Ventricular Septal Defect: Clinical Guidelines

List of Abbreviations

ВПС – congenital heart disease

RVOT – right ventricular outflow tract

SPDG – systolic pressure gradient

VSD – ventricular septal defect

ASD – atrial septal defect

ЕОК – European Society of Cardiology

CHD – coronary heart disease

ICD – implantable cardioverter-defibrillator

IE – infective endocarditis

CT – computed tomography

LV – left ventricle

PA – pulmonary artery

PAH – pulmonary arterial hypertension

PH – pulmonary hypertension

LA – left atrium

PVR – pulmonary vascular resistance

PCC – pulmonary circulation

INR – international normalized ratio

MRI – magnetic resonance imaging

CIR – circulatory insufficiency

RV – right ventricle

RA – right atrium

SVR – systemic vascular resistance

6MWT – 6-minute walk test

ECG – electrocardiography

EchoCG – echocardiography

Qp/Qs – pulmonary-to-systemic blood flow ratio

Terms and Definitions

Cardiac catheterization – an invasive procedure performed for therapeutic or diagnostic purposes in cardiovascular pathology by inserting catheters into the heart chamber or the lumen of great vessels.

Computed tomography (CT) – a non-invasive diagnostic imaging method that yields a series of submillimeter cross-sectional axial images of human body organs and structures, based on measuring and complex computer processing of X-ray attenuation differences by tissues of varying densities; to improve the differentiation of organs from one another, as well as normal and pathological structures, various contrast enhancement techniques are used with iodine-based radiocontrast agents. To visualize the structures of the cardiovascular system, CT angiography is used—a technique of intravenous bolus injection of a radiocontrast agent into the bloodstream using an intravascular contrast injection system at a preset injection rate and time, based on which computer post-processing with 3D reconstruction builds a three-dimensional model of the heart and vessels.

Pulmonary hypertension – a hemodynamic and pathophysiological state characterized by an increase in mean pulmonary artery pressure (mPAP) ≥ 20 mm Hg at rest, measured via transvenous cardiac catheterization.

Magnetic resonance imaging (MRI) – a non-invasive, non-X-ray computer method for obtaining tomographic medical images to study internal organs and tissues, based on the phenomenon of nuclear magnetic resonance and the measurement of the electromagnetic response of atomic nuclei placed in a strong static magnetic field in response to excitation by a specific combination of electromagnetic waves; such nuclei are hydrogen atoms present in the human body as part of water and other substances. MR angiography is a method for imaging the vascular lumen using an MRI scanner. The method allows for the evaluation of both anatomical and functional blood flow characteristics. MR angiography is based on the difference in signal between moving protons (blood) and surrounding stationary tissues, which allows for vascular imaging without the use of any contrast agents—non-contrast angiography (phase-contrast MR angiography). In some cases, intravenous bolus contrast enhancement using gadolinium-based paramagnetic contrast agents is applied.

Eisenmenger syndrome – systemic-level pulmonary hypertension with a venoarterial or bidirectional blood shunt between the ventricles, atria, or great arteries due to the progression of pulmonary vascular disease during the natural history of "simple" and "complex" congenital heart defects.

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].

Endocarditis – inflammation of the inner lining of the heart involving the valve structures.

Echocardiography – an ultrasound diagnostic method aimed at studying the 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

Ventricular septal defect (VSD) is a congenital heart defect characterized by the presence of a communication (opening) between the right and left ventricles.

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

The formation of the heart with chambers and great vessels is completed by the end of the first trimester of pregnancy. The main developmental defects of the heart and great vessels belong to disorders of organogenesis and occur predominantly at 3–8 weeks of pregnancy. Ventricular septal defects (VSDs), like other congenital heart defects, are inherited polygenically and multifactorially in 90% of cases. In 5% of cases, the congenital heart defect is part of chromosomal abnormalities (Down syndrome, Sotos syndrome, Patau syndrome), and in another 5% of cases, it is caused by single-gene mutations [2,3].

VSD is characterized by a pathological blood shunt from the LV to the RV. Hemodynamic changes depend on the following factors: the location and size of the defect, pulmonary vascular resistance (PVR), the state of the right (RV) and left ventricular (LV) myocardium, and pressure in the systemic and pulmonary circulations. Continuous blood shunt from the LV to the RV leads to pulmonary hypervolemia, volume overload of the LV, with subsequent development of PH. In the case of long-standing PH, Eisenmenger syndrome may develop [3,4].

The key pathogenetic mechanism in Eisenmenger syndrome is endothelial dysfunction [5,6]. Initiating processes include increased pulmonary blood flow, elevated pressure, and shear stress. Initially, morphological changes in the form of medial and intimal hypertrophy are potentially reversible. As the disease progresses, usually in adulthood, irreversible processes develop—plexiform lesions and arteritis [6].

1.3 Epidemiology of the Disease or Condition

Ventricular septal defect is the most common congenital heart defect (CHD). In the structure of CHD, ventricular septal defect accounts for 20–32% and occurs both in isolation and in combination with other heart defects. In isolated form, it occurs in 25% of all CHDs; in combination with other defects, in 50% of all CHDs [7]. Perimembranous defects account for 61.4–80% of all VSD cases, and muscular defects account for 5–20%. Sex distribution is almost equal: girls (47–52%), boys (48–53%). Due to the high rate of spontaneous closure of small ventricular septal defects, the prevalence of this condition decreases with age, especially in adults.

In the Euro Heart Survey registry of adults with CHD, out of 1877 patients with ASD or VSD, 28% had PH and 12% had Eisenmenger syndrome [8]. Large VSDs, not prone to spontaneous closure and accompanied by pronounced hemodynamic disturbances and a severe clinical course, result in low patient survival, with a median survival ranging from 5 to 15 years [2,3,4,9-11].

The survival of patients with Eisenmenger syndrome significantly exceeds that of idiopathic PAH of a comparable functional class, but is worse compared to population data [12]. Many patients survive into their 3rd or 4th decade, and some into their 7th decade of life [13]. Right ventricular heart failure and progressive deterioration in exercise tolerance are negative prognostic factors [13].

1.4 Features of Coding the Disease or Condition

Q21.0 – Ventricular septal defect.

1.5 Classification of the disease or condition

By localization [4,14,15]:

• Perimembranous VSDs (central fibrous body limits the defect on one side):

- perimembranous inlet VSDs;

- perimembranous trabecular VSDs;

- perimembranous outflow.

• Muscular (all borders are muscular):

- muscular inflow;

- muscular trabecular;

- muscular outflow.

• Subarterial (the upper edge of the defect is formed by semilunar valves).

By size [16]:

• restrictive (defect diameter up to 1/2 of the aortic diameter);

• non-restrictive (greater than 1/2 of the aortic diameter).

By hemodynamic significance:

• Small: pulmonary-to-systemic systolic pressure ratio <0.3 and Qp/Qs<1.4.

• Moderate: pulmonary-to-systemic systolic pressure ratio <0.3 and Qp/Qs=1.4–2.2.

• Large: pulmonary-to-systemic systolic pressure ratio >0.3 and Qp/Qs>2.2.

• VSD with Eisenmenger syndrome: pulmonary-to-systemic systolic pressure ratio >0.9 and Qp/Qs<1.5 [17-134].

According to the 2009 ESC Guidelines for the diagnosis and treatment of PH, the anatomical and pathophysiological classification of PH due to VSD should take into account the following parameters for a detailed patient characterization (Table 1) [18].

Table 1. Anatomical and pathophysiological classification of congenital systemic-to-pulmonary shunts associated with pulmonary arterial hypertension

According to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of PH, the clinical classification distinguishes four groups of PAH associated with CHD: 1) Eisenmenger syndrome, 2) PAH associated with predominantly systemic-to-pulmonary shunts, 3) PAH with small, incidental defects, 4) PAH after CHD corrective surgery [19].

1.6 Clinical presentation of the disease or condition

For VSD, excluding the terminal stage, a left-to-right shunt is characteristic. Blood shunting from the LV to the RV occurs during systole. Since LV and RV contraction occurs simultaneously, the entire VSD blood flow is directed into the PA, pulmonary vasculature, and, after passing through the pulmonary circulation, returns to the LA and LV. Thus, the PA, LA, and LV experience volume overload, leading to their dilation. The direction and volume of the shunt are determined by the ventricular pressure gradient, defect size, and pulmonary vascular resistance (PVR). Low PVR results in a larger shunt volume, which is especially significant in large non-restrictive VSDs. Prolonged pulmonary circulation volume overload leads to increased pulmonary vascular resistance and elevated pressure in the PA and RV, i.e., the development of PH. The volume of the left-to-right shunt consequently decreases. As PH progresses, the shunt may become bidirectional or even right-to-left. Severe pulmonary hypertension and a right-to-left shunt through the VSD are signs of Eisenmenger syndrome.

Clinical manifestations of the disease depend on the volume of the left-to-right shunt and the degree of volume overload of the pulmonary circulation and the LV:

- children with restrictive VSD are generally asymptomatic;

- in non-restrictive VSD, there are signs of heart failure due to pulmonary circulation hypervolemia and LV volume overload (growth retardation, reduced exercise tolerance, dyspnea, tachycardia, frequent bronchopulmonary infections);

- with the development of Eisenmenger syndrome, varying degrees of cyanosis of the mucous membranes and skin appear [3,23,138].

