Aortic Regurgitation: Clinical Guidelines

List of Abbreviations

VKA – vitamin K antagonists

AH – arterial hypertension

BP – blood pressure

AV – aortic valve

ALT – alanine aminotransferase

AR – aortic regurgitation

Anticoagulants – B01A: Antithrombotic agents

AST – aspartate aminotransferase

BB – beta-blockers

ARB – angiotensin receptor blocker (angiotensin II receptor antagonists)

AA – ascending aorta

BAV – bicuspid aortic valve

DAPT – dual antiplatelet therapy

Antiplatelet agent – B01AC Platelet aggregation inhibitors excluding heparin

PCWP – pulmonary capillary wedge pressure

CHD – coronary heart disease

ACEi – angiotensin-converting enzyme inhibitors

IE – infective endocarditis

CAG – coronary angiography

Right heart catheterization – transvenous heart catheterization

LVEDD – left ventricular end-diastolic dimension

ESD – end-systolic dimension

CT – computed tomography

Coronary CTA – computed tomography coronary angiography (optical coherence tomography of the coronary arteries)

Aortic CTA – computed tomography angiography of the aorta

LV – left ventricle

LA – left atrium

Mechanical prosthesis – mechanical bileaflet aortic valve prosthesis ***

Biological prosthesis – aortic valve bioprosthesis***

INR – international normalized ratio

MRI – magnetic resonance imaging

Cardiovascular MRI – magnetic resonance imaging of the heart and great vessels

Multidisciplinary team – cardiologist, cardiovascular surgeon, physician of any other subspecialty depending on concomitant pathology

Occluder – cardiac occluder***

SAVR – surgical aortic valve replacement under cardiopulmonary bypass

SAVR with a biological prosthesis – surgical aortic valve replacement with an aortic valve bioprosthesis under cardiopulmonary bypass***

DOACs – direct oral anticoagulants, B01A: Antithrombotic agents

CRP – C-reactive protein

Statins – C10AA HMG-CoA reductase inhibitors

TG – triglycerides

TAVR – transcatheter aortic valve implantation (A16.10.003.032 Endovascular aortic valve replacement)

US – ultrasound examination

EF – ejection fraction

AV – aortic valve annulus

LDL-C – low-density lipoprotein cholesterol

TEE – transesophageal echocardiography

ECG – electrocardiography

EchoCG – echocardiography (transthoracic)

CHA2DS2-VASc – risk score for stroke and thromboembolic complications in patients with atrial flutter and fibrillation (Appendix G4)

NYHA – New York Heart Association

** – the drug is included in the list of vital and essential drugs

*** – medical device implanted when providing medical care under the state guarantee program for free medical care to citizens

# – off-label drug prescription (use for indications not approved by state regulatory authorities and not mentioned in the instructions for use)

Terms and Definitions

ESC – European Society of Cardiology. These clinical guidelines additionally indicate recommendations corresponding to the European Society of Cardiology (ESC) guidelines. In accordance with international documents, classes of recommendations and levels of evidence are distinguished.

Aortic valve – the heart valve located at the aortic orifice between the initial segment of the aorta and the left ventricular outflow tract.

Aortic regurgitation – retrograde blood flow from the aorta into the left ventricle during diastole [1].

Outcome – any possible result arising from exposure to a causal factor, prophylactic or therapeutic intervention, all established changes in health status occurring as a consequence of the intervention.

Conflict of interest – a situation in which a medical or pharmaceutical worker, in the exercise of their professional activities, has a personal interest, whether acting individually or through a representative of a company, in obtaining material gain or another advantage that affects or may affect the proper performance of their professional duties due to a contradiction between the personal interest of the medical or pharmaceutical worker and the interests of the patient.

Valvular heart disease – cardiac disorders caused by morphological and/or functional changes in one or more of its valves. Valvular changes may present as stenosis, regurgitation, or a combination thereof.

Clinical trial – any investigation involving human subjects intended to discover or verify the clinical and/or pharmacological effects of investigational products, and/or to identify any adverse reactions to investigational products, and/or to study absorption, distribution, metabolism, and excretion in order to ascertain their safety and/or efficacy. The terms "clinical trial" and "clinical study" are synonymous.

Computed tomography (CT) – a non-invasive diagnostic imaging method that produces a series of submillimeter cross-sectional axial images of human organs and structures.

Laboratory diagnostics – a set of methods aimed at analyzing test material using various specialized equipment.

Medicinal products – pharmacological agents in the form of dosage forms used for the prevention, diagnosis, and treatment of diseases, rehabilitation, as well as for the maintenance, prevention, or termination of pregnancy.

Magnetic resonance imaging (MRI) – a non-invasive method for acquiring tomographic medical images without ionizing radiation to examine internal organs and tissues.

Medical intervention — a set of medical examinations and/or procedures performed by a medical worker or other professional authorized to provide medical care, affecting the physical or mental state of a person and having a preventive, diagnostic, therapeutic, rehabilitative, or research orientation.

Medical worker – an individual who has a medical or other education, works in a medical organization, and whose job (official) duties include the provision of medical care, or an individual who is an individual entrepreneur directly engaged in medical activities.

Patient – an individual who receives medical care or who applies for medical care regardless of the presence of a disease and their condition.

First medical contact – the time of the initial examination of a patient by a physician, paramedic, nurse, or ambulance crew members who record an ECG (and have its interpretation results) and can perform primary interventions (e.g., cardiac defibrillation). First medical contact may occur at the pre-hospital stage or upon the patient's initial hospital admission.

Valve replacement – the replacement of a native valve with a prosthetic device that performs its function.

Working group on the development/updating of clinical guidelines – a team of specialists working together and in a coordinated manner to develop/update clinical guidelines and bearing joint responsibility for the results of this work.

Valve repair – the restoration of valve function without its replacement.

Symptom (from Greek symptomos – sign, coincidence) is a manifestation of a disease, a statistically significant deviation of an indicator from its normal range, or the emergence of a qualitatively new phenomenon uncharacteristic of a healthy organism.

Syndrome – a stable set of several symptoms with a single pathogenesis.

Condition — changes in the body resulting from the impact of pathogenic and/or physiological factors that require medical care.

Thesis-recommendation – a statement reflecting the procedure and correctness of performing a particular medical intervention with proven efficacy and safety.

Level of evidence reliability – the degree of confidence that the observed effect of a medical intervention is true.

Level of убедительности рекомендаций (Class of Recommendation, CoR) – the degree of certainty in the reliability of the intervention effect and that adherence to recommendations will bring more benefit than harm in a specific clinical situation.

Surgical treatment is a method of treating diseases by dividing and uniting tissues during a surgical operation.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Aortic regurgitation (AR) – a valvular disorder characterized by impaired closure or destruction of the aortic valve (AV) cusps, leading to loss of its barrier function and the development of retrograde blood flow into the left ventricle (LV) during diastole [1, 2].

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

Causes of AR may include structural changes in the AV cusps that impair valve closure: atherosclerotic cusp changes, infective endocarditis (IE) with cusp destruction [1, 3]. Congenital anomalies are frequent etiological factors of AR: bicuspid (BAV), unicuspid, or quadricuspid AV [156, 157]. Traumatic injury is a relatively uncommon cause of AR [4]. In the absence of morphological changes in the semilunar cusps, AR can develop due to dilation of the AV annulus, sinuses of Valsalva, sinotubular junction (STJ), and alteration of the spatial geometry of the aortic root structures, which accompanies root and ascending aortic aneurysms [5]. Aortic regurgitation frequently complicates ascending aortic dissection. Other frequent causes of AR include sclerotic degeneration, rheumatic fever, connective tissue dysplasia, and less commonly ankylosing spondylitis, syphilitic aortitis, rheumatoid arthritis, osteoarthritis, giant cell aortitis, ventricular septal defect with AV prolapse, and AV tumors. Most of these causes lead to chronic AR with progressive and insidious LV dilation, typically accompanied by a prolonged asymptomatic period [2, 6, 7]. Other causes, notably IE, iatrogenesis, acute aortic dissection, and trauma, more frequently result in acute severe AR, which can cause a sudden, catastrophic increase in LV filling pressures and a drop in cardiac output.

In acute severe AR, a large volume of blood returns to a normal-sized left ventricle, and the LV does not have time to adapt to the volume overload. The ventricle's inability to undergo rapid compensatory cavity dilation leads to a reduction in stroke volume. Tachycardia, which develops as a compensatory mechanism to maintain cardiac output, is often insufficient for such compensation. As the LV end-diastolic pressure approaches diastolic pressure in the aorta and coronary arteries, subendocardial myocardial perfusion decreases. LV dilation and wall thinning due to increased afterload, combined with tachycardia, lead to increased myocardial oxygen demand; therefore, acute severe AR frequently leads to ischemia, the complications of which can result in sudden death. In response to volume overload in chronic AR, the LV develops a series of compensatory mechanisms, including an increase in end-diastolic volume and LV chamber compliance, which allows volume expansion without raising LV filling pressures, as well as a combination of eccentric and concentric hypertrophy. Thus, AR creates conditions for a combination of volume and pressure overload [2]. LV systolic dysfunction (most commonly defined as a decrease in ejection fraction below normal at rest) is primarily associated with an increase in afterload and may be reversible in the early stages following AV replacement [7, 8]. Gradually, as dilation progresses, the LV assumes a spherical shape. Myocardial contractility decreases due to excessive load, leading to persistent systolic dysfunction, and the expected surgical benefit (restoration of LV function, increased survival) can no longer be achieved [8, 9].

1.3 Epidemiology of the Disease or Condition

According to the Framingham Heart Study, the prevalence of AR is 4.9% in the general population, with moderate or severe regurgitation observed in 0.5% of examined individuals [2]. According to other researchers, the incidence of chronic AR can reach nearly 20%, its prevalence increases with patient age, and there is no significant difference between men and women [10].

1.4 Features of Coding the Disease or Condition

I06.1 – Rheumatic aortic regurgitation

I35.1 – Nonrheumatic aortic (valvular) incompetence

Q23.1 – Congenital insufficiency of aortic valve

Q23.8 – Other congenital malformations of aortic and mitral valves

Q23.9 – Congenital malformation of aortic and mitral valves, unspecified

Diagnosis formatting examples:

Primary diagnosis: Congenital heart disease: Bicuspid AV with severe AR.

Complications: Chronic heart failure with preserved ejection fraction (60%), Stage 1, NYHA Class II.

1.5 Classification of the disease or condition

Regarding the timing and onset characteristics, AR is classified as congenital or acquired, acute or chronic. By severity, there are 3 grades of aortic regurgitation: mild, moderate, and severe. Chronic AR is assessed using structural, qualitative, semi-quantitative, and quantitative parameters during transthoracic echocardiography (TTE) with color Doppler mapping (Table PB-1, Appendix B) [11, 12, 13].

