Single Ventricle: Clinical Practice Guidelines

List of Abbreviations

AV – atrioventricular

ACG — angiocardiography (transvenous cardiac catheterization, cardiac chamber probing)

Ao – aorta

aPTT – activated partial thromboplastin time

BVO — bulboventricular foramen

PLE — protein-losing enteropathy

SVC – superior vena cava

CHD – congenital heart disease

ASCC — additional source of pulmonary blood flow

BCPA – bidirectional cavopulmonary anastomosis

VSD – ventricular septal defect

SV — single ventricle

CT – computed tomography

PA – pulmonary artery

PVR – pulmonary vascular resistance

LV – left ventricle

INR – international normalized ratio

IAC – interatrial communication

MRI – magnetic resonance imaging

CIR – circulatory insufficiency

IVC – inferior vena cava

NSAIDs – nonsteroidal anti-inflammatory drugs

PDA – patent ductus arteriosus

RV – right ventricle

RCT – randomized controlled trial

SyV — systemic ventricle

SPA — systemic-to-pulmonary artery shunt

HF – heart failure

TGA — transposition of the great arteries

TEC – thromboembolic complications

ECG – electrocardiography

ECC — extracardiac conduit (synthetic vascular prosthesis)

EchoCG – echocardiography

Terms and Definitions

Nakata index (synonym: pulmonary artery index) — the ratio of the total cross-sectional area of the right and left pulmonary arteries to the body surface area.

McGoon index — the ratio of the sum of the diameters of the pulmonary arteries at their bifurcation to the diameter of the descending aorta.

Reddy index (synonym: lower lobe pulmonary artery index) — the ratio of the sum of the cross-sectional areas of the lower lobe branches of the right and left pulmonary arteries to the body surface area.

Critical congenital heart defects — conditions characterized by acute cardiac output deficiency, rapid progression of heart failure, tissue oxygen starvation with the development of decompensated metabolic acidosis, and impaired vital organ function [1].

Computed tomography — a non-invasive diagnostic imaging method that provides a series of cross-sectional submillimeter axial images of organs and human body structures, based on the measurement and complex computer processing of the difference in X-ray attenuation by tissues of different densities, used to improve the differentiation of organs from each other, as well as normal and pathological structures. Various contrast-enhancement techniques are used, employing iodine-based radiopaque agents. To visualize the cardiovascular structures, CT angiography is used — a technique of intravenous bolus injection of a radiopaque agent into the bloodstream using an intravascular contrast administration system at a set injection rate and time. Based on the obtained data, a three-dimensional model of the heart and blood vessels is constructed via computer post-processing with 3D reconstruction.

Pulmonary venous index — the ratio of the sums of the cross-sectional areas of the pulmonary veins to the body surface area.

Magnetic resonance imaging — a non-invasive method for obtaining tomographic medical images without ionizing radiation to study internal organs and tissues, based on the phenomenon of nuclear magnetic resonance and the measurement of the electromagnetic response of atomic nuclei located in a strong constant magnetic field in response to excitation by a specific combination of electromagnetic waves; such nuclei are hydrogen atoms present in the human body as part of water and other substances. MR angiography is a method for imaging the vascular lumen using an MR scanner. The method allows the assessment of both anatomical and functional features of blood flow. MR angiography is based on the difference in signal between moving protons (blood) and surrounding stationary tissues, making it possible to obtain images of blood vessels without using any contrast agents — non-contrast angiography (e.g., phase-contrast MR angiography). In some cases, intravenous bolus contrast enhancement using paramagnetic-based contrast agents (gadolinium) is applied.

Rashkind procedure (synonym: balloon atrioseptostomy) — an endovascular procedure consisting of advancing a catheter with an expansion balloon into the oval fossa of the interatrial septum followed by dilation of the interatrial communication.

Restrictive — creating an obstruction to blood flow.

Transudation — a condition characterized by prolonged fluid accumulation from serous cavities.

Echocardiography — an ultrasound imaging method aimed at studying morphological and functional changes in the heart, its valve apparatus, and great vessels.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Single ventricle (SV) — a congenital heart defect (CHD) characterized by impaired atrioventricular connection, where the atrial cavities connect via the mitral and tricuspid valves to only a single, well-developed dominant ventricle. In this condition, pulmonary and systemic circulations occur in parallel rather than in series as in normal anatomy [1-3].

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

Predisposing factors for the development of SV, like other CHDs, include the following: 1) chromosomal abnormalities — 5%; 2) single-gene mutations — 2–3%; 3) environmental factors (parental alcoholism, rubella, medications, etc.) — 1–2%; 4) polygenic-multifactorial inheritance — 90%.

It was previously believed that these causes lead to agenesis of the interventricular septum, which was linked to the occurrence of SV. However, studies by R. Van Praagh [4] showed that this mechanism is not universal, as it represents only one of the variants of SV origin; from the standpoint of embryological development and anatomy, this defect most frequently occurs when there is a delayed development of one or both cardiac ventricles. To understand the developmental mechanisms of various anatomical variants of SV, some aspects of normal cardiac embryogenesis should be recalled. In the early stages of cardiac development, both atria communicate with the primary ventricle, which in turn communicates with the bulbus cordis, giving rise to the truncus arteriosus. The left ventricle (LV) develops from the primary ventricle, the inflow and principal parts of the right ventricle (RV) develop from the sinus part of the bulbus cordis, and the outflow tracts of both ventricles develop from the conus part. Consequently, delayed development of the sinus part of the bulbus cordis will result in the absence of the RV, and the single ventricular chamber acquires left ventricular structure. In such cases, only the outflow (infundibular) chamber remains of the RV — the "outlet" — from which, as a rule, the vessel that should originate from the RV arises: in the normal arrangement of the great vessels, the pulmonary artery (PA), and in transposition of the great vessels (TGA), the aorta (Ao). With delayed development of the primary ventricle, the single ventricular chamber has the structure of an RV, and the great vessels, regardless of their interrelationship type, arise from the outflow chamber. When there is delayed development of the primary ventricle and the sinus part of the bulbus cordis along with agenesis of the interventricular septum, the single ventricular cavity is similar in its internal structure to the outflow tract of the RV [1].

The features of hemodynamic disorders in SV are determined by the mixing of oxygenated blood streams from the pulmonary veins (oxygen saturation of 95–100%) and deoxygenated blood from the systemic veins (oxygen saturation of 55–60%) within a single chamber, which leads to varying degrees of arterial hypoxemia. With equal pulmonary and systemic blood flow, the resulting oxygenation will be 75–80%. As pulmonary blood flow increases, systemic saturation also increases. In turn, the volume of blood flow through the pulmonary and systemic circulations (in the absence of anatomical obstructions) is determined by the relative resistance of the respective vessels. With a persistently high pulmonary blood flow, volume overload of the SV rapidly develops, as it supports both systemic and pulmonary circulation. As a result, congestive heart failure (HF) develops; the ventricle loses its ability to eject blood against high systemic resistance, and an increasing fraction of blood recirculates through the pulmonary vasculature. Long-term persistence of enhanced pulmonary blood flow leads to changes in the pulmonary vessels, up to sclerosis and elevated pulmonary vascular resistance (pulmonary hypertension). In the case of concomitant PA stenosis, the ratio of pulmonary to systemic blood flow drops below 1.0, leading to a significant decrease in systemic saturation, although HF is less pronounced.

When the aorta originates from the rudimentary ventricular chamber, there is a so-called bulboventricular foramen along the blood flow pathway from the systemic ventricle to the aorta, which is essentially a ventricular septal defect (VSD). Over time, obstruction increases at the BVO level (subaortic stenosis), which impedes systemic blood flow. In some observations, obstructions are present along both the systemic and pulmonary blood flow pathways simultaneously.

A patent ductus arteriosus can play an important role in maintaining adequate hemodynamics of both the pulmonary and systemic circulations (ductus-dependent conditions) [3].

1.3 Epidemiology of the Disease or Condition

The incidence of a single ventricle (SV) is approximately 0.13 per 1,000 newborns, accounting for 2.5% of all congenital heart defects (CHD) and 5.5% of "critical" CHD, with an untreated first-year mortality rate of 75% [1,5]. The most frequent variant is a double-inlet left ventricle with transposition of the great arteries [1].

The prognosis of the natural course of SV is unfavorable: without surgery, 55–67% of children die within the first year of life, and up to 90% by 10 years of age [2].

1.4 Features of Coding the Disease or Condition

In accordance with the International Classification of Diseases, 10th Revision – Congenital malformations of cardiac chambers and connections (Q20):

Q20.4 – Double inlet ventricle (Common ventricle. Three-chambered heart. Single ventricle).

1.5 Classification of the disease or condition

SV is characterized using the classification by K. Van Praagh et al. (1964), which is based on the anatomical structure of the ventricular chamber and the arrangement of the great vessels [4], or the system proposed by R.H. Anderson et al. (1975), which characterizes the sequential arrangement of the heart chambers [6]. According to K. Van Praagh, the internal architectonics of an SV may have the structure of:

• a left ventricle;

• a right ventricle;

• both left and right ventricles;

• the right ventricular outflow tract, or an indeterminate structure.

