Coronary Vessel Development Anomalies: Clinical Guidelines

List of Abbreviations

- ACG – angiocardiography (retrograde left heart catheterization with coronary angiography and panaortography);

- Ao – aorta;

- CA – coronary artery;

- CAG – coronary angiography;

- EDV – end-diastolic volume;

- EDD – end-diastolic dimension;

- ESV – end-systolic volume;

- ESD – end-systolic dimension;

- CT – computed tomography;

- CCF – coronary-cardiac fistula;

- PA – pulmonary artery;

- PH – pulmonary hypertension;

- LCA – left coronary artery;

- PA – pulmonary artery;

- LV – left ventricle;

- MV – mitral valve;

- MRI – magnetic resonance imaging;

- PDA – patent ductus arteriosus;

- LCx – left circumflex branch;

- SPECT – single-photon emission computed tomography;

- RCA – right coronary artery;

- LAD – left anterior descending branch;

- PET – positron emission tomography;

- Radiopharmaceutical (V09 Diagnostic radiopharmaceuticals)

- BwG – Bland-White-Garland syndrome;

- EF – ejection fraction;

- FA – fibrous annulus;

- AF – atrial fibrillation;

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

- EchoCG – echocardiography.

Terms and Definitions

Bland-White-Garland syndrome (BWGS) is a congenital heart defect with anomalous origin of the left coronary artery from the pulmonary artery, characterized by the development of severe heart failure as early as infancy and a strongly unfavorable prognostic course.

Infantile type of coronary circulation is a clinical variant of BWGS characterized by the absence of well-developed collaterals between the right and left coronary artery systems, leading to severe ischemic myocardial injury of the left ventricle immediately after birth, which in some cases manifests as terminal heart failure.

Cardiac catheterization (retrograde left heart catheterization) is an invasive procedure performed for therapeutic or diagnostic purposes in cardiovascular diseases by inserting catheters into the heart chambers or the lumen of major vessels.

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

Magnetic resonance imaging (MRI) is a non-invasive method of obtaining tomographic medical images without ionizing radiation to study internal organs and tissues. It is 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 following excitation by a specific combination of electromagnetic waves; such nuclei are hydrogen atoms present in the human body as water and other substances. MR angiography is a method for visualizing the vascular lumen using a magnetic resonance scanner. The method allows for the assessment of both anatomical and functional features of blood flow. MR angiography is based on the signal difference between moving protons (blood) and surrounding stationary tissues, enabling vascular imaging without contrast agents (e.g., phase-contrast MR angiography). In some cases, intravenous bolus contrast enhancement using paramagnetic contrast agents (gadolinium) is applied.

Positron emission tomography is a radionuclide myocardial perfusion imaging method that allows the identification of areas of altered coronary blood flow using fluorodeoxyglucose [18F], which accumulates exclusively in viable myocardium.

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

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

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

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Coronary artery anomalies (CAAs) represent a diverse group of congenital abnormalities of the coronary vessels resulting from anomalous origin, course, or structure of the terminal coronary bed. The incidence of isolated coronary artery anomalies ranges from 0.6% to 1.8% of all coronary angiographies performed [2].

The Bakulev National Medical Research Center for Cardiovascular Surgery has developed the following classification of coronary artery anomalies, reflecting the morphological features of the aforementioned congenital heart defect [3]:

I. Anomalies of coronary artery origin from the aorta.

1. Variants of single coronary artery (SCA).

1.1. Anomalous SCA with normal coronary distribution.

1.2. SCA combined with coronary fistulas.

1.3. SCA combined with other congenital heart defects.

1.4. Anomalous SCA with an anomalous interarterial course of major coronary branches.

A) Interarterial course of the anomalous left coronary branch.

B) Interarterial course of the anomalous right coronary branch.

2. Intramural coronary arteries.

3. Coronary ectopia.

II. Anomalies of coronary artery origin from the pulmonary artery.

1. Anomalous origin of the left coronary artery from the pulmonary artery—90% of all coronary anomaly cases.

2. Anomalous origin of the right coronary artery from the pulmonary artery—0.003% according to coronary angiography data. High incidence of combination with aortopulmonary window and bicuspid aortic valve.

3. Anomalous origin of right and left coronary artery branches from the pulmonary artery.

4. Total anomalous origin of coronary arteries from the pulmonary artery.

III. Anomalies of the course and branching of coronary arteries originating from the aorta.

1. Absence of the circumflex branch.

2. Absence of the left anterior descending branch.

IV. Coronary-cardiac fistulas.

A. Anomalous origin of the left coronary artery from the pulmonary artery (Bland-White-Garland syndrome) is a rare congenital heart defect (CHD) characterized by an unfavorable course during the neonatal and infancy periods and an extremely dubious prognosis with natural history.

B. Coronary-cardiac fistulas (CCFs) are anomalous communications between the coronary arteries and a heart chamber or other vascular structures bypassing the capillary bed, leading to structural impairment of the coronary arteries and altered blood flow within them [2,3,5,6-10].

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

A. In BWGS, the right coronary artery originates from the first anterior aortic sinus, and its course is preserved. Its characteristic feature is marked dilation (its diameter exceeds that of the left coronary artery by 1.5–2 times in 86.5% of cases) and tortuosity [4].

Characteristic of the anomalous origin of the left coronary artery from the pulmonary artery is a right-dominant coronary circulation with a posterior descending branch formed by the right coronary artery. The left coronary artery (LCA) originates from the posterior surface of the pulmonary artery, dividing almost immediately into the left anterior descending (LAD) branch and the circumflex (LCx) branch, with subsequent unchanged distribution and arterial course.

Among the characteristic anatomical features of the anomalously originating LCA, it should be noted that the LCA trunk is very short or may be entirely absent; the LCA and its branches do not encircle the pulmonary artery trunk as they normally do. The LCA may originate from the posterior wall of the pulmonary artery in the projection of the posterior or non-posterior sinuses of the pulmonary valve, or at their border. A network of collateral vessels exists, providing shunts from the right coronary artery system into the anomalously originating left coronary artery. Typically, these are anastomoses between branches of the right coronary artery (conus branch, acute marginal branch, posterior descending branch, and septal collaterals) and the LAD. The LAD and LCx join at an acute angle (as in hearts with a normal dual-coronary circulation system), while filling of the LCx basin occurs predominantly retrogradely from the LAD [4].

Due to a disruption in the embryological development of the ventricular complex in this defect, so-called left ventricular "dominance" is formed, accompanied by corresponding hemodynamic changes. This phenomenon arises from an alteration in the spatial relationship between the anterior and posterior interventricular septa, which in BWGS form an average angle of 97° (±7.6°±1.1°). Such abnormalities result from the displacement of the posterior interventricular septum into the right ventricular cavity. As a result, the right ventricular cavity is diminished in both the inflow and outflow tracts, and the patency of the tricuspid valve orifice is sharply narrowed due to a proportional enlargement of the left one [3].

The hemodynamic disorders in this defect are based on perfusion deficits or pathological redistribution of blood with reduced oxygen content through the LCA system. Thus, the circulatory characteristics in BWGS depend on the pressure ratio between the aorta and the pulmonary artery.

In the prenatal period, anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) does not lead to impaired myocardial blood supply of the left ventricle; both coronary vessels show an anterograde blood flow with approximately the same oxygenation. After birth, the prognosis and manifestation of the disease are determined by the degree of development of intercoronary anastomoses and the severity of left ventricular myocardial ischemia. Without surgical treatment, about 90% of patients die in the first year of life [3,27,30-32]. The cause of death in the absence of good collaterals between the LCA and RCA systems is acute left ventricular myocardial ischemia developing after birth, up to the formation of extensive infarctions. According to statistics, the incidence of myocardial infarction in the pediatric population is approximately 20 cases per 100,000 of this population. At the same time, mortality from acute myocardial infarction in children under 1 year of age is 0.2 per 100,000, and in 20% of cases, the cause is precisely the anomalous origin of the LCA from the pulmonary artery [33]. Thus, in the absence of timely diagnosis and surgical correction, only patients with a well-developed network of collateral vessels survive the neonatal period. However, even among patients who survived this age, cases of so-called sudden death as a result of ischemic myocardial damage and the occurrence of ventricular arrhythmias are frequent [34]. According to the literature, 80-90% of these patients die suddenly at the age of 35 [3,16,31,33,34]. Nevertheless, the literature describes cases of primary diagnosis of the defect in adult patients, even older than 70 years; the only manifestation of ALCAPA in these situations was rhythm disturbances or mitral regurgitation [24,34-39].