This classification is preferred for diagnosis; the use of numerical regurgitation grades (1, 2, 3, 4) is not recommended [11, 12, 13, 14, 15]. Based on the mechanism of formation, there are 3 types of AR: type I (normal AV cusps, impaired coaptation due to aortic root dilation, central regurgitant jet), type II (AV cusp prolapse and eccentric regurgitant stream), and type III (AV cusp deformation and retraction with a central or eccentric regurgitant stream). L. de Kerchove and G. El Khoury expanded this classification in terms of selecting the AR surgical repair method (Table PB-2, Appendix B) [11, 16].

1.6 Clinical presentation of the disease or condition

Most patients with chronic AR remain asymptomatic throughout the compensation phase, which can last for years or decades [2, 7, 17]. When valve decompensation occurs, progressive dyspnea, orthopnea, attacks of cardiac asthma, and fatigue develop. Patients may also present with typical anginal pain even in the absence of coronary artery disease. Acute AR causes symptoms of heart failure. The patient is troubled by dyspnea upon minor physical exertion and at rest, weakness, and lower extremity edema. In severe AR, there is a high risk of pulmonary edema or cardiogenic shock. When taking a patient's history, it is recommended to pay attention to the presence of dyspnea on exertion and at rest, attacks of suffocation, and chest pain. With decompensation of the valve defect, dyspnea appears on exertion, and subsequently at rest. This is followed by attacks of suffocation (cardiac asthma and/or pulmonary edema) and cardiac arrhythmias. Cardiac pain (angina pectoris) can also occur in AR, but it is not always associated with triggering factors like anginal pain in coronary artery disease (CAD). In no less than a quarter of patients, left ventricular (LV) systolic dysfunction progresses before the onset of symptoms, leading to death [2, 17, 18]. Therefore, a clinical examination is not sufficient for evaluating asymptomatic patients; performing an echocardiogram for quantitative assessment of LV function is mandatory.

2. Diagnostics, medical indications and contraindications for diagnostic methods

2.1 Complaints and Anamnesis

ESC/ACC I B (LoE C, GoR 5)

Comments: in chronic AR in the compensation stage, clinical manifestations may be absent for a prolonged period of time. As decompensation approaches and sets in, there is a gradual decrease in exercise tolerance, the appearance of dyspnea upon exertion (initially with high-intensity exertion), and a sensation of "palpitations" in the chest and "pulsations" in the head. The occurrence of AR in young individuals is characteristic of congenital AV anomalies, primarily in patients with BAV. In this category of patients, clinical manifestations of congestive heart failure may manifest from a young age [21]. Frequent manifestations of chronic AR are discomfort, uneasiness, and pain in the heart area and chest. Peripheral edema, orthopnea, and pulmonary edema can be observed in both chronic and acute AR. Acute AR is typically characterized by the sudden onset of severe dyspnea and/or suffocation. Myocardial ischemia, which frequently develops in acute AR, may present with chest pain [22]. Anamnestic indications of a current infectious process (high fever, recent dental procedures or other surgical interventions) or transcatheter manipulations (CAG and/or percutaneous coronary intervention, direct aortography, transcatheter aortic or AV operations) provide grounds to suspect AR due to mechanical destruction of the AV cusps. Information regarding an existing aneurysm and/or aortic dissection makes it possible to suspect a secondary nature of AR [23, 24, 25].

2.2 Physical Examination

ESC/ACC I B (LoE C, GoR 5)

Comments: when examining a patient with AR, it is recommended to pay attention to the pulsation of the neck and lower extremity arteries, and to measure blood pressure (measurement of blood pressure on peripheral arteries). Systolic blood pressure in severe AR is often elevated, diastolic blood pressure is significantly reduced, and pulse pressure is high. Pathognomonic external signs of severe AR include visible pulsation of the common carotid arteries (Corrigan's sign), sometimes temporal and subclavian veins ("carotid dance"), a high pulse with a rapid rise and fall (bounding or collapsing pulse, water-hammer pulse), an enhanced and inferiorly-leftward displaced apical impulse, pseudo-capillary pulse (Quinque's sign, best determined with light pressure), head bobbing (de Musset's sign), and pulsation in the right hypochondrium. Other visible symptoms of severe AR include pulsation of the uvula capillaries (Müller's sign), pupillary pulsation (Landolfi's sign), hepatic pulsation (Rosenbach's sign), or splenic pulsation (Gerhardt's sign).

In severe AR, the following auscultatory phenomena are detected: a diastolic murmur in the 2nd intercostal space to the right and away from the sternum and in the 3rd-4th intercostal spaces at the left sternal border and radiating to the apex of the heart, high-pitched in character, most often decrescendo, associated with a rapid decrease in volume or degree of regurgitation during diastole; weakening of the 1st heart sound at the apex, weakening of the 2nd heart sound over the aorta; Austin Flint murmur – a specific sign of severe AR, a low-pitched rumbling diastolic murmur that is often auscultated at the apex, which can be mid-diastolic or presystolic. A pathological 3rd heart sound is often auscultated at the apex of the heart, indicating LV volume overload. Two sounds may be auscultated over the femoral arteries (Traube's double sound and Duroziez's double murmur) [2, 18].

2.3 Laboratory Diagnostics

Specific laboratory tests are not required to establish the diagnosis of AR [12, 17, 19, 20]. However, there are a number of situations when it is necessary to perform additional laboratory testing.

ESC/ACC IIa C (LoE C, LoR 5)

Comments: testing for hepatitis B surface antigen (HbsAg), hepatitis C virus antibodies, Treponema pallidum antibodies, and human immunodeficiency virus (HIV) 1/2 IgM and IgG antibodies as part of preoperative preparation may be performed within primary health care.

ESC/ACC I C (LoE C, LoR 5)

ESC/ACC IIa C (LoE C, LoR 5)

ESC/ACC IIa C (LoE C, LoR 5)

2.4 Instrumental Diagnostics

2.4.1. Non-invasive Diagnostic Methods

• Patients with AR are recommended to undergo resting electrocardiography (ECG), including interpretation, description, and analysis of electrocardiographic data (12-lead ECG) to assess heart rhythm, detect QRS complex abnormalities, arrhythmias, and conduction disturbances, as well as in cases of surgical treatment when necessary in the pre- and/or postoperative period [20, 158, 172].

ESC/ACC I B (LoE C, GoR 5)

Comment: non-invasive diagnostic methods play the primary role in the initial diagnosis, monitoring, and determination of indications for surgical interventions in AR. ECG is recommended to detect rhythm and conduction disorders in patients with chronic and acute AR. ECG changes are nonspecific and may include signs of left ventricular hypertrophy, left axis deviation, and left atrial enlargement. In acute AR, ECG abnormalities may include nonspecific ST-segment changes and sinus tachycardia due to increased sympathetic nervous system activation [28, 29].

ESC/ACC I B (LoE C, GoR 5)

Comments: targeted chest X-ray allows assessment of the lung condition and presence of pleural effusion. A typical radiological manifestation of chronic AR is enlargement of the cardiac silhouette due to the left ventricle. Acute AR may manifest as pulmonary edema. In AR caused by ascending aortic dissection, widening of the mediastinal shadow may be visualized. Additionally, the size of the heart and ascending aorta can be roughly estimated, although chest radiography is not the method of choice for this purpose [28, 29, 30].

ESC/ACC I B (LoE C, GoR 5)

Comments: echocardiography is the key diagnostic method for confirming heart valve disease, assessing severity and prognosis, and selecting the timing and methods of treatment. The examination must follow the parameters listed in Table PB-1. It is recommended to index LV dimensions to body surface area, especially in patients with a BSA ≤ 1.68 m². To plan surgical intervention and determine the feasibility of valve-sparing correction, the mechanism of AR formation must be analyzed according to the principles described in Table PB-2 [159].

• Echocardiography is recommended for the diagnosis and etiology assessment of chronic AR in all patients with suspected AR [6, 17, 31, 32, 33, 159].

ESC/RCS I B (LoE B, GoR 2)

• Patients with a diagnosed bicuspid aortic valve are recommended to undergo baseline echocardiography to assess the diameter of the aortic root and ascending aorta [6, 17, 31, 32, 33, 159].

ESC/RCS I B (LoE B, GoR 2)

ESC/ACC I B (LoE C, GoR 5)

ESC/RCS IIa B (LoE B, GoR 2)

Comments: exercise testing in asymptomatic patients should only be performed under the supervision of an experienced physician with continuous blood pressure and ECG monitoring. The test has low diagnostic accuracy for detecting concomitant coronary artery disease. This is due to baseline ECG abnormalities, left ventricular hypertrophy, and reduced coronary reserve.

ESC/RCS IIa B (LoE B, GoR 2)

• Exercise testing (exercise ECG, exercise echocardiography, bicycle ergometry) is not recommended in patients with significant valvular heart disease due to low diagnostic value and high risk of complications [6, 17, 31, 32, 33].

ESC/ACC III A (LoE B, LoR 2)

ESC/ACC IIa C (LoE C, GoR 5)

ESC/ACC III A (LoE C, QoE 5)

Comment: TEE should not be used for routine or serial evaluation of mitral regurgitation when transthoracic echocardiographic imaging is adequate. TEE is advisable as an adjunctive imaging modality when infective endocarditis of a native or prosthetic aortic valve is suspected.

ESC/ACC IIa C (LoE C, GoR 5)

ESC/ACC IIa C (LoE C, GoR 5)

• If dilation of the aortic root and/or ascending aorta >40 mm is detected in patients with AR, especially in patients with connective tissue disorders (Marfan, Ehlers-Danlos, Loeys-Dietz syndromes, etc.), congenital aortic valve anomalies, aortic coarctation, or ventricular septal defect, it is recommended to perform ECG-gated contrast-enhanced aortic computed tomography angiography (CTA) or contrast-enhanced CMR of the heart and great vessels to verify thoracic aorta dimensions at various levels, evaluate the aortic wall status, rule out dissection, intramural hematoma, and/or aneurysmal dilation, as well as in cases of surgical treatment when necessary in the pre- and/or postoperative period [13, 34, 35, 36].

ESC/RCS I B (LoE B, GoR 3)

Comments: Aortic CTA or CMR is recommended in patients with AR, particularly in the presence of congenital aortic valve anomalies (bicuspid or unicuspid aortic valve), to evaluate the ascending aorta (sinuses of Valsalva, sinotubular junction) if echocardiographic visualization is suboptimal [7, 19, 37, 38]. To improve reproducibility, aortic diameters should be measured in late diastole including the aortic wall, strictly perpendicular to the vessel axis. When measuring aortic root dimensions, peak-to-peak "sinus-to-sinus" diameters should be preferred over "sinus-to-commissure". Additionally, thoracic aortic CTA assesses the severity of calcification of the aortic valve, adjacent cardiac structures, and the thoracic aorta. Maximum Intensity Projection (MIP) and Volume Rendering Technique (VRT) reconstructions allow optimal planning of surgical or transcatheter interventions on the aortic valve and ascending aorta. CMR can be used in addition to or instead of echocardiography for initial and follow-up assessment of LV volumes, function, and regurgitation severity in patients with AR when echocardiographic visualization is suboptimal [1]. CMR can also evaluate thoracic aorta parameters and the extent of myocardial fibrosis [34, 39, 40]. Cinefluoroscopy is used to evaluate the function of mechanical heart valve occluders when dysfunction is suspected. Additionally, cinefluoroscopy can be useful for visualizing and assessing the mobility of previously implanted intracardiac devices (e.g., occluders).

