Aortopulmonary septal defect: clinical guidelines

List of Abbreviations

SVR — systemic vascular resistance

CHD — congenital heart disease

RVOT — right ventricular outflow tract

APVSD — aortopulmonary window

ASD — atrial septal defect

ESC — European Society of Cardiology

IE — infective endocarditis

CT — computed tomography

LV — left ventricle

PA — pulmonary artery

PH — pulmonary hypertension

LA — left atrium

PVR — pulmonary vascular resistance

PVR — pulmonary circulation

CIR — circulatory insufficiency

PVR — peripheral vascular resistance

RV — right ventricle

RA — right atrium

6MWT — 6-minute walk test

ECG — electrocardiography

EchoCG — echocardiography

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

Terms and Definitions

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

Pulmonary hypertension is a pathophysiological condition characterized by an increase in mean pulmonary arterial pressure > 25 mm Hg, leading to right ventricular heart failure as the most frequent cause of patient mortality.

Eisenmenger syndrome encompasses all large intracardiac and extracardiac systemic-to-pulmonary shunts that lead to a significant increase in PVR, reverse or bidirectional blood shunting, development of cyanosis, secondary erythrocytosis, and multiorgan damage.

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

Grade of recommendation (GoR) – the degree of certainty that the effect of an intervention is reliable and that following the recommendations will bring more benefit than harm in a specific situation [1].

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

Echocardiography is an ultrasound imaging method aimed at studying the morphological and functional changes of the heart and its valvular apparatus.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Aortopulmonary window (APVSD) is a congenital heart defect (CHD) characterized by the presence of a communication (window) between the adjacent parts of the ascending aorta and the pulmonary trunk, with two separately formed semilunar valves. Synonyms: aortopulmonary window, aortopulmonary fistula, fenestration or septal defect.

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

The first trimester of pregnancy is critical for the formation of the heart with its chambers and great vessels, since exposure to damaging factors or spontaneous mutations during this specific period leads to impaired organogenesis. Therefore, major malformations of the heart and great vessels arise predominantly between the 3rd and 8th weeks of pregnancy. Cardiac structures are particularly vulnerable during stages X–XX of development according to Streeter's classification [2,3]. Aortopulmonary window defects (APVSD), like other congenital heart defects, predominantly follow a polygenic-multifactorial inheritance pattern; however, exact mechanisms have not been established. Furthermore, this CHD is virtually never part of other chromosomal anomalies typical of a number of other malformations (22q11.2 deletion syndrome or DiGeorge syndrome, Down syndrome, Sotos syndrome, Patau syndrome, CHARGE, etc.) and presents with a normal karyotype. Nevertheless, the incidence of concomitant cardiac pathology remains high, including complex congenital heart defects [3,4,5].

APVSD is characterized by pathological blood shunting from the Ao to the PA and exhibits a number of patterns typical of congenital heart defects with a left-to-right shunt. Hemodynamic changes depend on the following factors: the location and size of the defect, pulmonary vascular resistance (PVR) and its ratio to systemic vascular resistance (SVR), the condition of the right (RV) and left (LV) ventricular myocardium, and pressures in the systemic and pulmonary circulations. Changes in the RV manifest as concentric hypertrophy, since the RV myocardium works under conditions of increased pressure. There is no volume overload of the RV, as the pathological blood shunting from the Ao to the PA occurs distally. However, the LV exhibits volume overload, because continuous blood shunting into the pulmonary circulation leads to LV dilation. In some cases, this can lead to heart failure at an early age. If patients survive this period, pulmonary hypertension develops very rapidly due to pulmonary hypervolemia, the pulsing factor of systolic pressure, and the damaging effect of oxygenated blood on the pulmonary vascular endothelium. Without surgical correction of the defect and, consequently, the persistence of pulmonary hypertension, Eisenmenger syndrome subsequently develops [6-9].

Eisenmenger syndrome is a consequence of an arteriovenous blood shunt accompanied at various stages by increased blood flow velocity in the pulmonary circulation, vasospasm with the appearance of shear stress phenomena, and blood flow turbulence. In the early stages, morphological changes, including intimal hyperplasia and medial hypertrophy of pulmonary vessels, are reversible. The disease course is accompanied by a cascade reaction featuring ongoing endothelial damage, platelet aggregation, release of thromboxane A2, vasospasm, and rising pulmonary arterial pressure alongside turbulent blood flow. Progression of pulmonary hypertension ultimately leads to irreversible pulmonary vascular changes in the form of plexiform lesions and arteritis [1,9-12].

1.3 Epidemiology of the Disease or Condition

APVSD is not a common congenital heart defect (CHD). Within the structure of CHDs, APVSD accounts for 0.2–0.3% [1,13,14]. According to other data, the frequency is even lower at 0.1% [15]. However, the unfavorable course of the defect highlights the importance of its timely diagnosis. This is reflected in autopsy data, according to which APVSD accounts for 1% of all CHDs [15]. APVSD is frequently found in combination with other CHDs. While it was previously believed that APVSD most commonly occurred with a patent ductus arteriosus (PDA) (up to 12%), recent data indicate that various anomalies and CHDs are present in more than 50% of cases with this defect [4,5]. The latter include both common CHDs (transposition of the great arteries, Tetralogy of Fallot, septal defects, partial anomalous pulmonary venous drainage, right-sided aortic arch, etc.) and very rare ones, yet with typical combinations (aberrant origin of the right coronary artery from the pulmonary trunk) [5-9]. The combination of distal APVSD with hypoplasia of the aortic arch isthmus, origin of the right pulmonary artery from the aorta, and an intact interventricular septum is considered fatal (Berry syndrome) [16]. Autopsy material also describes combinations with pulmonary artery sling, pulmonary valve stenosis, mitral valve stenosis, persistent left superior vena cava, etc. [17]. Male predominance with a 3:1 ratio has been reported [18]. According to other data, gender distribution shows no obvious disproportion [19].

Unlike other, more common septal defects, the development of pulmonary hypertension and Eisenmenger syndrome is more rapid and malignant. For instance, in the Euro Heart Survey registry of adult patients with ASD or VSD, at least 28% had pulmonary hypertension and 12% had Eisenmenger syndrome [20]. Observations concerning adult patients with APVSD are, firstly, relatively sparse due to the natural unfavorable clinical course. Secondly, pulmonary hypertension or Eisenmenger syndrome is present in all cases [1,21-25].

APVSD dimensions are important for prognosis, and the defect is large in at least 90% of cases [26]. However, regardless of size, APVSD shows no tendency toward spontaneous closure [27]. Large APVSDs are accompanied by pronounced hemodynamic disturbances and a severe clinical course, resulting in low patient survival and an average life expectancy of only up to 15 years, which is significantly lower than in other septal defects or patent ductus arteriosus [13]. Early mortality in infancy is also characteristic of the defect, with 40% of patients dying within the first year of life without surgical treatment [28]. In rare cases where the defect is diagnosed at an older age, pulmonary hypertension or Eisenmenger syndrome comes to the forefront.

The survival of patients with APUD and Eisenmenger syndrome is similar to that of large VSDs or PDA. However, few patients survive into the 3rd or 4th decade, let alone reach the age of fifty [26,29]. Right ventricular heart failure and progressive deterioration in exercise tolerance are negative prognostic factors, as in other congenital heart diseases complicated by severe PH with a reverse or "right-to-left" shunt [13].

1.4 Features of Coding the Disease or Condition

Q 21.4 – Aortopulmonary septal defect (Aortopulmonary window – ICD-10).

I 27.8 – Other specified forms of pulmonary heart disease.

1.5 Classification of the disease or condition

• By location in accordance with the classification used by the Society of Thoracic Surgeons (STS Congenital Heart Surgery Database Committee) and the European Association for Cardiothoracic Surgery, Mori K. et al. (1978) as modified by Ho S. et al. (1994) [2,13,30-32,36]:

  Type I, proximal (directly or a few mm above the semilunar valves);

  Type II, distal (located in the upper part of the ascending aortic arch);

  III type, complete or total (only a truncal septum is present for the semilunar valves, with no separation of the aorta and pulmonary artery throughout);

  IV type, intermediate (distant defect, but with edges suitable for endovascular closure).

• By location in accordance with the classification of the Bakulev National Medical Research Center of Cardiovascular Surgery (1987).

  1. The defect between the aorta and the pulmonary artery is located in the middle part of the aortopulmonary septum and has well-defined edges.

  2. The aortopulmonary window proper, located directly above the sinuses of Valsalva, has a significant length (classic form).