In accordance with the degree of hemodynamic disturbance, J.I. Edwards, who first described the pathophysiological changes in ALCAPA, proposed distinguishing 3 phases in the clinical course of the disease. The first includes the period of placental circulation and the first 6-8 weeks of life, when, due to high pressure in the pulmonary artery, sufficient pressure is maintained in the anomalous coronary vessel, and signs of coronary insufficiency are absent. The second or "critical" phase, caused by the physiological decrease in pressure in the pulmonary artery, occurs at 6-8 weeks of age and usually lasts from 1.5 to 4 months. Most children die at this age due to myocardial ischemia associated with decreased blood flow in the LCA [70,71]. Only children with a well-developed network of intercoronary anastomoses survive. Survival at this age depends both on the rate of formation of intercoronary anastomoses and their density, and on the type of cardiac blood supply and the rate of pressure decrease in the pulmonary artery. At this stage, diagnosis of the defect is already possible due to the existing characteristic clinical symptoms. The third phase (the "compensation" phase), characterized by blood supply to the LCA basin due to perfusion of the RCA and the presence of retrograde blood flow in the anomalous coronary artery, is observed in patients with a well-developed network of intercoronary collaterals.

Some authors [59,60] proposed distinguishing a 4th hemodynamic stage of the defect's course, in which the formation of a single-coronary blood supply system is already completed, and an increase in the coronary steal syndrome occurs due to an increase in shunt from the right coronary artery to the pulmonary artery, which leads to a secondary increase in ischemic symptoms and a sharp (sometimes sudden) deterioration in condition due to the development of severe heart failure and life-threatening arrhythmias.

When ALCAPA is combined with other intracardiac anomalies, the hemodynamics of the defect can change cardinally. In some cases, a concomitant congenital heart disease can compensate for the coronary anomaly (when combined with heart defects accompanied by pulmonary hypervolemia), while in others, anomalous origin of the LCA acts as an aggravating factor (in "blue" type defects with insufficient blood flow in the pulmonary artery system).

B. Communications between the coronary arteries and heart chambers (coronary-cameral fistulas) are formed as a result of an anomaly in the embryonic development of the vessels of the coronary arterial tree.

Coronary-cameral fistulas originate from the RCA in approximately 50-60% of cases, the anterior interventricular branch of the LCA in 32% of cases, and the circumflex branch of the LCA in 18% of cases [11]. More than 90% of coronary fistulas drain into the right chambers of the heart. In the right chambers, the fistula drains into the right ventricle in 40% of cases. Next in frequency are the right atrium, pulmonary trunk, and coronary sinus [12], and even less frequently, the left chambers of the heart [13,14].

Fistulas can be localized in any segment of the coronary artery, but they are more often located in its distal segments, with the communication being in the form of one or several openings, in most cases having a small diameter. The artery, as a rule, is dilated, tortuous, and the wall is thinned. This is a consequence of the compensatory mechanism in response to blood shunting bypassing the coronary bed. At the site of communication with the heart cavity, these changes are more pronounced and resemble aneurysmal dilation of the vessel [8-10]. The fistula is most often drained into the heart cavity by a single small opening, while the mouth and proximal section of the artery are dilated, and the distal section (at the site of drainage) is significantly narrowed [8-10].

Hemodynamics in coronary-cameral fistulas is caused by blood shunting from the affected coronary artery into the heart chamber or main vessel [3,8,9]. Hemodynamic disturbance and the development of clinical symptoms are determined by the volume of arterial blood shunting directly into the cardiac chamber, as well as deterioration of blood supply to the entire myocardial zone fed by the pathologically altered artery, spontaneous rupture of the fistula, heart rhythm disorders, and the development of infective endocarditis [9,40]. The volume of blood shunted through the fistula can reach 50% of the left ventricular (LV) cardiac output, and only a small part of this blood enters the distal bed of the coronary artery [8,9,16,41]. The magnitude of myocardial blood flow is determined by the pressure difference at the level of the fistula opening and in the intramural myocardial vessels. Since the resistance of the latter is always higher, with large dimensions of the fistula, most of the arterial blood enters through it, and a certain zone of the heart muscle receives insufficient blood supply, which leads to a progressive decrease in diastolic myocardial perfusion. The anomalous coronary artery dilates, aneurysms form, media degeneration, intima ulceration, cracks, atherosclerotic changes and calcification, obstruction of side branches, mural thrombosis, and arterial rupture occur [5,9,41].

When communicating with the right heart chambers, there is a left-to-right shunt and a corresponding volume overload of the right and left chambers of the heart, caused by the pressure gradient of the coronary bed system and the drainage chamber. Communication with the left ventricle and left atrium causes overload of the left heart chambers and can subsequently lead to the development of mitral and aortic valve insufficiency [9,42].

It should be noted that the heart can endure the presence of a coronary-cameral communication for a quite long time without significant impairment of its function, although signs of focal myocardial ischemia can be observed both in the zone located distally to the fistula and in the entire zone supplied by the artery [3,8,9,15].

Coronary-cameral fistulas can be asymptomatic and cause no complications in the first two decades of life. However, despite the fact that the majority of pediatric patients with congenital coronary-cameral fistulas are asymptomatic, this defect in most cases represents a hemodynamically significant coronary anomaly and leads to complications with age. The latter include myocardial steal syndrome, thrombosis and embolism, heart failure, atrial fibrillation and other arrhythmias, endocarditis/endarteritis [8,43]. Fistula thrombosis is rare, but can cause myocardial infarction, paroxysmal atrial fibrillation, and ventricular arrhythmias [8]. Spontaneous rupture of the aneurysmal dilation of the fistula leading to hemopericardium is also possible [8,9,12,41]. In rare cases, coronary-cameral fistulas may close spontaneously.

1.3 Epidemiology of the Disease or Condition

A. According to the literature, the incidence of anomalous origin of the LCA from the pulmonary artery is 0.25-0.5% among all congenital heart defects [4,16-23]. According to various authors, the defect occurs in 1 out of 300,000 live newborns [17-19,22-26]. At the same time, among all coronary artery defects, this pathology is the most common—in 90% of all cases [3,4,16,27].

B. The incidence of coronary-cameral fistulas among all congenital heart defects is 0.2-2%, and among congenital coronary artery anomalies, it holds the second position after anomalous origin of the coronary arteries (48.7%) [2,5,6-10,28,29]. In 33,000 patients who underwent coronary angiography, coronary-cameral fistulas were detected in 0.1% of cases [15].

This pathology can be combined with congenital heart defects such as critical pulmonary valve stenosis, pulmonary atresia with intact ventricular septum, peripheral pulmonary stenoses, coarctation and interruption of the aortic arch, as well as with various coronary diseases and traumatic heart injuries [2,3,10,15].

Iatrogenic coronary fistulas account for 20–25% of all coronary fistulas. Most commonly, they develop after right ventricular outflow tract reconstruction surgeries for congenital heart disease that are accompanied by decreased pulmonary blood flow (Tetralogy of Fallot, pulmonary atresia, isolated pulmonary stenosis) [9,15].

1.4 Features of Coding the Disease or Condition

Q24.5 – Congenital malformation of coronary vessels

1.5 Classification of the disease or condition

A. There are 2 variants of anomalous origin of the left coronary artery from the pulmonary artery (Bland-White-Garland syndrome) that differ in clinical and instrumental parameters and prognosis [45]:

1. infantile

2. adult.

Infantile type – occurs in 85–90% of all cases of the anomaly and is characterized by the origin of the left coronary artery from the pulmonary artery and the absence of well-developed collaterals between the right and left coronary artery systems. As a result, immediately after the child's birth, a severe ischemic lesion of the left ventricular myocardium develops, accompanied by decreased contractility and cavity dilation. Mitral regurgitation also occurs due to papillary muscle ischemia and annular dilation [46,47].

