Aortic coarctation: clinical guidelines

List of Abbreviations

BP – blood pressure

ACG – angiocardiography

CHD – congenital heart disease

BAV – bicuspid aortic valve

VSD – ventricular septal defect

DT – ductal tissue

CoA – coarctation of the aorta

CM – contrast medium

CT – computed tomography

CTA – CT angiography

LV – left ventricle

MV – mitral valve

MRA – MR angiography

MRI – magnetic resonance imaging

CIR – circulatory insufficiency

PDA – patent ductus arteriosus

AoRC – aortic recoarctation

HF – heart failure

TBA – transluminal balloon angioplasty

ECG – electrocardiography

EchoCG – echocardiography

Terms and Definitions

Angiocardiography is an invasive diagnostic imaging method that involves the visualization of the heart chambers and blood vessels by administering a radiopaque agent into the bloodstream, directly measuring pressure in the heart chambers and blood vessels, obtaining blood samples from them to assess blood gas composition, and performing morphometric calculations based on the obtained radiopaque images of the cardiovascular system.

Computed tomography (CT) is a non-invasive diagnostic imaging method that produces a series of submillimeter cross-sectional axial images of human body organs and structures. It is based on the measurement and complex computer processing of differences in X-ray attenuation by tissues of varying density. Various contrast-enhancement techniques using iodine-based radiopaque agents are employed to improve the differentiation of organs from one another, as well as normal and pathological structures. To visualize the structures of the cardiovascular system, CT angiography is used—a technique involving the intravenous bolus injection of a radiopaque agent into the bloodstream using an automated contrast injection system at a predetermined flow rate and injection time. Based on the acquired data and through computer post-processing with 3D reconstruction, a three-dimensional model of the heart and blood vessels is constructed.

Magnetic resonance imaging (MRI) is a non-invasive, non-ionizing computerized method for producing tomographic medical images 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 placed in a strong constant magnetic field in response to excitation by a specific combination of electromagnetic waves; these nuclei are hydrogen atoms present in the human body as part of water and other substances. MR angiography is a method for imaging the lumen of blood vessels using a magnetic resonance scanner. The method makes it possible to evaluate both the anatomical and functional features of blood flow. MR angiography is based on the difference in signal between moving protons (blood) and surrounding stationary tissues, which allows for vascular imaging without the use of any contrast agents (non-contrast magnetic resonance angiography). In certain cases, intravenous bolus contrast enhancement using paramagnetic contrast agents (gadolinium) is applied.

Direct isthmoplasty is a method of aortic coarctation repair that involves a longitudinal incision of the aortic wall through the area of obstruction, followed by transverse closure of the incision.

Indirect isthmoplasty is a method of aortic coarctation repair that involves a longitudinal incision of the aortic wall through the area of obstruction, followed by sewing an autologous or heterologous (biological or synthetic) patch material into the resulting incision.

Transluminal balloon angioplasty (TBA) is an interventional radiology method for correcting obstructive vascular lesions by inflating a balloon at the tip of a specialized catheter—introduced percutaneously through a major vessel—within the lumen of the narrowed vessel.

Aortic isthmus is the segment of the aorta located immediately after the origin of the brachiocephalic vessels, connecting the aortic arch to the thoracic descending aorta,

Ductus-dependent lesion is a congenital heart defect in which the maintenance of adequate hemodynamics depends on the function of the patent ductus arteriosus. Clinical decompensation develops as the ductus arteriosus closes.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Aortic coarctation (CoA) is a congenital narrowing of the upper descending thoracic aorta bordering the insertion area of the patent ductus arteriosus (the so-called aortic isthmus). The most severe forms feature atresia of the aortic lumen while maintaining the continuity of the aortic wall.

Aortic coarctation is caused by the interposition of ductal tissue (DT), which forms a concentric fold resembling a membrane [1]. "Ductal tissue" refers to an accumulation of hyaluronic extracellular matrix—the so-called "neointima"—in the subendothelial layer of the intima of the arterial duct and adjacent structures [1,2,3].

Aortic recoarctation is a recurrence of blood flow obstruction along the aortic arch in the long-term period following surgical repair of CoA [4].

Morphological criteria of the defect [2-3,5-7]:

1. local narrowing of the aortic lumen at the border of the arch and the descending segment;

2. presence of a membrane (interposition of ductal neointima within the aortic wall) with or without an opening (hemodynamic interruption of the arch);

3. ductal tissue may exhibit varying degrees and directions of extension within the aortic wall (onto the descending segment and/or aortic isthmus), as well as invading the ostial regions of nearby brachiocephalic vessels—typically the left subclavian artery, less commonly the aberrant right subclavian artery or the left vertebral artery originating from a separate ostium.

4. the natural evolution of the CoA region is morphologically similar to the natural evolution of a patent ductus arteriosus: initially, the obstruction is caused by an excessive volume of DT, meaning the diameter of the aortic lumen does not correlate with its external transverse dimension; as the DT undergoes fibrous metamorphosis, its volume decreases, and the coarctation region assumes a characteristic hourglass shape.

5. the degree of persistence of the patent ductus arteriosus varies, up to complete closure of the duct in patients older than 1 month of life.

6. from the moment of natural closure of the patent ductus arteriosus in patients surviving this period, intersystemic collaterals continuously develop throughout their subsequent life;

7. turbulent blood flow distal to the obstruction site determines the potential for post-stenotic dilatation of this portion of the aorta;

8. in adult patients with the natural history of the disease, secondary extracardiac morphological changes develop due to systemic hypertension in the preductal aortic basin and the development of intersystemic collaterals.

Associated defects [8,9]:

1. patent ductus arteriosus—detected in all newborns with aortic coarctation and may subsequently remain patent (up to 33%) to varying degrees of significance, or close.

2. hypoplasia of the distal aortic arch segments; typically observed in patients with a non-restrictive ventricular septal defect that permits a left-to-right blood shunt; the hypoplastic segments of the aortic arch may have excessive length for a newborn (> 5 mm, tubular hypoplasia) and, less frequently, pathological tortuosity (kinking) [10-12].

3. bicuspid aortic valve (up to 60%);

4. ventricular septal defect (up to 48%);

5. single ventricle heart (up to 7%);

6. transposition of the great arteries (up to 6%);

7. atrioventricular septal defect (up to 4%);

8. various forms of double-outlet right ventricle, including Taussig-Bing anomaly (up to 3%);

9. other congenital anomalies of the heart and great vessels accompany aortic coarctation in less than 1% of cases.

10. CoA accompanies hypoplastic left heart syndrome in 80% of cases or more [13], although with this anatomy it should be considered one of the morphological components of the syndrome.

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

The genesis of CoA is associated with an excess amount of ductal-derived hyaluronic extracellular matrix in the subendothelial layer of the intima of the aortic segment immediately adjacent to the patent ductus arteriosus ostium (juxtaductal aorta, the border of the aortic arch and descending aorta, the border of the pre- and postductal segments of the embryonic aorta) [14].

Natural tissue metamorphosis of the aortic wall in the coarctation area resembles that of the patent ductus arteriosus wall. Immediately after birth, an increase in arterial oxygen partial pressure and a decrease in chorionic prostaglandin E2 levels lead to the production and accumulation of hyaluronic extracellular matrix ("neointima") in the subendothelial layer of the intima, which progressively reduces the vessel lumen, causing increasing blood flow obstruction up to complete occlusion.

Later, undifferentiated smooth muscle cell precursors that migrated into the neointima and transformed into fibroblasts cause connective tissue metamorphosis (thickening and volume reduction) of this tissue of ductal origin, resulting in the formation of a characteristic membrane in the aortic lumen ("maturation" of aortic coarctation).

The hemodynamics of aortic coarctation is characterized by obstruction of antegrade main blood flow at the border between the preductal and postductal embryonic segments of the thoracic aorta.

After birth, as the patent ductus arteriosus (PDA) closes, blood flow in the descending aorta changes from main ductus-dependent to main antegrade, which has varying degrees of deficit depending on the degree of obstruction.

In patients who survive natural closure of the PDA, the reduced main blood flow in the descending aortic basin is eventually compensated by collateral circulation.

In persistent PDA, the direction of blood shunting through it can change from right-to-left to bidirectional or left-to-right, depending on the nature and predominant localization of the obstruction in the aortic coarctation region.

Hemodynamics in the aortic basin proximal to the aortic coarctation region is characterized by progressive arterial hypertension, which determines the characteristic morphological changes of the main and peripheral vessels, as well as the left ventricle (LV).

