Truncus Arteriosus: Clinical Guidelines

List of Abbreviations

SVR – systemic vascular resistance (БКК)

ВПС – congenital heart disease

RVOT – right ventricular outflow tract

APSD – aortopulmonary septal defect

VSD – ventricular septal defect

ASD – atrial septal defect

ЕОК – European Society of Cardiology

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

CIR – circulatory insufficiency

TA – truncus arteriosus

PVR – pulmonary vascular resistance

SVR – systemic vascular resistance

RV – right ventricle

RA – right atrium

6MWT – 6-minute walk test

ECG – electrocardiogram recording (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.

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

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

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

Level of evidence (LoE) – the degree of certainty in the validity of the intervention effect and that following the recommendations will bring more benefit than harm in a specific situation [1].

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

Truncus arteriosus (TA) is a congenital heart defect (CHD) in which a single great vessel arises from the base of the heart and, via a single undivided semilunar truncal valve, supplies coronary, systemic, and (via one or two pulmonary artery branches) pulmonary circulation. The pulmonary artery branch or branches must arise from the ascending portion of the common great vessel proximal to the origin of the brachiocephalic arteries. Synonyms: persistent truncus arteriosus, common arterial truncus, common truncus, common aortopulmonary trunk.

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

The etiology is not precisely established; however, as with most other congenital heart defects, risk factors are known and formation mechanisms have been studied. Cardiac developmental abnormalities occur during the first trimester of pregnancy, which is critical for the formation of the cardiovascular system. Exposure to damaging factors, gene or chromosomal mutations (totaling 10%), or polygenic-multifactorial inheritance (about 90%) accompany the occurrence of CHD, including TA [2,3,4]. According to the classification of embryonic and fetal developmental stages, the most vulnerable period occurs in early pregnancy and at least up to 12 weeks, when the formation of the adventitia of blood vessels is completed [3]. Congenital defects of the heart and great vessels predominantly arise at stages X–XX according to Streeter's classification with refinements by Ijffy L. et al. [3,5]. These stages are particularly important in teratogenesis, but even after this period, cardiovascular system formation is not yet complete, as the myocardium is still developing by week 16 of gestation [3]. Importantly, TA can be part of other chromosomal abnormalities. In 70% of cases, TA is associated with 22q11.2 deletion syndrome (DiGeorge syndrome). Other chromosomal disorders may also be observed (trisomy 18 syndrome, trisomy 21 syndrome) [4,6–10]. Maternal diabetes mellitus is a serious risk factor for TA [11].

TA is characterized by pathological blood shunting from the right and left ventricles through a ventricular septal defect into the common vessel with blood mixing therein. The defect exhibits both general patterns typical of CHDs with a large left-to-right shunt and associated hemodynamic features, as well as specific unique features. Due to the lack of flow separation in the single great vessel, the magnitude of left-to-right shunting is, in most cases, of a "total" character due to the anatomy of the defect. Unlike most septal defects where the shunt size is restricted by the defect dimensions, the volume of blood shunting to the lungs is determined almost exclusively by the magnitude of pulmonary vascular resistance (PVR) and its ratio to systemic vascular resistance (SVR). The functional state of the right and left ventricular myocardium plays a certain role, but in any case, in the absence of pulmonary artery branch stenoses, left-to-right blood shunting is aggressive [4]. Systolic pressure in the heart ventricles, truncus, and pulmonary artery branches is equal immediately after birth, leading to severe pulmonary circulation overload [3,12]. Only in the first days of life are pulmonary and systemic blood flows relatively balanced due to elevated pulmonary vascular resistance [4]. As PVR drops with the natural maturation of pulmonary vascular bed vessels, the volume of shunted blood increases sharply. Blood shunting occurs continuously in both systole and diastole, up to the appearance of diastolic retrograde blood flow in systemic arteries, which leads to the "steal" phenomenon in respective internal organs. As a result, the development of heart failure is highly likely, the severity of which is exacerbated by truncal valve insufficiency [13]. Often, the heart failure state becomes critical, with a mortality rate of 50% within the first two months of life [4]. According to autopsy studies, two-thirds of deceased patients do not exceed 6 months of age [7]. Branch stenoses may be present in 10% of cases, which hinders the development of pulmonary hypertension to varying degrees [12]. Indeed, with such CHD combinations, only isolated patients with TA surviving into adolescence or older age have been described [14]. In all other cases, pulmonary hypertension is an early and inevitable complication of this defect.

If the critical period of the first months of life is survived, pulmonary hypertension subsequently develops in all patients with TA. The contributing factors are as follows: pulmonary circulation hypervolemia, high pulse and systolic pressure, and the damaging effect of a large volume of left-to-right shunted arterial blood on the pulmonary vascular endothelium. Without surgical correction of the defect and, consequently, the persistence of pulmonary hypertension, Eisenmenger syndrome subsequently develops [15–17]. The latter represents an advanced stage of pulmonary hypertension in which blood shunting reverses direction and becomes "right-to-left." While morphological changes in early pulmonary hypertension—including intimal hyperplasia and medial hypertrophy of pulmonary vessels—are reversible, regression of the sclerotic stage of pulmonary hypertension in those lung segments where such changes have occurred becomes impossible from a certain point onward. Stage IV according to D. Heath and J. Edwards is currently considered the threshold where radical correction of the CHD is still possible [18]. Progression of pulmonary hypertension ultimately leads to stages V–VI according to the morphological classification of D. Heath and J. Edwards, accompanied by irreversible pulmonary vascular changes in the form of plexiform lesions and arteritis [3,15–20].

1.3 Epidemiology of the Disease or Condition

TA is not a common congenital heart defect (CHD), and its clinical frequency varies according to various sources from less than 0.5–0.8% to 1.7% of all congenital cardiac pathologies [21,22]. Autopsy data show a higher frequency, indicating insufficient clinical detection and confirming the unfavorable prognosis of the defect. Literature reports autopsy frequencies ranging from 2.1 to 3.9% [23,24]. TA is frequently found in combination with other CHDs. A typical combination is interrupted aortic arch or coarctation of the aorta, detected in 10 to 20% of cases with a patent ductus arteriosus (PDA) [7]. In other situations, the PDA is usually entirely absent. Approximately 10% of cases each involve combinations with an atrial septal defect, right-sided aortic arch, persistent left superior vena cava, anomalies of the aortic arch branches, mitral valve, and coronary arteries [4,25]. Rarer combinations include forms with a double aortic arch, atrioventricular septal defect or discordance, dextrocardia, asplenia and polysplenia, situs inversus, and double-outlet left ventricle [24,25].

In TA, the anatomy of the semilunar truncal valve is frequently abnormal. The number of cusps ranges from two to six, but in half to two-thirds of cases, the valve is tricuspid; in other cases, it is quadricuspid or, less commonly, bicuspid [4,7,12]. Morphological changes of a myxomatous type may also be present [32]. This quite frequently affects truncal valve function, manifesting as regurgitation in half of the cases or stenosis in a third [4]. Such frequent valve abnormalities identified in autopsy studies indicate a more severe clinical course with the development of severe heart failure and death [7,24].

Another feature is the high frequency of concomitant extracardiac pathology, which sets this CHD apart, despite the relatively high risk of associated anomalies characteristic of CHDs in general. Developmental disorders of other organs and systems are detected in 43–48% of cases, including corpus callosum agenesis, ventriculomegaly, holoprosencephaly, cleft palate, renal anomalies, and duodenal atresia [26].

Furthermore, the combination of thymic, parathyroid, and great vessel malformations is known as DiGeorge syndrome, which is frequently accompanied by a right-sided aortic arch and truncus arteriosus development defects or conotruncal anomalies [4]. The latter include truncus arteriosus communis, which is identified in one-third of patients with this genetic disorder [6]. This combination is typical, and 22q11.2 deletion syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome can be considered factual synonyms [7]. Importantly, DiGeorge syndrome itself is etiologically heterogeneous and can be caused not only by various chromosomal abnormalities, but also by the teratogenic effects of alcohol and certain medications (isotretinoin) [4]. Much less frequently, but also reported, is the combination of truncus arteriosus communis with trisomy 21 (Down syndrome) and trisomy 18 (Edwards syndrome) [8,9]. On the other hand, the CHARGE syndromic complex, which carries an extremely high probability of congenital heart disease (up to 75–80%) also belonging to the conotruncal group (Tetralogy of Fallot), is not mentioned as frequently in the context of truncus arteriosus communis [4]. However, combinations of CHARGE syndrome with the DiGeorge phenotype characterized by truncus arteriosus communis pathology are known [10].

The defect has no clear gender predilection [24,27]. A distinctive feature of truncus arteriosus communis is typically the rapid and malignant development of pulmonary hypertension and Eisenmenger syndrome, with low chances of reaching adulthood without surgery. Thus, in the Euro Heart Survey registry of adult patients among 1,877 observations with various congenital heart diseases, only 4 cases (0.21%) referred to unoperated truncus arteriosus communis. Eisenmenger syndrome was present in all of these cases [28]. Thus, without treatment, the probability of surviving to adolescence and, furthermore, adulthood is very low [14,29,30]. The number of observations in the literature reporting truncus arteriosus communis in adults does not exceed a dozen [31]. Based on generalized data, it can be determined that in the natural history of truncus arteriosus communis, only 50% survive the first month of life, 30% three months, 15% six months, and 10% survive infancy [3,7,12,14,29,30]. In case reports where truncus arteriosus communis is diagnosed at an older age, the main manifestation will be symptoms associated with severe pulmonary hypertension or Eisenmenger syndrome. With the development of this complication, the survival of patients with truncus arteriosus communis and Eisenmenger syndrome will be similar to other congenital heart diseases characterized by the development of hypertensive sclerotic changes in the lungs. The issue of surgical treatment in such cases is usually not considered [29,30]. In some exceptional cases, when pulmonary hypertension is balanced due to branch stenosis, surgical treatment is still possible, provided Eisenmenger syndrome is absent [14]. In other cases, with the progression of Eisenmenger syndrome, there is a progressive deterioration in exercise tolerance with the development of heart failure against the background of a reversed or "right-to-left" shunt [3,4,7,12].

