Mitral Regurgitation: Clinical Guidelines

List of Abbreviations

VKA – vitamin K antagonists

ALT – alanine aminotransferase

ARB II – angiotensin II receptor blockers

AST – aspartate aminotransferase

ЕОК – European Society of Cardiology

ACEi – angiotensin-converting enzyme inhibitors

CHD – coronary heart disease

IE – infective endocarditis

CT – computed tomography

LDH – lactate dehydrogenase

LV – left ventricle

LA – left atrium

MV – mitral valve

MR – mitral regurgitation

INR – international normalized ratio

MR – mitral regurgitation

MRI – magnetic resonance imaging

CVA – cerebrovascular accident

RV – right ventricle

MVP – mitral valve prolapse

CXR – chest X-ray

CRP – C-reactive protein

TEER – transcatheter edge-to-edge mitral valve repair

SV – stroke volume

EF – ejection fraction

FC – functional class

AF – atrial fibrillation

RF – regurgitation fraction

LDL-C – low-density lipoprotein cholesterol

HF – heart failure

TEE – transesophageal echocardiography

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

EP study – electrophysiological study

EchoCG – echocardiography (transthoracic)

B01A: Antithrombotic agents. Direct oral anticoagulants

ERO – effective regurgitant orifice

CHA2DS2-VASc – stroke and thromboembolic risk score for patients with atrial flutter and atrial fibrillation

NYHA – New York Heart Association

PISA – proximal isovelocity surface area

** – 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 prescription of a medicinal product not approved by state regulatory bodies 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 where a medical or pharmaceutical worker, in the exercise of their professional activities, has a personal interest—either directly or through a representative of a company—in obtaining material gain or other advantage that affects or may affect the proper performance of their professional duties due to a contradiction between the personal interest of the medical or pharmaceutical worker and the interests of the patient [1].

Clinical trial – any investigation conducted in human subjects to identify or verify clinical and/or pharmacological effects of investigational products, and/or to identify adverse reactions to investigational products, and/or to study their absorption, distribution, metabolism, and excretion with the objective of assessing their safety and/or efficacy. The terms "clinical trial" and "clinical study" are synonymous [2].

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

Medicinal products – pharmacological agents in the form of dosage forms used for the prevention, diagnosis, and treatment of a disease, rehabilitation, as well as for the maintenance, prevention, or termination of pregnancy [3].

Medical intervention – types of medical examinations and/or medical procedures, as well as artificial termination of pregnancy, performed by a medical worker or other employee authorized to carry out medical activities in relation to a patient, affecting the physical or mental state of a person and having a preventive, diagnostic, therapeutic, rehabilitative, or research focus [1].

Medical worker – an individual who has a medical or other education, works in a medical organization, and whose job (official) duties include the implementation of medical activities, or an individual who is an individual entrepreneur directly engaged in medical activities [1].

Mitral valve – left atrioventricular valve

Mitral regurgitation – backward flow of blood into the left atrium during ventricular systole as a result of impaired integrity of the mitral valve and/or its closing function [1].

Patient – an individual receiving medical care or applying for medical care, regardless of the presence of a disease and their condition [1].

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

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 – restoration of valve function without its replacement

Symptom (from Greek *symptoma* – sign, occurrence) is a sign of a disease, a statistically significant deviation of a certain indicator from its normal range, or the emergence of a qualitatively new phenomenon uncharacteristic of a healthy organism.

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

Condition – changes in the body arising from the action of pathogenic and/or physiological factors and requiring medical care [1].

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

Level of Evidence (LoE) – the degree of certainty that the estimated effect of a medical intervention is true

Grade of Recommendation (GoR) – the degree of certainty in the reliability of the intervention effect and that following the recommendations will bring more benefit than harm in a particular situation

Surgical treatment – a method of treating diseases by dividing and joining tissues during a surgical operation.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Mitral regurgitation (MR) – impairment of mitral valve leaflet coaptation during systole with blood regurgitation from the left ventricle into the left atrium [1].

Minimal mitral regurgitation (MR) is observed in the majority of healthy individuals. A large volume of regurgitation caused by mitral valve disease is considered a valvular heart disease [2].

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

The causes of acute MR are most commonly rupture of mitral valve (MV) cords – idiopathic (spontaneous), in the setting of myxomatous degeneration (in MVP, Marfan syndrome, Ehlers-Danlos syndrome) [3], infective endocarditis, acute rheumatic fever, blunt chest trauma; and papillary muscle involvement in acute myocardial infarction (papillary muscle dysfunction or rupture); but it can also be MV ring involvement – ring abscess in infective endocarditis, blunt chest trauma; MV leaflets – infective endocarditis (leaflet perforation or vegetation preventing MV leaflet closure), myxomatous degeneration of leaflets, tumors (left atrial (LA) myxoma) [1, 2].