ESC/ACC IIa C (LoE C, GoR 5)

ESC/RSC IIa B (Level of Evidence C, Grade of Recommendation 5)

ESC/ACC IIa C (LoE C, GoR 5)

2.4.2. Invasive research methods

• Coronary angiography is recommended for all patients with AR to detect hemodynamically significant coronary artery stenoses prior to open surgical, transcatheter, or hybrid intervention in the following clinical scenarios: age >40 years, history and/or symptoms of IHD, signs of myocardial ischemia, reduced LVEF <50%, one or more IHD risk factors, or post-radiation injury to rule out concomitant hemodynamically significant coronary stenosis prior to valve surgery [13].

ESC/RSC I A (Level of Evidence C, Grade of Recommendation 5)

Comments: in patients undergoing coronary angiography, direct root aortography and hemodynamic measurements may additionally be performed, and the severity of aortic regurgitation assessed. Due to the low diagnostic value of direct aortography in diagnosing thoracic aortic pathology, direct aortography is not recommended if CTA or aortic MRI is feasible [28, 41].

ESC/RSC IIa C (Level of Evidence C, Grade of Recommendation 5)

ESC/RSC IIb B (LoE C, GoR 5)

Comments: cardiac catheterization with root aortography and LV pressure measurement may be used to assess the severity of regurgitation, LV function, or to determine aortic root dimensions when non-invasive diagnostic methods are uninformative or contradict clinical data in patients with AR. If CTA or aortic MRI is available, invasive aortography is impractical. Invasive measurement of pulmonary artery pressure is strictly indicated only when the severity of pulmonary hypertension determines the indication for surgical or transcatheter intervention [19].

ESC IIa B (Level of Evidence B, Grade of Recommendation 3)

2.5 Other Procedures

Other diagnostic examinations are not routinely required for the diagnosis of AR; diagnostic workup may be expanded at the physician's discretion depending on the clinical situation and the patient's condition.

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

Key questions in determining the management strategy for a patient with aortic regurgitation (adapted from H. Baumgartner et al., 2017) [19]:

• What is the severity of the valve lesion?

• What is the etiology of the valve lesion?

• Are symptoms present?

• Are the existing symptoms related to the valve lesion?

• Are there signs suggesting a potentially poor outcome in an asymptomatic patient if treatment is delayed?

• What is the patient's expected life expectancy and quality of life?

• Do the expected benefits of the intervention outweigh its risks?

• What is the optimal strategy? (open valve replacement using a mechanical or biological prosthesis, open valve-sparing reconstruction, transcatheter intervention, other option)

• How optimal are the hospital's capabilities and outcomes for the patient's planned treatment?

• What are the patient's personal preferences?

3.1 Risk stratification when planning surgical treatment for a patient with aortic regurgitation

To select surgical tactics and optimize treatment, a crucial task is identifying risk factors and predicting surgical outcomes. For this purpose, formulas for assessing mortality risk are used, as presented on the websites of the Society of Thoracic Surgeons (STS) [42] and the European System for Cardiac Operative Risk Evaluation (European System for Cardiac Operative Risk Evaluation – EuroSCORE) [43]. A logistic EuroSCORE ≥ 10%, EuroSCORE II ≥ 4%, or an operative risk level ≥ 10% according to the STS scale are proposed as high-risk criteria [44, 45]. The choice of additional diagnostic methods to verify comorbidities is determined by the clinical situation. When planning patient treatment, it is important to consider a number of factors not included in the EuroSCORE and STS scales, but which affect the risk of complications from aortic valve interventions. Frailty is a decline in physiological reserve and the ability to maintain homeostasis, which increases stress sensitivity and, consequently, the risk of complications during surgical and transcatheter interventions. Frailty assessment is based on a number of objective criteria, and corresponding scales have been developed for this purpose [46, 47, 48]. Malnutrition, cachexia, and cognitive impairment are associated with a high risk of complications and poor prognosis following surgical or transcatheter aortic valve interventions [49, 50]. Individual anatomical features affecting the surgical correction technique: "porcelain" aorta, severe calcification of the aortic valve annulus and adjacent structures of the left ventricular outflow tract [51, 52]. Pathology of other organs and systems: kidney, liver, and lung diseases. Preoperative liver failure is associated with an increased risk of complications. Chronic kidney disease stage 4 or 5 (glomerular filtration rate <30 mL/min) present in the patient entails a high risk of acute renal failure in the early postoperative period, the need for dialysis, severe complications, and an unfavorable outcome. Pulmonary pathology combined with pain syndrome in the early postoperative period after aortic valve intervention using full median sternotomy in cases of prolonged mechanical ventilation is a risk factor for respiratory complications [53, 54, 55, 56]. Since the prevalence and severity of comorbidities increase with age, accurate risk-benefit assessment of a given treatment method becomes more complicated. When planning patient treatment, it is necessary to take into account the capabilities, experience, and outcomes of the specific clinic where the patient will be treated. A multidisciplinary team of specialists should play the primary role in addressing these tasks.

3.2 Conservative treatment

Prevention of rheumatic fever exacerbation

ESC/ESC I A (LoE C, GoR 5)

Comments: prophylactic administration of penicillin-series antibiotics is recommended for 10 years after the last attack of rheumatic fever or until the age of 40 years. Patients who have had a single rheumatic attack are at high risk for recurrent rheumatic episodes. Those suffering from rheumatic carditis have an increased propensity for recurrent rheumatic attacks; therefore, secondary prevention is of great clinical importance to prevent disease progression, decompensation of chronic heart failure (CHF), and thromboembolic events into major vessels. Continuous antibiotic prophylaxis, combined with the identification of a laboratory-confirmed etiological agent of rheumatism, has proven effective. Lifelong prophylaxis is indicated for high-risk patients with AR (group A streptococcus carriers).

Prevention of infective endocarditis

ESC/RSC I B (LoE C, GoR 5)

Treatment of arterial hypertension and lipid-lowering therapy

ESC/ACC IIa B (GoR C, LoE 5)

Comments: first-line drugs in patients with AR and concomitant aortic dilatation are ACE inhibitors or beta-blockers; for hypertension management without dilatation, ACE inhibitors/ARBs, beta-blockers, and other antihypertensive drugs including calcium channel blockers can also be used [161].

• The use of statins is recommended for all patients with AR for primary and secondary prevention of cardiovascular complications based on standard risk scales in accordance with current clinical guidelines "Lipid Metabolism Disorders" [13, 17, 28, 61, 63, 64, 162, 172].

ESC/RSC IA (Level of Evidence C, Grade of Recommendation 5)

Comment: patients with symptomatic valvular disease require surgical intervention rather than medical therapy. At the same time, careful assessment and management of atherosclerosis risk factors are important in patients with aortic valve disease to prevent concomitant CAD.

Treatment of heart failure

• In patients with severe AR, presence of clinical symptoms, left ventricular enlargement (LVESD >50 mm or LVESD index >25 mm/m²) and/or LV dysfunction (LVEF <50%), but with an expected risk of an adverse surgical outcome exceeding that of medical therapy, or with an expected life expectancy <1 year, conservative therapy for the management of hypertension and heart failure is recommended [13, 17, 28, 61, 63, 64].

ESC/RCS I B (LoE B, GoR 3)

• Medical therapy for CHF is recommended for all patients with severe AR in accordance with current clinical guidelines "Chronic Heart Failure" [13, 17, 28, 61, 63, 64, 65, 165, 172].

ESC/RSC I A (Level of Evidence C, Grade of Recommendation 5)

Comments: AR therapy must necessarily include standard CHF medical treatment—diuretics, ACE inhibitors or angiotensin II receptor blockers, beta-blockers, potassium-sparing diuretics, angiotensin II receptor blockers in combination with other agents, sodium-glucose cotransporter 2 (SGLT2) inhibitors (flozins)—which helps improve both patient symptoms and prognosis. ACE inhibitors/valsartan + sacubitril**, beta-blockers (BBs), aldosterone receptor antagonists, dapagliflozin**/empagliflozin** (SGLT2 inhibitors) are indicated as part of a combination four-drug therapy for treating all patients with symptomatic HFrEF (LVEF ≤40%) to reduce CHF-related hospitalizations and mortality. In patients with HFmrEF, the use of ACE inhibitors/ARBs, BBs approved for HFrEF, and aldosterone antagonists may be indicated to reduce the risk of CHF-related hospitalizations and mortality. For ACE inhibitors and ARBs, there is limited evidence of their ability to reduce symptom severity and improve functional class in HFpEF. In patients with HFpEF, BBs may be prescribed when additional indications are present [13, 17, 28, 61, 63, 64, 65, 165].

Following successful surgical treatment of AR with persistent CHF, standard CHF therapy is not contraindicated [66, 67].

Anticoagulant therapy

ESC/ESC I B (GOP A, LoE 1)

• All patients on VKA therapy are recommended to perform self-monitoring of INR, provided they have undergone prior appropriate training in a patient school and medical supervision is maintained (remote monitoring of laboratory parameters or regular doctor visits) [13, 68, 172, 177].

ESC/ESC I B (GOP A, LoE 1)

ESC/ESC I B (Level of Evidence C, LoE 5)

Comments: it is recommended to use the mean INR value as the target rather than a range to prevent extreme values from being regarded as normal targets. High INR variability is a significant predisposing factor for decreased survival and adverse thromboembolic events following heart valve replacement.

Mechanical heart valves with low thrombogenicity include Carbomedics, Medtronic Hall, ATS, Medtronic Open-Pivot, St Jude Medical, Sorin Bicarbon, and the MedInzh-2 bileaflet mechanical prosthesis. Mechanical heart valves with moderate thrombogenicity include other bileaflet prostheses with insufficient clinical data. Mechanical heart valves with high thrombogenicity include Lillehei-Kaster, Omniscience, Starr-Edwards (ball-and-cage prostheses), Bjork-Shiley, and other tilting-disc prostheses [13, 69, 70, 71].

• Direct oral anticoagulants (DOACs) and/or dual antiplatelet therapy (DAPT) are not recommended in patients with installed mechanical heart valve prostheses [13, 172].

ESC/ESC III B (GOP C, LoE 5)

• The addition of low-dose #acetylsalicylic acid (75-100 mg/day) to VKAs is recommended after thromboembolic events occurring despite proper INR control [13, 69, 172].

