Diagnosis of myocarditis in children

All patients with suspected myocarditis should undergo the following studies:

• collection of life history, family history, and disease history;
• physical examination;
• laboratory tests;
• instrumental studies.

The diagnostic search necessarily includes a thorough analysis of the anamnesis of the disease, paying special attention to the connection of cardiac symptoms with previous episodes of viral, bacterial infections and unclear fever, all kinds of allergic reactions, vaccinations. However, in pediatric practice, there are often cases of myocarditis, where there is no specific link between the heart disease and specific etiological causes.

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Clinical diagnostics of myocarditis in children

During examination, cyanosis of a certain localization (acrocyanosis, cyanosis of the mucous membranes) is usually detected; it is often transient, which distinguishes it from that in lung diseases. A weakened and slightly shifted to the left apical impulse, expanded or normal borders of cardiac dullness are determined. Moist fine-bubble rales are possible above the lower sections of both lungs. Heart sounds are often muffled, there may be a "gallop rhythm" and other disturbances of rhythmic activity. Tachycardia does not correspond to the body temperature and emotional arousal of the child, is resistant to drug therapy, and persists during sleep. A low-intensity blowing systolic murmur at the apex of the heart either appears, or the intensity of the previously present murmur weakens. Enlargement of the liver, and in young children and the spleen, peripheral edema and ascites are determined in right ventricular or total insufficiency.

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Laboratory diagnostics of myocarditis in children

In the process of verifying myocarditis, laboratory diagnostics are carried out in the following areas:

• determination of the activity of cardioselective enzymes in plasma, reflecting damage to cardiomyocytes;
• identification of biochemical markers of inflammation;
• assessment of the severity of immune inflammation; identification of etiological factors;
• diagnostics of foci of chronic infection.

It is known that in case of damage to cardiomyocytes of any etiology (hypoxic, inflammatory or toxic), an increase in the activity of cardioselective enzymes and proteins (CPK, CPK-MB, LDH, troponin T) is observed. However, it should be borne in mind that these biochemical markers reflect damage to cardiomyocytes with varying degrees of specificity.

The concentration of LDH (mainly LDH fraction I) in the blood reflects the intensity of anaerobic glycolysis and the presence of lactic acidosis in the myocardium.

Damage to cardiomyocytes or weakening of tissue respiration is accompanied by an increase in the level of anaerobic glycolysis, which leads to lactic acidosis and an increase in LDH activity, so an increase in its concentration is possible without the destruction of cardiomyocytes.

Increased CPK activity may occur with damage to any myocytes, including striated muscles. In this case, an increase in the concentration of its cardiac isoenzyme CPK-MB in the blood is a consequence of the destruction of cardiomyocytes only.

The cardioselective proteins troponin T and troponin I also appear in plasma only when cardiomyocytes are damaged due to many causes.

The degree of damage and destruction of cardiomyocytes in myocarditis in most cases is not massive, therefore the concentration of cardioselective enzymes increases only 1.5-2 times.

The inflammatory process of any localization causes changes in the protein composition of the blood (proportions of alpha-, beta-, y-globulins, the content of sialic acids, fibrinogen, C-reactive protein, etc.). However, changes in these generally accepted biochemical markers of inflammation, as well as leukocytosis, an increase in ESR are not specific for myocardial inflammation, therefore they are not taken into account as criteria for myocarditis itself.

In recent years, an increase in the CD4 count and a change in the CD4/CD8 ratio, an increase in the CD22, IgM, IgG, IgA and CIC counts are considered to be a reflection of inflammatory myocardial damage. One of the most sensitive laboratory tests is the lymphocyte migration inhibition reaction with a cardiac antigen. In myocarditis, the basophil degranulation test is also sensitive, reflecting the percentage of degranulated forms in the peripheral blood. A sensitive immunological test is the determination of a cardiac antigen and specific circulating immune complexes containing a cardiac antigen, antibodies to cardiomyocytes, to the cardiac conduction system, which serves as a kind of indicator of autoimmune inflammation in the heart muscle.

Data from various studies indicate an increase in the formation of proinflammatory cytokines (IL-1beta, 6, 8, 10, tumor necrosis factor a [TNF-a]), which support the process of immune inflammation in patients with myocarditis.

It is important to determine the cause of myocarditis (especially viral), but it is extremely rare to isolate the pathogen in cases of chronic inflammatory heart disease. The search for the pathogen of acute and chronic infectious pathogens in the blood, nasopharynx, tracheal aspirate (viruses, bacteria, spirochetes, protozoa, etc.) and antibodies to them is carried out using cultural methods, PCR, ELISA, etc. An increase in the titer of virus-neutralizing antibodies in plasma by 4 times or more is considered diagnostically significant, but the clinical significance of this method has not yet been proven.

Along with the search for the causative agent of myocarditis in children, it is necessary to identify and sanitize foci of chronic infection (chronic tonsillitis, chronic sinusitis, periapical dental granulomas, pulpitis, chronic cholecystitis, etc.). Analysis of literary sources indicates that, on the one hand, chronic focal infection can be a source of infection development penetrating the myocardium, on the other hand, it can become an unfavorable background for the formation of an inadequate immune response to the penetration of another infectious agent into the myocardium. It should be taken into account that constant intoxication and sensitization of the body are an unfavorable background for the development of myocarditis.

Instrumental diagnostics of myocarditis in children

ECG and echocardiography are of great importance in establishing the diagnosis of myocarditis. It is especially important to note the need for Holter (daily) monitoring of ECG data, which allows identifying rhythm and conduction disturbances not detected by a regular ECG.

