Mitral Stenosis: Clinical Guidelines

List of Abbreviations

VKA – vitamin K antagonists

BP – blood pressure

CABG – coronary artery bypass grafting

Anticoagulants – B01A: Antithrombotic agents

ALT – alanine aminotransferase

AST – aspartate aminotransferase

BB – beta-blockers

Biological prosthesis – mitral valve bioprosthesis***

ARB – angiotensin receptor blocker (angiotensin II receptor antagonists)

Antiplatelet agent – B01AC Platelet aggregation inhibitors excluding heparin

PAP – pulmonary artery pressure

ЕОК – European Society of Cardiology

CHD – coronary heart disease

ACE inhibitor – angiotensin-converting enzyme inhibitors (C09AA ACE inhibitors)

CAG – coronary angiography

CT – computed tomography

LV – left ventricle

LA – left atrium

Mechanical prosthesis – mechanical bileaflet mitral valve prosthesis ***

MV – mitral valve

INR – international normalized ratio

MR – mitral regurgitation

MRI – magnetic resonance imaging

MS – mitral stenosis

LMWH – low molecular weight heparin (ATC B01AB Heparin group)

UFH – unfractionated heparin (sodium heparin**)

RV – right ventricle

DOACs – direct oral anticoagulants (B01A: Antithrombotic agents)

MVR – mitral valve replacement

CVD – cardiovascular events

Statins – C10AA HMG-CoA reductase inhibitors

TG – triglycerides

TV – tricuspid valve

TEC – thromboembolic complication

EF – ejection fraction

FC – functional class

AF – atrial fibrillation

LDL-C – low-density lipoprotein cholesterol

CHF – chronic heart failure

TEE – transesophageal echocardiography

PMC – percutaneous mitral commissurotomy

HR – heart rate

ECG – resting electrocardiogram acquisition, recording, description, and interpretation

EchoCG – echocardiography (transthoracic)

CHA2DS2-VASc – scale for assessing the risk of stroke and thromboembolic complications in patients with atrial flutter and fibrillation (Appendix G3).

MVG – mean mitral valve pressure gradient

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. The text of these clinical guidelines additionally indicates the class of recommendations in accordance with the guidelines of the European Society of Cardiology (ESC). In accordance with international standards, recommendation classes and levels of evidence are distinguished.

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, directly or indirectly through a representative, in obtaining material gain or another advantage that influences or may influence 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.

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 cross-sectional submillimeter axial images of human body organs and structures based on measuring and complex computer processing of X-ray attenuation differences by tissues of varying density, aimed at improving the differentiation of organs and normal versus pathological structures. Various contrast-enhancement techniques using iodine-containing X-ray contrast media are applied. To visualize cardiovascular structures, CT angiography is used—a technique involving the intravenous bolus injection of a contrast agent into the bloodstream via an automated injector system at a set injection rate and time. Based on the acquired data, computer post-processing with 3D reconstruction generates a three-dimensional model of the heart and blood vessels.

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

Medicinal products – pharmacological substances in the form of dosage forms used for the prevention, diagnosis, and treatment of diseases, rehabilitation, and for the preservation, prevention, or termination of pregnancy.

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

Medical intervention – diagnostic and/or therapeutic medical examinations and/or procedures, as well as artificial termination of pregnancy, performed by a medical professional or other employee authorized to carry out medical activities, affecting the physical or mental state of a person and having a preventive, diagnostic, therapeutic, rehabilitative, or research focus.

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.

Mitral valve – the left atrioventricular valve.

Patient – an individual who is receiving medical care or has applied for medical care, regardless of whether they have a disease or what their condition is.

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

Working Group for the Development/Updating of Clinical Guidelines – a team of specialists working together and in coordination 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) – a sign of a disease, a statistically significant deviation of a certain indicator from its normal limits, or the emergence of a qualitatively new phenomenon not characteristic of a healthy organism.

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

Condition is an alteration of the organism arising from the impact of pathogenic and/or physiological factors that requires medical care.

Valve stenosis – obstruction to blood flow resulting from structural deformation of the valve.

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.

Percutaneous balloon valvuloplasty – restoration of valve function using interventional catheterization techniques.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Mitral stenosis (MS) – left ventricular (LV) inflow obstruction at the mitral valve (MV) level resulting from structural deformation of the MV apparatus, which hinders the necessary opening of the MV during diastolic filling of the left ventricle [1].

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

The most common cause of MS is rheumatic carditis, although its incidence in industrialized countries has significantly declined recently [2]. Isolated MS is identified in 40% of patients with rheumatic heart disease, while a history of rheumatic fever is present in approximately 60% of patients with pure MS [1]. The female-to-male ratio in isolated MS is 2:1. Congenital MV disease is rare and occurs primarily in children [3], with parachute mitral valve (a single papillary muscle giving rise to chordae tendineae to both valve leaflets) being the main cause. The rheumatic process leads to leaflet thickening and calcification, commissural and chordal fusion, or a combination thereof. The result is a funnel-shaped mitral apparatus with a significant reduction in orifice area [4–7]. Commissural fusion of the leaflets narrows the main orifice, and chordal fusion further aggravates the stenosis. Symmetrical fusion of the leaflets occurs along the commissures, which in turn leads to very limited diastolic leaflet opening, forming an oval-shaped orifice resembling a "fish mouth" or "buttonhole" [1]. Approximately 10 years elapse from the onset of initial symptoms of MS to the point where they severely impair daily life. Thereafter, 10-year survival is approximately 10% [6].

The normal mitral valve (MV) area is 4.0 to 5.0 cm². When the valve area decreases due to a rheumatic process, blood flow from the left atrium to the left ventricle creates a pressure gradient, which is a fundamental manifestation of mitral stenosis (MS) and leads to an increase in left atrial pressure, affecting pulmonary venous blood flow [8]. Reduced pulmonary vein compliance (partially resulting from elevated pulmonary endothelin-1) may also contribute to the increase in pulmonary venous pressure [9]. Increased pressure and distension of pulmonary veins and capillaries can lead to pulmonary edema as pulmonary venous pressure exceeds plasma oncotic pressure. In patients with severe MS and very high pulmonary venous pressure, pulmonary edema may not occur due to a marked decrease in pulmonary capillary permeability. Pulmonary arterioles respond with vasoconstriction (Kitaev reflex), intimal and medial hyperplasia, which lead to pulmonary hypertension [1, 2, 9, 10].

When the mitral valve area is greater than 1.5 cm² at rest, symptoms are usually absent [11]. However, if transmitricular blood flow increases or the diastolic filling period decreases, left atrial pressure rises and symptoms appear. According to the laws of hydraulics, the transmitral gradient is a function of the square of the transvalvular blood flow velocity and depends on the diastolic filling period. Thus, the onset of initial dyspnea symptoms in patients with mild MS is usually associated with physical exertion, emotional stress, infection, pregnancy, or atrial fibrillation with a high ventricular response rate [11]. As the obstruction progresses, exercise tolerance decreases.

As the severity of stenosis progresses, resting cardiac output falls below normal [11] and fails to increase during exercise [12]. The severity of pulmonary hypertension also contributes to symptoms in patients with MS [9, 13, 14]. The next barrier to blood flow is increased pulmonary arteriolar resistance, which protects the lungs from edema [15, 16]. In some patients, a reversible barrier additionally develops at the level of the pulmonary veins [9, 16]. Reduced cardiac output and pulmonary arteriolar resistance, which lead to functional and structural changes (thickening of the alveolar basement membrane, neuroreceptor adaptation, increased lymphatic drainage, and increased transpulmonary endothelin), contribute to the prolonged absence of clinical symptoms in patients with severe MS [1, 9].

Mitral stenosis is a continuously progressive disease, typically with a stable initial course and rapid progression in later stages [11]. The clinical history features of untreated MS were established in studies from the 1950s–1960s [9]. In developed countries, an early prolonged latent period lasts 20–40 years from the onset of rheumatic fever to the appearance of symptoms. From the onset of symptoms to marked disability takes about 10 years [9]. Overall, the 10-year survival rate of untreated patients with MS ranges from 50 to 60% depending on symptom severity [4, 5]. In asymptomatic or mildly symptomatic patients, survival is greater than 80% at 10 years, and 60% in patients without symptom progression. However, once significant, life-limiting symptoms develop, 10-year survival is 0–15% [4, 6, 9]. When severe pulmonary hypertension develops, mean survival drops to 3 years or less [9, 17]. Death in patients with MS is caused by progressive pulmonary and systemic failure in 60–70% of cases, systemic embolism in 20–30%, pulmonary embolism in 10%, and infection in 1–5% of cases [6, 10]. A milder disease course with rare rheumatic attacks is typical for North America and Europe [9, 18]. The average age of symptom manifestation occurs in the fifth to sixth decade [10, 19]; one-third of patients undergo valvulotomy over the age of 65 [20]. In some geographic regions, MS progresses more rapidly, apparently due to repeated episodes of rheumatic carditis from recurrent streptococcal infection, leading to severe MS in late adolescence and the early third decade of life [4]. Hemodynamic studies have shown that the annual decrease in MV area is 0.09–0.32 cm² [16]. The severity of MS is determined based on hemodynamic data and clinical history.

1.3 Epidemiology of the Disease or Condition

According to many experts, comprehensive data on the prevalence of valvular heart disease do not exist globally, making a worldwide epidemiological study necessary. In the United States and Western Europe, cases of acute rheumatic fever have become less frequent since the 1970s. However, starting in 1987, the incidence of acute rheumatic fever began to increase [1, 2].