1.4 Features of Coding the Disease or Condition

Q20.0 – Truncus arteriosus – ICD-10.

I27.8 – Other specified pulmonary heart diseases.

1.5 Classification of the disease or condition

• According to the level of branch origin in accordance with the classification by Collet R., Edwards Y., (1949) used by the Society of Thoracic Surgeons (STS Congenital Heart Surgery Database Committee) and the European Association for Cardiothoracic Surgery [4,12,33,34]:

Type I: a pulmonary artery segment is present, which arises from the truncus arteriosus communis and gives rise to the pulmonary artery branches (partial preservation of the aortopulmonary septum);

Type II: the pulmonary artery branches arise from orifices located close to each other and from the posterior wall of the truncus arteriosus communis;

Type III: the pulmonary artery branches arise from orifices located at a distance from each other, respectively from the right and left posterolateral aspects of the truncus arteriosus communis.

Regarding this classification, Type IV according to the Collet R., Edwards Y., 1949 classification previously existed but has been excluded from truncus arteriosus communis, since true pulmonary artery branches are absent in this case and pulmonary blood flow is carried out through aortopulmonary collateral arteries. The previously used term "pseudotruncus" for this variant is no longer used by the majority, as it is a form of pulmonary atresia with ventricular septal defect (Tetralogy of Fallot with pulmonary atresia) [34].

• According to the degree of development of the aortopulmonary septum, presence or absence of ventricular septal defect and/or aortic arch interruption (Van Praagh, 1965):

Type I is characterized by the presence of a partially formed aortopulmonary septum and, accordingly, the presence of a pulmonary trunk segment.

Type II is characterized by the absence of the aortopulmonary septum and, accordingly, the absence of the pulmonary trunk segment with the pulmonary artery branches arising from the truncus arteriosus communis (the distance between the orifices of the pulmonary artery branches is not specified).

Type III: absence of truncal origin of one of the pulmonary artery branches with ductal or aortic origin of the latter.

Type IV: hypoplasia or interruption of the aortic arch with a large PDA continuing into the descending aorta.

Subtypes with a VSD (A) and without a VSD (B) imply the alphanumeric designation of truncus arteriosus in accordance with this classification [25].

According to the 2015 European Society of Cardiology guidelines for the diagnosis and treatment of PH, the clinical classification identifies four groups of PAH due to CHD: 1) Eisenmenger syndrome, 2) PAH associated with predominantly systemic-to-pulmonary shunts, 3) PAH associated with small, incidental defects, 4) PAH after surgical correction of truncus arteriosus [35].

• A complete surgical description of truncus arteriosus is based on describing additional features supplementary to the main classification [36]:

1) Number of truncal valve cusps;

2) Dysplasia of the truncal valve (if present);

3) Functional assessment of the degree of truncal valve stenosis or regurgitation;

4) Relationship of the truncal valve to the true IVS;

5) Assessment of the degree of hypoplasia of each ventricle, if present;

6) Hypoplasia or absence of the thymus.

1.6 Clinical presentation of the disease or condition

Initial clinical manifestations resemble CHD characterized by a massive left-to-right shunt with overt signs of pulmonary hypervolemia and severe heart failure [3,4,12]. Heart failure is biventricular, caused both by large volume return to the LV and by the obstruction to ejection due to the predominant origin of the truncus arteriosus from the RV, frequent truncal valve pathology, and increased afterload for the RV [3]. Clinical signs of heart failure begin to develop within several days to several weeks after birth [3,37]. Typical signs include resting dyspnea worsening during feeding, poor weight gain, and frequent respiratory infections [3]. In terms of the risk of developing a number of severe complications, truncus arteriosus is not inferior to other critical CHDs at this age. For example, the risk of developing necrotizing enterocolitis in truncus arteriosus is higher than in transposition of the great arteries [38]. Cyanosis may be detected immediately after birth or later. The defect is characterized by high early mortality, and in rare cases when patients survive infancy without surgical treatment, the clinical picture of pulmonary hypertension joins. The course of pulmonary hypertension is malignant, and the condition is described as severe due to asthenia with marked limitation of physical activity and progressive cyanosis. The appearance or intensification of initial cyanosis is explained by progressive sclerosis of the pulmonary vasculature with an increase in the volume of the right-to-left blood shunt [3,4,12,37].

As pulmonary hypertension persists, the volume of the left-to-right shunt progressively decreases, and subsequently, severe pulmonary hypertension transforms into its terminal stage known as Eisenmenger syndrome [16,18,28]:

- the development of Eisenmenger syndrome may be accompanied by a false impression of clinical improvement, as a decrease in the frequency of respiratory infections may be observed. The main manifestation of Eisenmenger syndrome will be varying degrees of cyanosis of the mucous membranes and skin;

- Eisenmenger syndrome is identified in cases of refusal of surgical treatment, and untimely diagnosed and corrected CHD. The course of this complication gradually acquires the clinical picture characteristic of a progressive multiorgan disease, including central cyanosis, dyspnea, fatigue, hemoptysis, syncope, and, in late stages, right ventricular heart failure [45-49]. The clinical signs of Eisenmenger syndrome in truncus arteriosus and other CHDs complicated by this syndrome generally do not differ [52];

- the prognosis in case of successful surgical treatment differs radically from the natural course of the disease. Despite the complexity of surgical correction compared to most other congenital heart defects (CHD), early mortality is currently mainly due to concomitant risk factors [39]. Improvements in diagnostics and surgical techniques in recent years have made it possible to reduce the number of fatal postoperative complications by an order of magnitude, but the search for ways to improve outcomes continues. Long-term results are usually accompanied by acceptable actuarial survival [39,40]. Nevertheless, the authors note a relatively high frequency of reoperations for truncus arteriosus (TA) in the long-term period [40,41,43,44]. Most adult patients who underwent TA correction in childhood or with a small residual defect remaining after surgery are asymptomatic [34,37]. As a rule, after timely correction of the defect, normalization of pulmonary circulation pressure and complete regression of pulmonary hypertension (PH) are observed [38].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria:

1. Clinical presentation of heart failure with evidence of critical congenital heart defect with a large left-to-right shunt, accompanied by pulmonary hypervolemia and systemic hypoperfusion.

2. Confirmation of the anatomical diagnosis of TA based on a comprehensive examination, including both clinical evaluation by a specialist and the use of a range of modern imaging techniques for the heart and blood vessels.

2.1 Complaints and Anamnesis

No ESC guideline (LoE C, GoR 5)

Comments: variability in the clinical course of TA is acceptable; however, the defect does not present entirely asymptomatically. The patient's condition depends on the type of defect, pulmonary vascular resistance (PVR), and their changes with age. In the neonatal period, infancy, and early childhood, information regarding a child with suspected congenital heart disease is collected from the mother or caregivers. It is necessary to clarify whether the patients have dyspnea, palpitations, decreased exercise tolerance; poor weight gain, frequent bronchopulmonary infections [3,4,7,12,27,37].

2.2 Physical Examination

• In all patients with suspected TA, it is recommended to conduct an initial consultation with a pediatric cardiologist and/or cardiovascular surgeon in order to verify the diagnosis [3,4,7,12,27,37,204].

No ESC guideline (LoE C, GoR 5)

• In all patients with TA, it is recommended to perform a physical examination with determination of the chest shape and palpation of the cardiac region, assessment of the presence and degree of cyanosis [3,4,7,12,27,37,204].

No ESC guideline (LoE C, GoR 5)

Comments: at the patient's bedside, a topical diagnosis of TA is impossible to establish [50]. Physical examination is aimed at identifying general signs that may indicate the presence of congenital heart disease as such. In newborns and infants, the search is aimed at identifying symptoms of heart failure (HF) or congestive heart failure in forms of the defect accompanied by significant pulmonary hypervolemia. The appearance of older children is characterized by signs of delayed physical development, a subtle "fragile" physique, and varying degrees of malnutrition. Cyanosis may be present from birth, but in some cases it is not pronounced or is even absent [27]. A precordial bulge rapidly forms, which is observed predominantly on the left precordium and is detected upon examination in all patients older than one year [4,13,37]. The mechanism of its formation for children in the first year of life with TA is similar to that in other CHDs accompanied by a pronounced "left-to-right" blood shunt. The resulting cardiomegaly leads, due to the age-related characteristics of the growing organism, to deformation of the chest skeleton. Considering the high frequency of DiGeorge syndrome, identifying signs of this syndrome is an important aspect of diagnosis [4,51]. Typical features are hypertelorism, low-set ears, micrognathia, a small "fish-like" mouth, a short philtrum, bilateral cataract, single palmar creases, cleft lip, high arched cleft palate, deformity or absence of auricles, nasal malformation [53].