Electrocardiography and Holter monitoring data

The nature of changes on the ECG varies widely, the most frequently noted are the following:

• sinus tachycardia;
• reduction of tooth voltage;
• disturbances of rhythm (usually extrasystole) and conduction (AV block I-II degree) of the heart, most often detected during Holter monitoring of ECG data;
• non-specific changes in the ST segment and T wave.

Changes in ECG data during the acute period are characterized by a rapid change in pathological signs, often a combination of them; upon recovery, complete normalization of the parameters occurs.

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Echocardiography data

Echocardiographic examination often reveals the following changes:

• violation of systolic and/or diastolic function of the left ventricle;
• dilation of the heart cavities, primarily the left ventricle;
• symptoms of mitral regurgitation due to relative mitral valve insufficiency;
• exudate in the pericardial cavity.

In focal myocarditis, there may also be normal values. The value of echocardiography in cardiomegaly is mainly in excluding other possible causes of deterioration of the child's condition (congenital heart disease, etc.).

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Chest X-ray

An important role in identifying cardiomegaly in children is played by the X-ray examination method, as it allows one to obtain a more accurate idea of the degree of enlargement of the heart than with percussion, as well as to assess the state of the pulmonary circulation (pulmonary congestion).

Myocardial scintigraphy

Necrotic and inflammatory changes in the myocardium are detected using scintigraphy with ⁶⁷ Ga and antimyosin antibodies labeled with ¹¹¹ In. However, the value of this method for clinical practice in children has not been proven.

Cardiac catheterization and transvenous endomyocardial biopsy

Cardiac catheterization allows for histological and immunological examination of the myocardium to detect signs of inflammation. However, despite its high information content, myocardial biopsy, especially in children, is used sparingly, which is due to a number of reasons: there are many difficulties in interpreting the results (possibility of obtaining false positive and false negative results), the method is technically complex and requires specially trained personnel, the cost is high, and there is a risk of severe complications.

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Diagnostic criteria for myocarditis in children

Diagnosis of myocarditis in children is based on the dynamics of pathological changes in ECG, EchoCG data, the presence of cardiomegaly, acute onset and progressing congestive heart failure, and increased activity of cardiac-specific enzymes. These changes are detected 2-3 weeks after the infectious process, and are accompanied by typical subjective signs.

The clinical picture of chronic myocarditis consists of a successive series of exacerbations occurring at indefinite intervals. Each of the exacerbations is initially taken for ARI, and only subsequent disturbances in the functional state of the heart allow us to identify the true cause of the deterioration of the condition.

There are no generally accepted criteria for establishing the diagnosis of myocarditis. The most well-known are the NYHA criteria (1964-1973), which have been supplemented and refined over time.

• Big signs:
  • pathological changes in ECG data (repolarization disorders, rhythm and conduction disorders);
  • increased concentration of cardioselective enzymes and proteins in the blood (CPK, CPK-MB, LDH, troponin T):
  • enlargement of the heart according to radiography or echocardiography;
  • congestive circulatory failure;
  • cardiogenic shock.
• Minor signs:
  • laboratory confirmation of a previous viral disease (isolation of the pathogen, results of the neutralization reaction, complement fixation reaction, hemagglutination reaction, increased ESR, appearance of C-reactive protein);
  • tachycardia (sometimes bradycardia);
  • weakening of the first tone;
  • "gallop rhythm".

The diagnosis of myocarditis is valid when a previous infection is combined with one major and two minor signs.

NYHA criteria are the initial stage of diagnostics of non-coronary myocardial diseases. To establish a final diagnosis in modern conditions, additional examination with visual (single-photon emission CT, magnetic resonance imaging [MRI]) or histological confirmation of the clinical (preliminary) diagnosis is necessary.

Criteria for the final diagnosis of myocarditis

Survey	Inflammatory myocardial lesion	Myocarditic cardiosclerosis
Histology	Cellular infiltration (more than 5 cells per field of view at 400 magnification) in myocardial morphobiopsy specimens	The presence of "reticular" fibrosis in myocardial morphobioptates
Single photon emission CT	Accumulation of radiopharmaceutical in the myocardium during single-photon emission CT with labeled leukocytes or gallium citrate	Myocardial perfusion abnormalities during single-photon emission CT with Tc-tetraphosmin
MRI	Detection of extracellular water in cardiac MRI with contrast	Myocardial perfusion abnormalities during cardiac MRI with contrast
Laboratory methods	Exceeds the norm of the basophil degranulation test, reveals the presence of cardiac antigen and antibodies to the myocardium, as well as a positive reaction of inhibition of lymphocyte migration with cardiac antigen

Instrumental and laboratory research methods can confirm the presence of myocarditis, but negative results are not considered a criterion for excluding the diagnosis.

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Differential diagnosis of myocarditis in children

Due to the non-specificity of the clinical picture of myocarditis and the data of instrumental studies, recognition of this disease in some cases is a certain complexity and is associated with a large number of diagnostic errors. Therefore, when myocarditis is suspected, differential diagnostics is of great importance.

When cardiomegaly and signs of myocardial dysfunction are detected in newborns, it is necessary to exclude post-hypoxic syndrome of cardiovascular maladaptation, drug-induced morpho-functional damage to the myocardium, diabetic fetopathy, and genetically determined pathology.

In young children, it is first necessary to differentiate myocarditis from congenital heart defects, such as coarctation of the aorta, anomalous origin of the left coronary artery from the pulmonary trunk, and mitral insufficiency.

In older children, differential diagnosis must be carried out with rheumatism, infective endocarditis, arrhythmogenic myocardial dysfunction, and vasorenal hypertension.

The most difficult differential diagnosis is severe myocarditis with dilated cardiomyopathy; in this case, it is often impossible to do without a myocardial biopsy.

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