In the Russian Federation, according to the Russian Ministry of Health, the primary incidence of acute rheumatic fever in 2006 was 1.7 per 100,000 adult population, and 3.1 among children. The overall incidence of chronic rheumatic heart disease among adults was 425 per 100,000 adult population in 1992, and 208.4 in 2007; among children under 14 years of age, it was 58.5 and 27.9, respectively. The overall incidence of rheumatic heart disease (RHD) shows a distinct downward trend among the adult population and fluctuating dynamics among the pediatric population of the Russian Federation. In 1993, the overall incidence of RHD was 232 per 100,000 adults, and 175 in 2006; the incidence decreased by 75.4%. Among children, the opposite trend is noted: in 1993, the overall incidence of RHD was 8.3, and 12.5 per 100,000 children (under 14 years of age) in 2006.

1.4 Features of Coding the Disease or Condition

I05.0 – Mitral stenosis

I05.2 – Mitral stenosis with insufficiency

I08.0 – Combined disorders of mitral and aortic valves

I08.1 – Combined disorders of mitral and tricuspid valves

I08.3 – Combined disorders of mitral, aortic and tricuspid valves

I34.2 – Nonrheumatic mitral (valve) stenosis

Q23.2 – Congenital mitral stenosis

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

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

T82.0 – Mechanical complication of cardiac valve prosthesis

I09.8 – Other specified rheumatic heart diseases

Diagnosis formatting examples:

• Primary: Chronic rheumatic heart disease. Severe mitral stenosis.

Complications: Heart failure with preserved ejection fraction (HFpEF) (70%), stage 1. NYHA functional class (FC) I-II.

• Primary: Degenerative mitral valve disease with moderate stenosis.

Complications: Heart failure with preserved ejection fraction (HFpEF) (63%), stage 1. NYHA functional class II-III.

1.5 Classification of the disease or condition

According to the nature of mitral valve involvement, the classification includes:

• Congenital mitral stenosis;

• Acquired mitral stenosis:

1) rheumatic;

2) nonrheumatic;

3) combined.

According to the severity of mitral stenosis, see Table 1. Appendix B.

1.6 Clinical presentation of the disease or condition

The clinical diagnosis of mitral stenosis may go unmade for a long time due to the absence of typical symptoms. Initial hospitalizations are usually associated with the appearance of a heart murmur, the onset of arrhythmia (paroxysmal atrial fibrillation), or the manifestation of signs of heart failure (extremity edema, dyspnea at rest). Upon decompensation of mitral stenosis, patients are hospitalized with a presentation of pulmonary edema. In most cases, patients complain of exertional and resting dyspnea, fatigue, and occasionally stabbing precordial chest pain [11, 18]. Blood stasis occurs in the enlarged left atrium, especially in the presence of atrial fibrillation, which can cause thrombosis and embolism. This frequently acts as the cause of myocardial, renal, and cerebral infarctions [9].

Symptoms may appear or significantly worsen under the influence of triggering factors: physical exertion, emotional stress, pregnancy, infection, or atrial fibrillation with a high ventricular response rate. All these factors increase the transvalvular pressure gradient and elevate left atrial pressure [2].

Patients with severe mitral stenosis typically assume a forced position (orthopnea)—sitting or lying in bed with the head elevated. A characteristic sign is facies mitralis: against a pale skin background, there is a bright purple or crimson flush on the cheeks, with the same coloration of the lips and the tip of the nose. With the development of right ventricular heart failure, there is edema or puffiness of the legs and feet. When the defect develops in childhood, delayed physical development and infantilism (mitral nanism) may be observed. Anisocoria is rarely detected, resulting from compression of the sympathetic nerve by the enlarged left atrium (Ortner's syndrome). Even more rarely, patients may present with complaints of hemoptysis, which is associated with the rupture of small bronchial veins due to high left atrial pressure [11, 18].

Auscultation over the apex of the heart (at auscultation point 1) reveals:

-  Accentuated, loud ("clacking") first heart sound (more than twice as loud as the second heart sound);

-  Opening snap of the mitral valve – occurs 0.06–0.11 seconds after the beginning of the second heart sound. The shorter the interval between the second heart sound and the mitral opening snap, the higher the atrioventricular pressure gradient and the more severe the stenosis. The mitral opening snap does not disappear in atrial fibrillation. It is best auscultated at the cardiac apex or to the left of the sternum in the 4th–5th intercostal spaces during expiration;

-  "Quail rhythm" – a triple rhythm characteristic of mitral stenosis, resulting from the combination of a loud/clacking first heart sound with the second sound and the mitral opening snap;

-  Early mesodiastolic murmur. It begins after the mitral opening snap and occurs due to blood movement through the narrowed orifice as a result of an increased pressure gradient between the left atrium and ventricle. Its intensity is decrescendo. At the end of diastole, a presystolic accentuation of the murmur is observed due to active systole of the left atrium and increased blood flow. The mesodiastolic murmur is thus characterized by increasing intensity [9]. With the development of atrial fibrillation, this murmur disappears due to impaired atrial contractility. The diastolic murmur has a low, rumbling pitch, is auscultated at the apex, and is not radiated anywhere. It is best auscultated with the patient lying on their left side, after physical exertion, and during breath-holding at the end of expiration, since under these conditions the heart comes into closer contact with the anterior chest wall [11, 18].

At auscultation point 3, the following are heard:

-  Accent of the second heart sound over the pulmonary artery, caused by elevated pressure in the pulmonary circulation;

-  Splitting or duplication of the second heart sound associated with asynchronous closure of the pulmonary and aortic valves due to prolongation of right ventricular systole under conditions of elevated pulmonary artery pressure;

-  Graham Steell murmur, appears due to relative pulmonary valve regurgitation, which develops as a result of dilation of the fibrous ring of the pulmonary trunk valve in patients with mitral stenosis and marked pulmonary hypertension. This murmur is functional, diastolic, high-frequency, decrescendo, soft, has a blowing character, and occurs immediately after the second heart sound. Patients with mitral stenosis exhibit pulsus differens (Popov's sign) (the pulse is unequal on the right and left arms because with significant dilation of the left atrium, the left subclavian artery is compressed, and pulse volume on the left is decreased). The pulse is soft, of low volume, small (due to a decrease in left ventricular stroke volume in significant mitral narrowing), frequent, uneven, and arrhythmic (in the presence of atrial fibrillation) [9].

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of mitral stenosis is established based on a combination of symptoms, medical history, and diagnostic findings. Once the diagnosis is established, indications for surgical treatment are determined [9].

2.1 Complaints and Anamnesis

At the diagnostic stage, an analysis of symptoms and medical history is performed for all patients with suspected mitral stenosis (MS). During history-taking in a patient with suspected MS, the following details are clarified: a history of streptococcal sore throat, previous medical encounters and their outcomes, the availability of instrumental examination reports and their conclusions to assess various parameters dynamically, known comorbidities to assess additional risks, all currently used medications to adjust therapy, and all medications previously discontinued due to intolerance or inefficacy to reduce the risk of allergic and anaphylactic reactions and to optimize therapy selection [21].

ESC/RSC I A (LE Level C, SOR 5)

Comments: in the early stages, patients may be asymptomatic; as MS progresses, complaints appear of dyspnoea, initially on exertion and later at rest, acquiring orthopnoeic features, dry cough, asthma attacks, haemoptysis, increased fatigue, muscular weakness occurring upon exertion, palpitations, heart palpitations and skipped beats, cardiac pain, dysphagia, and hoarseness of voice. Complaints of oedema, right upper quadrant heaviness, and dyspeptic disorders (anorexia, nausea, vomiting) are characteristic of late stages of the disease. MS may manifest as newly onset atrial fibrillation or thromboembolism.

2.2 Physical Examination

For diagnostic purposes, a physical examination is performed in all patients with suspected MS, as well as to identify comorbidities. In the early stages of MS, physical examination has low specificity. Physical examination may become more informative as the pressure gradient between the LA and LV increases.

During the physical examination, all patients with MS or suspected MS undergo: a general examination, assessment of the skin of the face, trunk, and extremities, inspection and palpation of the precordial area, percussion and auscultation of the heart and lungs, which reveals an early mesodiastolic murmur—the most characteristic finding in mitral stenosis. The diastolic murmur begins after the opening snap of the mitral valve and results from blood flowing through the narrowed orifice. Its intensity is decreasing (decrescendo). Examination of the pulse on the radial and dorsal pedis arteries, measurement of blood pressure on peripheral arteries using the Korotkoff method in the supine, sitting, and standing positions, heart rate and pulse rate measurement, inspection of the neck veins, palpation of the anterior surface of the lower leg to detect signs of venous congestion, determination of pulse deficit, auscultation of projection points of the carotid arteries, abdominal aorta, and iliac arteries, and palpation of the abdomen, parasternal points, and intercostal spaces are performed to identify various signs of both the primary and comorbid conditions [21].

ESC/RSC I A (LE Level C, SOR 5)

Comments: upon examination of patients with MS, signs of poor general physical development, acrocyanosis, facies mitralis, orthopnea, and edema are noteworthy; inspection and palpation of the precordial area may reveal a heaving impulse, diastolic thrill ("cat's purr"), enhanced pulsation in the 2nd intercostal space to the left of the sternum associated with pulmonary artery trunk dilatation, and a precordial bulge. Upon cardiac percussion, the boundaries of relative and absolute dullness are displaced upward and to the right. Auscultation typically reveals an accentuated, "snapping" first heart sound (S1), a mitral valve opening snap (OS), a low-frequency mesodiastolic murmur, and a triple-rhythm melody—the "quail rhythm." However, these findings may also be present in patients with non-rheumatic mitral stenosis and, conversely, may be absent in severe pulmonary hypertension, low cardiac output, and heavily calcified immobile mitral valves. A shorter A2–OS interval and increased duration of the diastolic murmur indicate more severe MS. An A2–OS interval of less than 0.08 s suggests severe MS [15, 16]. Signs of pulmonary hypertension on examination, such as an accentuated second sound or right ventricular (RV) pulsation, also indicate severe MS.