LV changes are manifested by compensatory hypertrophy of its myocardium and, subsequently (or in case of severe obstruction), by dilation of its cavity.

The presence of a significant left-to-right shunt through a persistent PDA in aortic coarctation is accompanied by pulmonary hypervolemia and progressive pulmonary hypertension.

1.3 Epidemiology of the Disease or Condition

Aortic coarctation occurs in approximately 2 to 5 per 10,000 newborns, accounting to 6 – 7% of all detected congenital heart defects (CHD). Aortic coarctation in newborns is classified as a critical CHD. Ductus-dependent hemodynamics requires surgical treatment in the first weeks of the child's life. About 80% of all detected cases of aortic coarctation are not combined with any concomitant CHD. Aortic coarctation is 2 times more common in males [15-17].

1.4 Features of Coding the Disease or Condition

Q25.1 – Coarctation of aorta.

1.5 Classification of the disease or condition

Coarctation of the aorta:

1. With ductus-dependent hemodynamics:

   • Isolated (incl. with atrial septal defect)

   • With ventricular septal defect

   • With complex CHD

2. With hemodynamics independent of arterial duct persistence:

   • Isolated (incl. with atrial septal defect)

   • With ventricular septal defect

   • With complex CHD

3. Coarctation of the aorta with hypoplasia of the aortic isthmus:

   1. With ductus-dependent hemodynamics:

      • Isolated (incl. with atrial septal defect)

      • With ventricular septal defect

      • With complex CHD

   2. With hemodynamics independent of arterial duct persistence:

      • Isolated (incl. with atrial septal defect)

      • With ventricular septal defect

      • With complex CHD

4. Aortic coarctation with hypoplasia of the isthmus and distal aortic arch:

   1. With ductus-dependent hemodynamics:

      • Isolated (incl. with atrial septal defect)

      • With ventricular septal defect

      • With complex CHD

   2. With hemodynamics independent of arterial duct persistence:

      • Isolated (incl. with atrial septal defect)

      • With ventricular septal defect

      • With complex CHD [18]

1.6 Clinical presentation of the disease or condition

Critical coarctation of the aorta (preductal aortic coarctation): is characterized by "ductus-dependent" hemodynamics in the descending thoracic aorta. During natural closure of the arterial duct, manifestations of blood flow deficit dominate over symptoms of heart failure. Progressive ischemia is noted, which primarily affects the function of the kidneys and gastrointestinal tract, manifesting as a progressive decrease in urine output and weakening of gastrointestinal motility, followed by the development of multiple organ failure (cardiac, renal, hepatic, respiratory) against the background of tissue hypoxia. The prognosis for life in these cases is unfavorable, even if emergency surgery is performed.

The consequences of ischemic gastrointestinal injury appear later, typically among operated patients. In addition to intestinal tube dysfunction, they may manifest as the development of a number of life-threatening complications (gastrointestinal bleeding, necrotizing enterocolitis) in the early postoperative period.

Therefore, in this group of patients, it is important to medically maintain PDA function at the preoperative stage in patients with "ductus-dependent" hemodynamics [7,19-20].

Non-critical coarctation of the aorta. Heart failure determines the severity of the condition in infants with systemic hemodynamics independent of arterial duct function. Clinically, it manifests as general symptoms (tachycardia, tachypnea, acrocyanosis, crepitant rales in the lungs, cardiomegaly and hepatomegaly, peripheral edema) and symptoms typical of infancy (increased anxiety, sweating, fatigue during crying and feeding, underweight, anemia, etc.). There is a difference in the growth rate of the upper and lower halves of the body [7,19].

With age, the course of the disease transitions into a phase of relative compensation, primarily manifested by the development of numerous intersystem collaterals. The clinical picture of the disease is dominated by arterial hypertension recorded in the upper extremities. Patients complain of headaches, tinnitus, regular nosebleeds, visual disturbances (floaters, flashes in the visual field), and a tendency to bleed during injuries to the upper body. Depletion of myocardial compensatory resources is accompanied by heart failure [19,21-24].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for the disease/severity of the condition based on complaints/physical examination:

1. For critical aortic coarctation in the neonatal period, these are: progressive ischemia of the lower half of the body, which primarily affects the function of the kidneys and gastrointestinal tract and manifests as a progressive decrease in urine output and weakened gastrointestinal motility. A critical condition is also characterized by a weakening of the pulse (up to its complete absence) in the vessels of the lower extremities, a difference in blood pressure (measured on the arms and legs: blood pressure is lower on the legs or cannot be determined), and a difference in blood oxygen saturation between the upper and lower extremities of more than 3% according to pulse oximetry [8,19-20,25-26].

2. For non-critical aortic coarctation in patients under 1 year of age, these are: general signs (tachycardia, tachypnea, acrocyanosis, cardiomegaly and hepatomegaly, peripheral edema), signs of heart failure (dyspnea at rest or with exertion, palpitations, increased fatigue, poor appetite, delayed weight gain). In patients older than one year, the main criteria for CHD are arterial hypertension recorded in the upper extremities, complaints of headaches, tinnitus, regular nosebleeds, visual disturbances (floaters, flashes in the visual field), and a tendency to bleed during injuries to the upper body. A difference in the growth rates of the upper and lower halves of the body is noted [7,19,21,27-29].

2.1 Complaints and Anamnesis

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: in newborns with critical aortic coarctation and "ductus-dependent" hemodynamics, clinical deterioration develops in the first days of life due to increasing ischemia of internal organs in the descending aortic basin. This is primarily manifested by a progressive decrease in urine output and depression of gastrointestinal function. The deficit of ductus-dependent blood flow in the descending aorta is manifested by a weakening of the pulse (up to its complete absence) in the vessels of the lower extremities, a difference in blood pressure (BP) measured on the arms and legs (BP is lower on the legs or cannot be determined), as well as a difference in blood oxygen saturation between the upper and lower extremities [8,25-26].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: in infants with non-critical aortic coarctation, the clinical picture is dominated by signs of heart failure (HF) (dyspnea at rest or with exertion, palpitations, anxiety and increased fatigue, poor appetite, delayed weight gain, delayed physical development, pallor of the skin and mucous membranes, chest deformity in the form of a cardiac hump) [21,27-28].

Children aged 1 to 15 years usually have no complaints; aortic coarctation is discovered during a routine examination and screening for other reasons. At the same time, a murmur over the heart area and elevated blood pressure in the vessels of the upper half of the body are usually found (difference in the growth rates of the upper and lower halves of the body, headaches, tinnitus, regular nosebleeds, visual disturbances in the form of floaters, flashes in the visual field, tendency to heavy bleeding during injuries to the upper body). In patients who have survived infancy, complaints associated with manifestations of arterial hypertension predominate. Only 5% of patients at this age have signs of heart failure [27,29].

2.2 Physical Examination

• In children and adults, to determine the hemodynamic and clinical significance of aortic coarctation, it is recommended to perform symmetrical comparative palpation of peripheral arteries and measure blood pressure (BP) in all 4 limbs, followed by determining the difference between the obtained values [7,29-31].

            LoE 5, GoR C

Comments: Patients present with systolic arterial hypertension in the arms, and absence of normal asymmetry of systolic blood pressure between the upper and lower extremities (normally, SBP in the arms is lower than in the legs by 20 mm Hg or more). Blood pressure in patients with heart failure can only be measured after hemodynamic stabilization and IV infusion of inotropic drugs. In rare cases where the left subclavian and/or right aberrant subclavian arteries originate from the descending aorta, the diagnostic value of these signs is nullified. In newborns with compensated duct-dependent systemic blood flow in the descending aorta basin, pulsation and BP in the vessels of the legs may be comparable to those in the arms even with a critical degree of obstruction.

Comments: Detecting collateral pulsation is important in adult patients to rule out pathologies such as atherosclerotic occlusion of the abdominal aorta or femoral arteries.

            LoE 5, GoR C

• In children and adults with aortic coarctation, pulse oximetry of the upper and lower extremities is recommended [29–31].

            LoE 5, GoR C

Comments: if there is a difference in blood oxygen saturation of more than 3% between the right arm and the lower extremities, aortic coarctation should be suspected and additional instrumental diagnostics for congenital heart disease should be performed.

• Auscultation is recommended in children and adults with aortic coarctation. A systolic murmur heard along the left sternal border is characteristic of aortic coarctation, with the point of maximum auscultation located in the interscapular region to the left of the spine [27, 101].

