Congenital subaortic stenosis: clinical guidelines

List of Abbreviations

ACG – angiocardiography (retrograde left heart catheterization; panaortography);

Ao – aorta;

AV – aortic valve;

LVOT – left ventricular outflow tract;

CHD – congenital heart disease;

LV/Ao PSG – peak systolic pressure gradient between the left ventricle and aorta;

VSD – ventricular septal defect;

CAG – coronarography;

SAS – subaortic stenosis;

CT – computed tomography;

LV – left ventricle;

MV – mitral valve;

MRI – magnetic resonance imaging;

PDA – patent ductus arteriosus;

EF – ejection fraction;

FR – fibrous ring;

ECG – electrocardiography (electrocardiogram recording; interpretation, description, and analysis of electrocardiographic data);

EchoCG – echocardiography.

Terms and Definitions

Heart catheterization (retrograde left heart catheterization; panaortography) is an invasive procedure performed for therapeutic or diagnostic purposes in cardiovascular pathology by inserting catheters (angiographic catheter) into the heart chamber or the lumen of great vessels.

Left ventricular-aortic peak systolic gradient is a Doppler echocardiographic index reflecting the pressure gradient between cavities, based on measuring blood flow velocity across the aortic valve and characterizing the degree of stenosis.

Computed tomography (CT) is a non-invasive diagnostic imaging method that provides a series of submillimeter cross-sectional axial images of human body organs and structures. It is based on measurement and complex computer processing of X-ray attenuation differences among tissues of varying density to improve differentiation between organs, as well as normal and pathological structures. Various contrast-enhancement techniques are used with iodine-containing radiopaque agents. CT angiography (contrast-enhanced cardiac computed tomography)—an intravenous bolus injection technique using an automated injector at a set flow rate and injection time—is used to visualize the cardiovascular structures. Based on the acquired data, computer post-processing with 3D reconstruction generates a three-dimensional model of the heart and vessels.

Shone syndrome – a congenital heart disease characterized by the fusion of MV chordae into a single cord attached to a single papillary muscle; supravalvular mitral stenosis combined with combined aortic stenosis, and often coarctation of the aorta.

Membranectomy (excisional removal of the subaortic fibrous membrane under cardiopulmonary bypass) is a surgical procedure to excise the subaortic membrane.

Myectomy (Morrow myectomy under cardiopulmonary bypass) is a surgical procedure to relieve SAS by resecting the hypertrophied portion of the interventricular septum.

Modified Konno procedure (Konno operation under cardiopulmonary bypass) – performed without aortic valve replacement; used in tunnel-form subaortic stenosis without involvement of the aortic valve and without hypoplasia of its fibrous ring.

Level of Certainty of Evidence (LoE) – the degree of confidence that the estimated effect of a medical intervention is true [1].

Grade of Recommendation (GoR) – the degree of confidence in the certainty of the intervention's effect and that following the recommendations will bring more benefit than harm in a specific situation [1].

Echocardiography – an ultrasound method aimed at studying morphological and functional changes of the heart and its valve apparatus.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Congenital subaortic stenosis (SAS) – characterized by an obstruction to blood flow located in the subaortic space.

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

The anatomical substrate of congenital SAS can be represented by both changes in the structures of the subvalvular space of the AoV and developmental anomalies of adjacent anatomical structures, in particular, the MV. In the membranous-diaphragmatic type of SAS, obstruction can be caused by the presence of a circular fibrous membrane with one or more openings in the LVOT, or by a fibrous crescentic fold stenosing the left ventricular outflow tract. The size of the opening in the membrane can range from 0.5 to 1.5 cm. As a rule, the membrane is located directly beneath the AoV annulus or slightly lower, and can be attached along the base of the anterior mitral leaflet and to the interventricular septum beneath the non-coronary or right coronary cusps [2-4].

The ridge-like type of congenital SAS is characterized by a ridge-like fibrous thickening localized 0.5-2 cm below the AoV and circularly surrounding the LVOT. The fibromuscular type of SAS represents a fibrous-muscular "collar" located 1-3 cm below the aortic valve, in contact with the anterior mitral leaflet and surrounding the LVOT circularly or as a crescentic ridge. The narrowing in this type of SAS can be extensive, reaching 2-3 cm. Quite frequently, this type of stenosis is combined with hypoplasia of the aortic valve annulus and fibrotic changes of the valve cusps.

The tunnel-like form of congenital SAS is essentially the extreme degree of severity of the anatomical defect form described above. This type of stenosis is characterized by marked hypertrophy of the LV outflow tract muscles, leading to the formation of a fibrous-muscular tunnel of considerable length (from 1 to 3 cm) [2-4]. The lumen of the tunnel can be significantly narrowed due to markedly thickened fibrous deposits extending from the AoV annulus to the anterior mitral leaflet and along the parietal and septal walls of the LV. The LV myocardium is usually concentrically hypertrophied. Subendocardial ischemia and fibrosis occur just as in congenital VAS [5,6]. In some cases, excessive hypertrophy of the interventricular septum (compared to the thickening of the posterior LV wall) and histological disarray of muscle fibers can be observed [7,8]. The presence of pronounced LV hypertrophy in this LVOT obstruction in a number of clinical situations dictates the need to differentiate this type of congenital SAS from hypertrophic cardiomyopathy with left ventricular outflow tract obstruction, which is of great importance for determining treatment tactics.

Various mitral valve anomalies can also lead to left ventricular outflow tract stenosis. These anomalies include [9]:

– anomalous attachment of the anterior mitral leaflet directly or via altered chordae to the interventricular septum;

– accessory tissue on the MV that bulges into the subaortic space and creates an obstruction;

– isolated cleft of the anterior mitral leaflet with additional chordae inserting into the interventricular septum;

– parachute-like deformity of the MV.

Subaortic stenosis can develop dynamically after the correction of certain congenital heart defects (VSD, double outlet right ventricle, etc.). Due to changes in the geometry of the left ventricular outflow tract, a turbulent flow may appear, which affects the interventricular septum and can lead to the formation of SAS [62].