  3. The defect between the aorta and the pulmonary artery is located distally, yet below the origins of the pulmonary artery branches. A crest is pronounced in the proximal section, separating the origins of the aorta and the pulmonary artery.

  4. The defect is located distally and involves the region of origin of the right pulmonary artery. As a result, the aorta communicates with both the pulmonary artery and its right branch.

  5. Complete absence of the aortopulmonary septum. Both pulmonary arteries originate from the posterior surface of the common trunk, but the absence of a ventricular septal defect and the presence of mutually isolated aortic and pulmonary valves are characteristic features that distinguish this form of anomaly from truncus arteriosus type I–II.

• By size [30,32]:

  1. Restrictive (3–4 mm, Qp/Qs ratio ≥ 1.5);

  2. Non-restrictive (Qp/Qs ratio < 1.5, accompanied by heart failure and/or the development of PH).

• By hemodynamic significance (applicable to all septal congenital heart diseases with an initial "left-to-right" shunt) [32-35]:

  1. Small: ratio of pulmonary artery systolic pressure to systemic systolic arterial pressure < 0.3 and Qp/Qs < 1.4.

  2. Moderate: ratio of pulmonary artery systolic pressure to systemic systolic arterial pressure < 0.3 and Qp/Qs = 1.4–2.2.

  3. Large: ratio of pulmonary artery systolic pressure to systemic systolic arterial pressure > 0.3 and Qp/Qs > 2.2.

  4. APUD with Eisenmenger syndrome: ratio of pulmonary artery systolic pressure to systemic systolic arterial pressure > 0.9 and Qp/Qs < 1.5.

With a certain allowance for the more malignant course of APUD compared with most other, more common septal defects, one should be guided by the 2009 ESC Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension regarding the anatomical and pathophysiological classification of PH due to septal defects for a detailed patient characterization (Table 1) [34,35].

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

* a diameter exceeding 1 cm is considered large or non-restrictive, which is roughly applicable to any ventricular septal defect and applies only to adults. Regarding APUD, a non-restrictive diameter can be used when the size exceeds 3–4 mm.

According to the 2015 ESC Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension, the clinical classification distinguishes four groups of PH due to congenital heart disease: 1) Eisenmenger syndrome, 2) PH associated with predominantly systemic-pulmonary shunts, 3) PH with small, incidental defects, 4) PH after surgical correction of VSD [35].

1.6 Clinical presentation of the disease or condition

In 90% of cases, APUD is non-restrictive and, in approximately the same percentage of cases, belongs to proximal defects, i.e., type I by location. In these cases, the aortopulmonary window can alter the spatial anatomy of the coronary artery ostia. The absence of a septum on the pulmonary artery side can lead to the transposition of the coronary artery ostium into the lumen of the aforementioned great vessel. Thus, an anomalous origin of the coronary artery, most commonly the right, from the pulmonary artery trunk can form.

APUD, excluding late-detected cases and the terminal stage, is characterized by a left-to-right blood shunt. Blood shunting from the aorta into the pulmonary circulation occurs in both systole and diastole, which is similar to the hemodynamics in patent ductus arteriosus. Immediately after birth, due to the physiological characteristics of the newborn, the shunt may be bidirectional or a minor left-to-right. Physiological involution in the structure of pulmonary microvessels leads to a decrease in pulmonary vascular resistance (PVR) and pulmonary artery pressure, which promotes an increase in the left-to-right shunt volume. During this period, a "hypervolemic" stage of PH occurs, which may be accompanied by symptoms of heart failure with a sharp predominance of pulmonary blood flow over systemic blood flow [2,13,15,26].

Thus, the "shunting" blood flow through the APUD is directed into the pulmonary artery, the pulmonary vasculature, and, having passed through the pulmonary circulation, returns to the left atrium and left ventricle. Consequently, the pulmonary artery, left atrium, and left ventricle experience volume overload, leading to their dilation. The direction and volume of the shunt are determined by the different pressure values in the aorta and pulmonary artery, the size of the defect, and the magnitude of total pulmonary vascular resistance. A low PVR level causes a larger volume of blood shunting, which is especially significant for large non-restrictive APUDs. Prolonged volume overload of the pulmonary circulation leads to an increase in pulmonary vascular resistance and an elevation of pressure in the pulmonary artery and right ventricle, i.e., the development of PH. The volume of the left-to-right blood shunt thereby decreases. With the progression of PH, the shunt may become bidirectional or even right-to-left. Severe pulmonary hypertension and right-to-left blood shunting through the APUD 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 APUD may be asymptomatic;

- in practice, however, non-restrictive APUDs are more common and present with signs of circulatory failure caused by pulmonary hypervolemia and left ventricular volume overload (decreased exercise tolerance, dyspnea, tachycardia, followed later by growth retardation, frequent bronchopulmonary infections);

- the most pronounced symptoms are characteristic of infants older than 1 month with large (non-restrictive) APUDs, when the maximum physiological post-natal decrease in PVR is observed and, consequently, a significant increase in the left-to-right blood shunt;

- with the development of Eisenmenger syndrome, varying degrees of cyanosis of the mucous membranes and skin appear. At the same time, an apparent improvement in condition may occur, manifested by a decrease in the frequency of respiratory infections;

In most adult patients with APUD corrected in childhood or with the persistence of a small residual defect after surgical intervention, the disease is usually asymptomatic [34,37]. As a rule, with timely correction of the anomaly, a complete regression of PH is observed [38].

With the onset of Eisenmenger syndrome, usually in cases without surgical treatment or further progression of PH in untimely diagnosed and corrected congenital heart disease, a clinical picture characteristic of a progressive multi-organ disease gradually develops, including central cyanosis, dyspnea, fatigue, hemoptysis, syncope, and, in late stages, right ventricular heart failure [39-42].

Symptoms of hyperviscosity include headache, syncope, dizziness, fatigue, tinnitus, blurred vision, paresthesias of the lips, fingers, and toes, and myalgia [4,13,43].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria:

1. Clinical presentation of heart failure with data supporting critical congenital heart disease with a large left-to-right blood shunt, accompanied by pulmonary hypervolemia and underperfusion of the systemic circulation.

2. Confirmation of the anatomical diagnosis of APUD based on a comprehensive examination, including both clinical evaluation by a specialist and the use of a range of modern cardiovascular imaging techniques.

2.1 Complaints and Anamnesis

No ESC guideline (LoE C, GoR 5)

Comments: this is not a diagnostic criterion, as the complaints are nonspecific and typical of a whole group of congenital heart defects with left-to-right blood shunting. Depending on the degree of hemodynamic impairment, the clinical course of APWD may vary significantly; however, the defect is rarely completely asymptomatic. The patient's condition depends on the defect size, PVR, and their changes with age. It is necessary to assess patients for dyspnea, palpitations, decreased exercise tolerance, poor weight gain, and frequent bronchopulmonary infections [3,4,13,15,16,26].

2.2 Physical Examination

• All patients with suspected APWD are recommended an initial consultation with a pediatric cardiologist and/or a cardiologist, and/or a cardiovascular surgeon to establish a diagnosis [2,4,13,26].

No ESC guideline (LoE C, GoR 5)

• All patients with APWD are recommended to undergo a physical examination including assessment of the chest shape and palpation of the precordial region [3,4,13,15,16,26].

No ESC guideline (LoE C, GoR 5)

Comments: a precordial bulge develops rather quickly, observed predominantly on the left precordium and detected on inspection in 70% of cases [4,13]. The mechanism of its formation in infants in the first year of life with large (non-restrictive) APWD is similar to that in other congenital heart defects accompanied by a large volume of blood shunting resulting from prolonged pressure of enlarged heart chambers on the anterior chest wall. Patients with Eisenmenger syndrome present with central cyanosis and, in late stages, signs of right ventricular heart failure, which is clinically indistinguishable from any other congenital heart defect whose natural history without surgical treatment leads to this complication [4,22,44]. The borders of cardiac dullness are expanded in both directions, and a systolic thrill ("cat's purr") is detected in the third intercostal space on the left in cases of large defect sizes. This sign is present only when there is a left-to-right blood shunt and is absent in high PAH or small APWD sizes.

• All patients are recommended to undergo heart auscultation (auscultation in heart and pericardial pathology) [3,4,15,16,26,44].

