Atrioventricular Septal Defect (Atrioventricular Canal): Clinical Guidelines

List of Abbreviations

AV – atrioventricular

AVSD – atrioventricular septal defect

BP – blood pressure

ACG – angiocardiography

SPH – severe pulmonary hypertension

LVOT – left ventricular outflow tract

CHD – congenital heart disease

IMV – invasive mechanical ventilation

IPMC – invasive pulmonary artery pressure monitoring

CT – computed tomography

LV – left ventricle

PDA – patent ductus arteriosus

PVR – pulmonary vascular resistance

VSD – ventricular septal defect

ASD – atrial septal defect

IVS – interventricular septum

IAS – interatrial septum

MRI – magnetic resonance imaging

NSAIDs – nonsteroidal anti-inflammatory drugs

RV – right ventricle

HF – heart failure

MODS - multiple organ dysfunction syndrome

ECG - electrocardiogram

EchoCG – echocardiography

Terms and Definitions

Partial (incomplete) form of atrioventricular septal defect - characterized by the presence of a primary interatrial communication without a ventricular septal defect and varying degrees of cleft anterior mitral valve leaflet.

Complete form of atrioventricular septal defect – characterized by the presence of a primary interatrial communication, a non-restrictive inlet ventricular septal defect, and a common atrioventricular valve.

Angiocardiography is an invasive diagnostic imaging method that involves the visualization of the heart chambers and blood vessels by administering a radiopaque agent into the bloodstream, directly measuring pressure in the heart chambers and blood vessels, obtaining blood samples from them to assess blood gas composition, and performing morphometric calculations based on the obtained radiopaque images of the cardiovascular system.

Eisenmenger syndrome - is a complication of long-standing, untreated large intra- and extracardiac shunts with an initial left-to-right direction of flow. The long-term persistence of such shunts leads to increased pulmonary vascular resistance and the gradual development of irreversible changes in the vessel wall structure, resulting initially in bidirectional blood flow at the level of these shunts, followed by unidirectional right-to-left shunting. Thus, deoxygenated venous blood enters the systemic circulation, leading to the appearance and progression of arterial hypoxemia. The diagnosis is established using echocardiography or cardiac catheterization. Eisenmenger syndrome develops only in the absence of surgical treatment and represents an irreversible condition. Treatment is conservative and palliative, aimed at prolonging duration and improving quality of life. The only possible surgical treatment option in the case of uncontrolled progression of irreversible pulmonary vascular changes remains heart-lung transplantation.

Muller procedure, pulmonary artery banding – is a palliative staged surgical intervention preceding radical correction, consisting of placing a band around the pulmonary artery trunk to reduce blood flow toward the pulmonary circulation, thereby preventing the development of irreversible pulmonary vascular changes and achieving a balance between the pulmonary and systemic circulations.

Hemi-Fontan procedure - so-called hemi-Fontan circulation is an intermediate type of hemodynamics between normal biventricular circulation and single-ventricle circulation according to Fontan. This intervention involves the creation of a bidirectional cavopulmonary anastomosis while maintaining antegrade blood flow into the pulmonary artery from the inferior vena cava system. This operation allows for unloading the right ventricle, reducing systolic overload, and preserving pulsatile pulmonary blood flow. Furthermore, the potential for growth of the right ventricle and tricuspid valve is preserved. The hemi-Fontan procedure is performed at 6–18 months of age. The indication for this type of surgery is a negative shunt and interatrial communication occlusion test, indicating that the right ventricle cannot provide complete cardiac output. However, it is capable of pumping blood in the volume of venous return from the inferior vena cava. After performing the bidirectional cavopulmonary anastomosis, blood from the superior vena cava is directed bypassing the right ventricle and right atrium directly into the pulmonary arteries.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Atrioventricular septal defect (AVSD) – is characterized by a deficiency or absence of septal tissue directly above and below the common atrioventricular valve in biventricular hearts [1]. Thus, both atria communicate with the ventricles through a single common valve, above which an interatrial defect remains, and below which an interventricular defect remains. This results in the so-called "complete form" of AVSD. In the presence of a small ventricular septal defect, the anomaly may assume a more "favorable" transitional form, and in the absence of the latter, the valves are conventionally divided into right and left portions, in which case the anomaly acquires an "incomplete" form (partial AVSD).

Synonyms: atrioventricular canal, atrioventricular septal defects, atrioventricular defects, persistent atrioventricular canal, endocardial cushion defect.

Morphological criteria of the anomaly [2-4]:

1. The defining characteristics of AVSD are a deficiency or absence of the atrioventricular septum, which leads to the appearance of a primary atrial septal defect (ASD) immediately above the common atrioventricular valve and a ventricular septal defect (VSD) in the inlet (basal) portion, immediately below the common atrioventricular valve.

2. A common morphological feature for all AVSD subtypes is the presence of a common atrioventricular valve located at the same level, regardless of the volume and dimensions of the heart chambers. The valve may have a single common orifice or be divided into two orifices due to the presence of bridging tissue segments.

3. Most commonly, the common atrioventricular valve is characterized by the presence of 5 or more leaflets (no more than 7 leaflets) with significant variability in the degree of commissure expression and leaflet dimensions.

4. The complete form of AVSD is characterized by the displacement of the left (mitral) portion of the common AV valve toward the left ventricular outflow tract.

5. The complete form of AVSD is characterized by shortening of the inlet and lengthening and narrowing of the left ventricular outflow tract with anterior and rightward displacement of the aortic root.

6. Patients with partial AVSD exhibit a normal length of the interatrial septum, and the primary ASD is a consequence of the absence of only a small segment of the interatrial septum combined with tissue deficiency of the inlet VSD.

Associated anomalies [3,5]:

• most commonly, AVSD is combined with a secondary atrial septal defect (ASD) in 11 to 21%

• the second most frequent associated CHD combined with AVSD is the presence of a patent ductus arteriosus (up to 10%)

• Tetralogy of Fallot (up to 6.5%)

• unroofed coronary sinus combined with a persistent left superior vena cava (up to 3%)

• situs ambiguus (до 2.5%)

• double outlet right ventricle without pulmonary stenosis (up to 2%)

• additional muscular ventricular septal defect (up to 1.5%)

• double outlet right ventricle with pulmonary stenosis (up to 1%)

• situs inversus totalis (до 1%)

• total anomalous pulmonary venous return (up to 1%)

• left ventricular outflow tract obstruction (up to 0.6%)

• transposition of the great arteries (up to 0.3%)

Regarding extracardiac pathology, the combination of AVSD with Down syndrome is most frequently noted. Furthermore, the combination with Down syndrome occurs most commonly in the complete form of atrioventricular septal defect with large septal defects (up to 75%) and rarely occurs in the partial form of AVSD (less than 5%). The combination of AVSD and Down syndrome is not characterized by obstructive left heart pathology, but rather is characterized by increased pulmonary resistance with a tendency to develop pulmonary hypertension [6,7].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

During embryogenesis, the interatrial and interventricular septa develop toward each other. During the same period, there is growth of the endocardial cushions at the border of the atria and ventricles in a plane perpendicular to the growth of the intracardiac septa. These endocardial cushions also grow toward each other, which ultimately should lead to the hemodynamic separation of the right and left halves of the heart and the formation of two atrioventricular valves (the right - tricuspid and the left – mitral) at the border between the atria and ventricles, which normally allow blood to pass only in the direction from the atria to the ventricles of the heart. Thus, impaired development of the endocardial cushions can lead to a spectrum of anomalies characterized by impaired separation of the right and left halves of the heart and the formation of two separate atrioventricular valves. Depending on the size of the primary ASD and inlet VSD, these defects form a group of atrioventricular septal defects.