In patients with Eisenmenger syndrome, central cyanosis is determined, and in late stages — signs of right ventricular heart failure, which is clinically indistinguishable from any other congenital heart defect whose natural course without surgical treatment leads to this complication [4,22,44]. Mortality in Eisenmenger syndrome, according to some data, is 35% over a 7-year follow-up period and in more than half of the cases it is sudden, as a result of pulmonary hemorrhage, rupture of the pulmonary artery trunk, ascending aorta, bronchial artery, ischemic stroke, or for an unknown reason [52]. The boundaries of cardiac dullness are expanded in both directions, and a systolic thrill ("cat's purr") is determined in the middle of the sternum on the left. This symptom is detected only in the presence of a left-to-right blood shunt due to increased cardiac output through the VSD into the TA and is absent in severe PH. Palpation reveals an enhanced cardiac impulse caused by volume overload of the LV, accompanied by an RV impulse in the xiphoid and parasternal region. In adults, with the development of PH, LV volume overload is not as pronounced or is absent, but systemic pressure in the RV persists, and the precordial impulse is formed by the RV. In the presence of truncal regurgitation, palpation reveals a biventricular cardiac impulse regardless of the presence or absence of PH. The presence of pulsation in the sternoclavicular junction area on the right indicates a right-sided aortic arch [27].

• All patients with TA are recommended to undergo heart auscultation (auscultation in heart and pericardial pathology) to detect murmurs that may help suspect associated congenital heart defects [3,4,7,12,27,37].

No ESC guideline (LoE C, GoR 5)

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

However, the characteristic findings upon auscultation in patients with TA are as follows:

– enhanced 1st sound due to the ejection phenomenon into the enlarged great vessel, which is the TA;

– the 2nd sound of truncal valve closure is loud, which is due to the close location of the TA to the sternum and systemic pressure without splitting of the sounds, since there is a single semilunar valve;

– a harsh systolic murmur of VSD in the 3rd-4th intercostal spaces on the left, grade 3/6-4/6, which radiates upward and to the right along the course of the ascending aorta;

– blood flow through the truncal valve with thickening, leaflet dysplasia, and stenosis is similar to the murmur of aortic stenosis;

– 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;

– a mesodiastolic murmur of relative hemodynamic mitral valve stenosis at the apex of the heart with a significant volume of left-to-right shunt;

– the presence of a diastolic murmur at the base of the heart is detected in truncal valve regurgitation, and the appearance of an Austin Flint mesodiastolic or presystolic murmur is possible;

– in patients with severe PH and Eisenmenger syndrome, the auscultatory pattern may be less diverse with the absence of the mesodiastolic murmur of relative mitral stenosis. The existing truncal valve regurgitation progresses over time, which manifests as a regurgitation murmur spreading along the left sternal border [3,4,7,12,27,37].

2.3 Laboratory Diagnostics

In patients with TA, they are not specific.

• All patients with TA are recommended to undergo a general (clinical) urinalysis and a general (clinical) blood test including hemoglobin level and hematocrit assessment, erythrocyte, leukocyte, and platelet counts, and erythrocyte sedimentation rate (ESR) measurement as part of the initial examination, upon admission to the hospital, incl. for surgical treatment, during dynamic follow-up at least once a year, and in the postoperative period if necessary [4,82,92].

ESC IC (LoE C, GoR 5)

Comments: performing a general (clinical) blood test for all patients with TA during dispensary follow-up and before surgical treatment is important from the standpoint of detecting anemia and its timely correction. In patients with a mean corpuscular volume (MCV) of less than 80 fL, it is advisable to test serum iron levels, serum ferritin levels, serum transferrin levels, and total iron-binding capacity to timely correct iron deficiency states. In patients with an MCV of more than 100 fL, it is advisable to determine blood vitamin B12 (cyanocobalamin) levels and serum folic acid levels 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 results of surgical treatment [82,228,229].

ESC IC (LoE C, GoR 5)

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

• In all patients with a single ventricle heart and suspected concomitant Di George syndrome, it is recommended to test for blood ionized calcium, parathyroid hormone, serum free thyroxine (fT4), blood immunoglobulins, and cellular immunity, including lymphocyte proliferative activity, lymphocyte proliferative activity with mitogens, and lymphocyte subset analysis [55].

ESC IC (LoE C, GoR 5)

Comments: identification of concomitant genetic anomalies aims to detect those associated with a single ventricle heart [35,48]. Determining the corresponding biochemical and immunological parameters is required for the diagnosis and treatment of potential complications [55].

• In all patients with a single ventricle heart and suspected concomitant Di George syndrome and other CATCH22 genetic anomalies, it is recommended to perform blood cell analysis for karyotyping using differential chromosome banding in various genetic disorders [55].

ESC IIa B-NR (LoE C, GoR 5)

Comments: identification of concomitant genetic anomalies aims to detect those associated with a single ventricle heart [35,48]. Detection is not limited to CATCH22 anomalies alone. If necessary and in the presence of phenotypic features, diagnostic evaluation should also target trisomy 21 (Down syndrome) and trisomy 18 (Edwards syndrome) [55,57,58].

ESC not stated (CGR B, LOR 3)

Comments: if laboratory signs of hemostatic disorders are present, it is prudent to postpone surgical intervention until the causes of these disorders are identified and corrected.

• In all patients with a single ventricle heart receiving thromboprophylaxis with unfractionated or low-molecular-weight heparin preparations (heparin group) after surgical treatment, laboratory monitoring of the efficacy of these medicinal products is recommended [219,239,241,242].

ESC not stated (CGR B, LOR 3)

Comments: when using unfractionated heparin (heparin group), the activated partial thromboplastin time (optimal range for adults: 40–60 s, for children: 60–85 s) and blood heparin level (anti-Xa activity) (optimal range: 0.35–0.7) are monitored. Until the optimal range is reached, these parameters are determined 4 hours after each change in the infusion rate. Once the optimal range is achieved, monitoring is performed once every 12 hours (see Appendix A3). When using low-molecular-weight heparin preparations (heparin group), blood heparin level (anti-Xa activity) must be determined (optimal range: 0.5–1.0). Prior to reaching the optimal range, it is measured 3–4 hours after each injection; once the optimal range is achieved and the patient's clinical and laboratory status is stable, further monitoring is not required [219,239,241,242].

No ESC guideline (LoE C, GoR 5)

No ESC guideline (LoE C, GoR 5)

2.4 Instrumental Diagnostics

• In all patients with a single ventricle heart, it is recommended to record an electrocardiogram (ECG) to assess left and right heart chamber overload, cardiac rhythm, and conduction, when planning surgical treatment and upon discharge from the hospital [3,4,7,12,27,37].

No ESC guideline (LoE C, GoR 5)

• An ECG at 12-month intervals is recommended during outpatient follow-up for patients with a single ventricle heart, severe pulmonary hypertension, and Eisenmenger syndrome to detect or evaluate changes in the degree of hypertrophy and/or dilation of the right heart chambers over time [35,49,54,204].

No ESC guideline (LoE C, GoR 5)

Comments: pathological ECG findings, such as tall P waves in the precordial leads, are often accompanied by notched P waves due to the left atrial component and left atrial enlargement [60]. In patients with increased pulmonary blood flow, ECG signs of left and right ventricular hypertrophy and volume overload are observed, featuring tall biphasic QRS complexes in the mid-leads without a shift in the transition zone, and either left axis deviation or a normal electrical axis. In the presence of pulmonary hypertension, ECG signs of right ventricular hypertrophy are detected, including right axis deviation and counterclockwise depolarization patterns resulting from the combined workload of both ventricles and predominant right ventricular overload [27]. Rhythm disturbances occur in advanced stages of the disease and lead to heart failure decompensation [45]. Flutter or atrial fibrillation significantly worsens the patient prognosis [61]. In the presence of pulmonary hypertension, P pulmonale, right axis deviation, right ventricular hypertrophy, strain-type right ventricular overload, complete right bundle branch block, and QT interval prolongation are also identified [62]. The latter two signs indicate advanced disease severity, whereas hypertrophy and overload signs possess sufficient sensitivity and specificity for screening studies [35,49,63,64].

• In all patients with a single ventricle heart, it is recommended to perform targeted chest X-ray to determine cardiac configuration and the status of the lesser circulation (upon diagnosis, when planning surgical treatment, and/or during follow-up) [3,4,7,12,27,37].

No ESC guideline (LoE C, GoR 5)

• If patients with a single ventricle heart develop Eisenmenger syndrome with symptoms (functional class III–IV), it is recommended to perform a targeted chest X-ray every 12–24 months [35,48].

No ESC guideline (LoE C, GoR 5)

Comments: in other cases, as clinically indicated.

Radiological findings resemble those in infants and, in the absence of Eisenmenger syndrome, in older children with hemodynamically significant congenital heart disease and massive left-to-right shunting [46,50,60].

Particularly characteristic of type I anomaly: the heart is globular in shape, and both ventricles are enlarged and hypertrophied. The vascular shadow of the great vessels is markedly widened, and the branches of the pulmonary artery are widened to an equal degree. Initially, the increase in pulmonary blood flow is driven by both arterial and venous (congestive) components. In type II single ventricle heart, the pulmonary artery arch is not differentiated because both pulmonary artery branches originate from the single ventricle. Consequently, in the right anterior oblique view, an impression on the contour of the vascular arch is present. In type I, the pulmonary artery trunk segment is differentiated in the anteroposterior view, but lies higher than the normal origin of the pulmonary artery [3,4,12].

Children from the neonatal period and the first 3 months of life are characterized by a progressive increase in the severity of pulmonary hypervolemia over time, which is associated with a physiological decrease in pulmonary vascular resistance (PVR) 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 LV enlargement, along with enhanced pulmonary vascular markings. In patients with severe PH, LV enlargement is absent, but there is no typical bulging of the pulmonary artery trunk, which is due to the anatomy of the vascular bundle in truncus arteriosus communis (TAC) [27]. However, in adults with Eisenmenger syndrome, the PA segment in type 1 TAC bulges markedly, forming a corresponding arch at an atypically high level.