1.3 Epidemiology of the Disease or Condition

According to literature data, the proportion of congenital SAS among all CHD accounts for 1-1.5%, and among all obstructive LVOT lesions – from 10 to 31.2% [2,5,10-15]. The need for surgical correction of congenital SAS in the Russian Federation is 0.59% with an average mortality of 1.06% among all CHD surgeries [16]

A more frequent development (1.5-2 times) of subaortic stenosis in males has been noted [2,11,17]. SAS is combined with other heart defects in 20-88% of cases [2,5,6,18-22]. Among associated CHDs, the combination of SAS with bicuspid AoV, VAS, aortic coarctation, PDA, VSD, Tetralogy of Fallot, and complete atrioventricular septal defect is most commonly noted [2,5,6,18-21]. In half of the diagnosed SAS cases, progressive aortic regurgitation occurs, caused by hemodynamic disturbances in the presence of the defect [23-25]. This is due to the fact that the high-velocity blood jet flowing through the stenosis injures the aortic valve. The decrease in diastolic pressure in the aorta during aortic regurgitation reduces coronary perfusion. This decrease in coronary perfusion and the increase in left ventricular oxygen demand make the left ventricular myocardium prone to ischemic injury.

Furthermore, congenital SAS may be a component of Shone syndrome [26].

Congenital SAS in an isolated form is rarely encountered in the neonatal period and in infants, and clinical symptoms most often manifest at an age older than 1 year. The rate of progression of subaortic stenosis is variable and unpredictable in children, whereas it progresses slowly in adults. Evidence of the rarity of isolated congenital SAS in newborns and infants is the extremely small number of surgeries performed for its relief in this age group [27-29].

In older children and even in adults, isolated congenital SAS can proceed for quite a long time without clinical manifestations [2,31,32]. In patients older than 30 years, congenital SAS is also rarely encountered. It is believed that survival beyond this time without surgical intervention is uncommon or that the lesion gradually acquires the appearance of hypertrophic obstructive cardiomyopathy with myocardial failure [3,33,34].

1.4 Features of Coding the Disease or Condition

Other congenital malformations [defects] of the heart (Q24):

Q24.4 – Congenital subaortic stenosis.

1.5 Classification of the disease or condition

Classifications of SAS are based on the morphological substrate of the stenosis and the angiographic picture, as well as the severity of hemodynamic disturbances.

Classification of congenital SAS by V.N. Getmansky [10]:

• Membranous-diaphragmatic;

• Ridge-like;

• Fibromuscular;

• Tunnel-like.

A more detailed anatomical classification was proposed by R. Freedom et al. (1996) [27]. This classification includes the following types of stenosis:

a) discrete fibrous membrane;

b) fibromuscular tunnel;

c) anomalous attachment of the MV chordal apparatus to the interventricular septum;

d) VSD with a discrete subaortic membrane;

d) subaortic obstruction caused by posterior displacement of the infundibular septum;

e) subvalvular aortic stenosis caused by hypertrophic cardiomyopathy.

1.6 Clinical presentation of the disease or condition

A small number of reported cases of discrete subaortic stenosis (DSS) in infancy and an increase in the number of patients older than one year indicate a progressive nature of the disease; however, the rate of stenosis progression varies among patients.

If left untreated, disease progression can lead to left ventricular hypertrophy, arrhythmias, aortic regurgitation, endocarditis, and sudden cardiac death. In early childhood, the clinical presentation is masked in most cases by concomitant congenital heart disease (CHD). Very often, DSS is detected during evaluation for coexisting CHD. In 25% of cases, DSS is asymptomatic.

The main complaints include: dyspnea, fatigue, diaphoresis, and developmental delay. In older patients, symptoms appear such as: syncopal episodes caused by decreased cerebral perfusion; cardiac pain due to relative coronary insufficiency; and congestive heart failure.

These symptoms occur in patients with moderate to severe left ventricular outflow tract (LVOT) obstruction and a peak systolic pressure gradient (PSPG) between the LV and Ao of more than 50 mm Hg. However, in most cases, the clinical presentation is absent despite a significant LV/Ao pressure gradient.

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of DSS is verified based on medical history taken from the patients' parents and/or the patients themselves (depending on age), the clinical manifestations of the defect, and instrumental diagnostic methods. The diagnosis can be made by a pediatric cardiologist based on complaints and examinations (ECG and echocardiography) in an outpatient setting.

The cornerstone in the diagnosis of DSS is the detection of a hemodynamically significant narrowing of the left ventricular outflow tract (LVOT). The most acceptable hemodynamic classification of LVOT stenosis severity is the grading based on the values of the maximum LV/Ao pressure gradient. According to this classification, all patients can be divided into 3 clinical groups [10]:

• Minimal subvalvular aortic stenosis – LV/Ao pressure gradient up to 30 mm Hg;

• Moderate subvalvular aortic stenosis – LV/Ao pressure gradient of 30–50 mm Hg;

• Severe subvalvular aortic stenosis – LV/Ao pressure gradient > 50 mm Hg.

2.1 Complaints and Anamnesis

• At the diagnostic stage, it is recommended to take a medical history and assess complaints in all patients (or their parents) with suspected DSS [2,3,5,6,10-12].

(LetC, Level of Evidence 4)

• When taking the history and assessing complaints, it is recommended to ask the patient's parents about the presence of fatigue, dyspnea (especially during physical activity), palpitations, and syncopal episodes in the child in order to assess the severity of the patient's condition [2,5,6,10-12].

(LetC, Level of Evidence 4)

Comments: As mentioned above, DSS rarely manifests in children under one year of age. As a rule, in this age group, the defect is a comorbid cardiac pathology, and its clinical picture is determined by the "dominant" CHD (VSD, mitral valve anomalies, atrioventricular septal defect). In older children and even in adults, isolated congenital DSS can remain clinically silent for a long time [2,5,6,10-12]. One of the poor prognostic signs in the course of the defect is a history of loss of consciousness. With significant obstruction during physical exertion, cardiac output decreases, leading to lower blood pressure and cerebral perfusion, presyncope, and syncope. Fainting and presyncopal states are rare in children. Arrhythmias are a more frequent cause of syncopal episodes. Decreased coronary perfusion combined with increased oxygen demand during exertion causes angina in 25% of patients with symptoms of left ventricular outflow tract obstruction. The occurrence of syncopal episodes is an absolute indication for surgical correction of the defect.

2.2 Physical Examination

(Level of Evidence C, Grade of Recommendation 5)

(LetC, Level of Evidence 4)

Comments: Examination of patients may reveal percussion-detected enlargement of the cardiac borders to the left due to left ventricular hypertrophy, while palpation determines a diffuse apical impulse. In some cases, a systolic thrill is palpated at the base of the heart, radiating to the jugular fossa and along the carotid arteries.

(LetC, Level of Evidence 4)

Comments: The auscultatory picture of congenital DSS is characterized by: 1) the presence of a harsh systolic murmur with a maximum in the II–III intercostal space on the right and radiation to the carotid arteries, sometimes along the left sternal border to the apex of the heart; The duration of the murmur is directly proportional to the degree of obstruction. 2) the presence of an aortic regurgitation diastolic murmur in some patients. 3) The absence of an ejection click in isolated subaortic stenosis, which is an important distinguishing feature from the murmur of aortic valve stenosis.