The main pathophysiological changes are due to left-to-right blood shunting caused by atrioventricular septal defects. When a large (non-restrictive) ventricular septal defect is present (complete AVSD), the left-to-right shunt is significant. This causes the pressure in the right ventricle and pulmonary artery to approach or equal systemic pressure. Against this background, pulmonary vascular resistance increases rapidly, and by the age of 6 to 12 months, and sometimes earlier, irreversible changes in the walls of the pulmonary circulation vessels begin to develop (irreversible pulmonary hypertension). In the presence of severe common AV valve regurgitation (up to 15% of patients with complete AVSD), the volume overload of the heart ventricles increases significantly (furthermore, right ventricular overload is usually much more pronounced than that of the LV).

In partial AVSD, the shunt is located only at the atrial level (the shunt is usually large, but sometimes may be moderate or even negligible). In such situations, the risk of developing irreversible pulmonary vascular changes is significantly lower than when a VSD is also present simultaneously, and even if irreversible vascular changes do develop, this requires a significantly longer time interval than in complete AVSD. In partial AVSD, the severity of the condition also depends on the presence and degree of regurgitation at the left component of the common AV valve. With severe regurgitation (10-15% of patients with partial AVSD), the left-to-right shunt increases and often the regurgitant jet is directed straight from the LV into the right atrium, which leads to an increase in the stroke volume of the left and right ventricles, and consequently, to the development of marked cardiomegaly and heart failure at an early age. One of the main causes of regurgitation is cleft formation between the upper and lower left leaflets of the mitral component of the common AV valve extending down to the base of the fibrous annulus. With such localization of the cleft, the regurgitant flow is usually directed straight into the right atrium, leading to its significant enlargement. Although the exact mechanism of AV valve regurgitation is often unclear and varies considerably depending on the number, size, and configuration of the leaflets and the features of subvalvular apparatus attachment of the common valve.

When AVSD is combined with severe right ventricular outflow tract obstruction or pulmonary valve stenosis, the development of pulmonary hypertension is uncharacteristic [8-11].

1.3 Epidemiology of the Disease or Condition

AVSD occurs in approximately 1 to 3 per 10⁴ newborns, accounting for 3-6% of all congenital heart defects. Despite the fact that isolated AVSD is a non-critical CHD, in 3-5% of patients surgical treatment may be required in the first weeks of life upon the development and progression of severe heart failure against the background of volume overload predominantly affecting the right heart chambers. In 75% of patients with AVSD, CHD is combined with Down syndrome [11-14].

1.4 Features of Coding the Disease or Condition

Q21.2 – Atrioventricular septal defect

1.5 Classification of the disease or condition

Depending on the degree of underdevelopment of the septa and AV valves of the heart, three forms are distinguished:

1. Incomplete (partial) form of AVSD – characterized by the presence of a ostium primum atrial septal defect and varying degrees of cleft formation in the anterior leaflet of the mitral valve.

2. Intermediate form of AVSD – characterized by the presence of two separate atrioventricular valves combined with a cleft of the anterior mitral leaflet, an ostium primum ASD, and usually a restrictive inflow VSD.

3. Complete form – characterized by the presence of an ostium primum atrial septal defect, an inflow non-restrictive ventricular septal defect, and a single atrioventricular valve [15,21].

Depending on the degree of ventricular development, the following are distinguished:

1. Balanced form – AVSD with two adequately sized and developed ventricles.

2. Unbalanced form – AVSD in which one of the ventricles is significantly smaller than the other, while the ventricular size is still considered sufficient to perform biventricular hemodynamic correction (long-axis LV/RV ratio > 0.65). An unbalanced form of AVSD in which the ventricular imbalance is pronounced (long-axis LV/RV ratio of 0.45-0.65 and/or right AV valve area to left AV valve area ratio < 0.5) precludes the possibility of biventricular correction. Unbalanced AVSD occurs in 7-10% of patients with AVSD. Furthermore, in 2/3 of cases, the right ventricle is dominant [15,74-75].

Rastelli classification of complete AVSD (based on the morphology of the anterior bridging leaflet) [16]:

Type A (about 69%): the anterior bridging leaflet is divided over the interventricular septum into two approximately equal parts: a mitral portion over the left ventricle and a tricuspid portion over the right ventricle. The division of the common bridging leaflet into left and right components is due to uniform attachment to the crest of the interventricular septum by chordae over a considerable length; the ventricular septal defect is located immediately below the plane of the annulus.

Type B (up to 9%): characterized by abnormal chordal attachment from the papillary muscles in the right ventricle to the surface of the mitral portion of the anterior bridging leaflet, leading to an uneven division of the common bridging leaflet into mitral and tricuspid components.

Type C (about 22%): characterized by the fact that the anterior bridging leaflet is not divided into portions and floats freely over the VSD due to the absence of chordal attachment to the crest of the interventricular septum.

1.6 Clinical presentation of the disease or condition

The clinical presentation in medically untreated patients with AVSD depends on the morphological and functional features of the defect.

In partial AVSD combined with mild left AV valve regurgitation and the absence of severe associated cardiac anomalies, the clinical presentation is similar to that of patients with ASD and rarely manifests before 1 year of life. Irreversible development of high pulmonary vascular resistance (high pulmonary hypertension [HPH]) develops only in a small number of patients, typically at the age of 20-40 years. Symptomatic deterioration in these patients is often associated with the onset of atrial fibrillation against the background of persistent volume overload and rarely occurs at an age younger than 18-20 years [8,11,17].

Patients with partial AVSD and moderate to severe left AV valve regurgitation are characterized by the absence or minor degree of left atrial overload and rare development of pulmonary venous hypertension, but due to a significant left-to-right blood shunt, they typically exhibit a marked increase in pulmonary artery pressure. Consequently, 20% of such patients already show serious symptoms in infancy (signs of pulmonary circulation overload, signs of progressive heart failure), and without surgical treatment, many of them will die in the first decade of life [8,11].

Patients with complete AVSD are characterized by an even more unfavorable disease course. Without surgical intervention, the majority of patients in this group die within the first 3-5 years of life. The main cause of death in the natural course of the disease is the rapid development and progression of high pulmonary hypertension. In the first two years, provided there is no surgical intervention, children's clinical picture is dominated by signs of progressive heart failure with recurrent pulmonary infections. These clinical manifestations are often exacerbated by the presence of moderate to severe AV valve regurgitation in 60% of patients in this group. If children survive this period, the dominant factors determining the severity of the condition become the progression of regurgitation on the common AV valve and the progression of irreversible HPH [3,7,8,18].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria

Symptoms:

• dyspnea;

• frequent respiratory infections;

• poor weight gain;

• sweating during feeding;

• refusal to breastfeed;

• palpitations.

Anamnesis: prenatal diagnosis of congenital heart disease.

Physical examination:

• tachycardia;

• dyspnea;

• hepatomegaly;

• cyanosis of varying degrees – upon the development of pulmonary hypertension or the combination of AVSD with other CHDs;

• systolic murmur of varying intensity, accentuation of the second heart sound over the pulmonary artery. As pulmonary hypertension progresses, the systolic murmur may become quieter.

Laboratory tests: do not provide characteristic information for AVSD.

Instrumental Studies:

Chest X-ray:

• cardiomegaly of varying degree;

• increased pulmonary vascular markings and bulging of the pulmonary artery segment.

ECG:

• left axis deviation;

• biatrial overload;

• signs of right ventricular hypertrophy rsR’ or RSR’.

Echocardiography:

• visualization of an ostium primum atrial septal defect;

• intact interventricular septum in the incomplete form, restrictive ventricular septal defect in the intermediate form, or a large inflow VSD in the complete form of AVSD;

• determination of AV valve morphology (number of fibrous annuli and their size);

• visualization of cleft formation in the mitral component leaflet;

• ventricular size ratio (in cases of unbalanced AVSD).