The tricuspid and mitral valves, or a common atrioventricular valve, open into a single or common ventricle.

In each anatomical variant, the arrangement of the great vessels may be:

• normal (type I);

• the aorta may be positioned to the right of the pulmonary trunk (type II);

• the aorta may be positioned to the left of the pulmonary trunk (type III);

• the position of the great vessels may be the reverse of normal (type IV).

The indicated variants may occur in the setting of normal, inverted, or indeterminate visceral situs. A disadvantage of the K. Van Praagh classification is the exclusion of mitral and tricuspid valve atresia from it. Similarly, the R.H. Anderson system emphasizes the nature of atrioventricular connections, stating that the unifying criterion for a single-ventricle heart is that the atria connect to only one ventricle, whereas the second ventricle, if present, is severely hypoplastic [6,7]. At the same time, the absence of one atrioventricular connection allows a heart with tricuspid atresia to be considered a single-ventricle heart [6,7].

According to the CHD Database and the European Association for Cardiothoracic Surgery, SV includes [5]:

• double-inlet left ventricle;

• double-inlet right ventricle;

• a heart with the absence of one atrioventricular connection (mitral atresia, tricuspid atresia);

• a heart with a common atrioventricular valve and only one fully developed ventricle (unbalanced common atrioventricular septal defect);

• a heart with only one fully developed ventricle and heterotaxy syndrome;

• other rare forms of single-ventricle hearts that do not fit into any of the specified categories.

1.6 Clinical presentation of the disease or condition

Clinical symptoms are determined by volume overload of the heart and pulmonary hypertension in patients without concomitant pulmonary artery (PA) stenosis, and by marked hypoxemia in patients with PA stenosis.

In cases of decreased pulmonary blood flow, cyanosis develops from birth or shortly thereafter. Blood oxygen saturation is 70–80%. Cyanosis increases with exertion (movement, crying, feeding), including as the child grows older and taller. In 10–15% of patients, hypoxic (cyanotic) spells are observed; their nature is the same as in tetralogy of Fallot (spells are caused by spasm of the RV outflow tract, restricting blood flow into the PA). Thus, most patients with SV are in a severe condition caused primarily by chronic arterial hypoxemia. Excessive pulmonary blood flow in SV is much less common. Cyanosis in such patients in early infancy is often absent or mild. The progression of cyanosis in older children is usually associated with a progressive decrease in pulmonary blood flow as a result of morphological changes in the pulmonary arterial vessels caused by excessive blood flow.

Dyspnea is present in the majority of patients. In cases of decreased pulmonary blood flow, it is present even at rest and also increases with exertion. In cases of excessive pulmonary blood flow, dyspnea is frequently combined with signs of heart failure of varying severity (ranging from excessive sweating and tachycardia to hepatomegaly, edema, ascites, and/or hydrothorax).

Gradual remodeling of the distal phalanges of the fingers into "clubbed fingers" and "watch-glass nails" occurs due to chronic arterial hypoxemia. The described finger changes are more common in children who survive past the age of two, but can sometimes develop as early as 3–4 months.

In cases of concomitant subaortic stenosis, aortic arch hypoplasia, or coarctation of the aorta, symptoms of inadequate organ and tissue perfusion can rapidly develop and progress, up to shock. Patients with simultaneous systemic and pulmonary outflow tract obstruction are generally not viable.

In addition to the specific clinical presentation, about 70% of patients exhibit physical developmental delay as well as scoliosis.

Pulmonary auscultation may reveal congestive rales, which are characteristic of excessive pulmonary blood flow and the development of heart failure. Cardiac auscultation findings are determined primarily by the presence and severity of obstruction at the level of the bulbo-ventricular opening (BVO) and/or pulmonary trunk. A systolic murmur is heard over the cardiac area, and in patients without PA stenosis, it is maximally pronounced in the 3rd–4th intercostal spaces. The origin of the systolic murmur may be due either to blood flowing from the systemic ventricle (SV) through the BVO into the outlet chamber and further into the aorta. In PA stenosis, the murmur is harsh and maximally pronounced over the base of the heart, corresponding to the level of the stenosis. A systolic murmur at the apex corresponds to atrioventricular valve regurgitation. It should be kept in mind that SV is often combined with anomalies of cardiac position, which alter the localization of murmurs [1-3,8-11].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria:

• Physical examination findings: cyanosis, signs of circulatory failure;

• Echocardiography / angiocardiography data: absence of the interventricular septum, presence of atrioventricular valves opening into the SV, presence of an outlet chamber (rudimentary ventricle) with a great vessel arising from it.

2.1 Complaints and Anamnesis

• When taking the history of a patient (or their relatives in the case of small children) with suspected single ventricle, it is recommended to determine the time of onset of cyanosis, the presence or absence of its progression, and to inquire about the presence and nature of dyspnea to verify the diagnosis and assess the general condition [1-3,8-11].

(Level of Evidence C, Grade of Recommendation 5)

• When taking the medical history and collecting complaints in patients with suspected single ventricle, to assess the severity of circulatory failure (CF), it is recommended to evaluate the presence and nature of sweating in the patient (or their relatives) [1-3,8-12].

(Level of Evidence C, Grade of Recommendation 5)

2.2 Physical Examination

• All patients with suspected single ventricle are recommended to undergo an outpatient visit (examination, consultation) with a pediatric cardiologist and/or cardiologist, and/or cardiovascular surgeon to clarify the diagnosis [1-3,8-11].

(CQR C, LOE 5)

• During the physical examination of patients with suspected single ventricle, it is recommended to assess signs of chronic arterial hypoxemia (finger clubbing, watch-glass nails) [1-3,8-11].

(CQR C, LOE 5)

• For an indirect assessment of the pulmonary-to-systemic blood flow ratio, as well as the severity of the patient's condition, during the physical examination of patients with suspected single ventricle, it is recommended to determine the level of systemic oxygenation (blood oxygen saturation) using pulse oximetry [1-3,8-11].

(Level of Evidence C, Grade of Recommendation 5)

• During the physical examination of patients with suspected single ventricle, to assess the severity of CF and the patient's condition, it is recommended to evaluate the character and rate of respiration [1-3,8-12].

(CQR C, LOE 5)

Comments: on inspection, the patient's breathing may be physiological, with moderate (intercostal retractions) or marked (dyspnea) involvement of accessory muscles.

• During the physical examination of patients with suspected single ventricle, lung auscultation is recommended to detect the presence or absence of congestive rales [1-3,8-11].

(CQR C, LOE 5)

• During the physical examination of patients with suspected single ventricle, to determine the character of murmurs and indirectly assess the state of pulmonary blood flow, it is recommended to perform cardiac auscultation (see section 1.6) [1-3,8-12].

(Level of Evidence C, Grade of Recommendation 5)

• During the physical examination of patients with suspected single ventricle, abdominal palpation is recommended to detect the presence or absence of hepatomegaly [1-3,8-11].

(Level of Evidence C, Grade of Recommendation 5)

• For pediatric patients with suspected single ventricle, it is recommended to use the modified Ross R.D. scale for assessing the severity of circulatory failure and functional status in children for a rapid evaluation of the severity of heart failure [12] (Appendix G1).

(Level of Evidence C, Grade of Recommendation 5)

2.3 Laboratory Diagnostics

There is no specific laboratory diagnostic test for a single ventricle of the heart.

• All patients with a single ventricle of the heart are recommended to undergo a general (clinical) urinalysis and a general (clinical) blood test including hemoglobin, hematocrit, red blood cells, white blood cells, platelets, and erythrocyte sedimentation rate (ESR) as part of the initial examination, upon admission to the hospital (including for surgical treatment), during follow-up at least once a year, and in the postoperative period if necessary [1-3,8-11,79].

(Level of Evidence C, Grade of Recommendation 5)

• All patients with a single ventricle of the heart are recommended to undergo a general biochemical blood test (levels of potassium, sodium, chlorides, glucose, creatinine, total protein, albumin, urea, total and conjugated bilirubin, serum iron, and activities of aspartate aminotransferase and alanine aminotransferase in the blood) to assess renal and hepatic function as part of the initial examination, upon admission to the hospital (including for surgical treatment), during follow-up at least once a year, and in the postoperative period if necessary [1-3,13-16,77,78,79].

(Level of Evidence C, Grade of Recommendation 5)

• All patients with a single ventricle of the heart are recommended to undergo an acid-base balance and blood gas analysis (pH, BE, pCO₂, pO₂, SatO₂, lactate level [lactic acid in the blood] — capillary/arterial/venous blood gas analysis) to assess the severity of hypoxemia and the degree of metabolic disorders [1-3,8-11,79].

(Level of Evidence C, Grade of Recommendation 5)

• During the examination stage, including prior to surgery, all patients with a single ventricle of the heart are recommended to undergo a coagulogram (screening hemostasis test) (activated partial thromboplastin time [APTT], international normalized ratio [INR], and fibrinogen level) to rule out congenital and acquired blood coagulation disorders, predict postoperative thromboses and bleeding, and evaluate the efficacy of subsequent (postoperative) thromboprophylaxis [8,17-20,37,80-82].