2.3 Laboratory Diagnostics

In patients with DSS, laboratory diagnostics are non-specific.

• All patients with DSS are recommended to undergo a complete blood count (CBC) and urinalysis, including hemoglobin level, hematocrit, erythrocyte, leukocyte, and platelet counts, and erythrocyte sedimentation rate (ESR) as part of the initial evaluation, upon hospital admission (including for surgical treatment), during follow-up at least once a year, and in the postoperative period [2,43,44,63].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Performing a complete blood count in all patients with DSS during dispensary monitoring and prior to surgical treatment is important for detecting anemia and providing timely correction. In patients with a mean corpuscular volume (MCV) of less than 80 fL, it is advisable to test serum iron, serum transferrin, serum ferritin, and total iron-binding capacity for the timely correction of iron deficiency states. In patients with an MCV greater than 100 fL, it is advisable to determine blood vitamin B12 (cyanocobalamin) and serum folic acid levels for the timely correction of B12 or folate deficiency states. The above conditions can negatively affect the clinical and functional status and the course of the patient's disease, as well as the outcomes of surgical treatment [63-65].

(Level of Evidence C, Grade of Recommendation 5)

(LetC, Level of Evidence 4)

(CQR C, LCE 5)

Comments: if there are laboratory signs of hemostatic disorders, surgical intervention should reasonably be postponed until the causes of these disorders are identified and corrected.

• All patients with DSS who receive thromboprophylaxis with unfractionated or low-molecular-weight heparin (antithrombotic agents; heparin group) after surgical treatment are recommended laboratory monitoring of therapy with these medicinal products (direct anticoagulants) [50,74,76,77].

(Translational Research Level B, Evidence Level 3)

Comments: When using unfractionated sodium heparin** (heparin group drugs), it is necessary to determine aPTT (optimal range for adults is 40–60 s, for children 60–85 s) and test blood heparin levels (anti-Xa activity) (optimal range is 0.35–0.7). Until the optimal range is reached, these parameters are measured 4 hours after each change in the infusion rate. Once the optimal range is achieved, testing is performed once every 12 hours (see Appendix A3). When using low-molecular-weight heparin preparations (heparin group), it is necessary to test blood heparin levels (anti-Xa activity determination) (optimal range is 0.5–1.0). Until the optimal range is reached, this is measured 3–4 hours after each injection; once the optimal range is achieved and the patient's clinical and laboratory status is stable, monitoring is not required [50,74,76,77].

(Level of Evidence C, Grade of Recommendation 5)

(Level of Evidence C, Grade of Recommendation 5)

2.4 Instrumental Diagnostics

(Level of Evidence C, Grade of Recommendation 5)

Comments: The ECG may be normal in patients with minor or moderately hemodynamically significant SAS. In the presence of a hemodynamically significant subvalvular aortic narrowing, signs of left heart overload and hypertrophy appear. Additionally, cardiac arrhythmias may be detected.

(Level of Evidence C, Grade of Recommendation 5)

Comments: The radiological presentation of congenital SAS is characterized by enhanced pulmonary vascular markings and enlargement of the left heart chambers (in the presence of hemodynamically significant subvalvular narrowing) and lacks specific features, except for the absence of ascending aorta dilatation.

(GPR C, EL 4)

Comments: Performing an echocardiographic examination in patients with suspected SAS allows for the determination of the morphological form of the defect, estimation of the severity of stenosis, and identification of concomitant cardiac pathology. The main imaging views for the left ventricular outflow tract (LVOT) are: the parasternal long-axis view of the left ventricle (LV), the apical 5-chamber view, and the subcostal long-axis view of the LVOT. During the echocardiogram, the morphology and degree of obstruction, dimensions of the LVOT, aortic valve annulus (AVA), ascending aorta, LV function, and associated congenital heart defects are assessed. When determining the degree of LVOT stenosis, the peak and mean pressure gradients are evaluated. It is mandatory to assess the degree of LV myocardial hypertrophy and the endocardial status (presence or absence of fibroelastosis).

The severity of subaortic stenosis may be under- or overestimated in the presence of a ventricular septal defect (VSD), as shunting of blood through the defect can distort the true pressure gradient between the LV and the aorta.

Transesophageal echocardiography (TEE) for diagnostic purposes can sometimes be useful in patients with a narrow acoustic window when transthoracic results are unsatisfactory. In some cases, a hypertrophied interventricular septum may mask the presence of a subaortic membrane. In such cases, TEE can be used for precise diagnosis of the subaortic membrane and helps differentiate subvalvular aortic stenosis from a hypertrophied interventricular septum [81].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Stress testing may record an increase in the systolic pressure gradient between the LV and the aorta, which may lead to a change in patient management.

(Level of Evidence C, Grade of Recommendation 5)

Comments: Contrast-enhanced cardiac CT is used as a supplement to echocardiography and as an alternative to invasive diagnostic methods to clarify the morphology of the defect, optimize surgical technique, and enable 3D modeling of the upcoming surgery. CT diagnostics are indicated to clarify the anatomy in patients with multi-component left heart chamber obstruction, improve visualization and 3D reconstruction of the ascending aorta, aortic arch, and isthmus. CT is also indicated in patients with SAS after correction of other heart defects. The primary value of tomographic techniques in children lies in their superior spatial resolution of extracardiac structures [36,37].

• Retrograde left heart catheterization and left ventriculography are recommended for patients with SAS combined with other cardiac anomalies when echocardiography or contrast-enhanced cardiac CT data are insufficient [2,5,6,10-12,35].

(Level of Evidence C, Grade of Recommendation 5)

Comments: In isolated subvalvular stenosis, catheterization is not a routine diagnostic method. Performing retrograde left heart catheterization and left ventriculography can be useful in the presence of multiple levels of obstruction to clarify the localization and predominant level of LVOT obstruction, determine hemodynamic parameters of the stenosis, the degree of aortic regurgitation, and rule out significant coronary artery disease [82]. The angiographic presentation of congenital SAS is characterized by filling defects in the subvalvular space in the form of a transverse band, a radiolucent strip along the entire circumference of the LVOT, or tubular narrowing with uneven marginal filling defects. Frequently, in roll-like and fibromuscular types of SAS, a subvalvular pocket is visualized—the so-called "secondary ventricle"—a space located between the aortic valve and the obstructing substrate. An absolute sign of congenital SAS is the detection of a pressure gradient between the LV and the subvalvular space [2,10-12,35].