The incidence of the "adult" type of Bland-White-Garland syndrome is 10–15% [17,23,40,47,48]. In this type of defect, the left coronary artery also arises from the pulmonary artery, but there is a network of numerous and well-developed intercoronary anastomoses within the coronary artery system. This type of defect features dominance of the right coronary artery, and the connection between the left coronary artery and the pulmonary artery is restrictive (Fig. 3B) [41,45-47].

B. There are several classifications of coronary fistulas:

I. By etiology:

1. Congenital isolated.

2. Congenital combined with other congenital heart diseases:

• Hypoplastic left heart syndrome with aortic atresia;

• Pulmonary atresia with intact ventricular septum;

• Tetralogy of Fallot;

3. Acquired:

• after radical correction of Tetralogy of Fallot with resection of the muscle bundle;

• due to chest trauma;

• after endomyocardial resection/biopsy;

• after catheter ablation;

• as a complication of percutaneous coronary intervention.

II. According to the origin of the coronary artery:

1. Right coronary artery – 40–50%.

2. Left anterior descending artery – 30–40%.

3. Circumflex artery – 10–20%.

4. Left main coronary artery trunk – 10–20%.

5. Single coronary artery* [10,49].

* - isolated case reports

III. Depending on the size of the coronary fistula:

1. Small – smaller than the diameter of the distal coronary artery.

2. Medium – > 1–2 times larger than the distal coronary artery.

3. Large – > 2–3 times the distal coronary artery [50].

1.6 Clinical presentation of the disease or condition

A. The clinical presentation of the infantile course of Bland-White-Garland syndrome may manifest immediately after birth with the development of a terminal state due to extensive myocardial infarction or multiple infarctions (in some infants – with cardiogenic shock). With a more favorable disease course, the first symptoms may manifest in the first 3 months of life, less frequently in the second half of the year. The initial signs include deterioration of the general condition – lethargy, skin pallor, excessive sweating, vomiting, regurgitation, dyspnea, and tachycardia. Half of the infants experience episodes of sudden acute distress accompanied by worsening dyspnea, pallor, sweating, and tachycardia – these sometimes become the first signs of the disease. As a rule, anxiety attacks occur after or during feeding and can last for several minutes. Between attacks, the child appears completely healthy, and the only alarming factor may be the presence of dyspnea. In the literature, these episodes are termed "feeding angina" due to their similarity to angina pectoris in adults. This commonality is also confirmed by autopsy data (evidence of old and fresh myocardial infarctions).

Many children at this stage of the disease exhibit delayed physical development. They develop left-sided precordial bulge early on. As the child grows, mitral regurgitation joins the clinical manifestations of the defect, arising as a result of chronic ischemia or infarction of the papillary muscles, left ventricular cavity dilation, and valve leaflet deformation. In a number of clinical cases (with severe ischemic damage to the valvular and subvalvular structures), mitral regurgitation may develop at an earlier (infantile) age, masking the manifestations of the primary defect, which can lead to diagnostic error and inappropriate surgical management [51]. Thus, at this stage of the disease, the child exhibits predominantly left ventricular heart failure, and the clinical picture of the "infantile" type of the defect in young children may resemble that of myocarditis, dilated cardiomyopathy, congenital mitral regurgitation, or obstructive left ventricular outflow tract lesions (aortic stenosis, coarctation of the aorta).

In the "adult" type of the defect, right coronary artery dominance is noted, and the connection between the left coronary artery and the pulmonary artery is restrictive [45,52-54]. Parents of these children generally report no complaints indicative of cardiac disease, and child development may be age-appropriate. With such a compensated course of the defect, clinical manifestations may be absent for a long time and appear only in adolescence and/or even adulthood. The first symptoms of Bland-White-Garland syndrome in adolescents may include malaise or discomfort in the cardiac region during physical exercise, and in rare cases, typical retrosternal anginal pain may occur. In isolated cases, the defect is so paucisymptomatic that it is first detected in adults aged 50–60 years during standard electrocardiography performed due to myocardial infarction and/or coronary angiography [33]. An important point in this clinical variant of the defect is that even in the absence of clinical symptoms, myocardial ischemia continues to progress due to collateral blood flow between the right and left coronary arteries at the level of high coronary branching (2nd–3rd order), while the myocardium supplied by smaller coronary arteries continues to experience hypoxia. Therefore, in this patient subgroup, there is an 80–90% risk of sudden cardiac death [31,32,34,36,52,53], and the diagnosis of Bland-White-Garland syndrome is often an autopsy finding.

In adults, arrhythmias are frequently the first manifestations of the defect, which can lead to diagnostic errors. Consequently, the diagnostic algorithm for examining such patients should be expanded to include diagnostic methods that allow the detection of latent myocardial ischemia and coronary anomalies [52].

The literature contains isolated reports of primary diagnosis of Bland-White-Garland syndrome in elderly patients during evaluations for arrhythmias or mitral regurgitation [24,34,36-40]. Such situations are a rarity in cardiological practice.

B. Clinical manifestations of coronary fistulas are non-specific and depend on their size and the magnitude of the coronary blood shunt. The most frequent complaint is dyspnea disproportionate to normal exertion, associated with the gradual enlargement of the fistula, increasing severity of pulmonary hypertension, and an increased left-to-right shunt [2,5,8-10,16].

Compared to adults, asymptomatic fistulas are rare in children. Cases have been described where coronary fistulas are diagnosed in the neonatal period [5]. Medium and large coronary fistulas can lead to a continuous murmur. Angina attacks in infants are recognized by the onset of irritability, sweating, pallor, dyspnea, and tachycardia. In children, coronary fistulas often manifest at the age of 2–3 months when pulmonary vascular resistance decreases. At an older age, manifestations may include heart failure, arrhythmias, syncope, chest pain, and occasionally endocarditis. A large blood shunt can result in a picture of congestive heart failure and angina.

Conditions that typically require differential diagnosis with coronary fistulas include:

• anomalous origin of the left coronary artery from the pulmonary artery;

• pulmonary arteriovenous fistulas;

• myocardial infarction in children;

• patent ductus arteriosus;

• sinus of Valsalva aneurysm;

• ventricular septal defect.

Adult patients seeking medical care are most frequently troubled by dyspnea, cardiac pain upon physical exertion, and palpitations. Clinical examination may reveal cardiomegaly and a continuous systolodiastolic murmur with maximum intensity in the third to fourth intercostal space. These findings serve as indications for further evaluation.

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of a coronary artery anomaly is verified based on aggregated data including patient parental complaints, clinical manifestations of the defect, and the results of laboratory and instrumental research methods.

The diagnosis is established based on:

1. Electrocardiography;

2. Echocardiography;

3. Retrograde left heart catheterization with coronary angiography and panaortography;

4. Myocardial scintigraphy;

5. Single-photon emission computed tomography myocardial perfusion imaging;

6. ECG-gated spiral computed tomography of the heart;

7. Magnetic resonance imaging of the heart and great vessels.

2.1 Complaints and Anamnesis

(LetC, Level of Evidence 4)

Comments: If a patient has an adult-type ALCA origin anomaly, symptoms may be absent. This statement is also valid for children with small-sized coronary-cameral fistulas.

(LetC, Level of Evidence 4)

Comments: Such symptoms may indicate an infantile clinical course of ALCA origin anomaly or hemodynamically significant large coronary-cameral fistulas requiring urgent diagnosis and subsequent surgical intervention.

(CRA C, LOR 4).

• During the physical examination of all patients with suspected coronary artery anomalies, it is recommended to check for chest deformity in the form of a precordial bulge to determine the hemodynamic significance of the detected anomaly [23,27,30,33,35,51,56,57].

(Level of Evidence C, Grade of Recommendation 5)

Comments: In an unfavorable clinical course of ALCA origin anomaly (infantile type of the defect), early formation of a left-sided precordial bulge may occur against the background of rapidly developing left ventricular dilation.

2.2 Physical Examination

(Level of Evidence C, Grade of Recommendation 5)

Comments: In anomalous origin of the left coronary artery from the pulmonary artery, palpation may reveal a diffuse, weakened apex beat shifted to the sixth intercostal space. Percussion reveals enlargement of the cardiac borders, predominantly to the left. With medium and large coronary-cameral fistulas, percussion may also reveal cardiac border enlargement mainly due to the left heart chambers.

