial pain, cold extremities, or myalgia. Infants may exhibit refusal to feed, cyanosis, cold limbs, or fixed gaze. Neonates can be diagnosed based on the mother's epidemiological history; ③ Marked dullness of the first heart sound at the apex or tachycardia at rest; ④ Grade I ECG abnormalities, i.e., ECG changes other than those listed in the major criteria, or positive exercise test; ⑤ Early in the course of the disease, serum levels of CPK, CPK-MB, GOT, or LDH may be elevated (preferably with isoenzyme testing). Anti-myocardial antibodies (AHA, HRA) are often elevated during the course of the disease.
3. Definitive diagnostic conditions
(1) Patients meeting two major criteria or one major criterion plus two minor criteria (all requiring ECG criteria) can be clinically diagnosed with myocarditis.
(2) Patients meeting one of the three etiological criteria can be diagnosed with viral myocarditis. If myocarditis occurs concurrently with obvious viral infection in other systems but viral isolation is not feasible, the combination of disease history may suggest viral etiology.
(3) Patients not fully meeting the above criteria but clinically suspected of having myocarditis can be classified as "suspected myocarditis" for long-term follow-up. If systematic dynamic changes are observed, myocarditis may be considered or ruled out during follow-up.
(4) When applying the above criteria, other conditions must first be excluded, including: rheumatic myocarditis, toxic myocarditis, subcutaneous nodular pericarditis, congenital heart disease, myocardial damage due to connective tissue or metabolic disorders (including vitamin B1 deficiency), primary cardiomyopathy, congenital atrioventricular block, high-altitude heart disease, Keshan disease, autonomic dysfunction, and ECG changes caused by electrolyte imbalances or medications.
4. Endomyocardial biopsy histological diagnosis Endomyocardial biopsy via cardiac catheterization provides reliable pathological diagnostic evidence for myocarditis. The Dallas Conference in 1984 established the following histological diagnostic criteria for myocarditis: ①Active myocarditis: Requires inflammatory cell infiltration and adjacent cell damage, including clear cell necrosis, or the presence of vacuoles, irregular cell morphology, and cell disintegration. ②Borderline myocarditis: Sparse inflammatory infiltration with no cell injury visible under light microscopy. Approximately 70% of biopsy specimens are helpful in diagnosing various cardiomyopathies. Due to the small and limited sample size, the specimen itself can cause cell contraction, leading to some pathological artifacts. Additionally, differences in histological interpretation result in a poor correlation between clinical manifestations and histology. Endomyocardial biopsy is an invasive procedure with certain risks, including serious complications such as pneumothorax, right ventricular perforation, and ventricular arrhythmias. Therefore, except in special circumstances, it is generally not performed as a routine examination.
bubble_chart Treatment Measures
There is currently no effective treatment for viral myocarditis. Comprehensive therapeutic measures are generally adopted.
1. Bed rest: Patients should rest in bed to reduce cardiac burden and oxygen consumption. Those with cardiac enlargement and concurrent heart failure should extend bed rest for at least 3 to 6 months. Activity can be gradually resumed once the condition improves or the heart size decreases.
2. Sedation and analgesia: For patients with dysphoria, precordial pain, or abdominal pain, timely symptomatic treatment is necessary. Analgesics such as phenobarbital, aspirin, somidon, or codeine can be used, and morphine injections may be administered if necessary.
3. Immunosuppressants: With research into the disease mechanism, the exploration of immunosuppressant therapy has gradually increased since the 1980s, primarily using prednisone with or without azathioprine. This is mainly for rescuing acute-phase complications such as cardiogenic shock, complete atrioventricular block, and heart failure that are unresponsive to other treatments. It is generally not recommended for routine use in early-stage myocarditis. Treatment typically begins with hydrocortisone at 5–10 mg/(kg·d) or dexamethasone at 0.25–0.5 mg/(kg·d) via intravenous drip. This is followed by oral prednisone at 1–2 mg/(kg·d), tapered after one month. Azathioprine may be added at 2 mg/(kg·d) orally, with a treatment course lasting over 6 months, while preventing and treating secondary infections. A report documented 13 severe infant and child myocarditis cases confirmed by endomyocardial biopsy, all treated with prednisone (one case also received azathioprine). Except for one fatality, survivors showed improved clinical symptoms, normalized ECG findings, and restored heart size and contractile function. Repeat biopsies in 8 cases revealed improvement, with inflammatory infiltration resolved in 6.
4. Other treatments: Vitamin C eliminates free radicals; 100–200 mg/(kg·d) is injected intravenously with 20–50 ml glucose solution for 3–4 weeks per course. Coenzyme Q10 protects the myocardium; 5 mg is injected intramuscularly daily for 2–3 weeks. Fructose-1,6-diphosphate improves myocardial metabolism; 100–250 mg/kg is injected intravenously daily for 2–3 weeks. Astragalus Root has antiviral and cardioprotective effects and can be taken orally or injected intramuscularly long-term.
5. Symptomatic treatment: Address complications such as arrhythmias, cardiogenic shock, and heart failure.
Most patients have a good prognosis and gradually recover over weeks, months, or even years. A few experience a fulminant course, dying within hours or days due to cardiogenic shock or acute congestive heart failure, with some cases suffering sudden death from arrhythmias. A small number of cases progress to chronic conditions—some exhibiting only ECG changes without clinical symptoms, while others experience persistent heart failure leading to eventual death. Chronic cases may persist for years. Whether chronic inflammation can transition to dilated cardiomyopathy remains undetermined. Some reports describe neonatal Coxsackie viral myocarditis following a chronic course. Some researchers suggest that chronic myocarditis may harbor latent viruses that reactivate under certain conditions, leading to recurrent symptoms and worsening damage, or that immune mechanisms trigger flare-ups. Viral antigens have been detected in the myocardium of deceased dilated cardiomyopathy patients, and endomyocardial biopsies in many children clinically presenting as dilated cardiomyopathy revealed pathological changes consistent with myocarditis, suggesting that some cases of dilated cardiomyopathy result from viral myocarditis. The prognosis largely depends on the severity of myocardial damage and is influenced by the following factors: ① the type of infecting virus—Coxsackievirus B3 tends to cause more severe myocarditis than A9; ② patient age—neonates have the highest mortality, while older children fare better; ③ disease recurrence—poor prognosis in relapsing cases; ④ significant cardiac enlargement with heart failure—poor prognosis.
In daily life, it is important to strengthen physical exercise, enhance the immune system, receive preventive vaccinations against various viral infections, and reduce exposure to adverse factors such as cold and fever. During treatment, it is necessary to prevent recurrent common colds. For neonatal prevention, it is crucial to protect pregnant women from viral infections.
The diagnosis of viral myocarditis, in the absence of virological evidence, primarily relies on comprehensive clinical data, as there is a lack of specific diagnostic methods. Therefore, careful observation is necessary to exclude other cardiac diseases. In infancy, it must also be distinguished from bronchiolitis or bronchopneumonia. Such children exhibit significant dyspnea and tachycardia, but signs of heart failure are not prominent, the cardiac borders are not enlarged, and liver enlargement is minimal with non-blunted edges. In childhood, differentiation should be made from acute nephritis complicated by heart failure, the latter often presenting with hypertension, proteinuria, and hematuria, making it relatively easier to diagnose. If frequent premature beats are the main manifestation, differentiation from functional premature beats is required. For cases presenting with tachycardia and nonspecific ST-T changes, β-receptor hyperfunction should be ruled out. Additionally, cardiogenic shock caused by myocarditis must be differentiated from septic shock or surgical shock.