• All patients with suspected TAC are recommended to undergo echocardiography (EchoCG) using color Doppler mapping to clarify the diagnosis, determine the type of TAC, truncal valve function, volume and direction of blood shunting, when planning surgical treatment, and at discharge from the hospital [3,4,7,12,27,37].

ESC IC (CBR A, LCE 2)

Comments: Echocardiography (EchoCG) is a valuable diagnostic method for establishing the diagnosis of TAC and detailed anatomical assessment: it provides information on the location and size of the VSD, the severity of volume overload and ventricular hypertrophy, their balance, stenosis or regurgitation of the truncal valve, the anatomy of the aortic arch, and the degree of PH. The accuracy of this imaging method for TAC is very high [66]. An echocardiographic sign of TAC is the presence of a single vessel arising from the base of the heart, which is determined from the subcostal view [4]. The same approach can be used to assess the anatomy of the PA branches and truncal valve function. In the parasternal long-axis view, the VSD is identified by the echo dropout in the interventricular septum, and the displacement of the truncus with the mitral-aortic continuity is assessed. In the short-axis view, the origin of the PA segment from the TAC and the absence of RV outflow are revealed. By changing the probe position here, the anatomy and function of the truncal valve are assessed [44]. When making a diagnosis, it is necessary to rule out separately formed aortic and pulmonary valves, which differentiates this defect from aortopulmonary window. Compared to angiography, 2D EchoCG has advantages in differentiating from aortopulmonary window [58]. Overall, EchoCG is comparable to angiography in its diagnostic value [67]. A frequent associated anomaly of TAC in the form of a right-sided aortic arch is detected from the suprasternal view. This same view is used to rule out aortic arch pathology (coarctation or interruption). Also, in types of TAC without obstruction or interruption of the aortic arch, a PDA is absent. Assessment of the coronary vasculature by EchoCG is difficult; nevertheless, potential coronary artery anomalies require echocardiographic evaluation [65].

In newborns, EchoCG may be the sole and sufficient method for planning the scope of surgical treatment [4].

For the correct assessment of the severity of PH in TAC in children older than 6 months, echocardiography alone is insufficient, and cardiac catheterization (transvenous cardiac catheterization; heart chamber probing) should be considered in these cases [7,67].

In Eisenmenger syndrome, the frequency of EchoCG examinations in symptomatic cases and functional class III-IV is once every 12 months. In other cases, once every 12–24 months. [35,49].

• Fetal ultrasound and fetal cardiovascular duplex scanning are recommended for the evaluation of pregnant women, both for the primary diagnosis of TAC and when findings require differential diagnosis [68,69].

ESC IC (LOC C, LOR 4)

Comments: fetal cardiovascular ultrasound has high diagnostic value with the ability to accurately establish the diagnosis in more than 87% of cases [68]. Currently, the resolving power of the method is improving, making it possible to differentiate types 2/3 TAC and pulmonary atresia with collateral vessels ("pseudotruncus") prenatally [69].

• Transesophageal echocardiography (TEE) is recommended for patients with TAC when transthoracic imaging data are inconclusive or technically limited [31,40,70].

No ESC guideline (LoE C, GoR 5)

Comments: most often, this method is described as an intraoperative procedure to monitor the efficacy of the intervention performed [70].

Also, transesophageal and/or contrast EchoCG combined with other imaging modalities (MRI, contrast-enhanced MSCT) significantly improves diagnostic capabilities in TAC, including the detection of coronary artery anomalies [71].

ESC IIaC (LoE C, GoR 4)

Comments: CT plays an important role in the diagnosis of TAC in both pediatric and adult patients, as it provides high spatial resolution and also allows visualization of the coronary arteries and detection of parenchymal lung disease.

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 MRI-incompatible pacemakers or defibrillators.

The main disadvantages of CT are the high dose of ionizing radiation and relatively low image quality in children due to the high heart rate. However, the introduction of ECG-gating and new rotational techniques in scanners reduces the radiation dose, which in coming years may make CT an even more attractive imaging method, especially in the pediatric population [35,49,54,61,62,72,73].

In adolescence and adulthood, the study is particularly relevant for planning re-intervention due to dysfunction of a previously implanted conduit or progression of truncal valve disease [73].

ESC not specified (LoE B, GoR 2)

Comments: the method allows obtaining three-dimensional anatomical reconstructions with high spatial and temporal resolution, performing volumetric measurements, and assessing myocardial fibrosis.

MRI is used in patients with TAC in the following clinical scenarios:

- as an alternative to EchoCG when it is insufficiently informative [49];

- as an additional method when ambiguous or borderline EchoCG data are obtained, such as LV volumes and ejection fraction, which may be critical in the management strategy of adult patients with TAC, for example, in assessing the volume of overload and valvular regurgitation;

- MRI is more informative compared to EchoCG in the quantitative assessment of RV volumes and ejection fraction, RV 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 (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 (LV and RV), detection and quantification of myocardial fibrosis/scar (gadolinium-enhanced imaging reveals late gadolinium enhancement); tissue characterization (fibrosis, fat, etc.) [72];

- for more accurate non-invasive measurement of hemodynamic parameters based on velocity-encoded phase-contrast mapping to determine the degree of regurgitation and the Qp/Qs ratio in TAC [77].

In infants and newborns, EchoCG, catheterization, and/or CT are generally sufficient. Performing an MRI scan in newborns has technical difficulties and limited availability, so it is not routinely performed [73,76]. At the same time, cardiac MRI improves imaging capabilities, especially for assessing ventricular functional status and quantifying blood shunting.

ESC IC-EO (CBR C, LCE 5)

Comments: today, cardiac catheterization is not routinely used for the diagnosis of isolated forms of patent ductus arteriosus (PDA) in children under 6 months of age [7].

This technique is reserved for cases with an atypical presentation, such as severe cyanosis, or suspected complex anatomy of the pulmonary artery branches, e.g., unilateral blood supply to the lung via collaterals [7,30,39,41].

The evaluation plan for PDA combined with Eisenmenger syndrome or severe pulmonary hypertension (PH) should not be excessive; angiography of the pulmonary artery and its branches should be avoided altogether if the anatomy of the defect is already known from other imaging modalities, limiting the procedure to cardiac catheterization (transvenous cardiac catheterization; heart chamber catheterization) with pressure measurements and calculation of pulmonary vascular resistance (assessment of peripheral vascular resistance).

ESC I C-EO (LoE C, GoR 5)

ESC IC (RR S, ELD 5)

Comments: see the clinical guidelines for PH, including chronic thromboembolic PH, approved by the Russian Ministry of Health [204].

ESC IIaB (LoE C, GoE 5)

Comments: in patients with low or intermediate risk of coronary atherosclerosis, coronary computed tomography angiography may be considered as an alternative to conventional coronary angiography prior to surgery in adults with PDA [34,71,134,136,138,175].

2.5 Other Procedures

ESC IC (LoE C, SoR 5)

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 functional class.

The test is usually supplemented by assessing the Borg dyspnea index and pulse oximetry [35]. A drop in arterial blood oxygen saturation of more than 10% during the 6MWT indicates an increased risk of mortality [35,48].

• Prior to hospital discharge, an electrocardiogram is recommended for all patients with PDA following surgical intervention for monitoring purposes [37,47,49].

No ESC guideline (LoE C, GoR 5)

• Prior to hospital discharge, echocardiography is recommended for all patients with PDA following surgical intervention for monitoring purposes [37,47,49].

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 PDA is determined by the severity of hemodynamically significant alterations and the known prognosis. Surgical treatment is indicated in all cases except for inoperable ones. For children who respond to medical therapy, surgery may be postponed in cases of high surgical risk.

• In the absence of progressive circulatory failure, worsening PH, and if the child has adequate weight gain, surgical intervention is recommended upon reaching 3–6 weeks of age [89,90].

ESC I (LoE C, GoR 5)

Comments: in neonatal patients, the timing of surgical treatment must be decided within the first week of life [4]. The optimal timing of surgery at 3–6 weeks implies performing the procedure within this timeframe provided that heart failure can be medically controlled prior to surgery.

In cases of progressive heart failure despite adequate medical therapy, or lack of response to treatment, the possibility of earlier surgical intervention should be considered (potentially off-pump or via a hybrid approach) [72,73,89,90].

• In neonates presenting with signs of pulmonary overcirculation and symptoms of heart failure and/or circulatory failure, appropriate medical therapy is recommended along with evaluating the possibility of earlier surgical intervention [7,37,47,91,92].

ESC I (LoE C, GoR 5)

Comments: in neonatal patients with a high surgical risk due to associated congenital heart defects and/or other aggravating factors combined with symptoms of heart failure, it is advisable to resort to conservative therapy using diuretics (furosemide**) (C03), beta-blockers (#Metoprolol**, #Carvedilol**) (C07A), and ACE inhibitors (#Captopril**, #Enalapril**) (C09AA). The treatment regimen is selected by the attending physician individually for each patient in accordance with the drug prescribing information and serves as a short-term "bridge" (lasting from one to several weeks) prior to surgical correction of the congenital heart defect.

Possible dosage regimens: #Captopril** is used in children at a starting dose of 0.18-0.33 mg/kg/day divided into 3 doses, transitioning to a therapeutic dose of 0.5-2.0 mg/kg/day divided into 3 doses. If necessary, the dose may be increased to a maximum of 6 mg/kg/day. [189,249-250].

#Enalapril** is used at a dose of 0.1-0.5 mg/kg/day divided into 2 doses, with an average dose of 0.38 mg/kg/day and a maximum dose used in children of 1.2 mg/kg/day [189,251-253]. ACE inhibitors should be initiated cautiously, at a low dose, and only after correcting hypovolemia, as they may induce hypotension in some patients even at low doses.