(Level of Evidence C, Grade of Recommendation 5)

Comments: During auscultation of a patient with anomalous origin of the left coronary artery from the pulmonary artery, heart sounds are typically muffled, and any murmurs may be inaudible during the first year of life. By the 2nd-3rd year of life, a prolonged, soft systolic murmur may appear over the precordium, peaking in the second left intercostal space, resembling the murmur of a patent ductus arteriosus and reflecting blood shunting from the left coronary artery into the pulmonary artery. As the child grows, mitral regurgitation joins the clinical manifestations of the defect, resulting from chronic ischemia or papillary muscle infarction, left ventricular cavity dilation, and valve leaflet deformation. As a result, a holosystolic murmur of mitral regurgitation with a maximum at the apex begins to be heard on auscultation.

Auscultation of medium and large coronary-cameral fistulas may reveal a prolonged murmur resembling that of a patent ductus arteriosus, but with an atypical location (lower down near the sternal border), with accentuation in mid/late diastole rather than during systole, as seen in patients with patent ductus arteriosus. A pathological third heart sound (S3) is detected in large fistulas. Heart sounds are often muffled. A holosystolic murmur of mitral regurgitation may be heard at the apex.

2.3 Laboratory Diagnostics

(CQR C, LCE 5)

(Level of Evidence C, Grade of Recommendation 5)

Comment: Performing a complete (clinical) blood count in all patients with coronary artery anomalies during follow-up and prior to surgical treatment is important for detecting anemia and providing timely correction. In patients with a mean corpuscular volume of less than 80 fL, it is advisable to test serum iron, ferritin, transferrin, and total iron-binding capacity for the timely correction of iron deficiency states. In patients with a mean corpuscular volume of greater than 100 fL, it is advisable to determine blood vitamin B₁₂ (cyanocobalamin) and serum folic acid levels for the timely correction of vitamin B₁₂- or folate-deficiency states. The aforementioned conditions can negatively affect the clinical and functional status, the course of the patient's disease, and the outcomes of surgical treatment [99].

(CQR C, LCE 5)

(CQR C, LCE 5)

(Level of Evidence C, Grade of Recommendation 5)

(Level of Evidence C, Grade of Recommendation 5)

(CQR C, LCE 4)

(Level of Evidence C, Grade of Recommendation 5)

• For all patients with coronary artery anomalies who receive thromboprophylaxis with heparin and its derivatives (B01AB Heparin group) after surgical treatment, it is recommended to perform laboratory monitoring of the efficacy of these medicinal products [119,121-123].

ESC no (CQR D, LCE 3)

Comments: When using unfractionated heparin (sodium heparin**, B01AB Heparin group), it is necessary to determine aPTT (the optimal range in adults is 40–60 s, in children — 60–85 s) and anti-Xa activity (the optimal range is 0.35–0.7). When using low-molecular-weight heparin preparations (B01AB Heparin group), it is necessary to determine anti-Xa activity (the optimal range is 0.5–1.0) [119,121-123].

2.4 Instrumental Diagnostics

(CRA C, LOR 4).

Comments: Characteristic ECG signs indicating anomalous origin of the LCA from the pulmonary artery (ALCAPA) are [66,70,76,81,86] a deep (> 3 mm) and wide (> 30 ms) Q wave in leads I, aVL, V5-6, combination of a deep Q wave with an inverted T wave in lead aVL (in acute infarction), ST-segment elevation above the isoelectric line and a decrease in R-wave amplitude (in acute infarction), "drop" in R-wave amplitude in leads V3 and V4 — formation of rS, QS, Qr type complexes (indicating a prior myocardial infarction and scar formation).

Differential ECG signs distinguishing ALCAPA from dilated cardiomyopathy and myocarditis are the presence of a Q wave greater than 3 mm in depth and greater than 30 ms in width in at least one of the following leads — I, aVL, V5-7, a QR complex of the same localization, the absence of a Q wave in leads II, III, and aVF, and ST-segment elevation in lead aVL [64].

In 15–20% of cases, typical ECG signs of ALCAPA may be absent. As a rule, this applies to older patients and adults with well-developed collateral vessels between the LCA and RCA and a relatively preserved LV myocardium. In this age cohort, the aforementioned electrocardiographic criteria may be absent, "masked", and/or manifest only during exercise stress tests. As noted earlier, the initial manifestation of ALCAPA in adults is often various rhythm disorders carrying a risk of "sudden" cardiac death. Nevertheless, ECG signs of left heart hypertrophy and overload are present in 100% of all patients with ALCAPA.

In small and medium-sized coronary-cameral fistulas (CCFs), the ECG is usually normal. With large fistulas, manifestations of volume overload of the left atrium and left ventricle may occur; in coronary steal, signs of ischemia and/or rhythm disturbances [5,8,10,56].

(LetC, Level of Evidence 4)

Comments: Targeted chest X-ray is the simplest and most widely available method that allows suspecting anomalous origin of the LCA even before the onset of the first clinical symptoms. Analysis of radiographs includes assessing the state of the pulmonary vasculature and heart size [51,55,57].

In patients with ALCAPA, the pulmonary vasculature may be unchanged and/or enhanced in a "venous" pattern, indicating the presence of mitral regurgitation and decreased LV pumping function. If the patient has long-standing progressive mitral regurgitation against the background of ALCAPA, radiological signs of chronic alveolar pulmonary edema may form.

Cardiomegaly may be one of the first markers alerting the physician to a possible coronary anomaly and prompting an expansion of the diagnostic algorithm, which can facilitate timely diagnosis of the defect. Enlargement of the heart size is a pathognomonic symptom for patients with anomalous origin of the LCA from the pulmonary artery, especially in the neonatal and infant periods [4,17,27,33,35,51,54,55,57].

When analyzing targeted chest X-rays in patients with CCFs, there are usually no abnormalities, but with large fistulas, cardiomegaly, signs of venous congestion, and interstitial pulmonary edema may be detected [56].

(GPR C, EL 4)

Comments: Echocardiography, which includes M-mode, two-dimensional, and Doppler echocardiographic techniques, is one of the most important diagnostic methods for the defect, allowing non-invasive assessment of the anatomy of coronary artery origin, heart chamber dimensions, morphological state of the atrioventricular valves, and myocardial function, as well as providing qualitative and quantitative assessment of hemodynamic parameters of intracardiac blood flow.

Echocardiography makes it possible to visualize the ostia and proximal segments of the coronary arteries: RCA, LCA, their bifurcation, to determine the diameter of these segments, and to visualize the site of origin of the coronary arteries [66-70], to assess the size of the cardiac chambers and the contractile function (global or regional) of the LV, and signs of endocardial fibroelastosis [71-73]. In ALCAPA, color two-dimensional Doppler mapping registers blood flow in the LCA and retrograde flow from the LCA into the proximal pulmonary trunk [74-76], visualizes abnormal diastolic flow across the interventricular septum associated with dilated intercoronary collaterals [77,78], and may also reveal antegrade flow directed from the pulmonary artery into the anomalously originating LCA [70].

There are 9 indirect Doppler echocardiographic signs whose presence may indicate an anomalous origin of the LCA from the pulmonary artery, namely: pronounced LV dilation (in 95% of cases), decreased LV pumping function (68% of cases), LV aneurysm formation (47% of cases), compaction of the LV endocardium (42% of cases), dilation of the mitral valve fibrous ring (95% of cases), mitral regurgitation (97% of cases), dilation of the ostium and proximal segment of the RCA (68% of cases), non-visualization of the LCA ostium at its usual site of origin (100% of cases), and systolic-diastolic flow in the pulmonary artery according to echocardiography (79% of cases) [79,80].

Also, during echocardiography, an important point is the assessment of the functional state of the mitral valve, as it can be a "target" for surgical interventions during the surgical correction of the primary defect.

An echocardiographic examination in a patient with a coronary artery fistula in most cases makes it possible to diagnose coronary fistulas. Echocardiographic signs of coronary artery fistulas may include:

• enlargement of the left atrium and left ventricle resulting from a significant volume blood shunt, and local or diffuse reduction in LV contractility due to ischemia;

• dilation of the coronary arteries;

• high-velocity blood flow detected by color Doppler imaging at the site of origin or along the course of the vessel;

• the site of fistula drainage may appear upon careful examination as a zone of turbulent blood flow, typically in the right ventricle;

• holodiastolic flow in the descending aorta;

• dilation of the coronary sinus when the fistula empties into it.