ESC/ESC IIa C (GOP C, LoE 5)

ESC/ESC IIa C (GOP C, LoE 5)

ESC/ESC IIb C (Level of Evidence C, Grade of Recommendation 5)

• In patients at high hemorrhagic risk with implanted coronary stents and a mechanical aortic valve prosthesis, it is recommended to consider triple therapy with #acetylsalicylic acid** (75-100 mg/day), #clopidogrel** (75 mg/day), and a VKA for a duration of 1 week, regardless of the stent type used and the clinical presentation (acute coronary syndrome or stable coronary artery disease) [78, 170, 171, 172].

ESC/ESC IIa B (GOP C, LoE 5)

Comments: after discontinuing #acetylsalicylic acid** (75-100 mg/day), continue dual therapy, preferably including #clopidogrel** (75 mg/day) and a VKA, with discontinuation of the antiplatelet agent and transition to monotherapy at 6 months after elective PCI and 12 months after ACS [78, 170, 171, 172].

• In patients with a mechanical aortic valve prosthesis and implanted coronary stents who are at high ischemic risk (acute coronary syndrome or presence of anatomical/procedural complexities) exceeding the bleeding risk, it is recommended to consider prescribing triple therapy including #acetylsalicylic acid** (75-100 mg/day), #clopidogrel** (75 mg/day), and a VKA for up to 30 days [78, 170, 171, 172].

ESC/ACC IIa B (Level of Evidence C, Quality of Evidence 5)

Comments: the addition of #low doses (75-100 mg/day) of acetylsalicylic acid** to vitamin K antagonist therapy may reduce the incidence of thromboembolic events at the cost of an increased bleeding risk [112]. Consequently, the addition of antiplatelet agents (B01AC Platelet aggregation inhibitors excluding heparin) to vitamin K antagonists should be restricted to patients at very high risk of thromboembolic complications, where benefits clearly outweigh risks [78, 166, 167]. In patients experiencing thromboembolic events despite target INR levels, #low doses (75-100 mg/day) of acetylsalicylic acid** should be added to vitamin K antagonists.

• In patients with a mechanical aortic valve prosthesis requiring #acetylsalicylic acid** and/or #clopidogrel** in addition to VKAs, it is recommended to maintain VKA dosage in the lower part of the target therapeutic INR range (and time in therapeutic range should be >65-70%) [17, 166, 172].

ESC IIa B (GOP C, LoE 5)

ESC/RSC I C (LOC C, LOE 5)

• Anticoagulant therapy is recommended for patients following bioprosthesis implantation (heart aortic valve bioprosthesis***) who have other indications for anticoagulant therapy (atrial fibrillation with CHA2DS2-VASc score $\ge$3 in women, $\ge$2 in men, venous thrombosis, hypercoagulation, or, with a lower level of evidence, severe left ventricular dysfunction with LVEF <35%) [13, 172].

ESC/ESC I C (GOP C, LoE 5)

• DOACs are recommended as preferred over VKAs starting 3 months after heart valve replacement with a biological prosthesis in patients with atrial fibrillation for the prevention of thromboembolic complications when indicated [72, 73, 74, 75, 76].

ESC/ESC IIa B (GOP B, LoE 1)

• In patients without indications for anticoagulant therapy, the administration of low-dose #acetylsalicylic acid (75-100 mg/day) or anticoagulant therapy with VKAs is recommended during the first 3 months following aortic valve replacement with a biological prosthesis [13, 172].

ESC/ESC IIa B (GOP C, LoE 5)

• Lifelong anticoagulant therapy is recommended in patients after transcatheter aortic valve implantation if other indications for anticoagulant therapy are present (atrial fibrillation, venous thrombosis, hypercoagulation, or, with a lower level of evidence, severe left ventricular dysfunction with LVEF <35%) [13, 69, 172].

ESC/RSC I B (LOC C, LOE 5)

• Lifelong single antiplatelet therapy with low-dose #ASA (75–100 mg/day) is recommended after transcatheter aortic valve implantation in patients without indications for anticoagulant therapy [13, 69, 172].

ESC/RSC I A (LOC C, LOE 5)

• Single antiplatelet therapy with low-dose #acetylsalicylic acid (75-100 mg/day) is recommended for the first 3 months after valve-sparing aortic valve procedures in the absence of other indications for anticoagulant therapy [13, 69, 172].

ESC/ACC IIa C (LoE C, LoR 5)

• DAPT is not recommended for patients after transcatheter aortic valve implantation for thrombosis prevention in the absence of clear indications [172, 178].

ESC/ESC IIa C (GOP B, LoE 2)

• Routine use of anticoagulant therapy is not recommended after transcatheter aortic valve implantation in patients without indications for anticoagulant therapy [13, 78, 172].

ESC/ESC III B (GOP C, LoE 5)

• To prevent stroke in patients with atrial fibrillation and aortic regurgitation, direct oral anticoagulants are recommended as preferred over VKAs for anticoagulant therapy [13, 72-74, 172].

ESC/ESC I A (GOP B, LoE 1)

Comments: in patients with severe aortic regurgitation who will soon have indications for surgical treatment with a mechanical valve prosthesis, VKAs are preferred.

3.3 Surgical Treatment

• Surgical correction of aortic regurgitation (aortic valve replacement under cardiopulmonary bypass) is recommended for patients with symptoms of heart failure regardless of left ventricular function to alleviate clinical symptoms, prevent complications, and improve life expectancy [13, 172].

ESC/ESC I B (GOP C, LoE 5)

• Surgical correction of aortic regurgitation (aortic valve replacement under cardiopulmonary bypass) is recommended for asymptomatic patients with left ventricular dilatation (LVESD >50 mm or LVESD index >25 mm/m² in patients of small height and weight) or with LVEF <50% to prevent complications and improve life expectancy [13, 80, 81, 82, 172].

ESC/ESC I B (GOP B, LoE 3)

• Surgical correction of aortic regurgitation (aortic valve replacement under cardiopulmonary bypass) is recommended for symptomatic and asymptomatic patients with severe regurgitation who have indications for coronary artery bypass grafting and/or "open" surgery on another heart valve to alleviate clinical symptoms, prevent complications, and improve life expectancy [7, 13, 19, 172].

ESC/RCS I C (LoE C, GoR 5)

ESC/SCO IIb C (LoE B, GoR 3)

ESC/SCO I B (LoE C, GoR 4)

Comments:in the case of unchanged (soft, non-fibrosed, and non-calcified) aortic valve cusps, valve-sparing intervention (aortic valve repair under cardiopulmonary bypass) may be performed. The optimal candidates for this treatment method are patients with type I (aortic root dilatation combined with morphologically normal cusps) and type II (cusp prolapse) aortic regurgitation [16, 85]..The pioneering role in the development and clinical implementation of aortic root replacement with aortic valve preservation for the surgical treatment of aortic root aneurysms combined with aortic regurgitation belongs to M. Yacoub [86]. In 1983, a team of authors under his leadership presented a brief description of a valve-sparing technique for treating aneurysm and dissection of the aortic root. Undoubtedly, a giant contribution to the development of surgical treatment for aortic root aneurysms was made by T. David. He became one of the first to use the very concept of valve-sparing aortic replacement. In 1992, T. David et al. published an article describing aortic root replacement with aortic valve preservation via its reimplantation into an aortic graft [87]. A distinctive feature of this approach is the stabilization of the aortic root at all levels (aortic valve annulus, sinuses of Valsalva, sinotubular junction). A year later, M. Sarsam and M. Yacoub described valve-sparing aortic root replacement with aortic valve remodeling [88]. Aortic root remodeling differs fundamentally from T. David's reimplantation technique by the absence of aortic stabilization at the level of the aortic valve annulus, which can potentially lead to recurrent aortic regurgitation. There are several modifications of aortic root replacement with aortic valve preservation: creation of pseudo-sinuses by suture plication of the aortic graft, use of a prefabricated sinusoid graft (synthetic blood vessel graft***), and a combination of aortic valve remodeling and aortic root stabilization by implanting a Teflon strip or a support ring (aortic valve annuloplasty ring***) [89, 90, 91]..One of the variants of valve-sparing aortic root replacement is the Florida sleeve technique proposed by P. Hess et al. in 2005 [92]. Unlike the David procedure, the Florida sleeve variant does not involve excision of the sinuses of Valsalva—the entire aortic root is implanted into the graft. The diameter of the graft is chosen to achieve restoration of normal aortic valve coaptation function. If necessary, one or both coronary arteries are reimplanted into the aortic graft. Aortic root reimplantation into the graft demonstrates consistently good clinical results in the early postoperative period and can become an alternative to the classic David procedure [93]..According to clinics with extensive experience in valve-sparing ascending aorta replacement, additional interventions on the aortic valve cusps do not significantly worsen the immediate and long-term surgical outcomes. Valve-sparing aortic root replacement reduces the risk of long-term adverse events associated with the prosthetic aortic valve and improves patients' quality of life [94, 95, 96]..Valve-sparing aortic root replacement in bicuspid aortic valve remains debatable. Due to initial cusp asymmetry, adequate restoration of planimetry and aortic valve function is a challenging task. Nevertheless, a number of studies have shown good short- and long-term results of aortic root replacement with preservation of the bicuspid aortic valve [97, 98].

ESC/SCO IIa B (LoE C, GoR 4)

ESC/SCO IIa A (LoE B, GoR 3)

• Surgery on the ascending aorta (reconstruction of the ascending aorta with aortic valve replacement) is recommended in patients with syndromic forms (Marfan syndrome, etc.) of root and/or tubular ascending aorta aneurysms and a maximum ascending aorta diameter >50 mm to prevent complications and improve life expectancy [13, 34].

ESC/RSC I C (LoE C, GoR 5)

• Surgical correction of ascending aorta dilatation (reconstruction of the ascending aorta with aortic valve replacement) is recommended in all cases of root and/or tubular ascending aorta aneurysm with a maximum diameter >55 mm, regardless of the severity of aortic regurgitation [13, 34].

ESC/ACC IIa C (LoE C, GoR 5)

• Surgical correction of ascending aorta dilatation (reconstruction of the ascending aorta with aortic valve replacement) is recommended in patients with syndromic forms of ascending aorta aneurysms and additional risk factors (family history of aneurysms, aortic dissections, and sudden deaths, personal history of dissections of any other arteries, severe aortic or mitral regurgitation, planned pregnancy, uncontrolled hypertension, ascending aorta expansion >3 mm/year) confirmed by TGFBR1 or TGFBR2 gene mutations, with root and/or tubular ascending aorta dilatation and a maximum diameter >45 mm, regardless of the severity of aortic regurgitation, to prevent complications and improve life expectancy [13, 34].