No ESC guideline (LoE C, GoR 5)

Comments: despite the possibility of suspecting this pathology upon auscultation, the defect has no specific auscultatory pattern.

auscultation in patients with APWD reveals:

– in individuals with high PAH, there is a significant predominance of the pulmonary component of the second heart sound, defined as an accentuated second sound at the pulmonary artery auscultation point;

– the classic "machinery" murmur of a systolic-diastolic shunt is heard in small APWD in the absence of high PAH, i.e., in approximately 10-15% of cases, maximally in the II-III intercostal space, which is slightly lower than the punctum maximum in PDA;

– more frequently, only a systolic murmur of varying intensity is detected due to blood shunting through the APWD at the base of the heart, also maximally in the II-III intercostal space and slightly lower than in PDA;

– a soft diastolic murmur of relative hemodynamic mitral stenosis at the cardiac apex (with a substantial volume of left-to-right shunt);

– in patients with high PAH, a soft diastolic murmur of relative pulmonary valve incompetence (Graham Steell murmur) may be heard over the pulmonary artery projection against the background of its marked dilatation [2,4,10,16,26,44].

2.3 Laboratory Diagnostics

In patients with uncomplicated congenital heart disease, they are nonspecific.

• All patients with congenital heart disease are recommended to undergo a general (clinical) urinalysis and a general (clinical) blood test with the determination of total blood hemoglobin and assessment of hematocrit, red blood cells, white blood cells, platelets, and erythrocyte sedimentation rate 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 if clinically indicated [44,66,102].

ESC IC (LoE C, GoR 5)

Comments: performing a general (clinical) blood test in all patients with congenital heart disease during follow-up 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 assess serum iron, serum ferritin, serum transferrin, and total iron-binding capacity to timely correct iron deficiency states. In patients with a mean corpuscular volume (MCV) greater than 100 fL, it is advisable to determine blood vitamin B12 (cyanocobalamin) and serum folic acid to timely correct 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 [66,188,189].

ESC IC (LoE C, GoR 5)

ESC I C-EO (LoE B, GoR 3)

ESC not stated (CGR B, LOR 3)

Comments: in the presence of laboratory signs of hemostatic disorders, it is prudent to postpone the surgical intervention until the causes of these disorders are identified and eliminated.

• All patients with congenital heart disease who receive thromboprophylaxis with unfractionated or low-molecular-weight heparin after surgical treatment are recommended laboratory monitoring of drug efficacy [198,199,201,202].

ESC not stated (CGR B, LOR 3)

Comments: when using unfractionated heparin (heparin group), it is necessary to determine the activated partial thromboplastin time (optimal range for adults is 40–60 s, for children 60–85 s) and blood heparin level (anti-Xa activity) (optimal range is 0.35–0.7). Until the optimal range is achieved, these parameters are determined 4 hours after each infusion rate change. Once the optimal range is achieved, they are determined once every 12 hours (see Appendix A3). When using low-molecular-weight heparin preparations (heparin group), it is necessary to determine the blood heparin level (anti-Xa activity) (optimal range is 0.5–1.0). Until the optimal range is achieved, it is determined 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 [198,199,201,202].

No ESC guideline (LoE C, GoR 5)

No ESC guideline (LoE C, GoR 5)

2.4 Instrumental Diagnostics

• All patients with APW should undergo an electrocardiogram (ECG) to assess left and right heart chamber overload, heart rhythm, and conduction [3, 4, 15, 16, 35, 48, 187].

No ESC guideline (LoE C, GoR 5)

Comments: in small (restrictive) APW, pathological ECG signs may be absent. Patients with non-restrictive APW exhibit ECG signs of left ventricular hypertrophy and overload, and occasionally left atrial overload. In the presence of pulmonary hypertension (PH), ECG signs of right ventricular hypertrophy are detected. Rhythm disorders occur in the late stages of the disease and lead to heart failure decompensation [45]. Atrial flutter or fibrillation significantly worsens the patient prognosis [51].

• An electrocardiogram every 12 months is recommended during outpatient follow-up of patients with APW, severe PH, and Eisenmenger syndrome to detect or assess changes in the degree of hypertrophy and/or dilation of the right heart chambers [35, 48].

No ESC guideline (LoE C, GoR 5)

Comments: in the presence of PH, P pulmonale, right axis deviation, right ventricular hypertrophy, right ventricular strain pattern, complete right bundle branch block, and QT interval prolongation are observed [52]. The last two signs indicate advanced disease severity, whereas hypertrophy and overload signs have sufficient sensitivity and specificity for screening studies [53, 54, 187].

• All patients with APW are recommended to undergo targeted chest X-ray to determine cardiac configuration and the state of the pulmonary circulation [3, 4, 15, 16, 19, 23, 35, 48, 55]. In Eisenmenger syndrome, if symptoms are present and in functional class III-IV, the study is recommended every 12–24 months. In other cases, as clinically indicated [35, 48, 187].

No ESC guideline (LoE C, GoR 5)

Comments: radiological findings are similar to those in infants and older children with hemodynamically significant ventricular septal defects (VSD) or patent ductus arteriosus (PDA) [55]. The degree of cardiomegaly and pulmonary vascular marking prominence directly depends on the shunt magnitude. Infants in the first 1.5–3 months of life with large (non-restrictive) defects are characterized by progressive pulmonary hypervolemia over time, due to the physiological decrease in total pulmonary vascular resistance and an increase in left-to-right shunting. In the presence of a large left-to-right shunt, there are signs of left atrial and left ventricular enlargement along with enhanced pulmonary vascular markings. Patients with severe PH do not show left ventricular enlargement, but present with a prominent pulmonary artery segment and attenuated pulmonary vascular markings in the lung periphery [19]. Chest X-ray will be normal in patients with small (restrictive) APW.

• All patients with APW are recommended to undergo echocardiography (EchoCG) with color Doppler ultrasound, which is the primary diagnostic tool for establishing the diagnosis of APW and determining its size, location, volume, and direction of blood shunting [3, 4, 19, 35, 48]. In Eisenmenger syndrome, if symptoms are present and in functional class III-IV, the study is recommended every 12 months. In other cases, every 12–24 months [35, 48, 187].

ESC I C (LOE C, SOR 5)

Comments: echocardiography (EchoCG) is a key diagnostic method for establishing the diagnosis of APW and assessing patient severity: it provides information on the location and size of the defect, the severity of left ventricular volume overload, and the degree of PH. Until relatively recently, this was the primary imaging modality for APW [56]. The echocardiographic sign of APW is an echo dropout in the septum between the aorta and the pulmonary artery with a shunt detected by color and continuous-wave Doppler [44]. The blood flow is directed antegrade into the pulmonary artery [57]. Important information is also provided by measuring the pressure gradient between the aorta and the pulmonary artery using continuous-wave Doppler. Similar to restrictive septal defects and PDA, a high-gradient shunt is considered when it exceeds 50 mmHg, and a low-gradient shunt when it is less than 30 mmHg. It is also important to determine the shunt direction, relationship with other structures, left ventricular dimensions, and Qp/Qs (in case of isolated APW). Various imaging windows can be used, including parasternal and subcostal views. The diagnosis requires confirming the presence of well-formed aortic and pulmonary valves, which rules out truncus arteriosus. Types I and III APW, i.e., those located close to the semilunar valves, are best visualized using two-dimensional echocardiography combined with color Doppler mapping [58]. For defects located distally (types II and IV), the capabilities of echocardiographic visualization are limited. Additionally, for a correct assessment of PH severity in patients with APW older than 6 months, echocardiography alone is insufficient, and cardiac catheterization and angiography should be considered (cardiac chamber catheterization; retrograde left heart catheterization; panaortography) [56, 59, 60].

It is important to note that in the presence of severe PH, when the blood shunt across the APW is minimal, absent, or balanced, the diagnostic value of EchoCG and Doppler ultrasound in particular decreases. APW may be diagnosed incidentally following delivery-related events or for other reasons [106, 107]. Cases of postmortem diagnosis without any symptoms in the medical history have been described in sudden deaths among adults and pregnant women [108, 109].

• Transesophageal echocardiography (TEE) is recommended for adult patients with APW when transthoracic imaging data are inconclusive (small defect) or technically limited (patient obesity, chest wall deformities, congenital heart anomalies, or other features reducing transthoracic EchoCG diagnostic capabilities, or when APW is combined with valvular or other intracardiac pathology) [34, 45, 59, 133, 134].

ESC not specified (LoE B, GoR 2)

Comments: transesophageal and/or three-dimensional EchoCG combined with other imaging modalities (cardiac and great vessel magnetic resonance imaging, ECG-gated cardiac multidetector computed tomography) significantly improves diagnostic capabilities in APW. Currently, advanced EchoCG technologies utilizing 3D imaging and tissue Doppler ultrasound are being introduced.