(Level of Evidence C, Grade of Recommendation 5)

Comments: pre-existing hemostatic abnormalities are a well-documented finding in patients with single ventricle hemodynamics. If a patient exhibits hemorrhagic syndrome and/or laboratory signs of coagulation disorders in the preoperative period, it is advisable to postpone surgery until the cause of these disorders is identified and corrected.

• All patients with a single ventricle of the heart who receive thromboprophylaxis with unfractionated or low-molecular-weight heparin following surgery are recommended to undergo laboratory monitoring of drug efficacy [37,80,82,83].

(Translational Research Level B, Evidence Level 3)

Comments: when using unfractionated heparin, it is recommended to determine the APTT (optimal target range in adults is 40–60 s, in children 60–85 s) and anti-Xa activity (blood heparin level assay — optimal range 0.35–0.7). When using low-molecular-weight heparin preparations, it is recommended to determine anti-Xa activity (blood heparin level assay: optimal range 0.5–1.0) [37,80,82,83].

• All patients with a single ventricle of the heart admitted to a hospital for surgical treatment are recommended to undergo testing for hepatitis B surface antigen (HbsAg) in the blood; antibodies to hepatitis C virus (HCV) in the blood; antibodies to Treponema pallidum in the blood; human immunodeficiency virus HIV-1 IgM and IgG antibodies in the blood; and human immunodeficiency virus HIV-2 IgM and IgG antibodies in the blood to rule out association with HIV infection, hepatitis, and syphilis [2,8,11,84].

(Level of Evidence C, Grade of Recommendation 5)

• All patients with a single ventricle of the heart admitted to a specialized hospital for surgical treatment of the defect who are expected to receive blood transfusion and/or blood components are recommended to undergo ABO blood group typing, Rhesus factor (Rh antigen D) testing, C, c, E, e, Cw, K, k phenotype determination, and anti-erythrocyte antibody screening [2,8,11,85,86].

(Level of Evidence C, Grade of Recommendation 5)

2.4 Instrumental Diagnostics

• During the examination stage, including prior to surgery, all patients are recommended to undergo electrocardiography (ECG) to rule out rhythm and conduction disturbances as well as myocardial ischemia [1-3,8-11,21].

(LetC, Level of Evidence 4)

Comments: right axis deviation (in over 70% of patients) with signs of right ventricular hypertrophy (in over 94% of patients) is the most consistent finding. Signs of left ventricular hypertrophy are also observed in 50% of patients. A single ventricle is characterized by a high-voltage ECG in the chest leads, except for V₁, with S waves exceeding R waves or equivalent RS complexes. Patients with TGA may lack Q waves in the left chest leads and present them in the right chest leads. Conduction and rhythm disturbances of various types are highly characteristic of single ventricle patients.

• During the examination stage, including prior to surgery, all patients with a single ventricle are recommended to undergo targeted chest X-ray to assess the size and configuration of the heart, evaluate the pulmonary circulation, and identify areas of hypo- or hyperventilation of the lungs [1-3,8-11].

(Level of Evidence C, Grade of Recommendation 5)

Comments: all patients with a single ventricle, regardless of the position of the great arteries, exhibit transverse cardiomegaly. This is more pronounced in patients with increased pulmonary blood flow. Signs of right ventricular enlargement are frequently present, and left ventricular enlargement is less common. All patients show enlargement of the right atrium. Patients with unobstructed pulmonary blood flow show enhanced pulmonary vascular markings and widened pulmonary roots. In the peripheral regions, pulmonary markings are represented by narrow arterial vessels, and the "pruned tree" sign of large arterial branches is also noted (imaging picture of severe pulmonary hypertension). In patients with normally positioned great arteries or with complete transposition associated with pulmonary stenosis, in the posteroanterior projection, a concavity in the region of the second arch is noted, similar to that typically seen in tetralogy of Fallot. In corrected TGA, the left heart border is not differentiated into the first and second arches and is represented by a continuous, slightly convex, or straight shadow due to the left-sided position of the ascending aorta. Meanwhile, in patients with pulmonary stenosis, bulging of the third arch is detected along the left heart border due to the location of the aortic root and the outlet chamber in this area.

• Echocardiography (EchoCG) is recommended for all patients with suspected single ventricle as the primary diagnostic method to establish a definitive diagnosis [1-3,8-11].

(Level of Evidence C, Grade of Recommendation 5)

Comments: absence of the interventricular septum and presence of atrioventricular valves opening into the single ventricle are recorded. The outlet chamber and the great vessel originating from it can be identified. With normal great artery relationships, a mitral-aortic continuity is determined; with TGA, a mitral-pulmonary continuity is determined. When performing an echocardiogram, attention should be paid to the following points: 1) assessment of the morphology of the single ventricle (left or right), its volume and contractility, and the position of the rudimentary ventricle; 2) position of the great arteries, their dimensions, and semilunar valve anatomy; 3) in discordant great artery positions — the dimensions of the bulboventricular opening and its relation to the aortic valve annulus; 4) anatomy of the AV valves and the degree of their regurgitation/stenosis; 5) dimensions of the interatrial communication (IAC), patent ductus arteriosus (PDA), and the direction of shunting through them; 6) presence of associated defects (coarctation of the aorta, interrupted aortic arch, anomalous pulmonary and systemic venous drainage).

• Contrast-enhanced cardiac computed tomography (CT) is recommended for patients with a suspected single ventricle in critical condition prior to surgery [8-11,14,22].

(Level of Evidence C, Grade of Recommendation 5)

Comments: in addition to clarifying the diagnosis, contrast-enhanced cardiac and vascular CT allows for the assessment of pulmonary artery development indices (Nakata, McGoon, Reddy) as well as the pulmonary-venous index.

(Level of Evidence C, Grade of Recommendation 5)

Comments: Cardiac MRI is the most accurate method for assessing cardiac function and the primary imaging modality for myocardial fibrosis. Cardiac MRI is currently considered the gold standard imaging technique for assessing heart chamber function. MRI is a unique method that allows for the non-invasive assessment of focal and diffuse myocardial fibrosis using contrast enhancement.

1. to clarify the diagnosis when data obtained from echocardiography, CT, and/or MRI are insufficient;

2. to assess the dimensions of the pulmonary arteries;

3. to assess the presence of additional pulmonary blood supply sources (aortopulmonary, arteriovenous, or venovenous collaterals);

4. to determine pulmonary vascular resistance;

5. to identify blood flow obstruction in venous and arterial vessels;

6. to perform coronary angiography in the presence of ischemic changes detected by other methods.

(Level of Evidence C, Grade of Recommendation 5)

Comments: the examination includes measuring pressure and oxygen saturation in the pulmonary artery (PA) (with mean pressure assessment being of primary importance), aorta, atria, single ventricle, and determining pulmonary and systemic blood flow as well as pulmonary vascular resistance (PVR). PVR is a derivative of PA pressure that evaluates the capacity of the pulmonary arteries to respond to volume overload. In most cases, surgeries performed for SV correction aim to increase pulmonary blood flow; therefore, determining PA pressure and PVR are crucial steps in the diagnostic and therapeutic workup, influencing the choice of subsequent surgical strategy. Angiocardiography allows for the evaluation of great artery anatomy and myocardial hypertrophy. Ventriculography is extremely important for deciding on the surgical treatment method. It provides an understanding of the size of the bulboventricular opening, the cavity volume of the hypoplastic ventricle, the severity of pulmonary stenosis, AV valve competence, and the spatial arrangement of the great arteries. When contrast is injected into the SV, regardless of the presence or absence of PA stenosis, a large ventricular cavity is visualized, occupying almost the entire cardiac silhouette in both the anteroposterior and lateral projections. Smooth internal contours, corresponding to left ventricular angioarchitecture, are much more frequently observed in the SV, whereas rough trabeculation characteristic of the right ventricle is less common. According to the nomenclature of medical services, the examination includes: aortic catheterization, selective pulmonary angiography, angiography of the pulmonary artery and its branches, cardiac chamber catheterization, superior vena cava phlebography, inferior vena cava phlebography, cardiac ventriculography, and coronary angiography (for a specific category of patients in accordance with the recommendation text).

2.5 Other Procedures

• Before hospital discharge, all patients are recommended to undergo electrocardiography as a postoperative control measure [24,25].

(Level of Evidence C, Grade of Recommendation 5)

• Before hospital discharge, all patients are recommended to undergo echocardiography [24,25].

(Level of Evidence C, Grade of Recommendation 5)

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

3.1 Conservative Treatment

Conservative measures are aimed at regulating pulmonary or systemic vascular resistance.

• In newborns with severely restricted pulmonary blood flow, it is recommended to use prostaglandins to maintain patent ductus arteriosus (PDA) patency [3,26,27].