2.3 Laboratory Diagnostics

ESC/RSC I C (LE Level 5, SOR C)

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

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

• In all patients with MS admitted to the hospital for surgical treatment, it is recommended to perform acid-base balance and blood gas analysis (pH, base excess (BE), partial pressure of carbon dioxide (pCO₂), partial pressure of oxygen (pO₂), blood lactic acid (Lac) level — capillary/arterial/venous blood sample) to assess the severity of hypoxemia and the degree of metabolic disorders, as well as a coagulogram (screening hemostasis assay) (activated partial thromboplastin time, prothrombin time in blood or plasma, blood D-dimer concentration, blood fibrinogen level, antithrombin III activity); determination of the international normalized ratio (INR) to predict the risk of perioperative bleeding and blood loss volume, determination of ABO blood groups, and Rhesus antigen D (Rh factor). Determination of C, c, E, e, Cw, K, k phenotypes and screening for red blood cell antibodies. Determination of hepatitis B virus surface antigen (HBsAg) in blood. Determination of antibodies to hepatitis C virus in blood. Determination of antibodies to Treponema pallidum in blood. Determination of IgM and IgG antibodies to human immunodeficiency virus (HIV)-1 in blood, and determination of IgM and IgG antibodies to HIV-2 in blood to rule out association with HIV infection and hepatitis, as well as in the case of surgical treatment, if necessary, in the pre- and/or postoperative period [30, 156-159].

ESC/ACC IIa C (LoE 5 GoR C)

Comments: determination of hepatitis B virus surface antigen (HBsAg) in blood, antibodies to hepatitis C virus in blood, antibodies to Treponema pallidum in blood, IgM and IgG antibodies to human immunodeficiency virus (HIV)-1 in blood, and IgM and IgG antibodies to HIV-2 in blood as part of preoperative preparation may be performed within primary health care.

2.4 Instrumental Diagnostics

2.4.1 Non-invasive diagnostic methods

Electrocardiographic examination

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

Comments: the most characteristic electrocardiographic manifestations of MS with preserved sinus rhythm are signs of right ventricular and left atrial hypertrophy (p-mitrale). When atrial fibrillation develops, the electrocardiogram shows signs of right ventricular hypertrophy and coarse atrial fibrillation.

Echocardiographic examination

ESC/RSC I A (LE Level C, SOR 5)

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

Comments:Echocardiography (transthoracic echocardiography) is the key diagnostic method for mitral stenosis, assessing its severity and hemodynamic changes. Mitral valve area using planimetry is the gold standard for assessing the severity of mitral stenosis, whereas the mean transvalvular gradient and pulmonary artery pressure reflect its consequences and have prognostic value [33]. Transthoracic echocardiography generally provides sufficient data for routine patient management. Criteria for assessing the severity of MS are summarized in Table 1,Appendix A3-2.They are applicable when the heart rate is from 60 to 90 bpm. To determine indications for percutaneous mitral commissurotomy, echocardiographic scales are used: the Wilkins score (Table 2,Appendix A3-2), the Cormier score: echocardiographic grouping based on the assessment of valve leaflet mobility, subvalvular fusion, leaflet calcification, and the presence of calcium in the commissures (Table 3,Appendix A3-2). To assess the immediate prognosis, the «Re-examination» echocardiographic scale is used (Table 4,Appendix A3-2) [32]. The use of the «Re-examination» scale is justified in rare clinical situations as an adjunct to clinical and instrumental data. Three-dimensional echocardiography and 3D transesophageal echocardiography provide more accurate and detailed topical and morphological information [32, 41-43].

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

Stress echocardiography

ESC/ACC I B (LoE C, QoE 4)

Comments: according to study results, stress echocardiography can be performed using either physical exercise (cycle ergometry) or dobutamine**, but physical stress echocardiography remains preferred as it is more physiological. Simple functional load helps to quantify the patient's symptoms. During the study, changes in the transmitral pressure gradient and pulmonary artery systolic pressure must be determined. If the patient is unable to perform exercises that increase heart rate, leg exercises and squats can be used as a physical load.

Stress echocardiography can be performed in women with mitral stenosis planning pregnancy. During pregnancy, there is an increase in cardiac output, heart rate, and total blood volume, which contributes to an increase in the transmitral pressure gradient across the mitral valve and, consequently, left atrial pressure. Thus, in many women with mitral stenosis, symptoms appear for the first time during pregnancy due to elevated pulmonary venous pressure (secondary to increased left atrial pressure). Stress echocardiography can help in decision-making regarding risk reduction during pregnancy, as well as in determining the treatment method.

In all cases, the risks of such a study should be weighed against the potential benefit to the patient.

ECG monitoring (Holter)

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

Targeted chest X-ray

ESC/RSC I A (LE Level C, SOR 5)

Comments: targeted chest X-ray in patients with MS makes it possible to detect left atrial and right ventricular enlargement, dilation of the pulmonary artery trunk and central branches, straightening of the left cardiac contour and flattening of the cardiac "waist" (mitral configuration), radiological signs of pulmonary arterial hypertension and venous congestion.

Computed tomography (CT)

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

Comments. Cardiac computed tomography is used in patients with MS during preoperative preparation or in the presence of absolute contraindications to MRI. The diagnostic value of contrast-enhanced cardiac CT is significantly inferior to cardiac MRI [30, 59].

Contrast-enhanced cardiac magnetic resonance imaging (MRI)

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

Abdominal ultrasound (comprehensive)

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

2.4.2 Invasive diagnostic methods

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

Comments: right heart catheterization (transvenous cardiac catheterization) may be considered when elevated estimated systolic pulmonary artery pressure is detected by transthoracic echocardiography in the presence of severe tricuspid regurgitation. Currently, echocardiography and transesophageal echocardiography are used to diagnose patients with MS. However, there is a group of patients who show discrepancies between clinical data and data obtained using the aforementioned methods. In elderly patients, other factors may worsen symptoms, such as diastolic dysfunction or preexisting pulmonary vascular disease. Cardiac catheterization may be performed in these categories of patients to determine hemodynamic features and the etiology of symptoms, as this method allows the measurement of left ventricular, left atrial, and pulmonary circulation pressures at rest and during exercise. In most cases, echocardiographic measurements of the transmitral gradient, valve area, and pulmonary artery pressure correlate well with each other. However, the absolute value of pulmonary capillary wedge pressure, its ratio to left ventricular diastolic pressure, and pulmonary artery pressure can provide additional clinical information. The Gorlin equation can be used to determine the mitral valve area [30, 32].

With the use of Doppler echocardiography, cardiac catheterization is no longer required for hemodynamic assessment in patients with isolated MS. Only the measurement of exact pulmonary artery pressure and pulmonary vascular resistance, as well as the reversibility of severe pulmonary hypertension, should be measured to determine the strategy and prognosis of surgical treatment. Invasive hemodynamic assessment is also necessary to identify the severity and hemodynamic cause of increased pulmonary vascular resistance and to adjust therapy using peripheral vasodilators (C04A). With a slowly progressive disease course, patients with severe mitral stenosis may remain asymptomatic due to reduced physical activity. Increased pulmonary vascular resistance and/or low cardiac output may also play an adaptive role in preventing congestive symptoms in patients with severe MS [31].

CT coronary angiography

ESC/ESC IIa C (Level of Evidence C, LoE 2)

Coronary angiography

• CAG is recommended in all patients with MS to detect hemodynamically significant coronary artery stenosis prior to open surgical, transcatheter, or hybrid intervention in the following situations: age over 40 years, history and/or symptoms of CAD, evidence of myocardial ischemia, decreased LVEF < 50%, one or more risk factors for CAD, and/or post-radiation injury, in order to exclude concomitant hemodynamically significant coronary stenosis prior to valve surgery [32].

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

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

Risk stratification when planning surgical treatment for a patient with mitral stenosis

To select a surgical strategy and optimize treatment, the most important task is to identify risk factors and predict the outcome of the surgery. For this purpose, formulas for assessing the risk of mortality are used, presented on the websites of the Society of Thoracic Surgeons (STS) [175] and the European System for Cardiac Operative Risk Evaluation ( EuroSCORE) (Appendix G5, G6) [176]. Logistic EuroSCORE ≥ 10%, EuroSCORE II ≥ 4%, or operative risk level ≥ 10% according to the STS scale are proposed as high-risk criteria [177, 178]. The choice of additional diagnostic methods to verify comorbid conditions 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 affecting the risk of complications from mitral valve (MV) interventions. Frailty is a reduction in physiological reserve and the ability to maintain homeostasis, which increases sensitivity to stress and, accordingly, the risks 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 task [179-181]. Malnutrition, cachexia, and cognitive impairment are associated with a high risk of complications and poor prognosis after MV surgery [182, 183]. Pathology of other organs and systems includes kidney, liver, and lung diseases. Preoperative liver failure is associated with an increased risk of complications. Chronic kidney disease stages 4 and 5 (glomerular filtration rate < 30 mL/min.) in the patient causes a high risk of acute renal failure in the early postoperative period, the need for dialysis, severe complications, and an adverse outcome. Pulmonary pathology combined with pain syndrome in the early postoperative period after MV intervention using full median sternotomy in the case of prolonged mechanical ventilation is a risk factor for respiratory complications [184-186]. Since the prevalence and severity of comorbidities increase with the patient's age, the correct assessment of the risk-benefit ratio of a particular treatment method becomes more complicated. When planning patient treatment, it is necessary to take into account the capabilities, experience, and results of the specific clinic where the patient will be treated. A multidisciplinary team of specialists should play the primary role in solving these tasks.