LoE 5, GoR C for children

LoE 4, GoR C for adults

Comments: In symptomatic newborns the 2nd heart sound at the base of the heart is significantly accentuated, a «gallop rhythm» is frequent, a systolic murmur over the precordium is nonspecific and occurs in 50% of patients, and the murmur may increase against the background of hemodynamic stabilization. In asymptomatic newborns and older patients, the 2nd heart sound at the base of the heart is normal, its aortic component may be muffled, a medium-intensity (2–4/6) systolic ejection murmur is heard in the 2nd intercostal space to the right of the sternum and in the left interscapular region, and a diastolic murmur of bicuspid aortic valve regurgitation is sometimes heard in the 3rd intercostal space to the left of the sternum.

• In children and adults with aortic coarctation, it is recommended to assess peristalsis by abdominal auscultation, and assess intestinal pneumatosis and the presence of free fluid in the abdominal cavity in newborns by percussion and palpation [27].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: impaired blood flow in the descending aorta leads to intestinal dysfunction, which manifests as a sharp decrease or absence of peristalsis.

2.3 Laboratory Diagnostics

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: if there is a difference in blood oxygen saturation of more than 3% between the upper and lower extremities, aortic coarctation should be suspected and additional instrumental diagnostics for congenital heart disease should be performed.

2.4 Instrumental Diagnostics

• Transthoracic echocardiography (TTE) is recommended in children and adults with aortic coarctation: determining the severity and nature of obstruction at the border of the aortic arch and descending aorta, the presence and hemodynamic significance of a patent ductus arteriosus (PDA), aortic arch anatomy (arch position, diameter and length of each segment, origin pattern of brachiocephalic branches, presence of other structural features), dimensions of the ascending aorta and its valve annulus (including Z-score), aortic valve anatomy and hemodynamics (number and function of leaflets, stenosis/regurgitation), and assessing the degree of «mainline» blood flow in the abdominal aorta [19,29,31–32].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

• Duplex scanning of the arteries of the upper and lower extremities is recommended in children and adults with aortic coarctation to determine the pathological blood pressure gradient between the arms and legs, as well as to determine the nature of blood flow in the lower extremity arteries (mainline/collateral) [26,29,31, 110].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

• 24-hour ambulatory blood pressure monitoring is recommended in older children and adult patients with aortic coarctation to determine the severity of arterial hypertension and its clinical course [26–27,31, 110].

       LoE 5, GoR C

Level of Proof 5, Grade of Recommendation C

Comments: direct visualization of the arch and proximal descending thoracic aorta is often limited on transthoracic echocardiography; furthermore, in the presence of extensive collaterals, the severity of aortic coarctation obstruction is difficult to assess using Doppler echocardiography alone. In such cases, tomography helps determine or confirm the exact location, length, degree of obstruction, presence of hypoplasia, elongation, tortuosity, kinking without lumen narrowing, or aortic arch interruption, as well as the presence and development of collateral vessels, variant anatomy of thoracic aortic branches, and rules out vascular rings with tracheal and bronchial compression, and concomitant thoracic pathology. Multimodal imaging in patients with aortic coarctation increases the efficiency and quality of diagnostics; non-invasive and patient-safe research methods should be preferred. MRI is a universal method for assessing the aorta and pathologies associated with aortic diseases (applicable to patients with aortic coarctation: presence of a bicuspid aortic valve (BAV) and aneurysms of the aortic root and ascending aorta). MRI is recommended for pre-operative and post-operative assessment of the aorta, its branches, and adjacent structures. In addition to morphological changes, MRI provides accurate and reproducible functional data, including quantitative characterization of forward and reverse aortic blood flow, blood flow vector and velocity mapping, determination of the severity of blood flow obstruction, evaluation of aortic wall stiffness and elasticity, as well as the morphology and motion of aortic valve leaflets. The absolute advantages of the method are: non-invasiveness, the ability to obtain information without ionizing radiation exposure and, in some cases, without the need for intravenous contrast administration. When planning surgical correction of aortic coarctation and the need to use MRI, magnetic resonance angiography (MRA) is mandatory to obtain a three-dimensional dataset of the aorta and its branches. In critical patient conditions, lack of technical capability and/or qualified personnel to perform cardiac and vascular MRI with intravenous bolus contrast enhancement, and/or in the presence of absolute contraindications to MRI, it can be replaced by CT angiography; this is due to the wide availability, high acquisition speed, and high diagnostic efficacy of CTA in diagnosing aortic diseases. The high information yield and detail of three-dimensional models make it possible to predict the technical feasibility of various methods of surgical correction of aortic coarctation and, on this basis, choose the optimal surgical treatment tactics for each specific case.

• In complex congenital heart disease (CHD) or according to clinical indications, brain MRI (or CT, only in cases where this method is used, e.g., in patients with critical aortic coarctation) is recommended when planning surgical treatment of aortic coarctation to detect pathological changes that affect the results of surgical correction and may influence the choice of anesthetic and perfusion management [19,33–35,106].

Level of Proof 5, Grade of Recommendation C

• When aortic coarctation is combined with other congenital heart diseases requiring invasive diagnostics, transvenous cardiac catheterization with contrast media injection may be recommended as an alternative to contrast tomographic imaging [19,31,36].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: Aortic catheterization is performed in cases of interventional treatment (balloon angioplasty, aortic stenting). In patients with isolated aortic coarctation, diagnostic invasive radiopaque cardiac and aortic catheterization is not recommended [106].

• Patients with mild aortic coarctation (CoA) not requiring intervention are recommended to undergo annual transthoracic echocardiography and periodic (every 3–5 years) cardiac and magnetic resonance imaging (MRI) of the great vessels or computed tomography (CT) to monitor aortic dimensions [19,33-35,106].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: the same method and measurement protocol must be used for follow-up imaging. The protocol and measurement technique should be standardized.

—During routine examination, all patients based on clinical indications and/or patients with a history of arch hypoplasia are recommended to undergo cardiac and vascular MRI, with the timing and frequency determined on an individual basis (3–5 years) depending on annual echocardiographic findings.

In the presence of clinical manifestations, brain MRI and ultrasound / MRI of the brachiocephalic and renal vessels and kidneys with non-contrast MR angiography in the scanning protocol are additionally recommended to assess vascular anatomy and blood flow parameters.

—When planning repeat surgical interventions, all patients are recommended to undergo cardiac and great vessel MRI with intravenous bolus contrast enhancement (preferred) or cardiac and thoracic aorta CT with intravenous bolus contrast enhancement.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: patients with prior CoA repair require regular cardiovascular monitoring using imaging modalities (Echocardiography, ultrasound, MRI, CT) to assess clinical status and cardiovascular complications, such as recurrent CoA, dilatation of the ascending and descending thoracic aorta, and aortic dissection. Performing echocardiography or MRI of the heart, brain, kidneys, and vessels aims at early detection of potential long-term postoperative complications affecting the heart and extra-cardiac target organs. Scanning and MR image processing programs to obtain data on not only LV but also RV function, chamber morphometry, and vessel diameter at various levels without contrast administration provide comprehensive hemodynamic information. The protocol should include 3D MR angiography to assess the aorta and its branches, and delayed-enhancement myocardial MR imaging to identify foci of left and right ventricular fibrosis, which play a role in the onset of arrhythmias and the development of decompensation. Patients with complex recoarctation and/or comorbid cardiovascular diseases requiring surgical or endovascular intervention, such as coronary artery disease or aortic stenosis, require comprehensive imaging using MRI and/or CT methods.

2.5 Other Procedures

In pediatric and adult patients with CoA, other laboratory and instrumental diagnostic methods are not applied [27, 85, 90].

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

3.1 Conservative Treatment

• All newborns with CoA and ductus-dependent systemic circulation in the descending aorta are recommended to receive intravenous prostaglandin infusion [19, 37-40].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments:

• All newborns with CoA and ductus-dependent systemic circulation in the descending aorta are recommended to receive intravenous prostaglandin infusion [19, 37-40, 106-108].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: Prostaglandin infusion is continued until surgery [106-108].