2.5 Other Procedures

(Level of Evidence C, Grade of Recommendation 5)

(CQR C, LCE 5)

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

3.1 Conservative Treatment

• In the early postoperative period following surgical treatment for SAS, patients at high risk for thrombosis are recommended to receive thromboprophylaxis with low-molecular-weight or unfractionated heparin preparations (antithrombotic agents; heparin group) [50,74,76,77].

(Translational Research Level B, Evidence Level 3)

Comments: The high-risk thrombosis group includes patients with a history of thrombotic episodes, thrombophilia, infectious complications, and cardiac or multiorgan failure [74].

Thromboprophylaxis with sodium heparin** should be initiated with a bolus dose of 80 IU/kg for adults and 75 IU/kg for children, followed by continuous intravenous infusion at a rate of: 28 IU/kg/h for children under 1 year of age, and 20 IU/kg/h for children over 1 year of age (contraindication: newborns, especially premature infants or those with low body weight, due to the presence of benzyl alcohol in the preparation, which may cause toxic and anaphylactoid reactions in infants and children under 3 years of age). Dose adjustment is made based on laboratory test results (see section 2.3, Appendix A3) [76].

Thromboprophylaxis with low-molecular-weight heparin (heparin group) is administered as follows: #enoxaparin sodium** (off-label in children under 18 years of age) in children under 2 months of age – 0.75 mg/kg, in children over 2 months of age – 0.5 mg/kg every 12 hours subcutaneously; #dalteparin sodium – in children aged 1 month to 2 years, 150 IU/kg, from 2 to 8 years – 125 IU/kg, over 8 years – 100 IU/kg, every 12 hours subcutaneously. #Fondaparinux sodium may be used in children older than 1 year (off-label in children under 17 years of age) at a dose of 0.1 mg/kg, and in adults at 2.5 mg once daily subcutaneously. Dose adjustment is made based on laboratory test results (see section 2.3) [50, 74, 76, 77].

• In patients with SAS following heart defect correction with aortic valve replacement, lifelong thromboprophylaxis is recommended [50, 54, 64, 74, 76, 77].

(RRR B, LOR 3)

Comments: In the early postoperative period, thromboprophylaxis should be carried out with unfractionated or low-molecular-weight heparin preparations (antithrombotic agents; heparin group) (see above). Subsequently, the choice of thromboprophylaxis method depends on the type of valve prosthesis. Following the implantation of a mechanical prosthesis (mechanical bileaflet aortic valve prosthesis***), the use of vitamin K antagonists is indicated (warfarin** is prescribed in children older than 3 years with an initial dose of 0.2 mg/kg per day and its subsequent adjustment under INR monitoring [first check 3 days after starting warfarin**, then daily until stable target values are achieved for at least one week, after which it is checked 1-2 times a week]. The optimal INR range is 2.0–3.0) [50]. Following the implantation of a bioprosthetic valve (cardiac aortic bioprosthesis***) in the absence of patient risk factors for thrombosis, vitamin K antagonists are indicated for 3 months (optimal INR 2.0–3.0), followed by #acetylsalicylic acid** at a dose of 1-5 mg/kg (contraindication for use as an antiplatelet agent is childhood) [50, 76]. In patients at high risk of thrombosis after bioprosthetic valve implantation (cardiac aortic bioprosthesis***), continuous administration of vitamin K antagonists is indicated (optimal INR 2.0–3.0) [50].

3.2 Surgical Treatment

• In patients with congenital SAS, surgical intervention is recommended when the maximum peak systolic pressure gradient between the LV and Ao is 50 mmHg or more, or when the mean systolic pressure gradient between the LV and Ao is 30 mmHg or more, as determined by Doppler echocardiography [2, 5, 6, 10–12].

(Level of Evidence C, Grade of Recommendation 5)

• In patients with congenital SAS, in the presence of syncope or anginal symptoms, it is recommended to consider surgical intervention as a choice option even when the peak systolic pressure gradient between the LV and Ao is less than 50 mmHg and the mean systolic pressure gradient between the LV and Ao is less than 30 mmHg [83–85].

(Level of Evidence C, Grade of Recommendation 5)

• In patients with congenital SAS combined with progressive moderate-to-severe aortic regurgitation and increased LV dimensions, surgical intervention is recommended when the maximum peak systolic pressure gradient between the LV and Ao is less than 50 mmHg and the mean systolic pressure gradient between the LV and Ao is below 30 mmHg [2, 5, 6, 10–12, 24, 25].

(Level of Evidence C, Grade of Recommendation 5)

• In asymptomatic patients with congenital SAS in the presence of ST-segment changes at rest and during exercise, and progressive left ventricular hypertrophy, it is recommended to consider surgical intervention as a choice option even when the peak systolic pressure gradient between the LV and Ao is less than 50 mmHg and the mean systolic pressure gradient between the LV and Ao is less than 30 mmHg [83–86].

(Level of Evidence C, Grade of Recommendation 5)

• Surgical treatment of congenital SAS is recommended in patients with a maximum systolic pressure gradient between the LV and Ao of less than 50 mmHg and a mean pressure gradient of less than 30 mmHg in the event of progressive moderate-to-severe mitral regurgitation [2, 5, 6, 10–12].

(Level of Evidence C, Grade of Recommendation 5)

• In patients with congenital SAS in the case of a decrease in left ventricular ejection fraction to less than 50%, it is recommended to consider surgical intervention as a choice option even when the maximum systolic pressure gradient between the LV and Ao is less than 50 mmHg and the mean systolic pressure gradient between the LV and Ao is less than 30 mmHg [2, 5, 6, 10–12, 87].

(Level of Evidence C, Grade of Recommendation 5)

• For the surgical treatment of discrete subaortic stenosis, it is recommended to perform excision of the subaortic membrane or myectomy (excising the subaortic fibrous membrane under cardiopulmonary bypass, Morrow myectomy under cardiopulmonary bypass) [2, 5, 10, 14, 17, 38–40].

(LetC, Level of Evidence 4)

Comments: Potential complications of such surgical interventions include: injury to the aortic or mitral valve, the development of cardiac arrhythmias in the form of third-degree atrioventricular block, and the creation of an iatrogenic ventricular septal defect. However, if all rules of surgical technique are observed, the risk of such complications can be minimized. The 15-year survival rate after surgery ranges from 85% to 95% among patients operated on for discrete subaortic stenosis [23, 40].

• In the presence of a tunnel-like form of subaortic stenosis without involvement of the aortic valve in the pathological process and in the absence of aortic valve annulus hypoplasia, patients are recommended to undergo a modified Konno procedure (Konno operation under cardiopulmonary bypass) without aortic valve replacement [2, 5, 6, 10, 40, 41, 42].