3.1 Conservative Treatment

Prevention of rheumatic fever exacerbation

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

Comments: prophylactic administration of penicillin antibiotics is recommended for 10 years after the last rheumatic fever exacerbation or until the age of 40. Patients who have had a single rheumatic attack are at high risk for recurrent rheumatic flares. Patients with rheumatic carditis have an increased propensity for recurrent rheumatic attacks; therefore, their secondary prevention is of great clinical importance, preventing the progression of the defect, decompensation of chronic heart failure (CHF), and thromboembolic events in major vessels. Continuous antibacterial prophylaxis, combined with the identification of a laboratory-confirmed etiological agent of rheumatism, has proven to be effective. Lifelong prophylaxis is indicated for high-risk MS patients (Group A Streptococcus carriers).

Prevention of infective endocarditis

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

Treatment of arterial hypertension and lipid-lowering therapy

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

• The use of statins is recommended for all patients with MS for the primary and secondary prevention of cardiovascular complications, based on standard risk scales in accordance with current clinical guidelines "Lipid Metabolism Disorders" [30, 32, 190].

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

Comment: patients with clinical manifestations of valvular heart disease require surgical intervention rather than medical therapy. At the same time, thorough evaluation and management of atherosclerosis risk factors are important in patients with mitral valve disease to prevent concomitant coronary artery disease.

Treatment of cardiac arrhythmias

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

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

• When other rate-controlling drugs are ineffective or cannot be used, as well as in patients with unstable hemodynamics or significantly reduced LVEF, it is recommended to consider the intravenous administration of #amiodarone** for heart rate control [71-73].

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

Comments: although rate-controlling beta-blockers and calcium channel blockers may temporarily improve symptoms, the use of negative dromotropic agents in patients with mitral stenosis and sinus rhythm remains controversial. Despite the fact that heart rate reduction and increased diastolic filling decrease the transvalvular pressure gradient, according to clinical studies, beta-blockers may reduce exercise tolerance, mainly due to a decrease in cardiac output resulting from a fixed stroke volume. Nevertheless, several randomized trials currently exist showing that beta-blockers and ivabradine** can improve exercise tolerance and reduce symptoms in patients with mitral stenosis. In case of pulmonary congestion symptoms, salt restriction and intermittent diuretic therapy are indicated. Digoxin** is ineffective in patients with mitral stenosis in sinus rhythm, except for cases of confirmed left or right ventricular dysfunction [60-66, 74].

Anticoagulant therapy prior to mitral valve replacement

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

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

ESC/ESC IIb A (LoE C, GoR 4)

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

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

Comments: during the titration of an individual warfarin** dose, the INR must be monitored every 1–3 days until two consecutive similar INR values within the target range are obtained. This indicates that the therapeutic anticoagulation range has been reached. Subsequently, INR monitoring should be performed once every 3–4 weeks. In the event of excessive hypocoagulation, changes in warfarin** dose, or the initiation of concomitant therapy that may affect the INR level, its value must be checked within 4–5 days to confirm that the INR remains within the therapeutic range [43].

Efforts should be made to maintain the INR within the target range of 2.0–3.0, including in elderly patients. An INR time in the therapeutic range of ≥ 65% is considered optimal. Previously accepted INR values of 1.6–2.2 for elderly patients are now considered unjustifiably low due to a twofold increase in stroke risk when INR values are < 2.0.

Lower INR values within the target range (2.0–2.5) should be aimed for when warfarin** is used in combination with acetylsalicylic acid** or clopidogrel**, or when therapy is resumed after bleeding.

Systemic thromboembolism occurs in 10–20% of patients with mitral stenosis. The risk of thromboembolism increases with age and the presence of atrial fibrillation. One-third of thromboembolic events occur within the first month after the onset of atrial fibrillation, and two-thirds within a year. There is no evidence that the frequency of thromboembolic events correlates with the severity of mitral stenosis, cardiac output, left atrial size, or even the presence of heart failure symptoms. Thromboembolism may be the initial manifestation of mitral stenosis. In patients with a history of thromboembolism, recurrence is observed in 15–40 cases per 100 patient-years [16, 45-48, 87].

Retrospective studies have demonstrated a 4- to 15-fold reduction in thromboembolic events—both systemic and pulmonary—with anticoagulant therapy. The majority of these studies included patients who had experienced a single thromboembolic episode prior to initiating anticoagulant therapy [45, 88]. The greatest efficacy of anticoagulant therapy has been identified in patients at high risk for thromboembolism. Patients with mitral stenosis who are at high risk for future thromboembolism include those with a prior history of thromboembolism or those with paroxysmal or permanent atrial fibrillation [16, 45-48, 87, 88].

• DOACs (B01A: Antithrombotic agents) are not recommended for the prevention of thromboembolic events in patients with moderate and severe mitral stenosis [16, 32, 45-48].

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

Anticoagulant therapy following mitral valve replacement

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

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

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

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

Comments: efforts should be made to maintain the INR in the target range of 2.5–3.5 in patients with a mitral valve prosthesis and no risk factors for thrombosis, and at least 3.0–3.5 in patients with a mechanical bileaflet mitral valve prosthesis*** who have risk factors for thrombosis (atrial fibrillation, left atrium > 5 cm, EF < 35%, spontaneous echo contrast, concomitant tricuspid valve replacement) [103].

• All patients receiving VKA therapy are recommended to perform self-monitoring of INR, provided they have undergone appropriate training in a patient education school and are under medical supervision (remote laboratory monitoring or regular medical visits) [59, 110, 111].

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

ESC/ESC IIa C (LoE A, GoR 1)

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

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

• In high-risk patients according to the CHA2DS2-VASc score (Appendix G3) with implanted coronary stents and a mechanical mitral valve prosthesis, it is recommended to consider a duration of triple therapy with acetylsalicylic acid** (100 mg/day), clopidogrel** (75 mg/day), and VKA for 1 week, regardless of the stent type used and the clinical presentation (ACS or stable CAD) [100, 104, 114, 192, 193].

ESC/ESC IIa B (Level of Evidence B, Grade of Recommendation 2)

Comments: after discontinuation of acetylsalicylic acid** (100 mg/day), continue dual therapy preferably including clopidogrel** (75 mg/day) and VKA, with discontinuation of the antiplatelet agent (B01AC: Platelet aggregation inhibitors excluding heparin) in patients at high bleeding risk after 6 months, and monotherapy with VKA in patients at low bleeding risk after 12 months.

• In patients with any mechanical mitral valve prosthesis and implanted coronary stents who are at high ischemic risk (ACS or presence of anatomical/procedural features) exceeding the bleeding risk, it is recommended to consider prescribing triple therapy including acetylsalicylic acid* (100 mg/day), clopidogrel** (75 mg/day), and VKA for a duration of up to 30 days [104, 114, 192, 193].

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

Comments: the addition of low doses (75–100 mg/day) of acetylsalicylic acid** to VKA therapy may reduce the incidence of thromboembolic events at the cost of an increased bleeding risk. Therefore, the addition of antiplatelet agents (B01AC Platelet aggregation inhibitors excluding heparin) to VKA should be performed in patients with a very high risk of thromboembolic complications when the benefits significantly outweigh the risks [104, 114]. In patients experiencing thromboembolic events despite target INR levels with VKA, low doses (75–100 mg/day) of acetylsalicylic acid** should be added.

• In high bleeding risk patients with implanted coronary stents and a mechanical mitral valve prosthesis, it is recommended to consider a duration of triple therapy with acetylsalicylic acid** (75–100 mg/day), clopidogrel** (75 mg/day), and VKA for 1 week, regardless of the stent type used and the clinical manifestation (acute coronary syndrome or stable CAD) [104, 114, 192, 193].

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

Comments: after discontinuation of acetylsalicylic acid** (75–100 mg/day), continue dual therapy preferably including clopidogrel** (75 mg/day) and VKA, with discontinuation of the antiplatelet agent and monotherapy after 6 months following elective PCI and after 12 months following ACS.

• In patients with a mechanical mitral valve prosthesis requiring acetylsalicylic acid** and/or clopidogrel** in addition to VKA, the VKA dosage should be carefully maintained in the lower part of the target therapeutic INR range, and the time in therapeutic range should be > 65–70% [101, 104].

ESC IIa B (Level of Evidence B, Grade of Recommendation 2)

• DOACs are not recommended in patients with a mechanical mitral valve prosthesis [102].

ESC/ESC III B (Level of Evidence A, Grade of Recommendation 2)

Treatment of heart failure

• Medical therapy for chronic heart failure is recommended for all patients with severe mitral stenosis in accordance with current clinical guidelines on "Chronic Heart Failure" [30, 32, 89, 90, 191].

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

Comments: HF therapy in severe MS includes diuretics, beta-blockers, potassium-sparing diuretics, sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins) and is carried out in accordance with the approved clinical guideline "Chronic Heart Failure" [89-94, 191].

ACE inhibitors / valsartan + sacubitril**, beta-blockers (BBs), aldosterone antagonists, dapagliflozin** / empagliflozin** (sodium-glucose cotransporter 2 inhibitors) are indicated as part of a combined four-drug therapy for all patients with symptomatic HFrEF (EF ≤ 40%) to reduce heart failure hospitalization and death. In patients with HFmrEF, the administration of ACE inhibitors / ARBs, BBs approved for HFrEF, and aldosterone antagonists may be recommended to reduce the risk of heart failure hospitalization and death. 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 if there are additional indications.

In all cases of diuretic prescription, it is indicated to carefully monitor blood electrolyte levels as well as renal function.

Following successfully performed surgical treatment for MS with persistent HF, standard HF therapy is not contraindicated.

ESC III B (Level of Evidence C, Grade of Recommendation 5)

Comments: if atrial fibrillation is recent and the left atrium is only moderately enlarged, cardioversion should be performed shortly after a successful intervention [32].