• In infants with CoA and signs of heart failure, the following are recommended: energy expenditure restriction, including reduced work of breathing, inotropic therapy, balanced fluid intake (fluid administration below physiological requirements, with diuresis stimulation if necessary) [19,40].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: in non-progressive heart failure, it is optimal to use drugs from the alpha- and beta-adrenomimetic pharmacotherapeutic group without adrenergic and dopaminergic agents. However, if heart failure progresses, it is necessary to prescribe drugs from the adrenergic and dopaminergic pharmacotherapeutic group: dobutamine** or dopamine** is recommended (at initial doses from 2.5 mcg/kg/min with subsequent dose titration to achieve the desired effect); if the aforementioned drugs are insufficiently effective, additional administration of #epinephrine** is required (at an initial dose of 0.01 mcg/kg/min with subsequent titration under blood pressure and blood gas monitoring until the desired effect is achieved) [94-96].

• In children and adults with aortic coarctation, therapy with high doses of alpha- and beta-adrenomimetics and heart rate-lowering agents (cardiac glycosides) is not recommended [19,40].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

• If necessary, newborn patients with critical CoA and ductus-dependent circulation receiving prostaglandin E1 infusion are recommended to receive supplemental oxygen [19,40].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: patients with ductus-dependent circulation are not recommended to receive supplemental oxygen, as oxygen promotes ductus arteriosus closure. Prostaglandin infusion has the opposite effect—it maintains ductal patency. However, in cases of extreme critical condition (most often with concomitant respiratory pathology or associated congenital heart disease) and low blood oxygen saturation, supplemental oxygen may be administered to such patients with ductus-dependent circulation to stabilize their condition and transport them to a specialized cardiac surgery hospital.

• Newborns with borderline obstruction, left-to-right shunt via PDA, and absence of pulmonary hypertension are recommended to undergo clinical surveillance throughout the period of natural hemodynamic PDA closure [19,41-46].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

3.2 Surgical Treatment

The presence of aortic coarctation is an indication for surgical/endovascular treatment.

Surgical treatment of aortic coarctation is divided into surgical and endovascular treatment. Surgical correction techniques are represented by the following methods.

Patch aortoplasty with synthetic patches. Requires minimal aortic cross-clamp time and eliminates the formation of a continuous running whipstitch suture. However, this technique is characterized by a high incidence of not only aortic recoarctation but also a high risk of aneurysm formation with subsequent rupture potential (due to the inelasticity of synthetic materials and excessive pressure created on the opposite aortic wall). Due to the high probability of false aneurysm formation and residual arterial hypertension, this technique is currently very rarely used in both pediatric and adult patients [47-51].

Subclavian flap aortoplasty (indirect aortoplasty). This technique does not excise ductal tissue and the hypoplastic aortic arch segment. There is no need for extensive mobilization of the descending aorta and a continuous running whipstitch suture. However, ligation of the left subclavian artery leads to cerebral vascular insufficiency due to subclavian steal syndrome, impaired arterial blood supply and delayed growth of the left arm, as well as a high incidence of aortic recoarctation [52-54].

Extended end-to-end anastomosis The gold standard for treating aortic coarctation became the extended end-to-end coarctation resection technique proposed in 1977 by Joseph J. Amato [55], which effectively eliminates aortic arch hypoplasia, excises ductal tissue, preserves the subclavian artery, and allows adequate growth of the aortic arch. Over the past two decades, extended oblique end-to-end anastomosis has become the method of choice worldwide in infants under one year of age with or without aortic arch hypoplasia, as well as in adult patients. An aberrant right subclavian artery is the only procedural and recoarctation risk factor with this technique [48,56-60].

End-to-side anastomosis. In 1990, this technique was first applied in patients with aortic coarctation and proximal aortic arch hypoplasia by S. Sano and R. B. Mee (Royal Children's Hospital, Melbourne, Australia) [61]. Indications for this technique: 1) extensive hypoplasia of the proximal arch; 2) origin of the brachiocephalic trunk and left common carotid artery as a single trunk; 3) long, greater than 10 mm, marked hypoplasia of the distal arch. Since this technique requires a median sternotomy and cardiopulmonary bypass, simultaneous correction of intracardiac anomalies with arch reconstruction in the neonatal period is considered mandatory. The end-to-side anastomosis technique is associated with low mortality, a low incidence of aortic recoarctation, and arterial hypertension [62-63]. In older children and adult patients, this technique is not used.

Resection of aortic coarctation with graft replacement. Considering the lower tissue elasticity in adults and the absence of significant somatic growth, surgical correction of native coarctation in these patients most often requires the use of grafts (prostheses), as performing a direct anastomosis is frequently impossible (especially if the coarctation is long-segment or if there is hypoplasia of the proximal arch). In adult patients, lateral thoracotomy is preferred because they rarely have concomitant intracardiac pathology [64-65]. The main indications for resection of aortic coarctation with graft replacement in older children and adults are the presence of a long coarctation segment, hypoplasia of the pre- and/or post-stenotic aortic segments, and the presence of paracoarctation aneurysms.

Extra-anatomic bypass technique. It is used in adult patients with recoarctation, a long segment of narrowing in the distal arch and aortic isthmus, low cerebral ischemia tolerance during cross-clamping of the carotid arteries, and severe adhesions in the surgical area [66-68]. The method of choice for extra-anatomic surgery is aorto-aortic bypass from the ascending to the descending thoracic aorta via a right-sided thoracotomy.

• Emergency surgical correction of aortic coarctation is recommended for patients with critical (ductus-dependent) aortic coarctation regardless of the measured gradient across the aortic isthmus [19, 41-46, 106].

Level of Evidence 5, Strength of Recommendation C.

• Patients with stable hemodynamics independent of patent ductus arteriosus function and with a systolic blood pressure gradient at the site of aortic narrowing > 20 mm Hg are recommended to undergo elective surgical correction [19, 41-46, 106].

Level of Evidence 5, Strength of Recommendation C.

• Surgical or endovascular correction of aortic coarctation is recommended for patients with a systolic gradient across the aortic isthmus < 20 mm Hg in the presence of arterial hypertension (at rest, during exercise, or according to ambulatory blood pressure monitoring data) or significant narrowing of the isthmus (ratio of the narrowed aortic diameter to the aortic diameter at the diaphragmatic level < 80%) [19, 41-46, 106].

Level of Evidence 5, Strength of Recommendation C.

• Correction of isolated coarctation is recommended to be performed either via a lateral thoracotomy through the 3rd–4th intercostal space on the side of the aortic arch (i.e., in typical anatomy, to the left of the spine, access is via a left-sided lateral thoracotomy) or via a median sternotomy using cardiopulmonary bypass [19, 44-46, 69-73].

Level of Evidence 4, Strength of Recommendation C.

• The recommended method for coarctation correction in neonates and infants is resection of the obstructed segment (in neonates, with the maximal possible excision of aortic wall areas containing ductal tissue in the subendothelial layer) with creation of a direct, "oblique" end-to-end anastomosis (widened by additional longitudinal incisions of the coapted aortic segments) between the arch and the descending aorta, using suture material of the minimum permissible caliber (determined by the patient's weight and individual characteristics of the aortic wall) [19, 41-46].

Level of Evidence 4, Strength of Recommendation C.

• In cases of concomitant hypoplasia of the proximal aortic arch in neonates and infants, creation of a direct end-to-side anastomosis between the descending aorta and the ascending aorta under cardiopulmonary bypass is recommended [61-63, 74-75].

Level of Evidence 4, Strength of Recommendation C.

Comment: in older children and adults in such cases, the method of choice is extra-anatomic bypass from the ascending to the descending thoracic aorta [93].

• Correction via direct isthmoplasty in neonates with preservation of ductal tissue or a membrane of ductal origin is not recommended due to the high risk of residual and/or recurrent obstruction [19, 46, 52-54].

Level of Evidence 5, Strength of Recommendation C.

Comments: due to the high risk of residual and/or recurrent obstruction.

• Correction via patch aortoplasty (indirect isthmoplasty) is not recommended in neonates, older children, or adults [19, 46-51].

Level of Evidence 4, Strength of Recommendation C.

Comments: besides recurrence of obstruction due to persistent ductal tissue/membrane, it carries the risk of false aneurysm formation in the long-term postoperative period.

• Correction via subclavian flap aortoplasty according to Waldhausen–Nahrwold is not recommended in neonates due to the persistence of ductal tissue/membrane, the probability of aneurysm formation in the long-term postoperative period, the risk of vertebral-basilar subclavian steal syndrome via the vertebral artery, and the loss of the main blood supply pathway to the left arm [19, 52-54, 76-77].

Level of Evidence 4, Strength of Recommendation C.

Comments: if indirect isthmoplasty is performed, in order to avoid vertebral-basilar subclavian steal syndrome via the vertebral artery and the loss of the main blood supply to the left arm, it is advisable to perform reimplantation of the severed subclavian artery into the left common carotid artery.

• The use of biological or synthetic conduits for aortic reconstruction during coarctation correction in early childhood is not recommended [19, 76-77].

Level of Evidence 5, Strength of Recommendation C.

• Adult patients with aortic coarctation and clinical manifestations due to left ventricular dysfunction, severe arterial hypertension, or lower limb ischemia are recommended to undergo open surgical or endovascular interventions [29, 31].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

3.3 Interventional radiology treatment

There are two methods of percutaneous endovascular treatment for patients with aortic coarctation and recoarctation: transluminal balloon angioplasty and stenting.

3.3.1 Transluminal balloon angioplasty

• Transluminal balloon angioplasty is recommended as the method of choice in the treatment of aortic recoarctation (with a systolic pressure gradient >20 mm Hg) after open surgical correction, regardless of the patient's age [19, 36, 41-45, 97-99].

Level of Proof 5, Grade of Recommendation C

• Balloon angioplasty of recoarctation is recommended with a systolic pressure gradient across the aortic isthmus <20 mm Hg in the presence of large collateral vessels in children, as well as in patients with complex congenital heart disease (single ventricle, double-outlet right or left ventricle, etc.) or significant ventricular dysfunction [36, 97-99].

Level of Proof 5, Grade of Recommendation C

• Transluminal balloon angioplasty of coarctation is recommended in children older than 1 year with an "adult-type" coarctation without concomitant aortic arch hypoplasia and with moderately severe, localized ("hourglass") obstruction [19, 29, 36, 97-99].

Level of Proof 5, Grade of Recommendation C

Level of Proof 5, Grade of Recommendation C

• Transluminal balloon angioplasty of coarctation in infants with concomitant aortic arch hypoplasia is not recommended [41-47, 77].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: complications such as aortic dissection and rupture are extremely rare during transluminal balloon angioplasty. In the postoperative period following transluminal balloon angioplasty, the incidence of restenosis ranges from 18% to 53%, and aortic aneurysm formation may occur (6-55%) [47, 51, 78-81, 97-99].

3.3.2 Stenting

Two stenting technologies are used: bare-metal stents and covered stents.

• Stenting is recommended for all patients with aortic recoarctation and a systolic pressure gradient across the isthmus >20 mm Hg, if the isthmus anatomy, patient age, and weight allow for the implantation of a stent that can subsequently be dilated to adult aortic dimensions [36, 97, 100-101].

Level of Evidence 5, Strength of Recommendation C

• Stenting of aortic coarctation or recoarctation is recommended on par with surgical treatment in adult patients with arterial hypertension and a gradient >20 mm Hg across the aortic isthmus [31, 36, 102-105, 110].

Level of Evidence 5, Strength of Recommendation C

Comments: performing coarctation and recoarctation stenting in children under 10 years of age requires repeat redilatation in the long-term period due to somatic growth of the patient [82-84, 97, 100-101].

• Stenting is recommended for all patients with aortic coarctation and a systolic pressure gradient across the isthmus >20 mm Hg, if the isthmus anatomy, patient age, and weight allow for the implantation of a stent that can subsequently be dilated to adult aortic dimensions [36, 97, 100-101].

Level of Evidence 4, Strength of Recommendation C

Comment: Stenting demonstrates higher efficacy compared to isolated balloon angioplasty. Stenting is rarely used in neonates due to the impossibility of implanting a stent that can be subsequently dilated to adult size. Stenting has gradually become the procedure of choice in older children and adults, except in cases where coarctation is combined with hypoplasia of the aortic isthmus or arch, tortuosity of the isthmus, or tubular aortic coarctation. However, even with such combinations, stenting using covered stents is possible. In patients with critical aortic coarctation, covered stents must also be used to prevent potential complications (aneurysm formation and aortic rupture). Covered stents can be used when aortic coarctation is combined with a patent ductus arteriosus for simultaneous correction of the defects [97, 100, 101]

• Stenting is not recommended for children weighing less than 15 kg due to the size of the delivery systems and the necessity of passing them through the femoral artery (this leads to a high risk of femoral artery injury with subsequent probable development of thrombosis in the damaged femoral artery) [31,36,82-84,103-105].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comment: In the presence of a VSD, stenting of aortic coarctation and recoarctation in children via a transvenous approach is possible to prevent potential arterial thrombosis [97,100,101].

• Stenting of the aortic isthmus is recommended in exceptional cases in neonates and infants following ineffective surgical or endovascular procedures, if reoperation carries a high risk [36, 97].

Level of Proof 5, Grade of Recommendation C

Comments: implantation of a stent whose diameter cannot be expanded to the diameter of the adult aorta obligates the surgical team to subsequently remove such a stent when its maximum diameter begins to limit blood flow through the aorta [36, 97].

3.4 Other treatment

No.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• Patients following surgical correction of CoA are recommended to avoid traction loads on the upper extremity on the side of the postoperative suture for the subsequent 4–6 months of life [19, 27].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

• Infants following surgical correction of CoA are recommended to avoid therapeutic gymnastics procedures for the subsequent 4 months [19, 27].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

5. Prevention and Dispensary Observation

• Patients who have undergone surgical correction of CoA are recommended to undergo examination at least twice during the first year after surgery (consultation with a pediatric cardiologist or cardiologist, echocardiography). Subsequently, if there is no need for reoperation, follow-up can be performed at the place of residence at least once a year [41,69].

Level of Proof 5, Grade of Recommendation C

Comments: the most significant long-term complication after surgery is the development of restenosis in the surgical area—recoarctation, which in turn can trigger other complications such as arterial hypertension, development of aortic and cerebral aneurysms, left ventricular dysfunction, arrhythmias, and cerebrovascular accidents. Patients who have undergone repair of aortic coarctation remain under the constant threat of developing aortic recoarctation. Even after a successful operation, patients must remain under the lifelong supervision of a cardiologist. Routine examinations should include annual outpatient 24-hour blood pressure monitoring and echocardiography with measurement of the dimensions of the proximal and distal aortic arch calculated using Z-scores, and measurement of the peak Doppler pressure gradient [85-86].

• All patients with a history of surgical repair of aortic coarctation are recommended to undergo dynamic follow-up for the timely detection of complications [41,69].

Comments: in case of detection of recurrent obstruction, the schedule for the next outpatient examination or inpatient admission is determined by the cardiologist.

Level of Proof 5, Grade of Recommendation C

• Patients following surgical correction of CoA are recommended to have their blood pressure measured on both upper and lower limbs to assess the pressure gradient and the efficacy of the performed surgery, as well as the appropriateness of prescribing/continuing antihypertensive drug therapy [41,69].

Level of Evidence 5, Strength of Recommendation C

Comments: the most common complication is the development of arterial hypertension, which affects up to half of patients by the age of 40 [47,87-88].

• Patients following surgical correction of CoA, in the case of persistent residual arterial hypertension, are recommended to undergo examinations and treatment in accordance with the clinical guidelines for arterial hypertension [19, 27, 109].

Level of Evidence 5, Strength of Recommendation C.

• Patients following surgical correction of CoA, as part of an outpatient echocardiographic examination, are recommended to evaluate the blood flow pattern in the aortic arch, the presence of a pressure gradient in the anastomosis area, morphofunctional parameters of the left ventricle and mitral valve, as well as the aortic valve and subaortic region [41,69].

Level of Proof 5, Grade of Recommendation C

6. Organization of Medical Care

Stages of medical care and indications for hospitalization:

1. clarification of the diagnosis;

2. in case of confirmation of "critical" aortic coarctation, initiation of conservative therapy and arrangement of emergency transfer to a cardiosurgical hospital for urgent surgical care immediately after medical stabilization of the clinical condition;

3. asymptomatic forms of aortic coarctation—close to physiological pressure gradient values at the isthmus in neonates and a "borderline" degree of obstruction in older patients (greater than 20 mmHg)—require dynamic monitoring.

4. the indication for surgical treatment of aortic coarctation is any clinically manifesting form of the pathology. Therefore, if clinical manifestations of aortic coarctation are initially absent and the clinical picture develops with a delay, transfer of patients to a specialized cardiosurgical hospital is also recommended to determine further management tactics.

Basics of conservative therapy

• The key role in preoperative conservative therapy for «critical» coarctation of the aorta is given to intravenous infusion of prostaglandins PGE1 maintaining patency of the ductus arteriosus;

• The criteria for the effectiveness of preoperative conservative therapy are the normalization of acid-base balance, regression of serum lactate levels, a trend toward normalization of diuresis, and a reduction in blood plasma residual nitrogen levels.

7. Additional Information

In the neonatal period, the severity of the patient's condition with obstructive anomalies of the aortic arch development and the prognosis of the natural course of the disease are determined by the following factors:

1. The nature of blood flow in the descending aorta basin: it can be "ductus-dependent" or compensated main-vessel flow. In the second case, even with the closure of the ductus arteriosus, adequate blood supply to the lower half of the body is provided through the narrowed aortic isthmus. Developed intersystem collaterals capable of providing compensated collateral blood flow in the descending aorta are, as a rule, absent in newborns.

2. "Left-to-right" blood shunting through a non-restrictive VSD or aortopulmonary window exacerbates the severity of the patient's condition and the prognosis.

3. Features of intracardiac anatomy: an isolated form of coarctation generally has a more favorable course and prognosis than its combination with a septal defect (VSD, aortopulmonary window) and, even more so, aortic arch interruption. Complex intracardiac anatomy, both in coarctation and in arch interruption, makes the prognosis much more guarded.

4. Among extracardiac risk factors, low birth weight, prematurity and morphofunctional immaturity at birth, perinatal infection, concomitant extracardiac malformations, and stigmata of dysembryogenesis should be highlighted [19,89-92].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Avramenko AA (Samara)

2. Alekyan BG, Academician of the RAS (Moscow), "Russian Scientific Society of Interventional Radiology and Endovascular Diagnostics and Treatment"

3. Arakelyan VS, Prof. (Moscow)

4. Bogdanov VN (Chelyabinsk)

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

6. Boriskov MV, DSc (Krasnodar)

7. Brodsky AG, PhD (Surgut)

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

9. Grigoryan AM, PhD (Moscow), "Russian Scientific Society of Interventional Radiology and Endovascular Diagnostics and Treatment"

10. Gorbatikov KV, DSc (Tyumen)

11. Gorbatykh YuN, DSc (Novosibirsk)

12. Esayan AA, PhD (Moscow)

13. Kalashnikov SV, PhD (Moscow)

14. Kim AI, Prof. (Moscow), "Association of Cardiovascular Surgeons of Russia"

15. Kovalev IA, DSc (Moscow), "Association of Pediatric Cardiologists of Russia"

16. Kokshenev IV, Prof. (Moscow), "Association of Cardiovascular Surgeons of Russia"

17. Krivoshchekov EV, DSc (Tomsk), "Association of Cardiovascular Surgeons of Russia"

18. Kupryashov AA, Prof. (Moscow)

19. Levchenko EG, DSc (Moscow)

20. Movsesyan RR, Corresponding Member of the RAS (Saint Petersburg), "Association of Cardiovascular Surgeons of Russia"

21. Nalimov KA, PhD (Khabarovsk)

22. Petrushenko DYu, PhD (Kazan)

23. Plotnikov MV, PhD (Astrakhan), "Association of Cardiovascular Surgeons of Russia"

24. Svobodov AA, Prof. (Moscow)

25. Sinelnikov YuS, DSc (Perm)

26. Teplov PV (Krasnoyarsk)

27. Trunina II, Prof. (Moscow), "Association of Pediatric Cardiologists of Russia"

28. Alexandrova SA, PhD (Moscow), All-Russian Public Organization for Assistance to the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists"

29. Baryshnikova IYu, PhD (Moscow), All-Russian Public Organization for Assistance to the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists"

30. Bergen TA, DSc (Novosibirsk), All-Russian Public Organization for Assistance to the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists"

31. Rychina IE, PhD (Moscow), All-Russian Public Organization for Assistance to the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists"

32. Sinitsyn VE, DSc, Prof. (Moscow), All-Russian Public Organization for Assistance to the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists"

33. Yurpolskaya LA, DSc (Moscow), All-Russian Public Organization for Assistance to the Development of Diagnostic Radiology and Therapy "Russian Society of Radiologists"

No conflict of interest. All members of the Working Group confirmed the absence of financial support/conflict of interest that needs to be disclosed.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Pediatrician

2. Cardiologist

3. Pediatric Cardiologist

4. Radiologist

5. Ultrasound Diagnostics Physician

6. Functional Diagnostics Physician

7. Cardiovascular Surgeon

8. residents.

Methods used for collecting/selecting evidence: electronic database search.

Description of methods used to assess the quality and strength of evidence: the evidence base for the guidelines includes publications indexed in the PubMed and Scopus databases. The literature search depth was 30 years.

Methods used to assess the quality and strength of evidence

· expert consensus;

· evaluation of the quality of recommendations in accordance with the rating scheme (Table А1).

· evaluation of the strength of evidence in accordance with the rating scheme (Table А2).

During the development of the clinical guidelines, a new grading system for levels of evidence (LE) and grades of recommendation (GR) for therapeutic, rehabilitative, preventive, and diagnostic interventions was used (Tables P1, P2, and P3), introduced in 2018 by the Center for Healthcare Quality Assessment and Control of the Russian Ministry of Health. The National Guidelines were formulated based on the ESC guidelines, taking into account national specifics, diagnostic and treatment features, and the availability of medical care.

Table P1. Scale for grading levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table P2. Scale for grading levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table А3

Grading system for the levels of evidentiary certainty (LEC) of recommendations for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

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

Appendix A3. Reference Materials

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

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. "On the classification and criteria used in the implementation of medical and social evaluation of citizens by federal state institutions of medical and social evaluation" (Order of the Russian Ministry of Health No. 1024n of December 17, 2015)

4. Order of the Russian Ministry of Health No. 103n of February 28, 2019, "On approval of the procedure and deadlines for the development of clinical guidelines, their revision, the standard form of clinical guidelines and requirements for their structure, composition and scientific validity of the information included in clinical guidelines" (Registered with the Russian Ministry of Justice on May 8, 2019, No. 54588);

5. Order of the Ministry of Health of the Russian Federation No. 203n of May 10, 2017, "On approval of criteria for evaluating the quality of medical care";

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

7. Order of the Ministry of Health of the Russian Federation No. 700n of October 7, 2015, "On the nomenclature of specialties of specialists with higher medical and pharmaceutical education"; Order of the Russian Ministry of Health No. 1183n of December 20, 2012 (as amended on August 1, 2014) "On approval of the Nomenclature of positions of medical and pharmaceutical workers";

8. Order of the Russian Ministry of Health No. 4n of June 6, 2012 (as amended on September 25, 2014) "On approval of the nomenclature classification of medical devices"

9. Order of the Russian Ministry of Health No. 560n of June 9, 2020, "On approval of the Rules for performing X-ray examinations"

Transthoracic echocardiography performance technique

Requirements:

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

Contraindications: none.

Limitations: cases of an inadequate acoustic window

Important indicators when analyzing and interpreting the obtained images:

Performance of transthoracic echocardiography

Overview echocardiography (prior to aortic examination) to rule out associated congenital heart disease, assess heart size and contractile function, and evaluate valve competence (mitral and aortic). Measurement of the left ventricular (LV) end-diastolic dimension and quantitative assessment of LV contractile function are performed in M-mode from the left parasternal approach in the LV long-axis or short-axis view at the level of the mitral valve (MV) leaflet tips, which serve as a reference point for cursor placement perpendicular to the line of MV leaflet coaptation. Measurements are taken from the posterior surface of the interventricular septum to the anterior surface of the LV posterior wall. Visual assessment of the LV: from the apical four-chamber view in comparison with the right heart chambers. Left parasternal approach: assessment of the aortic valve annulus diameter in the long-axis view, along with the dimensions of the aortic root and ascending aorta.

Ascending aorta (in infants), aortic arch and isthmus, proximal part of the thoracic aorta: suprasternal approach.

Descending aorta: assessment at or below the diaphragm level, but not close to the mesenteric vessels using pulsed-wave Doppler. Particular attention should be paid to aligning the ultrasound beam with the long axis of the descending aorta. Sign of coarctation of the aorta (CoA): altered (non-master, collateral) flow in the abdominal aorta and a decrease in the maximum linear blood flow velocity (norm in newborns is 60–80 cm/s with ultrasound beam angle correction). On the Doppler spectrogram: low-velocity systolic-diastolic flow with minimal phase changes. In adolescents and adults, a maximum velocity of less than 50 cm/s and a diastolic flow velocity in the descending aorta of more than 25 cm/s indicate collateral blood flow.