(LetC, Level of Evidence 4)

• In patients with diagnosed SAS and concomitant hemodynamically significant aortic regurgitation and/or stenosis and aortic valve annulus hypoplasia, performing Ross-Konno or Konno-Rastan procedures is recommended [2, 5, 6, 10, 21, 40, 42].

(Level of Evidence C, Grade of Recommendation 5)

3.3 Endovascular interventions

• For certain types of discrete subvalvular stenosis (isolated thin discrete membrane no more than 3 mm thick), it is recommended to consider as an alternative to open surgery – the possibility of performing transluminal balloon dilation of SAS (transluminal balloon valvuloplasty of aortic valve stenosis) [46].

(LetC, Level of Evidence 4)

Comments: According to some authors [De Lezo J.S. et al., 2011], an alternative to open surgical intervention is balloon dilation of SAS (transluminal balloon valvuloplasty of aortic valve stenosis). The study presents the results of SAS treatment by balloon dilation in 76 patients aged 2 to 67 years at the time of surgery (mean 19±16 years), of whom 39 were children, 17 were adolescents, and 20 were adults. Good immediate and long-term results were observed in 77% of cases: a decrease in the LV/Ao pressure gradient, lower rates of restenosis, and no repeat interventions. According to the authors, a limitation to this technique is the morphological substrate of SAS, which must be represented by an isolated thin discrete membrane no more than 3 mm thick [46].

3.4 Other treatment

No

4. Medical Rehabilitation and Sanatorium-Resort Treatment

(Level of Evidence C, Grade of Recommendation 4)

Comment: Thanks to the introduction of advanced surgical and interventional techniques, including perioperative intensive care, the survival of children with congenital heart defects has markedly improved over recent decades, leading to an increase in the number of survivors reaching adulthood [92]. As patients with congenital heart defects grow older, their heart health can be additionally affected by acquired cardiovascular risk factors (e.g., hypertension, obesity, diabetes) commonly seen in the general population, which increases the risk of metabolic diseases, stroke, and coronary artery disease [93, 94]. It is known that the development of atherosclerotic and metabolic diseases manifesting in adulthood usually begins as early as early childhood. Childhood obesity and a sedentary lifestyle are known to be major contributing factors [95]. This underscores the need for primary prevention, and lifestyle interventions are therefore required to increase physical activity (PA) in children with congenital heart defects, as physical activity is essential for the physical, emotional, and psychosocial development of children [96–100].

• Children with mild left ventricular outflow tract obstruction are recommended daily physical activity defined by WHO as > 60 minutes without restrictions, as well as participation in all types of recreational/competitive sports with mandatory assessment of the severity of cardiovascular anomalies at least once a year [58,102].

(Level of Evidence C, Grade of Recommendation 5)

• Children with moderate left ventricular outflow tract obstruction are recommended daily physical activity of moderate and low intensity, as well as participation in dynamic and static sports of low and moderate intensity, excluding competitive sports, provided that exercise testing demonstrates satisfactory exercise tolerance [58,102].

(Level of Evidence C, Grade of Recommendation 5)

• Children with severe left ventricular outflow tract obstruction are recommended to engage only in low-intensity dynamic and static sports and physical activity depending on symptoms and exercise test results, excluding competitive sports [102].

(Level of Evidence C, Grade of Recommendation 5)

(Level of Evidence C, Grade of Recommendation 5)

Comments: The following conditions may occur after correction of left ventricular outflow tract obstruction:

- Residual hemodynamically significant left ventricular/aortic peak systolic gradient;

- Recurrence of subvalvular obstruction;

- Development and/or progression of aortic regurgitation against the background of the natural course of the defect or due to aortic valve damage during resection of the left ventricular outflow tract stenosis [23-25];

- Development and/or progression of mitral regurgitation against the background of the natural course of the defect or due to mitral valve damage during surgical correction of left ventricular outflow tract obstruction [23-25];

- Formation of iatrogenic ventricular septal defect during resection of subvalvular obstruction;

- Development of cardiac rhythm disturbances in the form of 3rd degree atrioventricular block, leading in turn to the need for pacemaker implantation (dual-chamber, rate-responsive implantable pacemaker***).

- Development of prosthesis-related complications (endocarditis, thrombosis, systemic embolisms, periprosthetic regurgitation or occlusion associated with pannus formation) during the implantation of mechanical prostheses (bileaflet mechanical aortic valve prosthesis***) during aortoventriculoplasty (Kono procedure under cardiopulmonary bypass) [2,5,6,10,12,38,41,42];

- Dilatation of the neo-aortic valve with the development of hemodynamically significant regurgitation after the Ross procedure;

- Stenosis/occlusion of the neo-pulmonary trunk after the Ross procedure;

- Development of myocardial ischemia due to occlusion/kinking of re-implanted coronary arteries during the Ross procedure;

- Development of cardiac rhythm disturbances, in some cases leading to sudden cardiac death [1,4,57].

(Level of Evidence C, Grade of Recommendation 5)

Comment: intense physical loads and competitive sports are excluded for 6 months after surgical treatment. Further activity restriction depends on the degree of residual hemodynamic disturbances. Physical activity restrictions persist for more than 6 months in case of: 1) Clinically significant residual left ventricular outflow tract obstruction (peak LV/Ao gradient greater than 50 mmHg); 2) Marked left ventricular myocardial hypertrophy; 3) Clinically significant ventricular or supraventricular arrhythmias; 4) More than mild aortic regurgitation [86].

(Reliability of Evidence Level B, Confidence Level in Data 3)

(Level of Evidence C, Grade of Recommendation 5)

Comment: climatic and balneological resorts provide comprehensive sanatorium-resort treatment including: heliotherapy (A20.30.021), climate therapy (A20.30.012), dry-air baths (A20.30.022), local (2-4 chamber) therapeutic baths (A20.30.009).

5. Prevention and Dispensary Observation

(Level of Evidence C, Grade of Recommendation 5)

• Children and adolescents with a mean Doppler gradient of less than 30 mmHg with no left ventricular hypertrophy and no symptoms are recommended dispensary follow-up without surgical intervention [84,88-89].

(LetC, Level of Evidence 4)

• Patients with moderate and severe left ventricular outflow tract obstruction according to the hemodynamic classification are not recommended intense physical loads and competitive sports [2,5,6,10,12,47].

(Level of Evidence C, Grade of Recommendation 5)

• Unoperated asymptomatic patients with diagnosed left ventricular outflow tract obstruction and a peak systolic pressure gradient between the left ventricle and aorta of 30-50 mmHg, with no signs of left ventricular hypertrophy or hemodynamically significant aortic valve regurgitation, are recommended to undergo routine examination (ECG, echocardiography) once a year [6,10,12,47].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Infants and young children should be monitored more frequently (every 3-6 months) to understand the rate of progression, since subaortic aortic stenosis is a progressive disease.