#Carvedilol** (off-label in children) is administered orally at an initial dose starting from 0.1 mg/kg/day divided into 2 doses, followed by titration up to the maximum tolerated dose of 0.7-0.8 mg/kg/day [254-257].

#Metoprolol** is used in children at a dose of 0.1-1 mg/kg/day [254-255].

According to the prescribing information, furosemide** is administered intravenously at a dose of 1 mg/kg/day [258-260].

• Anticoagulant therapy is not recommended for patients with PDA and PH in the absence of atrial fibrillation or any prosthetic valves (mechanical bileaflet aortic valve prosthesis***, mechanical bileaflet mitral valve prosthesis***, or synthetic vascular graft***) [93,94].

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

Comments: in adult patients with PDA and PH presenting with atrial flutter/fibrillation, the target international normalized ratio (INR) is 2–2.5; in the presence of a mechanical valve (mechanical bileaflet aortic valve prosthesis***, mechanical bileaflet mitral valve prosthesis***), the target INR is 2–3.

Patients with severe PH have an increased risk of thrombosis, but they also have an elevated risk of bleeding. Female sex, low venous blood oxygen saturation, older age, biventricular dysfunction, and dilated pulmonary arteries are risk factors for thrombotic complications in patients with congenital heart disease complicated by severe PH, including patients with PDA; in such cases, the decision to prescribe anticoagulant therapy is made on an individual basis [62].

• The prescription of antithrombotic agents (B01) is not recommended for patients with PDA and PH due to an increased risk of bleeding and unproven efficacy [37,93].

ESC IIaB (LoE C, GoR 5)

Comments: randomized controlled trials evaluating the efficacy/safety of antithrombotic therapy (B01) in patients with PDA, including those with PH, have not been conducted. Antithrombotic agents are used solely when indicated for the treatment of comorbid conditions.

• Loop diuretics are recommended for patients with PDA and heart failure to relieve edema [42,56,182,183,184].

No ESC guideline (LoE C, GoR 5)

Comments: randomized controlled trials on the use of diuretics in PDA, as in many other congenital heart defects, are lacking; however, clinical data demonstrate clear symptom improvement 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 urea nitrogen, serum creatinine, and hematocrit must be closely monitored to prevent hemoconcentration in response to reduced intravascular volume, hypokalemia, and prerenal failure.

In conditions of severe systemic hypotension and anasarca, continuous intravenous infusion of furosemide** (according to the manufacturer's instructions) is advisable, monitored by systemic blood pressure (measurement of blood pressure in peripheral arteries), central venous pressure (measurement of central venous pressure), and hourly urine output. If indicated, inotropic support under hemodynamic monitoring should also be considered in an intensive care unit setting.

• Prescription of maintenance doses of #digoxin** is recommended for patients with congenital heart defects (CHD) and heart failure with an EF < 40% and symptoms of HF, including for heart rate control in HF (solid dosage form off-label in children under 3 years of age) [37,98,185,186,188,246-248].

ESC IB (LoE C, GoR 5)

Comments: #Digoxin** allows heart rate control in patients with supraventricular arrhythmias associated with ventricular dysfunction. The drug improves RV contractility in patients with pulmonary hypertension (PH), pulmonary pathology, and biventricular chronic heart failure. Monitoring of therapeutic serum digoxin** levels (therapeutic drug monitoring in blood) (from 0.8 to 2 ng/mL) is required [37].

Maintenance daily dose for infants under 1 year and neonates is 8 mcg/kg/day, for children from 1 year to 2 years 10-12 mcg/kg/day, over 2 years 8-10 mcg/kg/day. [37,98,185,186,188].

• In infants with CHD and decompensated circulatory failure, to improve regional perfusion, ventricular contractility, and relieve congestion, it is recommended to prescribe combination therapy according to the (approximate) scheme: beta-blockers, #digoxin**, and diuretics [37,97,98,133].

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 [97].

Dosage regimens: #metoprolol** in cases of dilated cardiomyopathy, starting dose 0.1 mg/kg per dose twice daily with gradual titration up to 0.9 mg/kg/day orally (the standard dose of #metoprolol** is 0.25 mg/kg/day with a 12-hour dosing interval [188]), #propranolol** 1-2 mg/kg per dose three times a day, furosemide** 0.5-2 mg/kg per dose twice daily [37]. For the #digoxin** dosage, see above.

No ESC guideline (LoE C, GoR 5)

Comments: to increase cardiac output, cardiac stimulants excluding cardiac glycosides, ATC code C01C and C01CX, are used (dobutamine**, dopamine, and, if necessary to maintain blood pressure, norepinephrine**). Dobutamine** is the preferred choice in severe PH, given the drug's effect on pulmonary vascular resistance (PVR) [45,142].

ESC IB (LoE C, GoR 5)

Comments: clinical guidelines for PH, including chronic thromboembolic PH, are approved and applied depending on the specific clinical situation at each stage of examination and treatment, including specific studies and tests for PH reversibility, prescribing specific modern mono- and combination therapy for PH with drugs from all known groups, and evaluating the feasibility of surgical treatment of the underlying CHD that led to PH development [25,34,44,45,48,78,81,82,84,86,143-151,169,171,204].

• Patients with SAO at high risk of thrombosis after surgical treatment are recommended thromboprophylaxis with low-molecular-weight or unfractionated heparin (heparin group) [219,239,241,242].

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** must be initiated with an intravenous bolus of 80 IU/kg in adults and 75 IU/kg in children, followed by continuous intravenous infusion at a rate of: 28 IU/kg/h in children under 1 year of age, 20 IU/kg/h in children over 1 year of age, and 18 IU/kg/h in adults. Dose adjustment is performed based on laboratory test results (see section 2.3, Appendix A3) [239,241].

Thromboprophylaxis with low-molecular-weight heparin preparations (heparin group) is administered at the following doses: #enoxaparin sodium** (off-label in children under 18 years) in children under 2 months – 0.75 mg/kg, in children over 2 months – 0.5 mg/kg, in adults – 20 mg subcutaneously every 12 hours; #dalteparin sodium – in children from 1 month to 2 years – 150 IU/kg, from 2 to 8 years – 125 IU/kg, over 8 years – 100 IU/kg, in adults – 2500 IU subcutaneously every 12 hours. #Fondaparinux sodium may be used in children over 1 year of age (off-label in children under 17 years) at a dose of 0.1 mg/kg, and in adults at 2.5 mg once daily subcutaneously. Dose adjustment is performed based on laboratory test results [219,239,241,242].

3.2 Surgical Treatment

The presence of acute aortic syndrome (AAS) is an indication for surgical treatment in all cases, provided the patient is operable.

• Surgical treatment is recommended for stable patients with aortopulmonary window aged 3–6 weeks and/or at an earlier age in case of heart failure refractory to medical treatment (provided the patient is operable) [4,12,48-49,82,89-90,92].

ESC IC (LoE C, GoR 5)

Comments: given the poor prognosis and the severity of hemodynamic disorders in the vast majority of typical cases due to a large left-to-right shunt, one should bear in mind the high probability of early development of pulmonary hypertension, cardiomegaly, recurrent pneumonia, myocardial changes, and death. Accordingly, timely surgical treatment should be performed in infants and electively in newborns. Radical treatment has also been reported in patient groups older than one year and even in adolescence [46]. However, at an age older than one year, these are rare, isolated observations of patients who remain curable and have reversible pulmonary changes with positive vasoreactivity tests [3,28,34,41,42,46,52,70,74]. The mechanisms of such compensation are poorly understood, but these patients more often have pulmonary artery branch stenoses with so-called "protected" pulmonary blood flow [122]. Successful surgical treatment in adults is the subject of extremely rare reports. Descriptions of inoperability in older patients and the prescription of conservative therapy against the background of Eisenmenger syndrome development are much more common [52,70,74].

• Surgical treatment is recommended for patients with aortopulmonary window older than 6 months with persistent left-to-right shunt at a pulmonary-to-systemic blood flow ratio (Qp/Qs) greater than 1.5 and a pulmonary artery systolic pressure less than 50% of the systemic pressure, as well as pulmonary vascular resistance no more than 1/3 of the systemic resistance [47,49,82,90].

ESC IC (LoE C, GoR 5)

Comments: if the age of patients with aortopulmonary window is older than 6 months, as a rule, the Qp/Qs ratio decreases due to the development of severe pulmonary arterial hypertension. The possibility of reversing the Qp/Qs ratio to values of 1.5 and higher should be evaluated by performing a vasoreactivity test. The purpose of the study is to decide on the possibility of radical correction [7,43,47].

Today, the nitric oxide test is widely used for vasoreactivity testing. Examination data are optimally obtained in specialized centers where care is provided by a multidisciplinary team (cardiologists, anesthesiologists and intensivists, cardiovascular surgery service, clinical nurses (ward nurses/ward nurse brothers), radiologists, psychological support, and other specialists) [37,66,77,78,80,81].

Rough estimation of the degree of pulmonary hypertension takes oxygenation into account. Blood oxygen saturation within 85% and higher in infants with typical physiology usually indicates a high level of pulmonary blood flow with a high Qp/Qs ratio and moderately elevated pulmonary vascular resistance (within 2–4 Wood units/m²) [84]. A decrease in blood oxygen saturation to less than 80% indicates a decrease in pulmonary blood flow (Qp) and a sharply increased pulmonary vascular resistance with a doubtful prospect for radical correction.

• Surgical treatment is recommended for patients with truncus arteriosus with a left-to-right shunt or predominantly left-to-right shunt and symptoms of heart failure amenable to medical therapy at the age of 3–6 weeks (provided the patient is operable) [44, 48, 66, 74, 102, 123, 124].