ESC/ACC IIa C (LoE C, GoR 5)

• Surgical correction of ascending aorta dilatation (reconstruction of the ascending aorta with aortic valve replacement) is recommended in patients with bicuspid aortic valve combined with risk factors (family history of aneurysms, aortic dissections, and sudden deaths, personal history of dissections of any other arteries, severe aortic or mitral regurgitation, planned pregnancy, uncontrolled hypertension, ascending aorta expansion >3 mm/year according to aortic CT angiography) or with aortic coarctation, and a maximum root and/or tubular ascending aorta diameter >50 mm, regardless of the severity of aortic regurgitation, to prevent complications and improve life expectancy [13, 34].

ESC/ACC IIa C (LoE C, GoR 5)

ESC/ACC IIa C (LoE C, GoR 5)

ESC/RSC I C (LoE C, GoR 5)

ESC/ACC IIa C (LoE C, GoR 5)

ESC/ACC IIa C (LoE C, GoR 5)

Recommendations on the choice of artificial heart valve type

• Aortic valve replacement with a mechanical prosthesis is recommended provided there is written informed consent from the patient and no contraindications to long-term anticoagulant therapy (increased bleeding risk due to comorbidities, poor treatment adherence, as well as geographical, domestic, and occupational conditions) [13, 172].

ESC/RSC I C (LoE C, GoR 5)

• Aortic valve replacement with a mechanical prosthesis is recommended for patients already receiving anticoagulant therapy due to the presence of a mechanical heart valve in another position [13, 172].

ESC/RCS IIa C (LoE C, GoR 5)

• Aortic valve replacement with a mechanical prosthesis is recommended to be discussed for patients under 65 years of age [13, 103, 104].

ESC/RSC IIa B (LoE B, GoR )

• Aortic valve replacement with a mechanical prosthesis is recommended for patients at risk for rapid structural degradation of a bioprosthesis (hyperparathyroidism, hemodialysis) [13].

ESC/RSC I C (LoE C, GoR 5)

• Aortic valve replacement with a mechanical prosthesis is recommended for patients with an optimal life expectancy (taking into account age, gender, comorbidities, and national life expectancy) in whom repeat valve surgery (if feasible) would be associated with a high risk of complications (low LVEF, deep vein thrombosis, pulmonary embolism (PE), hypercoagulability, antiphospholipid syndrome, etc.) [13, 172].

ESC/RSC IIa C (LoE C, GoR 5)

Comments: the choice of the implanted prosthesis type (mechanical or biological) is the result of balancing the risks of bleeding/embolism associated with a mechanical prosthesis against the risk of degenerative changes in bioprostheses. A mechanical prosthesis is preferable for patients under 65 years of age in the absence of additional bleeding risk factors. In patients with aortic regurgitation aged 65 years and older, either type of prosthesis is acceptable, taking into account the risk of bleeding, the patient's social status (living in a rural area, difficulties with INR monitoring), expected adherence to anticoagulant therapy, presence of comorbid conditions (severe CHF, AF) requiring anticoagulants, and patient preferences [12, 13, 19, 103, 104].

• Aortic valve replacement with a mechanical prosthesis is recommended for patients with an optimal life expectancy in the absence of contraindications to long-term anticoagulant therapy [172, 179-181].

ESC/RSC IIa B (LoE B, GoR 2)

• ·Aortic valve replacement with a biological prosthesis is recommended in the presence of written informed consent from the patient or in the presence of contraindications to long-term anticoagulant therapy (high risk of hemorrhagic complications, comorbidities, lack of treatment adherence, poor therapy accessibility, personal preferences, lifestyle, and occupation), as well as in patients with a life expectancy shorter than the expected durability of the bioprosthesis [13, 172].

ESC/RSC I C (LoE C, GoR 5)

• Aortic valve replacement with a biological prosthesis is recommended when effective anticoagulation is unlikely (poor treatment adherence, limited availability) or contraindicated due to a high bleeding risk (prior major bleeding, comorbidities, poor treatment adherence, patient refusal, lifestyle, profession), in patients whose life expectancy is shorter than the expected durability of the bioprosthesis (life expectancy >10 years is estimated based on age, gender, comorbid conditions, and national life expectancy data) [13, 172].

ESC/RSC I C (LoE C, GoR 5)

• Aortic valve replacement with a biological prosthesis is recommended to be discussed in re-operations for mechanical valve thrombosis despite adequate long-term anticoagulant therapy [13, 172].

ESC/RSC I C (LoE C, GoR 5)

• Aortic valve replacement with a biological prosthesis is recommended to be discussed in patients with low probability and/or low surgical risk when undergoing reintervention on the valve [13, 172].

ESC/RCS IIa C (LoE C, GoR 5)

• Aortic valve replacement with a biological prosthesis is recommended to be discussed in young women planning pregnancy [13, 172].

ESC/RCS IIa C (LoE C, GoR 5)

ESC/RSC IIb B (LoE B, GoR 2)

Comments: to date, there are no new high-quality data supporting a reduction in the established age threshold when deciding on the implantation of a mechanical or biological aortic valve prosthesis [61, 83]. The issue of the optimal aortic valve substitute in young patients remains debatable. In a certain group of specially selected patients, aortic valve replacement with a pulmonary autograft (Ross procedure) can be performed, but the clinic must have extensive experience in reconstructive surgery of the aortic valve and aortic root [105]. Treatment strategies for patients with a "narrow" aortic valve annulus include aortic root-enlarging procedures and implantation of sutureless prostheses. Also, the use of sutureless and rapid-deployment aortic valve prostheses (biological prosthesis) can reduce trauma, duration of cardiopulmonary bypass and myocardial anoxia, and potentially lower the risks of perioperative complications of "open" surgical aortic valve replacement. However, currently there are no data from large randomized trials on the short- and long-term safety, efficacy of such approaches, and hemodynamic effects compared with traditional aortic valve replacement, which remains the "gold standard" of treatment [13].

• In patients with isolated aortic regurgitation, transcatheter aortic valve implantation (TAVI) is not recommended [12, 172].

ESC/RSC III, B (LoE C, GoR 5)

Comments: in certain patients with aortic regurgitation who have contraindications to surgery under cardiopulmonary bypass, TAVI may be considered as a life-saving intervention at a center with extensive TAVI experience, provided certain criteria are met (appropriate aortic annulus size, presence of minimal calcification).

3.4 Other treatment

Analgesic therapy in adults

Perioperative pain management is routine; the analgesic strategy is determined by the attending physician and the anesthesiologist-resuscitator depending on the scope of the surgical intervention.

• All patients with aortic regurgitation admitted to the hospital for surgical treatment are recommended to receive anxiolytics in the evening before surgery as part of premedication for sedation and emotional stability to reduce emotional stress. Opioids and/or benzodiazepine derivatives are used for premedication before transferring the patient to the operating room to provide sedation and emotional stability [152].

ESC \ RSC I C (Level of Evidence C, Quality of Evidence 5)

Comments: in the evening before surgery: benzodiazepine derivatives in individual dosages. Before transfer to the operating room: intramuscular trimeperidine** and/or diazepam**/midazolam**. Drugs that increase heart rate should be excluded from premedication.

• All patients with aortic regurgitation admitted to the hospital for surgical treatment are recommended to use the following for intraoperative anesthesia: propofol**, benzodiazepine derivatives, halogenated hydrocarbons. Fentanyl** (for premedication before surgery), Diazepam** (as part of preoperative preparation) [152, 153, 168].

ESC / RSC I C (LoE B, GoR 2)

Comments: the following drugs are used for intraoperative anesthesia: midazolam**/diazepam**/propofol** and fentanyl**, sodium oxybutyrate**; halogenated hydrocarbons can be used in combination with intravenous fentanyl** in calculated dosages. A multicenter randomized controlled trial revealed no differences in clinical outcomes when using total intravenous anesthesia based on propofol** and fentanyl** versus combined anesthesia using halogenated gaseous anesthetics (N01AB Halogenated hydrocarbons) and fentanyl** during cardiac surgery [169].

• All patients with aortic regurgitation admitted to the hospital for surgical treatment are recommended to use age-appropriate doses of opioids for analgesia in the early postoperative period [152].

ESC / RSC I C (LoE C, GoR 3)

Comments: drugs used for postoperative analgesia: first day after surgery — trimeperidine** or morphine** intramuscularly every 4–8 hours, NSAIDs (M01A Non-steroidal anti-inflammatory and antirheumatic products). If special infusion pumps are available, patient-controlled analgesia with fentanyl** is effective. If severe pain persists, trimeperidine**/morphine**/fentanyl** as indicated.

Use of nitric oxide in the postoperative period

• In the surgical treatment of aortic regurgitation in patients with precapillary pulmonary hypertension (mean pulmonary artery pressure ≥ 20 mm Hg, pulmonary capillary wedge pressure ≤ 15 mm Hg) with pulmonary vascular resistance greater than 5 Wood units and echocardiographic signs of right ventricular dysfunction, it is recommended to consider the use of inhaled nitric oxide during the intra- and postoperative periods [106].

ESC/RSC IIa B (LoE A, GoR 1)

Comments: patients with AV pathology often exhibit an increase in pulmonary circulation pressure (group 2 pulmonary hypertension, post-capillary pulmonary hypertension). Over time, such patients begin to develop increased pulmonary vascular resistance, i.e., a pre-capillary component appears (reactive pulmonary hypertension). Surgical intervention on the AV effectively relieves the post-capillary component of pulmonary hypertension. However, the increased pulmonary vascular resistance (pre-capillary component) persists in the postoperative period, adversely affecting hemodynamic parameters, up to the development of RV dysfunction. The performed meta-analysis confirmed a significant improvement in clinical parameters—a reduction in the duration of mechanical ventilation and the length of stay in the intensive care unit with inhaled nitric oxide [106].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Medical rehabilitation programs for patients after surgical correction of AR are aimed at limiting the psychological and physiological stress associated with cardiac surgery, reducing the risk of mortality and disability, modifying lifestyle, and improving cardiovascular function in order to maximize the possible quality of life of patients [107].

Medical (cardiac) rehabilitation is presented as a three-stage system through which patient routing is implemented (Appendix B Fig. PB-3) [108]. Medical rehabilitation care for patients with AR is provided on a scheduled basis after the establishment of a diagnosis (upon initial contact with the patient) or in the chronic course of the disease, regardless of the disease duration, provided the patient's clinical state is stable, medical indications are met, and contraindications to specific rehabilitation methods are taken into account.

When planning surgical correction of AR, patient preparation for effective recovery is recommended to begin in the preoperative period—at the rehabilitation stage—in order to inform the patient about the nature and scope of the surgical intervention, teach them to optimally perceive their well-being after surgery, and properly follow postoperative recommendations. Rehabilitation measures and methods should be applied taking into account the rehabilitation stage and the patient's clinical and physical condition.

Cardiac rehabilitation is carried out by a multidisciplinary team of medical professionals to achieve optimal physical and psychosocial health for patients with AR, with the participation of partners, other family members, and caregivers [109].