The main purpose of routine annual examinations is to monitor the increase in the degree of stenosis, the development or progression of aortic regurgitation, and to assess left ventricular systolic function.

• Patients with left ventricular outflow tract obstruction after surgical treatment are recommended an examination by a pediatric cardiologist (dispensary examination (examination, consultation) by a pediatric cardiologist) at least once every 7 days during the first month after defect correction [47].

(Level of Evidence C, Grade of Recommendation 5)

• Patients with left ventricular outflow tract obstruction after surgical treatment are recommended an examination by a pediatric cardiologist at least once every 3 months during 2-12 months after defect correction [47].

(Level of Evidence C, Grade of Recommendation 5)

• Patients with left ventricular outflow tract obstruction after surgical correction are recommended to undergo dynamic echocardiographic examination (once a year in a stable clinical condition) or perform additional echocardiography studies if necessary [2,5,6,10,12].

(Level of Evidence C, Grade of Recommendation 5)

Comments: When performing an echocardiographic examination, attention should be paid to the anatomy of the left ventricular outflow tract, the presence of blood flow obstruction and the LV/Ao gradient, the function of the "neo" aortic valve and the state of the conduit between the right ventricle and the pulmonary artery (during the Ross-Konno operation), the function of the implanted prosthesis after the Konno-Rastan operation (mobility of occluders, presence of thrombotic deposits on them, magnitude of peak and mean systolic pressure gradients across the prosthesis, presence of periprosthetic fistulas); morphofunctional parameters of the ventricles; presence of aortic valve regurgitation; magnitude of the residual systolic pressure gradient between the LV and Ao.

Patients with valve prostheses (bileaflet mechanical aortic valve prosthesis***) after aortoventriculoplasty (Kono procedure under cardiopulmonary bypass) are candidates for repeated prosthesis replacement surgeries due to the development of a mismatch between the prosthesis diameter and the volume of blood passing through it during growth.

When performing the Ross-Konno operation, patients subsequently become candidates for repeat surgeries to replace the conduit (vascular xenograft***) implanted between the right ventricle and the pulmonary artery, as well as interventions on the "neo" aortic valve due to its possible dysfunction.

• Patients with a mechanical bileaflet aortic valve prosthesis implanted in the aortic position*** are recommended lifelong oral administration of indirect anticoagulants (vitamin K antagonists) (#warfarin** with an average required dose of 0.33 mg/kg/day for infants and 0.09 mg/kg/day for adolescents to achieve the target INR of 2.0–3.0) followed by dose titration with continuous monitoring of blood coagulation parameters: INR (first check 3 days after starting #warfarin**, then daily until stable target values are achieved for at least one week, after which 1–2 times a week) [2,5,6,10,12,47,50–54,76,90].

(Level of Evidence C, Grade of Recommendation 5)

Comments: When administering antithrombotic agents orally, one should target INR values of 2.0 to 3.0 in low-risk patients and INR values of 2.5–3.5 in high-risk patients. The high-risk group includes patients with concomitant 1) atrial fibrillation, 2) decreased left ventricular systolic function, 3) history of thromboembolic episodes, 4) confirmed hypercoagulation. It is necessary to adjust the prescribed dose of the drug depending on body weight (as the child grows) and comorbid conditions (fever, dehydration). A diet limiting the intake of foods high in vitamin K must be followed (mayonnaise, soybean oil, spinach, various types of cabbage (Chinese, sareptassa, leaf, curly, as well as sauerkraut), Brussels sprouts, broccoli, dandelion (leaves), various types of lettuce, parsley greens, asparagus, bulb onions (green onions and shallots), beets, mustard, turnip, chicory, as well as grapefruit and grapefruit juice, cranberry juice, green tea, mango, fish oil, avocado (in large quantities)). It is necessary to monitor the intake of medications that affect blood levels of #warfarin** (the list of drugs that enhance or weaken the effect of #warfarin** is quite extensive (over 182 drugs). Pay attention to the "drug interactions" section in the medication package inserts. If #warfarin** is listed there, it is mandatory to check the INR 5 days after starting the drug in order to adjust the #warfarin** dose if necessary).

If various elective surgical interventions (abdominal, cavitary, orthopedic, neurosurgical) are necessary, withdrawal of indirect anticoagulants (vitamin K antagonists) for at least 5 days is required, and the patient should be switched to anticoagulant therapy with low-molecular-weight heparins (heparin group) at a therapeutic dose (administered twice daily) or, if low-molecular-weight heparin cannot be used, #heparin sodium** at a dose of 200 IU/kg/day administered parenterally. The efficacy and safety of ongoing anticoagulant therapy with #heparin sodium** should be monitored via the aPTT level, aiming for a 1.5- to 2-fold prolongation. If emergency surgery is required, vitamin K (phytomenadione / menadione sodium bisulfite**) can be administered subcutaneously at a dose of 0.5–2 mg, which reduces the INR to less than 2.0 within 12–24 hours. During preparation, anticoagulant therapy with low-molecular-weight heparins or #heparin sodium** must be maintained. The duration of the interruption in the intake of indirect anticoagulants (vitamin K antagonists) is determined by the specific clinical situation. In the absence of signs of postoperative bleeding (after the performed intervention), administration of indirect anticoagulants (vitamin K antagonists) can be resumed 6–12 hours later, and #heparin sodium** discontinued once the INR exceeds 2.0 [50–54, 76, 90].

• Patients with subaortic stenosis after the Ross-Konno procedure are recommended oral administration of indirect anticoagulants (vitamin K antagonists) (#warfarin** at an average dose of 0.09 mg/kg/day for adolescents and 0.33 mg/kg/day for infants) for 6 months, followed by a switch to antiplatelet agents [52, 54, 76, 90].

(Level of Evidence C, Grade of Recommendation 5)

Comments: When taking antithrombotic agents, it is necessary to target INR values within the range of 2–3. Subsequent antiplatelet therapy utilizes #acetylsalicylic acid** (off-label in children under 15 years of age) at a dose of 3–5 mg/kg/day (no more than 325 mg/day) or #clopidogrel** (off-label in children under 18 years of age) at a dose of 0.2–0.5 mg/kg/day [49, 50, 52, 54].

• When monitoring patients after surgical or percutaneous intervention, infective endocarditis prophylaxis is recommended for 6 months [48].