(Level of Evidence C, Grade of Recommendation 5)

Comments: among the medications, #alprostadil** is most commonly used (off-label use in pediatric practice). The drug is administered intravenously, typically in the intensive care unit. The starting dose is 0.02 mcg/kg/min with the possibility of increasing to 0.05-0.1 mcg/kg/min, and the maintenance dose is 0.002 mcg/kg/min [25]. The duration of therapy is determined individually.

(Level of Evidence C, Grade of Recommendation 5)

Comment: age-appropriate dosages of #furosemide** are most frequently used (tablet formulations are contraindicated in children under 3 years of age), with a pediatric dose of 0.5-2 mg/kg intravenously or 1-2 mg/kg per os every 6-12 hours [29,31]; #spironolactone**, with a pediatric dose of 1-4 mg/kg/day [30,31].

• In the early period after a systemic-to-pulmonary shunt (SPS), as well as following staged palliative palliation (bidirectional cavopulmonary anastomosis (BCPA) or Fontan procedure) (see section 3.2.1), patients are recommended to receive thromboprophylaxis with low-molecular-weight or unfractionated heparin [20,32-37,80,82,83].

(Translational Research Level B, Evidence Level 3)

Comments: thromboembolic complications are among the leading causes of both early and long-term mortality following functional single ventricle palliation. On the one hand, right-heart bypass procedures create conditions that reduce blood flow velocity and alter its phasic characteristics; on the other hand, endothelial activation and injury are proven facts. Combined, these factors increase the likelihood of postoperative thrombosis, the risk of which is elevated in patients with a history of thrombosis, thrombophilia, infectious complications, or multi-organ failure [80].

Thromboprophylaxis with unfractionated sodium heparin** should be initiated with a bolus of 80 IU/kg in adults and 75 IU/kg in children, followed by 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) [37].

Thromboprophylaxis with low-molecular-weight heparins is administered at the following dosages: #enoxaparin** (off-label in children under 18 years of age) at 0.75 mg/kg in children under 2 months of age, 0.5 mg/kg in children over 2 months of age, and 20 mg subcutaneously every 12 hours in adults; dalteparin** at 150 IU/kg in children aged 1 month to 2 years, 125 IU/kg in children aged 2 to 8 years, 100 IU/kg in children older than 8 years, and 2500 IU subcutaneously every 12 hours in adults. Fondaparinux** may be used in children older than 1 year at a dose of 0.1 mg/kg, and in adults at 2.5 mg once daily subcutaneously. Dose adjustment is based on laboratory test results (see section 2.3) [37,80,82,83].

(Level of Evidence C, Grade of Recommendation 5)

Comments: it is optimal to monitor blood platelet counts every three days [35-37].

• Patients with a single ventricle heart after an SPS are recommended to receive thromboprophylaxis [37,80,82,83].

(LoE A, GoR 3)

Comments: in the early postoperative period, thromboprophylaxis should be carried out using unfractionated or low-molecular-weight heparin (see above), and subsequently with acetylsalicylic acid** at a dose of 1-5 mg/kg [37].

• Patients with a single ventricle heart after undergoing BCPA or the Fontan procedure are recommended lifelong thromboprophylaxis [20,32,35-38,80,82,83,87].

(LoE A, GoR 3)

Comments: in the early postoperative period, thromboprophylaxis should be carried out using unfractionated or low-molecular-weight heparin (see above), and subsequently with vitamin K antagonists starting at a dose of 0.2 mg/kg with further dose adjustment monitored by INR (target range: 2.0-3.0) [37] or #rivaroxaban** (off-label in children under 18 years of age) at a dose of 0.2-0.3 mg/kg/day monitored by anti-Xa activity (blood heparin level assay: target range: 0.5-1.0) [87].

3.2 Surgical Treatment

Surgical correction of a single ventricle is palliative (single-ventricle palliation) in nature. The choice of a specific palliative operation depends primarily on the state of pulmonary blood flow.

Surgical Treatment Stage

The main objectives of this stage are to balance systemic and pulmonary blood flow as much as possible, ensure unobstructed blood mixing at the atrial level, and provide an unobstructed outflow tract from the single ventricle [1].

Palliative procedures include the following:

• The Rashkind procedure (balloon atrioseptostomy) is recommended as an emergency supportive measure in neonates with a restrictive atrial septal defect (ASD) in patients with hemodynamics dependent on ASD size, including obstruction at the level of the atrioventricular valves [1-3,8].

(Level of Evidence C, Grade of Recommendation 5)

Comments: a restrictive ASD is defined as the presence of a communication at the atrial level across which a pressure gradient exists between the right and left atria. In this case, resistance to blood flow may occur at the level of this ASD.

• Pulmonary artery banding (Muller procedure) and ligation of a patent ductus arteriosus (PDA, if present) are recommended in the neonatal period in the presence of markedly increased pulmonary blood flow to limit pulmonary blood flow and "protect" the pulmonary circulation from the development of sclerotic changes [1,2,8,10,11,23,33,35].

(Level of Evidence C, Grade of Recommendation 5)

Comments: excessive pulmonary blood flow contributes to the development of severe heart failure and high pulmonary hypertension. These interventions are performed under the age of 6 months or later, after evaluation of pulmonary vascular resistance (PVR).

(Level of Evidence C, Grade of Recommendation 5)

Comments: pronounced hypoxemia is often characteristic of severe pulmonary artery stenosis (frequently with PDA-dependent pulmonary blood flow). The preferred age for performing a modified Blalock-Taussig shunt is under 3 months.

Hemodynamic correction

The next stage involves the so-called "hemodynamic" (single-ventricle) correction, which consists of creating a total cavopulmonary connection (synonym: "total bypass" of the right heart). The goal of this stage is to reduce systemic ventricle preload and increase systemic oxygenation [2,8].

• As the first stage of hemodynamic correction in children, it is recommended to perform a bidirectional cavopulmonary anastomosis (BCPA) [1,2,8,10,11,23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: BCPA consists of creating an end-to-side anastomosis between the superior vena cava (SVC) and the corresponding main branch of the pulmonary artery. The preferred timing is between 4 months and 1 year of age. In most cases, following BCPA, blood oxygen saturation settles within 80%. As an alternative to BCPA, the Hemi-Fontan procedure may be used, which involves creating a wide anastomosis between the SVC, the right atrium, and the pulmonary artery. The latter option is preferred if a lateral tunnel is planned for the total cavopulmonary connection (TCPC).

• As the second (final) stage of hemodynamic correction in children, it is recommended to create an anastomosis between the inferior vena cava (IVC) and the pulmonary artery (creation of a cavopulmonary anastomosis) [1,2,8,10,11,23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: performing a single-stage total cavopulmonary connection was associated with high mortality, so it was proposed to divide the operation into 2 independent stages. This strategy significantly improved the outcomes of hemodynamic correction. The most common modification of the Fontan procedure currently used is the insertion of a vascular graft (synthetic blood vessel prosthesis***), implanted directly between the IVC and the pulmonary artery (extracardiac conduit modification). As an alternative to this technique (for example, in heterotaxy syndrome and anomalous venous return), a total cavopulmonary connection in the lateral tunnel modification can be used. To reduce the risk of the Fontan procedure, it is often supplemented with a fenestration between the cavopulmonary pathway and the atrium.

(Level of Evidence C, Grade of Recommendation 4)

Comments: young age is currently not a barrier to performing BCPA; however, the optimal timing for the operation has not yet been defined. Some authors recommend BCPA before 6 months, citing the benefits of early "unloading" of the systemic ventricle, but not earlier than 3 months [19-21,23], while others consider its creation optimal between 6 months and 2 years, attributing this to the maximum increase in blood oxygen saturation after the procedure in this age group [25,26]. Doubts regarding surgery before 3 months are justified and related to higher PVR in such infants, a potential increase in complication rates and mortality, uncertainty regarding adequate growth of the pulmonary arteries postoperatively, and the risk of adverse effects of the procedure on cerebral circulation [41,43-45,47]. The "age" for performing the Fontan procedure is also debated. Some authors lean towards performing this stage at an older age, citing the limited "lifespan" of unphysiological single-ventricle circulation and its inevitable decompensation. The main indications for surgery in this case are factors such as the progression of systemic hypoxemia and a decrease in exercise tolerance. Conversely, others strive to proceed to total cavopulmonary connection at an earlier age, explaining this tactic by the benefits of the aforementioned early reduction in systemic ventricle preload [41,43]. The average optimal age for the extracardiac conduit Fontan procedure is 3-4 years with a weight of more than 15 kg, which generally allows placement of an optimally sized prosthesis (18-20 mm) in the child's chest. For the lateral tunnel, patient age and weight are not as critical, since this modification does not use a prosthetic graft.

(Level of Evidence C, Grade of Recommendation 4)

Comments: despite the aforementioned tentative indicators of pulmonary arterial bed development, it is believed that small pulmonary artery dimensions (Nakata index ≤ 100 mm²/m² and McGoon index ≤ 1.2) do not significantly affect the early outcomes of hemodynamic correction [48]. As known, pulmonary artery dimensions may depend on the amount of blood flowing into them [49], therefore absolute values may not be the most critical risk factor [50]. Obviously, a more important factor may be the functional capacity of the pulmonary arteries to respond to increased pulmonary blood flow after surgery, expressed as PVR (see section 2.4).

