Diagnosis of myocarditis in children

All patients with suspected myocarditis should conduct the following studies:

• collection of anamnesis of life, family history, history of the disease;
• physical examination;
• laboratory research;
• instrumental research.

The diagnostic search necessarily includes a thorough analysis of the history of the disease, focusing on the relationship of cardiac symptoms with previous episodes of viral, bacterial infections and vague fever, allergic reactions, and vaccinations. However, it is not uncommon in pediatric practice to encounter cases of myocarditis, where there is no definite binding of heart disease to specific etiological causes.

[1], [2], [3], [4], [5]

Clinical diagnosis of myocarditis in children

During the examination, cyanosis of definite localization (acrocyanosis, cyanosis of the mucous membranes) is usually detected, it is often transient, which distinguishes it from that of lung diseases. Define a weakened and slightly shifted left apical impulse, extended or normal borders of cardiac dullness. Above the lower sections of both lungs, wet, finely bubbling rales are possible. Cardiac tones are more often muffled, maybe "rhythm of canter" and other disturbances of rhythmic activity. Tachycardia does not correspond to body temperature and emotional excitement of a child, it is resistant to drug therapy, it persists during sleep. A non-intense blowing systolic murmur at the apex of the heart either appears, or the intensity of the noise present before it weakens. Enlarged liver, and in young children and spleen, peripheral edema and ascites are determined with right ventricular or total insufficiency.

[6], [7], [8], [9], [10], [11]

Laboratory diagnosis of myocarditis in children

In the process of verification of myocarditis, laboratory diagnostics is carried out in the following directions:

• determination of activity in the plasma of cardioselective enzymes, reflecting damage to cardiomyocytes;
• detection of biochemical markers of inflammation;
• Evaluation of the expression of immune inflammation; on the identification of etiological factors;
• diagnosis of foci of chronic infection.

It is known that when cardiomyocytes damage any etiology (hypoxic, inflammatory or toxic), an increase in the activity of cardioselective enzymes and proteins (KFK, KFK-MB, LDH, troponin T) is noted. 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 the fraction of LDH 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 increased LDH activity, so an increase in its concentration is possible without destroying the cardiomyocytes.

An increase in the activity of CK can occur when any of the myocytes, including striated muscle, is damaged. In this case, the increase in the blood concentration of his cardiac isoenzyme KFK-MB is a consequence of the destruction of only cardiomyocytes.

Cardioselective proteins troponin T and troponin I also appear in the plasma only when cardiomyocytes are damaged due to many reasons.

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

Inflammatory process of any localization causes changes in the protein composition of the blood (proportions of alpha, beta, y-globulin, sialic acid, fibrinogen, C-reactive protein, etc.). However, changing the data of conventional biochemical markers of inflammation, as well as leukocytosis, an increase in ESR, do not have specificity for inflammation of the myocardium, therefore they are not considered as criteria for the actual myocarditis.

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

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

To determine the cause of myocarditis (especially viral) is important, but it is extremely rare to isolate the causative agent in cases of a chronic course of inflammatory heart disease. Search for the causative agent of acute and chronic infectious pathogens in the blood, nasopharynx, aspirate from the trachea (viruses, bacteria, spirochaetes, protozoa, etc.) and antibodies to them are carried out by means of culture methods, PCR, ELISA, etc. Diagnostically significant increase in the virus neutralizing titer antibodies in plasma 4 times or more, but the clinical significance of this method has not yet been proved.

Along with the search for a pathogen 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.). The analysis of literature sources indicates that, on the one hand, chronic focal infection can be a source of development of an infection that enters the myocardium, on the other hand it can become an unfavorable background for the formation of an inadequate immune response to the introduction of another infectious agent into the myocardium. It should be borne in mind that the constant intoxication and sensitization of the body is an unfavorable background in the development of myocarditis.

Instrumental diagnosis of myocarditis in children

Essential in the establishment of the diagnosis of myocarditis have ECG and EchoCG. Particular mention should be made of the need for Holter (daily) monitoring of ECG data, which allows to detect abnormalities in rhythm and conductivity that were not detected in the usual ECG.

Electrocardiography and Holter monitoring data

The nature of ECG changes varies widely, most often the following:

• sinus tachycardia;
• reduction in the voltage of the teeth;
• disturbances of rhythm (more often extrasystole) and conduction (AV blockade of I-II degree) of the heart, more often detected during Holter monitoring of ECG data;
• nonspecific changes in the segment ST and the tooth T.