ESC IC (LoE C, GoR 4)

Comments: for cases where the severity of clinical manifestations and the degree of pulmonary hypertension are minimal, and standard heart failure therapy allows the patient's condition to be controlled, a conservative management strategy is permissible until an even older age is reached: from 1.5 to 3 months [4, 123, 124].

• Single-stage surgical treatment is recommended for patients with truncus arteriosus with a left-to-right shunt or predominantly left-to-right shunt and symptoms of heart failure, in combination with other congenital heart defects (provided the patient is operable) [7, 84, 125, 126].

ESC IC (LoE C, GoR 4)

Comments: for cases where the severity of clinical manifestations and the degree of pulmonary hypertension are significant, and heart failure therapy does not allow for stabilization of the patient with truncus arteriosus in combination with other congenital heart defects, the issue of earlier single-stage repair must be considered [127–130]. Despite the high postoperative mortality in these cases, the strategy of long-term postponement of surgical treatment is inappropriate in the presence of concomitant critical congenital heart defects that require surgical treatment and have an unfavorable prognosis without surgery [4, 127–130].

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 [4, 127–130].

• Surgery for the correction of isolated truncus arteriosus is recommended in typical cases for all patients using any certified material (medical device with a registration certificate: cardiovascular patch of animal origin***; synthetic cardiovascular patch***; vascular xenograft***) [4, 7, 133].

ESC IC (RR S, ELD 5)

Comments: correction of isolated truncus arteriosus includes four main stages: 1. Separation of the truncus and pulmonary artery branches; 2. Restoration of aortic integrity; 3. Closure of ventricular septal defect; 4. Creation of an outflow tract from the right ventricle into the pulmonary artery system using various methods (using native tissues, using conduits) [4, 12, 45].

Opening the truncus at the first stage makes it possible to control the coronary artery ostia, assess the anatomy, and determine the need for truncal valve plasty [7]. The defect in the aortic wall resulting from the excision of the pulmonary artery branch ostia on a patch or as separate ostia, depending on the type of truncus arteriosus, is closed with a patch (aortic patch plasty) made of autopericardium or another certified material, or by closure with a double-row continuous suture (aortorrhaphy) [4, 12, 45, 136]. The first method is more reliable in terms of preventing deformation of the neo-aortic root and coronary artery ostia [7].

A method of complete transection of the truncus arteriosus at the level of the pulmonary arteries is possible, which some authors use in all cases, including the so-called type I ½, except for type I [136]. This subsequently makes it possible to restore the integrity of the neo-aorta without using additional patches, to ensure the symmetry of the root and its reduction in diameter during anastomosis with the distal segment [136].

Closure of the ventricular septal defect is performed from a right ventriculotomy approach using a patch of synthetic or biological material (cardiovascular patch of animal origin***; synthetic cardiovascular patch***) with fixation by a continuous locking suture or interrupted sutures [4, 7].

Creation of the outflow tract into the pulmonary artery is carried out using a conduit of the required diameter (vascular xenograft***) with fixation of the distal and proximal anastomoses by a continuous suture (radical correction of truncus arteriosus using a conduit under cardiopulmonary bypass) [4, 7].

If there is a sufficiently developed segment of the pulmonary artery trunk and/or an accessible distance to create a direct anastomosis with the pulmonary artery tissues and the edges of the intended ventriculotomy incision, it is possible to create a right ventricular outflow tract using native tissues (Barbero-Marcial technique). When choosing this method, the stage of separating the truncus arteriosus and pulmonary artery branches is performed without transecting the latter. For this purpose, the anterosuperior aspect of the left pulmonary artery is opened with extension of the incision onto the root of the truncus arteriosus in the direction of the left sinus of Valsalva, and after revision of the coronary artery ostia, pulmonary artery branches, and truncal valve, septation of the neo-aorta and pulmonary artery trunk is performed. After closing the ventricular septal defect from the ventriculotomy access, the posterior wall of the tunnel into the pulmonary artery from the right ventricle is formed in a "flap" fashion using the pulmonary artery wall and the incised tissues of the truncus arteriosus. The anterior wall is formed by a separate patch of autopericardium or another material (cardiovascular patch of animal origin***; synthetic cardiovascular patch***) [7]. A modification of the method is the use of left atrial appendage tissue as an "insert" [137].

The final choice of technique is determined by the specific anatomical situation, as well as the preferences of the cardiovascular surgeon [2,4,26,38,136-140].

• Surgical treatment (radical correction of truncus arteriosus using a conduit under cardiopulmonary bypass) for patients with truncus arteriosus and pulmonary hypertension is recommended at pulmonary vascular resistance values of 3–5 Wood units/m² (acceptable up to 8 Wood units/m² with a positive vasoreactivity test) and a persistently hemodynamically significant left-to-right shunt (Qp/Qs > 1.5) [81, 131, 132].

ESC IIaC (LoE C, GoR 5)

Comments: for cases where pulmonary vascular resistance exceeds 8 Wood units/m² the vasoreactivity test is considered positive if there is a greater than 20% decrease in pulmonary vascular resistance and pulmonary vascular resistance/systemic vascular resistance ratio relative to baseline values, with corresponding final pulmonary vascular resistance values of less than 6 Wood units/m² and pulmonary vascular resistance/systemic vascular resistance ratio of less than 0.3 [3, 47, 131, 132].

In adult patients, a decrease in saturation during exercise is a highly probable sign of inoperability, as it indicates a fixed level of pulmonary blood flow and an increase in the level of right-to-left shunt in response to the decrease in systemic vascular resistance that occurs during exercise [7]. However, in each case, the decision should be made individually [47, 131, 132].

• During correction of truncus arteriosus under cardiopulmonary bypass to ensure adequate perfusion and effective delivery of cardioplegic solution to the myocardium, control of the pulmonary artery branches with the ability to clamp them at the necessary stages of the operation is recommended for all patients [2, 4, 26, 38].

ESC I C (LoE C, GoR 5)

Comments: at the initiation of cardiopulmonary bypass, it is necessary to clamp the pulmonary artery branches, which are pre-looped and controlled with tourniquets or tape straps. After aortic cross-clamping and antegrade administration of cardioplegia into the root of the truncus arteriosus, the branches must also remain clamped [136].

• In the presence of pronounced truncal valve regurgitation during truncus arteriosus correction, simultaneous elimination of valvular pathology is recommended for all patients (provided the patient is operable) [2, 4, 26, 38].

ESC I C (LoE C, GoR 5)

Comments: in the presence of significant truncal valve regurgitation, there are specific features of cardioplegic solution delivery to the myocardium. Thus, at the initiation of cardiopulmonary bypass, the risk of myocardial overdistension as a consequence of weakened contractile activity when using hypothermia should be taken into account. Placement of a left ventricular vent may not solve the problem, as this can additionally cause systemic steal during perfusion. Furthermore, in newborns, its function is not always reliable [136].

In such a situation, rapid aortic cross-clamping is required, followed by opening the aortic aneurysm, with administration of, for example, the first dose of cardioplegia antegrade and the second dose selectively into the coronary ostia or retrogradely via the coronary sinus [4,12,34,45,136].

• Surgical correction of truncus arteriosus is not recommended for patients with Eisenmenger syndrome and severe pulmonary hypertension accompanied by exercise-induced desaturation [39, 46, 50, 52].

ESC IIIC (LoE C, GoR 5)

Comments: clinical data do not allow for the precise determination of threshold desaturation values in truncus arteriosus; however, based on the experience of most researchers, arterial blood oxygen saturation of less than 80% is taken as the threshold value [84].

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

1. development of Eisenmenger syndrome;

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 failure [141].

ESC IIbC (LoE C, GoR 5)

Comments: lung transplantation with correction of congenital heart disease 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 registry of the International Society for Heart and Lung Transplantation, in Eisenmenger syndrome due to simple defects, isolated lung transplantation with simultaneous defect correction may be the method of choice. However, for septal defects, better outcomes are observed with transplantation of the heart–lung complex [49, 142]. In recent years, transplantation outcomes have improved: 5- and 10-year survival rates have reached 52–75% and 45–66%, respectively [49, 142, 143]. According to the same registry, the proportion of heart-lung transplantations performed for congenital heart disease accounts for 35.7% of the total diagnoses in recipients, and pulmonary hypertension for 27.6%, respectively. It should be noted that indications for such treatment are not standardized; comparative studies have not been conducted, and data on successful outcomes are limited [144, 145, 146, 147].

• In patients with a history of radical surgery for congenital heart disease using a conduit (vascular xenograft***) who have moderate or greater regurgitation and/or moderate or more pronounced stenosis of the conduit (vascular xenograft***), it is recommended to perform a re-intervention if there are complaints of decreased physical activity or cardiac arrhythmias [39, 40-44, 149].

ESC IIa B-NR (LoE C, GoR 4)

Comments: residual or newly emerging abnormalities of the right ventricular outflow tract into the pulmonary artery system after the correction of a number of conotruncal congenital heart defects, including after the correction of congenital heart disease, is a widely recognized problem. When implanting a conduit (vascular xenograft***) both obstruction and progression of valve regurgitation may be observed. When using the technique of right ventricular outflow tract reconstruction with autologous tissues, there is also a risk of obstruction, along with the development of insufficiency of the monocuspid valvar element, or progression of right heart dilation with the valve-sparing technique [4, 12, 34, 45, 136, 155].