In most adult patients who underwent VSD repair in childhood; patients with small, uncorrected VSDs; or those with a residual defect after surgery, the disease is usually asymptomatic [20]. The clinical presentation of Eisenmenger syndrome, a multi-organ progressive disease, includes central cyanosis, dyspnea, fatigue, hemoptysis, syncope, and, in advanced stages, right-sided heart failure [21,22].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria:

The diagnosis of ventricular septal defect is established based on the presence of typical patient complaints (dyspnea, palpitations, decreased exercise tolerance, poor weight gain, frequent bronchopulmonary infections), physical examination findings (poor weight gain, systolic murmur across the entire precordium, possible precordial bulge in older children), confirmed by chest radiography (cardiomegaly, increased pulmonary vasculature markings depending on shunt size), electrocardiography (signs of LV hypertrophy, and in the presence of PH — signs of RV hypertrophy), and is confirmed by echocardiography (which provides information on the location, size, number of defects, severity of left ventricular volume overload, and signs of PH).

2.1 Complaints and Anamnesis

ESC/ACC I C (LOE C, GoE 5)

Comments: Depending on the degree of hemodynamic impairment, there is significant variability in the clinical course of VSD. The patient's condition depends on defect size, PVR, and their changes with age. It is important to inquire about dyspnea, palpitations, decreased exercise tolerance, poor weight gain, and frequent infectious bronchopulmonary diseases in patients [3,4,15,16,23].

2.2 Physical Examination

• All patients with VSD are recommended to undergo a physical examination including chest shape assessment and cardiac palpation [3,4,15,16,23].

ESC/ACC I C (LOE C, GoE 5)

Comments: infants in their first year of life with large (non-restrictive) VSDs are characterized by the development of a precordial bulge resulting from prolonged pressure of enlarged heart chambers on the anterior chest wall. Patients with Eisenmenger syndrome exhibit central cyanosis, and in late stages, signs of right-sided heart failure [22,24]. A systolic thrill ("thrill" or "cat's purr") is usually best palpated approximately in the middle of the sternum near its left border in the presence of a left-to-right shunt. As a rule, the "thrill" sign is quite distinct and ranks among the most important signs of a ventricular septal defect.

• All patients are recommended to undergo cardiac auscultation to assess the severity of the VSD shunt and potential development of tricuspid and/or pulmonary valve regurgitation (less commonly mitral and/or aortic) [3,4,15,16,23].

ESC/ACC I C (LOE C, GoE 5)

Comments: auscultation in patients with VSD reveals:

- in individuals with severe PH, a marked accentuation of the pulmonary component of the second heart sound (P2) is noted, heard as an accentuated P2 at the pulmonary auscultation area;

- a medium- to high-intensity (3–5/6) holosystolic or early systolic shunting murmur along the lower left sternal border;

- a diastolic rumble of relative mitral stenosis at the cardiac apex (in the presence of a large left-to-right shunt);

- patients with subarterial VSD may present with a diastolic murmur of aortic regurgitation due to prolapse of the semilunar cusps into the VSD;

- patients with severe PH may present with a diastolic murmur of functional pulmonary valve regurgitation secondary to marked pulmonary trunk dilation.

2.3 Laboratory Diagnostics

In patients with uncomplicated VSD, it is non-specific.

ESC/ACC I C (LOE C, GoE 5)

ESC/ACC I C (LOE C, GoE 5)

ESC/ACC I C (LOE C, GoE 5)

ESC/ACC I C (LOE C, GOR 5)

Comments: Secondary erythrocytosis is common in VSD patients with developing pulmonary hypertension (PH) and concomitant pulmonary pathology. Hematocrit should be measured automatically, as blood centrifugation yields falsely high hematocrit values due to plasma trapping [18]. Hemoglobin levels should be monitored dynamically in all patients receiving endothelin receptor antagonists, which can lead to a decrease in hemoglobin due to hemodilution in approximately 10-15% of patients [137]. Patients with PH associated with VSD exhibit hemostatic abnormalities, including thrombocytopenia, and an increased risk of bleeding and thrombosis [134].

ESC/ACC IIa C (LOE C, GOR 5)

Comments: Anemia is an independent risk factor for postoperative mortality and complications. Iron deficiency anemia is the leading cause of preoperative anemia. Timely management of preoperative anemia improves surgical outcomes [134,145-146].

ESC/ACC I C (LOE C, GOR 5)

Comments: Glucose levels may be reduced in patients with Eisenmenger syndrome due to increased in vitro glycolysis secondary to erythrocytosis. In patients with PH due to VSD, increased red blood cell/hemoglobin turnover and impaired urate metabolism lead to hyperuricemia [26]. Elevated unconjugated bilirubin in cyanotic patients is associated with the risk of gallstone formation. Approximately half of patients with Eisenmenger syndrome have iron deficiency. Therefore, serum iron levels should be measured at least once a year to determine the need for iron supplementation [134].

ESC/ACC IIa C (LOE C, GOR 4)

• All VSD patients receiving thromboprophylaxis with unfractionated or low-molecular-weight heparin after surgical treatment are recommended laboratory monitoring of drug efficacy [90,151,156-157].

ESC/ACC IIa C (LOE C, GOR 5)

Comments: When using unfractionated heparin, it is recommended to determine aPTT (optimal target range: 40-60 s in adults, 60-85 s in children) and anti-Xa activity (optimal range: 0.35-0.7). When using low-molecular-weight heparin, anti-Xa activity monitoring is recommended (optimal range: 0.5-1.0) [90,151,156-157].

2.4 Instrumental Diagnostics

• All patients are recommended to undergo an electrocardiogram (ECG) to assess left and right heart chamber overload, heart rhythm, and conduction [3,4,15,16,23-24,132,137].

ESC/ACC I C (LOE C, GoE 5)

Comments: ECG changes may be absent in small (restrictive) VSDs. Patients with moderate and large VSDs show ECG signs of left ventricular (LV) hypertrophy and, rarely, left atrial enlargement. In the presence of PH, ECG signs of right ventricular (RV) hypertrophy are detected. Arrhythmias occur in the later stages of the disease and lead to heart failure decompensation [137]. Atrial flutter or fibrillation significantly worsens patient prognosis [24].

• All patients are recommended to undergo echocardiography (ECHO) with color Doppler mapping, which is the primary diagnostic tool for diagnosing VSD, determining its size, location, volume, and direction of the blood shunt, as well as associated congenital heart defects [131-134,137].

ESC/ACC I C (LOE C, GOR 5)

Comments: Echocardiography (ECHO) is a key diagnostic method for establishing the diagnosis of VSD and assessing the severity of hemodynamic changes in patients. The method provides information on the location, size, number of defects, severity of left ventricular volume overload, and signs of PH. All types of ventricular septal defects cannot be neatly categorized into the most detailed classifications. Furthermore, classifications do not preclude the overlap of multiple categories in a single VSD. Muscular defects combined with other large VSDs and in the presence of severe pulmonary hypertension may be difficult to visualize.

When planning transcatheter closure of a VSD, it is important to determine the type of defect: muscular defects, perimembranous defects with a distance to the aortic valve margin of greater than 4 mm, and residual defects after surgical repair are optimal.

In non-restrictive VSD, 100% pulmonary hypertension is present from birth, driven by direct transmission of pressure from the systemic ventricle, and the magnitude of the arteriovenous shunt depends on the pulmonary-to-systemic vascular resistance ratio. Pulmonary hypertension is usually accompanied by relatively good RV adaptation with marked hypertrophy, minimal dilation, and preserved systolic function. In this scenario, both ventricles function almost like a single contracting chamber, providing systemic and pulmonary blood flow, and adapt better to high PVR.

In restrictive VSDs, the magnitude of the arteriovenous shunt depends on both the size of the defect and the pulmonary-to-systemic resistance ratio. In this case, the pressure gradient across the defect reflects the systolic pressure in the RV and pulmonary artery (the higher the gradient, the lower the pressure). It is important to remember that with high PVR (in neonates), the systolic pressure gradient may be small even with a small VSD, or only mild left heart enlargement may be detected with a large VSD. The evaluation includes cardiac morphometry, shunt direction, relationship with other structures, and Qp/Qs ratio.

Intraoperative and postoperative echocardiographic monitoring includes assessment of residual VSDs, heart valve and ventricular function, and signs of pulmonary hypertension.

• Transesophageal echocardiography (TEE) is recommended when transthoracic ECHO has technical limitations for visualization (adult patients with obesity, lung disease, or during planning and performance of transcatheter VSD closure) [134,28,131-133].

ESC/ACC IIa C (LOE C, GOR 5)

Comments: Performing transesophageal and/or contrast ECHO is justified only by technical limitations of transthoracic ECHO. The study can be combined with other imaging modalities (MRI, contrast-enhanced CT), which significantly improves diagnostic capabilities in VSD. Three-dimensional echocardiography technologies are currently being introduced to improve diagnostics.

• All patients are recommended to undergo chest radiography in the anteroposterior projection to detect pulmonary pathology [3,4,15,16,134,23]

ESC/ACC IIa C (LOE C, GOR 5)

Comments: When performing a computed tomography (CT) scan of the chest organs, chest X-ray should not be performed because it would duplicate the CT scan. The degree of cardiomegaly and the prominence of the pulmonary vascular pattern directly depend on the magnitude of the shunt. In patients with small (restrictive) ventricular septal defects (VSD), the X-ray will be unremarkable. In infants during the first 1.5–3 months of life with large (non-restrictive) defects, progressive severity of pulmonary hypervolemia over time is characteristic, which is associated with a physiological decrease in total pulmonary vascular resistance and an increase in left-to-right shunting. In the presence of a large left-to-right blood shunt, there are signs of left atrial and left ventricular enlargement and an enhanced pulmonary vascular pattern. In patients with severe pulmonary hypertension (PH), there is no left ventricular enlargement, but there is bulging of the pulmonary artery trunk and attenuation of the pulmonary vascular pattern in the peripheral lung fields [134, 137].