2.1 Complaints and Anamnesis

• All patients with AVSD are recommended to undergo a detailed history taking and symptom assessment in order to determine the severity of the condition [4,8,11,19-21].

Level of evidence 5 (grade of recommendation C).

Comments: 1) Patients with AVSD without a VSD (partial AVSD) and minimal insufficiency of the left component of the AV valve typically present with no symptoms in the first decade of life. Sometimes the asymptomatic period can last significantly longer than the first decade of life, extending into the third or even the fourth decade. The clinical presentation is virtually identical to that of patients with an ASD, except that an apical systolic murmur may be auscultated in the presence of mild left AV valve regurgitation. 2) Patients with partial AVSD and moderate to severe left AV component regurgitation most frequently develop symptoms earlier (usually between one and two years of age), and progressive severe heart failure may often require treatment in infancy. In addition to the usual signs characteristic of ASD, this group of patients is characterized by a prominent apical pansystolic murmur; tachypnea and hepatomegaly are also frequently observed. 3) Clinical manifestations and symptoms in patients with complete AVSD typically appear within the first year of life (often during the first months of life) and are caused by manifestations of progressive severe heart failure (signs of heart failure (HF) in children with AVSD include shortness of breath at rest or during exertion (crying, feeding), tachycardia, hepatomegaly, diaphoresis, poor appetite, failure to gain weight, and delayed physical development in the absence of other urgent conditions). Heart failure is usually difficult to control with conservative therapy. This leads to worsening tachypnea, impaired peripheral perfusion, and developmental delay. Occasionally, heart failure is minimal in early life, and its initial manifestation and progression may only be noted after one year of age, driven not by volume overload of the heart chambers, but by the development of severe pulmonary vascular disease and even Eisenmenger syndrome [4,8,11,19-23].

2.2 Physical Examination

• All patients with AVSD undergoing physical examination are recommended to be evaluated for dyspnea, tachycardia, hepatomegaly, and diaphoresis to determine the presence and severity of HF [8,11].

Level of evidence 5 (grade of recommendation C).

Comments: the clinical presentation after birth can vary significantly depending on the size of the intracardiac shunts (VSD and ASD) as well as the degree of regurgitation of the common AV valve's left component. Patients with large shunts and severe left AV valve regurgitation almost always present with signs of HF (tachycardia; dyspnea; hepatomegaly; diaphoresis). In severe heart failure, multi-organ failure (MOF) rapidly develops; therefore, the progression of heart failure is an indication for hospitalization and transfer to a cardiac surgery unit to determine further management strategy.

• All patients with suspected AVSD undergoing cardiac auscultation are recommended to be assessed for the presence of murmurs in order to evaluate the severity of regurgitation at the atrioventricular valves (components) [8,11].

Level of evidence 5 (grade of recommendation C).

Comments: the following auscultatory pattern is characteristic (though not pathognomonic) of AVSD: the second heart sound is split and accentuated due to elevated pulmonary artery pressure. A systolic murmur is heard over the entire precordium and increases in intensity at the apex, particularly in the presence of severe left AV valve regurgitation.

2.3 Laboratory Diagnostics

• All hospitalized patients with AVSD are recommended to undergo blood gas and acid-base analysis (pH, BE, pCO2, PO2, Lac — capillary/arterial/venous blood sample) to assess the severity of hypoxemia and the extent of metabolic disturbances [22-24].

Level of evidence 5 (grade of recommendation C).

• All patients with AVSD are recommended to undergo a complete blood count (CBC) with hemoglobin, hematocrit, erythrocyte, leukocyte, and platelet counts, as well as an erythrocyte sedimentation rate (ESR) test as part of the initial evaluation, during follow-up at least once a year, upon hospital admission, and when indicated in the pre- and/or postoperative period in case of surgical treatment [8,11,115].

Level of evidence 5 (grade of recommendation C)

Comments: performing a complete blood count in all patients with AVSD during dispensary follow-up and prior to surgical treatment is important for detecting and timely correcting anemia. In patients with decreased hemoglobin and hematocrit levels, further testing of serum iron, serum ferritin, transferrin, and total iron-binding capacity is advisable for the timely correction of iron deficiency states, which can affect the clinical and functional status and the disease course [116].

• Prior to surgical intervention, all patients with AVSD are recommended to undergo coagulation testing (screening hemostasis assay) (activated partial thromboplastin time, prothrombin time, prothrombin index, plasma fibrinogen, antithrombin III activity, and international normalized ratio [INR]) to predict the risk of intra- and postoperative bleeding [8,11].

Level of evidence 5 (grade of recommendation C)

• Prior to surgical intervention, all patients with AVSD are recommended to undergo ABO blood grouping, Rh factor (D antigen) testing, C, c, E, e, Cw, K, k phenotype determination, screening for red blood cell antibodies, testing for hepatitis B surface antigen (HBsAg) in blood, hepatitis C virus antibody testing, Treponema pallidum antibody testing, human immunodeficiency virus (HIV-1) IgM/IgG antibody testing, and human immunodeficiency virus (HIV-2) IgM/IgG antibody testing to rule out associated HIV infection and hepatitis [8,11,115].

Level of evidence 5 (grade of recommendation C)

• All patients with AVSD during their initial examination, upon hospital admission, when undergoing surgical intervention (as needed in the pre- and/or postoperative period), and at least once a year during follow-up visits, are recommended to undergo a general biochemical blood panel (testing for potassium, sodium, chlorides, glucose, creatinine, total protein, albumin, urea, total bilirubin, direct and indirect bilirubin, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) to assess renal and hepatic function and blood electrolyte levels [8,11,115-117].

Level of evidence 5 (grade of recommendation C)

Comments: additionally, especially when associated with Down syndrome, it may be required to measure free triiodothyronine (free T3), free thyroxine (free T4), and thyroid-stimulating hormone (TSH) in the blood, as well as serum C-reactive protein, to assess thyroid function and rule out inflammation [8, 11, 115-117].

• Patients with AVSD and signs of HF are recommended to undergo N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing as part of the initial evaluation for mortality risk stratification, as well as when indicated in the pre- and/or postoperative period in case of surgical treatment [115-118,123].

Level of evidence 5 (grade of recommendation C)

2.4 Instrumental Diagnostics

• All patients with suspected congenital heart disease, and specifically AVSD, are recommended to undergo four-limb pulse oximetry [24,25,81-83].

Level of evidence 2 (grade of recommendation B).

Comments: decreased saturation is not characteristic of AVSD in an uncomplicated course of the defect. A symmetrical decrease in saturation in the upper and lower limbs is usually observed with a significant increase in pulmonary vascular resistance (complicated course with the development of PAH), when the pressure in the right side of the heart begins to exceed that in the left, which leads to the entry of venous blood into the aorta and, consequently, to the appearance of arterial hypoxemia. If there is a difference in blood oxygen saturation of more than 3% between the upper and lower limbs, it is necessary to rule out or confirm the presence of associated pathology (PDA, aortic coarctation).

• In all patients with AVSD, as part of the initial examination, upon admission to the hospital, in case of surgical treatment if necessary in the pre- and/or postoperative period, and also at least once a year at a follow-up visit during dynamic observation, it is recommended to perform targeted chest X-ray to exclude infiltrative changes in the lungs [8,11].

Level of Evidence 5 (Grade of Recommendation C).