• In patients with a history of radical surgery for congenital heart disease using a conduit (vascular xenograft***) who are asymptomatic but have severe regurgitation or severe stenosis of the conduit (vascular xenograft***), it is recommended to perform a re-intervention if decreased right ventricular ejection fraction or right ventricular dilation is detected [39, 40-44, 149].

ESC IIb B-NR (LOE C, SOR 4)

Comments: the high predisposition to re-interventions after radical correction of congenital heart disease is due to the initial anatomy of the defect and the need to use conduits (vascular xenograft***) and other complex techniques for creating the right ventricular outflow tract into the pulmonary artery system. However, timely re-operation to eliminate progressive obstruction or long-standing pulmonary valve regurgitation can prevent pathological myocardial changes, cardiomegaly, and cardiac arrhythmias [4, 12, 34, 45, 136, 149, 226, 227].

3.3 Endovascular interventions

• In patients with a history of radical surgery for congenital heart disease using a conduit (vascular xenograft***) or another technique who have hemodynamically significant obstruction, it is recommended to perform transcatheter balloon vasodilation as a palliative measure to relieve the obstruction or as a trial procedure to assess the compliance of the obstructed area prior to stent implantation in the obstruction zone [156-158].

ESC IIb C (LoE C, GoR 5)

Comments: percutaneous balloon dilation of a stenosed conduit (vascular xenograft***) is currently considered a procedure with a relatively short-term and not always achievable positive effect [156]. This is explained by the nature of late conduit obstruction, which includes conduit overgrowth, intimal proliferation, kinking and external compression, calcification, and valve degeneration [156].

• Percutaneous stent implantation (conduit stenting) in patients after radical correction of congenital heart disease using a conduit (vascular xenograft***) is recommended for hemodynamically significant conduit obstruction, when it is anticipated that (a) stent implantation will significantly prolong conduit function until a subsequent intervention is required, (b) any resulting regurgitation will be well tolerated, and (c) stent implantation will not cause deformation of the pulmonary artery branch bifurcation or compromise coronary blood flow [156-158].

ESC I B (LoE C, GoR 4)

Comments: percutaneous stent implantation into a conduit (vascular xenograft***) represents a viable alternative to open surgical treatment in patients with conduit dysfunction. Despite its minimally invasive nature, serious complications are possible, including conduit rupture, development of severe valve regurgitation, and compression of the coronary arteries. To prevent this, when choosing a stent, one must avoid sizes exceeding the conduit diameter and evaluate the distance of the coronary arteries from the stent implantation site using coronary angiography [156].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

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

Comment. Thanks to the introduction of advanced 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 patients surviving into adulthood [262]. 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 diseases, stroke, and coronary artery disease [263, 264]. 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 [265]. 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 essential for the physical, emotional, and psychosocial development of children [266-270].

• Children with congenital heart disease and no signs of hemodynamic impairment are recommended daily physical activity as defined by the WHO at the level of > 60 minutes, without restrictions, as well as participation in recreational sports with mandatory evaluation of severity at least once a year [271-273].

No ESC guideline (LoE C, GoR 5)

• Children with congenital heart disease and mild signs of hemodynamic impairment are recommended daily physical activity of moderate and low intensity, as well as participation in low- and moderate-intensity dynamic and static sports, with the exception of competitive sports, provided that exercise testing demonstrates satisfactory exercise tolerance [271, 273].

No ESC guideline (LoE C, GoR 5)

• Children with congenital heart disease and severe hemodynamic impairment 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 [273].

No ESC guideline (LoE C, GoR 5)

• Within 6 months after surgical correction of truncus arteriosus under cardiopulmonary bypass, a patient with a complicated postoperative course (residual PH, heart failure, infectious complications, repeated surgical interventions during a single hospitalization) is recommended to undergo rehabilitation (medical rehabilitation services for a patient who has undergone heart and great vessel surgery) in a specialized cardiac inpatient facility [205,161,206,207].

No ESC guideline (LoE C, GoR 5)

Comments: the following conditions may occur after truncus arteriosus 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 [208].

– Persistence of PH may be observed even after successful CHD correction [81]. In the presence of clinical manifestations, its treatment is carried out in accordance with current guidelines [35].

– Aortic regurgitation. It may result from the initial anatomy of the defect or aortic valve cusps. Its frequency reaches 5–20% [209,210,211]. Aortic regurgitation may progress, and its incidence increases with age. It usually progresses slowly, but this process is highly individual. Monitoring and (if necessary) surgical treatment are carried out in accordance with accepted guidelines [212]. Although views on the optimal timing and method of correction remain controversial [211].

– Rhythm and conduction disturbances (ventricular and supraventricular arrhythmias, bundle branch block, atrioventricular blocks, and sudden cardiac death) may occur both immediately after surgical correction and at more remote times [208,213].

No ESC guideline (LoE C, GoR 5)

Comments: 6 months after truncus arteriosus 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 truncus arteriosus without significant hemodynamic disturbances, and without prognostically significant cardiac rhythm and conduction disorders [261].

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 truncus arteriosus is favorable provided that CHD 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 [7,215].

• Patients with truncus arteriosus after surgical or endovascular intervention are recommended to have a follow-up outpatient appointment (examination, consultation) with a pediatric cardiologist or a follow-up outpatient appointment (examination, consultation) with a cardiologist [133,216].

ESC IIaB (COR C, LOE 5)

Comments: the frequency of follow-up monitoring by a pediatric cardiologist/cardiologist is at 1 month, 3, 6, and 12 months after surgery. The follow-up monitoring package includes ECG and echocardiography, and, if necessary, exercise testing (exercise electrocardiography; exercise echocardiography; ergometer exercise test; ergospirometry) and pulse oximetry. Subsequent patient monitoring is carried out at intervals of 3–36 months [133,216,218].

Patients with LV dysfunction, residual shunt, PAH, aortic regurgitation, and ventricular outflow tract obstruction should be monitored annually in specialized centers. In patients with corrected truncus arteriosus with preserved LV function, absence of PH, and other complications, monitoring with control visits every 1–3 years is possible. After endovascular intervention, regular monitoring is necessary 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 whether a patient with corrected or uncorrected truncus arteriosus belongs to a particular group, different frequencies of monitoring and scopes of required examinations are recommended:

ESC IIbB (LoE C, GoR 4)

ESC IB (COR C, LOE 4)

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 developing complete atrioventricular block requires special attention in patients after truncus arteriosus correction.

• Children who have undergone truncus arteriosus correction surgery are recommended to be vaccinated no earlier than three months later in order to build active protective immunity against infections [221].

ESC none (COR C, LOE 5)

• When monitoring patients after truncus arteriosus correction or a developed complication, it is recommended to provide infective endocarditis prophylaxis for 6 months [222].

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

Comments: for any type of congenital heart defect for the correction of which synthetic materials/conduits were used (cardiovascular patch, synthetic***; vascular xenograft***; bi-leaflet mechanical aortic valve prosthesis***), bacterial endocarditis prophylaxis is carried out in the presence of indications for 6 months after surgery or for life if residual shunts or valve regurgitation persist. Endocarditis prophylaxis is performed during dental interventions accompanied by damage to the oral mucosa (tooth extraction, manipulations in the periapical zone of the tooth, etc.).

6. Organization of Medical Care

Indications for hospital admission to 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 discharging a patient 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 truncus arteriosus 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 [54,207].

ESC IB (LOR C, LOE 5)

ESC IIaA (LoE C, GoR 5)

ESC none (LOR C, LOE 5)

Pregnancy and childbirth

Pregnancy and childbirth are usually well tolerated [224]:

– with corrected truncus arteriosus;

– in patients with preserved LV function;

– at NYHA functional classes I–II;

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

– with small truncus arteriosus.

ESC IIIB (LoE C, GoR 5)

Comments: pregnancy is strictly contraindicated in Eisenmenger syndrome due to high maternal and infant mortality [224]. Pregnancy in female patients with cyanosis, in the absence of PH, is associated with significant risks for the mother and fetus. SpO₂ < 85% and hemoglobin >200 g/L before pregnancy are the most important predictors of maternal mortality [225].

• If pregnancy occurs, female patients with truncus arteriosus in the presence of cyanosis and PH are recommended to undergo artificial termination of pregnancy (abortion) [224].

ESC IC (LoE C, GoR 5)

Criteria for Evaluating the Quality of Medical Care

Quality assessment criteria for primary health care provided to adults and children with truncus arteriosus (ICD-10 codes: Q20.0, I27.8)

Quality assessment criteria for specialized medical care provided to adults and children with truncus arteriosus (ICD-10 codes: Q20.0, I27.8)