ESC/ACC IIa C (LOE C, GOR 5)

Comments: Cardiac MRI has an advantage in visualization, particularly for assessing cardiac ventricular overload and quantitative characteristics of the shunt. The method allows for the assessment of anatomical and functional changes and the evaluation of myocardial fibrosis. MRI is used in adults with VSD in the following clinical situations:

- as an additional method when ambiguous or borderline echocardiographic data are obtained, such as left ventricular volumes and ejection fraction, which may be crucial in the management strategy for adult patients with VSD, e.g., in assessing volume overload and valvular regurgitation;

- MRI is more informative compared to echocardiography in the quantitative assessment of right ventricular volumes and ejection fraction, right ventricular outflow tract obstruction, pulmonary regurgitation, evaluation of the pulmonary arteries (stenosis, aneurysms) and aorta (aneurysm, dissection, coarctation); systemic and pulmonary veins (anomalous drainage, obstructions, etc.), collaterals and arteriovenous malformations (comparable in capabilities to CT), in determining coronary artery pathology (inferior to CT), ruling out masses (including thrombi, lymph nodes) of intra- and extracardiac structures and detailing them if present, quantitative assessment of myocardial mass (left and right ventricles), detection and quantitative assessment of myocardial fibrosis/scar; tissue characterization (fibrosis, fat, etc.) [29, 132, 137].

ESC/ACC IIa C (LOE C, GOR 5)

Comments: CT plays a special role in emergency situations, but it is not the method of choice for diagnosing isolated VSD, including in adult patients, due to its limited functional analysis capabilities and radiation exposure. CT allows visualization of epicardial coronary arteries and collateral vessels, and detection of parenchymal lung diseases [24].

ESC/ACC IIa C (LOE C, GOR 5)

Comments: Cardiac catheterization is not routinely used for the diagnosis of isolated VSD forms. In cases of VSD combined with severe PH, angiocardiography should be avoided altogether, performing only cardiac chamber catheterization with pressure determination and calculation of hemodynamic parameters. Catheterization involves measuring pressures (systolic, diastolic, mean), determining blood gas composition in the heart chambers and great vessels, and calculating hemodynamic parameters.

ESC/ACC IIa C (LOE C, GOR 5)

Comments: Nitric oxide, inhaled iloprost, and oxygen can be used for the vasoreactivity test. A positive test in a patient with Qp:Qs > 1.5:1 should be considered when there is a decrease in the PVR index and PVR/systemic vascular resistance (SVR) index ratio by 20% or more, or when the PVR index reaches < 6 Wood units/m2 and the PVR/SVR ratio < 0.3 [35, 51, 75, 81].

ESC/RCS III C (LoE C, GoR 5)

Comments: evaluation of vasoreactivity in adult patients with VSD is not recommended due to the lack of universally accepted operability criteria [25, 51].

• In adult patients with low or intermediate pre-test probability of coronary artery disease (CAD), it is recommended to perform computed tomography coronary angiography (CTCA) when coronary anomalies are suspected [28, 34].

ESC/RCS IIb C (LoE C, GoR 5)

• In patients with a high pre-test probability of CAD, or in men over 40 years of age, or postmenopausal women prior to planned cardiac surgery, it is recommended to perform invasive coronary angiography when coronary anomalies are suspected [28, 34].

ESC/ACC I C (LOE C, GOR 5)

2.5 Other Procedures

ESC/ACC I C (LOE C, GOR 5)

Comments: The 6-minute walk test (6MWT) is the simplest method for assessing patients' functional capabilities [136]. The distance in the 6MWT inversely correlates with the functional class. The test is usually supplemented by the Borg dyspnea scale assessment and pulse oximetry [36]. A drop in arterial blood oxygen saturation of more than 10% during the 6MWT indicates an increased risk of mortality. Changes in the 6MWT distance serve as the primary endpoint in most randomized trials in patients with pulmonary arterial hypertension (PAH) [136].

ESC/RCS IIa C (LoE C, GoR 4)

Comments: cardiopulmonary exercise testing (Ergospirometry) is preferred. This method has age limitations. A cycle ergometer or treadmill is used during the test. The patient's subjective reaction, ECG changes, blood pressure, and peak oxygen consumption are evaluated. The results are compared with normal values adjusted for age, sex, and body surface area [139]. In routine practice, the 6-minute walk test serves as an alternative to cardiopulmonary exercise testing [140].

• Prior to discharge from the hospital, all patients are recommended to undergo an electrocardiogram recording for follow-up purposes (after surgical treatment) [23, 33, 137].

ESC/ACC I C (LOE C, GoE 5)

• Prior to discharge from the hospital, all patients are recommended to undergo a transthoracic echocardiogram for follow-up purposes (after surgical treatment) [23, 33, 137].

ESC/ACC I C (LOE C, GoE 5)

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

3.1 Conservative Treatment

Maintenance therapy

The management strategy for VSD is determined by the hemodynamic significance of the defect and its known prognosis. For children responding to therapy, surgical intervention may be delayed.

• In the absence of progressive circulatory failure, worsening pulmonary hypertension, and with adequate weight gain in the child, surgical intervention is recommended to be performed once the body weight reaches 4.5 kg [37].

ESC not specified (LoE C, GoR 4)

• In infants during the first weeks and months of life with signs of lesser circulation hypervolemia and symptoms of heart failure, symptomatic therapy is recommended [23, 141–144].

No ESC guideline (LoE C, GoR 5)

Comments: in patients with heart failure, it is advisable to resort to conservative therapy using diuretics as first-line therapy, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors. Treatment should not be prolonged and is used until surgical correction of congenital heart disease.

• In patients with VSD at high risk of thrombosis after surgical treatment, thromboprophylaxis with heparin preparations (B01AB Heparin group) and its derivatives is recommended [90,151,156-157].

ESC/ESC I B (LoE B, GoR 3)

Comments: The high-risk group for thrombosis includes patients with a history of thrombosis, thrombophilia, infectious complications, and multiple organ failure.

Thromboprophylaxis with unfractionated sodium heparin** should be initiated with a bolus of 80 IU/kg in adults and 75 IU/kg in children, followed by intravenous infusion at the following rates: in children under 1 year of age – 28 IU/kg/h, in children over 1 year of age – 20 IU/kg/h, in adults – 18 IU/kg/h. Dose adjustment is made based on laboratory test results.

Thromboprophylaxis with low-molecular-weight heparin preparations is administered at the following dosage: enoxaparin** (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, in adults – 20 mg every 12 hours subcutaneously; dalteparin** – in children from 1 month to 2 years of age – 150 IU/kg, from 2 to 8 years of age – 125 IU/kg, over 8 years of age – 100 IU/kg, in adults – 2500 IU every 12 hours subcutaneously. Fondaparinux** may be used in children over 1 year of age (off-label in children under 17 years of age) at a dose of 0.1 mg/kg, and in adults at 2.5 mg daily subcutaneously. Dose adjustment is made based on laboratory test results [90,151,156-157].

• Anticoagulant therapy (B01A Antithrombotic agents) is not recommended in adult patients with VSD and PAH in the absence of atrial fibrillation, any prosthetic valves, or vascular grafts [24,39].

ESC/ESC III C (LoE C, GoR 5)

Comments: in patients with VSD and atrial flutter/fibrillation, the target international normalized ratio (INR) is 2-2.5; in the presence of any mechanical valve, the target INR is 2-3.

Adult patients with VSD and PAH have an increased risk of thrombosis, but also an increased risk of bleeding. With the development of PAH, mural thrombi in dilated pulmonary arteries are frequently observed [40]. Female sex, low venous blood oxygen saturation, older age, biventricular dysfunction, and dilated pulmonary arteries are risk factors for thrombotic complications in patients with VSD [40].

Cerebrovascular disorders may be caused by paradoxical emboli, rheological factors (microcytosis), endothelial dysfunction, and atherosclerotic changes. The role of secondary erythrocytosis severity as a potential risk factor has not been established [41]. Microcytosis caused by iron deficiency due to phlebotomy is an independent predictor of cerebrovascular events [42].

• The prescription of antithrombotic agents (Antithrombotic agents) is not recommended for patients with VSD and PAH due to an increased risk of bleeding and unproven efficacy [39].

ESC/ESC III C (LoE C, GoR 5)

Comments: randomized controlled trials to evaluate the efficacy/safety of antithrombotic therapy in patients with VSD, including those with PAH, have not been conducted. Antithrombotic agents are used when there are indications for treating comorbid conditions.

Heart failure is the most frequent problem in adult patients with persistent VSD or following surgical correction of the defect. Therapy in such cases is carried out using accepted heart failure treatment guidelines [33,38].

• Loop diuretics are recommended for patients with VSD and heart failure to relieve edema syndrome [3,23].