(Level of Evidence C, Grade of Recommendation 5)

Comments: Angiographic semiotics of anomalous origin of the LCA from the pulmonary artery includes evaluation of the origin of the coronary arteries, assessment of the type of myocardial blood supply depending on the peripheral branching and termination of the coronary arteries, analysis of the degree of development of intercoronary collaterals, and determination of the direction of coronary blood flow.

The existing variants of the clinical course of ALCAPA ("infantile" and "adult" types) largely determine the outcome of the angiography and the specificity of the angiographic picture.

In the infantile type, pan-aortography and/or selective right coronary angiography reveals a single dilated RCA originating from the right sinus of Valsalva. The LCA fills retrogradely via the system of intercoronary anastomoses with blood runoff into the pulmonary artery. The development of collaterals can be judged by the degree of dilation and tortuosity of both CAs, the rate of filling of the LCA system, and the volume of runoff into the pulmonary artery. This type of defect is characterized by a narrow LCA filling retrogradely from the RCA basin through a system of poorly developed collaterals. Blood runoff from the LCA into the pulmonary artery generally does not exceed 15-20%, and in some cases may not be detectable. Sometimes it can be so small and rapid that when analyzing the angiogram in the anteroposterior projection, it may give the impression that the LCA originates from the aorta. In doubtful cases, evaluation of the lateral projection may be decisive, allowing visualization of the LCA ostium in the projection of the posterior wall of the pulmonary artery.

In the adult type, contrast injection into the aorta and/or selectively into the RCA ostium also reveals a single coronary artery arising from the aorta, markedly dilated and tortuous. The LCA appears as a markedly dilated, tortuous vessel, rapidly and retrogradely filled from the RCA basin via multiple, well-developed collaterals. From the LCA, the contrast medium enters the pulmonary artery with opacification of the pulmonary trunk and its branches. The volume of arterial blood shunting from the LCA to the pulmonary artery can be hemodynamically significant, leading to elevated pressure in the pulmonary artery system.

Ventriculography in ALCAPA enables the assessment of the functional state of the left ventricle, specifically: detecting regional left ventricle function abnormalities in the form of localized areas of akinesia, hypokinesia, and dyskinesia; diagnosing left ventricle aneurysm and assessing its location and size; identifying intracavitary masses (mural thrombi and tumors); calculating important and informative hemodynamic parameters — end-systolic volume and end-diastolic volume, stroke volume, cardiac output, cardiac index, stroke index; assessing left ventricle pumping function parameters — ejection fraction and left ventricle end-diastolic pressure; and visually assessing mitral regurgitation.

Ventriculography in patients with the "infantile" type of ALCAPA reveals marked dilation of the left ventricle and atrium, weak left ventricle contractions, almost complete absence of contractions in the apical zone of the heart with its bulging resembling a left ventricle aneurysm, and varying degrees of mitral regurgitation. Ventriculography in the "adult" type of the anomaly, in most cases, does not reveal left ventricle asynergy zones; mitral regurgitation is generally minimal [16,23,27,51,55-57].

For patients with diagnosed coronary-cameral fistulas, selective coronary angiography remains the method of choice for assessing coronary artery structure and coronary blood flow. In addition, cardiac and vascular catheterization may be performed for therapeutic purposes, such as coronary-cameral fistula embolization. Data from diagnostic retrograde left heart catheterization make it possible to assess the hemodynamic significance of the coronary-cameral fistula and provide a detailed angiographic characterization of the abnormal vessel, which serves as a starting point for choosing the treatment strategy. These diagnostic methods allow for the evaluation of the number of fistulas, the nature of the feeding vessel(s), drainage sites, the amount of myocardium at risk of developing ischemia, and the hemodynamic significance of the shunt [16,56].

(LetC, Level of Evidence 4)

Comments: According to myocardial scintigraphy data, patients with anomalous origin of the LCA from the PA are characterized by a decrease in perfusion predominantly in the region of the anterior (92%) and anterolateral (85%) LV walls [81,82], while in a number of cases, perfusion defects may extend to the apex, the anterior part of the interventricular septum, the posterolateral, and even the posterior LV wall. In the presence of well-developed collaterals between the RCA and LCA, the perfusion defect may be limited to the anterior and anterolateral walls. Poor development of intercoronary anastomoses leads to a greater extent of perfusion defects involving the posterior wall. Therefore, the detection of widespread perfusion abnormalities involving the posterior and posterolateral LV regions in young children can be regarded as an unfavorable prognostic sign.

In addition to high diagnostic value in patients with ALCAPA, myocardial scintigraphy is of great importance for assessing the results of performed surgical interventions. In patients with viable myocardium, regional and global left ventricle myocardial contractile function improves. Furthermore, this is observed both after ligation or closure of the anomalously arising LCA (A16.12.014 Vessel ligation), after the creation of mammary-coronary anastomoses (A16.12.004.001 Coronary artery bypass grafting under cardiopulmonary bypass), and after direct implantation of the LCA into the aorta (A16.12.004 Creation of anastomosis on coronary vessels).

This study is not an "ideal" prognostic marker for patients with anomalous origin of the left coronary artery from the pulmonary artery. Typically, radiopharmaceutical uptake defects detected at rest are interpreted as scar changes, which, in the absence of data on the metabolic state in this area, can lead to overdiagnosis and incorrect surgical tactics [81]. That is why it is important to compare myocardial scintigraphy data with myocardial metabolism parameters obtained using positron emission tomography (PET).

(LetC, Level of Evidence 4)

Comments: The principle of contrast-enhanced myocardial positron emission tomography combined with computed tomography (using 18F-FDG) is that normal or increased accumulation of 18F-FDG (an analog of regular glucose) is possible only in viable myocardium [81].

The use of contrast-enhanced myocardial positron emission tomography combined with computed tomography in the evaluation of patients with anomalous origin of the left coronary artery from the pulmonary artery makes it possible to detect viable myocardium in a hypermetabolic state, small-focal scar changes combined with viable myocardium, and large-focal scar changes. The latter two conditions may be combined with the presence of hypermetabolic myocardium in other left ventricle segments.

In addition, the capabilities of the method allow for calculating the areas of hibernating myocardium and scar changes, including the area of the aneurysm. The data obtained from the PET study allow for the selection of surgical tactics and have great prognostic significance for the outcomes. Of no small importance is the possibility of using contrast-enhanced myocardial positron emission tomography combined with computed tomography to assess the functional results of the performed coronary bed reconstruction in the long-term postoperative period [51].

(LetC, Level of Evidence 4)

Comments: CT coronary angiography is recommended to clarify the anatomy of the coronary vessels. CT coronary angiography surpasses all imaging modalities in evaluating coronary artery anatomy. The primary significance of CT coronary angiography lies in its superior spatial resolution [51,55-57,83,84].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Cardiac and great vessel magnetic resonance imaging (MRI) is the most accurate method for assessing cardiac function and the modality that visualizes myocardial fibrosis. Cardiac and great vessel magnetic resonance imaging (MRI) is currently considered the "gold standard" imaging modality for assessing cardiac chamber function. MRI is a unique method that allows non-invasive assessment of focal and diffuse myocardial fibrosis using contrast enhancement.

2.5 Other Procedures

(LetC, Level of Evidence 4)

(CRA C, LOR 4)

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

3.1 Conservative Treatment

Surgical correction of the defect remains the only recognized effective treatment option for heart failure in patients with anomalous origin of the left coronary artery from the pulmonary artery. However, in patients with pronounced manifestations of circulatory failure against the background of this congenital heart disease, medical therapy aimed at treating heart failure is indicated. Competent and timely administration of appropriate pharmacological agents helps stabilize the patient's condition and, in some cases, improves clinical status, allowing surgical correction of the defect to be performed on a more favorable background.

• In patients with coronary anomaly and a high risk of thrombosis after surgical treatment, thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin (heparin group B01AB) is recommended [119,121-123].

(CQR C, LCE 5)

Comments: The high-risk thrombosis group includes patients with a history of thrombosis, thrombophilia, infectious complications, and multiple organ failure [119].