References

Appendix A1. Working Group Composition

1. Avramenko A.A., (Samara).

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

3. Belov V.A., (Kaliningrad).

4. Bogdanov V.N., (Chelyabinsk).

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

6. Boriskov M.V., D.Sc. in Medicine, (Krasnodar).

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

8. Brodsky A.G., Ph.D. in Medicine, (Surgut).

9. Volkov S.S., Ph.D. in Medicine, (Moscow).

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

11. Grigoryan A.M., Ph.D. in Medicine, "Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists", (Moscow).

12. Gladyshev I.V., (Chelyabinsk).

13. Gorbatikov K.V., D.Sc. in Medicine, (Tyumen).

14. Gorbatykh Yu.N., D.Sc. in Medicine, (Novosibirsk).

15. Gulyaev Yu.V., (Moscow).

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

17. Zelenikin M.A., D.Sc. in Medicine, "Association of Cardiovascular Surgeons of Russia", (Moscow).

18. Zelenikin M.M., D.Sc. in Medicine, "Association of Cardiovascular Surgeons of Russia", (Moscow).

19. Ivanov S.N., D.Sc. in Medicine, "Russian Society of Cardiology", (Novosibirsk).

20. Kalashnikov S.V., Ph.D. in Medicine, "Association of Cardiovascular Surgeons of Russia", (Moscow).

21. Kim A.I., D.Sc. in Medicine, "Association of Cardiovascular Surgeons of Russia", (Moscow).

22. Kovalev I.A., D.Sc. in Medicine, "Association of Pediatric Cardiologists of Russia", (Moscow).

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

24. Krivoshchekov E.V., D.Sc. in Medicine, (Tomsk).

25. Krupyanko S.M., D.Sc. in Medicine, "Association of Pediatric Cardiologists of Russia", (Moscow).

26. Kupryashov A.A., D.Sc. in Medicine, (Moscow).

27. Levchenko E.G., (Moscow).

28. Lezhnev A.A., (Moscow).

29. Martynyuk T.V., "Russian Society of Cardiology", (Moscow).

30. Movsesyan R.R., D.Sc. in Medicine, "Association of Cardiovascular Surgeons of Russia", (Saint Petersburg).

31. Moiseeva O.M., D.Sc. in Medicine, "Russian Society of Cardiology", (Saint Petersburg).

32. Nalimov K.A., (Khabarovsk).

33. Nikiforov A.B., (Moscow).

34. Petrushenko D.Yu., (Kazan).

35. Plotnikov M.V., Ph.D. in Medicine, (Astrakhan).

36. Podoksenov A.Yu., (Tomsk).

37. Pursanov M.G., D.Sc. in Medicine, (Moscow).

38. Svobodov A.A., D.Sc. in Medicine, (Moscow).

39. Sinelnikov Yu.S., D.Sc. in Medicine, (Perm).

40. Teplov P.V., (Krasnoyarsk).

41. Trunina I.I., D.Sc. in Medicine, "Association of Pediatric Cardiologists of Russia", (Moscow).

42. Chernogrivov A.E., D.Sc. in Medicine, "Association of Cardiovascular Surgeons of Russia", (Moscow).

43. Shekhmametyev R.M., (Perm).

44. 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 specialist.

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 fundamentals of public health protection in the Russian Federation (Federal Law No. 323-FZ of November 21, 2011)

2. Procedure for providing medical care to patients with cardiovascular diseases (Order of the Russian Ministry of Health No. 918n of November 15, 2012)

Monitoring and correction of heparin sodium dose**[239,241]

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Truncus arteriosus is a critical congenital heart defect of the newborn period, where only a single arterial vessel arises from the base of the heart as the great artery. In addition, there is a ventricular septal defect, i.e., an opening in the septum separating the right and left ventricles, which in this case is present as a component of a more complex malformation. The interventricular septum is a robust muscular barrier forming the inner walls of both the right and left ventricles, accounting for approximately 1/3 of their total surface area in each. It participates in the contraction and relaxation of the heart during each cycle, just like the rest of the ventricular walls. In the fetus, it is formed from three constituent parts. By the 4th–5th week of gestation, all these components must precisely align and connect with each other. If this does not happen for any reason, an opening, or defect, remains in the septum. In the case of truncus arteriosus, this is not so much an "additional" defect as it is one of the components of the complex malformation that the aforementioned defect represents. Without an associated ventricular septal defect, newborns with truncus arteriosus are practically non-viable and perish very rapidly. However, even with the classical form, truncus arteriosus is classified as a critical heart defect. Soon after birth and the establishment of normal blood flow in both circulatory loops, a significant pressure difference arises between the left and right ventricles. Since in truncus arteriosus, mixed blood from the left and right ventricles is pumped simultaneously into both the aorta and the pulmonary artery, i.e., both where it should go and where it should not be. Thus, with every heartbeat, there is a massive, virtually unrestricted left-to-right shunt of blood. In such a situation, not only is the right ventricle forced to work with an increased load to pump this excess volume of already oxygenated blood back into the lungs and left heart chambers, but simultaneously the left ventricle also experiences pronounced volume overload, as it receives an increased "ballast" return of blood through the pulmonary veins.

As already mentioned, truncus arteriosus can be "typical", i.e., the most common variant. However, variations are possible in terms of the level of origin, branching anatomy, and degree of development of the pulmonary trunk. In some cases, stenoses or narrowing of these branches may be present, which to a certain extent protects the lesser circulation from excessive blood flow. Nevertheless, keep in mind that this defect is always complex for surgical treatment and carries an extremely unfavorable prognosis without it. Furthermore, complicating heart defects that worsen the already severe clinical course may be present. For example, coarctation of the aorta or pathology of the so-called truncal valve, which in this defect serves simultaneously as the equivalent of the aortic and pulmonary semilunar valves of the heart, significantly affects both the prognosis and the treatment strategy.

Overall, a scenario where a child reaches school age while remaining asymptomatic is practically impossible. Marked lag in physical development and frequent "colds" are inevitable, with the exception of isolated case reports of unoperated adult patients, which is a medical rarity. Such cases are explained by a chance combination of circumstances and a favorable anatomical constellation of the defect. Moreover, as a rule, by this age severe hypertensive changes will develop in the lungs, as described below, and in their presence, surgery may be offered only on the basis of invasive cardiac catheterization. If study findings show that the pulmonary hypertensive changes are irreversible, radical correction will not be feasible.

Such advanced cases, usually seen after the first year of life, represent a different and no less dangerous scenario. Immediately after the child's first breath, the blood flow from the left ventricle divides into two: through a ventricular septal defect, the common blood flow goes directly into the aorta and pulmonary artery. In the best case, their volumes are equal, but usually the blood flow into the lesser circulation, i.e., the lungs, is much larger. Therefore, not only the heart but also the pulmonary vessels find themselves in a severe situation: the pulmonary vessels become overloaded with the increased volume of excess blood ultimately arriving through aberrant branches of the pulmonary artery originating from the aorta. The most critical indicators of this course of events are the pulmonary artery pressure and the magnitude of the shunt. Today, these data are provided by ultrasound examination (echocardiography) and cardiac catheterization. An increase in pressure in the lesser circulation indicates pulmonary hypertension—the most formidable consequence of a large left-to-right shunt. Numerous compensatory mechanisms are activated: the muscle mass of the ventricles increases, and the pulmonary vessels adapt, initially accommodating the excess blood volume, and subsequently thickening the walls of arteries and arterioles, making them denser and less elastic. This period is hazardous because the child's condition may clinically improve significantly, but this improvement is deceptive, and the window for surgical intervention may be missed. However, unlike other congenital heart diseases with a left-to-right blood shunt, the development of pulmonary hypertension-like changes in the lungs occurs very rapidly. This period usually takes only a few months, after which the pressures in the right and left ventricles equalize across all phases of the cardiac cycle, and a large shunt into the pulmonary artery no longer occurs. Subsequently, the pressure in the right ventricle may exceed that in the left, initiating the so-called "reverse shunt," and more venous blood will enter the arterial system—the systemic circulation. The patient becomes even more "cyanotic." We have described this picture so that it is understood that a defect such as truncus arteriosus inevitably has a poor prognosis without surgery, and the development of various complications is unavoidable. Having survived the early period of heart failure manifestations, a patient with this diagnosis nevertheless does not recover, but transitions to another stage of the disease where at some point repairing the defect loses its meaning, and surgery is already too late. We are referring here, let us recall, only to the small fraction of patients who managed to pass through the neonatal period relatively successfully.

What should we look out for in order to prevent this course of events and other complications in time?

The main indicator of the neonatal period is weight gain. In older children against this background, frequent colds occur that become prolonged and can turn into pneumonia. This can last for several months, and if the cause is persistent truncus arteriosus (PTA), such a child must be under the constant supervision of a cardiologist, and if the symptoms do not resolve, drugs to manage signs of heart failure will likely be prescribed.

On the other hand, clinical manifestations of heart failure are usually pronounced, and even if the child has no dyspnea or sweating at rest and the breathing pattern is not concerning, these symptoms appear during exertion associated with feeding or agitation.

With drug therapy, symptoms may disappear or significantly decrease. But overall, nothing changes, and heart size only increases over time, while the ultrasound picture of complex congenital heart disease requires consultation with cardiologists and cardiac surgeons.

Importantly, PTA cannot resolve spontaneously, as is observed with some septal defects that can decrease or close on their own. If the child does not get better, waiting is not an option, as the situation may progress to the one described above and surgery will be too late.

The best surgical results are achieved after repairing PTA during the first weeks of life—according to some data, up to two to three months is acceptable—when the child has signs of heart failure, but pulmonary hypertension and other processes are still reversible. The heart rapidly decreases in size, and blood flow in both circulatory loops normalizes.

Surgical treatment is the only method and allows for the complete elimination of the defect and its consequences. PTA repair is an open-heart surgery because it requires opening the heart chambers and is therefore performed using cardiopulmonary bypass.

As already mentioned, in the absence of surgical treatment, PTA always leads to elevated pressure in the pulmonary vessels—pulmonary hypertension (PH), or pulmonary arterial hypertension (PAH) when additional hemodynamic signs are present. 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 the diagnosis, which your attending physician will discuss with you.

In the extremely few adult patients without surgery, pulmonary hypertension comes to the forefront. The chances of reaching adulthood are extremely small, and in these rare cases, the majority of patients already have pathology that is inoperable due to pulmonary hypertension. Gradually, they notice that the relatively active lifestyle they are accustomed to becomes beyond their capabilities. The pace of daily activity should be reviewed, and patients should 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 intake of table salt, which contains sodium that regulates fluid balance in the body, should be reduced. When tissue fluid increases, blood volume also increases, which places a higher load on your heart. One of the most effective ways to reduce the load on the heart is to decrease the amount of salt consumed in food. 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

No.