ESC \ RSC IIa C (Cochrane Grade A, Level of Evidence 1)

Comments: the presence of contraindications to exercise training is not a factor limiting patient participation in cardiac rehabilitation programs and does not preclude the use of other methods of physical rehabilitation (therapeutic gymnastics complexes, walking, etc.).

ESC/RSC IIa C (Level of Evidence C, Formulated Clinical Recommendations Grade 5)

Comments: the majority of cardiac rehabilitation programs are carried out at the outpatient stage, which is recommended to be conducted in an in-person, remote (at home using digital and mobile health tools), or mixed format to increase patient reach for rehabilitation measures, improve adherence to lifestyle changes, rehabilitation, and drug therapy [117, 118, 119, 120].

Cardiac rehabilitation begins as early as possible in intensive care units (if the patient is in a stable condition). The intensity of rehabilitation depends on the patient's condition and complications in the acute phase of the disease. A randomized controlled trial and systematic review show that early mobilization improves physical function (6-minute walk test distance improved by 54 m) at discharge in post-cardiac surgery patients [121].

A prospective randomized controlled trial showed that early initiation of cardiac rehabilitation improved postoperative functional capacity (6-minute walk test), reduced the duration of mechanical ventilation, oxygen dependency, and hospital stay in patients undergoing elective cardiac surgery [122, 123].

ESC \ RSC IIa C (Cochrane Grade C, Level of Evidence 5)

ESC/RSC IIa C (Level of Evidence C, Formulated Clinical Recommendations Grade 5)

Comments: to assess the patient's clinical status, level of functioning and daily activity, and the impact of personal and environmental factors, it is recommended to use standardized and valid diagnostic methods and assessment tools based on the International Classification of Functioning, Disability and Health (ICF) [108, 125, 126, 127].

ESC/RSC IIa C (Level of Evidence C, Formulated Clinical Recommendations Grade 5)

Comments: if indicated it is recommended to perform testing using the Hospital Anxiety and Depression Scale (HADS) to identify symptoms of anxiety/depression (Appendix G, Table PG-1).

ESC/ACC I A (LoE C, LoD 5)

Comments: patient information and education should be provided in any accessible format (individually, as part of rehabilitation counseling, and/or in the "School for Patients with Valvular Heart Disease") in person or online [110, 120, 130].

ESC/RSC IIa C (Level of Evidence C, Formulated Clinical Recommendations Grade 5)

ESC \ RSC IIa C (Cochrane Grade C, Level of Evidence 5)

Comments: a personalized exercise training program for patients with AR after surgical treatment (in the absence of contraindications, Appendix A3-2) is formed depending on the stage of cardiac rehabilitation and includes regular moderate-intensity aerobic (dynamic) physical exercises (low-intensity at the start), low-to-moderate-intensity strength training (as indicated, to increase and/or maintain lower extremity muscle endurance or strength in patients with low risk of postoperative complications, good wound healing after sternotomy, and no earlier than six weeks after surgery).

Both patients with aortic regurgitation (AR) who have undergone surgery and those without surgical treatment should have physical rehabilitation programs (in the absence of contraindications) including therapeutic exercise complexes with breathing exercises, inspiratory muscle training using breathing trainers (as indicated) and other breathing techniques (as indicated), and walking. For the safety of the physical rehabilitation program, it is recommended to monitor the patient's condition (complaints, clinical symptoms, blood pressure level, heart rate, and ECG as indicated), and to assess the level of physical exertion using the Borg scale (Borg Rating of Perceived Exertion, Borg RPE) during training (Appendix G, table PG-3) [110, 131].

ESC/RSC IIa C (Level of Evidence C, Formulated Clinical Recommendations Grade 5)

Comment: an indication for sanatorium-resort treatment is rheumatic aortic valve disease with stage IIA chronic heart failure (FC II) without prognostically unfavorable heart rhythm and conduction disorders, without signs of rheumatic process activity, and without angina attacks [140].

5. Prevention and Dispensary Observation

Dispensary follow-up (Active surveillance)

• All patients with AR, as well as those after aortic valve replacement, are recommended lifelong follow-up by a cardiologist, or in the absence of a cardiologist, by a general practitioner or family physician to determine the frequency of visits, monitor compliance with prescribed recommendations, timely modify therapy, assess cardiovascular risk, refer for additional studies, sanatorium-resort treatment, and, if necessary, hospitalization [19, 20, 110].

ESC/RSC I C (LoE C, GoR 5)

ESC/RSC I C (LOC C, LOE 5)

Comments: asymptomatic patients with mild AR, no left ventricular enlargement or systolic dysfunction, and no pulmonary hypertension may have cardiology visits once a year. Patients must be instructed to consult a physician immediately if symptoms change (worsen). Annual echocardiography is mandatory even in the absence of clinical data favoring AR progression. In patients with moderate AR, clinical evaluation, including echocardiography, should be performed annually or more frequently if new symptoms appear.

ESC/ACC IIa C (LoE C, LoR 5)

Comments: preoperative left ventricular ejection fraction is an important predictor of postoperative survival in patients with severe chronic AR [8, 72]. It is also advisable to measure LV end-systolic dimension (ESD) and LV ESD index by echocardiography as a criterion for selecting indications for surgical correction of asymptomatic AR. If patients develop clinical symptoms, surgery is necessary even if systolic function and left ventricular dimensions are within normal limits [13, 17].

• Performing echocardiography is recommended for the dynamic follow-up of asymptomatic patients with previously diagnosed AR: every 6–12 months for severe AR, every 1–2 years for moderate AR, and every 3–5 years for mild AR [12, 13].

ESC\ACC I A (GoR C, LoE 5)

ESC/ACC IIa C (LoE C, LoR 5)

Comments: the evaluation includes:

- Transthoracic echocardiography;

- Electrocardiogram recording (12 leads);

- Targeted chest X-ray in 2 projections (anteroposterior and left lateral);

- Complete blood count;

- Biochemical blood analysis;

- Determination of INR level (in case of VKA therapy);

- Imaging study of the ascending aorta (CT angiography or MRI of the heart and great vessels in case of concomitant ascending aorta intervention).

If the patient was operated on for infective endocarditis, a doctor's visit must be scheduled after the completion of the antibiotic therapy course (if imaging diagnostic methods are required – contrast-enhanced cardiac MRI) [110, 125].

ESC/ACC I C (LoE C, LoR 5)

ESC/ACC IIa C (LoE C, LoR 5)

ESC/ACC IIa C (LoE C, LoR 5)

• Patients with AR and after aortic valve replacement are recommended to have a resting ECG recorded, deciphered, described, and interpreted once a year during a control visit and additionally upon the appearance of arrhythmia, as well as when prescribing or changing treatment that affects intracardiac electrical conduction [20, 158].

ESC/RSC I C (LoE C, GoR 5)

ESC/ACC I B (LoE C, GoR 5)

• To resolve the issue of referring patients with AR for echocardiography, transesophageal echocardiography, MRI, CT, coronary angiography, and other imaging studies, it is recommended to consult a cardiologist [20].

ESC/RSC IIa C (LoE C, GoR 5)

ESC/RCS I C (LoE C, GoR 5)

• After the initial postoperative examination, it is recommended that the patient with AR be followed up and re-examined (with echocardiography) at 6 and 12 months, and then annually if the clinical course is uncomplicated [12, 13, 19, 111].

ESC/RCS IIa C (LoE C, GoR 5)

ESC/ACC I C (LOE C, GoE 5)

• Patients who have undergone "open" surgical reconstruction of the thoracic aorta are recommended to undergo CT angiography of the thoracic aorta within the first month after the procedure, then annually for the first 2 years after surgical treatment, and thereafter every 5 years if the aortic condition is stable [164].

ESC/RSC I B (LEL 5, GRD C)

Prevention

ESC/ESC I A (LoE C, GoR 5)

Comments: preventive prescription of penicillin-class antibiotics is recommended for 10 years after the last attack of rheumatic fever or until the age of 40. Patients who have had a single rheumatic attack are at high risk of recurrent rheumatic flare-ups. Those suffering from rheumatic carditis have an increased tendency to recurrent rheumatic attacks; therefore, their secondary prophylaxis is of great clinical importance, preventing the progression of valve disease, heart failure decompensation, and thromboembolic events in the great vessels. Continuous antibacterial prophylaxis, coupled with the establishment of a laboratory-confirmed etiological agent of rheumatism, has proven its effectiveness. Lifelong prophylaxis is indicated for patients with high-risk AR (group A streptococcus carriers)

• All patients with an implanted mechanical valve are recommended lifelong intake of VKAs under INR control for the prevention of thromboembolic complications [13, 68].

ESC/RSC I B (Level of Evidence C, Quality of Evidence 5)

ESC/ACC I C (LE C, LoE 5)

• All patients receiving VKA therapy are recommended to perform self-monitoring of INR, provided they have undergone appropriate training in a patient school and are under medical supervision (remote laboratory monitoring or regular doctor visits) [13, 68, 172, 177].

ESC/RSC I B (LOC C, LOE 5)

ESC/RSC I B (Level of Evidence C, Quality of Evidence 5)

Comments: history of thromboembolism, atrial fibrillation, hypercoagulability, venous thrombosis, severe left ventricular dysfunction (left ventricular ejection fraction less than 35%).

• Patients taking VKAs are recommended to discontinue the drug at least 4 days prior to elective non-cardiac surgery associated with a high risk of postoperative complications and death, aiming for an INR <1.5, and to resume VKA therapy within 24 hours after surgery in the absence of contraindications [172, 182–184].

ESC/RCS I B (Level of Evidence B, Grade of Recommendation 1)

ESC/RCS IIa B (Level of Evidence B, Grade of Recommendation 1)

ESC/ACC I A (LE B, LoE 1)

ESC/ACC IIb B (LE B, LoE 2)

• For the prevention of infective endocarditis, antibacterial therapy is recommended before dental procedures in all patients with mechanical and biological valves in accordance with the current clinical guidelines "Infective Endocarditis and Cardiac Device Infections" [12, 160].

ESC/ACC IIa B (LE C, LoE 5)

ESC/ACC IIa B (Level of Evidence C, Quality of Evidence 5)

• Patients after SAVR with LV dysfunction are recommended to undergo pharmacotherapy for heart failure in accordance with current clinical guidelines "Chronic Heart Failure" [7, 13, 28, 142, 143].

ESC/RCS I C (LoE C, GoR 5)

ESC/ACC I C (LE C, LoE 5)

6. Organization of Medical Care

Indications for hospitalization in a medical organization:

• All patients with suspected acute AR due to acute aortic dissection or IE are recommended urgent hospitalization in a hospital with cardiac surgery capabilities for diagnosis verification, complication detection, treatment, and improvement of life prognosis [13].