3.2 Surgical Treatment

Indications for surgery in mitral stenosis

1) percutaneous mitral balloon valvuloplasty is unavailable or impossible due to the lack of personnel qualified to perform such a procedure;

2) percutaneous mitral balloon valvuloplasty is contraindicated (see below);

3) valve morphology is unfavorable for percutaneous mitral balloon valvuloplasty in a patient with an acceptable operative risk [59, 62].

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

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

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

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

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

Comments: mitral valve replacement is a well-established surgical procedure in patients with severe MS who are not candidates for surgical commissurotomy or percutaneous mitral valvotomy. Perioperative mortality in mitral valve replacement depends on many factors, including functional status, age, left ventricular function, cardiac output, comorbidities, and concomitant coronary artery disease.

In young patients without comorbidities and complications, mitral valve replacement can be performed with a risk of less than 5%; however, in elderly patients with comorbidities or pulmonary hypertension at the baseline hypertensive level, perioperative mortality for mitral valve replacement can reach 10–20%.

Mitral valve replacement with preservation of the subvalvular apparatus helps maintain left ventricular function, but this may be difficult to achieve in patients with rheumatic MS [54]. An alternative approach exists, such as artificial chordal reconstruction prior to mitral valve replacement [55, 56]. Complications may occur: thrombosis, valve rupture or dysfunction, infective endocarditis, thromboembolism (see section 7.3). There is also a known risk of long-term anticoagulant therapy in patients with any mechanical prosthesis***.

Due to the increased risk, indications for MV surgery in patients with calcified fibrous valves are more stringent. However, in the presence of severe calcification, fibrosis, and fusion of the subvalvular structures, successful commissurotomy or catheter balloon valvuloplasty is unlikely; MV replacement is necessary. In patients with NYHA functional class III symptoms caused by severe MS or a combination of MS and mitral regurgitation (MR), MV replacement leads to a significant reduction in symptoms. Delaying surgery until the appearance of NYHA functional class IV symptoms should be avoided due to an increased risk of operative mortality and a worsened long-term prognosis. However, if a physician diagnoses a patient with MS and NYHA functional class IV heart failure for the first time, this is not a contraindication to surgery, because without surgical intervention the prognosis is much more unfavorable.

Expert opinions regarding the management strategy for asymptomatic or mildly symptomatic patients with severe MS (valve area less than 1.5 cm²) and severe pulmonary hypertension (systolic pulmonary artery pressure greater than 50 mmHg) vary, but the majority of specialists lean toward MV replacement.

It is well recognized that patients with such severe pulmonary hypertension are rarely asymptomatic [62].

Selection of Prosthesis Type for Mitral Valve Replacement

• MVR with a mechanical prosthesis (mechanical bileaflet mitral valve prosthesis***) is recommended in the presence of the patient's written informed consent and in the absence of contraindications to long-term anticoagulant therapy (increased bleeding risk due to comorbidities, low treatment adherence, as well as geographical, domestic, and occupational conditions) [59, 62].

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

• MVR with a mechanical prosthesis (mechanical bileaflet mitral valve prosthesis***) is recommended for patients at risk of rapid structural degeneration of a bioprosthetic valve (hyperparathyroidism, hemodialysis) [59, 62].

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

• MVR with a mechanical prosthesis (mechanical bileaflet mitral valve prosthesis***) is recommended to be considered in patients already receiving anticoagulant therapy due to the presence of a mechanical heart valve in another position [59, 62].

ESC/ACC IIa C (LOE C, GOR 5)

• MVR with a mechanical prosthesis (mechanical bileaflet mitral valve prosthesis***) is recommended for patients under 65 years of age [59, 62].

ESC/ACC IIa C (LOE C, GOR 5)

• MV replacement with a mechanical prosthesis (mechanical bileaflet mitral valve prosthesis***) is generally recommended for patients with an optimal life expectancy and a high risk of repeat surgical or transcatheter intervention on the MV [32].

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

Comments: the choice of the type of implanted prosthesis (mechanical or bioprosthetic) is the result of weighing the risks of bleeding/embolism with a mechanical prosthesis against the risk of degenerative changes in bioprosthetic valves. A mechanical prosthesis is preferable for patients under 65 years of age in the absence of additional bleeding risk factors. In patients with MS aged 65 years and older, both types of prosthesis are acceptable, taking into account the risk of bleeding, the patient's social status (living in a rural area, difficulty monitoring INR), expected patient adherence to antithrombotic therapy, and the presence of comorbid conditions (severe CHF, AF) requiring anticoagulants (B01A: Antithrombotic agents), as well as patient preferences [30, 32, 95-97].

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

• MVR with a bioprosthetic valve (mitral bioprosthesis***) is recommended in the presence of the patient's written informed consent, or in the presence of contraindications to long-term anticoagulant therapy, or when effective anticoagulation is unlikely (low treatment adherence, not always available) or contraindicated due to a high bleeding risk (prior major bleeding, comorbidities, low treatment adherence, unwillingness, lifestyle, occupation) [59, 62].

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

• MVR with a bioprosthetic valve (mitral bioprosthesis***) is recommended for repeat surgery due to mechanical valve thrombosis despite adequate long-term anticoagulant therapy [59, 62].

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

• MVR with a bioprosthetic valve (mitral bioprosthesis***) is recommended to be considered in patients with a low probability and/or low operative risk of future re-replacement [59, 62].

ESC/ACC IIa C (LOE C, GOR 5)

• MVR with a bioprosthetic valve (mitral bioprosthesis***) is recommended to be considered in young women planning pregnancy [59, 62].

ESC/ACC IIa C (LOE C, GOR 5)

• MVR with a bioprosthetic valve (mitral bioprosthesis***) is recommended to be considered in patients older than 70 years [59, 62].

ESC/ACC IIa C (LOE C, GOR 5)

• MVR with a bioprosthetic valve (mitral bioprosthesis***) is recommended to be considered in patients with a life expectancy shorter than the expected durability of the mitral bioprosthesis [59, 62].

ESC/ACC IIa C (LOE C, GOR 5)

Indications for Surgical Treatment of Mechanical Complications Associated with a Heart Valve Prosthesis

ESC/RSC I (LoE C, GoR 3)

ESC/RSC IIa (LoE B, GoR 2)

ESC/RSC I (LoE C, GoR 5)

ESC/RSC IIa (LoE B, GoR 2)

ESC/RSC I (LoE C, GoR 5)

ESC/RSC IIa (LoE C, GoR 4)

ESC/RSC I (LoE C, GoR 5)

ESC/RSC IIa (LoE C, GoR 5)

Indications for Percutaneous Catheter Mitral Balloon Valvuloplasty

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

Comments: catheter balloon mitral valvuloplasty should be performed in centers whose specialists have sufficient experience specifically in such interventions [14, 35-37].

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

ESC not specified (LoE C, GoR 4)

ESC not specified (LoE C, GoR 4)

ESC / RCS IIb C (LoE C, GoR 4)

ESC / RCS III C (LoE C, GoR 4)

ESC / RCS III C (LoE C, GoR 4)

Comments: the mechanism of improvement following surgical commissurotomy and percutaneous valvulotomy is associated with the successful splitting of commissures fused by the rheumatic process. This leads to a decrease in the gradient, an increase in the calculated MV area, and, consequently, an improvement in clinical symptoms.

The degree of hemodynamic and clinical improvement depends on the magnitude of the decrease in the transmitral gradient and the increase in valve area. Patients with mobile, non-calcified valve leaflets and minimal subvalvular apparatus fusion achieve the best immediate and long-term outcomes when a substantial increase in valve area is attained.

Percutaneous mitral balloon valvulotomy was first performed in the early 1980s and became a clinically established technique in 1994. Today, a single hourglass-shaped balloon (Inoue balloon) is used by most centers. Similar results have been achieved with the introduction of mechanical percutaneous mitral commissurotomy using a metal valvulatome. The advantage of this technique is the ability to reuse the metal device after sterilization and reduce treatment costs [33]; however, experience with this method is limited. The balloon valvulotomy procedure requires further investigation. In well-equipped centers, the success rate is high, and the complication rate is low [35]. The results of percutaneous mitral balloon valvulotomy largely depend on the expertise of the specialists.

Immediate results of catheter mitral valvotomy do not differ from those of mitral commissurotomy [14, 35-43]. The mean valve area usually doubles (from 1.0 to 2.0 cm²), and the transmitral gradient decreases by 50–60%. Overall, 80–95% of patients achieve a positive outcome: mitral valve area greater than 1.5 cm², left atrial pressure below 18 mmHg, and absence of complications. The most frequent acute complications reported in large studies include severe MR, which occurs in 2–10% of cases, and secondary atrial septal defect. A significant atrial septal defect is registered in 12% of patients when using a double-balloon and in less than 5% with the Inoue balloon. Smaller atrial septal defects can be detected by transesophageal echocardiography in a larger number of patients. Less common complications include left ventricular perforation (0.5–4.0%), thromboembolism (0.5–3%), and myocardial infarction (0.3–0.5%). Mortality from balloon valvotomy in large studies is 1–2% [14, 35-37, 43]; however, with growing procedural experience, mortality from percutaneous mitral valvotomy in individual patients may be less than 1% [38]. Intraprocedural echocardiography can be valuable for balloon positioning and hemodynamic assessment.

Symptom improvement occurs almost immediately after successful catheter balloon valvuloplasty or surgical commissurotomy, and skeletal muscle metabolism continues to improve gradually over several months [58]. Pre- and postoperative hemodynamic parameters following catheter valvuloplasty or surgical commissurotomy confirmed a decrease in left atrial pressure, pulmonary artery pressure, and pulmonary arteriolar resistance, as well as an increase in cardiac output [100-103]. Patients with significant right ventricular failure in the postoperative period are indicated for inhalation of nitric oxide and administration of an endothelin antagonist (C02KX04 Antihypertensives for pulmonary arterial hypertension) to reduce pulmonary vascular resistance and pulmonary hypertension [102]. Gradual regression of pulmonary hypertension over several months has been reported [100, 104].