Comments: in case of moderate or severe regurgitation of the left component of the common AV valve, chest radiography usually reveals pronounced cardiomegaly with signs of enlargement of the left and right ventricles, right atrium, as well as marked pulmonary plethora. In the complete form of AVSD in infants and newborns with heart failure, cardiomegaly and pulmonary plethora are also frequently observed. If a patient with complete AVSD has not been operated on in a timely manner, they may develop pulmonary hypertension disease. This condition on a plain chest radiograph is characterized by the fact that the heart size is slightly increased, and the main changes affect the pulmonary circulation vessels: the central pulmonary arteries are markedly dilated in combination with a sharp attenuation of the peripheral pulmonary pattern (distal lung fields are translucent).

• All patients with AVSD are recommended to undergo a 12-lead electrocardiogram (ECG) recording, decoding, description, and interpretation, both at the initial visit and during follow-up monitoring, as well as when needed in cases of surgical treatment in the pre- and postoperative periods, to detect rhythm and conduction disorders, right atrial and right ventricular hypertrophy, and axis deviation, which may be caused by right atrial hemodynamic overload or developmental (topographical) abnormalities of the cardiac conduction system [26-29,84].

Level of Evidence 4 (Grade of Recommendation C).

Comments: provided there are no rhythm disturbances according to electrocardiography data, characteristic but non-pathognomonic changes can also be detected, namely: signs of marked hypertrophy of the right (rsR’ or RSR’) and less frequently the left ventricle, prolongation of the PR interval and left axis deviation are frequently noted [26-29,84].

• Patients with AVSD and concomitant rhythm and/or conduction disturbances are recommended to undergo 24-hour Holter monitoring to clarify the nature and features of the latter, and if necessary, to select therapy [119-120,124-126].

Level of Evidence 5 (Grade of Recommendation C).

• All patients with AVSD at the initial appointment, in case of surgical treatment and if necessary in the pre- and/or postoperative period, are recommended to undergo transthoracic echocardiography (TTE) combined with Doppler mode [8,11,24,30-35, 85-88].

Level of Evidence 3 (Grade of Recommendation B).

Comments: two-dimensional echocardiography, especially in combination with Doppler mode, in the vast majority of cases provides complete information on the morphological features of the defect. It allows for highly accurate assessment of the size and localization of AV septal defects, the degree of ventricular imbalance in case of rightward or leftward shift of the interventricular septum, and evaluation of the morphology of the common AV valve and the degree of insufficiency of the right and left components (in the four-chamber view).

AVSD is characterized by the location of the left and right AV valves at the same level. Based on the echocardiographic results, the presence, degree of elongation, and deviation of the septal leaflet towards the left ventricular outflow tract can be identified in combination with an abnormal position of the aortic valve (AVSD is typically characterized by an upward and anterior displacement of the aortic valve relative to the left component of the AV valve). Echocardiography also allows assessing the nature and localization of chordal attachments and the number of AV valve leaflets. The limitations of echocardiography include low diagnostic accuracy in cases of double-orifice left component of the common AV valve and the inability to quantitatively assess pulmonary vascular resistance and pulmonary vascular reactivity.

• All patients with AVSD are recommended to determine the relative size of the right and left ventricles at the preoperative evaluation stage [8,41-43].

Level of Evidence 5 (Grade of Recommendation C).

Comments: severe hypoplasia of either ventricle must be detected before surgery, because such hypoplasia reduces the likelihood of successful anatomical (radical) correction.

• Transesophageal echocardiography is recommended for patients with AVSD when transthoracic echocardiography is insufficiently informative or for a detailed assessment of the valve apparatus and septal defects, ruling out infective endocarditis, as well as intraoperatively during surgical treatment to evaluate the results of reconstructive surgery and, if necessary, in the pre- and postoperative periods [8,11,24,30-35, 41-43, 85-88].

Level of Evidence 5 (Grade of Recommendation C).

Comments: Transesophageal echocardiography should not be used for routine or follow-up evaluation in patients with AVSD when transthoracic echocardiography visualization is adequate.

• Patients with AVSD under the age of 3–6 months, provided all necessary data on the morphological features of congenital heart disease are obtained via echocardiography and there is no evidence of PAH, are not recommended to additionally undergo transvenous cardiac catheterization with radiopaque contrast administration and measurement of pressures in the heart chambers and pulmonary artery [36-38].

Level of Evidence 4 (Grade of Recommendation C).

Comments: Left ventriculography (LVG) makes it possible to determine the direction and severity of blood shunting at the heart chamber level, provided an ASD and VSD are present. This study also makes it possible to determine the pressure in the right ventricle, left ventricle, aorta, and pulmonary artery, and to calculate total pulmonary and systemic vascular resistance. With high-quality studies, the leaflets of the left AV valve can be visualized in motion, which allows determining the degree, exact location, and mechanism of valvular regurgitation. However, at present, LVG is required only when AVSD is combined with other complex cardiac anomalies, and when the question of patient operability arises due to the presence of direct or indirect signs of severe pulmonary vascular hypertension [36-39].

• Invasive pulmonary artery pressure monitoring (IPAPM) with pharmacological tests is recommended for patients with AVSD older than 6 months in the presence of data on high pulmonary hypertension to determine the reversibility of pulmonary vascular disease and patient operability [40] + (see "Clinical guidelines for the management of patients with pulmonary arterial hypertension").

Level of Evidence 5 (Grade of Recommendation C).

Comments: during catheterization, the following direct parameters must be determined: pulmonary and systemic arterial pressure (systolic, diastolic, and mean), right atrial and right ventricular pressure, and pulmonary artery wedge pressure. The main purpose of invasive pulmonary artery pressure monitoring (IPAPM) with pharmacological tests is to determine the feasibility and choose the method of surgical treatment (radical or palliative) in patients with precapillary PAH.

2.5 Other Procedures

• In cases where echocardiographic data are insufficient to verify all morphological features of the defect or when AVSD is combined with left heart obstructive pathology, patients are recommended to undergo contrast-enhanced computed tomography of the heart and vessels or contrast-enhanced magnetic resonance imaging of the heart [44-45, 89-91].

Level of Evidence 4 (Grade of Recommendation C).

Comments: MRI and CT help to clarify the morphology of the defect, determine the spatial relationship of the cardiac structures and great vessels, and are also important for diagnosing concomitant intracardiac/extracardiac malformations. In addition, tomographic techniques are used in borderline sizes of the left heart chambers, which allows clarifying the feasibility of biventricular repair and surgical management in this group of patients.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

• In infants with AVSD and manifestations of heart failure, it is recommended to implement: energy expenditure restriction (patient sedation), respiratory support if necessary, inotropic therapy, adequate volume loading (fluid administration in a volume less than physiological requirements), and diuresis stimulation [11,21,46-47].

Level of Evidence 5 (Grade of Recommendation C).

Comments: among adrenergic and dopaminergic agents, dopamine** or #dobutamine** is preferred (starting at doses of 2-2.5 mcg/kg/min with subsequent titration to achieve the desired effect); if the aforementioned drugs are insufficiently effective, additional administration of #epinephrine** is required (at a starting dose of 0.01 mcg/kg/min with subsequent titration under blood pressure and blood gas monitoring to achieve the desired effect) [92,95,127-129]; with prolonged administration of #epinephrine** (more than 3-6 hours) at doses exceeding 0.05 mcg/kg/min, it is optimal to supplement therapy with an infusion of nitroprusside derivatives that have a systemic vasodilating effect (sodium nitroprusside dihydrate at an initial dose of 0.3 mcg/kg/min with subsequent titration under blood pressure and blood gas monitoring to achieve the desired effect) or to prescribe an infusion of #levosimendan** [92-94] (which belongs to other cardiotonic agents and additionally possesses vasodilating action) at a rate of 0.05-0.2 mcg/kg/min [92-94,127-129].

Level of evidence 5 (grade of recommendation C).

• In patients with AVSD presenting with severe desaturation (below 80% according to pulse oximetry), it is recommended to administer supplemental oxygen [11,21,95-96].