ESC IIaC (LoE C, GoR 5)

Comments: CT plays an increasingly important role in the diagnosis of APW in both pediatric and adult patients: it provides excellent spatial resolution and fast data acquisition, allows visualization of epicardial coronary arteries and arterial collaterals, and detects parenchymal lung disease. Ventricular size and function can be assessed with less time expenditure compared to MRI. CT is currently more widely available than MRI and therefore plays a special role in emergency situations. Cardiac CT is an alternative to MRI in patients with implanted pacemakers or defibrillators. The main drawbacks of most modern systems have been high ionizing radiation doses and reduced image quality in children due to high heart rates. However, recent advances such as ECG synchronization and novel rotation techniques reduce the radiation dose, which may make CT a more attractive imaging modality in the coming years [24, 34, 35, 48, 64]. The frequency of examinations during outpatient follow-up is determined individually.

ESC class III (CoRE C, LOE 3)

Comments: Cardiac MRI improves visualization capabilities, particularly for assessing ventricular volume overload and quantifying shunts. The method provides three-dimensional anatomical reconstructions with high spatial and temporal resolution, allowing for volumetric measurements, vascular assessment, and myocardial fibrosis evaluation. MRI is used in adults with left-to-right shunt congenital heart disease in the following clinical scenarios:

- as an alternative to echocardiography when both methods can provide comparable information. Echocardiography is superior to MRI in assessing gradients and pulmonary artery pressure levels, and in detecting small, highly mobile structures such as vegetations;

- as a supplementary method when echocardiographic findings are ambiguous or borderline, for instance regarding left ventricular volumes and ejection fraction, which may be critical for treatment strategy in adult patients with left-to-right shunts, such as evaluating volume overload and valvular regurgitation;

- MRI is more informative than 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, aneurysm) and aorta (aneurysm, dissection, coarctation); systemic and pulmonary veins (partial anomalous pulmonary venous drainage, obstructions, etc.), collaterals and arteriovenous malformations (superior to CT capabilities), in coronary artery disease (CAD) (inferior to CT), evaluation of intra- and extracardiac masses (inferior to CT), quantitative assessment of myocardial mass (left and right ventricles), detection and quantification of myocardial fibrosis/scar (late gadolinium enhancement shows improved visualization); tissue characterization (fibrosis, fat, etc.) [63].

- MRI is generally indicated when standard echocardiographic data are inconclusive [48].

In young children, the technique currently has limited utility due to technical constraints [64].

ESC IC-EO (CBR C, LCE 4)

Comments: for the diagnosis of isolated forms of left-to-right shunt congenital heart disease, cardiac catheterization is not currently performed routinely in children under 6 months of age [56,59,60]. Conversely, invasive evaluation is generally indicated when examining children older than 6 months and adults with pulmonary hypertension [60]. The diagnostic workup should not be excessive in this context; if left-to-right shunt congenital heart disease is combined with Eisenmenger syndrome or severe pulmonary hypertension, cardiac catheterization and pulmonary angiography of the main pulmonary artery and its branches may be omitted entirely if the defect anatomy is already known from other imaging modalities, limiting the procedure to right heart catheterization to measure intracardiac pressures and calculate peripheral vascular resistance. Right and left heart catheterization involves measuring pressures (systolic, diastolic, mean) in the pulmonary artery and aorta, assessing acid-base balance and blood gases in both atria, the pulmonary artery, and the aorta, and calculating pulmonary vascular resistance (PVR). Furthermore, cardiac catheterization (right and left heart catheterization) remains the standard procedure for accurately diagnosing pulmonary hypertension and selecting optimal treatment in adult patients with left-to-right shunts and pulmonary hypertension. More detailed information regarding the necessary steps of the diagnostic workup is presented in the clinical guidelines "Pulmonary Hypertension, Including Chronic Thromboembolic Pulmonary Hypertension" (ID 159_2) [187].

ESC class I C-EO (CoRE A, LOE 2)

Comments: cardiac catheterization and diagnostic imaging in Eisenmenger syndrome are necessary to obtain essential data and exclude other potential causes contributing to right-to-left shunting or pulmonary hypertension [34,35,43,45,48,49].

ESC IC (LoE B, LoR 2)

Comments: see clinical guidelines for pulmonary hypertension, including chronic thromboembolic pulmonary hypertension [187].

ESC IIaB (LoE C, GoR 4)

ESC IIaB (LoE C, GoE 5)

Comments: CT coronary angiography is a "semi-invasive" procedure, unlike conventional coronary angiography [34].

2.5 Other Procedures

ESC class I C (CoRE 4, LOE C)

Comments: the 6-minute walk test (6MWT) is the simplest method for assessing patients' functional capacity [35]. The distance walked in the 6MWT inversely correlates with the WHO functional class. The test is supplemented by the Borg dyspnea index and pulse oximetry [35]. A drop in arterial oxygen saturation of more than 10% during the 6MWT indicates an increased risk of mortality. Changes in the 6MWT distance served as the primary endpoint in most randomized trials involving patients with pulmonary hypertension [35,48].

• Prior to hospital discharge, all patients with left-to-right shunt congenital heart disease are recommended to undergo an electrocardiogram for postoperative monitoring [2,26,44,61].

No ESC guideline (LoE C, GoR 5)

• Prior to hospital discharge, all patients with left-to-right shunt congenital heart disease are recommended to undergo echocardiography for postoperative monitoring [2,26,44,61].

No ESC guideline (LoE C, GoR 5)

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

3.1 Conservative Treatment

Supportive therapy

The treatment strategy for left-to-right shunt congenital heart disease is determined by the hemodynamic significance of the defect and its known prognosis. For children responding to medical therapy, surgery may be postponed in cases of high surgical risk.

• In the absence of progressive circulatory failure, worsening pulmonary hypertension, and with adequate weight gain in the infant, surgical intervention is recommended at 3 months of age [74].

No ESC class (LoE C, GoR 5)

• In newborn infants and infants in the first 3 months of life at high surgical risk who present with clinical signs of pulmonary circulation overload (dyspnea, frequent respiratory infections, worsening pulmonary hypertension) and symptoms of circulatory failure, medical therapy is recommended [2,4,10,16,41,44,61,75].

No ESC guideline (LoE C, GoR 5)

Comments: in newborn infants with signs of heart failure and pulmonary circulation overload who are at high surgical risk due to associated congenital heart defects and/enr other aggravating factors, conservative therapy using diuretics, beta-blockers, and ACE inhibitors is advisable. Treatment should not be prolonged. If therapy is effective, surgical correction is performed when the infant reaches 2-3 months of age.

• In newborn infants and infants in the first 3 months of life who present with clinical signs of pulmonary circulation overload (dyspnea, frequent respiratory infections, worsening pulmonary hypertension) and symptoms of circulatory failure, and who do not respond to conservative therapy, surgical intervention is recommended before the age of 3 months [72,73].

No ESC class (LoE C, GoR 5)

Comments: the method of surgical correction of ALVP with or without cardiopulmonary bypass (including the use of a hybrid approach) is determined by the operating surgeon.

• The administration of antithrombotic agents is not recommended for adult patients with ALVP and PH due to the increased risk of bleeding and unproven efficacy [76].

ESC IIaB (LoE C, GoR 5)

Comments: randomized controlled trials to study the efficacy/safety of anticoagulant therapy in patients with ALVP, including those with PH, have not been conducted. Anticoagulants (antithrombotic agents) are used when indicated for the treatment of comorbid conditions.

Heart failure is the most likely problem for adult patients with persistent ALVP or residual ALVP after surgical correction of the defect. Therapy in such cases is carried out using accepted heart failure management guidelines [66,77].

• Loop diuretics and aldosterone antagonists are recommended for patients with ALVP presenting with heart failure to relieve edema syndrome [76,163,164,165].

No ESC guideline (LoE C, GoR 5)

Comments: randomized controlled trials on the use of diuretics in ALVP, as well as in many other congenital heart diseases, are lacking; however, clinical data demonstrate a distinct improvement in symptoms when loop diuretics are used in patients with circulatory insufficiency. When prescribing diuretics, forced diuresis should be avoided, and during the first few days, daily blood pressure monitoring, blood levels of sodium, potassium, and creatinine, blood urea levels, and hematocrit assessment should be performed to avoid hemoconcentration in response to decreased intravascular blood volume, hypokalemia, and prerenal failure. In conditions of severe systemic hypotension and anasarca, continuous intravenous administration of medicinal products (furosemide**) under systemic blood pressure monitoring (measuring blood pressure in peripheral arteries), central venous pressure measurement, and hourly diuresis measurement is advisable. The duration of therapy and dosage are selected individually by a pediatric cardiologist or cardiologist, but in accordance with the product monograph. If indicated, inotropic support under hemodynamic monitoring in an intensive care unit should be considered [27,140,141].