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

[12], [13], [14], [15], [16]

Echocardiography data

When echocardiographic research is often found such changes:

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

With focal myocarditis, there may be normal indices. The value of echocardiogram in cardiomegaly consists mainly in the exclusion of other possible causes of deterioration of the child's condition (congenital heart disease, etc.).

[17], [18], [19], [20], [21], [22]

Radiography of chest organs

An important role in the detection of cardiomegaly in children is played by the x-ray method of the study, since it allows to obtain a more accurate idea of the degree of cardiac enlargement than percussion, and also to assess the state of the small circle of circulation (stagnation in the lungs).

Myocardial scintigraphy

Necrotic and inflammatory changes in the myocardium are detected by scintigraphy with ⁶⁷ Ga and anti-myosin antibodies labeled with ¹¹¹ In. However, the value of this method for clinical practice in children is not proven.

Cardiac catheterization and transvene endomyocardial biopsy

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

[23], [24], [25], [26]

Criteria for diagnosis of myocarditis in children

Diagnosis of myocarditis in children is based on the dynamics of pathological changes in ECG data, echocardiography, the presence of cardiomegaly, acute and progressive congestive heart failure, increased activity of cardiospecific enzymes. These changes are revealed 2-3 weeks after the infectious process, they are accompanied by typical subjective signs.

The clinical picture of chronic myocarditis is made up of a series of exacerbations that occur at undefined intervals. Each of the exacerbations is first taken for ARI, and only subsequent violations of the functional state of the heart can reveal the true cause of deterioration.

To establish the diagnosis of "myocarditis," there are no universally recognized criteria. The most known criteria are NYHA (1964.1973), which are supplemented and refined with time.

• Great signs:
  • pathological changes in ECG data (repolarization disorders, rhythm disturbances and conduction);
  • increase in the concentration in the blood of cardioselective enzymes and proteins (CK, KFK-MB, LDH, troponin T):
  • an increase in the size of the heart according to radiography or EchoCG;
  • congestive circulatory failure;
  • cardiogenic shock.
• Small signs:
  • laboratory confirmation of the transferred viral disease (excretion of the pathogen, results of the neutralization reaction, complement fixation reaction, haemagglutination reaction, increase of ESR, appearance of C-reactive protein);
  • tachycardia (sometimes bradycardia);
  • weakening of the first tone;
  • "The rhythm of the gallop."

The diagnosis of "myocarditis" is competent when combining a previous infection with one large and two small signs.

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

Criteria for the final diagnosis of "myocarditis"

Examination	Inflammation of the myocardium	Myocarditis cardiosclerosis
Histology	Cellular infiltration (more than 5 cells in the field of vision with an increase of 400) in myocardial morphobioptates	The presence of "mesh" fibrosis in myocardial morphobiocytes
Single-photon emission CT	Accumulation of radiopharmaceutical in the myocardium during a single-photon emission CT with labeled leukocytes or citrate of gallium	Disturbance of myocardial perfusion during single-photon emission CT with Tc-tetrafosmin
MRI	Extracellular water detection with MRI of the heart with contrasting	Disturbance of myocardial perfusion during MRI of the heart with contrasting
Laboratory methods	Exceeds the norm of the test-degranulation of basophils, reveals the presence of cardiac antigen and antibodies to the myocardium, as well as a positive inhibition of migration of lymphocytes with cardiac antigen

Instrumental and laboratory methods of investigation make it possible to confirm the presence of myocarditis, however, negative results are not considered a criterion for excluding a diagnosis.

[27], [28], [29]

Differential diagnosis of myocarditis in children

In connection with the non-specificity of the clinical picture of myocarditis and the data of instrumental studies, the recognition of this disease in some cases presents a certain complexity and involves a large number of diagnostic errors. Therefore, when suspected of myocarditis, differential diagnosis becomes very important.

In detecting cardiomegaly and signs of myocardial dysfunction in neonates, posthypoxic syndrome of cardiovascular maladaptation, drug-induced morpho-functional damage to the myocardium, diabetic fetopathy, genetically determined pathology should be excluded.

In young children, first of all, it is necessary to differentiate myocarditis with congenital heart diseases, such as coarctation of the aorta, abnormal retraction of the left coronary artery from the pulmonary trunk, mitral insufficiency.

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

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

[30], [31]