Level of Evidence 5 (Grade of Recommendation C).

Comments: stable patients with AVSD whose peripheral blood oxygen saturation is above 85-90% are not indicated for supplemental oxygen therapy, because oxygen contributes to a decrease in pulmonary vascular resistance, which leads to a redistribution of blood flow toward the pulmonary circulation and, consequently, a decrease in systemic output and blood pressure. However, in extremely severe cases (most often in the presence of concomitant respiratory pathology or associated CHD) and low blood saturation, supplemental oxygen therapy may be administered to such patients to stabilize their condition and during transportation to a specialized cardiosurgical hospital.

• In newborns with AVSD without signs of heart failure, provided there is no severe pulmonary hypertension, it is not recommended to prescribe additional therapy except for diuretics during the pre-operative observation stage [11,21,46-48,97].

Level of evidence 5 (grade of recommendation C).

Comments: upon the appearance of signs of right heart overload (according to echocardiography or ECG), the drug of choice among diuretics is #spironolactone**, which is prescribed at a dose of 2-3.5 mg/kg/day in 2 divided doses. The second-line drug is #furosemide**, which is prescribed at an initial dose of 1-6 mg/kg/day in 2-4 divided doses with subsequent dose titration if necessary [92,98].

• Upon the development and progression of an infectious complication in patients with AVSD at the pre-operative or post-operative stage (which is frequently characteristic of patients with CHD), it is recommended to immediately initiate antibacterial therapy [11,77, 99, 112-114,130].

Level of evidence 5 (grade of recommendation C).

• In cases of residual pulmonary hypertension in children who underwent radical correction of AVSD, it is recommended to use antihypertensive agents for the treatment of pulmonary arterial hypertension (#bosentan**, prescribed at a dose of 3 mg/kg/day in infants and young children, or bosentan** in adolescents and adults according to the instructions) [100-101] and antiplatelet agents other than heparin/heparin group [11,24,40,46,102] + (see "Clinical guidelines for the management of patients with pulmonary arterial hypertension").

Level of Evidence 4 (Grade of Recommendation C).

• In patients with AVSD older than 6 months with severe pulmonary hypertension and a negative acute vasodilator test result who have contraindications to surgical treatment due to the irreversible nature of pulmonary vascular disease, it is recommended to administer medical therapy for pulmonary hypertension (antihypertensive agents for pulmonary arterial hypertension and antiplatelet agents other than heparin/heparin group) [8,11,21,24,40,46-49] + (see "Clinical guidelines for the management of patients with pulmonary arterial hypertension")

Level of evidence 5 (level of recommendation C).

3.2 Surgical Treatment

The presence of an atrioventricular septal defect is an indication for surgical treatment.

Surgical treatment of atrioventricular septal defects aims to: close the atrial communication, which is almost always present; close the ventricular communication, if present; prevent damage to the AV node and bundle of His; and create two competent AV valves without hemodynamically significant stenosis [8,50].

Several surgical correction techniques exist: two-patch AVSD repair, single-patch AVSD repair, and modified single-patch AVSD repair. The choice of method depends on the surgeon's preference and experience [8,50-56].

Two-patch AVSD repair: correction consists of closing the VSD with one patch (the patch is sewn to the right side of the interventricular septum crest using a continuous running suture) and the ASD with a second patch, dividing the common AV valve into two valves and, if necessary, performing left AV valve repair to eliminate cleft anterior leaflet [50-54].

Single-patch AVSD repair: correction using a single patch differs from the two-patch technique in the following features: a xenopericardial patch is almost always used in this method; it is very important to adjust the level of leaflet attachment on the patch to the level of the fibrous ring and to suture the bridging (superior and inferior) leaflets directly to the patch [50-54].

Modified single-patch AVSD repair: the advantages of this approach are the exclusion of one of the patches (for VSD closure) from the repair process and direct suturing of the bridging leaflets to the interventricular septal crest, which eliminates the need to divide the valve leaflets or chordae into two components and significantly reduces the total operation time. The downside is that this technique is applicable (does not lead to significant residual AV valve regurgitation) only in small inlet VSDs [55-56].

• In all patients with complete AVSD, severe heart failure, and rapidly developing pulmonary hypertension, surgical intervention is recommended to be performed in early infancy [8,11,21,48-59].

Level of Evidence 4 (Grade of Recommendation C).

• In patients with AVSD with severe signs of heart failure refractory to conservative treatment, emergency surgical care is recommended, which (if necessary) may be preceded by a limited scope of conservative therapy measures aimed at stabilizing and compensating the patient's clinical condition [8,11,21,48-59,103].

Level of evidence 4 (level of recommendation C).

• In all patients with complete AVSD without severe heart failure and rapidly developing pulmonary hypertension, primary radical correction is recommended at the age of 3-6 months (depending on clinical severity) [8,11,21,48-59].

Level of Evidence 4 (Grade of Recommendation C).

Comments: up to 1-2 months of age, total pulmonary vascular resistance (PVR) remains elevated, which limits pulmonary blood flow and prevents the development of pulmonary hypertension and severe symptoms of heart failure. Thereafter, PVR progressively decreases, and by the age of 6 months, severe forms of pulmonary hypertension may already develop.

Radical correction includes closure of the atrial and ventricular defects with division of the common AV valve and repair of its mitral and tricuspid components.

• In patients with AVSD, it is not recommended to perform pulmonary artery banding (Muller operation) as a first stage. Exceptions are made for small children in extremely critical condition (children with aortic arch pathology, severe circulatory failure, and severe pulmonary hypertension in the early neonatal period) in whom the risk of radical correction is extremely high [8,21,58-61,106].

Level of Evidence 4 (Grade of Recommendation C).

Comments: pulmonary artery banding allows these children to gain a delay to address previously identified high-risk factors for the failure of radical CHD correction, and then perform radical defect correction as a second stage at the age of 6-18 months.

• In patients with partial AVSD and moderate left AV valve regurgitation, it is recommended to perform a single-stage primary radical intervention at the age of 1 to 2 years [8,11,21,50-59,62-64].

Level of Evidence 4 (Grade of Recommendation C).

Comments: Radical correction of the defect in this case involves the closure of the primary ASD and mitral valve annuloplasty/repair.

• Patients with partial AVSD and significant left AV valve regurgitation are recommended to undergo a single-stage primary radical intervention at an earlier age (preferably under 6–12 months of age, depending on the patient's clinical status) [8,11,21,50-59, 62-64].

Level of Evidence 4 (Grade of Recommendation C).

• Patients with intermediate AVSD are recommended to undergo surgical intervention within the first year of life, with the timing depending on the VSD size and the severity of heart failure [8,11,21,50-59,62-64].

Level of Evidence 4 (Grade of Recommendation C).

• Patients with AVSD and severe morphological anomalies of the mitral component of the common AV valve (leaflet hypoplasia, double-orifice valve, parachute-like valve, etc.) are recommended to undergo a valve-sparing plastic repair as the first stage [8,11,50-51,53-54,65-70].

Level of Evidence 4 (Grade of Recommendation C).

• In case of an unsuccessful valve-sparing repair (persistence of significant regurgitation following the procedure), it is recommended to perform replacement of the mitral component of the common AV valve (mechanical bileaflet mitral valve prosthesis***) [8,11,50-51,53-54,65-70].

Level of Evidence 4 (Grade of Recommendation C).

• Patients with unbalanced AVSD and a long-axis LV/RV ratio greater than 0.65 are recommended to undergo single-stage biventricular radical correction of congenital heart disease [21,71-76].

Level of evidence reliability 2 (grade of recommendation strength A).