ESC IB (LoE A, GoR 2)

Comments: #Digoxin** (solid oral dosage form is off-label in children under 3 years of age) allows heart rate control in patients with supraventricular arrhythmias associated with ventricular dysfunction. The drug increases right ventricular contractility in patients with PH, pulmonary pathology, and biventricular chronic heart failure. Monitoring of the therapeutic level (testing of drug levels in the blood) of digoxin** in blood serum (from 0.8 to 2 ng/mL) is required [27,79].

No ESC guideline (LoE C, GoR 5)

Comments: isolated administration of #digoxin** in this situation is ineffective, and the clinical effect of monotherapy is significantly lower than that of combination treatment.

The dosage of #propranolol (oral solution) is increased over 10-15 days, starting from 1 mg/kg/day, until the target dose of 2 mg/kg/day is reached (titration is performed under the control of the clinical response [decrease in heart failure signs according to the Ross scale] and heart rate [optimal heart rate level: 110-120 bpm]). #Digoxin** (solid oral dosage form is off-label in children under 3 years of age) is prescribed in a maintenance daily dose divided into two doses (dosage 8-10 mcg/kg/day for newborns, in children past the neonatal period and up to 2 years of age – 10-12 mcg/kg/day) Monitoring is required until the therapeutic level of digoxin** in blood serum (from 0.8 to 2 ng/mL) is achieved. Furosemide is prescribed at 2-3 mg/kg/day. The duration of therapy and dose adjustment are selected individually by a pediatric cardiologist [27,79,166-168].

ESC no recommendation (LoE A, GoR 2)

Comments: to increase cardiac output, cardiotonic agents excluding cardiac glycosides are used (dobutamine**, dopamine**, #levosimendan**, the latter being off-label in children under 18 years of age at a loading dose of 10 mcg/kg followed by continuous infusion [continuous intravenous administration of medicinal products] for 24 hours at a dose of 0.1 mcg/kg/min; for adults, dosing regimens refer to the product monograph) [142] and, if necessary, norepinephrine** to maintain blood pressure. Dobutamine** is the preferred choice in severe PH, given the drug's effect on pulmonary vascular resistance [45,142].

ESC IB (LoE C, GoR 5)

Comments: clinical guidelines for PH, including chronic thromboembolic PH, are used depending on the specific clinical situation applied to each stage of examination and treatment, including specific studies and tests for PH reversibility, the appointment of specific modern mono- and combination therapy for PH with drugs of all known groups, and the assessment of the feasibility of surgical treatment of the underlying congenital heart disease that led to the development of PH [25,34,44,45,48,78,81,82,84,86,143-151,169,171,187].

• For patients with ALVP at high risk of thrombosis after surgical treatment, thromboprophylaxis with low-molecular-weight or unfractionated heparin preparations (antithrombotic agents or the heparin group) is recommended [198,199,201,202].

ESC not stated (CGR B, LOR 3)

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

Thromboprophylaxis with unfractionated sodium heparin** should be initiated with a bolus (intravenous administration of medicinal products) which in adults is 80 IU/kg, in children – 75 IU/kg, followed by intravenous infusion (continuous intravenous administration of medicinal products) at a rate of: 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 the results of laboratory tests (see section 2.3, Appendix A3) [198,201].

Thromboprophylaxis with low-molecular-weight heparin preparations (heparin group) is carried out based on: #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, in adults – 20 mg every 12 hours subcutaneously; dalteparin sodium – 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 sodium 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, in adults 2.5 mg daily subcutaneously. Dose adjustment is made based on the results of laboratory tests [198,199,201,202].

3.2 Surgical Treatment

• Surgical treatment is recommended for patients with ALVP with a left-to-right shunt or predominantly left-to-right shunt and manifestations of circulatory insufficiency refractory to medical treatment [44,48,66,74,102].

ESC IC (LoE C, GoR 5)

Comments: given the poor prognosis and severity of hemodynamic disturbances in typical cases—due to a large shunt present in more than 90% of aortopulmonary window (APW) observations—one must keep in mind the high probability of early pulmonary hypertension (PH), cardiomegaly, recurrent pneumonia, myocardial changes, and fatal outcome. Accordingly, timely surgical treatment should be performed in infants and electively in newborns. Radical treatment has also been reported in patient groups older than 2 years and even 4 years [103]. However, these are isolated observations or selective patient groups who maintained the ability to respond to treatment with reversible changes in the lungs and positive vasoreactivity tests [6-8,13,103]. Successful surgical treatment at an older age and in adults is the subject of rare reports [104]. At the same time, the impossibility of surgical treatment and the prescription of conservative therapy in adults with APW and Eisenmenger syndrome is described more frequently [23,105].

• Surgical treatment is recommended for patients with congenital heart disease (including APW) with a left-to-right shunt when the pulmonary-to-systemic blood flow ratio (Qp/Qs) is greater than 1.5, with a pulmonary artery systolic pressure of less than 50% of the systemic pressure, and PVR of no more than 1/3 of the systemic PVR [44,48,66].

ESC IC (LoE C, GoR 5)

• Surgical treatment is recommended for patients with APW with a left-to-right or predominantly left-to-right shunt and manifestations of heart failure amenable to medical treatment at the age of 3 months [44,48,66,74,102].

ESC IC (LoE C, GoR 5)

Comments: for cases where the severity of clinical manifestations and the degree of PH are minimal, and standard HF therapy allows controlling the patient's condition, a conservative management strategy is permitted until an older age is reached beyond the neonatal period [103]. Delaying surgical treatment until older than one year of age will most likely require invasive evaluation with assessment of the degree of PH [44].

• Simultaneous surgical treatment is recommended for patients with APW with a left-to-right or predominantly left-to-right shunt and manifestations of heart failure, in combination with other congenital heart defects [44,48,66,74,102].

ESC IC (LoE C, GoR 5)

Comments: for cases where the clinical manifestations and the degree of PH are significant and heart failure therapy does not allow for stabilization of the condition of a patient with APW combined with other congenital heart defects, the issue of single-stage correction must be considered [103]. Despite the fact that postoperative mortality in these cases is high, the strategy of delaying surgical treatment is inappropriate in concomitant critical congenital heart defects that require surgical treatment and have an unfavorable prognosis without surgery [16,44,110]. In cases where radical correction under cardiopulmonary bypass is associated with excessive risk (low body weight, prematurity, complex anatomy of concomitant congenital heart defects, etc.), the possibility of staged palliative treatment or a hybrid approach is considered [72,73].

• Surgery for isolated APW is recommended in typical cases to be performed by closure (closure of cardiac septal defect; endovascular closure of cardiac septal defect using an occluder) using any certified material (medical device with a registration certificate: cardiovascular patch of animal origin***, synthetic cardiovascular patch***, cardiac occluder***) [26,38,44,111].

No ESC guideline (LoE C, GoR 5)

Comments: for access to the APW, it is preferable to use aortotomy (aortic patch plasty) with the ability to visualize all edges of the defect, which, if necessary, allows the use of the "sandwich" technique when repairing the defect with a patch [112]. The use of a patch to repair the defect is the most frequently described technique today, although the details of access to the defect are a matter of discussion [119]. Opening the aorta also makes it possible to control the ostia of the coronary arteries and, taking into account their anatomy, to model the neo-septum between the aorta and the pulmonary artery. Authors with experience in comparing various techniques report a reduction in the number of complications and zero mortality precisely in operations where there is the opportunity to use cardiopulmonary bypass and aortotomy access to the APW [38].

• Surgical closure of APW (closure of cardiac septal defect; endovascular closure of cardiac septal defect using an occluder) is recommended for patients with developed pulmonary hypertension with PVR > 3–5 Wood units and a persistent hemodynamically significant left-to-right shunt (Qp/Qs > 1.5) [33,66].

ESC IIaC (LoE C, GoR 5)

• Division of isolated PDA with subsequent suturing or closure of the aortic and pulmonary ends, as well as ligation and clipping, is not recommended to be performed routinely unless required by the specific anatomical situation [2,26,38].