• To achieve the most optimal surgical results, it is recommended to perform hemodynamic correction in patients with comparable sizes of the venae cavae and pulmonary arteries [2,8,23].

(Level of Evidence C, Grade of Recommendation 5)

• When planning hemodynamic correction in patients, it is recommended to adhere to the following pulmonary hemodynamic parameters [2,8,23]:

  • mean pulmonary artery pressure ≤ 15 mm Hg;

  • pulmonary vascular resistance ≤ 4 Wood units/m²;

(Level of Evidence C, Grade of Recommendation 5)

• In patients with significant atrioventricular (AV) valve regurgitation (greater than grade 2), it is recommended to correct it prior to or during the stages of hemodynamic correction [2,8,23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: moderate AV valve regurgitation (grade 1-2) is considered acceptable and does not require correction.

• In patients with subaortic obstruction occurring in association with discordant (not from the concordant ventricle) aortic origin, it is recommended to relieve the obstruction during the stages of hemodynamic correction [2,8,23,51,52].

(Level of Evidence C, Grade of Recommendation 4)

Comments: indications for correction of subaortic obstruction are determined by the presence of a systolic pressure gradient between the systemic ventricle and the aorta, a restrictive ventricular septal defect (VSD) (a sign of VSD restrictiveness is a defect cross-sectional area of less than 2 cm²/m²), and the ratio of the diameters of the VSD and the aortic valve annulus. Surgical tactics consist either of enlarging the VSD or performing the Damus-Kaye-Stansel procedure simultaneously with hemodynamic correction. Following VSD enlargement, 3rd-degree AV blocks are frequently noted, making the Damus-Kaye-Stansel operation preferable when indications are met. One of the key criteria for performing the Damus-Kaye-Stansel operation is the preservation of pulmonary valve competence.

• Hemodynamic correction is recommended when patients have the following cardiac contractility parameters [2,8,23,53]:

  • ejection fraction > 55%;

  • end-diastolic pressure ≤ 12 mm Hg.

(Level of Evidence C, Grade of Recommendation 5)

Comments: an indirect sign of compromised systemic ventricular contractility is its end-diastolic volume index (mL/m²). Several studies have noted a correlation between baseline enlargement of the systemic ventricle end-diastolic volume and depression of its contractility in the postoperative period.

• When planning hemodynamic correction in patients, it is recommended to evaluate additional sources of pulmonary blood flow (ASPBF; synonym: hybrid pulmonary blood flow) [2,8,22].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Additional sources of pulmonary blood flow (ASPF) can be evaluated during contrast-enhanced chest computed tomography, retrograde thoracic aortography, and aortic catheterization. When performing bidirectional cavopulmonary anastomosis (BCPA), the decision to preserve or eliminate ASPF is made on an individual basis in each case. ASPF during the BCPA stage may be preserved if there is a downward trend in blood oxygen saturation below 80% and stable central hemodynamics (mean pulmonary artery pressure ≤ 15 mm Hg, absence of progressive hypotension). Parameters are evaluated immediately after BCPA, with an inspiratory oxygen fraction of 21-30%. When blood oxygen saturation increases above 90%, a trial clamping of the additional sources is performed, followed by management based on the blood oxygen saturation level (target value 80-90%). If the need to maintain hybrid pulmonary blood flow persists, an antegrade source (pulmonary trunk) is preferred. In some situations, mainly due to ostial stenosis of a pulmonary artery branch, it is possible to simultaneously preserve two sources of pulmonary blood flow: antegrade and either a systemic-to-pulmonary shunt (SPS) or a patent ductus arteriosus (PDA) distal to the pulmonary artery stenosis site.

• In a number of patients with complex congenital heart disease and a high risk for the Fontan procedure, due to certain anatomical and hemodynamic factors, it may be recommended to perform various palliative interventions: pulmonary artery banding, systemic-to-pulmonary shunting, or BCPA with ASPF (SPS, axillary arteriovenous fistula) as a "definitive" stage of hemodynamic correction or a "bridge" to heart transplantation [2,3,8,10,11,23,54].

(Level of Evidence C, Grade of Recommendation 5)

• Preservation of aortopulmonary collateral arteries (APCAs) during the Fontan procedure frequently leads to venous hypertension and the development of heart failure; therefore, elimination of APCAs (if present) is recommended for all patients at the stage of the Fontan operation [2,8,23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: ASPF may include aortopulmonary collateral arteries, functioning systemic-to-pulmonary shunts, and antegrade pulmonary blood flow. Aortopulmonary collateral arteries are eliminated before the Fontan procedure during retrograde thoracic aortography and aortic catheterization. Systemic-to-pulmonary shunts and antegrade pulmonary blood flow are eliminated by ligating the shunts and the pulmonary trunk during the Fontan procedure.

• To achieve optimal surgical results when planning hemodynamic correction, it is recommended to assess the state of systemic venous and pulmonary venous return in patients [2,8,23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: if obstructions to venous return are detected, surgical tactics are determined individually. The most common causes of venous return obstruction are anomalous pulmonary venous drainage, pulmonary vein ostial stenosis, and restrictive atrial septal defect.

• To achieve optimal results of hemodynamic correction, it is recommended to eliminate factors contributing to venous return obstruction at any stage upon their detection [2,8,23].

(Level of Evidence C, Grade of Recommendation 5)

• Primary BCPA is recommended in patients without critical pulmonary artery stenosis and PDA-dependent pulmonary blood flow, with a systemic saturation level > 70-75%, and without excessive pulmonary blood flow (mean pulmonary artery pressure < 15 mm Hg) [2,8,23].

(Level of Evidence C, Grade of Recommendation 5)

• In the presence of significant localized stenosis of pulmonary artery branches, patients are recommended to undergo stenosis correction using endovascular methods (transluminal balloon pulmonary angioplasty and/or pulmonary artery stenting) or open surgery (resection of pulmonary artery stenosis) simultaneously with the stages of hemodynamic correction [2].

(Level of Evidence C, Grade of Recommendation 5)

Comments: in case of endovascular methods for correcting pulmonary artery branch stenosis, strict monitoring of the patency of the main bronchi is necessary.

• When planning the final stage of hemodynamic correction in patients with borderline PA size (Nakata index ≤200 mm²/m²), elevated mean PA pressure (15-18 mmHg), low pulmonary venous index (<200 mm²/m²), it is recommended to refrain from the Fontan procedure [2,8,22,23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: in borderline situations, the possibility of creating ASPF (e.g., SPS, axillary arteriovenous fistula) should be considered.

(Level of Evidence C, Grade of Recommendation 5)

Comments: objective criteria for the state of pulmonary vessels are mean pulmonary artery pressure and pulmonary vascular resistance, and for systemic ventricle function—ejection fraction, end-diastolic pressure, and end-diastolic volume index.

• Heart transplantation is recommended for patients with severe systemic ventricle dysfunction [8,23,33,35,55-57].

(LetC, Level of Evidence 4)

Postoperative complications

The most frequent early complications after hemodynamic correction are neurological disorders, respiratory failure, venous hypertension and superior vena cava syndrome, increased transudation, and lymphatic drainage disorders [44,46,58].

• To reduce the risk of postoperative complications, early (1st day after surgery) extubation of patients after hemodynamic correction is recommended [59-64].

(Level of Evidence C, Grade of Recommendation 4)

Comments: major complications are frequently associated with elevated venous pressure in the cavopulmonary tract, which in turn may be caused by fluctuations in pulmonary vascular resistance in the early postoperative period and inadequate compensation of pulmonary circulation for increased blood flow. Mechanical ventilation increases intrathoracic pressure and slows down venous return through the systemic veins, which is an additional factor increasing venous pressure.

Among long-term complications after hemodynamic correction, the most important are venous hypertension, cardiac arrhythmias, protein-losing enteropathy, liver dysfunction, and thromboembolic complications [2,8].

Venous hypertension is the main cause of the development and progression of heart failure (hepatomegaly, ascites, hydrothorax, peripheral edema, cyanosis) in the medium- to long-term follow-up after the Fontan procedure. Factors increasing the likelihood of venous hypertension include pulmonary artery stenoses, ASPF, atrioventricular valve regurgitation, stenoses of the venae cavae or the vascular graft between the inferior vena cava and the pulmonary artery (e.g., due to graft "overgrowth"), development of venous collaterals, systemic ventricle dysfunction, protein-losing enteropathy (PLE), thromboembolic complications, and liver failure [2].

(Level of Evidence C, Grade of Recommendation 5)

Comments: in most cases, their elimination is possible via an endovascular approach.

(Level of Evidence C, Grade of Recommendation 5)

Comments: aortopulmonary collateral arteries may remain undiagnosed before surgery or develop in the early or long-term postoperative period. Recanalization of the pulmonary trunk can occur 1-2 years after surgery (this applies to cases where the pulmonary trunk was ligated intraoperatively and is not relevant for patients with associated pulmonary atresia).