ESC/ACC I C (LOE C, GoE 5)

Comments: randomized controlled trials on the use of diuretics in VSD are lacking, but clinical data demonstrate a clear improvement in symptoms with the use of loop diuretics in patients with circulatory failure. When prescribing diuretics, forced diuresis should be avoided, and systemic blood pressure, electrolyte levels, blood creatinine, blood urea, and hematocrit should be closely monitored to prevent hemoconcentration in response to decreased intravascular blood volume, hypokalemia, and prerenal failure. In cases of severe systemic hypotension and anasarca, #furosemide** (solution for intravenous and intramuscular administration, route of administration: intravenous) at a dose of 1 mg/kg/day (but not exceeding 20 mg/kg/day) is advisable under the control of systemic blood pressure, central venous pressure, and hourly diuresis [158]. If indicated, inotropic support should be considered under hemodynamic monitoring in an intensive care unit.

ESC/ESC I C (LoE C, GoR 5)

Comments: Digoxin** makes it possible to control heart rate in patients with supraventricular arrhythmias associated with ventricular dysfunction. The drug enhances right ventricular contractility in patients with PAH, pulmonary pathology, and biventricular chronic heart failure.

No ESC guideline (LoE C, GoR 5)

Comments: to increase cardiac output, adrenergic and dopaminergic agents (dobutamine**, dopamine**) and, if necessary, norepinephrine** to maintain blood pressure are used. Dobutamine** is the preferred choice in severe PAH, given the drug's effect on pulmonary vascular resistance (PVR) [135].

ESC/ESC III C (LoE C, GoR 5)

Comments: Conclusive evidence supporting the efficacy and safety of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, calcium channel blockers, beta-blockers, or ivabradine** (off-label in children under 18 years of age) in patients with VSD and PAH is lacking. The prescription of the aforementioned drug classes is justified in the presence of comorbid conditions, with an evaluation of the risk-benefit ratio regarding reduced cardiac output, systemic hypotension, and bradycardia.

ESC/ESC IIa B (LoE C, GoR 5)

Comments: patients with PAH associated with CHD exhibit resting arterial hypoxemia refractory to oxygen therapy due to right-to-left shunting. The use of oxygen therapy can alleviate patients' condition, improve exercise tolerance and quality of life, but cannot improve pulmonary hemodynamics or affect the clinical course of Eisenmenger syndrome [44,137]. Maintaining the required oxygenation level >89% in the presence of shunts is a challenging task. The standard oxygen therapy regimen is 2-4 L/min, and in some cases up to 20 L/min using home-use systems [135]. Specific PAH therapy does not provide clinical improvement if hypoxemia persists. Deterioration of gas exchange may occur upon initiation of specific therapy, which requires monitoring of blood gas composition during treatment.

Specific therapy

Modern specific therapy is used for PAH complicating the course of VSD. It is aimed at relieving symptoms, improving patients' quality of life, preventing disease progression as much as possible, and increasing life expectancy. It targets three key pathogenetic mechanisms: endothelin-1 (ET-1) system activation; prostacyclin (PGI2) and nitric oxide (NO) deficiency – endogenous vasodilators with antiproliferative and anti-inflammatory properties [18,19,25,31,35,39,52-59,96]. Therapy in such cases is carried out using accepted pulmonary hypertension treatment guidelines [25,31].

3.2 Surgical Treatment

• Surgical treatment is recommended for patients with VSD presenting with clinical symptoms of heart failure, significant left-to-right shunt and left heart chamber volume overload on imaging, aortic valve prolapse, a history of infective endocarditis, and no irreversible pulmonary vascular disease. Surgical correction of CHD is recommended for patients with VSD and aortic valve prolapse with progressive aortic regurgitation [18,33,60].

ESC/RSC I C (LoE C, GoR 5)

• Surgical correction of CHD is recommended for patients with VSD and aortic valve prolapse with progressive aortic regurgitation [18,33,60].

ESC/RSC IIa C (LoE C, GoR 5)

• Surgical closure of VSD is recommended for patients with a history of infective endocarditis [18,33,60].

ESC/RSC IIa C (LoE C, GoR 5)

• In infants under six months of age, primary VSD correction is recommended in the presence of large (non-restrictive) defects combined with heart failure refractory to medical therapy [4,15,60].

No ESC guideline (LoE C, GoR 5)

• In asymptomatic patients with small (restrictive) VSDs, surgical intervention is recommended to prevent the development of aortic valve regurgitation, in the presence of a history of bacterial endocarditis, or with left ventricular enlargement [4,15,16,23,33,60-62].

ESC/RSC IIa C (LoE C, GoR 5)

• Pulmonary artery banding is recommended when radical correction is not feasible: multiple VSDs, VSD with aortic coarctation, or biventricular attachment of the tricuspid valve [4,15].

No ESC guideline (LoE C, GoR 5)

Comment: currently, pulmonary artery banding is used only in the presence of associated anomalies and malformations that complicate primary VSD correction.

• Surgery for isolated VSD is recommended to be performed via closure or patching with any certified material (a medical device with a registration certificate: cardiovascular synthetic patch***, cardiac occluder***) [4,15,16,23,60-62].

No ESC guideline (LoE C, GoR 5)

• Surgical VSD closure in children with pulmonary hypertension is recommended at a PVR index <6 Wood units/m2 and a PVR/SVR ratio <0.3 [35,75,81].

ESC/RSC I C (LoE C, GoR 4)

• Surgical VSD closure in children with pulmonary hypertension may be recommended at a PVR index of 6–8 Wood units/m2 and a PVR/SVR ratio of 0.3–0.5 after individual evaluation at a cardiac surgery center [35,75,81].

ESC/RSC IIb C (LoE C, GoR 4)

• Surgical VSD closure with retention/creation of an atrial septal fenestration in children with pulmonary hypertension and a PVR index >8 Wood units/m2 and a PVR/SVR ratio >0.5 may be recommended if the vasoreactivity test is positive (decrease in PVR index <6 Wood units/m2 and PVR/SVR ratio <0.3) [35,75,81].

ESC/RSC IIb C (LoE C, GoR 4)

• Surgical VSD closure in adult patients with pulmonary hypertension is recommended at PVR <3 Wood units and a persistent hemodynamically significant left-to-right shunt (Qp/Qs > 1.5) [33].

ESC/RSC I C (LoE C, GoR 5)

• Surgical VSD closure in adult patients with pulmonary hypertension is recommended at PVR of 3–5 Wood units and a persistent hemodynamically significant left-to-right shunt (Qp/Qs > 1.5) [33].

ESC/RSC IIa C (LoE C, GoR 5)

• In adult patients with pulmonary hypertension and PVR ≥ 5 Wood units, VSD closure may be recommended if a hemodynamically significant left-to-right shunt (Qp/Qs > 1.5) persists; however, the decision should be made on an individual basis at a cardiac surgery center in each case [33].

ESC/RSC IIb C (LoE C, GoR 5)

• Surgical correction of VSD is not recommended in Eisenmenger syndrome and severe pulmonary hypertension accompanied by exercise-induced desaturation [18,25,33].

ESC/RSC IIIC (LoE C, GoR 5)

Comments: clinical data do not allow precise determination of desaturation thresholds; however, based on the experience of most researchers, an arterial blood oxygen saturation of less than 90% is accepted as the threshold value [33].

Persistence of VSD is associated with the following risks in adult patients:

1. development of Eisenmenger syndrome if the VSD size is underestimated;

2. risk of paradoxical embolisms in venous thrombosis or transvenous cardiac pacing;

3. risk of arrhythmias, including life-threatening arrhythmias, in Eisenmenger syndrome;

4. risk of development and progression of heart failure, most commonly right ventricular failure [63].

ESC/RSC IIa C (LoE C, GoR 5)

Comments: lung transplantation with CHD correction or combined heart-lung transplantation is indicated for patients with Eisenmenger syndrome in the presence of predictors of poor prognosis—progressive deterioration of functional and hemodynamic status, refractory heart failure. According to the International Society for Heart and Lung Transplantation registry, for Eisenmenger syndrome due to simple defects, isolated lung transplantation with simultaneous defect correction may be the method of choice. However, for VSD, better outcomes are observed with heart-lung transplantation [66]. Treatment outcomes have improved in recent years: 5- and 10-year survival rates have reached 52–75% and 45–66%, respectively [67].

3.3 Other treatments.

Endovascular interventions

• VSD closure with a cardiac occluder*** is recommended when the defect is located at a sufficient distance from the tricuspid and aortic valves [62,68-70].

No ESC guideline (LoE C, GoR 5)

Comments: percutaneous VSD closure is an alternative to surgery in patients with high surgical risk factors, multiple prior surgical interventions, and poorly accessible muscular VSDs and Swiss-cheese VSDs.

• Closure of muscular VSDs with various devices is recommended in infants weighing more than 5 kg, young children, and adolescents with hemodynamically significant muscular VSDs (left ventricular or left atrial volume overload, or pulmonary-to-systemic blood flow ratio Qp/Qs ≥ 2:1) [72].

No ESC guideline (LoE C, GoR 5)

Comments: indications for endovascular closure of muscular and perimembranous VSDs are based on the presence of left ventricular overload signs confirmed by echocardiography and ECG, and cardiomegaly detected on chest radiography. In muscular VSDs located in the center of the interventricular septum, VSD closure with a cardiac occluder*** is considered an alternative to surgery. In perimembranous VSDs, there is a risk of complete atrioventricular block and impingement of tricuspid valve tissue leading to tricuspid or aortic regurgitation, which is seen in children and remains to be evaluated in adults.