ESC III C (LoR C, LoE 5)

Comments: despite the preference for surgery under cardiopulmonary bypass with access for visualization of the APW through the aorta, the correction technique is chosen taking into account individual characteristics. The division technique is still considered outdated today, although it allows achieving the required result [113]. In some cases, given prominent edges and the presence of a "convenient" and sufficiently long "ampulla", clipping or ligation of the APW is also possible, especially if the situation justifies it (the need to avoid cardiopulmonary bypass, extremely low body weight, etc.). However, the risk of bleeding and the specifics of coronary anatomy must be taken into account [44].

• In patients with pulmonary hypertension with PVR ≥ 5 Wood units, closure of the APW (closure of cardiac septal defect; endovascular closure of cardiac septal defect using an occluder) may be recommended with a persistent hemodynamically significant left-to-right shunt (Qp/Qs > 1.5), however, the decision should be made individually in each case [33,66].

ESC IIbC (LoE C, GoR 5)

• Surgical correction of APW (closure of cardiac septal defect; endovascular closure of cardiac septal defect using an occluder) is not recommended in Eisenmenger syndrome and severe pulmonary hypertension accompanied by exercise-induced desaturation [66].

ESC IIIC (LoE C, GoR 5)

Comments: clinical data do not allow precise determination of desaturation threshold values; however, based on the experience of most researchers, an arterial blood oxygen saturation of less than 90% is taken as the threshold value [66].

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

1. development of Eisenmenger syndrome when underestimating the size of the defect;

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 often right ventricular [114].

ESC IIbC (LoE C, GoR 5)

Comments: lung transplantation with congenital heart defect 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, in Eisenmenger syndrome due to simple defects, isolated lung transplantation with simultaneous defect correction may be the method of choice. However, in septal defects, better outcomes are observed with transplantation of the heart–lung complex [115]. In recent years, treatment outcomes have improved: 5- and 10-year survival rates have reached 52–75% and 45–66%, respectively [115,116]. According to the same registry, the frequency of heart-lung transplantation for congenital heart disease accounts for 35.7% of all recipient diagnoses, and for PH, 27.6%, respectively.

3.3 Endovascular interventions

• Closure of APW in children with a cardiac occluder*** (closure of cardiac septal defect using an occluder) is currently not recommended when combined with complex congenital heart defects requiring open surgical correction [119].

ESC III C (LoE C, GoR 4)

Comments: percutaneous closure of ALSD is currently considered a complex procedure associated with a risk of complications, extremely rarely performed in patients with a body weight of less than 4 kg [120]. For example, in the case of PDA, if the latter has an "ALSD anatomy type" or type B, endovascular treatment is usually not recommended [117,118]. The same applies to low birth weight and any anatomical type other than type IV (intermediate) according to the accepted classification [30,121]. When planning an endovascular procedure, along with the anatomy of the so-called intermediate type of ALSD, the choice of device size is important, since complications may include damage to semilunar valves, device protrusion into the lumen of the great vessel, and coronary artery compression, and the limited size of ALSD in young children is reported to be around 8 mm [121-124].   

• Endovascular closure of a cardiac septal defect using an occluder (cardiac occluder***) in adult patients with ALSD is recommended if the defect is located at a sufficient distance from the semilunar valves of the aorta and pulmonary artery [121-128].

ESC not specified (LoE C, GoR 4)

Comments: percutaneous closure of ALSD is a certain alternative to surgical treatment in adult patients with suitable anatomy (type IV or intermediate) provided they meet operability criteria regarding the severity of PH before the development of irreversible changes and Eisenmenger syndrome. Despite literature data on the feasibility of closing ALSD up to 12 mm in size for adult patients, there is no consensus on the possibilities and optimal size [126]. Technical limitations are related to the sizes of the devices themselves, as well as the development of irreversible PH at an older age, the probability of which increases with large ALSD sizes, which is already an independent contraindication to ALSD closure.     

• If there are indications for closure of isolated types I, II, and III ALSD in children, it is recommended to give preference to open surgical treatment (closure of the cardiac septal defect) [125,126,132].

ESC not specified (LoE C, GoR 4)

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Not addressed in ESC guidelines (Level of Evidence C, Grade of Recommendation 5)

Comment. Due to the introduction of improved surgical and interventional techniques, including perioperative intensive care, the survival of children with congenital heart disease has markedly improved over recent decades, leading to an increase in the number of survivors reaching adulthood [207]. As patients with congenital heart disease grow older, their heart health may 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 disease, stroke, and coronary artery disease [208,209]. It is known that the development of atherosclerotic and metabolic diseases manifesting in adulthood usually begins in early childhood. Childhood obesity and a sedentary lifestyle are known to be major contributing factors [210]. This highlights the need for primary prevention, therefore lifestyle interventions are required to increase the physical activity (PA) of children with congenital heart disease, since physical activity is indispensable for the physical, emotional, and psychosocial development of children [211–215].

• Children with ALSD without signs of heart failure are recommended daily physical activity defined by WHO at > 60 minutes, without restrictions, as well as participation in all types of recreational/competitive sports with a mandatory health status assessment at least once a year [216-217].

No ESC guideline (LoE C, GoR 5)

• Children with ALSD and moderate signs of heart failure before or after surgical correction are recommended daily physical activity of moderate and low intensity, as well as participation in low- and moderate-intensity dynamic and static sports, excluding competitive sports, if stress testing demonstrates adequate exercise tolerance [216].

No ESC guideline (LoE C, GoR 5)

• Children with severe ALSD (pronounced signs of heart failure before or after surgical correction) 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 [216].

No ESC guideline (LoE C, GoR 5)

• Within 6 months after surgical correction of ALSD under cardiopulmonary bypass, a patient with a complicated postoperative course (residual PH, heart failure, infectious complications, repeated surgical interventions during the same hospitalization) is recommended to undergo rehabilitation in a specialized cardiological medical institution [16,76,79].

No ESC guideline (LoE C, GoR 5)

Comments: the following conditions may occur after ALSD correction:

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

– Persistence of PH may be observed even after successful correction of congenital heart disease. Persistent PH after ALSD correction belongs to group 1 [81]. If clinical manifestations are present, its treatment is carried out in accordance with available guidelines [19].

– Aortic regurgitation. It may be a consequence of the initial defect anatomy (cusp prolapse in subaortic or perimembranous ALSD), or involvement of the aortic valve cusp in the suture. Its frequency reaches 5-20% [82,83,84]. Aortic regurgitation may 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 accepted guidelines [85]. Although views on the optimal timing and method of correction remain controversial [84].

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

ESC not specified (LoE C, GoR 4)

Comments: 6 months after ALSD repair, patients may be cleared for 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.

• Referral for sanatorium-resort treatment is recommended for children with corrected ALSD without hemodynamic disturbance, without prognostically significant rhythm and conduction disturbances [206].

No ESC guideline (LoE C, GoR 5)

Comment: at climatic and balneological resorts, complex sanatorium-resort treatment is carried out, including: heliotherapy (A20.30.021), climatotherapy (A20.30.012), dry-air baths (A20.30.022), local therapeutic baths (2-4 chamber) (A20.30.009).

5. Prevention and Dispensary Observation

The prognosis after surgical or endovascular correction of ALSD is favorable provided the congenital heart disease is corrected in a timely manner. 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 ALSD, the prognosis is favorable in the absence of the risk of complications (infective endocarditis, aortic valve insufficiency) [15,20].

ESC IIaB (LOC C, LE 5)

Comments: the frequency of follow-up examinations by a pediatric cardiologist/cardiologist is at 1 month, 3, 6, and 12 months after surgery. The follow-up protocol includes electrocardiography (ECG) and echocardiography (EchoCG), as well as graded exercise tests when indicated (single-intensity exercise test, bicycle ergometry, ergospirometry) and pulse oximetry. Subsequent patient monitoring is carried out at intervals of 3–36 months [28,60].

Following surgery (open/endovascular), it is recommended to remain under dispensary observation for one year, and thereafter as clinically indicated. Patients with LV dysfunction, residual shunt, PH, aortic regurgitation, or ventricular outflow tract obstruction should be monitored annually in specialized centers. In patients with a small congenital or residual aortopulmonary window with preserved LV function, absence of PH, and no other lesions, follow-up visits every 3–5 years may be considered. Following endovascular intervention, regular monitoring is required during the first 2 years, and subsequently every 2–4 years depending on the outcome.

When determining the frequency of follow-up, one should be guided by the presence of heart failure symptoms, hemodynamic status, cardiac arrhythmias, hypoxemia, etc. Depending on these factors, all patients with CHD 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 (grade I),

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

- LVEF 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);

- LVEF 40–49%, RVEF 35–39%;

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

- moderately severe hypoxemia (SatpO₂ ≥ 85%);

- cardiac arrhythmias controlled by therapy;

- pulmonary hypertension (pulmonary hypertension functional class I–II);

- internal organ dysfunction controlled by therapy.