The main cause of primary chronic MR is mitral valve prolapse (MVP), less commonly infective endocarditis, inflammatory connective tissue diseases (systemic lupus erythematosus, scleroderma), rheumatic fever, mitral annular calcification, radiation-induced heart disease, and congenital anomalies – cleft MV leaflet or parachute MV in complete atrioventricular septal defect or transposition of the great arteries [4-6].

Secondary MR is the result of severe systolic dysfunction and global or local left ventricular (LV) remodeling. With preserved MV leaflets and chordal apparatus, secondary MR develops and progresses due to papillary muscle displacement, systolic tethering of the leaflets, and MV annular dilation [7].

Acute MR leads to acute volume overload of the LV and LA. This sharply increases LA pressure, which is accompanied by an elevation in pulmonary circulation pressure and leads to pulmonary edema. The absence of compensatory LV hypertrophy and dilation results in a decreased stroke volume (SV) and the development of clinical cardiogenic shock.

Chronic MR leads to a gradually increasing volume load on the LV, the development of eccentric LV hypertrophy, and LA enlargement. A compensatory increase in LV end-diastolic volume and ejection fraction (EF) serves to maintain effective SV, and compensation can last for many years. However, a decrease in LV contractility leads to a gradual reduction in effective SV, elevated pressure in the LA and pulmonary circulation, and the appearance of symptoms of heart failure (HF). Secondary MR of any degree, especially severe, significantly worsens LV systolic function due to prolonged overload. In addition, the severity of secondary MR may increase over time due to the progression of systolic dysfunction and LV remodeling [1, 2].

The etiology is presented in Appendix G (Figure 4).

1.3 Epidemiology of the Disease or Condition

MR is currently the second most frequent valvular pathology after aortic stenosis, yet it ranks first in individuals older than 55 years [8].

MVP – the main cause of primary MR – occurs in the population with a frequency of 2.4% [9].

Secondary MR is observed in almost half of patients who have suffered a myocardial infarction, and in 3-13% it can be severe. Severe MR is detected in every fourth patient with dilated cardiomyopathy [10-11].

1.4 Features of Coding the Disease or Condition

I34.0 Nonrheumatic mitral (valve) insufficiency

I34.1 Mitral (valve) prolapse

I34.8 Other nonrheumatic mitral valve disorders

I34.9 Nonrheumatic mitral valve disorder, unspecified

I05.1 Rheumatic mitral insufficiency

I05.2 Mitral stenosis with insufficiency

I05.8 Other mitral valve diseases

Q23.3 Congenital mitral insufficiency.

1.5 Classification of the disease or condition

By onset: [12, 13]

• Acute MR

• Chronic MR

By etiology: [12, 13]

• Primary MR

• Secondary MR:

  • ischemic

  • functional

By severity: [12]

• Mild

• Moderate

• Severe

This classification is preferred for diagnosis; using numerical grades of regurgitation (1, 2, 3, 4) is not recommended [12, 13].

Examples of diagnosis formulation:

1. Primary diagnosis: Primary mitral valve prolapse.

Complications: Chronic primary mild mitral regurgitation. Atrial extrasystole. CHF with preserved EF (70%), stage I. NYHA functional class (FC) I–II NYHA

2. Primary diagnosis: Mitral valve prolapse, rupture of posterior mitral leaflet chords.

Complications: Acute primary severe mitral regurgitation. CHF with preserved EF (63%), stage IIa. NYHA FC II–III

3. Primary diagnosis: CAD. Effort angina FC III. Post-infarction cardiosclerosis.

Complications: CHF with reduced EF (39%), stage IIa. NYHA FC II. Chronic secondary severe mitral regurgitation.

4. Primary diagnosis: Dilated cardiomyopathy.

Complications: CHF with reduced EF (32%), stage IIb. NYHA FC III. Complete left bundle branch block. Chronic secondary severe mitral regurgitation.

5. Primary diagnosis: Primary subacute infective endocarditis of the mitral valve.

Complications: CHF with preserved EF (65%), stage IIa. NYHA FC II. Chronic primary moderate mitral regurgitation.

Carpentier's functional classification of mitral regurgitation etiology [14]

Type I. Normal leaflet motion

• Annular dilation

• Cleft leaflets

• Leaflet perforation

Type II. Leaflet prolapse

• Absent chords

• Ruptured chords

• Elongated chords

• Elongated papillary muscles

Type III. Restricted leaflet motion

IIIa. Normal papillary muscles

• Commissural fusion

• Chordal shortening

• Ebstein anomaly of the valve

IIIb. Papillary muscle abnormality

• Parachute-like valve

• Hammock-like valve

• Agenesis, hypoplasia of papillary muscles

1.6 Clinical presentation of the disease or condition

MR has no specific symptoms, and the clinical presentation is primarily driven by signs of CHF developing as the MR volume increases and LV systolic function worsens [13].