• With the progression of atrioventricular valve regurgitation to greater than moderate degree, patients are recommended to undergo corrective surgery [2,10,11,23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: correction of atrioventricular valve regurgitation can be performed either as a standalone procedure or simultaneously with the Fontan procedure. In some cases, this complication occurs in the late postoperative period due to prior infective endocarditis or dilation of the valve annulus resulting from progressive systemic ventricle dysfunction.

• Following an extracardiac conduit Fontan modification, patients are recommended to undergo vascular graft replacement surgery if venous hypertension develops due to an inadequate conduit size relative to the patient's growth and development [2,10,11,23].

(Level of Evidence C, Grade of Recommendation 5)

• To increase blood oxygen saturation in the event of venous collateral development after BCPA, patients are recommended to undergo their embolization (embolization of veno-venous fistulas) [2,10,11,23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: in the absence of such factors as severe AV valve regurgitation, residual pulmonary artery stenosis, and elevated pulmonary vascular pressure, the results of the bidirectional cavopulmonary anastomosis (BCPA) procedure are favorable. However, as the patient grows, there is a gradual decrease in arterial oxygen saturation, which is caused by an age-related reduction in the proportion of venous return via the superior vena cava (SVC) system, as well as the development of pulmonary arteriovenous fistulas. Progressive cyanosis in the long-term post-BCPA period may also be associated with the development of collateral vessels between the superior and inferior vena cava systems due to the pressure gradient between them, leading to blood shunting from the SVC to the IVC and a reduction in pulmonary blood flow. Hemodynamic causes of this complication may also include pulmonary blood flow obstruction at various levels, elevated PVR, systemic ventricle (SV) or AV valve dysfunction, vena cava thrombosis, and other factors leading to increased venous pressure. According to A. Magee et al., venous collateral vessels develop in 31% of cases following the BCPA procedure. The azygos and hemiazygos veins, as well as pericardial and anterior chest wall veins, most frequently act as collateral vessels. Embolization of venous collaterals is an effective method for improving blood oxygen saturation in cases where the risk of the Fontan procedure is elevated.

(Level of Evidence C, Grade of Recommendation 5)

Comments: SV dysfunction can be caused by both its morphology, the initial severity of the congenital heart defect, or infectious diseases (including myocarditis) in the postoperative period [6].

• Patients are recommended immediate hospital admission if protein-losing enteropathy (PLE) is suspected [2, 55, 56].

(LoE C, GoR 3)

Comments: the term "protein-losing enteropathy" refers to a condition characterized by impaired protein absorption in the small intestine. The incidence of this complication averages 3.8%. The time to development of PLE ranges from 1 month to 16 years (mean 2.7 years), with one-third of patients developing the complication more than 5 years after surgery. The causes of PLE development after the Fontan procedure are still not fully understood. One of the probable mechanisms is the development of lymphangiectasia in the abdominal organs, including the intestine, as a result of persistently elevated venous and lymphatic pressure after the Fontan procedure. Clinically, PLE presents with hypoalbuminemia and, as a consequence, edema, ascites, pleural transudation or chylothorax, immunodeficiency, and hypocalcemia. In late stages, most manifestations of this complication correspond to the clinical picture of heart failure. A method for early diagnosis of PLE is the determination of fecal α₁-antitrypsin levels, the concentration of which is significantly increased in PLE. The prognosis for PLE is generally unfavorable. Most studies note high mortality among these patients. While the 5-year survival rate from the onset of the complication is about 60%, less than 20% of patients are alive after 10 years.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Patients with a single ventricle (SV) following any stage of surgical correction are recommended to avoid traction loads on the upper extremities for the subsequent 3 months of life [66].

(LoE 5, GoR C)

Comments: it is advisable to avoid excessive physical exertion (impulsive, strength games, fast running, heavy lifting), and excessive load on the upper shoulder girdle should be avoided in particular (this promotes proper sternal bone healing).

• All patients with an SV after each stage of surgical treatment are recommended to undergo a rehabilitation program lasting at least 6 weeks within an individualized regimen [66].

(LoE 5, GoR C)

Comments: rehabilitation can in most cases be carried out at home, provided there is periodic monitoring of the patient's condition by the local pediatrician (once every 2-3 weeks). The optimal duration of the rehabilitation period is 10-12 weeks. If rehabilitation is ineffective, requires the selection of an individual program, or frequent monitoring by a subspecialist, the question of sending the patient to a specialized rehabilitation center should be considered.

• As part of rehabilitation management, within up to 3 months following surgical treatment of an SV, patients are recommended fluid restriction [66].

(Level of Evidence C, Grade of Recommendation 5)

Comments: fluid intake (especially during the first month after surgery) is restricted to 60-80% of daily requirement.

• All patients with an SV after each stage of surgical treatment are recommended to have an individualized optimal physical activity regimen selected during the outpatient follow-up stage [66].

(LoE 5, GoR C)

5. Prevention and Dispensary Observation

(Level of Evidence C, Grade of Recommendation 5)

• All women of reproductive age with a history of the Fontan procedure are recommended to undergo a comprehensive evaluation, including mandatory echocardiography, prior to pregnancy planning [66].

(Level of Evidence C, Grade of Recommendation 5)

• Hepatic dysfunction may develop in the long-term post-operative period following the Fontan procedure; therefore, patients are recommended to undergo monitoring of biochemical blood parameters—such as total protein, albumin, AST, ALT, and bilirubin (total, conjugated, and unconjugated)—at least once every 6–12 months [2, 67].

(Level of Evidence C, Grade of Recommendation 5)

• To assess cardiac contractile function, atrioventricular valve competence, blood flow patterns across pulmonary artery banding (PAB), bidirectional cavopulmonary anastomosis (BCPA), and/or total cavopulmonary connection (TCPC), as well as to rule out hydrothorax/hydropericardium, all patients after various stages of single ventricle correction are recommended to undergo echocardiography within the first month after discharge, and subsequently at least once every 6–12 months [23, 66].

(Level of Evidence C, Grade of Recommendation 5)

• If echocardiographic data obtained after PAB or staged hemodynamic correction are insufficient to assess circulatory parameters (including when planning the next stage), patients are recommended to undergo angiocardiography (ACG) with cardiac catheterization, the timing of which is determined individually [10, 11, 23].

(Level of Evidence C, Grade of Recommendation 5)

Comments: following PAB, the procedure is performed within 6 to 12 months; following BCPA, no earlier than 12 months. The main objectives of ACG at these time points are to assess the feasibility of the next stage of surgical treatment, or, if unfeasible, to evaluate PAB and/or BCPA function and the degree of pulmonary vascular bed development. Following the Fontan procedure, the need for ACG is primarily driven by the necessity for endovascular interventions (such as dilation or stenting of stenotic pulmonary arteries, elimination of venovenous collaterals, or closure of the fenestration between the TCPC and the atrium), while the exact timing of ACG is not strictly regulated. According to the nomenclature of medical services, the examination may include: aortic catheterization, selective pulmonary angiography, angiography of the pulmonary artery and its branches, cardiac catheterization, superior vena cava phlebography, inferior vena cava phlebography, and ventriculography.

• All patients with a single ventricle of the heart receiving antithrombotic therapy are recommended to undergo a coagulogram (exploratory hemostasis assay) at least once a month [37, 80, 82, 83, 87].

(LoE A, GoR 3)

Comments: valuable laboratory information can be provided by a complete blood count (total hemoglobin, platelet count), platelet aggregation testing (for patients receiving acetylsalicylic acid**), INR (for patients receiving warfarin**), and anti-Xa activity (blood heparin level testing for patients receiving #rivaroxaban**).

(Level of Evidence C, Grade of Recommendation 5)

Comments: antibiotic prophylaxis is prescribed when outpatient surgical interventions, tooth extraction, etc., are necessary.

6. Organization of Medical Care

Indications for planned hospitalization:

1. Absence of signs of progressive circulatory failure and a stable functional status of the patient (functional class I–II) without a worsening trend within 6–12 months after PAB, or for at least 12 months after staged hemodynamic correction (heart failure is assessed in adult patients using the New York Heart Association (NYHA) classification, and in children using the Ross classification (Appendix G));

2. Stable blood oxygen saturation without a downward trend.

3. Elective surgical treatment.

Indications for emergency hospitalization:

1. Worsening of the patient's functional status with progressive signs of heart failure over the past 2–4 weeks or days (for evaluation in adult patients, the New York Heart Association (NYHA) heart failure classification is used; for evaluation in children, the Ross classification is used (Appendix G));

2. Progressive decrease in blood oxygen saturation to less than 80% over the past 2–4 weeks or days;

3. Suspicion of the development of protein-losing enteropathy (PLE) in the patient.

Indications for patient discharge from the hospital:

1. Following conservative treatment:

   • Reduction of clinical manifestations of heart failure;

   • Increase in blood oxygen saturation.