In patients with a history of atrial fibrillation, antithrombotic agents (warfarin** or other drugs) should be prescribed one to two days after the procedure. History taking, physical examination, targeted chest radiography, and electrocardiography (ECG) should be performed annually in asymptomatic or minimally symptomatic patients. Prevention of infective endocarditis and recurrent rheumatic fever is indicated. Anticoagulant therapy is recommended for patients with existing or a history of atrial fibrillation.

MS is relatively common in women of childbearing age. The increased circulating blood volume, increased cardiac output, and tachycardia associated with pregnancy can be accompanied by significant challenges.

Catheter mitral valvuloplasty can be performed with a low risk of maternal or fetal complications and with excellent clinical and hemodynamic outcomes [61].

3.3 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 MS 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 achieve sedation and emotional stability [23].

No ESC guideline (LoE C, GoR 5)

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

• All patients with MS admitted to the hospital for surgical treatment are recommended to use the following for intraoperative anesthesia: propofol**, benzodiazepine derivatives, halogenated hydrocarbons. Fentanyl** (for preoperative premedication), Diazepam** (as part of surgical preparation). For cardiac surgeries, either intravenous anesthesia based on propofol** and #fentanyl**, or combined anesthesia using halogenated hydrocarbons and #fentanyl** at all stages of surgery can be used [23, 164].

No ESC guideline (LoE C, GoR 5)

Comment: the following drugs are used for intraoperative anesthesia: midazolam**/#diazepam**/propofol** and #fentanyl**, sodium oxybutyrate**, and halogenated hydrocarbons in combination with #fentanyl** i.v. in calculated dosages can be used. 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 halogen-containing gaseous anesthetics and #fentanyl** during cardiac surgeries [164].

• All patients with MS admitted to the hospital for surgical treatment are recommended to use opioids in age-appropriate dosages for pain relief in the early postoperative period [23].

No ESC guideline (LoE C, GoR 5)

Comments: drugs used for postoperative analgesia: the first 24 hours after surgery — trimeperidine**, or morphine** i.m. every 4–8 hours, NSAIDs. If special dispensers are available, patient-controlled analgesia with fentanyl** is effective. If severe pain syndrome persists, trimeperidine**/morphine**/fentanyl** as clinically indicated.

Use of nitric oxide in the postoperative period

• In surgical treatment of MS in patients with precapillary pulmonary hypertension (mean pulmonary arterial pressure > 20 mm Hg, pulmonary capillary wedge pressure ≤ 15 mm Hg) with pulmonary vascular resistance > 5 Wood units and echocardiographic signs of RV failure in the intra- and postoperative period, it is recommended to consider the possibility of nitric oxide inhalation [115].

ESC/ACC IIaB (Level of Evidence B, Formulated Clinical Recommendations Grade 1)

Comments: patients with MV pathology are characterized by elevated pressure in the pulmonary circulation (Group 2 pulmonary hypertension, postcapillary pulmonary hypertension). Over time, such patients begin to exhibit increased pulmonary vascular resistance, i.e., a precapillary component appears (reactive pulmonary hypertension). Surgical intervention on the pulmonary circulation effectively relieves the postcapillary component of pulmonary hypertension. However, increased pulmonary vascular resistance (precapillary component) persists in the postoperative period, adversely affecting hemodynamic parameters up to the development of RV dysfunction. A completed meta-analysis confirmed a significant improvement in clinical parameters—reduction in the duration of mechanical ventilation and length of stay in the intensive care unit with nitric oxide inhalation [115].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Medical rehabilitation programs for patients after surgical correction of MS are aimed at limiting psychological and physiological stress associated with cardiac surgery, reducing the risk of mortality and disability, modifying lifestyle, and improving cardiovascular function to maximize the patient's quality of life [116].

Medical (cardiac) rehabilitation is presented as a three-stage system within which patient routing is implemented (Appendix B1) [116]. Medical rehabilitation care for patients with mitral stenosis is provided on a scheduled basis after diagnosis establishment (upon initial contact with the patient) or in chronic disease courses regardless of disease duration, provided the patient's clinical state is stable, medical indications are present, and contraindications to specific rehabilitation methods are accounted for.

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

Cardiac rehabilitation is carried out by a multidisciplinary team of medical professionals to achieve optimal physical and psychosocial health in patients with MS, with the participation of partners, other family members, and caregivers [117].

ESC/RSC IIa C (Level of Evidence A, Formulated Clinical Recommendations Grade 1)

Comments: the presence of contraindications to exercise training is not a factor limiting patient participation in cardiac rehabilitation programs and does not exclude the use of other physical rehabilitation methods (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 in the outpatient setting, which should be conducted in face-to-face, remote (at home using digital and mobile health tools), or mixed formats to increase patient coverage with rehabilitation measures and improve adherence to lifestyle modification, rehabilitation, and pharmacotherapy [122-125].

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. RCTs (randomized controlled trials) and systematic reviews show that early mobilization improves physical function (the distance covered in the 6-minute walk test improved by 54 m) at discharge in patients after heart surgery [126].

A prospective RCT demonstrated that early initiation of CR improved postoperative functional capacity (6-minute walk test), reduced the duration of mechanical ventilation, oxygen therapy dependence, and hospital stay in patients undergoing elective cardiac surgery [127, 128].

ESC/RSC IIa C (Level of Evidence C, Formulated Clinical Recommendations Grade 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) available for this purpose (www.icf-research-branch.org/download/category/12-cardiovascularandrespiratoryconditions) [121, 130-132]. The ICF is a tool for describing organ and system dysfunctions and daily functioning impairments (self-care, communication, performance of professional and social roles) resulting from disease/injury in a patient, taking into account environmental factors that may facilitate or hinder the patient's performance of these functions [118].

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) [118, 133, 134].

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

Comments: patient information and education should be provided in any available format (individually, within rehabilitation counseling, and/or in the "School for Patients with Valvular Heart Disease") in an in-person or online mode [118, 125, 135].

ESC/ACC IIa C (LoE C, LoD 4)

ESC/ACC IIa C (LoE C, LoD 4)

Comments: contraindications to physical training are presented in Appendix B2. A personalized physical training program in patients after surgical treatment of mitral stenosis is developed depending on the stage of cardiac rehabilitation and includes regular moderate-intensity aerobic (dynamic) physical exercises, low-to-moderate intensity strength exercises (indicated for: low risk of postoperative complications, good wound healing after sternotomy; for the upper extremities only after sternal stabilization and no earlier than six weeks after surgery).

Both in patients with mitral stenosis who have undergone surgery and in those without surgical treatment (in the absence of contraindications), the physical rehabilitation program should include therapeutic gymnastics with breathing exercises, inspiratory muscle training using breathing trainers (as indicated) and other breathing techniques (as indicated), and walking.

• To ensure the safety of the physical rehabilitation program, it is recommended to monitor the patient's condition (complaints, clinical symptoms, blood pressure, heart rate, and ECG as indicated), and assess the level of perceived exertion using the Borg Rating of Perceived Exertion (Borg RPE) during training (Appendix G) [118, 137].

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

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

Comment: indications for sanatorium-resort treatment include mitral stenosis, stage I CHF (FC I–II) without prognostically unfavorable cardiac rhythm and conduction disorders, and without signs of process activity [145].

5. Prevention and Dispensary Observation

Follow-up monitoring

Recommendations for follow-up monitoring of patients with MS are based on examination results, study data, and the choice of further management strategy. All patients must be informed that any change in their condition requires medical attention [146].

• All patients with MS, as well as those following mitral valve replacement, are recommended to have a dispensary appointment (examination, consultation) with a cardiologist, or in the absence of a cardiologist, with a general practitioner or family physician, at least once a year to determine the frequency of visits, monitor compliance with prescribed recommendations, adjust therapy in a timely manner, assess CVD risk, refer for additional studies, sanatorium-resort treatment, and, if necessary, hospitalization [147, 148].

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

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

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

• If new symptoms appear or old ones worsen in patients with MS, it is recommended to conduct a follow-up appointment (examination, consultation) with a cardiologist and perform echocardiography [147, 148].

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

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

Comments: echocardiography as a 1st-line non-invasive diagnostic test must be performed in all patients with suspected MS, MS symptoms, or an auscultatory murmur, serving as the "gold standard" of diagnostics. Echocardiography is considered the most valuable non-invasive diagnostic method for MS because it not only verifies MS but also in most cases identifies the etiology of MS, assesses its severity, evaluates left ventricular function and dimensions, sizes of other cardiac chambers, and determines prognosis and the timing of valve surgery.

Comprehensive assessment of MS includes:

– measurement of transvalvular flow;

– determination of the mean transvalvular pressure gradient;

– calculation of the effective valve area.

Attention to detail in accurately measuring pressure and flow is crucial, especially in patients with low cardiac output or low transvalvular pressure gradients.

• To decide on referring patients with MS for echocardiography, transesophageal echocardiography, cardiac MRI, cardiac CT, coronary angiography, and other imaging studies, it is recommended to conduct a follow-up appointment (examination, consultation) with a cardiologist [147, 148].

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

• The cardiologist is recommended to conduct secondary prevention of CVD in all patients with mitral stenosis, as well as after mitral valve replacement. Their follow-up visit to the doctor should be scheduled within 3 days after hospital discharge [147, 149].

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

Comments: the annual examination must include an physical examination, medical history taking, laboratory and biochemical blood tests (general clinical biochemical blood test, lipid profile biochemical blood test, coagulogram (exploratory assessment of the hemostatic system), determination of blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, etc.) — depending on the clinical presentation of the disease, echocardiography, and ECG. Patients complaining of palpitations are indicated for ambulatory ECG monitoring (electrocardiographic monitoring) to detect paroxysmal atrial fibrillation. If complaints of dyspnea, edema, or fever arise, echocardiography should be performed.