Group D

- heart failure FC IV;

- significant aortic dilation;

- severe hypoxemia (SatpO₂ < 85%);

- cardiac arrhythmias refractory to therapy;

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

- internal organ dysfunction refractory to ongoing therapy.

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

ESC IIbB (COR C, LOE 3)

ESC IB (LoE C, GoR 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 IB (LoE C, GoR 5)

Comments: the risk of complete atrioventricular block requires special attention in patients after aortopulmonary window closure if bifascicular block or transient trifascicular block develops.

• When monitoring patients after endovascular (transcatheter) closure of an aortopulmonary window, regardless of age, it is recommended to use antiplatelet agents (ATC group: other analgesics and antipyretics, antiplatelet agents excluding heparin) for 6 months [74,199,201,219].

ESC IIaB (COR C, LOE 5)

Comments: as antiplatelet agents (antithrombotic drugs), when the implanted device size is 30 mm or less, #acetylsalicylic acid** (off-label in children under 18 years) is used at a dose of 1–5 mg/kg/day once daily (not exceeding 325 mg/day) for 6 months; when the implanted device size is greater than 30 mm, #clopidogrel** is added to #acetylsalicylic acid** at the same dose, calculated as (off-label in children under 18 years) 0.2–1 mg/kg/day [74,199,201,219].

• It is recommended that children who have undergone surgical correction of an aortopulmonary window be vaccinated no earlier than three months later [23].

ESC none (COR C, LOE 5)

• During the follow-up of patients after surgical or endovascular (transcatheter) closure of an aortopulmonary window, it is recommended to provide infective endocarditis prophylaxis for 6 months regardless of age [74,91].

ESC IB (Level of Evidence C, Grade of Recommendation 5)

Comments: for any type of congenital heart disease where synthetic materials/prostheses were used during correction, bacterial endocarditis prophylaxis is carried out if indicated for 6 months after surgery or lifelong if residual shunts or valve 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.). Infective endocarditis prophylaxis consists of oral administration 30–60 minutes before the procedure of amoxicillin** at a dose of 50 mg/kg (pediatric dosage), but not exceeding 2 g (adult dosage), or intravenous administration (intravenous administration of medicinal products) (if oral administration is not possible) of ampicillin** at the same dose intramuscularly (intramuscular administration of medicinal products) or intravenously (intravenous administration of medicinal products) 30 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, but not exceeding 600 mg (adult dosage)) [36,177].

6. Organization of Medical Care

Indications for hospitalization in a medical organization:

1) presence of symptoms of heart failure;

2) presence of pulmonary hypertension;

3) elective surgical treatment.

Indications for emergency hospitalization:

1) deterioration of the patient's functional status due to the progression of circulatory insufficiency 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 symptoms of circulatory insufficiency.

7. Additional Information

• Patients with aortopulmonary window and PH are recommended to avoid excessive physical activity that provokes potentially dangerous symptoms such as severe dyspnea and weakness, dizziness, syncope, and chest pain [18,87].

ESC IB (COR C, LOE 4)

ESC IIaA (COR B, LOE 2)

ESC none (LOR C, LOE 5)

• In adult patients with a history of infective endocarditis, as well as with uncorrected aortopulmonary window or residual shunt, it is recommended to provide infective endocarditis prophylaxis [93].

ESC IA (COR A, LOE 1)

ESC IIaA (COR C, LOE 4)

Comments: air travel at altitudes up to 1500 m is usually well tolerated by patients [18,25].

Pregnancy and Childbirth

Pregnancy and childbirth are generally well tolerated [93]:

– against the background of corrected aortopulmonary window;

– in patients with preserved LV function;

– in NYHA functional classes I–II;

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

– in small aortopulmonary windows.

ESC IIIB (COR A, LOE 2)

Comments: pregnancy is absolutely contraindicated in Eisenmenger syndrome due to high maternal and infant mortality [93]. Pregnancy in female patients with cyanosis, in the absence of PH, is associated with significant risks for mother and fetus. SpO₂ < 85% and hemoglobin >200 g/L before pregnancy are the most important predictors of maternal mortality [94].

• If pregnancy occurs, termination of pregnancy (abortion) is recommended for female patients with aortopulmonary window in the presence of cyanosis and PH [93].

ESC IC (COR A, LOE 2)

Criteria for Evaluating the Quality of Medical Care

Quality assessment criteria for primary health care in adults and children with aortopulmonary window (ICD-10 codes: Q21.4, I27.8)

Quality assessment criteria for specialized medical care in adults and children with aortopulmonary window (ICD-10 codes: Q21.4, I27.8)

References

Appendix A1. Working Group Composition

1. Avramenko A.A. (Samara)

2. Belov V.A., (Kaliningrad)

3. Bogdanov V.N. (Chelyabinsk)

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

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

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

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

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

9. Gladyshev I.V., (Chelyabinsk)

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

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

12. Gulyaev YV (Moscow)

13. Evtushenko A.V., Russian Society of Cardiology, (Kemerovo)

14. Ermolenko M.L., MD, "Association of Pediatric Cardiologists of Russia", (Moscow)

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

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

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

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

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

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

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

22. Krupyanko S.M., MD, Association of Pediatric Cardiologists of Russia, (Moscow)

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

24. Levchenko E.G., (Moscow)

25. Lezhnev A.A., (Moscow)

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

27. Nalimov K.A., (Khabarovsk)

28. Nikiforov A.B., (Moscow)

29. Petrushenko D.Yu., (Kazan)

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

31. Podoksenov A.Yu., (Tomsk)

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

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

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

35. Teplov P.V. (Krasnoyarsk)

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

37. Tumanyan M.R., Prof., "Association of Pediatric Cardiologists of Russia", (Moscow)

38. Chernogrivov A.E., MD, Association of Cardiovascular Surgeons of Russia, (Moscow)

39. Shekhmametyev R.M., (Perm)

40. 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. Pediatrician;

7. Endovascular diagnostics and treatment physician.

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

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

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

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

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

Table 5. Scale for assessing the levels of persuasiveness of recommendations (LPR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation 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 health protection 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 Ministry of Health of Russia No. 918n of November 15, 2012)

Monitoring and dose adjustment of unfractionated heparin (heparin sodium**) [198,201]

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Aortopulmonary septal defect is a relatively rare congenital heart defect. The defect is an opening in the aortopulmonary septum, which in this case creates a communication between the aorta and the pulmonary artery. The latter two are major vessels, also known as great vessels, which normally supply the systemic and pulmonary circulations, respectively. The circulatory hemodynamics in these vessels differ significantly, and normally, the pressure in the aorta is substantially higher than in the pulmonary artery. Also, under normal conditions after birth, once the fetal shunts close, these vessels no longer communicate directly. In the fetus, the great vessels develop from an area related to the so-called second heart field, which forms the outflow tracts. At 4–5 weeks of gestation, the vascular pedicle region undergoes twisting, and the vessels separate from each other. If for some reason this does not occur, an opening, or defect, remains in the septum between the great vessels. Shortly after birth and the establishment of normal blood flow in both circulatory loops, a significant pressure difference arises between the left and right ventricles and, consequently, between the aorta and the pulmonary artery. As a result, blood from the aorta begins to be pumped simultaneously into both the aorta and the pulmonary artery—meaning where it should not be. Thus, with every heart contraction, there is a left-to-right shunt of blood. In this situation, the left ventricle is forced to work with an increased workload to pump this extra volume of already oxygenated blood back into the lungs and the left heart chambers. The workload also increases for the right ventricle, which operates under increased ejection pressure.

Aortopulmonary septal defects can vary in size and location, meaning a certain portion of the septum may be absent closer to or farther from the aortic and pulmonary valves. They can be small or, conversely, quite large, with the formation of marked tissue deficiency that poses challenges even for surgical treatment. However, keep in mind that typically, while not giant, hemodynamically significant or so-called non-restrictive aortopulmonary septal defects are encountered. The situation is aggravated by the fact that, unlike, for example, a ventricular septal defect, there are no descriptions of spontaneous closure or cure from this malformation. In most cases, such defects lead to the rapid development of severe pulmonary hypertension, often resulting in an inoperable condition within the next few years. Moreover, it is highly unlikely that a child would reach even early or preschool age while remaining asymptomatic. Even before the development of pulmonary hypertension, such children face a deterioration in their general condition, and this is not limited to delayed general development. The acute hemodynamic disturbances that occur with this congenital heart defect, typically accompanied by a large blood shunt into the lungs through the defect itself, lead to severe heart failure. This complication can develop within the very first weeks or even days after birth. In addition, medical therapy is far from always able to control the condition of such patients.