• In newborns, infants weighing less than 5 kg, and children with hemodynamically significant muscular VSDs (left ventricular or left atrial volume overload, or Qp/Qs ≥ 2:1) and/or associated congenital heart defects requiring correction under cardiopulmonary bypass, it is recommended to consider performing a hybrid transventricular beating-heart VSD correction followed by surgical correction of the remaining defects or placement of a cardiac occluder*** during cardiopulmonary bypass [72].

No ESC guideline (LoE C, GoR 5)

• In newborns, infants, and children with hemodynamically significant inlet VSDs (left ventricular or left atrial volume overload, or Qp/Qs ≥ 2:1) with an inadequate distance between the defect and the atrioventricular or semilunar valves, VSD closure with cardiac occluders*** (both hybrid and percutaneous) is not recommended [72].

No ESC guideline (LoE C, GoR 5)

Comments: optimal defects for closure are small and medium-sized perimembranous VSDs (up to 10 mm) where the distance between the upper edge of the defect and the aortic valve annulus is 2 millimeters or more. Contraindications for closing perimembranous VSDs are: 1) combination of the defect with other congenital heart defects requiring open-heart surgery; 2) distance between the upper edge of the defect and the aortic valve annulus of less than 2 mm, or absence of the upper edge of the VSD; 3) prolapse of the aortic valve leaflet into the defect; 4) abnormal attachment of atrioventricular valve chordae to the edges of the defect.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Within 6 months after surgical correction of a VSD under cardiopulmonary bypass, patients with a complicated postoperative course (residual pulmonary hypertension, heart failure, infectious complications, repeated surgical interventions during the same hospitalization) are recommended to undergo rehabilitation in a specialized cardiological medical facility [16,76,79,87].

No ESC guideline (LoE C, GoR 5)

Comments: the following conditions may occur after VSD correction:

- Residual shunt or VSD recanalization may occur in 30% of cases after defect correction. In such cases, reoperation is indicated only for a hemodynamically significant shunt [80].

- Persistence of pulmonary hypertension may also be observed after successful congenital heart disease correction. In the presence of clinical manifestations, its treatment is carried out in accordance with current guidelines [134].

- Aortic regurgitation. It can result from the initial anatomy of the defect (cusp prolapse in subaortic or perimembranous VSD) or involvement of the aortic valve cusp in the suture. Its frequency reaches 5-20% [82-84]. Aortic regurgitation can progress, and its incidence increases with age. It usually progresses slowly, and this process is highly individual. Monitoring and (if necessary) surgical treatment are carried out in accordance with the guidelines for aortic regurgitation [85], although views on the optimal timing and method of correction remain controversial [84].

- Rhythm and conduction disorders (ventricular, supraventricular arrhythmias, bundle branch block, atrioventricular blocks, and sudden cardiac death) may occur both immediately after surgical correction and at more remote periods [80,86].

No ESC guideline (LoE C, GoR 5)

Comments: 6 months after VSD repair, patients may be cleared for participation in all competitive sports in the absence of: 1) signs of pulmonary arterial hypertension; 2) symptomatic tachyarrhythmias or second- or third-degree AV block; 3) signs of myocardial dysfunction; 4) ventricular or atrial tachycardia.

No ESC guideline (LoE C, GoR 5)

• Sanatorium-resort treatment is recommended for children after surgical correction of VSD in the compensation stage, without hemodynamic disturbances, with heart failure not exceeding stage I, in their climatic residential zone, at balneological and climatic resorts with the aim of improving the function of the cardiovascular and respiratory systems, the child's adaptive and compensatory mechanisms, increasing immunological reactivity and nonspecific resistance, reducing physical deconditioning, and correcting the child's psycho-emotional state [100,102-104,108,109].

No ESC guideline (LoE 5, GoR C)

Comment: referral of children for sanatorium-resort treatment after surgical correction of VSD is carried out no earlier than 6 months after surgical treatment.

In the rehabilitation of children after surgical correction of VSD, it is important to take into account the presence of main syndromes dominating in the preoperative pathogenesis:

- heart failure,

- pulmonary hypertension,

- hypoxia and arterial hypoxemia syndrome,

- reduced immune reactivity,

- asthenoneurotic syndrome.

• Sanatorium-resort treatment is not recommended for children after surgical correction of VSD in the presence of: heart failure stage 2A and above (higher than functional class II according to ROSS), moderate and severe pulmonary arterial hypertension (with mPAP >35 mm Hg), life-threatening tachyarrhythmias and bradyarrhythmias, ventricular or atrial tachyarrhythmias, second- and third-degree AV blocks, decreased left ventricular ejection fraction, subacute myocarditis, pericarditis, presence of a pacemaker [103,104].

No ESC guideline (LoE 5, GoR C).

Comment: general contraindications for sanatorium-resort treatment and acute or subacute stage diseases, including acute infectious diseases until the isolation period ends, must also be taken into account [100].

Children aged 4 to 14 years inclusive, including those accompanied by a legal representative, and children aged 15 to 18 years unaccompanied, are sent to sanatorium-resort institutions under the jurisdiction of the Russian Ministry of Health. If the sanatorium-resort institution has a cardiological department, children aged 7 to 14 years inclusive are admitted without being accompanied by a legal representative, unless the need for accompaniment is due to medical indications [101].

The duration of sanatorium-resort treatment is 21 days. To assess the baseline clinical and functional status of patients with VSD upon admission to sanatorium-resort treatment, it is necessary to have ECG and echocardiography data, and for children with arrhythmic syndrome, Holter monitoring data.

Methods of sanatorium-resort treatment.

• Climatotherapy (air and sun baths, sea bathing) is recommended for children after surgical correction of VSD in the compensation stage, without hemodynamic disturbances, with heart failure not exceeding stage I, with the aim of increasing the nonspecific resistance and immune defense of the child's body [102,104,105,121-125].

No ESC guideline (LoE 5, GoR C)

Comments: climatotherapy is carried out according to generally accepted methods and taking into account special dosimetric tables, starting with regimen I (sparing, mild) for 3-5 days, then moving on to regimen II (sparing-training);

Air baths are prescribed depending on the season of the year, the regimen in the ward (sanatorium climate ward) or in the open air, daily, for 5-30 minutes (15-20 procedures per course);

Heliotherapy (sun baths) is prescribed according to regimen I (sparing, diffuse solar radiation) with dosing from 1 to 4 therapeutic doses and regimen II (sparing-training) with an increase in therapeutic doses from 1 to 8, daily, 1-2 times a day, course of treatment 15-18 procedures;

Sea bathing (thalassotherapy) is carried out according to regimen I (sparing) and regimen II (sparing-training) (when the sea water temperature is not lower than 22°C). It starts with rubbing, pouring, and dipping for 2-3 days.

• At the sanatorium-resort stage, the prescription of medical nutrition is recommended for children after surgical correction of VSD in the compensation stage, without hemodynamic disturbances, and with heart failure not exceeding stage I [102-104,110,115].

No ESC guideline (LoE 5, GoR C).

Comments: standard diet (Pevzner therapeutic diet table No. 15) is used in sanatorium-resort institutions without exceeding the age norm for carbohydrates, animal fats, fluids, and salt [102,104,110].

• The prescription of a physical activity regimen is recommended for patients after surgical correction of VSD in the compensation stage, without hemodynamic disturbances, with heart failure not exceeding stage I [104,111-116,119,120,122].

ESC/RSC IIa B (LoE 5, GoR C)

Comments: the physical activity regimen includes: morning hygienic gymnastics with self-monitoring of heart rate (HR), therapeutic gymnastics; walks in the fresh air along the sea and in the park area.

Therapeutic dosed walking is prescribed adequately to the patient's condition at a pace of 70-80 steps per minute according to regimen I and 80-90 steps per minute according to regimen II with short rest periods (3-5 min) on a bench. Pulse rate is measured before and after therapeutic walking to monitor load tolerance.

For patients with VSD and stage _I heart failure, exercise loads are prescribed according to regimen I.

If a deterioration in the tolerance of physical and emotional loads or a deterioration in myocardial functional abilities is registered in patients at the sanatorium-resort treatment stage, the child is transferred to regimen I (sparing) until the end of the sanatorium stay.

• In the sanatorium, the prescription of therapeutic massage of the collar zone is recommended for children after surgical correction of VSD in the compensation stage, without hemodynamic disturbances, with heart failure not exceeding stage I [102-104,117,118].

ESC/RSC IIa C (LoE 5, GoR C)

Comments: massage techniques are used – stroking, rubbing, kneading. Procedures are carried out daily, lasting 10-12 minutes, with 8-10 procedures per course.

• For children after surgical correction of a VSD in the compensation stage, without hemodynamic disorders, and with circulatory insufficiency of no higher than degree I, it is recommended to prescribe antihypoxic physical therapy methods that promote increased blood oxygenation, reduced tissue hypoxia, and enhanced oxygen utilization by the myocardium and brain [102,104].

No ESC guideline (LoE 5, GoR C)

Comment: sodium chloride baths [102,104]. Water temperature 36–37 °C, sodium chloride concentration 10–20 g/L, procedure duration 8–12 min, every other day, 8–10 procedures per course;

Carbon dioxide baths [102,104]. Water temperature 34–36 °C, CO₂ concentration – 0.6–0.9–1.3 g/L, every other day, procedure duration 6–10 min, course of 8–10 procedures;

Oxygen baths [102,104]. Water temperature 36–37 °C, oxygen pressure 0.3 atm, 8–10 min prescribed every other day, 8–10 procedures per course.

• For children in a sanatorium after surgical correction of a VSD in the compensation stage, without hemodynamic disorders, and with circulatory insufficiency of no higher than degree I, recommended treatments include sedative methods aimed at enhancing inhibitory processes in the central nervous system [102–104,117,118].