2. Following staged surgical treatment:

   • Systemic-pulmonary shunt / Rashkind procedure – increase in blood oxygen saturation / relief of restrictive atrial septal defect;

   • Staged hemodynamic correction – reduction of preload (decrease in end-diastolic volume) of the single ventricle, increase in blood oxygen saturation.

7. Additional Information

If pathology of the tracheobronchial tree is suspected prior to surgery, the patient must be evaluated by a pulmonologist [68].

Criteria for Evaluating the Quality of Medical Care

Quality assessment criteria for primary health care provided to adults and children with a single ventricle of the heart (ICD-10 codes: Q20.4)

Quality assessment criteria for specialized medical care provided to adults and children with a single ventricle of the heart (ICD-10 codes: Q20.4)

References

Appendix A1. Working Group Composition

1. Baryshnikova I.Yu., Candidate of Medical Sciences (Moscow; All-Russian Public Organization for Assistance to the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists").

2. Bokeria L.A., Academician of the Russian Academy of Sciences (Moscow; Association of Cardiovascular Surgeons of Russia, American Association for Thoracic Surgery, European Association for Cardio-Thoracic Surgery, Serbian Academy of Sciences and Arts).

3. Belov V.A., Doctor of Medical Sciences (Kaliningrad).

4. Boriskov M.V., Doctor of Medical Sciences (Krasnodar).

5. Gorbatikov K.V., Doctor of Medical Sciences (Tyumen).

6. Gorbatykh Yu.N., Doctor of Medical Sciences (Novosibirsk).

7. Gorbachevsky S.V., Doctor of Medical Sciences (Moscow).

8. Gushchin D.K., Candidate of Medical Sciences (Moscow).

9. Dorofeev Alexey Vladimirovich, Candidate of Medical Sciences (Moscow), All-Russian Public Organization for Assistance to the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists".

10. Zelenikin M.A., Doctor of Medical Sciences (Moscow; Association of Cardiovascular Surgeons of Russia).

11. Zelenikin M.M., Doctor of Medical Sciences (Moscow; Association of Cardiovascular Surgeons of Russia).

12. Ivanov A.S., Doctor of Medical Sciences (Moscow; Association of Cardiovascular Surgeons of Russia).

13. Kalashnikov S.V., Candidate of Medical Sciences (Moscow; Association of Cardiovascular Surgeons of Russia).

14. Kim A.I., Doctor of Medical Sciences (Moscow; Association of Cardiovascular Surgeons of Russia).

15. Kokshenev I.V., Doctor of Medical Sciences (Moscow).

16. Krivoshchekov E.V., Doctor of Medical Sciences (Kaliningrad; Association of Cardiovascular Surgeons of Russia, European Association for Cardio-Thoracic Surgery, World Society for Pediatric and Congenital Heart Surgery).

17. Kupryashov A.A., Doctor of Medical Sciences (Moscow).

18. Movsesyan R.R., Corresponding Member of the Russian Academy of Sciences (St. Petersburg; Association of Cardiovascular Surgeons of Russia, Association of Pediatric Cardiologists of Russia, European Association for Cardio-Thoracic Surgery, American Association for Thoracic Surgery).

19. Petrushenko D.Yu., Ph.D. in Medicine (Kazan).

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

21. Podzolkov V.P., Academician of the Russian Academy of Sciences (Moscow; Association of Cardiovascular Surgeons of Russia, European Association for Cardio-Thoracic Surgery).

22. Sinelnikov Yu.A., D.Sc. in Medicine (Perm; European Association for Cardio-Thoracic Surgery).

23. Sinitsyn V.E., D.Sc. in Medicine (Moscow; All-Russian Public Organization for Assistance to the Development of Radiology and Therapy "Russian Society of Radiologists").

24. Shatalov K.V., D.Sc. in Medicine (Moscow; Association of Cardiovascular Surgeons of Russia, European Association for Cardio-Thoracic Surgery, International Society for Cardiovascular Surgery, American Association for Thoracic Surgery).

25. Yurlov I.A., Ph.D. in Medicine (Moscow; Association of Cardiovascular Surgeons of Russia).

26. Yurpolskaya L.A., D.Sc. in Medicine (Moscow; All-Russian Public Organization for Assistance to the Development of Radiology and Therapy "Russian Society of Radiologists").

All Working Group members have declared no financial support or conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. pediatric cardiologist;

2. cardiologist;

3. general practitioner (family physician);

4. pediatrician;

5. exercise therapy physician;

6. medical rehabilitation physician;

7. cardiovascular surgeon and interventional radiologist;

8. sports medicine physician;

9. admitting department physician;

10. cardiovascular surgeon;

11. emergency physician;

12. general practitioner;

13. ultrasound diagnostics physician;

14. radiologist;

15. functional diagnostics physician;

16. neonatologist;

17. anesthesiologist-resuscitator.

During the development of these clinical guidelines, the updated system of levels of reliable evidence (LRE) and levels of recommendation grades (LRG) for therapeutic, rehabilitative, preventive, and diagnostic interventions (Tables 1–3), introduced in 2018 by the Center for Healthcare Quality Assessment and Control of the Russian Ministry of Health, was used.

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

Table 2. Scale for assessing the levels of reliable evidence (LRE) for methods of prevention, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitative interventions).

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

Procedure for updating clinical guidelines

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

Appendix A3. Reference Materials

1. On the Fundamentals of Protecting the Health of Citizens in the Russian Federation (Federal Law No. 323-FZ of November 21, 2011 (as amended on December 28, 2024)).

2. Procedure for the Provision of Medical Care to Patients with Cardiovascular Diseases (Order of the Russian Ministry of Health No. 918n of November 15, 2012 (as amended on February 21, 2020)).

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

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

Monitoring and correction of unfractionated heparin dose [80]

Important indicators when analyzing and interpreting the obtained images:

Performing transthoracic echocardiography

Echocardiography performed according to a segmental approach is of paramount importance in describing cardiac anatomy, function, and hemodynamics in patients with single ventricle heart (SVH) [70,71].

According to the segmental approach, the following should be determined:

1. the drainage of systemic and pulmonary veins, their location, and atrial dimensions;

2. anatomy and function of the atrioventricular valves;

3. morphology of the single ventricle, location and size of the bulboventricular foramen and outlet chamber;

4. origin and mutual spatial arrangement of the great arteries, anatomy and function of the semilunar valves. Exclude coarctation of the aorta.

Given the anatomical variability of SVH, all acoustic windows, projections, and scanning modes are used for echocardiographic diagnostics, taking into account the anatomical landmarks of cardiac structures.

Determining the location and drainage site of the systemic and pulmonary veins helps assess heart formation (normally, right-, or left-formed), and in the case of a single atrium, the type of isomerism.

Changes in the atrioventricular valves are assessed by leaflet morphology (thickening, fusion, number), subvalvular apparatus structure (if present), and the diameter of the annulus fibrosus.

Univentricular hemodynamics involves the connection of a common atrioventricular valve or two AV valves to a dominant or single ventricle (single- or double-inlet SVH). In both cases, one ventricle is of normal or increased size, while the other is hypoplastic with an absent inlet portion. It is possible to determine the morphology of the main ventricle (right or left) or, in some cases, it may be indeterminate, which implies the absence of development of the interventricular septum. The dimensions and function of the main ventricle should be determined.

Ventriculoarterial connection is concordant when the aorta originates from the left ventricle and the pulmonary artery from the right, or discordant when the aorta originates from the right ventricle and the pulmonary artery from the left. Double outlet is observed when more than one and a half great arteries originate from the ventricle. A condition where only one patent great artery originates from the heart is called single-outlet SVH. Changes in the semilunar valves are also assessed by leaflet morphology (thickening, fusion, number, atresia) and the diameter of the annulus fibrosus. The degree of hypoplasia of the aortic valve, various segments of the aorta, trunk, and branches of the pulmonary artery is assessed using standardized scores (z-score). Z-score values less than (-) 2.0 – (-) 2.5 are a criterion for hypoplasia [72].

Three-dimensional echocardiography, when optimal images are obtained, allows for a detailed study of the anatomy and function of the single ventricle, as well as the atrioventricular valves or common AV valve and subvalvular apparatus, and a more accurate calculation of the volumes and linear dimensions of the cardiac chambers.

To verify the great arteries, it is necessary to visualize the bifurcation of the pulmonary artery branches or the ostia of the coronary arteries. At the level of the semilunar valves in the short-axis view, the mutual spatial arrangement of the great arteries is determined: aorta anterior and to the right of the pulmonary artery; aorta anterior and to the left of the pulmonary artery; aorta to the right and adjacent to the pulmonary artery side-by-side. A thorough study of inflow anatomy and hemodynamics into the SVH and outflow into the systemic and pulmonary circulations is crucial for determining the strategy and scope of surgical intervention.

An atrial septal defect (ASD) may be restrictive; therefore, it is important to ensure unobstructed blood return from the pulmonary veins or venae cavae, depending on the variant anatomy. An atrial septal defect (patent foramen ovale) is assessed from the subcostal view in the atrial long-axis projection using color Doppler flow mapping. The restrictiveness of the atrial septal defect is determined by echocardiographic measurement of the interatrial communication size and the mean pressure gradient.