(Level of Evidence C, Grade of Recommendation 5)

Comments: For any type of congenital heart defect in the correction of which synthetic materials/prostheses were used (mechanical bileaflet aortic valve prosthesis***), if indicated, bacterial endocarditis prophylaxis is performed for 6 months after surgery or lifelong if residual shunts and valve regurgitation persist. Bacterial endocarditis prophylaxis is indicated for surgical procedures in the oral cavity and/or upper respiratory tract accompanied by mucosal damage (tooth extraction, manipulation in the periapical zone of a tooth, etc.). Infective endocarditis prophylaxis consists of oral administration of amoxicillin** at a dose of 50 mg/kg 30–60 minutes before the procedure (in case of allergy to benzylpenicillin** or ampicillin**, #clindamycin** (off-label in children under 12 years of age) is used at a dose of 20 mg/kg [90, 103].

6. Organization of Medical Care

Indications for hospital admission to a medical organization:

1) presence of symptoms of heart failure;

2) elective surgical treatment of subaortic stenosis, including in combination with other intra- and extracardiac anomalies;

3) correction of blood coagulation parameters if surgical manipulations/interventions are necessary in patients with mechanical heart valve prostheses implanted in the aortic position;

Indications for emergency hospitalization:

1) deterioration of the patient's functional status due to the progression of circulatory insufficiency symptoms or cardiac arrhythmias;

2) development of bleeding in patients with implanted prostheses;

3) acute prosthesis dysfunction/thrombosis;

4) development of acute coronary insufficiency (after the Ross-Konno procedure);

5) development of left ventricular dysfunction;

6) infective endocarditis.

Indications for discharging a patient from a medical organization:

1) absence of significant left ventricular outflow tract / aortic outflow tract LVOT gradient or implanted prosthetic valve;

2) absence/compensation of heart failure symptoms;

3) absence of hemodynamically significant cardiac arrhythmias;

4) well-managed anticoagulant therapy (in the presence of implanted prostheses).

7. Additional Information

Surgically treated congenital subaortic stenosis can recur. Thus, removal of the subaortic membrane in childhood does not prevent its reappearance, nor the appearance and/or progression of aortic valve regurgitation in the future. This phenomenon occurs in approximately 20% of patients within 10 years after surgery. In addition, aortic regurgitation may develop after the removal of the subaortic membrane.

Following the Ross-Konno operation, patients are at risk for autograft dilation with progressive "neo" aortic regurgitation, occlusion and/or regurgitation of the "neo" pulmonary trunk, and occasionally myocardial ischemia and/or infarction associated with occlusion or kinking of the proximal coronary arteries.

The outcomes of congenital subaortic stenosis correction according to various clinics are determined by the anatomical form of the obstruction, the type of intervention performed, and the patient's age. Thus, mortality during membranectomy or excision of the fibromuscular ridge approaches zero [2, 5, 6]. Complications of these surgeries may include: 1) development of an iatrogenic ventricular septal defect; 2) damage to the cardiac conduction system resulting in 3rd-degree atrioventricular block; 3) development of severe aortic and mitral valve regurgitation. However, if all technical guidelines for the procedure are followed, the risk of such complications can be minimized.

Performing more complex reconstructive operations on the left ventricular outflow tract is accompanied by an increase in mortality to 2–3% [39, 41]. A risk factor in this regard is the younger age group of patients due to the severity of obstruction requiring extended intervention. Mortality using extended aortoventriculoplasty procedures of the Rastan-Konno type can reach 8–34% [40], especially when patients are infants or toddlers. Fifteen-year survival after surgery ranges from 85% to 95% among patients operated on for discrete subaortic stenosis [21, 39].

The need for reoperation is generally caused by the dysfunction of implanted prostheses against the background of the child's active growth.

Criteria for Evaluating the Quality of Medical Care

Criteria for assessing the quality of primary health care provided to children with congenital subaortic stenosis (ICD-10 codes: Q24.4)

Criteria for assessing the quality of specialized medical care provided to children with congenital subaortic stenosis (ICD-10 codes: Q24.4)

References

Appendix A1. Working Group Composition

1. Avramenko A.A. (Samara)

2. Apkhanova T.V., MD, "National Association of Experts in Sanatorium-Resort Treatment" (Moscow)

3. Arnautova I.V., MD, "Association of Cardiovascular Surgeons of Russia", (Moscow)

4. Bogdanov V.N. (Chelyabinsk)

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

6. Boriskov M.V., DSc in Medical Sciences, (Krasnodar)

7. Borisova N.A., "Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists", (Saint Petersburg)

8. Gorbatikov K.V., DSc in Medical Sciences, (Tyumen)

9. Gorbatykh Yu.N., DSc in Medical Sciences, (Novosibirsk)

10. Kalashnikov S.V., PhD in Medical Sciences, (Moscow)

11. Kim A.I., DSc in Medical Sciences, "Association of Cardiovascular Surgeons of Russia", (Moscow)

12. Kovalev I.A., DSc in Medical Sciences, "Association of Pediatric Cardiologists of Russia", (Moscow)

13. Konchugova T.V., MD, "National Association of Experts in Sanatorium-Resort Treatment" (Moscow)

14. Krivoshchekov E.V., DSc in Medical Sciences, (Tomsk)

15. Kupryashov A.A., DSc in Medical Sciences, (Moscow)

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

17. Lyapunova A.A., PhD (Saint Petersburg)

18. Movsesyan R.R., DSc in Medical Sciences, "Association of Cardiovascular Surgeons of Russia", (Saint Petersburg)

19. Plotnikov M.V., Candidate of Medical Sciences, (Astrakhan)

20. Pursanov M.G., Doctor of Medical Sciences, (Moscow)

21. Sinelnikov Yu.S., Doctor of Medical Sciences, (Perm)

22. Trunina I.I., Doctor of Medical Sciences, "Association of Pediatric Cardiologists of Russia", (Moscow)

23. Shatalov K.V., MD, "Association of Cardiovascular Surgeons of Russia", (Moscow)

24. Baryshnikova I.Yu., PhD in Medical Sciences (Moscow) All-Russian Public Organization for the Promotion of the Development of Radiation Diagnostics and Therapy "Russian Society of Roentgenologists and Radiologists"

25. Sinitsyn V.E., MD, PhD, Professor (Moscow), All-Russian Public Organization for the Promotion of the Development of Diagnostic Radiology and Therapy "Russian Society of Roentgenologists and Radiologists"

There is no conflict of interest.