• Patients with unbalanced AVSD and a long-axis LV/RV ratio of 0.45–0.65 (or a right AV valve area to left AV valve area ratio of less than 0.5) are recommended to undergo one-and-a-half ventricular repair of congenital heart disease [8,21,71-76].

Level of Evidence 4 (Grade of Recommendation C).

• Patients with unbalanced AVSD not suitable for biventricular or one-and-a-half ventricular repair are recommended to undergo staged hemodynamic correction, including pulmonary artery banding in the neonatal period, bidirectional cavopulmonary anastomosis (Glenn procedure) at 4–8 months of age, and subsequently total cavopulmonary anastomosis (Fontan procedure) at 3–4 years of age [21,71-76].

Level of Evidence 4 (Grade of Recommendation C).

• Surgery is contraindicated (not recommended) in patients with AVSD and the sclerotic form of pulmonary vascular disease (especially upon the development of Eisenmenger syndrome) [8,11,21,50-59,77-78].

Level of evidence 5 (grade of recommendation C).

3.3. Other treatment

No.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Patients following surgical correction of AVSD are recommended to avoid traction loads on the upper extremities for the subsequent 4–6 months of life [11,22].

Level of evidence 5 (grade of recommendation C).

• Infants following surgical correction of AVSD are recommended to avoid therapeutic exercise procedures for the subsequent 2–4 months [11,22].

Level of evidence 5 (grade of recommendation C).

• Patients with serious clinical issues (pronounced AV valve regurgitation, residual pulmonary hypertension, arrhythmias, etc.) are recommended to restrict physical activity [11,104-105].

Level of evidence 5 (grade of recommendation C).

Comments: Recommendations for sports participation, if possible, are individual in nature. However, excessive physical exertion should be avoided.

• A patient with a complicated postoperative course (circulatory failure, infectious complications, repeated surgical interventions during a single hospitalization) is recommended to undergo rehabilitation in a specialized cardiological medical facility within 6 months after surgical correction of AVSD under cardiopulmonary bypass [121].

Level of evidence 5 (grade of recommendation C).

Comments: Following radical correction of the defect, the following conditions may occur: most commonly mitral valve (component) regurgitation, and less commonly tricuspid valve (component) regurgitation. In such cases, reoperation is indicated for hemodynamically significant regurgitation. Rhythm and conduction disorders (ventricular and supraventricular arrhythmias, bundle branch block, atrioventricular blocks, and sudden cardiac death) may occur both immediately after surgical correction and in the long-term postoperative period.

• Patients with an uncomplicated postoperative course are not recommended to restrict physical activity 2–4 months after radical correction of congenital heart disease [11].

Level of evidence 5 (grade of recommendation C).

Comments: Most patients who underwent surgery for AVSD with an uncomplicated postoperative course experience no restrictions in daily activities. In the majority, exercise tolerance is at a subnormal level, which does not affect their quality of life and lifestyle; therefore, there is no need to restrict physical activity in this group of patients.

5. Prevention and Dispensary Observation

The prognosis after surgical correction of AVSD is favorable provided timely correction of congenital heart disease is performed. Life expectancy and physical performance may be limited in the presence of iatrogenic or residual complications [121-122].

• All operated patients with AVSD are recommended dispensary follow-up by a pediatric cardiologist until the age of 18, and by a cardiologist/general practitioner (family physician) , therapist after the age of 18 to determine the frequency of visits, monitor compliance with prescribed recommendations, timely modify therapy, assess the risk of cardiovascular complications, and refer for additional studies or hospitalization if necessary [11,24,48,69,79].

Level of Evidence 4 (Grade of Recommendation C).

Comment: During the first month after hospital discharge, weekly medical examinations are necessary, and more frequent examinations are indicated clinically. In the first 30 days post-discharge, pericardial effusion and cardiac tamponade may appear, which must be monitored clinically and using two-dimensional echocardiography.

Level of evidence 5 (grade of recommendation C).

• During the first month after hospital discharge, all operated patients are recommended weekly, or more frequently as indicated, examinations by a pediatric cardiologist/cardiologist with an echocardiogram and electrocardiogram (ECG) [11,104-105].

Level of Evidence 5 (Grade of Recommendation C).

Comments: The frequency of dispensary follow-up by a pediatric cardiologist and cardiologist is at one month, 3, 6, and 12 months after surgery. The dispensary follow-up includes ECG and echocardiography, as well as pulse oximetry if necessary. Subsequent follow-up of patients is carried out at intervals of 3–36 months until the age of 18, after which the patient transitions to the adult outpatient clinic, where they continue to be monitored annually by a cardiologist, general practitioner (family physician), or therapist [11,104-105, 121-122].

• All patients with AVSD and concomitant rhythm and/or conduction disorders are recommended to undergo 24-hour Holter monitoring of heart rhythm and, if necessary, selection and adjustment of therapy once a year [119-120, 124-126].

Level of Evidence 5 (Grade of Recommendation C).

Comments: Holter ECG monitoring is necessary to exclude cardiac arrhythmias, which are common in AVSD, the most severe of which is complete atrioventricular block. Approximately 30–50% of patients have clinical symptoms of arrhythmias.

For patients with short runs of ventricular tachycardia without hemodynamic impairment, specific treatment is generally not performed, or medications that suppress ectopic activity (beta-blockers) are prescribed.

Patients with syncopal or presyncopal conditions receive more "aggressive" treatment. This includes antiarrhythmic therapy and implantable cardioverter-defibrillators***, which is the only method for preventing sudden cardiac death in this category of patients.

In patients with atrial re-entry tachycardia after radical correction, conservative treatment has low efficacy; all such patients require intracardiac electrophysiological study and radiofrequency ablation.

High degrees of atrioventricular block require the implantation of a pacemaker***.

• All patients following surgical correction of AVSD are recommended to undergo examinations at least twice a year during the first year after surgery (the exact timing and frequency of examinations are determined by the cardiologist upon hospital discharge and at each subsequent outpatient examination and depend on the severity of residual disorders). One year after radical correction of congenital heart disease and in the absence of residual mitral valve regurgitation or the need for reoperation, follow-up at the place of residence at least once a year is possible [11,24,48,69,79,121-122].

Level of Evidence 5 (Grade of Recommendation C).

Comments: patients, even after a successful operation, must be under the lifelong supervision of a cardiologist. The presence of a systolic murmur over the heart may be associated with a shunt at the interventricular septal level, valve regurgitation, or subaortic obstruction. Routine examinations must include echocardiography with measurement of the presence and severity of regurgitation at the mitral and aortic valves. Additionally, at each echocardiographic examination, it is necessary to measure the gradient across the left ventricular outflow tract, which is associated with the risk of delayed development of left ventricular outflow tract stenosis in this group of patients. Furthermore, at least once a year, all operated patients with AVSD must undergo an electrocardiogram to assess AV conduction and detect arrhythmias. If arrhythmias are detected, 24-hour ECG monitoring is indicated.

When determining the frequency of follow-up, one should be guided by the hemodynamic status, presence of iatrogenic residual complications, symptoms of heart failure, cardiac arrhythmias, hypoxemia, etc.

Depending on whether a patient with a corrected or uncorrected defect belongs to a particular functional class, different monitoring frequencies and scopes of required examinations are indicated:

• All patients with AVSD after surgical correction are recommended to undergo a general clinical blood biochemistry test (investigation of blood levels of potassium, sodium, chlorides, glucose, creatinine, total protein, albumin, urea, total bilirubin, free and conjugated bilirubin, determination of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase activities in the blood, investigation of blood levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), investigation of serum C-reactive protein level) to assess renal, hepatic, and thyroid function, and to rule out inflammation at least once a year during a follow-up visit at dynamic monitoring [115,117,121-122].