Thromboprophylaxis with #sodium heparin** should be initiated with a bolus dose of 75 IU/kg in children, followed by continuous intravenous infusion at a rate of 28 IU/kg for children under 1 year of age, 20 IU/kg for children over 1 year of age, and 18 IU/kg for adults. Dose adjustment is made based on laboratory test results [119].

Thromboprophylaxis with heparin and its derivatives (heparin group B01AB) is calculated as follows: #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 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 subcutaneously every 12 hours. #Fondaparinux sodium** can be used in children over 1 year of age (off-label in children under 17 years) at a dose of 0.1 mg/kg once daily subcutaneously. Dose adjustment is made based on laboratory test results [119,121,123].

3.2 Surgical Treatment

(Level of Evidence C, Grade of Recommendation 5)

Comments: The choice of surgical technique is determined primarily by the anatomy of the defect (characteristics of the coronary arterial system, location of the left coronary artery ostium relative to the pulmonary trunk, as well as the presence of complications such as mitral regurgitation and left ventricular aneurysm), the clinical condition of the patient, and the surgeon's experience and preference for a particular method.

Currently, there are two distinct approaches to the surgical treatment of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). The first approach is designed to stop blood runoff through the anomalously originating left coronary artery, thereby increasing perfusion pressure within the coronary arterial system. This is achieved by ligating or closing the ostium of the left coronary artery, with myocardial blood supply relying solely on a single coronary artery. The second approach aims to restore normal arterial blood flow in the coronary system (and consequently normalize perfusion of the damaged myocardium) through direct or indirect (using an intrapulmonary tunnel) implantation of the anomalous coronary artery into the aorta (A16.12.004 creation of anastomosis on coronary vessels) or by establishing an anastomosis between the systemic and coronary arteries using various types of allografts.

• When choosing the surgical method for ALCAPA, restoration of a dual-coronary myocardial blood supply is recommended to establish physiological blood flow in the coronary system [16,17,31,32,35,51,55-57].

(LetC, Level of Evidence 4)

Comments: Restoration of a dual-coronary myocardial blood supply using various techniques is currently the "gold standard" in the surgical treatment of Bland-White-Garland syndrome. The preferred technique for normalizing coronary blood flow in infants and young children is direct implantation of the left coronary artery into the aorta (A16.12.004 Creation of coronary anastomosis).

• In cases of unfavorable anatomy of the anomalously originating left coronary artery (short trunk, early branching), one of the modifications of direct coronary artery implantation utilizing autologous aortic and pulmonary trunk tissues for trunk lengthening is recommended [51,57,85-90].

(LetC, Level of Evidence 4)

Comments: These techniques help avoid tension on the reimplanted left coronary artery and prevent its stenosis when using synthetic or biological patches.

• In older children, when direct implantation of the left coronary artery into the aorta is not feasible, mammary-coronary artery bypass grafting (A16.12.004.001 Coronary artery bypass grafting with cardiopulmonary bypass) is recommended [16,36,38,39,51,56,57].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Direct implantation of the left coronary artery in older children can be technically difficult and hazardous due to reduced vessel elasticity, which hinders mobilization, leads to uneven tension, and carries a high risk of bleeding. In such cases, bypass grafting of the anomalous left coronary artery with the internal thoracic artery is preferred.

• During surgical correction of anomalous left coronary artery from the pulmonary artery in all patients presenting with baseline mitral valve insufficiency with regurgitation greater than grade 2 (moderate), repair of mitral regurgitation using valve-sparing procedures (mitral valve annuloplasty/repair with cardiopulmonary bypass) is recommended; if repair is not feasible, mitral valve replacement with cardiopulmonary bypass (mechanical bileaflet mitral valve prosthesis***) is indicated [51,55-57,91,93,131].

(LetC, Level of Evidence 4)

• In patients diagnosed with anomalous left coronary artery originating from the pulmonary trunk in the presence of a left ventricular aneurysm, one of the ventriculoplasty techniques (left ventricular reconstruction) is recommended during surgical correction of the coronary anomaly to normalize intracardiac hemodynamics and improve long-term survival prognosis [16,51,56-57,92,93].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Indications for performing one of the types of ventriculoplasty (left ventricular reconstruction) in the correction of Bland-White-Garland syndrome should include: 1) presence of a left ventricular aneurysm confirmed by echocardiography; 2) marked left ventricular cavity dilation with asynergy zones demonstrated by retrograde left heart catheterization; 3) signs of an aneurysm with scarred area coverage exceeding 20% on myocardial positron emission tomography (PET). The spectrum of surgical interventions for left ventricular aneurysm includes: 1) aneurysmorrhaphy; 2) Jatene left ventricular aneurysm repair; 3) Dor left ventricular aneurysm repair.

• In patients diagnosed with anomalous left coronary artery from the pulmonary trunk, transmyocardial laser revascularization is recommended in certain clinical scenarios to achieve long-term improvement in myocardial blood supply [51,56,57].

(LetC, Level of Evidence 4)

Comments: The use of transmyocardial laser revascularization in patients with Bland-White-Garland syndrome as an alternative to coronary artery bypass grafting with cardiopulmonary bypass may be justified in critically ill patients with the primary defect who have unfavorable coronary anatomy, absent or poorly developed intercoronary collaterals, and a large area of left ventricular scar tissue.

• In patients diagnosed with anomalous left coronary artery from the pulmonary trunk, heart transplantation is recommended in certain clinical scenarios as a lifesaving, non-alternative treatment option [51,56,57].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Heart transplantation is indicated in patients with massive myocardial infarction or left ventricular aneurysm, particularly when the expected myocardial revascularization will not completely eliminate pathomorphological changes in the heart, i.e., in the documented absence of viable myocardium (according to PET and SPECT data). Unfortunately, this recommendation is difficult to apply to young children in our country due to the lack of a legal framework for pediatric transplantology in Russia, and donors are generally limited to adults. In rare situations, heart transplantation from an adult donor to a pediatric recipient may be performed (depending on donor height and weight parameters).

• In a subset of patients diagnosed with anomalous left coronary artery from the pulmonary trunk undergoing surgical correction of the coronary anomaly, stem cell therapy is recommended [51,56,57,92].

(LetC, Level of Evidence 4)

Comments: The administration of stem cells (fetal cardiomyoblasts, CD133+ angiogenic cells) into the coronary bed and intramyocardially for Bland-White-Garland syndrome can be utilized either during the primary defect correction or during long-term postoperative follow-up in cases of persistently depressed left ventricular contractility.

• In patients diagnosed with large coronary-cameral fistulas (CCFs), closure of the CCF is recommended regardless of symptoms, using open surgical or endovascular techniques after analyzing their anatomy and occlusion feasibility [5-11,13,15,44,49,50].

(Level of Evidence C, Grade of Recommendation 5)

Comments: The success of surgical fistula closure is largely predetermined by preoperative determination of its exact localization and the possibility of adequate surgical exposure. If the anatomical features of the fistula and its difficult exposure are underestimated, especially the distal segment, inadequately appropriate correction with subsequent recanalization of the fistula is possible.

(Level of Evidence C, Grade of Recommendation 5)

(LetC, Level of Evidence 4)

3.3 Endovascular interventions

(LetC, Level of Evidence 4)

Comments: Numerous publications indicate successful partial or complete closure of CCFs by the endovascular method using vascular embolization coils*** or a cardiac occluder***. The main indications for CCF embolization are: 1) fistula diameter greater than 3 mm, 2) proximal location of the fistulous tract, 3) single CCF, 4) straight fistulous tract, 5) absence of concomitant intracardiac pathology [132-134].

3.4 Other treatment

No

4. Medical Rehabilitation and Sanatorium-Resort Treatment

(Level of Evidence C, Grade of Recommendation 5)

Comments: The following conditions may occur after the correction of coronary artery anomalies:

- formation of stenosis of the ostium and trunk of the reimplanted left coronary artery (LCA) after direct LCA implantation into the aorta (Ao) during correction of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA);

- progression of myocardial ischemia accompanied by a decrease in contractile function;

- formation of supravalvular pulmonary artery (PA) stenosis after direct LCA reimplantation into the aorta;

- development of graft dysfunction (occlusion, stenosis) during bypass grafting of an anomalously originating LCA in ALCAPA correction;

- recanalization of the intrapulmonary tunnel with the formation of coronary-pulmonary fistulas during hemodynamic correction operations such as Hamilton and Takeuchi;

- stenosis of the intrapulmonary tunnel during hemodynamic correction operations such as Hamilton and Takeuchi;

- progression of mitral regurgitation (MR);

- development of prosthesis-related complications during prosthesis implantation in the mitral position (mechanical bileaflet mitral valve prosthesis***) during ALCAPA correction (endocarditis, thrombosis, systemic embolisms, perivalvular leak, or occlusion associated with pannus formation);

- development of cardiac arrhythmias, in some cases leading to sudden cardiac death against the background of acute coronary insufficiency;

- recanalization of CCF.