ESC/RCS I C (LoE C, GoR 5)

Comments: since such patients may require advanced differential diagnosis, hospitalization in a multidisciplinary hospital with the capacity for emergency diagnostics and treatment of acute valvular and other pathology is optimal. Particular attention should be paid to patients with manifestations of congestive heart failure persisting at rest, cardiac asthma, hypotension, and history of syncopal episodes.

Indications for patient discharge from a medical organization

• Patients with AR are recommended to be discharged from the hospital provided their clinical condition has stabilized and the chosen treatment strategy has been implemented to prevent complications and improve life prognosis [13].

ESC/RCS I C (LoE C, GoR 5)

Comments: following the implementation of the treatment strategy, patients are recommended to be discharged to the outpatient stage with mandatory subsequent follow-up examinations.

• Following the patient's clinical stabilization, if another primary disease requiring priority hospitalization was identified during their hospital stay, the patient is recommended to be transferred to the appropriate department for diagnosis verification, complication detection, treatment, and improvement of life prognosis [13].

ESC/RCS I C (LoE C, GoR 5)

Criteria for Evaluating the Quality of Medical Care

Quality assessment criteria for primary health care provided to adults with aortic regurgitation (ICD-10 codes: I35.1/Q23.1/Q23.8/Q23.9/I06.1)

Quality assessment criteria for specialized medical care provided to adults with aortic regurgitation (ICD-10 codes: I35.1/Q23.1/Q23.8/Q23.9/I06.1)

References

Appendix A1. Working Group Composition

Working Group Chairs:

1. Bokeria L.A., Academician of the Russian Academy of Sciences (Moscow) ASSC

2. Uspensky V.E., MD (Saint Petersburg) RSC, ASSC

3. Kuts E.V., MD (Moscow) ASSC

4. Irtyuga O.B., MD (Saint Petersburg) RSC

Working Group Members:

5. Alexandrova S.A., PhD (Moscow) RSRS

6. Alekyan B.G., Academician of the Russian Academy of Sciences (Moscow) Chairman of RSRAIVS

7. Amiragov R.A., PhD (Moscow) ASSC

8. Aronov D.M., MD, Professor (Moscow) RSC, RCRS

9. Asatryan T.V., PhD (Moscow) ASSC

10. Babakekhyan M.V., (Saint Petersburg) RSC

11. Barbukhatti K.O., MD, Associate Professor (Krasnodar) ASSC

12. Bogachev-Prokofiev A.V., MD (Novosibirsk) RSC, ASSC

13. Boytsov S.A., Academician of the Russian Academy of Sciences (Moscow) RSC

14. Bubnova M.G., MD, Professor (Moscow) RSC, RCRS

15. Gordeev M.L., MD, Professor, Corresponding Member of the Russian Academy of Sciences (Saint Petersburg) RSC, ASSC

16. Dzhordzhikiya R.K., MD, Professor (Kazan) ASSC

17. Dorofeev A.V., PhD (Moscow) RSRS

18. Zheleznev S.I., Professor (Novosibirsk) ASSC

21. Karaskov A.M., Academician of the Russian Academy of Sciences (Novosibirsk) ASSC

22. Kovalev S.A., Professor (Voronezh) ACSV

23. Kozlov B.N. (Tomsk) ACSV

24. Komlev A.E., PhD in Medicine (Moscow) RSS

25. Matskeplishvili S.T., Corr. Member of the Russian Academy of Sciences (Moscow) RSS

27. Mironenko V.A., DSc in Medicine (Moscow) ACSV

28. Mironenko M.Yu., PhD in Medicine (Moscow) RSSR

29. Muratov R.M., DSc in Medicine, Professor (Moscow) ACSV

30. Nikitina T.G., Prof. (Moscow)

32. Pogosova N.V., DSc in Medicine, Professor (Moscow) RSS

33. Protopopov A.V., DSc in Medicine, Professor (Krasnoyarsk), RSSRDT

34. Pugina M.Yu., (Saint Petersburg) RSS

35. Rosseykin E.V. (Khabarovsk) ACSV

36. Sinitsyn V.E., DSc in Medicine, Professor (Moscow) RSSR

37. Skopin I.I., Corr. Member of the Russian Academy of Sciences (Moscow) ACSV

38. Sukhova I.V., PhD in Medicine, (Saint Petersburg) RSS

39. Tarasov D.G., PhD in Medicine (Astrakhan) ACSV

40. Tarkova A.R., PhD in Medicine (Novosibirsk) RSSR

41. Farulova I.Yu., PhD in Medicine (Moscow) RSSR

42. Khubulava G.G., Academician of the Russian Academy of Sciences (Saint Petersburg) ACSV

43. Charchyan E.R. (Moscow) ACSV

44. Chernov I.I., PhD in Medicine (Astrakhan) ACSV

45. Shlyakhto E.V., Academician of the Russian Academy of Sciences (Saint Petersburg) RSS

46. Schneider Yu.A., DSc in Medicine (Kaliningrad) ACSV

47. Yurpolskaya L.A., DSc in Medicine (Moscow) RSSR

The working group members confirmed no financial support/conflict of interest. In the event of a reported conflict of interest, the working group member(s) were excluded from discussions related to the area of conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

1. Cardiologist.

2. General practitioner / Physician.

3. General practitioner (family physician).

4. Cardiovascular surgeon.

Since the RSC is a member of the European Society of Cardiology (ESC) and RSC members are also ESC members, all European guidelines are formulated with the participation of Russian experts who are co-authors of the guidelines. Thus, existing ESC guidelines reflect the consensus of leading Russian and European cardiologists.

Therefore, the development of national guidelines was based on ESC guidelines, taking into account national specifics, examination and treatment features, and the availability of certain medical care. For this reason, during the development of Russian clinical guidelines by the RSC, international recommendation classes of indications were used, which make it possible to assess the necessity of implementing the recommendation statement and the levels of evidence for these classes (Tables 1/A2 and 2/A2).

In cases where the European guidelines lacked classes and levels of evidence, but in the opinion of RSC experts these statements were extremely necessary for clinical practice or conversely were strictly contraindicated, RSC experts, following the rules for formulating recommendation classes according to the European Society of Cardiology guidelines, assigned the classes and levels themselves. In such cases, the designation ESC/RSC indicates classes assigned by RSC experts.

In addition, a new system of levels of evidence (LE) and grades of recommendations (GR) scales for therapeutic, rehabilitative, preventive, and diagnostic interventions (Tables 3/A2, 4/A2, and 5/A2) introduced in 2018 by the Center for Healthcare Quality Assessment and Control of the Russian Ministry of Health was added. Thus, two scales were used simultaneously in the text of the clinical guidelines developed by RSC experts (Tables 1/A2, 2/A2, 3/A2, 4/A2, 5/A2).

Table 1/A2. Classes of recommendations according to the European Society of Cardiology (ESC) guidelines.

Table 2/A2. Levels of evidence according to the European Society of Cardiology (ESC) guidelines.

Table 3/A2. Scale for assessing levels of reliable evidence (LRE) for diagnostic methods (diagnostic interventions)

Table 4/A2. Scale for assessing levels of reliable evidence (LRE) for methods of prevention, treatment, and rehabilitation (preventive, therapeutic, and rehabilitative interventions)

Table 5/A2. Scale for assessing the levels of evidence (LE) for prevention, diagnostic, treatment and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation 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

Appendix A3-1

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

2. Order of the Russian Ministry of Health No. 918n dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to Patients with Cardiovascular Diseases");

3. "On Approval of Classifications and Criteria Used in Carrying Out Medical and Social Assessment of Citizens by Federal Medical and Social Assessment Institutions" (Order of the Russian Ministry of Health No. 374n dated July 26, 2024);

4. "On the Procedure for Organizing Medical Rehabilitation of Adults" (Order of the Russian Ministry of Health No. 788n dated July 31, 2020);

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

6. "On Approval of the Rules for Conducting Ultrasound Examinations" (Order of the Russian Ministry of Health No. 557n dated June 8, 2020).

7. Order of the Ministry of Health of the Russian Federation No. 203n dated April 14, 2025, "On approval of criteria for assessing the quality of medical care".

8. Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, "On Approval of the Procedure and Timelines for the Development of Clinical Practice Guidelines, Their Revision, the Standard Template of Clinical Practice Guidelines, and Requirements for Their Structure, Content, and the Scientific Validity of Information Included in Clinical Practice Guidelines" (registered on May 8, 2019, No. 54588).

Appendix A3-2. Contraindications to physical training in patients with aortic regurgitation after surgical treatment

• Recent intraoperative myocardial infarction (not earlier than 3 weeks from the onset of myocardial infarction);

• Postoperative complications (post-cardiotomy syndrome with pericarditis and/or pleurisy, pulmonary edema, endocarditis, newly developed cardiac dysfunction, postoperative wound suppuration, and septic conditions);

• Pronounced diastasis and/or pathological mobility of the sternum (contraindication for upper extremity and trunk exercises);

• Heart failure functional class IV;

• Uncontrolled arterial hypertension (BP >180/110 mm Hg);

• Angina attacks;

• Decrease in systolic BP ≥20 mm Hg in response to physical exertion;

• Cardiac arrhythmias (high-grade extrasystoles or tachyarrhythmias) and conduction disturbances (atrioventricular block grade II-III);

• Thromboembolism or thrombophlebitis (within up to 3 months);

• Acute cerebrovascular accident or transient ischemic attack (within up to 3 months);

• High bleeding risk;

• Uncontrolled diabetes mellitus;

• Severe cognitive impairment.

Figure A3-1. Etiology of aortic regurgitation

Appendix B. Physician Action Algorithms

Table PB-1. Grades of chronic aortic regurgitation [11, 159]

Notes. AV – aortic valve; AR – aortic regurgitation; LVOT – left ventricular outflow tract; CW – continuous-wave Doppler; PHT – pressure half-time; PW – pulsed-wave Doppler.

Table PB-2. El Khoury and de Kerchove functional classification of aortic regurgitation (adapted from de Kerchove L., El Khoury G., 2013) [16]

Notes: AV – aortic valve; AR – aortic regurgitation; NP – non-coronary cusp replacement; SCA – subcommissural annuloplasty; STJ – sinotubular junction; AA – anulus (fibrous ring).

Table PB-3. Target INR values after AV replacement with a low-thrombogenicity mechanical prosthesis requiring lifelong anticoagulant therapy

Note. AV – aortic valve; LV – left ventricle; EF – ejection fraction.

Optimization of the diagnostic process

The screening and verification stage for valvular heart disease is usually carried out at the outpatient diagnostic stage. Patients with severe valvular disease, or patients with other severity grades and stages but with severe comorbid conditions, are referred to a multidisciplinary center with a cardiac surgery department for a cardiologist consultation. If it is necessary to determine indications for surgical treatment of the valve defect, the patient is referred by the multidisciplinary center cardiologist for a consultation with a cardiac surgeon (Table 5).