Level of evidentiary reliability 5 (level of recommendation persuasiveness C).

• All patients after surgical treatment of AVSD, in the presence of residual disorders (pulmonary hypertension, AV valve regurgitation, arrhythmia, subaortic obstruction, etc.), are recommended more frequent monitoring and examination intervals [11,24,48,69,79,111].

Level of evidence 5 (grade of recommendation C).

Comments: in case of detection of residual disorders, the timing of the next outpatient examination or hospital admission is determined by the cardiologist / pediatric cardiologist.

• All patients after AVSD correction are recommended to undergo chest MRI every 2–5 years to assess intracardiac hemodynamics and detect residual complications [8,11, 44-45, 89-91,122].

Level of Evidence 5 (Grade of Recommendation C).

• Patients after surgical correction of AVSD, in case of persistence or progression of pulmonary hypertension, are recommended to undergo examinations in accordance with the clinical guidelines for the management and examination of patients with pulmonary hypertension [11,110].

Level of Evidence 5 (Grade of Recommendation C).

• Antibacterial prophylaxis before dental scaling and procedures is indicated for AVSD patients who have a prosthetic heart valve or artificial annuloplasty ring; a history of infective endocarditis; unoperated or following a palliative intervention (pulmonary artery banding); radically operated with residual septal defects; or radically operated within the first 6 months following the intervention [24].

Level of evidence 5 (grade of recommendation C).

• Children who have undergone AVSD correction surgery are recommended to receive vaccination no earlier than three months after the surgical procedure [8,122].

Level of evidence 5 (grade of recommendation C).

6. Organization of Medical Care

Stages of medical care and indications for hospitalization:

1. clarification of the diagnosis;

2. if a patient with AVSD shows signs of heart failure, the cardiologist in a cardiac surgery hospital must first prescribe conservative therapy aimed at treating heart failure (diuretics are the drugs of choice for heart failure in AVSD). If therapy is effective – elective radical correction at 3–6 months for complete AVSD and 1–2 years for partial AVSD. If therapy is ineffective and heart failure progresses – emergency surgery is indicated regardless of the patient's weight and age. The choice of correction method, whether staged with a primary pulmonary artery banding procedure followed by delayed radical correction in 6–18 months, or primary single-stage radical correction, depends on the presence of comorbidities.

3. patients with complete or partial forms of AVSD without clinical manifestations of heart failure and with stable heart chamber dimensions are followed by a cardiologist at their place of residence. Patients in this group are periodically referred at intervals of 2–3 months for a scheduled examination at a cardiac surgery hospital to assess the severity and determine the optimal timing for elective surgical correction of the congenital heart defect.

4. the indication for surgical treatment of AVSD is the congenital heart defect itself, however, the timing of surgical correction depends on the form (complete, partial, intermediate) and clinical manifestation of the defect. Progression of heart failure despite conservative therapy is a reason for hospital admission to a cardiac surgery hospital for adjustment of therapy or surgical treatment of the congenital heart defect.

Basics of conservative therapy

1. baseline therapy in the presence of heart failure in the preoperative period consists of prescribing diuretic drugs.

2. ineffectiveness of diuretic therapy with progressive heart failure is an indication for surgical correction of AVSD regardless of the patient's weight and age

Indications for transfer to the intensive care unit:

1. progressive heart failure, need for mechanical ventilation;

2. severe respiratory and metabolic acidosis;

3. life-threatening cardiac arrhythmias.

Indications for patient discharge from a medical organization:

• completed radical AVSD correction surgery or completed palliative intervention with a finished postoperative monitoring period;

• uneventful postoperative period;

• detected complication resolved conservatively or surgically;

• absence of heart failure;

• sinus heart rhythm.

7. Additional Information

• The long-term prognosis, life expectancy, and quality of life of children with AVSD are determined by the presence of concomitant cardiac and extracardiac pathology. It should be borne in mind that this pathology is frequently combined with Down syndrome, which affects the patient's life expectancy and quality of life. Furthermore, patients with Down syndrome have a higher risk of developing irreversible pulmonary hypertensive vascular disease compared to patients without the syndrome, which often requires earlier radical or palliative correction of the congenital heart defect.

• Additional intracardiac anomalies that worsen the long-term prognosis and increase the frequency of reoperations include left-sided obstructive pathology or the combination of AVSD with Tetralogy of Fallot.

• Extracardiac risk factors, in addition to Down syndrome, include prematurity and morphofunctional immaturity at birth, perinatal infection, and other chromosomal and genetic diseases (Williams syndrome, DiGeorge syndrome, etc.) [8,11,21].

• Following radical AVSD correction, complications may arise in the early or late period that require reoperation. Specific postoperative complications associated with the morphological features of AVSD include the development/occurrence of:

- severe mitral regurgitation/stenosis, requiring repeat mitral valve repair or replacement;

- severe tricuspid regurgitation/stenosis;

- residual VSD/ASD;

- left ventricular outflow tract obstruction;

- complete AV block requiring permanent pacemaker implantation;

- supraventricular arrhythmias [8,77].

• At the preoperative stage, it is important to timely recognize hemodynamically significant left ventricular outflow tract (LVOT) obstruction. LVOT narrowing is inherent in atrioventricular septal defects, but rarely leads to significant systolic pressure gradients at an age under 1 year. LVOT narrowing occurs due to a shortened LV inflow axis and anterior displacement of the left AV valve component. Thus, LVOT obstruction is most commonly found in patients with the morphological form of complete AVSD type A according to the Rastelli classification. As mentioned earlier, obstruction is rarely detected preoperatively, and significant LVOT narrowing typically develops after surgery. Furthermore, this complication can develop in both the early and late postoperative periods, usually presenting as discrete subaortic membranous stenosis, though sometimes the narrowing is diffuse throughout the entire LV outflow tract. Occasionally, LVOT stenosis may also result from improper patch selection (a narrow patch) used for VSD closure, which leads to the left AV valve being pulled toward the heart apex and anteriorly, causing dislocation of the subvalvular apparatus toward the LVOT. Thus, caudal displacement of the left AV valve toward the heart apex during initial AVSD repair can lead to LVOT obstruction, whereas its cephalic displacement toward the atria can lead to significant residual regurgitation [8].

• Another characteristic feature of patients with AVSD is a significantly higher prevalence of congenital heart disease (CHD) in their offspring (up to 14%) compared to parents without CHD or with CHD other than AVSD (2–4%). Most commonly, children of parents with AVSD present with similar forms of the defect or isolated septal defects, and tetralogy of Fallot is also frequent. The prevalence of other congenital heart defects does not differ from the general population [80].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Working Group Members

1. Avramenko A.A. (Samara)

2. B.G. Alekyan, Academician of the RAS (Moscow), "Russian Scientific Society of Endovascular Diagnostics and Treatment"

3. Arakelyan V.S., Prof. (Moscow)

4. Bogdanov V.N. (Chelyabinsk)

5. Boriskov M.V., MD (Krasnodar)

6. Bokeria L.A., Academician of RAS, "Association of Cardiovascular Surgeons of Russia", (Moscow)

7. A.G. Brodsky, Candidate of Medical Sciences (Surgut)

8. Gavrilov R.Yu. (Volgograd), "Association of Cardiovascular Surgeons of Russia"

9. Grigoryan A.M., PhD (Moscow), "Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists"

10. Gorbatikov K.V., MD (Tyumen)

11. Gorbatykh Yu.N., MD (Novosibirsk)

12. Kalashnikov S.V., PhD (Moscow)

13. Kim A.I., Prof. (Moscow), "Association of Cardiovascular Surgeons of Russia"

14. Kovalev I.A., MD, PhD (Moscow), "Association of Pediatric Cardiologists of Russia"

15. Kokshenev I.V., Prof. (Moscow), "Association of Cardiovascular Surgeons of Russia"

16. Krivoshchekov E.V., MD, PhD (Tomsk), "Association of Cardiovascular Surgeons of Russia"

17. Kupryashov A.A., Prof. (Moscow)

18. Levchenko E.G., MD (Moscow)

19. Movsesyan R.R., Corresponding Member of the RAS (Saint Petersburg), "Association of Cardiovascular Surgeons of Russia"