All members of the Working Group have confirmed that they have no financial support or conflicts of interest to disclose.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Pediatric Cardiologist

2. Cardiologist

3. Cardiovascular Surgeon

4. Ultrasound Diagnostics Physician

5. Pediatrician

6. Endovascular radiologist / X-ray endovascular diagnostic and treatment physician

7. Radiologist

8. Functional Diagnostics Physician

9. Neonatologist

During the development of the CPG, a new system of levels of evidence (LE) and grades of recommendation (GR) scales for therapeutic, rehabilitation, preventive, and diagnostic interventions (Tables 1, 2, and 3) introduced in 2018 by the Center for Expertise and Quality of Medical Care of the Russian Ministry of Health was used.

Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions).

Table 2. Levels of Evidence (LoE) grading scale for prevention, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for assessing the grades of recommendation (GR) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural therapeutic factors (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

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. Order of the Ministry of Health of Russia No. 560n dated June 9, 2020 "On approval of the Rules for conducting X-ray examinations"

4. Order of the Russian Ministry of Health No. 557n dated June 8, 2020, "On Approval of the Rules for Performing Ultrasound Examinations"

Transthoracic echocardiography performance technique

Comprehensive echocardiography to rule out associated congenital heart disease, assess heart dimensions and contractility, and evaluate the functional competence of the heart valves (mitral and aortic). Measurement of the left ventricular (LV) end-diastolic dimension and quantitative assessment of LV systolic function are performed in M-mode from the left parasternal long-axis view or short-axis view at the level of the mitral valve (MV) leaflet tips, which serve as a landmark for placing the cursor perpendicular to the MV leaflet coaptation line. Measurements are taken from the posterior surface of the interventricular septum to the anterior surface of the LV posterior wall. Visual assessment of the LV: from the apical four-chamber view in comparison with the right heart chambers. In the apical 4- and 2-chamber views, volumes and systolic function can be assessed using Simpson's method. Left parasternal view: long-axis evaluation of the aortic valve annulus diameter, root dimensions, and ascending aorta. In these modes and views, the thickness of the interventricular septum and the LV inferolateral wall is measured in diastole. LV wall thickening is diagnosed when the relative wall thickness (the sum of the thicknesses of the IVS and LVILW divided by the LV end-diastolic dimension) exceeds 0.42 [55].

Left ventricular outflow tract. The goal of echocardiographic assessment of subaortic stenosis is to comprehensively characterize the morphological features of the obstructive lesion, evaluate the severity of hemodynamic changes, and identify associated anomalies. The morphological substrate of left ventricular outflow tract obstruction may include several pathologies [56].

1) Discrete "membrane". In the LV long-axis view, a linear echoes-signal is visualized in the LVOT at a certain distance from the aortic valve leaflets or closely adhering, as a rule, to the right coronary cusp. LV outflow is characterized by a steeper angle between the IVS and the aortic root (aortoseptal angle), and some elongation of the mitro-aortic contact is possible.

2) "Tunnel-type" subaortic stenosis. Echocardiography reveals a long segment of LVOT narrowing, typically formed by thickened, altered fibromuscular LV walls involving the accessory anterolateral papillary muscle and hypertrophied IVS in the obstructive pathological process.

3) Posterior deviation of the conal septum when combined with other congenital heart defects can cause subaortic obstruction. This typically occurs in aortic arch interruption, coarctation of the aorta with VSD, and hypoplasia of the aortic valve and ascending aorta.

4) Muscular LVOT obstruction at end-systole due to a thickened IVS in hypertrophic cardiomyopathy.

Echocardiographic assessment of the severity of subaortic stenosis is based on anatomical and hemodynamic parameters. Measurement of the minimum flow dimension is performed at end-systole, and color Doppler flow mapping with optimal Nyquist limit settings is used to localize the site of narrowing. This method provides measurements in a single plane; for a more qualitative anatomical assessment of the degree of narrowing, three-dimensional echocardiography can be used (recommended in adolescents and adults, as this technique has technical limitations in obtaining informative echocardiograms in newborns and infants due to high heart rates and low frame rates). When performing transesophageal echocardiography, the manufacturer's weight limitations for the child must be considered (according to the instructions).

Hemodynamic assessment of subaortic stenosis is based on measuring the maximum blood flow velocity distal to the stenosis. To obtain optimal Doppler profiles, any approaches and LV long-axis views may be used, but the following rule must be followed: the angle of divergence between the blood flow through the narrowed area and the ultrasound beams must not exceed 15-20%. If multilevel LVOT obstruction is present, pulsed-wave and continuous-wave Doppler are recommended to determine the maximum narrowing. Muscular subaortic obstruction is accompanied by an increase in Doppler velocity in late systole, resulting in an asymmetrical Doppler spectral envelope shape ("dagger-shaped").

Monitoring and dose adjustment of unfractionated heparin (#heparin sodium**) [74,76]

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

The most frequent morphological substrate of subaortic obstruction requiring surgical correction in early childhood is a fibrous or fibromuscular membrane (79% of cases). The diffuse form of subaortic stenosis is represented by a muscular ridge in 13% of patients, and in 8% of cases by a tunnel-like narrowing of the subvalvar space due to marked hypertrophy of the interventricular septum.

In the absence of surgical treatment, disease progression can lead to left ventricular (LV) hypertrophy, arrhythmias, aortic valve (AV) regurgitation, endocarditis, and sudden cardiac death.

Patients with membrane-type obstruction have a more favorable clinical course compared to those with long-segment (tunnel-like) narrowing of the left ventricular outflow tract.

Mortality during surgical correction of simple forms is close to zero, whereas correction of complex tunnel-type forms is characterized by increased mortality rates. According to world literature, postoperative mortality is 0.7% for the simple form and 2.3% for the complex form.

According to the literature, the most frequent postoperative complications include cardiac arrhythmias, aortic and/or mitral valve injury, and iatrogenic VSD.

Despite good immediate surgical outcomes in most patients with subaortic stenosis, the risk of recurrence and reoperation remains high. Furthermore, the correction of complex forms of the defect (long-segment LVOT narrowing) is characterized by a higher rate of restenosis and reoperations.

Patients with subaortic stenosis are recommended to undergo follow-up echocardiography at least once a year in the long-term postoperative period. The evaluation includes: 1) aortic valve function and conduit status (following the Rosso-Konno procedure); 2) function of the implanted prosthesis after Konno-Rastan procedures (mobility of occluders, presence of thrombotic deposits, peak pressure gradient, presence of paraprosthetic leaks); 3) morphofunctional state of the ventricles; 4) presence of aortic regurgitation; 5) magnitude of the residual gradient between the LV and aorta.

In patients with an implanted mechanical prosthetic valve in the aortic position receiving antithrombotic therapy, meticulous monitoring of blood coagulation parameters is crucial to prevent both thromboembolism and bleeding complications.

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

No.