(Level of Evidence C, Grade of Recommendation 5)

• Within 6 months after surgical correction of coronary artery anomalies, a patient with a complicated postoperative course (residual pulmonary hypertension, heart failure, infectious complications, repeated surgical interventions during the same hospitalization) is recommended to undergo rehabilitation in a specialized cardiological sanatorium-resort facility [115-116].

(Level of Evidence C, Grade of Recommendation 5)

5. Prevention and Dispensary Observation

(Level of Evidence C, Grade of Recommendation 5)

• Patients who have undergone surgical correction of coronary artery anomalies are recommended to have a dispensary follow-up (examination, consultation) by a pediatric cardiologist with ECG and echocardiography performed every 7 days for 1 month after discharge from the cardiac surgery hospital. Subsequently, if the patient's clinical condition is stable, dispensary follow-up (examination, consultation) by a pediatric cardiologist with ECG and echocardiography should be performed once every 3 months for a year, and thereafter the frequency is determined individually [33,35,51,56,57].

(Level of Evidence C, Grade of Recommendation 5)

Comments: Conducting dispensary follow-up (examination, consultation) by a pediatric cardiologist with ECG and echocardiography at such intervals allows for the timely detection of the progression of myocardial ischemia, as well as potential complications of corrected coronary artery anomalies.

(Level of Evidence C, Grade of Recommendation 5)

Comments: The purpose of such examinations is to rule out the appearance of ischemic symptoms, arrhythmias, and cardiac chamber dilatation, which may affect the patient's further management tactics.

• Patients with coronary artery anomalies after surgical treatment are recommended to undergo inpatient examination at least once a year after surgical treatment of the defect for the timely detection and elimination of possible postoperative complications [93].

(Level of Evidence C, Grade of Recommendation 5)

(Level of Evidence C, Grade of Recommendation 5)

Comments: Performing this study in patients who have undergone surgical correction of coronary artery anomalies is necessary to detect left ventricular (LV) dysfunction, assess its volumetric characteristics and contractility, and detect possible coronary ischemia, areas of fibrosis, and scar changes.

6. Organization of Medical Care

Indications for scheduled hospitalization in a medical organization:

1. presence of heart failure symptoms;

2. planned surgical treatment of a coronary anomaly;

3. investigation of long-term results of previously performed surgical treatment;

Indications for emergency hospitalization:

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

2. development of acute coronary insufficiency;

3. development of LV dysfunction;

4. infective endocarditis;

Indications for discharging a patient from a medical organization:

1. presence of documented blood flow through the reimplanted LCA during ALCAPA correction;

2. absence of hemodynamically significant CCF recanalization;

3. absence/compensation of heart failure symptoms;

4. absence of signs of coronary ischemia;

5. absence of hemodynamically significant cardiac arrhythmias.

7. Additional Information

Patient cohort subject to the diagnostic algorithm to identify a coronary anomaly:

a) newborns with unexplained cardiomegaly combined with a history of "feeding angina" spells;

b) infants with signs of unexplained, documented LV heart dysfunction (ECG signs of myocardial ischemia and LV hypertrophy, increase in its linear and volumetric characteristics with decreased contractility according to echocardiography) and/or with newly diagnosed severe MR;

c) adolescents with newly detected anginal pain, cardiac arrhythmias, and/or the presence of newly detected severe mitral regurgitation.

Among the primary anatomical factors determining the survival of patients with anomalous origin of the LCA from the pulmonary artery after surgery, the following are of paramount importance: the degree of development of intercoronary anastomoses, the type of coronary dominance, and right ventricular hypoplasia. All other anatomical factors, such as myocardial damage, LV dilatation (sometimes with the formation of a giant aneurysm), and mitral regurgitation, are secondary [8,27,60].

Operative mortality for ligation or suture of the ostium of an anomalously originating LCA from the pulmonary artery lumen ranges from 20 to 50% [44,114], and in the long-term postoperative period, it can reach 33% [84,114,115]. In the mid-1980s, mortality after ligation or suture operations of the anomalously originating LCA ostium was 40.0% and 11.1% in the early and late postoperative periods, respectively [116]. Fairly high rates of postoperative mortality are explained by the fact that such interventions do not lead to the normalization of LV volume and the restoration of its contractility, which, in turn, leads to critical heart failure and, consequently, to the deterioration of long-term results [36,84,114,117,118]. At the same time, these surgical interventions are technically easy to perform and can serve as the first stage of defect correction aimed at preventing irreversible dysfunction of the myocardium, papillary muscles, and the cardiac valve apparatus [119].

When analyzing the results of shunt surgeries in the early postoperative period in patients with functioning anastomoses, the results are generally good [44,59]. However, due to their morphological characteristics, venous grafts tend to stenose or occlude over time. Thus, the main reasons for surgeons' dissatisfaction with the outcomes of these techniques are complications associated with stenosis, occlusion, or thrombosis of interposition grafts, particularly in young children.

Direct implantation of the left coronary artery (LCA) into the aorta (A16.12.004 creation of anastomosis on coronary vessels) is the most frequently performed procedure in cardiac surgery clinics. Mortality for this operation ranges from 0 to 16%.

Long-term outcomes of direct LCA implantation into the aorta (A16.12.004 creation of anastomosis on coronary vessels) are encouraging, especially if the intervention is performed in early childhood. In the long term after the procedure, the majority of patients (around 85–90%) remain asymptomatic; functional testing reveals recovery of left ventricular (LV) function manifested by a reduction in its linear dimensions and volumetric parameters, as well as an improvement in its pumping function. Mitral regurgitation typically regresses.

Regarding hemodynamic correction procedures, some authors prefer the Takeuchi operation in neonates and infants, whereas others consider this intervention the method of choice in adult patients. Mortality rates for this procedure range from 0 to 23%, which is comparable to the results of direct translocation of the anomalously arising LCA.

Dissatisfaction with the outcomes of this intervention is due to a fairly high percentage of postoperative complications, such as varying degrees of supravalvular pulmonary artery stenosis, a high probability of developing coronary-pulmonary fistulas during the creation of an intrapulmonary tunnel, and the development of aortic valve regurgitation. According to literature data, 30% of these patients require reoperation under cardiopulmonary bypass or endovascular procedures.

Currently, a significant improvement in the outcomes of surgical correction of ALCA (anomalous left coronary artery from the pulmonary artery) is associated with the development and wide clinical adoption of postoperative mechanical circulatory support systems as a "bridge" to the recovery of LV contractile function. Anomalous origin of the LCA from the pulmonary artery is a classic example of postcardiotomy LV dysfunction, where mechanical support is particularly effective. The most commonly used mechanical circulatory support systems are intra-aortic balloon counterpulsation (IABC), left ventricular assist (LVA), and extracorporeal membrane oxygenation (ECMO).

For patients with repaired coronary-cardiac fistulas (CCF), the prognosis is favorable if surgical treatment is successful. The long-term prognosis is determined by the likelihood of postoperative recanalization and/or the appearance of a new fistula, including previously undiagnosed ones.

Following open surgical interventions, mortality reaches 1% in the group of patients under 20 years of age and 7% in patients older than 20 years. Potential long-term postoperative complications include myocardial ischemia and infarction (3–7% of cases) and fistula recanalization (up to 4% of cases). Complete occlusion of the CCF on the operating table using microcoils for vascular embolization*** is achieved in 79% of cases, and in the long-term period, in 96% of cases. Reported complications of endovascular intervention include coil migration into the pulmonary artery, balloon migration, and myocardial infarction (potentially fatal).