20. Nalimov K.A., PhD (Khabarovsk)

21. Petrushenko D.Yu., PhD (Kazan)

22. Plotnikov M.V., PhD (Astrakhan), "Association of Cardiovascular Surgeons of Russia"

23. V.P. Podzolkov, Academician of the RAS (Moscow), "Association of Cardiovascular Surgeons of Russia"

24. Svobodov A.A., Prof. (Moscow)

25. Sinelnikov Yu.S., MD, PhD (Perm)

26. Teplov P.V. (Krasnoyarsk)

27. Trunina I.I., Prof. (Moscow), Association of Pediatric Cardiologists of Russia

28. K.V. Shatalov, Prof. (Moscow), "Association of Cardiovascular Surgeons of Russia"

No conflict of interest. All members of the Working Group confirmed the absence of financial support/conflict of interest that needs to be disclosed.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Pediatricians;

2. Cardiologists;

3. Pediatric cardiologists

4. Cardiovascular surgeons.

Methods used for collecting/selecting evidence: electronic database search.

Description of methods used to assess the quality and strength of evidence: the evidence base for the recommendations includes publications indexed in the PubMed and Scopus databases. The search depth was 20 years.

Methods used to assess the quality and strength of evidence

1. expert consensus;

2. assessment of the quality of recommendations in accordance with the rating scheme (Table S1, S2).

3. assessment of the strength of evidence in accordance with the rating scheme (Table S3).

Table A1.Scale for assessing levels of evidence certainty (LEC) for diagnostic methods (diagnostic interventions)

Table A2.Scale for assessing levels of evidence certainty (LEC) for preventive, therapeutic, and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)

Table A3. Scale for assessing levels of recommendation consensus (LRC) for preventive, diagnostic, therapeutic, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitation interventions)

To minimize potential bias, each study was evaluated independently. Any discrepancies in evaluations were discussed by the full panel of authors. If a consensus could not be reached, an independent expert was involved.

Methods used for formulating recommendations: expert consensus.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

1. On the Basics of Protecting the Health of Citizens in the Russian Federation (Federal Law No. 323-FZ of November 21, 2011)

2. Procedure for the Provision of Medical Care to Patients with Cardiovascular Diseases (Order of the Russian Ministry of Health No. 918n of November 15, 2012)

3. "On the Classification and Criteria Used in the Implementation of Medicosocial Expertise of Citizens by Federal State Institutions of Medicosocial Expertise" (Order of the Russian Ministry of Health No. 1024n of December 17, 2015)

4. Order of the Ministry of Health of Russia No. 103n dated February 28, 2019 "On approval of the procedure and timeframe for the development of clinical guidelines, their revision, the standard form of clinical guidelines and requirements for their structure, composition and scientific validity of the information included in the clinical guidelines" (Registered with the Ministry of Justice of Russia on May 8, 2019, No. 54588);

5. Order of the Ministry of Health of the Russian Federation No. 203n dated May 10, 2017 "On approval of criteria for assessing the quality of medical care";

6. Order of the Ministry of Health of the Russian Federation No. 804n dated October 13, 2017 "On approval of the nomenclature of medical services";

7. Order of the Ministry of Health of the Russian Federation No. 700n dated October 7, 2015, "On the nomenclature of specialties of specialists with higher medical and pharmaceutical education"; Order of the Russian Ministry of Health No. 1183n dated December 20, 2012 (as amended on August 1, 2014) "On Approval of the Nomenclature of Positions of Medical and Pharmaceutical Workers"

8. Order of the Russian Ministry of Health No. 4n dated June 6, 2012 (as amended on September 25, 2014) "On Approval of the Nomenclature Classification of Medical Devices."

Appendix B. Physician Action Algorithms

Appendix B1. Diagnostic algorithm for patients with AVSD

Appendix B2. Management algorithm for patients with AVSD

Appendix C. Patient Information

Dear patient (patient's parents), the examination results revealed that you (your child) have a congenital heart defect – atrioventricular septal defect. By voluntarily consenting to the surgery, you must understand the purpose and risks of the operation, which your attending physician will explain to you.

Atrioventricular septal defect develops in the early stages of fetal life. The causes of this defect are usually multifactorial: maternal infectious diseases in early pregnancy, parental chronic illnesses, parental bad habits, environmental and genetic factors, etc. Depending on the size of the septal defects (presence and size of the ventricular septal defect, size of the atrial septal defect), the presence and severity of left AV valve regurgitation, and the presence of associated cardiac and extracardiac anomalies, the clinical manifestations of the defect can vary significantly. Regardless of the patient's clinical status, the presence of any form of atrioventricular septal defect is an indication for surgical treatment. The need for surgical treatment may arise in the first days of your child's life or at a later date. In some cases, especially when associated congenital heart anomalies are present, multiple surgical interventions may be required at different stages of life. In any case, in the presence of an atrioventricular septal defect, without surgical treatment, your child's health will progressively deteriorate and a serious threat to life may arise.

When prenatal diagnosis of the defect is performed (during pregnancy), a geneticist consultation is necessary, as atrioventricular septal defect is frequently (in up to 75% of cases) associated with Down syndrome, which negatively affects the life expectancy and quality of life of children, regardless of the outcomes of surgical correction of the defect.

If an atrioventricular septal defect is detected at any age after the child's birth, it is necessary to schedule an appointment with a cardiologist as soon as possible (preferably at a cardio-surgical center) to clarify the anatomical features of the defect, prescribe drug therapy (if necessary), and obtain further recommendations regarding the optimal timing of correction for the identified heart defect.

It should be understood that without surgical treatment the prognosis is unfavorable, but surgical intervention is also associated with risks to life and health, especially if the operation is required in the first days or weeks of life. All surgeries for congenital heart defects (staged or single-stage) are performed under general anesthesia and with artificial lung ventilation (i.e., during the operation, a machine will breathe for your child). In addition, most heart surgeries are performed using cardiopulmonary bypass, which allows the child's heart to be temporarily stopped to repair the defect and then restore the child's hemodynamics (heartbeat). Also, during and after the operation, a transfusion of donor blood components may be required, which is vital and therefore requires your consent.

After the surgery, your child will spend some time in the intensive care unit, where they will be awakened (weaned from anesthesia), gradually weaned from mechanical ventilation, and only then transferred to a general ward. The first hours and days after surgery are the most difficult, as this is when various complications most frequently occur (postoperative bleeding, heart failure, respiratory failure requiring prolonged mechanical ventilation, acute renal failure, infectious complications, etc.), which can significantly complicate your child's treatment or even lead to irreversible consequences.

While staying in the ward with your child to care for them, you must strictly follow all prescriptions and recommendations of your attending physician and medical staff. Treatment of this congenital heart defect often requires a prolonged hospital stay, which also requires understanding and maximum responsibility from the parents.

In most cases, surgical treatment (staged or single-stage) leads to a cure or improvement in condition. Despite successful surgical treatment of this defect, it is important to remember complications that may arise not only in the early but also in the long-term period after surgery, affecting not only the heart but also other organs of the child. In some cases, emerging complications may necessitate repeat interventions. Therefore, it is important not to miss follow-up examinations after surgery to timely assess the results of correction and identify potential complications, as well as to follow the doctor's recommendations and timely take all prescribed medications.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Information is not available.