ESC/RSC IIa C (LoE 5, GoR C)

Comments: sedative effects are provided by:

Therapeutic massage of the collar zone (according to the above method) [102–104,117,118].

Conifer baths [102,104]. Used in children older than 6 years, at a temperature of 36–37 °C, every other day, for 7–10 min, with 8–10 procedures per course.

Iodine-bromine baths [102,104]. Water temperature 36–37 °C, for 8–10 min (depending on age), every other day, course of 8–12 baths.

Nitrogen baths [102,104]. Water temperature in the bath 36 °C, for 8–10 min, every other day, course of 8–10 baths.

Electrosleep therapy [102,104,121]. Performed using the orbital-occipital method with a current of 6–10 mA, duration 15–20 minutes, daily, course of 12–15 procedures.

• At the sanatorium-resort stage of treatment for children after surgical correction of a VSD in the compensation stage, without hemodynamic disorders, and with circulatory insufficiency of no higher than degree I, carbon dioxide baths (using the above method) aimed at stimulating cardiac activity are recommended as cardiotonic methods [102–104].

No ESC guideline (LoE 5, GoR C).

• For patients after surgical correction of a VSD in the compensation stage, without hemodynamic disorders, and with circulatory insufficiency of no higher than degree I, recommended are vasodilator methods aimed at improving microcirculation [102,104,105,111–116,119–125].

No ESC guideline (LoE 5, GoR C)

Comments: such methods include: climatotherapy (using the above method) [102,104,105,121–125].

Therapeutic massage of the collar zone (using the above method) [102–104,117, 118].

Conifer baths (using the above method) [102,104].

Medical physical education (using the above method) [104,111–116,119,120,122].

“Dry” carbon dioxide baths [104]. Carbon dioxide concentration 32%, temperature 32 °C, procedure duration 8–20 min (depending on age), daily or every other day, course of 8–10 procedures.

Amplipulse therapy [102]. Prescribed paravertebrally to the cervical-collar zone (C_IV–Th_II), current types IV and III, exposure frequency 30 Hz, modulation depth 50–75% for 5 min for each current type, daily, course of 10 procedures.

Galvanization of the collar region (Scherbak galvanic collar) [102–104]. Current intensity 2–8 mA, procedure duration 8–16 min according to the schedule, daily, course of 10 procedures.

Infrared laser therapy [102]. Prescribed paravertebrally at the level of C_IV–Th_II, labile technique, frequency 80 Hz, pulse power 2–4 W, procedure duration 2, 3, 4 min (depending on age), daily, course of 5–6 procedures.

Showers: circular and jet [102,104]. Water temperature 35–30 °C, administered for 2–3 minutes, every other day, course of 10–15 procedures.

Contrast shower [104]. Water temperatures 36 and 18 °C, administered for 8–10 min, every other day, course of 8–10 procedures.

• For patients after surgical correction of a VSD in the compensation stage, without hemodynamic disorders, and with circulatory insufficiency of no higher than degree I, recommended are vegetative-correcting methods aimed at correcting autonomic dysfunction [102,104,105,121–125].

No ESC guideline (LoE 5, GoR C)

Comments: applied: air baths (using the above method) [102,104,105,121–125].

Heliotherapy (using the above method) [102,104,105,121–125].

Thalassotherapy (using the above method) [102,104,105,121–125].

Conifer baths (using the above method) [102,104].

Hydrokinesitherapy (therapeutic swimming) [104]. Therapeutic swimming is performed in warm water of an open water body or swimming pool at a comfortable pace with a gradual increase in distance and duration of stay in the water.

• Psychotherapy is recommended for patients after surgical correction of a VSD inamarin compensation stage, without hemodynamic disorders, and with circulatory insufficiency of no higher than degree I to correct the child's relationships with the surrounding social environment, eliminate negative psycho-emotional factors, and form an adequate response to stressful situations [104,126,127].

No ESC guideline (LoE 5, GoR C)

Comments: individual, small-group, and family sessions are conducted.

In case of deterioration of the clinical and functional state of patients after surgical correction of a VSD at the sanatorium-resort stage of treatment, it is necessary to provide emergency professional assistance and further management of the child on basic drug therapy, a sparing climate-motor and therapeutic regimen.

5. Prevention and Dispensary Observation

The prognosis after surgical or endovascular correction of a VSD is favorable provided timely correction of congenital heart disease is performed.

Life expectancy and physical performance may be limited in the presence of pulmonary hypertension. This is most pronounced in patients with Eisenmenger syndrome.

In patients with unoperated hemodynamically insignificant VSDs, the prognosis is favorable in the absence of risk of complications (infective endocarditis, aortic valve regurgitation) [15,20].

ESC/ACC I C (LOE C, GOR 5)

Comments: frequency of dispensary observation by a pediatric cardiologist/cardiologist is at 1, 3, 6, and 12 months after surgery. The comprehensive dispensary observation includes ECG and echocardiography, and if necessary, graded exercise stress tests and pulse oximetry, chest radiography, complete blood count, levels of potassium, sodium, glucose, creatinine, total protein, urea, total bilirubin, and CRP (to rule out cardiac arrhythmias, heart failure decompensation, assess renal and hepatic function, and exclude inflammation and anemia). INR monitoring is required in the presence of a prosthetic valve.

Further patient follow-up is carried out at intervals of 3–36 months [28,33,60].

After performing the operation (open/endovascular), it is recommended to remain under dispensary registration for a year, and subsequently according to indications. Patients with left ventricular dysfunction, residual shunt, pulmonary arterial hypertension, aortic regurgitation, or ventricular outflow tract obstruction should be followed up annually in specialized centers.

In patients with a small congenital or residual VSD with preserved left ventricular function, absence of pulmonary hypertension, and no other lesions, follow-up visits may be considered at intervals of 3–5 years.

After endovascular intervention, regular monitoring is required during the first 2 years, and thereafter depending on the result – every 2–4 years.

When determining the frequency of monitoring, one should be guided by the presence of symptoms of heart failure, hemodynamic status, presence of cardiac arrhythmias, hypoxemia, etc. Depending on these factors, all patients with congenital heart disease can be divided into four groups (A, B, C, D):

Group A

- heart failure functional class I;

- absence of anatomical hemodynamic disorders;

- absence of cardiac arrhythmias;

- normal liver, kidney, and lung function.

Group B

- heart failure functional class II;

- minimal stenosis and/or valve regurgitation (degree I);

- mild dilation of the aorta or ventricle(s);

- left ventricular ejection fraction at least 50%, right ventricular ejection fraction at least 40%;

- hemodynamically insignificant intracardiac shunts (Qp/Qs < 1.5);

- absence of hypoxemia;

- cardiac arrhythmias not requiring treatment;

- absence of signs of pulmonary hypertension;

- normal kidney and liver function.

Group C

- heart failure functional class III;

- moderate or significant stenosis and/or valve regurgitation (degrees II–III), arterial or venous stenosis, moderate dilation of the aorta or ventricle(s);

- LV EF 40–49%, RV EF 35–39%;

- hemodynamically significant intracardiac shunts (Qp/Qs ≥1.5);

- mild hypoxemia (Sat O2 ≥85%);

- cardiac arrhythmias controlled by therapy;

- pulmonary hypertension (pulmonary hypertension FC I–II);

- internal organ dysfunction controlled by therapy.

Group D

- heart failure FC IV;

- significant aortic dilation;

- severe arterial hypoxemia (Sat O2 <85%);

- cardiac arrhythmias refractory to therapy;

- pulmonary hypertension (pulmonary hypertension FC III–IV);

- internal organ dysfunction refractory to ongoing therapy.

Depending on whether a patient with a corrected or uncorrected VSD belongs to a specific group, different follow-up frequencies and scopes of required examinations are recommended:

ESC/ACC I C (LoE C, LoR 5)

ESC/ACC IIa C (LoE C, LoR 5)

Comments: Echocardiography allows for the detection of aortic or tricuspid regurgitation, residual shunt, ventricular dysfunction, elevated pulmonary artery pressure, and the development of subaortic stenosis.

ESC/ACC I C (LOE C, GOR 5)

Comments: the risk of complete atrioventricular block requires special attention in patients after VSD closure (in case of bifascicular block or transient trifascicular block).

• During the follow-up of patients after endovascular (transcatheter) VSD closure, it is recommended to use antithrombotic agents for 6 months [33,60,90,97].

ESC/ACC IIa C (LOE C, GOR 5)

Comments: #Acetylsalicylic acid** (off-label in children under 15 years of age) orally at a dose of 1–5 mg/kg/day once daily or #clopidogrel** (off-label in children under 18 years of age) orally at a dose of 0.2 mg/kg/day once daily are used as antithrombotic agents [90,97].

• Children who have undergone VSD correction surgery are recommended to be vaccinated no earlier than three months later [23].

ESC/ACC IIa C (LOE C, GOR 5)

• During the follow-up of patients after surgical or endovascular (transcatheter) VSD closure, it is recommended to provide infective endocarditis prophylaxis for 6 months [91].

ESC/ACC I C (LOE C, GOR 5)

Comments: for any type of congenital heart disease treated with cardiovascular patches, synthetic***, if indicated, bacterial endocarditis prophylaxis is carried out for 6 months postoperatively or for life if residual shunts or valvular regurgitation persist.