Respiratory diseases pose a high risk, and patients with an aortopulmonary septal defect are very prone to them due to this malformation. The fact is that if a child contracts any childhood infection or even a common cold in the presence of an aortopulmonary septal defect, a severe condition may develop. In fact, these factors—namely the presence of the defect and pulmonary complications—are entirely interconnected, with the latter, being a complication of the heart defect itself, aggravating its clinical course. This is a situation that already involves cardiopulmonary failure.

Thus, the natural history of the defect in most cases has an unfavorable prognosis, and the majority of such children do not survive to their first birthday.

High pulmonary hypertension is a different story, which broadly concerns children past the neonatal period, but is no less dangerous than heart failure. That small cohort of children who survive the first difficult months of their life faces another challenge. Not only the heart but also the pulmonary vessels find themselves in a severe situation: the right heart chambers and pulmonary vessels become overloaded with the increased volume of excess blood entering through the defect. The most critical indicators of this progression are elevated pressure in the pulmonary artery and the magnitude of the shunt. Today, ultrasound examination (echocardiography) and cardiac catheterization provide these data. An increase in pressure within the lesser circulation indicates pulmonary hypertension, which is the most formidable consequence of a large left-to-right shunt. Numerous compensatory mechanisms are activated: the ventricular muscle mass increases, and the pulmonary vessels adapt as well—initially accommodating the excess blood volume, and subsequently thickening the walls of the arteries and arterioles to make them denser and less compliant. This period is dangerous because the child's clinical condition may improve significantly, but this improvement is deceptive, and the window for surgical intervention can be missed. If this situation persists for quite a long time—several months or years—at some point the pressures in the right and left ventricles equalize during all phases of the cardiac cycle, and shunting through the defect ceases. Later, the pressure in the right ventricle may exceed that in the left, initiating the so-called "reverse shunt," whereby deoxygenated venous blood enters the arterial system—the systemic circulation—through the defect. The patient turns "blue." We have described this picture so that it is understood that a defect like a ventricular septal defect, which is very simple and safe to close at early stages, turns into a defect where closure loses its purpose and it is already too late to operate. We are referring here, as a reminder, to significant defects, which unfortunately occur in the majority of cases.

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

The primary indicator of the neonatal period is weight gain. In older children against this background, frequent colds occur, which become prolonged and can progress to pneumonia. This can continue for several months, and if the cause is an APSD, the symptoms will not resolve on their own. Such a child must be under the constant supervision of a cardiologist from the moment of diagnosis, and if the manifestations persist, medications to manage signs of heart failure will likely be prescribed. Against the background of medical therapy, symptoms may resolve or significantly decrease, and surgical treatment can be performed while the patient is in a stable condition, which substantially reduces its risk. However, if nothing changes, if heart dimensions increase and the size of the defect on echocardiography remains the same, one must consult surgeons as quickly as possible.

It should be emphasized once again that even in the first few months of life, aortopulmonary septal defects are often accompanied by the development of severe complications. These communications between the aorta and the pulmonary artery, even when not very large, not only fail to decrease but certainly do not close spontaneously. If the child does not get better, one cannot wait, as the situation may progress to the one described above, and operating will then be too late.

The best surgical results are achieved after the repair of large APSDs during infancy, even when the child shows signs of heart failure. At that stage, all processes are still reversible. The heart rapidly decreases in size, and blood flow in both circulations normalizes.

Surgical treatment is the only method and allows for the complete elimination of the defect and its consequences. The operation to repair an aortopulmonary septal defect is classified as open heart surgery (although endovascular interventions are also described and periodically considered) because it requires opening the heart chambers, and therefore it is performed using cardiopulmonary bypass. Aortopulmonary septal defects are closed by ligation, clipping of the opening, or most commonly using a synthetic patch that is rapidly endothelialized by the heart's own tissue. As already mentioned, catheter-based methods of defect closure are now also used, but this is not always possible and depends on the anatomical location of the defect and the expertise of the specialist in endovascular diagnostics and treatment.

In the absence of surgical treatment, APSD leads to elevated pulmonary vascular pressure—PH, with the presence of additional hemodynamic signs—PH. Patients typically complain of shortness of breath, dizziness, fatigue, and weakness, and the severity of these signs 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 of the few patients who reach adulthood without surgical treatment note that they can no longer maintain the active lifestyle they are accustomed to. It is necessary to reconsider the daily activity rhythm and adapt to a level of physical exertion that does not cause discomfort. If pulmonary hypertension is complicated by heart failure, fluid intake should be limited: it is not recommended to drink more than 1.5 liters per day, and sodium intake from table salt, which regulates fluid balance in the body, should be reduced. When tissue fluid increases, the blood volume also increases, which places an additional burden on your heart. One of the most effective ways to reduce the load 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 combines 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

6-minute walk test

Russian title: 6-minute walk test.

Original title: The six minute walking test (6MWT).

Source (official developer website, validation publication): Laboratories, A. T. S. C. o. P. S. f. C. P. F. (2002) ["ATS statement: guidelines for the six-minute walk test." Am J Respir Crit Care Med 166(1): 111 - 117. [160].

Type (underline):

rating scale

index

questionnaire

other

Purpose: one of the diagnostic methods for heart failure, used not so much to confirm the diagnosis as to determine the functional class. It also involves assessing patient endurance to evaluate treatment efficacy.

Content: the test evaluates the distance in meters walked by the patient in 6 minutes without forced stops.

Key (interpretation): comparison with the results of a previously conducted test (before therapy, during therapy, etc.)

6MWT - 6-minute walking test (6 minutes walking test, 6MWT).

The test is simple to perform, requires no complex equipment, and can be carried out in both inpatient and outpatient settings. It allows assessment of patients' daily activity levels, and its results correlate well with quality of life indicators; moreover, they can be used as additional criteria for evaluating the effectiveness of treatment and rehabilitation.

Indications for the 6-minute walk test

Assessment of functional status in congenital heart disease accompanied by pulmonary hypertension

Assessment of prognosis in such patients regarding the development of complications in heart failure and pulmonary hypertension.

It should be remembered that this test has the following absolute contraindications: musculoskeletal disorders preventing test performance, unstable exertional angina, and myocardial infarction within the past 1 month. Relative contraindications include: resting heart rate above 120 bpm, systolic blood pressure > 180 mmHg, and diastolic blood pressure > 100 mmHg. Stable angina is not an absolute contraindication for the test, but it should be performed with caution, under anti-anginal therapy as indicated.

If the patient is on continuous oxygen support, the oxygen flow rate during the test should be maintained in accordance with the prescription of the physician who prescribed and monitors the therapy.

The test must be stopped immediately if the following occur:

1. Chest pain;

2. Intolerable dyspnea;

3. Leg cramps;

4. Severe instability and staggering while walking;

5. Excessive sweating;

6. Sharp change in skin color (pallor).

The 6MWT is conducted in a room familiar to the patient, featuring a sufficiently long, hard-surfaced corridor. The walking path length must be at least 30 meters with markings every 3 meters and turn/pivot points. The patient is instructed to walk as fast as possible (without running) for 6 minutes.

The test evaluates the distance in meters covered by the patient in 6 minutes without forced stops.

At the end of these 6 minutes, the distance covered in meters is determined. Based on this figure, the functional class is determined: greater than 550 meters is normal, 426–550 is FC I, 301–425 is FC II, 151–300 is FC III, and less than 150 is FC IV. Upon test completion, the severity of dyspnea is assessed using the Borg scale (see below).

Borg scale dyspnea severity assessment test:

Russian title: subjective rating scale for perceived exertion (Borg scale).

Original title: Borg rating of perceived exertion scale (RPE scale).

Source (official developer website, validation publication): https://www.brianmac.co.uk/borgscale.htm Borg GA (1982). "Psychophysical bases of perceived exertion". Med Sci Sports Exerc. 14 (5): 377–81. doi:10.1249/00005768-198205000-00012 [161].

Type (underline):

rating scale

index

questionnaire

other

Purpose: subjective assessment of exercise tolerance.

Content: The patient receives instructions on assessing dyspnea during physical exertion: from 0 points - calm breathing, no sensation of dyspnea, up to 10 points - maximal dyspnea.

Key (interpretation): comparison with the results of a previously conducted test (before therapy, during therapy, etc.)

10-point Borg rating scale of perceived breathlessness [161].