A patent ductus arteriosus (PDA) is assessed from the suprasternal or high left parasternal views in short-axis projections [73]. Obtaining an ultrasound slice along the left branch of the pulmonary artery is considered optimal. The PDA diameter is measured in B-mode along the internal contour of the duct at its narrowest point. In case of a "poor acoustic window", measurements are performed using color Doppler flow mapping. The direction of blood shunting through the PDA is also assessed in this mode.

The bulboventricular foramen is restrictive when its diameter is less than the diameter of an aortic valve considered normal for the child's height and weight.

Echocardiography in the postoperative period.

• detailed assessment of the size and function of the systemic ventricle.

Assessment of the systolic function of the SVH in terms of ejection fraction and/or fractional shortening of the systemic ventricle using Teichholz and Simpson methods has limitations in non-ellipsoidal geometry of the systemic ventricle, hypovolemia, severe mitral regurgitation, etc. To exclude systolic dysfunction of the systemic ventricle, if possible, it is recommended to switch to other assessment methods: tissue Doppler imaging, three-dimensional echocardiography, speckle tracking echocardiography [70,74].

• stenosis/regurgitation of atrioventricular valves

• growth dynamics of the pulmonary artery and its branches, diameter of the interatrial communication

Echocardiography after systemic-to-pulmonary artery shunt placement

Color Doppler mode maps blood flow through the created anastomosis in two areas: in the region of the brachiocephalic artery and at the insertion into the pulmonary artery.

Echocardiography after PDA stenting

The position of the stent and blood flow within it are assessed from the suprasternal or high left parasternal views in short-axis projections. Flow obstruction may occur in the center, or in the proximal or distal segments of the stent. Color Doppler flow mapping and continuous-wave Doppler allow for precise detection of obstruction, though the exact level of obstruction is not always identifiable.

Echocardiographic assessment of ASD

In single ventricle heart (SVH) and restrictive ASD, two types of interventions are possible at the hybrid stage: ASD stenting and the Rashkind procedure. In both cases, the blood flow velocity across the defect should be assessed dynamically, because in addition to obvious obstruction, a mismatch between the defect size and the volume of flowing blood (hemodynamic restriction) may develop as the patient grows. An increase in the retrograde flow velocity in the pulmonary veins may also indirectly indicate high pressure in the left atrium.

Echocardiography after Muller procedure

The position of the pulmonary artery band is assessed (displacement is ruled out) and the systolic pressure gradient across the narrowing site is measured, which is correlated with the systolic blood pressure. The heart rate at which the echocardiographic study was performed should also be indicated.

Echocardiography after Damus-Kaye-Stansel procedure

The size of the anastomosis between the pulmonary artery and the ascending aorta, the systolic pressure gradient, and the function of the systemic ventricle must be assessed.

Echocardiography after BCPS and Fontan procedure

The connection between the superior vena cava and the right pulmonary artery—the Glenn anastomosis—can be independent or part of a total cavopulmonary connection during the Fontan procedure. There are also patients with bilateral SVCs, each connected to the ipsilateral pulmonary artery. The best echocardiographic view is suprasternal or high right parasternal (and left in the presence of a left SVC). Blood flow through the anastomosis between the SVC and PA is assessed using color Doppler mapping (with a lowered Nyquist limit for better visualization) and pulsed-wave Doppler [75]. Laminar, low-velocity continuous flow with little dependence on respiratory phases is visualized.

The blood flow velocity through the conduit from the IVC to the PA should not exceed 20–30 cm/s.

A blood flow velocity across the fenestration of the IVC-to-PA conduit greater than 1.8 m/s is a sign of pulmonary hypertension [76].

Appendix B. Physician Action Algorithms

Appendix B1. Algorithm for the management of patients under 3 months of age with a single ventricle

Appendix B2. Algorithm for the management of patients older than 4 months of age with a single ventricle

Appendix B3. Protocol for the use of imaging and instrumental diagnostic methods in suspected and managed patients with single ventricle heart

Appendix C. Patient Information

In SVH, the heart has two normally developed atria, but they open into a single ventricular chamber (single ventricle). In the vast majority of cases, the single ventricle has the anatomical structure of either a left or a right ventricle, while the second (underdeveloped) ventricle remains as a small chamber connected to the "main" ventricle via a ventricular septal defect (in SVH, this defect is often referred to as the bulboventricular window). The aorta and pulmonary artery (great vessels) may arise from either the main (single) ventricle or the underdeveloped ventricle, which is referred to as the "outlet chamber".

Blood flows mix in the single chamber, while the ventricle works with a double workload, which ultimately leads to a gradual thickening of its muscular walls and, in the long term, to heart failure (inability to perform adequate function). After birth, if there is no concomitant pulmonary stenosis, an increased volume of blood from the ventricle enters the lungs; this can lead to heart failure and pulmonary hypertension (pulmonary vascular disease leading to their thickening due to excessive blood flow). Symptoms of heart failure include dyspnea (rapid, labored breathing) that worsens after exertion (in adults after walking, in children during active play or feeding), decreased exercise tolerance (difficulty in performing previously routine activities, e.g., running, climbing stairs, walking, etc.), abdominal distension (due to hepatomegaly and/or the appearance of free fluid in the abdominal cavity), sweating (initially after exertion, and at rest as it progresses). In cases where there is an additional obstruction to pulmonary blood flow, cyanosis (bluish discoloration) develops, and if it persists for a long time, children generally lag behind in development (due to systemic oxygen starvation).

In SVH, timely surgical intervention is necessary to prevent potential complications (pulmonary hypertension, heart failure). If the diagnosis is established immediately after birth and there is excessive pulmonary blood flow (i.e., without pulmonary stenosis), pulmonary artery banding (Muller procedure) may be indicated for the child as early as the first month of life to prevent the development of pulmonary hypertension. In cases of pulmonary stenosis in SVH, a systemic-to-pulmonary artery shunt is performed to improve pulmonary blood flow and reduce the severity of cyanosis. A few months later, preferably within the first year of life, an anastomosis between the SVC and PA (bidirectional cavopulmonary anastomosis) should be performed, directing venous blood from the upper half of the body directly into both lungs (hence the name—bidirectional). The goals of this stage are: 1) since blood from the upper half of the body enters the lungs bypassing the heart, the ventricle is "unloaded", protecting it from the potential development of heart failure in the future; 2) at the same time, pulmonary blood flow increases and blood oxygen saturation improves, i.e., cyanosis is reduced. The aforementioned contributes to an improvement in the child's condition and quality of life. In certain situations, BCPS is performed primarily (without a preceding systemic-to-pulmonary shunt) under the age of 1 year (but not earlier than 4 months), as determined by the cardiologist and cardiac surgeon who continuously monitor the child.

Finally, the last stage is the Fontan procedure, after which all venous blood is directed into the pulmonary vessels using a synthetic vascular graft. This stage is called the "extracardiac conduit Fontan procedure". This surgery is usually performed at an age older than 2 years. And if previously venous and arterial blood flows mixed, causing some degree of cyanosis, now these flows are separated. The child's skin turns pink. The Fontan procedure can also be performed later (at 4 years or older), but it should not be delayed for too long.

The described principle of surgical treatment does not cure the defect; it alleviates the patient's condition by optimizing circulation under conditions of complex intracardiac anatomy [67].

After discharge from a specialized center, the instructions specified in the discharge documents (discharge summary) must be strictly followed. Follow-up with a local cardiologist should be at least once every 6 months, strictly adhering to their instructions and prescriptions. Follow-up with a cardiologist at a specialized center should be at least once every 12 months. The fluid restriction regimen must be strictly followed, especially during the first month after surgery. Changes in regimens and doses of certain medications, as well as the prescription of additional or alternative medications, are carried out solely by the attending physician. If side effects from medications occur, they should be discussed with the attending physician as soon as possible. Excessive physical activity should be avoided. For any invasive procedures (dental, cosmetic, and other procedures that involve or carry a risk of compromising the integrity of the skin and mucous membranes), antibiotic prophylaxis is mandatory to prevent infective endocarditis. Planned invasive procedures must be coordinated with the cardiologist monitoring the patient locally. If the following symptoms occur or rapidly progress, an unscheduled consultation with a cardiologist is required as soon as possible: fatigue, dyspnea, cyanosis, edema, abdominal distension, arrhythmias, syncope, neurological deficits (loss of vision, hearing, speech, numbness of a limb, paresis and paralysis, including short-term ones), acute respiratory infections, fever of unknown origin.

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

Appendix G1. These clinical guidelines use the following scale:

Russian title: Modified Ross Heart Failure Classification for Children.

Original title: Modified Ross score.

Source: Ross R.D. The Ross classification for heart failure in children after 25 years: a review and an age-stratified revision. Pediatr. Cardiol. 2012; 33 (8): 1295-300. DOI: 10.1007/s00246-012-0306-8.

Type: rating scale.

Purpose: determination of the severity of circulatory failure and functional class in children.

Scale contents: