List of Abbreviations
CHD — congenital heart disease
Ao – aorta
AoV – aortic valve
LVOT – left ventricular outflow tract
LV/Ao PSG – left ventricular-aortic peak systolic gradient
VSD – ventricular septal defect
CAG – coronary angiography
SVAS – supravalvular aortic stenosis
CT – computed tomography
LV – left ventricle
MV – mitral valve
MRI – magnetic resonance imaging
PDA – patent ductus arteriosus
PET – positron emission tomography
EF – ejection fraction
AN – anulus
ECG – electrocardiography
Echo-CG – echocardiography
Terms and Definitions
Cardiac catheterization – an invasive procedure performed for therapeutic or diagnostic purposes in cardiovascular pathology by inserting catheters into the heart chamber or the lumen of great vessels.
Left ventricular-aortic peak systolic gradient is a Doppler echocardiographic index reflecting the pressure gradient between cavities, based on measuring blood flow velocity across the aortic valve and characterizing the degree of stenosis.
Computed tomography (CT) is a non-invasive diagnostic imaging method that produces a series of cross-sectional submillimeter axial images of human body organs and structures. It is based on measuring and complex computer processing of X-ray attenuation differences in tissues of varying density, used to improve the differentiation of organs from one another, as well as normal and pathological structures. Various contrast enhancement techniques are used with iodine-containing radiopaque agents. 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 intravascular contrast delivery system at a set injection rate and time. Based on the data obtained, a three-dimensional model of the heart and blood vessels is constructed via computer post-processing with 3D reconstruction.
Magnetic resonance imaging (MRI) is a non-invasive method for 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, in response to their 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 vascular lumen using an MRI 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 makes it possible to obtain vascular images without using any contrast agents — non-contrast angiography (e.g., phase-contrast MR angiography). In some cases, intravenous bolus contrast enhancement using paramagnetic contrast agents is used (ATC classification code: V08CA).
Williams-Beuren syndrome is a genetic symptom complex representing a combination of cardiovascular anomalies with multiple systemic anomalies, based on calcium metabolism disorders.
Positron emission tomography is a radionuclide method for studying myocardial perfusion, making it possible to identify areas of altered coronary blood flow.
Doty procedure is a technique for enlarging the ascending aorta using a "pants"-shaped patch.
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
Congenital supravalvular aortic stenosis (SVAS) is an obstruction caused by a localized or diffuse narrowing of the aortic lumen at and above the sinotubular junction. Moreover, the pathological process can affect all major systemic arteries: the aorta, brachiocephalic and abdominal vessels, and pulmonary arteries.
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
In a dominant percentage of cases, congenital pathology of the ascending Ao is genetically determined by a mutation or deletion of the elastin gene located on chromosome 7q11.23 [2-5]. Congenital SVAS may be part of Williams-Beuren syndrome, and in 5% of cases accompanies Marfan syndrome [5-7]. In Williams-Beuren syndrome, SVAS is typically accompanied by pulmonary valve stenosis and peripheral pulmonary stenoses. Rare reports in the literature describe a combination of pulmonary arterial and portal hypertension in patients with Williams-Beuren syndrome, similar to Alagille syndrome with cirrhosis [8]. There is evidence of congenital SVAS combined with PSAS, aortic coarctation, patent ductus arteriosus, and ventricular septal defect [2,6,7]. A well-known fact is the coronary artery pathology that accompanies SVAS [9]. Dilation or obstruction can be observed in the proximal parts of the vessels. In this case, structural changes in the arterial wall can be caused by both high pressure and being part of a generalized arteriopathy [10].
The morphological spectrum of congenital SVAS is currently quite well studied [3,11-14], and it is quite obvious that SVAS exists in most cases as part of a general disease of the arterial wall of genetic origin [6]. Stenosis can be localized or diffuse. The localized membranous form of SVAS most often presents as a semilunar or annular membrane protruding into the Ao lumen (resembling a valve cusp) [4] located directly at the level of the aortic valve commissures or slightly above. The external diameter of the Ao in this form may be unchanged [3], and post-stenotic dilation may be absent [15]. Another localized form of SVAS features a narrowing of the Ao at the site of stenosis with simultaneous hourglass-type dilation of the sinuses of Valsalva, hence its name. In this form of the anomaly, intimal thickening occurs in the form of an internal fold or ridge, which significantly increases the stenosis and may even close the ostium of the left coronary artery [16]. In addition, the commissural parts of the aortic valve cusps may adhere to varying extents to the stenotic ridge (most often the left coronary cusp) [4,13], which also increases coronary ostial obstruction. However, dilation of the coronary artery ostia due to elevated pressure below the level of the stenosis is more frequently noted [17]. Coronary artery pathology is a recognized feature of SVAS [9,10].
The diffuse form of congenital SVAS is rarer; it is a tubular narrowing extending along the entire length of the ascending Ao, involving the aortic arch and even the ostia of the brachiocephalic vessels. In this case, diffuse compaction and thickening of the Ao wall up to 5-6 mm is typically noted. This form of SVAS is also characterized by altered and thickened valve cusps, which in some cases may adhere to the Ao wall in the sinotubular junction zone [4]. According to histological studies, the morphological substrate of the Ao wall pathology is dysplasia of the vascular muscle layer and replacement of the endothelium with connective tissue rich in collagen. The pathological process in the aortic wall can extend distally beyond the arch and even involve the abdominal Ao with the renal arteries.
1.3 Epidemiology of the Disease or Condition
Data on the prevalence of complete SVAS syndrome are contradictory. According to some researchers, its incidence is 1:100,000, while according to others, it is 1:25,000 newborns [2,6]. According to M.G. Blyumina's observations in our country, the syndrome is much more common — in one out of 3,500 newborns [18]. The number of surgical corrections for SVAS in Russia accounts for 0.27% of all surgeries performed for congenital heart defects. Mortality from such surgeries was 0% in 2015 [19]. SVAS occurs with equal frequency in both female and male children.
In Williams-Beuren syndrome, congenital SVAS is quite frequently (up to 83% of cases) combined with pulmonary trunk stenosis and peripheral pulmonary artery stenoses, the presence of which leads to right ventricular overload and hypertrophy [21-23].
In addition to its association with Williams syndrome, supravalvular aortic stenosis (SVAS) occurs in an inherited, autosomal dominant familial form without the non-vascular features of Williams syndrome, and as sporadic cases of "isolated" SVAS [3,6]. Histological studies initially indicated similarities in the underlying pathology across all three forms of SVAS [4]. It is now established that in patients with Williams syndrome, the elastin gene is deleted or disrupted along with many neighboring genes that are likely important for other features of the syndrome [23,24]. In patients with the familial form of SVAS (non-Williams), the elastin gene undergoes only translocation or a loss-of-function point mutation [25,26]. Patients with the "sporadic" form of SVAS are either members of a family carrying an elastin gene mutation with a subclinical phenotype, or harbor an elastin gene defect as a de novo mutation [5].
The combination of congenital SVAS with multisystem pathology (in a high percentage of cases) determines the natural history of the defect and its complications. According to literature data, progression of supravalvular aortic obstruction and some regression of the severity of pulmonary stenosis are observed over time [27-29]. Since genetic syndromes associated with SVAS involve multi-arterial disease, progressive stenosis of the renal vessels can lead to renovascular hypertension, and that of cerebral vessels to neurological complications.
1.4 Features of Coding the Disease or Condition
Q25.3 – Supravalvular aortic stenosis
1.5 Classification of the disease or condition
To assess the severity of congenital SVAS, hemodynamic classifications based on the values of the maximum and mean LV/Ao pressure gradient (PG), which are presented in the clinical guidelines for congenital aortic stenosis (AS), are also used.
In 2003, at the Bakulev National Medical Research Center of Cardiovascular Surgery, to facilitate the choice of surgical treatment strategy for congenital SVAS, the following classification based on the morphological types of the defect was proposed [6]:
I. Form of supravalvular aortic stenosis
1. Localized form:
A. membranous;
B. "hourglass";
2. Diffuse form:
A. by extent
ascending aorta up to the origin of the brachiocephalic vessels;
ascending aorta + aortic arch.
B. by degree of hypoplasia
moderate;
severe.
II. Involvement of the coronary arteries:
No significant coronary artery pathology;
Coronary artery pathology present:
A. coronary artery dilation (left coronary artery, right coronary artery, both coronary arteries);
B. coronary artery stenosis (left coronary artery, right coronary artery, both coronary arteries).
III. Involvement of the aortic valve (AoV):
No valve pathology.
Presence of valve pathology:
A. pathology of the valve annulus (degree of hypoplasia)
B. pathology of the valve cusps.
1.6 Clinical presentation of the disease or condition
A clinical distinguishing feature of congenital SVAS from other forms of left ventricular outflow tract (LVOT) obstruction is the frequent association of this defect type with multiple systemic anomalies and genetic syndromes. As noted above, congenital SVAS is part of the symptom complex of Williams-Beuren syndrome, which represents a combination of cardiovascular anomalies with multiple systemic anomalies and is based on calcium metabolism disorders. Children with this genetic syndrome experience delayed physical development, have gastrointestinal problems (intestinal colic, constipation, diarrhea), and exhibit hypersensitivity to sounds. A characteristic feature is the child's appearance – an "elfin" facies develops with a high, wide, and prominent forehead, prominent cheekbones, and large, round auricles. Quite often, there is maxillofacial pathology, various dental developmental anomalies, iris pathology, strabismus, and inguinal hernia. As the child grows, the syndrome may be complicated by the development of systemic hypertension, gastrointestinal diseases, and urological diseases [2,23,24].
In addition to its association with Williams syndrome, SVAS occurs in an inherited, autosomal dominant familial form without the non-vascular features of Williams syndrome, and as sporadic cases of "isolated" SVAS [3,5]. Histological studies initially indicated similarities in the underlying pathology across all three forms of SVAS. It is now established that in patients with Williams syndrome, the elastin gene is deleted or disrupted along with many neighboring genes that are likely important for other features of the syndrome [23,24]. In patients with the familial form of SVAS (non-Williams), the elastin gene undergoes only translocation or a loss-of-function point mutation [25,26]. Patients with the "sporadic" form of SVAS are either members of a family carrying an elastin gene mutation with a subclinical phenotype, or harbor an elastin gene defect as a de novo mutation [5].
The combination of congenital SVAS with multisystem pathology (in a high percentage of cases) determines the natural history of the defect and its complications. According to literature data, progression of supravalvular aortic obstruction and some regression of the severity of pulmonary stenosis are observed over time [5,27-29]. Since genetic syndromes associated with SVAS involve multi-arterial disease, progressive renal vessel stenosis can lead to renovascular hypertension, and cerebral vessel stenosis to neurological complications. Patients with congenital SVAS are also at risk for sudden cardiac death due to increasing coronary artery obstruction or progressive stenosis of the outflow tracts of both ventricles.
2. Diagnostics, medical indications and contraindications for diagnostic methods
The diagnosis of SVAS is verified based on the summary data of patient parents' complaints, clinical manifestations of the defect, and laboratory and instrumental research methods.
Fundamental to the diagnosis of SVAS is the detection of a hemodynamically significant aortic narrowing located above the valve level. The most acceptable hemodynamic classification of LVOT stenosis severity is the gradation based on the values of the maximum LV/Ao PG. According to this classification, all patients can be divided into 3 clinical groups [30]:
moderate aortic stenosis – LV/Ao PG up to 50 mm Hg;
severe aortic stenosis – LV/Ao PG of 50–80 mm Hg;
critical aortic stenosis – LV/Ao PG > 80 mm Hg.
According to the guidelines on valvular heart disease developed in 2006 by the American College of Cardiology and the American Association of Cardiologists (ACC/AHA), the severity of aortic stenosis can be assessed by the mean LV/Ao pressure gradient (PG). Accordingly, the following are distinguished:
mild stenosis (mean LV/Ao pressure gradient less than 25 mm Hg),
moderate stenosis (mean LV/Ao pressure gradient – 25–40 mm Hg),
severe stenosis (mean LV/Ao pressure gradient greater than 40 mm Hg).
2.1 Complaints and Anamnesis
It is recommended to collect anamnesis and complaints in all patients (parents of patients) with suspected SVAS at the diagnostic stage [2,6,7,18].
(Level of Evidence C, Grade of Recommendation 5)
It is recommended, when collecting anamnesis and complaints, to ask the patient's parents about delayed physical development, fatigue, shortness of breath (especially during physical activity), palpitations, syncopal episodes, and anginal pain in the child. Patients (or their relatives) may also present with complaints characteristic of comorbid genetic syndromes [2,6,7,18].
(Level of Evidence C, Grade of Recommendation 5)
Comments: Children with Williams-Beuren syndrome experience delayed physical development, have gastrointestinal problems (intestinal colic, constipation, diarrhea), and exhibit hypersensitivity to sounds.
It is recommended, when taking the medical history, to ask parents about a geneticist consultation with documentary confirmation and/or exclusion of concomitant genetic pathology [5,23,24].
(LetC, Level of Evidence 4)
During physical examination, it is recommended to pay attention to the patient's appearance, which may be quite characteristic in the presence of concomitant genetic pathology [2,5,23,24].
(LetC, Level of Evidence 4)
Comments: Patients with Williams-Beuren syndrome typically have an appearance characterized by an "elfin" facies with a high, wide, and prominent forehead, prominent cheekbones, and large, round auricles. Quite often, there is maxillofacial pathology, various dental developmental anomalies, iris pathology, strabismus, and inguinal hernia.
2.2 Physical Examination
It is recommended during the physical examination to focus on palpation and percussion of the heart and neck vessels [2,18,21,23,24].
(Level of Evidence C, Grade of Recommendation 5)
Comments: Examination of patients may reveal percussion-determined enlargement of the heart borders to the left due to LV hypertrophy, and palpation determines a diffuse apex beat. In some cases, a systolic thrill is palpated at the base of the heart, radiating to the jugular fossa and along the carotid arteries.
It is recommended during the physical examination to focus on auscultation of the heart and carotid arteries in order to assess the severity of SVAS [2,18,21,23,24].
(Level of Evidence C, Grade of Recommendation 5)
Comments: During physical examination of patients with congenital SVAS, a somewhat different auscultatory picture of the defect draws attention: 1) there is no systolic click over the AoV, and the epicenter of the systolic murmur over the aorta is shifted higher than in subaortic obstruction; 2) an accent of the AoV closure sound is noted; 3) the diastolic murmur of AoV regurgitation is heard extremely rarely; 4) a systolic murmur may be heard over the projection of the pulmonary trunk.
It is recommended to evaluate the pulse on both upper extremities of the patient during physical examination and perform a comparative analysis of the obtained result [2,18,21,23,24].
(Level of Evidence C, Grade of Recommendation 5)
Comments: When stenosis extends to the aortic arch and subclavian artery, pulse asymmetry may be observed – the pulse on the left arm may be weakened.
It is recommended to measure blood pressure on the peripheral arteries of both upper extremities of the patient during physical examination and perform a comparative analysis of the obtained result [2,18,21,23,24].
(Level of Evidence C, Grade of Recommendation 5)
Comments: When measuring blood pressure, readings on the right arm may be higher than on the left (if stenosis extends to the aortic arch and subclavian artery).
2.3 Laboratory Diagnostics
It is recommended that all patients undergo a coagulogram (exploratory hemostasis test) and a blood platelet count before surgical intervention to predict the risk of perioperative bleeding and blood loss volume [41,42].
(Level of Evidence C, Grade of Recommendation 5)
It is recommended that all patients undergo a complete blood count (CBC) before surgical intervention to detect preoperative anemia and provide timely treatment [41,42].
(Level of Evidence C, Grade of Recommendation 5)
It is recommended that all patients with supravalvular aortic stenosis (SVAS) and Williams syndrome undergo a blood total calcium test before surgical intervention to predict the postoperative course [5,18,21,23,24,28] .
(LetC, Level of Evidence 4)
Comments: In patients with Williams syndrome, blood calcium levels are typically significantly elevated.
2.4 Instrumental Diagnostics
It is recommended to perform an electrocardiogram in all patients with suspected SVAS [2,6,7,18].
(Level of Evidence C, Grade of Recommendation 5)
Comments: ECG may reveal left ventricular hypertrophy of varying degrees. Ischemic changes are also possible depending on the severity of left ventricular outflow tract occlusion and the extent of coronary artery disease.
It is recommended that all patients with diagnosed SVAS who have a history of syncopal episodes undergo 24-hour Holter ECG monitoring to detect possible transient arrhythmias [2,6,7,18].
(Level of Evidence C, Grade of Recommendation 5)
It is recommended that all patients with SVAS undergo targeted chest X-ray in the anteroposterior projection [2,6,7,18]. In all patients with SVAS undergoing targeted chest X-ray, attention should be paid, as indicated, to cardiac configuration and dimensions, and the state of the pulmonary circulation.
(Reliability of Evidence Level C, Confidence Level in Recommendations 5).
Comments: This study is performed to assess cardiac configuration and pulmonary vasculature. The radiological pattern of congenital SVAS is characterized by enhanced pulmonary vasculature and enlargement of the left heart chambers (in the presence of a hemodynamically significant supravalvular narrowing) and lacks specific features, except for the absence of ascending aorta dilation.
It is recommended that all patients with SVAS undergo transthoracic echocardiography (TTE) [2,6,7,18,45].
(GPR C, EL 4)
Comments: The main views for visualizing the left ventricular outflow tract (LVOT) and ascending aorta are: parasternal long-axis view of the LV and short-axis view at the aortic valve level, apical 5-chamber view, as well as subcostal long-axis view of the LVOT and suprasternal long-axis view of the ascending aorta. Echocardiography is used to assess the morphology at the level of obstruction of the ascending and thoracic aorta, determine the hemodynamic significance of the narrowing, dimensions of the LVOT and aortic valve annulus, LV function, and associated congenital heart defects. The state of the right ventricular outflow tract and the presence/absence of obstruction in the pulmonary arterial bed are also evaluated
It is recommended that all patients with diagnosed SVAS undergo color duplex ultrasound of the upper extremity arteries and brachiocephalic arteries [2,6,7,18].
(Reliability of Evidence Level C, Confidence Level in Recommendations 5).
Comments: Patients with SVAS and Williams syndrome may have obstructive lesions of the aortic arch vessels as a manifestation of generalized arteriopathy.
It is recommended that all patients with diagnosed SVAS undergo duplex scanning of the abdominal aorta and its visceral branches [2,6,7,18,46].
(Level of Evidence C, Grade of Recommendation 5)
Comments: Patients with SVAS and Williams syndrome may present with obstructive lesions of the primary aortic branches as a manifestation of generalized arteriopathy, which can lead to renovascular hypertension and abdominal ischemic events.
It is recommended that all patients diagnosed with SVAS by echocardiography with a peak pressure gradient across the LV/aorta of >60 mmHg (severe and critical aortic stenosis according to the hemodynamic classification) undergo transvenous cardiac catheterization and retrograde left heart catheterization with left ventriculography [2,6,7,18,30].
(Level of Evidence C, Grade of Recommendation 5)
Comments: Performing retrograde left heart catheterization and left ventriculography in SVAS helps to clarify the level and extent of LVOT obstruction and determine the hemodynamic parameters of stenosis. Including left ventriculography in the study protocol makes it possible to assess LV cavity dimensions and the degree of hypertrophy, detect the presence/absence of intraventricular obstruction, evaluate contractility, and check for the presence/absence of an aneurysm. Transvenous cardiac catheterization allows evaluation of the right ventricular outflow tract and the pulmonary vascular bed (central and peripheral sections), which in turn may influence surgical tactics and alter the scope of congenital heart defect correction.
It is recommended that all patients diagnosed with SVAS by echocardiography with a peak pressure gradient across the LV/aorta of >60 mmHg (severe and critical aortic stenosis according to the hemodynamic classification) undergo panaortography with coronary angiography [2,6,7,17,18,30].
(Reliability of Evidence Level C, Confidence Level in Recommendations 5).
Comments: Cardiac catheterization and angiocardiography should be performed with caution in patients with a high gradient between the left ventricle and aorta (>70 mmHg on echocardiography), especially when combined with pulmonary artery obstruction, as this significantly increases the risk of hemodynamic disturbances during the procedure, up to and including death. In such cases, sufficient information can be obtained from computed tomography [47].
Including panaortography with coronary angiography in the study protocol allows evaluation of the aortic arch vessels and coronary arteries. Patients with SVAS may have stenotic lesions of the aortic arch vessels and coronary arteries, which in some cases may require various interventional procedures as the first stage of surgical treatment
It is recommended that patients with diagnosed SVAS in critical condition and in preparation for surgery undergo contrast-enhanced cardiac computed tomography (CT) with coronary vessel evaluation [2,7,17,18,30-32].
(Level of Evidence C, Grade of Recommendation 5)
Comments: Contrast-enhanced cardiac CT is recommended to clarify the morphology of the defect, optimize surgical technique, and perform three-dimensional modeling of the upcoming surgery. The primary advantage of CT lies in its superior spatial resolution [31,32].
It is recommended that patients with diagnosed SVAS undergo CT coronary angiography as a standalone study (if contrast-enhanced cardiac CT is not performed) or in combination with contrast-enhanced cardiac CT [2,7,17,18,30-32].
(Level of Evidence C, Grade of Recommendation 5)
Comments: CT coronary angiography is necessary to clarify coronary anatomy. CT coronary angiography surpasses all diagnostic imaging modalities in evaluating coronary artery anatomy. The primary advantage of CT lies in its superior spatial resolution [31,32].
In cases of insufficient or contradictory Echo-CG data in patients with diagnosed NSA combined with other complex CHD, it is recommended to perform contrast-enhanced cardiac magnetic resonance imaging (MRI) and MRI of the great vessels to determine the strategy and timing of surgical intervention, or during routine postoperative examination [2,7,17,18,30-32].
(Level of Evidence C, Grade of Recommendation 5)
Comments: Cardiac MRI is the most accurate method for assessing cardiac function and visualizing myocardial fibrosis. Cardiac MRI is currently considered the "gold standard" imaging modality for evaluating heart chamber function. MRI is a unique technique that allows non-invasive assessment of focal and diffuse myocardial fibrosis using contrast enhancement.
The timing and frequency are determined on an individual basis (every 3–5 years) depending on echocardiographic findings during annual follow-up to obtain volumetric heart data, determine ventricular function, and assess regurgitation volume [2,7,17,18,30-32].
It is recommended that patients with diagnosed supravalvular aortic stenosis (SVAS) and suspected involvement of the coronary artery ostia in the pathological process, or with existing signs of coronary ischemia according to ECG data, undergo myocardial positron emission tomography (PET) to assess myocardial perfusion [2,6,7].
(Reliability of Evidence Level C, Confidence Level in Recommendations 5).
Comments: Based on myocardial perfusion data, a surgical treatment strategy may be chosen that involves correcting coronary blood flow using interventional procedures as the first stage of treatment or simultaneously with the correction of SVAS during open-heart surgery.
It is recommended that patients with diagnosed SVAS and documented impaired myocardial perfusion undergo stress echocardiography [2,6,7].
(Reliability of Evidence Level C, Confidence Level in Recommendations 5).
Comments: Stress echocardiography may be useful in assessing the reliability of ischemic myocardial perfusion.
2.5 Other Procedures
It is recommended that all patients undergo electrocardiography registration before discharge from the hospital to monitor the postoperative period and detect any potential rhythm and conduction disorders [2,6,7,30, 33-36].
(Level of Evidence C, Grade of Recommendation 5)
It is recommended that all patients undergo echocardiography before hospital discharge to assess the efficacy of surgical correction of the defect [2,6,7,30, 33-36].
(CQR C, LCE 5)
It is recommended that patients with diagnosed SVAS and suspected Williams syndrome undergo molecular genetic testing using a specialized DNA microarray that detects chromosome 7 aberrations, in order to rule out or confirm Williams syndrome [4,21,23,24,28].
(LetC, Level of Evidence 4)
Comments: This test is the most accurate diagnostic method for Williams syndrome.
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
3.1 Conservative Treatment
There is no medical treatment for congenital SVAS, with the exception of endocarditis prophylaxis.
3.2 Surgical Treatment
It is recommended to perform surgical intervention for supravalvular stenosis in asymptomatic patients with isolated supravalvular stenosis, satisfactory left ventricular function, and an echocardiography-derived peak gradient greater than 70 mm Hg and a mean gradient greater than 50 mm Hg, or an invasive peak gradient greater than 60 mm Hg [2,6,7,30,47].
(Level of Evidence C, Grade of Recommendation 5)
Comments: If there are indications for surgical treatment, patients with SVAS should be operated on immediately, as prolonged presence of the defect leads to its progression, the development of combined forms, as well as aortic and mitral valve dysfunction, left ventricular dysfunction, and rhythm disorders, resulting in surgery under worse conditions and yielding a less optimistic prognosis.
An additional indication may be the emergence or progression of left ventricular myocardial hypertrophy and the presence of repolarization abnormalities on the ECG [2,6,7,30,47].
As a surgical intervention for patients with SVAS, it is recommended to perform aortic patch plasty (A16.12.055.001) [2,6,75,17,22,29,33-36].
(LetC, Level of Evidence 4)
Comments: When choosing the surgical technique for SVAS, one of the following methods of plastic enlargement of the ascending aorta is used: McGoon, Doty, Brom, Myers.
The use of these techniques allows for adequate expansion of the ascending aorta with a good hemodynamic result. The choice of method is determined by the nature and extent of the SVAS, as well as the surgeon's preference and experience [2,6,75,17,22,29,33-36].
In children with SVAS combined with severe aortic arch hypoplasia, a hemodynamically significant systolic pressure gradient between the left ventricle and aorta, and in those who have previously undergone surgery on the ascending aorta, extra-anatomic aortic bypass grafting (A16.12.056.002) between the left ventricle and descending aorta (using a synthetic vascular prosthesis ***) is recommended as the operation of choice [2,30,37,38].
(LetC, Level of Evidence 4)
Comments: This technique allows for adequate unloading of the left ventricle and stabilizes the child's critical condition, allowing the issue of surgical correction of the pathology to be revisited at an older age.
In this case, the use of valved conduits is optimal.
Given that congenital SVAS is sometimes combined with coronary artery stenosis, visualization and inspection of the coronary artery ostia are strongly recommended during open surgery for defect correction [2,6,7,29].
(Level of Evidence C, Grade of Recommendation 5)
If coronary ostial stenosis is diagnosed before SVAS correction surgery, it is recommended to administer cardioplegic solution retrogradely (via the coronary sinus) [2,6,7,30].
(Level of Evidence C, Grade of Recommendation 5)
If coronary ostial stenosis is diagnosed prior to surgery, it is recommended to relieve the coronary blood flow obstruction during SVAS correction using various plastic techniques (vessel plasty (A16.12.055)) or coronary artery bypass grafting (off-pump coronary artery bypass grafting without cardiopulmonary bypass (A16.12.004.002) or coronary artery bypass grafting with cardiopulmonary bypass (A16.12.004.001)) [2,6,7,30].
(Level of Evidence C, Grade of Recommendation 5)
3.3 Endovascular interventions
When SVAS is combined with pathology of the aortic arch branches as well as the renal artery ostia, it is recommended to consider endovascular procedures as the first stage of surgical treatment (transluminal balloon angioplasty of the renal artery (A16.12.026.009), endovascular angioplasty and stenting of brachiocephalic vessels (A16.12.026.020), coronary artery stenting (A16.12.028.003), renal artery stenting (A16.12.028.009)) of the respective arterial ostia [2,6,7,30].
(Level of Evidence C, Grade of Recommendation 5)
3.4 Other treatment
No.
4. Medical Rehabilitation and Sanatorium-Resort Treatment
It is recommended that within 6 months after surgical correction of SVAS under cardiopulmonary bypass, patients with a complicated postoperative course (heart failure, infectious complications, re-operations during the same hospitalization) undergo rehabilitation in a specialized cardiac rehabilitation facility [44].
(Level of Evidence C, Grade of Recommendation 5)
Comments: The following conditions may occur after SVAS correction:
- Hemodynamically significant residual left ventricular/aortic systolic pressure gradient;
- Hemodynamically significant residual peripheral arterial stenoses;
- Recurrence of aortic obstruction;
- Development of prosthesis-related complications (endocarditis, thrombosis, systemic embolisms, paravalvular leak, or occlusion due to pannus formation) when a synthetic vascular prosthesis *** (or vascular xenograft***) is implanted between the left ventricle and descending aorta;
- Progression of myocardial ischemia caused by generalized arteriopathy;
- Development of cardiac arrhythmias, in some cases leading to sudden cardiac death against the background of acute coronary insufficiency
It is recommended to limit physical activity for three months following hospital discharge [44].
(Level of Evidence C, Grade of Recommendation 5)
5. Prevention and Dispensary Observation
It is recommended that all operated or non-operated patients with diagnosed SVAS are followed up by a pediatric cardiologist [2,6,7,18,44].
(Level of Evidence C, Grade of Recommendation 5)
Patients with moderate to severe SVAS are not recommended to engage in intense physical exertion [2,6,7,18,44].
(Level of Evidence C, Grade of Recommendation 5)
It is recommended that asymptomatic children with diagnosed congenital SVAS, having a peak systolic pressure gradient across the ascending aorta of up to 50 mm Hg or a mean systolic pressure gradient of less than 30 mm Hg, undergo routine follow-up with echocardiography every 6 months at their place of residence [2,6,7,18,30,44].
(Level of Evidence C, Grade of Recommendation 5)
Comments: performing echocardiography every 6 months is mandatory to assess the functional state of the left ventricle and ascending aorta, detect any increase in the systolic pressure gradient between the left ventricle and aorta, and accordingly determine the optimal timing for surgical treatment in case of negative dynamics.
It is recommended that patients with SVAS undergo a pediatric cardiology examination with echocardiography at least once every 3 months during the first year after surgical correction and hospital discharge [44].
(Level of Evidence C, Grade of Recommendation 5)
Patients with SVAS are recommended to undergo inpatient evaluation at least once a year following surgical treatment of the defect [44].
(Level of Evidence C, Grade of Recommendation 5)
It is recommended that all operated patients with SVAS undergo long-term follow-up monitoring based on electrocardiography, echocardiography, Doppler sonography of main arteries, and contrast-enhanced magnetic resonance imaging (MRI) of the great vessels and heart [2,6,7,18,30,46].
(Level of Evidence C, Grade of Recommendation 5)
Comments: Implementing this follow-up algorithm in the long-term period after SVAS correction is necessary to detect any increase in the residual systolic pressure gradient across the ascending aorta, identify left ventricular dysfunction, detect potential coronary ischemia, and spot stenoses in other central and peripheral arteries.
It is recommended that all unoperated and operated patients with supravalvular aortic stenosis (SVAS) combined with Williams syndrome undergo a consultation with a pediatric urologist-andrologist, pediatric endocrinologist, ophthalmologist, neurologist, and orthopedic trauma surgeon [2,6,7,18,30,46].
(Level of Evidence C, Grade of Recommendation 5)
Comments: Follow-up monitoring of patients with SVAS by related specialists is necessary for the timely detection of potential complications of Williams syndrome and their management.
6. Organization of Medical Care
Indications for hospital admission to a medical organization:
1) presence of symptoms of heart failure;
2) elective surgical treatment for SVAS;
3) prior aortic interventions aimed at relieving stenosis;
Indications for emergency hospitalization:
1) deterioration of the patient's functional status due to the progression of circulatory insufficiency symptoms or cardiac arrhythmias;
2) development of acute coronary insufficiency;
3) development of left ventricular dysfunction;
4) infective endocarditis;
5) appearance of signs of ischemia in various organs.
Indications for discharging a patient from a medical organization:
1) presence of a gradient between the left ventricle and the aorta not exceeding severe supravalvular aortic stenosis;
2) absence/compensation of heart failure symptoms;
3) absence of signs of coronary ischemia;
4) absence of hemodynamically significant cardiac rhythm disturbances.
7. Additional Information
Methods for treating localized congenital SVAS are well established and provide favorable hemodynamic results. The Brom and Meyers techniques for SVAS enlargement are more effective than the Doty and McGoon techniques because they allow for a more effective reconstruction of the aortic root. According to various authors, survival after such interventions ranges from 66% to 97% at 20 years postoperatively [33-36].
Congenital diffuse SVAS remains an unresolved challenge, where attempts to correct the stenosis do not eliminate the morphological substrate and normalize hemodynamics, but merely shift the level of stenosis distal to the aortic arch, involving the ostia of the brachiocephalic vessels in the pathological process.
Criteria for Evaluating the Quality of Medical Care
№ | Quality criteria | |||
|---|---|---|---|---|
Diagnosis stage | ||||
1 | Patient history and complaints were collected | C | 5 | |
2 | Heart auscultation was performed | C | 5 | |
3 | Electrocardiogram recording performed | C | 5 | |
4 | Holter heart rhythm monitoring was performed | |||
5 | Chest X-ray performed | C | 5 | |
6 | Echocardiography performed | C | 4 | |
7 | Ultrasound Doppler examination of the upper extremity arteries and duplex scanning of brachiocephalic arteries with color Doppler mapping were performed. | C | 5 | |
8 | Duplex scanning of the abdominal aorta and its visceral branches was performed. | C | 2 | |
9 | Transvenous cardiac catheterization and retrograde left heart catheterization with left ventriculography were performed (for patients with marked and severe aortic stenosis according to the hemodynamic classification). | C | 5 | |
10 | Panaortography with coronary angiography was performed (for patients with marked and severe aortic stenosis according to the hemodynamic classification). | C | 5 | |
11 | Contrast-enhanced computed tomography of the heart was performed. | C | 5 | |
12 | Stress echocardiography was performed if involvement of the coronary artery ostia in the pathological process is suspected or if there are signs of coronary ischemia on the ECG. | C | 5 | |
13 | Myocardial positron emission tomography was performed when involvement of the coronary artery ostia in the pathological process was diagnosed. | C | 5 | |
14 | Molecular genetic testing was performed when Williams syndrome was suspected. | C | 4 | |
Conservative and surgical treatment stage | ||||
1 | Surgical treatment to correct SVAS was performed when indicated (percutaneous intervention or open-heart surgery). | C | 4 | |
Postoperative Monitoring Stage | ||||
1 | Electrocardiography was recorded prior to hospital discharge. | C | 5 | |
2 | Echocardiography was performed before hospital discharge | C | 5 | |
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Appendix A1. Working Group Composition
1. Avramenko A.A. (Samara)
2. Arnautova I.V., D.Sc. (Med.), Association of Cardiovascular Surgeons of Russia (Moscow)
3. Baryshnikova I.Yu., Ph.D. (Med.) (Moscow), Russian Society of Radiologists
4. Bogdanov V.N. (Chelyabinsk)
5. Bockeria L.A., Academician of the Russian Academy of Sciences, Association of Cardiovascular Surgeons of Russia (Moscow)
6. Boriskov M.V., D.Sc. (Med.) (Krasnodar)
7. Borisova N.A., Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists (Saint Petersburg)
8. Gorbatikov K.V., D.Sc. (Med.) (Tyumen)
9. Gorbatykh Yu.N., D.Sc. (Med.) (Novosibirsk)
10. Kalashnikov S.V., Ph.D. (Med.) (Moscow)
11. Kim A.I., D.Sc. (Med.), Association of Cardiovascular Surgeons of Russia (Moscow)
12. Kovalev I.A., D.Sc. (Med.), Association of Pediatric Cardiologists of Russia (Moscow)
13. Krivoshchekov E.V., D.Sc. (Med.) (Tomsk)
14. Kupryashov A.A., D.Sc. (Med.) (Moscow)
15. Levchenko E.G., D.Sc. (Med.) (Moscow)
16. Movsesyan R.R., D.Sc. (Med.), Association of Cardiovascular Surgeons of Russia (Saint Petersburg)
17. Plotnikov M.V., Ph.D. (Med.) (Astrakhan)
18. Pursanov M.G., D.Sc. (Med.) (Moscow)
19. Rychina Inna Evgenievna – Ph.D. (Med.) (Moscow), Russian Society of Radiologists
20. Sinelnikov Yu.S., D.Sc. (Med.) (Perm)
21. Sinitsyn V.E., D.Sc. (Med.), Professor (Moscow), Russian Society of Radiologists
22. Trunina I.I., D.Sc. (Med.), Association of Pediatric Cardiologists of Russia (Moscow)
23. Chernogrivov A.E., D.Sc. (Med.), Association of Cardiovascular Surgeons of Russia (Moscow)
24. Shatalov K.V., D.Sc. (Med.), Association of Cardiovascular Surgeons of Russia (Moscow)
25. Yurpolskaya L.A., D.Sc. (Med.) (Moscow), Russian Society of Radiologists
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
1. Pediatric cardiologist
2. Cardiologist
3. Cardiovascular surgeon
4. Ultrasound diagnostics physician
5. Pediatrician
6. Cardiovascular surgeon / Endovascular diagnostic and treatment specialist
7. Radiologist
8. Functional diagnostics physician
9. Neonatologist
Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions).
LoE | Definition |
|---|---|
1 | Systematic reviews of studies with reference standard control or systematic reviews of randomized controlled trials with meta-analysis |
2 | Individual studies with reference method control or individual randomized clinical trials and systematic reviews of studies of any design, except for randomized clinical trials with meta-analysis |
3 | Studies without consecutive reference method control, or studies with a reference method that is not independent of the studied method, or non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
Table 2. Scale for assessing levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, rehabilitation interventions).
LoE | Definition |
|---|---|
1 | Systematic review of RCTs with meta-analysis |
2 | Individual RCTs and systematic reviews of studies of any design except RCTs, with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | Only justification of the mechanism of action of the intervention (preclinical studies) or expert opinion is available |
Table 3. Scale for grading the levels of evidence (LE) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions).
GoR | Definition |
|---|---|
A | Strong recommendation (all considered efficacy criteria (outcomes) are important, all studies are of high or acceptable methodological quality, and their conclusions on the outcomes of interest are consistent) |
B | Conditional recommendation (not all considered efficacy criteria (outcomes) are important, not all studies are of high or acceptable methodological quality, and/or their conclusions on the outcomes of interest are inconsistent) |
C | Weak recommendation (lack of adequate quality evidence (all considered efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Procedure for updating clinical guidelines.
The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.
Appendix A3. Reference Materials
1. On the Fundamentals of Protecting the Health of Citizens in the Russian Federation (Federal Law No. 323-FZ of November 21, 2011)
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 Russian Ministry of Health No. 560n of June 9, 2020 "On Approval of the Rules for Conducting Radiological Examinations"
4. Order of the Russian Ministry of Health No. 557n of June 8, 2020 "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 a suboptimal acoustic window.
Important indicators when analyzing and interpreting the obtained images:
Performing transthoracic echocardiography (TTE)
Comprehensive EchoCG (prior to aortic examination) to rule out associated congenital heart disease, assess cardiac dimensions 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 view 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 placing the cursor perpendicularly to the MV leaflet closure line. 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 chambers. Left parasternal view: long-axis assessment of the aortic valve annulus diameter, root dimensions, and ascending aorta. In these modes and views in diastole, the thickness of the interventricular septum and the LV inferolateral wall is measured. LV wall thickening is considered present when the relative wall thickness (the sum of the thickness of the IVS and LVILW divided by the LV end-diastolic dimension) exceeds 0.42 [47, 48].
Ascending aorta. The purpose of echocardiographic evaluation of supravalvular aortic stenosis is to comprehensively characterize the morphological features of the obstructive lesion, assess the severity of hemodynamic changes, and identify associated anomalies. The morphological substrate of ascending aortic obstruction can be a discrete membrane, a localized "hourglass" type narrowing, or a diffuse narrowing/thickening of the aortic wall, including of first-order arteries [49].
Echocardiographic assessment of the severity of supravalvular aortic stenosis is based on anatomical and hemodynamic parameters. Measurement of the minimum dimension and flow is performed at end-systole, and color Doppler flow imaging with optimal Nyquist limit settings is used to localize the level of narrowing. The obtained value is evaluated using Z-scores [50]. This method yields dimensions in a single plane, and for a more qualitative anatomical assessment of the degree of narrowing, three-dimensional EchoCG may be used in older children and adults, as it has technical limitations in obtaining informative echocardiograms in newborns and infants due to high heart rates and low frame rates. When performing transesophageal EchoCG, the manufacturer's weight limitations for the child (per the instructions) must be taken into account.
Hemodynamic assessment of supravalvular aortic stenosis is based on measuring the maximum/mean blood flow velocity immediately distal to the site of narrowing and converting it into the systolic pressure gradient (SPG). To obtain optimal Doppler curves, any approaches and LV long-axis views may be used, but the rule must be followed: the angle of divergence between the blood flow through the narrowed area and the ultrasound beams must not exceed 15%.
The most acceptable hemodynamic classification of the severity of supravalvular aortic stenosis is the grading based on maximum and mean SPG values. According to this classification, all patients should be divided into 3 groups [51]:
Minimal supravalvular aortic stenosis – maximum LV/Ao SPG up to 34 mmHg; mean SPG < 20 mmHg
Moderate supravalvular aortic stenosis – maximum LV/Ao SPG 34–64 mmHg; mean SPG 20–40 mmHg
Severe supravalvular aortic stenosis – maximum LV/Ao SPG > 64 mmHg, mean SPG > 40 mmHg
Assessment of proximal coronary artery stenosis is performed in the left parasternal short-axis view at the aortic valve level, optimizing the image for the coronary arteries. The dimensions of the coronary ostia are evaluated using Z-scores (http://parameterz.blogspot.com/2008/12/coronary-artery-z-score-menu.html?m=1).
Important indicators in the analysis and interpretation of the obtained images:
presence/absence of obstructive changes in the ascending aorta;
localization of aortic narrowing; type of supravalvular aortic narrowing;
on color Doppler flow imaging: accelerated turbulent blood flow at the site of narrowing (determination of systolic/mean pressure gradient).
Stenosis of first-order arteries (coronary arteries, brachiocephalic arteries, renal arteries)
LV myocardial systolic function, mitral regurgitation
Challenges: Obtaining a good acoustic window to evaluate the ascending aorta may be difficult; additionally, the right parasternal LV long-axis view may be used [52]. If there is multilevel disease or diffuse aortic narrowing, the obtained SPG may be underestimated.
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Currently, it is quite evident that supravalvular aortic stenosis (SAS) exists in the majority of cases as part of a generalized arterial wall disease of genetic origin. This is supported by the frequent association of congenital heart disease with genetic syndromes, particularly Williams-Beuren syndrome. The stenosis may be localized or diffuse and constitute a component of multi-vessel disease.
Given these features, the clinical symptoms of the anomaly manifest not only from the cardiovascular system but also from other organs and systems.
Surgery is indicated for patients with congenital SAS when the systolic pressure gradient across the stenosis is 50 mmHg or greater. Age cannot be a contraindication for SAS correction due to the progressive nature of the pathology. Timely surgical treatment of congenital SAS in early childhood prevents the development of coronary artery disease and, consequently, the progression of myocardial ischemia. Furthermore, timely correction of supravalvular aortic narrowing prevents the development of such complications as the formation of an ascending aortic aneurysm with dissection and pathological changes of the aortic valve leading to significant regurgitation.
Patients with operated and unoperated SAS must be under continuous dynamic monitoring not only by a cardiologist but also by other subspecialists due to the possibility of multi-vessel disease leading to multi-organ and systemic dysfunction.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
No.