• Patients with mitral stenosis and after mitral valve replacement are recommended to undergo resting ECG recording, analysis, description, and interpretation of electrocardiographic data once a year during a routine visit and additionally upon the occurrence of arrhythmia, as well as when prescribing or modifying treatment that affects intracardiac electrical conduction [147, 148].

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

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

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

Comments: the evaluation includes:

- Transthoracic echocardiography;

- 12-lead electrocardiography;

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

- Complete blood count;

- General clinical biochemical blood test;

- Determination of INR (in case of warfarin therapy**).

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

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

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

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

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

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

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

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

• 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 under physician supervision (remote monitoring of laboratory parameters or regular doctor visits) [32, 147, 148].

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

ESC/RCS I A (LoE A, GoR 1)

Comment: high INR variability is a significant independent predictor of reduced survival after valve replacement. Current data indicate that INR self-monitoring reduces INR variability and the incidence of clinical events, including in patients with prosthetic heart valves; however, appropriate patient training and regular quality control are essential. Nevertheless, patients with unstable INR or complications related to anticoagulant therapy should have their anticoagulation monitored in a clinical setting [32]. Patients must be informed about the ongoing anticoagulant therapy, target INR values, and interactions of oral VKAs with other medications and food products [150].

Major risk factors for thromboembolism include: left ventricular dysfunction, hypercoagulation, presence of atrial fibrillation, and history of thromboembolism [150].

ESC/RSC I A (LE Level C, SOR 5)

Comments: persistence of HF after surgical correction of MS may be due to left ventricular systolic dysfunction caused by: pre-existing preoperative left ventricular systolic dysfunction; perioperative myocardial injury; progression of unoperated valve pathology; complications associated with prosthetic valves; presence of comorbid conditions (coronary artery disease, arterial hypertension, cardiac arrhythmias), as well as HF with preserved ejection fraction (HFpEF) phenotype. Optimal medical therapy can prevent HF progression [30, 32, 89, 94].

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

ESC/RSC IIa (LoE C, GoR 5)

ESC/RCS IIa (LoE C, GoR 5)

• For the prevention of infective endocarditis, antibiotic prophylaxis before dental procedures is recommended for all patients with mechanical and biological valves in accordance with current clinical guidelines on "Infective Endocarditis and Intracardiac Device Infections" [32, 160, 161, 188].

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

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

Comment: antibiotic prophylaxis for infective endocarditis during dental procedures involving the gums, periapical region, root canal work, scaling, and oral mucosal perforation is presented in Table 5, Appendix A3-2 [32, 160, 161].

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

Comments: patients who have had a single rheumatic attack are at high risk for recurrent rheumatic flare-ups.

Patients suffering from rheumatic carditis have an increased propensity for recurrent rheumatic attacks, which makes their secondary prevention of great clinical importance in preventing disease progression, HF decompensation, and thromboembolic events in major vessels. Continuous antibiotic prophylaxis, combined with the identification of a laboratory-confirmed etiological agent of rheumatism, has proven to be effective [147, 149, 150].

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

6. Organization of Medical Care

Indications for elective hospitalization:

1) diagnostic ambiguity and the need for special diagnostic methods (procedures that cannot or should not be performed in an outpatient setting) to clarify the cause and severity of mitral stenosis, and to determine the scope and tactics of treatment;

2) scheduled surgery for mitral valve replacement or reconstruction.

Indications for emergency hospitalization:

1) decompensated heart failure complicated by pulmonary edema, cardiogenic shock, or hemodynamic instability;

2) paroxysm of atrial fibrillation.

Indications for patient discharge from the hospital:

1) establishment of a diagnosis of mitral stenosis using special investigative methods, determining the cause and severity;

2) completed mitral valve replacement or reconstruction surgery with a finalized follow-up period and management of perioperative complications;

3) optimized medical therapy in case of refusal of surgical treatment;

4) termination of an atrial fibrillation paroxysm.

7. Additional Information

No.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Chairpersons:

1. Bokeria LA, Academician of the RAS (Moscow), Russian Association of Cardiovascular Surgeons (ACVS)

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

3. Asatryan TV, PhD (Moscow), ACVS

4. Irtyuga OB, MD, PhD (Saint Petersburg), RSC

Working Group Members:

1. Aleksandrova SA, PhD (Moscow), All-Russian Public Organization for the Promotion of the Development of Diagnostic and Interventional Radiology “Russian Society of Radiologists”

2. Apkhanova TV, PhD, member of the Russian Society of Cardiology (RSC), member of the European Society of Cardiology (ESC), member of the American Vein and Lymphatic Society (USA)

3. Aronov DM, Prof., MD, PhD (Moscow), RSC, RosOKR

4. Babicheva OV, PhD (Krasnodar), RSC

5. Barbukhatti K.O., MD, Assoc. Prof. (Krasnodar), CVSS, RSC

6. Belan I.A., cardiologist (Krasnodar), RSC

7. Bergen T.A., MD (Novosibirsk), All-Russian Public Organization for Assistance to the Development of Radiation Diagnostics and Therapy "Russian Society of Radiologists"

8. Bogachev-Prokofiev A.V., MD (Novosibirsk), CVSS

9. Bodrova D.V., cardiologist (Krasnodar), RSC

10. Bubnova M.G., Prof., MD (Moscow), RSC, ROSOKhR

11. Gendlin G.E., Prof., MD (Moscow), RSC

12. Golukhova E.Z., Academician of the RAS (Moscow), RSC, CVSS

13. Gordeev M.L., Prof., MD (St. Petersburg), CVSS

14. Demchenko E.A., Prof., MD (St. Petersburg), RSC

15. Dzhordzhikiya R.K., Prof., MD (Kazan), CVSS

16. Dorofeev A.V., PhD (Moscow), All-Russian Public Organization for Assistance to the Development of Radiation Diagnostics and Therapy "Russian Society of Radiologists"

17. Kalashnikov S.V., PhD (Moscow), CVSS

18. Karaskov A.M., Academician of the RAS (Novosibirsk), CVSS

19. Konchugova T.V., MD, Prof., Member of the National Association of Spa Treatment Experts

20. Lyapina I.N., PhD (Kemerovo), RSC

21. Malev E.G., MD (St. Petersburg), RSC

22. Mironenko M.Yu., PhD (Moscow), All-Russian Public Organization for Assistance to the Development of Radiation Diagnostics and Therapy "Russian Society of Radiologists"

23. Petrosyan K.V., Prof. (Moscow), Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists

24. Rychina I.E., PhD (Moscow), All-Russian Public Organization for Assistance to the Development of Radiation Diagnostics and Therapy "Russian Society of Radiologists"

25. Sinitsyn V.E., MD, Prof. (Moscow), All-Russian Public Organization for Assistance to the Development of Radiation Diagnostics and Therapy "Russian Society of Radiologists"

26. Skopin I.I., Corresponding Member of the RAS, MD, Prof. (Moscow), CVSS

27. Sukhova I.V., PhD (St. Petersburg), RSC

28. Tarasov D.G., PhD (Astrakhan), CVSS

29. Tarasov R.S., MD (Kemerovo), Russian Scientific Society of Endovascular Diagnostics and Treatment Specialists

30. Tarkova A.R., PhD (Novosibirsk), All-Russian Public Organization for Assistance to the Development of Radiation Diagnostics and Therapy "Russian Society of Radiologists"

31. Tatarintseva Z.G., PhD (Krasnodar), RSC

32. Farulova I.Yu., PhD (Moscow), All-Russian Public Organization for Assistance to the Development of Radiation Diagnostics and Therapy "Russian Society of Radiologists"

33. Khubulava G.G., Academician of the RAS (St. Petersburg), CVSS

34. Chernov I.I., PhD (Astrakhan), CVSS

35. Shlyakhto E.V., Academician of the RAS (St. Petersburg), RSC

36. Shneider Yu.A., MD (Kaliningrad), CVSS

37. Yurova O.V., MD, Prof., Member of the National Association of Spa Treatment Experts

38. Yurpolskaya L.A., MD (Moscow), All-Russian Public Organization for Assistance to the Development of Radiation Diagnostics and Therapy "Russian Society of Radiologists"

All working group members confirmed the absence of financial support/conflict of interest that needs to be disclosed.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the developed clinical guidelines:

• Cardiovascular Surgeon

• Cardiologist

• Ultrasound Diagnostics Physician

• General Practitioner (Family Doctor)

• Functional Diagnostics Physician

• Radiologist

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

Description of methods used to assess the quality and strength of evidence: the evidence base for the recommendations includes publications indexed in PubMed and Scopus databases. The search depth was more than 40 years.

Methods used for assessing the quality and strength of evidence:

• expert consensus;

• assessment of the quality of recommendations in accordance with the grading scheme;

• assessment of the strength of evidence in accordance with the grading scheme.

Since the RSC is part of the European Society of Cardiology (ESC) and RSC members are also members of the ESC, 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, national guidelines were developed based on the ESC guidelines, taking into account national specifics, examination and treatment features, and the availability of specific medical care. For this reason, when developing the Russian clinical guidelines of the RSC, international classes of recommendation were used to assess the necessity of implementing recommendation statements and the levels of evidence for these classes (Tables S1 and S2).

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 implementation or, conversely, strictly not recommended for use, RSC experts, based on the rules for formulating classes of recommendations according to the ESC 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 (LoE) and grades of recommendation (GoR) scales for therapeutic, rehabilitation, preventive, and diagnostic interventions (Tables S3, S4, and S5) introduced in 2018 by the Center for Healthcare Quality Assessment and Control of the Russian Ministry of Health has been added. Thus, two scales are used simultaneously in the text of clinical guidelines developed by RSC experts.