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Avramenko A.A. (Samara)

2. Apkhanova T.V., MD, "National Association of Experts in Spa Treatment"

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

4. Bogdanov V.N. (Chelyabinsk)

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

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

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

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

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

10. Kalashnikov S.V., PhD (Moscow)

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

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

13. Konchugova T.V., MD, Professor, "National Association of Experts in Spa and Resort Treatment", Krivoshchekov E.V., MD, (Tomsk)

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

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

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

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

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

19. Rucheva N.A., PhD (Moscow), All-Russian Public Organization for the Promotion of the Development of Diagnostic Radiology and Therapy "Russian Society of Roentgenologists and Radiologists"

20. Sinitsyn V.E., MD, Professor (Moscow) All-Russian Public Organization for the Promotion of the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists", Sinelnikov Yu.S., MD, (Perm)

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

22. Fesyun Anatoly Dmitrievich, MD, PhD, Associate Professor, President of the National Association of Experts in Spa Treatment and Balneology

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

24. Yakovlev Maxim Yuryevich, MD, PhD, "National Association of Experts in Spa Treatment and Balneology"

There is no conflict of interest.

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

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Pediatric Cardiologist

2. Cardiologist

3. Cardiovascular Surgeon

4. Ultrasound Diagnostics Physician

5. Pediatrician

6. X-ray Endovascular Diagnostics and Treatment Physician

7. Radiologist

8. Functional Diagnostics Physician

9. Neonatologist

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

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

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

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

Procedure for updating clinical guidelines.

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

Appendix A3. Reference Materials

1. On the Basics of Protecting the Health of Citizens in the Russian Federation (Federal Law No. 323-FZ of November 21, 2011)

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

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

4. Order of the Ministry of Health of Russia dated 08.06.2020 N 557n "On approval of the Rules for conducting ultrasound examinations".

Transthoracic echocardiography performance technique

Requirements:

In newborns and infants: transducers with a frequency of 7.5-12 MHz, in adolescents and adults – 2.5-7 MHz.

Contraindications: impaired integrity of the skin at the examination site.

Limitations: cases of an unsatisfactory acoustic window.

Appendix B. Physician Action Algorithms

Algorithms for physician actions in suspected coronary anomalies

Algorithm for physician actions in a patient with suspected anomalous origin of the left coronary artery from the pulmonary artery

Algorithm for managing patients with diagnosed coronary-cameral fistulas depending on size and localization [50].

Appendix C. Patient Information

Dear patient (patient's parents), the examination results revealed that you (your child) have a congenital heart defect – coronary artery anomalies.

Coronary artery anomalies represent a diverse group of congenital pathological changes in the coronary vessels, forming as a result of anomalous origin, course, or structure of the terminal bed of the coronary arteries.

Most coronary artery anomalies are incidental findings during routine health screenings of patients and often pose no threat to the patient (therefore requiring neither conservative nor surgical treatment). However, it should be understood that there are exceptions. Life-threatening CA anomalies include:

1) Anomalous origin of the left coronary artery from the pulmonary artery (Bland-White-Garland syndrome - BWGS) is a rare congenital heart defect (CHD) characterized by an unfavorable course already in the neonatal and infancy periods and an extremely dubious prognosis with natural progression.

2) Coronary-cameral fistulas (CCF) - an anomalous communication between the coronary arteries and the cardiac cavity or other vascular structures bypassing the capillary bed, leading to disruption of the structure of the coronary arteries and blood flow through them.

The clinical presentation of the infantile type of BWGS can manifest immediately after birth with the development of a terminal state due to extensive myocardial infarction or multiple infarctions (in some infants – with cardiogenic shock). With a more favorable course of the disease, the first symptoms may manifest in the first 3 months of life, less often – in the second half of the year. The first signs are deterioration of the general condition – lethargy, skin pallor, excessive sweating, vomiting, regurgitation, shortness of breath, and tachycardia. In half of the infants, there are episodes of sudden severe anxiety with increased shortness of breath, pallor, and sweating – these sometimes become the first signs of the disease. As a rule, episodes of anxiety occur after or during feeding and can last for several minutes. Between episodes, the child looks completely healthy, and the only warning sign may be the presence of shortness of breath. In literature, these episodes are termed "feeding angina" due to their similarity to the clinical picture of angina in adults. The commonality of these phenomena is also confirmed by autopsy data (signs of old and recent myocardial infarctions). Many children at this stage of the disease lag behind in physical development. They develop a left-sided precordial bulge early on. As the child grows, mitral regurgitation joins the clinical manifestations of the defect, arising due to chronic ischemia or infarction of the papillary muscles, left ventricular cavity dilation, and valve leaflet deformation. In a number of clinical cases (with severe ischemic damage to the valvular and subvalvular structures), mitral valve regurgitation may develop at an earlier (infancy) age, masking the manifestations of the underlying defect, which can lead to a diagnostic error and incorrect surgical tactics [51].

Thus, at this stage of the disease, signs of heart failure predominantly of the left ventricular type prevail in the child, and the clinical picture of the "infantile" type of the defect in young children may resemble that of myocarditis, dilated cardiomyopathy, congenital mitral valve regurgitation, or left ventricular outflow tract obstruction (aortic stenosis, coarctation of the aorta). If any of the above signs are present in your child, you should immediately contact a cardiac surgery hospital to clarify the diagnosis.

In the "adult" type of the defect (BWGS), dominance of the right CA is noted, and the communication between the LCA and PA is restrictive [45,52-54]. Parents of children, as a rule, do not report complaints indicating heart disease, and the child's development may correspond to age. With such a compensated course of the defect, clinical manifestations may be absent for a long time and appear only in adolescence and/or even adulthood. The first symptoms of BWGS in adolescents may be malaise or the appearance of discomfort in the heart area during sports activities, and in rare cases, typical retrosternal anginal pain may occur. An important point in this clinical variant of the defect's course is that even in the absence of clinical symptoms, myocardial ischemia progresses, which is associated with the presence of collateral blood flow between the RCA and LCA at the level of high division of the coronary arteries – 2nd-3rd order, while the myocardium supplied by smaller coronary arteries continues to experience hypoxia. Therefore, in this subgroup of patients, in 80-90% of cases, there is a risk of sudden cardiac death [31,32, 34,36,52,53]. Therefore, if any of the above signs are present in your child, you should immediately contact a cardiac surgery hospital to clarify the diagnosis.

In adults, arrhythmias are frequently the first manifestations of the defect, which can lead to diagnostic errors. Consequently, the diagnostic algorithm for examining such patients should be expanded to include diagnostic methods that allow the detection of latent myocardial ischemia and coronary anomalies [52].

The clinical manifestations of coronary artery fistula (CAF) are non-specific and depend on its size and the magnitude of the coronary blood shunt. The most frequent complaint is the onset of dyspnea disproportionate to usual exertion, associated with the gradual enlargement of the fistula, progression of pulmonary hypertension, and an increase in the left-to-right blood shunt [2,5,8-10,16].

Compared to adults, asymptomatic fistulas are rare in children. Cases have been described where coronary fistulas are diagnosed in the neonatal period [5]. Medium and large coronary fistulas can lead to a continuous murmur. Angina attacks in infants are recognized by the onset of irritability, sweating, pallor, dyspnea, and tachycardia. In children, coronary fistulas often manifest at the age of 2–3 months when pulmonary vascular resistance decreases. At an older age, manifestations may include heart failure, arrhythmias, syncope, chest pain, and occasionally endocarditis. A large blood shunt can result in a picture of congestive heart failure and angina.

Adult patients are most commonly troubled by dyspnea, cardiac pain upon physical exertion, and palpitations. Clinical examination of patients may reveal cardiomegaly and a continuous systolic-diastolic murmur with maximum intensity in the third to fourth intercostal spaces. Any of the aforementioned signs or complaints serve as indications for patient evaluation in a specialized cardiac surgery hospital.

With timely detection of these anomalies, the prognosis in the overwhelming majority of cases is favorable, but only on condition of surgical correction of the anomaly. In case of delayed presentation or postponed surgical correction, the prognosis is highly likely to be unfavorable.

Therefore, if you or your child experience the complaints described above, you should immediately consult a specialist (pediatric/adult cardiologist) for further recommendations.

By voluntarily consenting to surgery, you must understand the purpose and potential complications of the operation, which your attending physician will explain to you.

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

No.