Endocarditis prophylaxis is performed during dental procedures accompanied by damage to the oral mucosa (tooth extraction, manipulation in the periapical zone of the tooth, etc.).

6. Organization of Medical Care

Indications for hospitalization in a medical organization:

1. presence of heart failure symptoms;

2. presence of pulmonary hypertension;

3. planned surgical treatment.

Indications for emergency hospitalization:

1. deterioration of the patient's functional status due to progressive circulatory failure symptoms or cardiac arrhythmias;

2. infective endocarditis;

3. pulmonary hypertension requiring selection/adjustment of therapy.

Indications for patient discharge from a medical organization:

1. absence of a significant shunt across the interventricular septum after surgical correction of the defect;

2. absence/compensation of circulatory failure symptoms.

7. Additional Information

• Patients with VSD and PH are recommended to avoid excessive physical activity that provokes potential-risk symptoms such as severe dyspnea and weakness, dizziness, syncope, and chest pain [18,87].

ESC/ACC IIa C (LoE C, LoR 5)

ESC/ACC IIa C (LoE C, LoR 5)

• In patients with a history of infective endocarditis, as well as uncorrected VSD or a residual shunt, infective endocarditis prophylaxis is recommended [91].

ESC/ESC I C (LoE C, GoR 5)

ESC/ACC IIa C (LoE C, LoR 5)

Comments: air travel is generally well tolerated by patients [18,137].

Measures should be taken to prevent deep vein thrombosis of the lower extremities.

Pregnancy and childbirth

Pregnancy and childbirth are generally well tolerated [93]:

- against the background of corrected VSD;

- in patients with preserved LV function;

- in NYHA functional classes I–II NYHA;

- in the absence of significant pulmonary hypertension and significant right ventricular outflow tract obstruction;

- in small VSDs.

ESC/ACC III C (LoE C, LoR 5)

Comments: pregnancy is strictly contraindicated in Eisenmenger syndrome due to high maternal and infant mortality [93]. Pregnancy in patients with cyanosis in the absence of PH carries a significant risk to the mother and fetus.

Sat O2 <85% and hemoglobin >200 g/L prior to pregnancy are the most important predictors of maternal mortality [94].

• In pregnant patients with ventricular septal defect (VSD) presenting with cyanosis and pulmonary hypertension, artificial termination of pregnancy is recommended [93].

ESC/ESC I C (LoE C, GoR 5)

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Avramenko A.A. (Samara)

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

3. 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"

4. Belov V.A., (Kaliningrad)

5. Bogdanov V.N. (Chelyabinsk)

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

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

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

9. Brodsky A.G., PhD in Medical Sciences, (Surgut)

10. Volkov S.S., PhD in Medical Sciences, (Moscow)

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

12. Garmash O.I., DSc in Medical Sciences (Yevpatoria)

13. Gladyshev I.V., (Chelyabinsk)

14. Golubova T.F., DSc in Medical Sciences, Professor (Yevpatoria)

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

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

17. Gorbachevsky S.V., DSc in Medical Sciences, "Association of Cardiovascular Surgeons of Russia", (Moscow)

18. Grigoryan A.M., PhD in Medical Sciences, "Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists", (Moscow)

19. Eliseeva L.V., (Yevpatoria)

20. Evtushenko A.V., DSc in Medical Sciences, "Russian Society of Cardiology" (Kemerovo)

21. Zelenikin M.A., DSc in Medical Sciences, "Association of Cardiovascular Surgeons of Russia", (Moscow)

22. Zelenikin M.M., DSc in Medical Sciences, "Association of Cardiovascular Surgeons of Russia", (Moscow)

23. Irtyuga O.B., DSc in Medical Sciences, Russian Society of Cardiology (Saint Petersburg)

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

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

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

27. Komissarov M.I., (Saint Petersburg)

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

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

30. Kurganova A.V., PhD in Medical Sciences (Yevpatoria)

31. Levchenko E.G., (Moscow)

32. Lezhnev A.A., (Moscow)

33. Lyubchik V.N., DSc in Medical Sciences (Yevpatoria)

34. Martynyuk T.V., DSc in Medical Sciences, "Russian Society of Cardiology", (Moscow)

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

36. Nalimov K.A., (Khabarovsk)

37. Nikiforov A.B., (Moscow)

38. Petrushenko D.Yu., (Kazan)

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

40. Podoksenov A.Yu., (Tomsk)

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

42. Rychina Inna Evgenyevna – Candidate of Medical Sciences (Moscow) All-Russian Public Organization for Assistance to the Development of Radiology and Therapy "Russian Society of Radiologists"

43. Svobodov A.A., Doctor of Medical Sciences, (Moscow)

44. Semenyak E.G. (Yevpatoria)

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

46. 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"

47. Tataurova V.P., (Yevpatoria)

48. Teplov P.V. (Krasnoyarsk)

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

50. Shekhmametyev R.M., (Perm)

51. Shlyakhto E.V., Academician of the Russian Academy of Sciences, Russian Society of Cardiology (Saint Petersburg)

52. Schmaltz A.A., Doctor of Medical Sciences, (Moscow)

53. Yurpolskaya L.A., Doctor of Medical Sciences (Moscow) All-Russian Public Organization for Assistance to the Development of Radiology and Therapy "Russian Society of Radiologists"

54. Yakovleva A.N., (Saint Petersburg)

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. Surgeon

5. Ultrasound Diagnostics Physician

6. Functional Diagnostics Physician

7. Pediatrician

8. X-ray Endovascular Diagnostics and Treatment Physician

9. Radiologist

During the development of the clinical guidelines, international scales for the levels of recommendation persuasiveness and levels of evidence reliability were used (Tables 1 and 2), as well as a new system of scales for the levels of evidence reliability (LER) and levels of recommendation persuasiveness (LRP) for therapeutic, rehabilitative, preventive, and diagnostic interventions (Tables 3, 4, and 5), introduced in 2018 by the Center for Healthcare Quality Assessment and Control of the Russian Ministry of Health. The National Guidelines were formulated based on ESC recommendations, taking into account national specifics, examination and treatment features, and the availability of medical care. For this reason, the text of these clinical guidelines simultaneously uses two scales for evaluating the reliability of evidence for recommendation theses: the ESC levels of evidence reliability with LRP and LER. ESC recommendation classes have been added to assess the necessity of executing the recommendation thesis.

Table 1. Classes of recommendations according to the European Society of Cardiology (ESC) guidelines.

Table 2. Levels of evidence reliability according to the European Society of Cardiology (ESC) guidelines.

Table 3. Scale for assessing the levels of evidence reliability (LER) for diagnostic methods (diagnostic interventions).

Table 4. Scale for assessing the levels of evidence reliability (LER) for methods of prevention, treatment, and rehabilitation (preventive, therapeutic, and rehabilitative interventions).

Table 5. Scale for assessing the levels of recommendation persuasiveness (LRP) for methods of prevention, diagnostics, treatment, and rehabilitation (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 dated November 21, 2011);

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

3. Order of the Ministry of Health of Russia No. 103n dated February 28, 2019 "On Approval of the Procedure and Timeframes for the Development of Clinical Guidelines, Their Revision, the Standard Form of Clinical Guidelines and Requirements for Their Structure, Composition, and Scientific Validity of Information Included in Clinical Guidelines" (Registered with the Ministry of Justice of Russia on May 8, 2019, No. 54588);

4. Order of the Russian Ministry of Health No. 203n dated May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care";

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

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

7. "On Approval of the Rules for Performing X-ray Examinations" (Order of the Ministry of Health of Russia No. 560n dated June 9, 2020 (as amended on February 18, 2021))

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

Appendix B. Physician Action Algorithms

Use of diagnostic imaging methods in VSD

Transthoracic echocardiography performance technique

Requirements:

In newborns: transducers with a frequency of 7.5–12 MHz; in adults: 2.5–7 MHz.

Contraindications: none.

Limitations: cases of an unsatisfactory acoustic window.

Important indicators when analyzing and interpreting the obtained images:

Defect localization:

Examination in multiple long- and short-axis views (the interventricular septum has a complex spatial geometry). Views:

- the four-chamber view of the heart from the apical or subcostal approaches visualizes the inflow part of the interventricular septum,

- the five- or three-chamber views from the apical or subcostal approaches / the left ventricular long-axis view from the left parasternal approach / the right ventricular long-axis view from the parasternal or subcostal approaches visualize the outflow part of the interventricular septum.

In the short-axis view of the LV, scanning from the base to the apex, evaluate anterior VSDs (between 12 and 2 o'clock on the conventional clock face), central (mid) muscular VSDs (between 10 and 12 o'clock), and inferoposterior VSDs (between 7 and 10 o'clock).

In the left parasternal position in the short-axis view just below the level of the aortic valve, the perimembranous part of the septum is identified, originating from the level of the tricuspid valve annulus (between 9 and 11 o'clock). Conal septum: between 11 o'clock and the pulmonary valve (2 o'clock). Defects at 9–11 o'clock are perimembranous, subaortic; at 11–13 o'clock are subarterial; 12–15 o'clock are subpulmonary. Anterior or posterior displacement of the conal septum constitutes a malalignment defect.

Defect size:

Measurements should be performed in B-mode or across the edges of the color jet using color Doppler flow imaging (ultrasound beam orientation: perpendicular to the septum, parallel to the blood flow).

The measured defect diameter should be compared with the normal aortic valve size (aortic annulus diameter is measured in the left ventricular long-axis view) and evaluated using Z-scores [131]:

- defects less than 1/2 of the aortic diameter are restrictive (small);

- greater than or equal to half the aortic diameter are non-restrictive (moderate, large).