To diagnose CoA, it is necessary to consider a combination of hemodynamic parameters (systolic pressure gradient in the narrowing area, linear blood flow velocity, and flow spectrum in the abdominal aorta), anatomical features of the aortic structure, and associated pathology.

Quantitative assessment:

Z-score. A Z-score of less than -2 and an aortic isthmus diameter of less than 50% of the abdominal aorta diameter are also criteria confirming aortic arch and isthmus hypoplasia.

Compare the diameters of the ascending aorta to the diameter of the aortic arch segment of interest. CoA: less than 60% for the proximal arch segment; less than 50% for the distal arch segment; less than 40% for the aortic isthmus.

Formula for the normal diameter of the newborn aortic isthmus: normally, the minimum transverse size of the aortic isthmus should equal the newborn's body weight + 1 mm.

Important indicators in the analysis and interpretation of the obtained images:

·               aortic arch type (right/left);

·               presence/absence of obstructive changes in the aortic arch;

·               localization of aortic narrowing;

·               type of coarctation;

·               dimensions, pulsation, intensity, and comparison of antegrade and retrograde blood flow in pre- and post-stenotic aortic segments;

·               in color Doppler mapping mode: accelerated turbulent blood flow at the site of narrowing (determination of the systolic pressure gradient – indirectly reflects the severity of coarctation).

Particular attention should be paid to:

The maximum (peak) systolic pressure gradient (the measurement cursor is placed immediately distal to the obstruction area) of more than 20 mmHg with a typical "jagged" pattern on the spectrogram.

Difficulties: hemodynamic decoupling of the thoracic aorta distal to the 3rd brachiocephalic vessel in the presence of a large patent ductus arteriosus. During Doppler examination, due to decreased flow velocity and volume through the obstruction area, underestimated hemodynamic characteristics are possible: in the presence of well-developed arterial collaterals; a patent ductus arteriosus; aortic arch hypoplasia; decreased ventricular systolic function; hemodynamically significant atrioventricular valve regurgitation. Overestimated gradient values are possible: with a moderate increase in descending aorta flow velocity due to normal acceleration in the aortic arch after surgical intervention without signs of vessel narrowing; an increase in systolic flow velocity and its turbulence due to the lack of aortic rigidity in the patch area in the absence of significant narrowing.

Technique of cardiac and thoracic aorta CT angiography with intravenous contrast enhancement

Conditions for the procedure

CT is performed in medical facilities providing medical care in the profile of "cardiovascular surgery" and having experience in cardiac and vascular CT examinations in children and adults with congenital heart defects. CT is performed in a CT room using an intravascular contrast agent (CA) injection system.

Specialists performing CT: radiologist, radiologic technologist; anesthesiologist-resuscitologist when examining young children or critically ill patients.

CT is performed as prescribed by the attending physician. The referral content includes clearly stated goals of the study, the glomerular filtration rate (GFR) or creatinine level, and a mandatory indication of the presence or absence of contraindications to contrast agents in the patient.

Required technical parameters

-              computed tomography scanner with at least 64 detector rows (multi-detector scanners and dual-source scanners are preferred),

-               intravascular CA injection system (dual-syringe models are preferred).

Before performing aortic CTA:

-               placement of a peripheral venous catheter,

-               absence of contraindications to CA administration (allergies, severe renal impairment, etc.),

-               the study is preferably performed on an empty stomach (at least 3 hours after a meal),

-               evaluation of previous radiological or instrumental examination data,

- availability of an echocardiography report.

Aortic CTA protocol:

Patient positioning: supine (with arms raised above the head if possible).

Scan area: thorax from a level below the diaphragm (mid-liver) to the origin of the brachiocephalic vessels. Minimum scan range: from the aortic arch, including the origin of the brachiocephalic trunk, to 1-2 cm below the cardiac apex; the range may vary depending on clinical requirements (e.g., visualization of vascular access for an endovascular procedure). For peripheral access planning, the scan is performed without ECG gating: 1 for femoral access – abdominal aorta from the celiac trunk to the femoral head; 2 for subclavian access – from the origin of the subclavian artery to the anterior midline; 3 for combined access – from the origin of the subclavian artery to the femoral head.

ECG gating: yes.

Non-contrast scan: no.

Breath-holding: on inspiration.

Intravenous contrast administration: in all cases.

It is preferable to use a dual- or triple-phase contrast injection protocol, involving the administration of 10-30 ml of saline as the first phase, contrast agent as the second phase, and saline as the third phase. More complex contrast administration protocols may also be used.

A contrast agent with an iodine concentration of 300-400 mg/ml (most commonly 350-370 mg/ml) is used.

Selection of contrast agent and saline injection rates

1. Contrast injection rate – depending on the tube voltage.

2. Contrast volume = scan time + technical delay + 2 × contrast injection rate

3. Monitoring: at the ascending aorta 120-140 HU using bolus tracking techniques (BolusTracking, SureStart, SmartPrep).

4. Scan range: entire thorax – 1 ECG-gated series + a non-gated series after 25 seconds if a venous contrast phase is required.

5. 0.75 mm reconstructions using an angiographic filter.

Injection rates for adult patients

Pediatric scanning

1. Contrast injection rate:

· at 70 kV scan settings – injection rate: 0.6–0.7 ml/s

· at 80 kV scan settings – injection rate: 0.8 ml/s

· at 100 kV scan settings – injection rate: at least 1 ml/s

2. Contrast volume for 70 kV scans = weight + 2. Contrast volume for scans at 80 kV and above = weight × 2

3. Scan range – entire thorax. 1 ECG-gated series + non-gated series after 10-15 sec may be used.

4. Contrast monitoring: start at the left atrium – at 70 kV – 80 HU, at voltages above 80 kV – 60 HU using bolus tracking techniques (BolusTracking, SureStart, SmartPrep).

Automatic scan triggering upon reaching a target density threshold of >120 HU above baseline in the region of interest is possible (e.g., in the lumen of the descending aorta at the level of the tracheal bifurcation, distal to the stenosis; note that this approach does not guarantee optimal opacification of the heart and great vessels in newborns and young children).

Key points for image interpretation: universal segmental analysis of the anatomy of the heart and great vessels; morphometry of the vessels and cardiac chambers; location, dimensions, and severity of aortic obstruction; position of the arch and branching pattern of the brachiocephalic arteries; presence and dimensions of PDA; morphology of the aortic valve; presence of aneurysm, dissection, or collateral vessels of the descending aorta; calculation of functional parameters of the right and left heart chambers depending on the study objectives; topographical anatomy of the heart and vessels (when choosing the surgical approach); analysis of images of other thoracic organs to detect concomitant extracardiac pathology; for patients after surgical or endovascular operations, analysis to assess the results of interventions and check for complications.

Cardiac and great vessel MRI with intravenous bolus contrast enhancement

Conditions for the procedure

MRI is performed in specialized medical institutions with experience in cardiac and vascular MRI studies in children and adults with congenital heart disease (CHD). MRI is performed in the MRI suite using an intravascular contrast agent (CA) injection system.

Specialists performing MRI: radiologist, radiographer; anesthesiologist-resuscitator when performing the study in young children or critically ill patients.

MRI is performed as prescribed by the attending physician. The referral contains clearly stated objectives of the study, the necessity of contrast administration, the glomerular filtration rate (GFR) or creatinine level, and a mandatory indication of the presence or absence of contraindications to contrast agents in the patient.

Required technical parameters

- magnetic resonance imager with a field strength of at least 1.5 T

- necessary technical equipment for cardiac MRI studies (surface multichannel coils, head coil, ECG gating, cardiac software package for scanning and post-processing of cardiac and vascular MR images with blood flow parameter calculation capabilities)

- if contrast administration is necessary, an intravascular CA injection system (dual-syringe models preferred)

- availability of appropriate non-magnetic life support and monitoring equipment when performing MRI studies in infants, young children, and critically ill patients under anesthesia or deep sedation

MRI procedure: the study is performed in the absence of contraindications; with intravenous contrast enhancement - on an empty stomach; any available vein is used to place a peripheral catheter (cubital vein preferred).