Table S1. Classes of recommendations according to the European Society of Cardiology (ESC) guidelines

Table S2. Levels of evidence according to the European Society of Cardiology (ESC) guidelines

Table S3. Scale for assessing levels of evidence (LoE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)

Table S4. Scale for assessing levels of evidence (LoE) for diagnostic methods (diagnostic interventions)

Table S5. Scale for assessing grades of recommendation (GoR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)

Procedure for updating clinical guidelines

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

Appendix A3. Reference Materials

Appendix A3-1

1. On Protection of Public Health in the Russian Federation (Federal Law No. 323-FZ of November 21, 2011);

2. Procedure for providing medical care to patients with cardiovascular diseases (Order of the Russian Ministry of Health No. 918n of November 15, 2012);

3. "On the Procedure for Organizing Medical Rehabilitation for Adults" (Order of the Russian Ministry of Health No. 778n of July 31, 2020);

4. "On Amendments to Certain Legislative Acts of the Russian Federation Regarding the Application of Information Technologies in Healthcare" (Federal Law No. 242-FZ of July 29, 2017);

5. "On Approval of the Rules for Performing 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 Performing 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. 1029n dated September 28, 2020, "On approval of lists of medical indications and contraindications for spa treatment".

Appendix A3-2

Table 1. EchoCG classification of mitral stenosis severity [32]

Table 2. Wilkins Echocardiographic Score [151]

Risk groups for the Wilkins echo score: low (0–3 points), intermediate (4–5 points), high (6–11 points).

Table 3. Cormier Echocardiographic Score [152]

Table 4. Re-examination Echo Score for assessing immediate prognosis [33]

Risk categories for the Echo scoring system “Re-examination”: low (score 0–3), intermediate (score 4–5), high (score 6–11). The use of the scale is justified in rare clinical situations as an adjunct to clinical and instrumental data.

Table 5. Recommendations for antibiotic prophylaxis of infective endocarditis during dental procedures

Note. An alternative to amoxicillin** and ampicillin** – Cefazolin** or Ceftriaxone** 1 g IV. Cephalosporins (Other beta-lactam antibacterials) should not be used in patients with anaphylaxis, angioedema, or urticaria following benzylpenicillin** administration due to cross-reactivity [160, 161].

Table 6. Target INR values following mechanical mitral valve replacement requiring lifelong anticoagulant therapy

Table 7. Secondary prevention of rheumatic fever

Table 8. New York Heart Association Functional Classification (Chronic Heart Failure).

Adopted in 1964 by the New York Heart Association (NYHA). This classification is used to describe symptom severity, establishing four functional classes (FC) of the disease

Appendix B. Physician Action Algorithms

Fig. 1 Algorithm for choosing the treatment strategy in mitral stenosis

Appendix B1. Algorithm for organizing cardiac rehabilitation in patients with mitral stenosis (Figure P1)

Appendix B2. Contraindications to physical exercise in patients after surgical correction of mitral stenosis

• Recent intraoperative myocardial infarction (less than 3 weeks from the onset of myocardial infarction).

• Postoperative complications (post-cardiotomy syndrome with pericarditis and/or pleuritis, pulmonary edema, acute cardiac dysfunction, wound suppuration, and septic conditions).

• Prosthesis-related complications (prosthesis dysfunction, thromboembolic complications, prosthetic valve infective endocarditis).

• Pronounced sternal diastasis (contraindication to upper extremity and trunk exercise routines).

• 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 disorders (second- to third-degree atrioventricular block).

• Thromboembolism or thrombophlebitis (within the past 3 months).

• Acute cerebrovascular accident or transient ischemic attack (within the past 3 months).

• High bleeding risk.

• Uncontrolled diabetes mellitus.

• Severe renal impairment.

• Cognitive impairment.

Appendix B3. Algorithm for utilizing diagnostic imaging and instrumental methods in patients with mitral stenosis

Appendix C. Patient Information

Mitral stenosis – an acquired heart valve disease, most commonly a consequence of prior rheumatic fever or frequent purulent lacunar tonsillitis in childhood. It is characterized by changes in the mitral valve leaflets such as fusion, thickening, and calcification, resulting in a severely narrowed mitral valve orifice that prevents the left atrium from pushing an adequate volume of blood into the left ventricle. Blood stagnates in the pulmonary circulation (lungs). Advanced mitral stenosis leads to heart failure, cardiac arrhythmias, and strokes. Therefore, essential rules must be followed before and after surgery for mitral stenosis.

1. Mitral valve disease can manifest anywhere from a complete absence of symptoms to severe critical manifestations such as exertional dyspnea, dyspnea at rest or in the supine position, lower extremity edema, abdominal distension, dizziness, fainting episodes, weakness, and palpitations.

2. The definitive diagnosis of mitral stenosis is established solely by a physician based on clinical, physical, and instrumental data.

3. Treatment of the heart valve disease includes not only drug therapy, diet, and lifestyle modifications, but also timely surgical treatment when indicated, as determined exclusively by a physician.

4. Regular medical visits are necessary to monitor disease progression, detect symptoms early, assess cardiac status dynamically, and timely identify indications for surgical treatment.

5. If your condition worsens or new symptoms appear, you should consult a physician for early detection of disease progression and complications.

6. Only your attending physician is qualified to provide recommendations on diet, physical activity programs, drug support, and symptom monitoring both before and after surgery.

7. Food should be easily digestible and contain plenty of greens and vegetables. Among animal proteins, preference should be given to poultry and fish. If heart failure symptoms appear, dietary salt intake must be reduced. Meals should be frequent (4–5 times a day) in small portions.

8. Prescription of drug therapy is carried out solely by the attending physician. The specified drug dosage must be strictly followed. Irregular intake may impair the therapeutic effect. Do not discontinue medications when you start feeling better.

10. Do not skip doses or independently make adjustments to the treatment regimen. If a dose is accidentally missed, take the next dose at the scheduled time; never take a double dose to make up for a forgotten one.

1. If Warfarin** is prescribed, the INR must be monitored monthly, and in some cases even more frequently, with dose adjustments made as necessary to maintain the INR within the target range. In the event of bleeding of any localization, immediately inform your physician or go to the nearest clinic.

2. If the following symptoms occur or rapidly progress: fatigue, dyspnea, edema, 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, an unscheduled cardiologist consultation is recommended.

3. For any invasive procedures (dental, cosmetic, and other procedures that involve or carry a risk of compromising the integrity of the skin and mucous membranes), antibiotic prophylaxis for infective endocarditis must be performed.

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

5. Follow-up with a local cardiologist is recommended at least once every 6 months, strictly adhering to their instructions and prescriptions.

6. Follow-up with a cardiologist at a specialized center is recommended at least once every 12 months.

7. Cases of planned invasive procedures must be coordinated with the cardiologist providing outpatient follow-up at the patient's place of residence.

8. Changing the doses and regimens of certain medications, as well as prescribing additional or alternative medications, is performed solely by the attending physician.

9. If adverse drug reactions occur, it is recommended to discuss this with the attending physician as soon as possible.

Preparation for CT coronary angiography:

• Refrain from eating and smoking 3–4 hours before the procedure.

• Study of blood creatinine level.

• Inform the referring physician and radiologist about any thyroid diseases, bronchial asthma, diabetes mellitus, iodine allergies, nitrate intolerance, or beta-blocker intolerance.

• Avoid caffeine for 12 hours.

Preparation for contrast-enhanced cardiac MRI and contrast-enhanced aortic MRI:

• Refrain from eating and smoking 3–4 hours before the procedure.

• Study of blood creatinine level.

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 title (if applicable): Hospital Anxiety and Depression Scale.

Source: [153].

Type: rating scale.

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

Content (template):

Table P6. 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 – borderline anxiety/depression; 11 points and above – abnormal (clinical) anxiety/depression.

Explanatory notes: Each item on the HADS scale has 4 response options. The patient is asked to choose the answer that best reflects their state over the past 7 days, and scores are then summed up separately for each subscale.

Appendix G2. Original Borg Scale (Borg RPE, Rating of Perceived Exertion)

Russian title: Original Borg Scale.

Original title: Borg Rating of Perceived Exertion.

Sources: [154, 155].

Type: rating scale.

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

Content (template):

Table P7. Original Borg Scale (Borg RPE, Rating of Perceived Exertion)

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 G3. CHA2DS2-VASc Score

Russian title: CHA₂DS₂-VASc score.

Original title: CHA₂DS₂-VASc score.

Sources: [170, 171].

Type: rating scale.

Purpose: CHA₂DS₂-VASc is a clinical risk stratification score for ischemic stroke in patients with non-valvular atrial fibrillation. It is used to guide decisions on anticoagulant therapy and is recommended by international guidelines (ESC, AHA/ACC/HRS) as the basis for thromboembolic risk stratification [170, 171].

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 (prior myocardial infarction, peripheral artery disease, etc.) — 1 point

• A — Age 65–74 years — 1 point

• Sc — Sex category (i.e., female gender) — 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, treatment decisions should be individualized.

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

Clinical application:

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

Appendix G4. EuroSCORE Perioperative Risk Assessment Scale

Russian title: EuroSCORE scale.

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

Sources: [176].

Type: rating scale.

Purpose: EuroSCORE is a risk scoring system for predicting 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 points)

• 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 G5. 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 name: EuroSCORE II scale.

Original name (if any): European System for Cardiac Operative Risk Evaluation II.

Source: [177,178] (official developers' website, validation publication: https://euroscore.org)

Type: rating scale.

Purpose: assessment of the risk of adverse outcome 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 G6. STS Score

Russian name: STS Score.

Original name: The Society of Thoracic Surgeons Score.

Sources: [175] (official developers' 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.