Associated cardiac pathology

When diagnosing an isolated VSD:

- exclude "complex" congenital heart disease,

- double-chamber right ventricle,

- determine the presence of aortic regurgitation and/or prolapse of the right or non-coronary cusps, especially in the presence of perimembranous, muscular outlet, and subarterial defects.

Determination of the hemodynamic significance of blood shunting in VSD: cardiac morphometry, pulmonary-to-systemic flow ratio, severity of pulmonary hypertension.

Left atrial and left ventricular enlargement: left-to-right shunting across a VSD causes enlargement of the LA, followed by LV dilatation. Transducer position: from the left parasternal long-axis view using M-mode with the cursor perpendicular to the aorta at the level of the aortic valve. The ratio of the aortic diameter at end-diastole to the left atrial diameter at end-systole is measured. A ratio greater than 1.5 indicates LA enlargement. The left atrium-to-aorta ratio serves as a marker of increased pulmonary venous return, given the relatively fixed structure of the aortic annulus, which does not dilate during left heart volume overload.

Visual assessment of the LV is performed from the apical four-chamber view in comparison with the right heart chambers.

The LV end-diastolic dimension (EDD) and quantitative assessment of LV systolic function are determined in M-mode from the left parasternal long-axis or LV short-axis view at the level of the mitral valve (MV) leaflet tips, which serve as a reference 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.

Z-scores will assist in the quantitative assessment of the LV EDD [131].

Pulmonary-to-systemic flow ratio (Qp/Qs)

Measurement of the pulmonary-to-systemic blood flow ratio: the diameters of the aortic and pulmonary valve annuli and the velocity-time integrals for the aorta and pulmonary artery are obtained using pulsed-wave Doppler.

The semilunar valves must be free of stenosis and significant regurgitation; furthermore, measuring the Qp/Qs ratio is not meaningful in the presence of high pulmonary vascular resistance (e.g., in newborns) or severe pulmonary hypertension. There are no clear recommendations for moderate pulmonary hypertension (e.g., the clinical significance of the Qp/Qs ratio in patients with pneumonia, bronchopulmonary dysplasia, or chronic obstructive pulmonary disease is unclear).

Pulmonary hypertension

For echocardiographic diagnosis of the probability of pulmonary hypertension and for assessing RV function, use the techniques described in the relevant guidelines [132, 133, 137].

Appendix C. Patient Information

Ventricular septal defect is the most common congenital heart defect. A defect, i.e., an opening in the septum separating the right and left ventricles, may be the sole anomaly of normal cardiac development or part of a more complex heart defect.

The interventricular septum is a robust muscular partition forming the inner walls of both the right and left ventricles, comprising approximately 1/3 of their total surface area in each. Like the rest of the ventricular wall, it participates in the contraction and relaxation of the heart during every cardiac cycle. In the fetus, it develops from three component parts. By the 4th–5th week of gestation, all these components must precisely align and fuse with one another. If this fails to happen for any reason, an opening, or defect, remains in the septum. Shortly after birth and the establishment of normal circulation in both circuits, a significant pressure gradient arises between the left and right ventricles. Blood from the left ventricle then begins to be pumped simultaneously into the aorta—its correct destination—and through the defect into the right ventricle, where it does not belong. That is, with every cardiac contraction, a left-to-right shunt occurs. In this situation, the right ventricle is forced to work with an increased workload to pump this extra volume of already deoxygenated blood back into the lungs and the left heart.

Ventricular septal defects can be "typical," i.e., most common, occupying the upper portion of the septum. They can be muscular, i.e., located closer to the apex, and finally, high (subarterial), located beneath the pulmonary valve, either single or multiple (i.e., more than one). Remember: the louder the heart murmur, the smaller the defect. In the majority of cases—approximately 65–75%—such defects close spontaneously, and if no additional symptoms appear, one can safely wait for 4–5 years or even longer. However, if a child reaches school age remaining asymptomatic, surgery may still be proposed to you. The fact is that if the child contracts a childhood infection or even undergoes a simple dental extraction in the presence of a ventricular septal defect, infective endocarditis—an inflammatory process of the inner lining of the heart chambers—may develop. Although this probability is very low, only 1–2% of cases, it does exist. In such cases, the defect is closed for prophylactic rather than clinical reasons [95].

Large defects are a different story entirely, and far more dangerous. Immediately after the child's first breath, blood flow from the left ventricle is divided into two streams—into the aorta and through the defect—and they are equal in volume. Not only the heart but also the pulmonary vasculature is subjected to severe strain: the right heart chambers and pulmonary vessels become overloaded with the increased volume of excess blood entering via the defect. The most critical indicators of this progression are pulmonary artery pressure and the magnitude of the shunt. Today, these data are provided by echocardiography and cardiac catheterization. An increase in pulmonary circulation pressure indicates pulmonary hypertension, the most formidable consequence of a large left-to-right shunt. Numerous compensatory mechanisms are recruited: ventricular muscle mass increases, and the pulmonary vessels adapt—initially accommodating the excess blood volume, and subsequently thickening the walls of arteries and arterioles, making them stiffer and less compliant. This period is hazardous because the child's clinical condition may improve substantially; however, this improvement is deceptive, and the window for surgical intervention may be missed. If this situation persists for quite some time—several months or years—pressures in the right and left ventricles eventually equalize across all phases of the cardiac cycle, and shunting through the defect ceases. Subsequently, pressure in the right ventricle may exceed that in the left, initiating a so-called "reverse shunt," whereby deoxygenated blood flows through the defect into the arterial system—the systemic circulation. The patient becomes cyanotic. We have described this scenario so that it is understood that a ventricular septal defect, which can be very easily and safely closed in the early stages, can progress to a defect where closure loses its purpose and surgery is no longer timely. We are referring here, as a reminder, only to large defects or cases where there are multiple holes in the septum [95].

What should you pay attention to in order to avoid such developments in time?

The main indicator in the neonatal period is weight gain. In older children, this is accompanied by frequent colds that become prolonged and can progress to pneumonia. This can continue for several months, and if the cause is a VSD, such a child must be under the constant supervision of a cardiologist; if the symptoms do not resolve, medications to manage signs of heart failure will likely be prescribed.

With drug therapy, symptoms may disappear or significantly decrease. However, if nothing changes, if the heart size increases and the defect size on ultrasound remains the same, surgical consultation is necessary.

In the first few months of life, ventricular septal defects, even large ones, may decrease or close spontaneously. If the child does not improve, waiting is not an option, as the situation may progress to the scenario described above, and surgery will be too late.

The best surgical results are achieved after repairing large VSDs at the age of under two to two and a half years, when the child exhibits signs of heart failure. At this stage, all processes are still reversible. The heart rapidly decreases in size, and blood flow in both circulations normalizes [95].

Surgical treatment is the only method that completely eliminates the defect and its consequences. VSD repair is classified as open-heart surgery because it requires opening the heart chambers and is therefore performed using cardiopulmonary bypass. VSDs are closed by suturing the opening or, more commonly, using a synthetic patch that is rapidly endothelialized by the patient's own heart tissue. Interventional catheter-based methods are also currently used to close defects, but this is not always possible and depends on the anatomical location of the defect and the interventional cardiologist's expertise.

In the absence of surgical treatment, VSD leads to increased pressure in the pulmonary vessels—pulmonary hypertension (PH), and with additional hemodynamic signs—pulmonary arterial hypertension (PAH). Patients typically complain of shortness of breath, dizziness, fatigue, and weakness, and the severity of these symptoms usually worsens as the disease progresses. There are numerous diagnostic tests and examination methods used to establish a diagnosis, which your attending physician will discuss with you.

Most patients note that they can no longer maintain the active lifestyle they are accustomed to. It is necessary to reconsider your daily activity rhythm and adapt to a level of physical exertion that does not cause discomfort. If PH is complicated by the development of heart failure, fluid intake should be restricted: it is not recommended to drink more than 1.5 liters per day, and dietary sodium intake should be reduced, as sodium regulates fluid balance in the body. When tissue fluid content increases, blood volume also increases, which raises the workload on your heart. One of the most effective ways to reduce the workload on the heart is to decrease the amount of salt in your diet. A low-salt diet will have a greater impact on your health if it incorporates foods rich in calcium, magnesium, potassium, and phosphorus.

To normalize your fluid balance, measure the amount of fluid you drink every day for at least the first few weeks. Account for water used to swallow pills, as well as soups, fresh fruits and vegetables, ice cream, and gelatin. Weigh yourself daily. Weight gain is one of the first signs of fluid retention. If you notice weight gain while maintaining your usual diet, you must inform your doctor.

If you led an athletic lifestyle before the illness, consult your physician to determine how appropriate sports activities are for you. Exercise must be stopped if you experience lightheadedness, fatigue, chest tightness, palpitations, or worsening shortness of breath. Avoid outdoor physical activity in cold weather and high humidity.

Currently, there is no cure for PH. However, there are other medications that improve condition and help patients enhance their physical capacity. The physician will select appropriate treatment and explain the benefits and advantages of its various options. Therapy is selected individually; remember that all patients are different, and your doctor will choose the treatment option best suited for your case. Patients with a confirmed diagnosis of PH require careful outpatient follow-up with doctor visits every 6–12 months.

All patients taking international flights are recommended to carry medical documents regarding their diagnosis, the location of the nearest local PH center, and its contact information.

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

No.