Table PB-4. Stages of diagnostic care for patients with valvular heart disease

Figure PB-1. Algorithm for primary diagnosis and surgical treatment of severe aortic regurgitation

Note: - potential patient mobility during the provision of specialized and primary medical care, including medical rehabilitation; MDRT – multidisciplinary rehabilitation team; - participation of the MDRT in the medical rehabilitation process.

Figure PB-4. Algorithm for the use of diagnostic imaging and instrumental diagnostic methods in patients with aortic regurgitation

Appendix C. Patient Information

Aortic regurgitation is a congenital or acquired heart defect characterized by impaired closing function of the aortic valve. During diastole (relaxation and filling of the left ventricle), part of the blood ejected by the left ventricle into the aorta flows back through the incompetent aortic valve. Aortic regurgitation can be congenital or acquired, developing both in patients with an initially normally formed tricuspid aortic valve and in individuals with congenital anomalies—bicuspid, unicuspid, or quadricuspid aortic valves. The causes of aortic regurgitation can include changes in the aortic valve cusps themselves (stretching and thinning of the cusps, destruction due to infectious involvement, sclerosis and fibrosis in atherosclerosis or rheumatic disease), as well as diseases of the ascending aorta leading to impaired valve opening and closing mechanisms: aneurysm, dissection, or rupture of the ascending aorta.

Severe aortic regurgitation may be asymptomatic for a long time, but it leads to serious changes in your heart.

Severe aortic regurgitation typically manifests as shortness of breath with moderate and minor exertion, rapid fatigue, and in some cases, a feeling of discomfort in the chest. In advanced cases, patients experience shortness of breath at rest, inability to lie flat in bed ("cardiac asthma"), cardiac arrhythmias, fluid accumulation in the pleural and abdominal cavities (ascites), and lower extremity edema. The only method to effectively treat severe aortic regurgitation is surgical intervention. In the presence of severe aortic regurgitation and indications for surgery, refusal or delay of surgical correction significantly worsens treatment outcomes, increases the risk of severe complications, and worsens the long-term prognosis for life, even if surgery is performed later.

• After discharge from a specialized center, it is recommended to strictly follow the instructions specified in the discharge documents (discharge summary).

• Follow-up by a local cardiologist (physical examination, transthoracic echocardiography, ECG) is recommended at least once a year, strictly following their prescriptions and appointments.

• Cardiologist follow-up at a specialized center (physical examination, transthoracic echocardiography, ECG) is recommended at least once a year.

• For any invasive procedures (dental, cosmetic, or other procedures that involve or carry a risk of compromising the skin and mucous membranes), it is mandatory to proactively take recommended antibiotics to prevent infective endocarditis of a reconstructed or prosthetic heart valve.

• Planned invasive procedures and/or surgeries must be coordinated with the cardiologist providing local follow-up care.

• Changes in the doses and regimens of certain medications, as well as the prescription of additional or alternative medications, are carried out solely by the attending physician.

• If side effects from medications occur, it is recommended to discuss this with the attending physician as soon as possible.

• If the following symptoms appear or rapidly progress, an unscheduled cardiologist consultation is recommended as soon as possible: fatigue, shortness of breath, edema, acute chest or abdominal pain, increased abdominal girth, arrhythmias, syncope, neurological deficits (loss of vision, hearing, speech, limb numbness, paresis and paralysis, including transient ones), acute respiratory infections, or fever of unknown origin.

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

Appendix G1. Hospital Anxiety and Depression Scale (HADS)

Russian title: Hospital Anxiety and Depression Scale

Original name (if any): Hospital Anxiety and Depression Scale

Source: [190]

Type: rating scale

Purpose: assessment of the presence of anxiety (A) and depression (D) symptoms

Content (template):

Each statement on the HADS scale has 4 possible answers. The patient is asked to choose the answer that best describes their state over the past 7 days, after which the scores are summed separately for each section.

Table PG-1. Hospital Anxiety and Depression Scale (HADS)

Note: A – Anxiety subscale; D – Depression subscale.

Key (interpretation):

0–7 points – normal (no significant symptoms of anxiety/depression);

8–10 points – subclinically expressed anxiety/depression;

11 points and above – clinically expressed anxiety/depression.

Appendix G2. Timed Up and Go test

Russian title: Timed “Up and Go” test

Original title (if any): Timed “Up and go” test

Source: [189]

Type: test

Purpose: assessment of gait, balance, and fall risk

Content (template):

Required equipment: chair with armrests, tape measure, colored tape or marker, stopwatch. Measure a distance of 3 meters from the chair and mark it with a marker or colored tape so that the mark is visible to the patient.

Test conditions. The patient must be instructed that the test is timed. They may perform the first trial run without timing. During the test, the patient must wear their usual footwear and may use assistive devices that they normally use (e.g., a cane or walker). If necessary, the patient may stop to rest during the test.

Procedure (Figure PG-1):

• The patient should sit in the chair with their back against the backrest and thighs fully supported by the seat. The chair must be stable. The patient is allowed to use the armrests when sitting and standing up.

• Patient instruction: When I say 'Go', you will need to stand up, walk the marked distance, turn around, return to the chair, and sit down. You should walk at your usual pace.

• Start timing after saying the word 'Go' and stop timing when the patient sits back down properly in the chair with their back resting against the backrest.

• During the test, pay attention to signs of gait and balance disorders.

Figure PG-1. Diagram of the timed Up and Go test execution.

Appendix G3. Original Borg Scale (Borg RPE, Rating of Perceived Exertion)

Russian title: Original Borg scale

Original title (if any): Borg Rating of Perceived Exertion

Source: [191, 192]

Type: rating scale

Purpose: Subjective assessment of perceived exertion / exercise load tolerance.

Table PG-2. Borg Rating of Perceived Exertion (Borg RPE Scale)

Key (Interpretation): The patient receives instructions on the subjective assessment of physical exertion / training load tolerance: from 6 points – virtually no effort, 9 – light walking pace, 12 to 14 – exertion equivalent to brisk walking or jogging; 15 and above – high-intensity zone, comparable to very fast running.

Appendix G4. CHA2DS2-VASc score

Russian title: CHA2DS2-VASc score

Original name: CHA2DS2-VASc

Sources: [170, 171]

Type: rating scale

Purpose: CHA2DS2-VASc is a clinical scoring system for assessing the risk of ischemic stroke in patients with nonvalvular atrial fibrillation. It is used to guide decisions regarding anticoagulant therapy. It is recommended in international guidelines (ESC, AHA/ACC/HRS) as the basis for thromboembolic risk stratification [72].

Content (template):

• C — Congestive heart failure — 1 point

• H — hypertension — 1 point

• A2 — age ≥75 years — 2 points

• D — diabetes mellitus — 1 point

• S2 — prior stroke or TIA — 2 points

• V — vascular disease (myocardial infarction, obliterating atherosclerosis, etc.) — 1 point

• A — age 65–74 years — 1 point

• Sc — female sex — 1 point

Maximum: 9 points.

Result interpretation:

• 0 points (in men) / 1 point (in women) — low risk; anticoagulant therapy is generally not required.

• 1 point (in men) / 2 points (in women) — moderate risk; the decision on therapy is made individually.

• ≥2 points (in men) / ≥3 points (in women) — high risk; anticoagulant therapy is indicated.

Practical application: The scale is used during the initial evaluation of a patient with atrial fibrillation and during follow-up monitoring. It helps justify the prescription of direct oral anticoagulants or vitamin K antagonists.

Appendix G5. EuroSCORE perioperative risk assessment scale

Russian title: EuroSCORE scale

Original title: EuroSCORE (European System for Cardiac Operative Risk Evaluation)

Sources: [43]

Type: rating scale

Purpose: EuroSCORE is a risk assessment scale for mortality after cardiac surgery

Content (template):

Age

• <60 (0 point(s))

• 60-64 (1 point)

• 65-69 (2 point(s))

• 70-74 (3 point(s))

• 75-79 (4 point(s))

• 80-84 (5 point(s))

• 85-89 (6 point(s))

• 90-94 (7 point(s))

• 95-100 (8 point(s))

Gender

• Female (1 point)

• Male (0 points)

Ejection fraction

• 30–50% (1 point)

• < 30 % (3 point(s))

• Renal impairment (2 points)

• Peripheral vascular disease (2 points)

• Respiratory disease (1 point)

• Cerebrovascular disease (2 points)

• Previous cardiac surgery (3 points)

• Active endocarditis (3 points)

• Critical preoperative state (3 points)

• Unstable angina (2 points)

• Recent myocardial infarction (2 points)

• Pulmonary hypertension (2 points)

• Emergency surgery (2 points)

• Surgery other than isolated CABG (2 points)

• Post-infarct ventricular septal rupture (4 points)

• Thoracic aortic surgery (3 points)

Result interpretation:

Appendix G6. EuroSCORE II perioperative risk assessment scale

The EuroSCORE II (European System for Cardiac Operative Risk Evaluation) scale is designed to assess the risk of adverse outcomes in cardiac surgery (in this case, coronary artery bypass grafting). The table presents risk factors that increase mortality in cardiac surgical interventions. Each of these factors has been assigned a specific score. The EuroSCORE II risk indicator is calculated from the sum of these scores. In patients with a high EuroSCORE II score, PCI is advisable due to the high risk of complications and mortality following CABG surgery. This scale can be used to assess the risk of surgical interventions (including valvular heart disease) both with and without cardiopulmonary bypass.

Russian title: EuroSCORE II scale

Original title (if available): European System for Cardiac Operative Risk Evaluation II

Source: [44, 45] (official developer website, validation publication: https://euroscore.org)

Type: rating scale

Purpose: assessment of the risk of adverse outcomes in cardiac surgery

Content (template):

EUROSCORE II PERIOPERATIVE RISK ASSESSMENT SCALE

Note: the listed coefficients are substituted into the equation:

predicted mortality =

where B0 is the logistic regression constant, Bi is the variability coefficient of Xi, for age Xi = 1 if the patient is younger than 60 years, Xi increases by 1 for each year after 60 (at 61 Xi = 2, at 62 Xi = 3, and so on). CABG - coronary artery bypass grafting, MI - myocardial infarction, DM - diabetes mellitus, SPAP - systolic pulmonary artery pressure, GFR - glomerular filtration rate (calculated by Cockcroft-Gault), CPR - cardiopulmonary resuscitation, HF - heart failure, CCS - Canadian Cardiovascular Society, NYHA - New York Heart Association.

Appendix G7. STS Score

Russian title: STS Score scale

Original title: The Society of Thoracic Surgeons Score

Sources: [42] (official developer website, validation publication: https://acsdriskcalc.research.sts.org)

Type: rating scale

Purpose: STS Score is a surgical risk assessment scale associated with CABG

Content (template):

• Low risk: less than 4%

• Intermediate risk: 4-8%

• High risk: 8% or more