Patient positioning: supine

Intravenous contrast enhancement: the dose of the contrast agent is calculated individually in each specific case and depends on the clinical situation, purpose, and body weight (mmol/kg); approximate doses are given in the table (Table 1)

Table 1 Standard contrast-enhanced MR protocol

Region of interest: thorax from below the diaphragm level (mid-liver) to the origins of the brachiocephalic vessels

Scanning protocol

Mandatory sequences

1. Scout in 3 standard planes for subsequent positioning

2. Module for assessing defect anatomy (spin echo)

3. Cine MRI: long-axis plane of the aortic arch with visualization of the entire thoracic aorta and origins of the brachiocephalic arteries

4. Module for function assessment (cine MRI): in 2- and 4-chamber LV planes, along the short axis of the heart (series of slices through the entire heart)

5. Non-contrast 3D MR angiography of the aorta (SSFP) or IV bolus contrast-enhanced MR angiography (Angio-3D in the coronal plane); the scan range must cover the entire thoracic aorta with brachiocephalic vessels. Post-processing includes maximum intensity projection (MIP) and volume-rendered reconstructions (VRT)

6. Phase-contrast sequence for quantitative assessment of blood flow parameters; slices are set at the following levels of the thoracic aorta: aortic valve, ascending aorta, arch (additionally in the area of hypoplasia, if present), isthmus, descending aorta below the coarctation, and descending aorta at the diaphragmatic level, as well as in the pulmonary trunk, approximately VENC = 120-250 cm/sec, depending on the degree of stenosis

Additional sequences

7. Spin echo: long-axis plane of the aortic arch

8. Cine MRI: short-axis plane of the aortic root for morphology

9. Delayed LV and right ventricular myocardial contrast enhancement module (in 2- and 4-chamber planes, along the short axis of the heart at 3 levels)

Comment: slice thickness is selected depending on the size of the area of interest and the patient's age (usually 5-7 mm)

Key points of image interpretation: Segmental analysis of the anatomy of the heart and vessels; morphometry of vessels and cardiac chambers; location, dimensions, and severity of aortic obstruction; arch location and branching pattern; presence of aneurysm, dissection, or collateral vessels of the descending aorta; peak and volumetric blood flow velocity parameters at the studied levels of the thoracic aorta; ventricular parameters including left ventricular myocardial mass, absolute and body surface area-indexed values; right and left ventricular ejection fraction; aortic valve morphology, degree of stenosis and regurgitation; when performing delayed myocardial enhancement, the presence, location, pattern, and type of contrast agent uptake must be specified.

MRI of the brain, kidneys, brachiocephalic arteries, and renal vessels

Required technical parameters

- magnetic resonance imager with a field strength of at least 1.5 T

- necessary technical equipment for MRI studies (surface coils: for head, neck vessels; for kidneys and renal vessels; if contrast administration is necessary, an intravascular CA injection system, software for scanning and processing images of the brain, kidneys, and vessels with blood flow parameter calculation capabilities)

- availability of appropriate non-magnetic life support and monitoring equipment when performing MRI studies in infants, young children, and critically ill patients under anesthesia or deep sedation

MRI procedure

The study is performed in the absence of contraindications; if contrast administration is necessary - on an empty stomach; any available vein is used to place a peripheral catheter (cubital vein preferred).

Patient positioning: supine

Brain scanning protocol children under 6 months: mandatory inclusion of a 3D T1-weighted imaging block, dual-echo images, axial slice block of diffusion-weighted images, T2*/SWI. Age over 6 months: mandatory inclusion of axial T2-weighted imaging block, T1-weighted images (preferably 3D T1); inversion-recovery FLAIR coronal slice block; axial slice block of diffusion-weighted images, T2*/SWI block.

Brachiocephalic artery MRI: non-contrast angiography (time-of-flight (TOF) or phase-contrast angiography (PC)) with venous blood suppression, scan range from the bifurcation of the common carotid arteries including intracranial arteries with 3D reconstructions to assess the anatomy of extracranial segments and the circle of Willis. Contrast agent administration as indicated.

Key points for image interpretation: anatomy of the extracranial and intracranial segments of the brachiocephalic arteries with a mandatory description of the anatomy of the circle of Willis, noting whether it is complete (closed).

MRI of the kidneys and renal vessels with mandatory inclusion of T1 and T2 images of the kidneys in transverse, coronal, and sagittal planes. To assess blood flow velocity parameters in renal vessels, a phase-contrast scanning sequence is used; the encoding velocity is selected individually depending on the blood flow velocity: on average, in the absence of stenosis, VENC for arteries = 40-80 cm/sec, for veins = 30-40 cm/sec; slices are oriented "perpendicular" to the vessel: renal artery at the level prior to its branching into segments, and the vein.

Key points for image interpretation: mandatory indication of kidney dimensions, presence of accessory arteries, course of veins and arteries, their diameters, description of the renal hilum, parenchymal status, pelvicalyceal system, cortical thickness, and medullary status. Blood flow parameters analyzed include blood volume per second and peak blood flow velocity at the described levels.

Appendix B. Physician Action Algorithms

Diagnostic algorithm for aortic coarctation (CoA)

Management algorithm for patients with hemodynamically significant CoA

Management algorithm for patients with hemodynamically insignificant (borderline degree of obstruction) CoA

Use of diagnostic imaging methods in suspected aortic coarctation and the management of patients with aortic coarctation

Appendix C. Patient Information

Dear patient (patient's parents), the diagnostic results have revealed a congenital heart defect in you (your child) – aortic coarctation. By voluntarily consenting to the surgery, you must understand the purpose and risks of the operation, which your attending physician will explain to you.

The prerequisites for the development of juvenile coarctation of the aorta (CoA) are laid down during the prenatal period. Their causes are numerous. Possible risk factors include intrauterine infection, maternal viral infections in the first trimester of pregnancy, parental bad habits, environmental and hereditary factors, etc. Depending on the degree of obstruction to aortic blood flow, the presence and nature of concomitant cardiac anomalies, hemodynamic disturbances, and clinical manifestations of the defect can vary significantly. The need for surgical treatment may arise in the first days of your child's life, at a later date, or surgery may not be required at all. In some cases, instead of open surgery, a minimally invasive procedure can be performed using special flexible tubes (catheters) with a small balloon at the tip, guided radiologically through a tiny puncture in the groin. In some cases, especially when concomitant cardiac anomalies are present, multiple surgical interventions at different stages of life may be required. In any case, if a hemodynamically significant CoA is present, without proper surgical treatment, your child's health will progressively deteriorate and a serious threat to life may arise.

The surgical intervention itself also carries risks to life and health, especially in infants. The surgery is performed under general anesthesia, and all associated surgical manipulations are performed under general or local anesthesia. During the operation, a mechanical ventilator will breathe for your child. Also, during and after surgery, a transfusion of donor blood components may be required, which is vital and therefore requires your consent.

During the operation, the surgeon will isolate the aorta from surrounding tissues, ligate the arterial duct, and exclude the segment of the aorta with the coarctation from the bloodstream using special clamps. The coarctation area will be excised (cut out), and an anastomosis will be formed between the adjacent edges of the aorta using ultra-fine sutures. After removing the clamps from the aorta, blood flow through it will no longer have significant obstruction. A minor residual obstruction to blood flow in the suture area is permissible. However, it is important to remember that as growth continues, the suture area will lag slightly in development compared to the rest of the aorta, which may (!) lead to recurrence of obstruction over time – recoarctation. If the degree of recoarctation is hemodynamically significant, surgical correction will be necessary. In most cases, recoarctation can be eliminated without repeat open surgery, using the balloon endovascular procedure described above, which generally does not require anesthesia, drug-induced sleep, or mechanical ventilation.

After surgery, your child will spend some time in the intensive care unit, where they will be awakened (weaned from anesthesia), gradually weaned off the mechanical ventilator, and only after that transferred to the general ward. The first hours and days after surgery are the most critical. While staying in the ward to care for your child, you must strictly follow all prescriptions and recommendations of your attending physician and medical staff. It is important to remember the complications that can occur in the early postoperative period and affect not only the heart, but also other organs of the child. The operating surgeon will inform you about possible complications.

In most cases, surgery leads to an improvement in condition and the disappearance of symptoms. In some cases, repeat interventions may be required, most commonly associated with the child's growth.

Follow-up examinations after surgery are particularly important to timely assess the results of correction and detect potential long-term (late) complications.

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

No.