While asymptomatic during the compensation stage, as the MR volume increases and LV systolic function deteriorates, patients begin to report dyspnea, fatigue, and palpitations on exertion, and eventually at rest. As the right heart becomes involved due to elevated pulmonary artery systolic pressure and decreased right ventricular (RV) contractility, peripheral edema and hydrothorax may develop [13].

In patients with secondary ischemic MR (see MR classification by etiology), coronary artery disease (CAD) symptoms may predominate in the clinical picture [11].

Patients with asymptomatic severe MR typically come to medical attention either due to a cardiac murmur detected during routine screening or management of comorbid conditions, or due to the onset of arrhythmias (most commonly atrial fibrillation [AF]). In the decompensation stage, MR may manifest with signs of congestive heart failure (dyspnea at rest, peripheral edema) [1, 2].

In acute severe MR (chordal rupture in MVP or papillary muscle rupture in acute myocardial infarction), the disease presents with acute pulmonary edema [1, 2].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria [12, 13].

1) Mild mitral regurgitation: small central jet with an area <20% of the LA; Vena contracta <0.3 cm; no hemodynamic consequences;

2) Moderate mitral regurgitation: central jet with an area of 20–30% of the LA or late-systolic eccentric jet; Vena contracta <0.7 cm; regurgitant volume <60 mL; regurgitant fraction <50%; ERO <0.40 cm²; hemodynamically – mild LA enlargement and no LV enlargement + normal pulmonary artery pressure;

3) Severe mitral regurgitation: central jet area >40% of LA or holosystolic eccentric jet; vena contracta ≥0.7 cm; regurgitant volume ≥60 mL; regurgitant fraction ≥50%; ERO ≥0.40 cm²; hemodynamically – moderate or marked dilatation of the pulmonary artery, enlargement of the LV + pulmonary hypertension at rest or during physical exertion.

2.1 Complaints and Anamnesis

ESC IB (Level of Evidence C, Grade of Recommendation 5)

Comments: In acute MR, patients typically report the sudden onset of severe dyspnea, and frequently the development of suffocation with clinical presentation of cardiac asthma.

In chronic MR, symptoms of heart failure may be absent for many years. In the decompensation stage (stage D), there is a decrease in exercise tolerance, exertional dyspnea, and palpitations [2].

The onset of MR at a young age is characteristic of patients with myxomatous MVP (Barlow's disease); a heart murmur in such patients may be auscultated since childhood. At an older age, in patients without prior history, rupture of chordae tendineae of the MV leaflets (more often the posterior) is possible in fibroelastic deficiency (deficiency of fibrillar structures – collagen and elastin fibers) [3, 4].

Frequent sore throats in childhood and ongoing benzathine benzylpenicillin prophylaxis suggest a rheumatic origin of MR, although the prevalence of rheumatic fever is decreasing worldwide. A history of prior infective endocarditis (IE) may be indicated by a prolonged fever episode.

A previous myocardial infarction, interventional and surgical procedures on the coronary arteries suggest a secondary ischemic origin of MR [1].

2.2 Physical Examination

ESC IB (Level of Evidence C, Grade of Recommendation 5)

Comments: Physical examination of patients with chronic MR reveals a leftward and downward displacement of the apex beat and its intensification as a manifestation of LV eccentric hypertrophy. The auscultatory pattern is characterized by weakening of the first heart sound and a systolic murmur over the apex that merges with the first sound and radiates to the axillary region [2]. A pathognomonic auscultatory sign of MVP is a mid-systolic click—a short, high-frequency sound resulting from tension and vibration of the MV chordae during prolapse—and a late systolic murmur. Dynamic auscultation yields a very characteristic picture: in the upright position, with decreased LV filling, the systolic click shifts toward the first sound, and the murmur becomes more prolonged [3, 4]. With leaflet perforation in IE, the murmur may acquire a musical character. The appearance of the third heart sound, associated with the increased blood volume entering the LV cavity, and the appearance of a gallop rhythm are highly characteristic of MR. A diastolic murmur (Austin Flint / Coombs murmur) occurs only in significant mitral regurgitation, is functional, short, and mid-diastolic, and is caused by relative stenosis of the left atrioventricular orifice [1]. Despite the current availability of precise imaging methods that allow the detection of prosthetic heart valve dysfunction, there are quite a few situations where a cardiologist and/or general physician must examine a patient with an implanted valve prosthesis and make a quick decision (e.g., when suspecting early or late prosthetic IE, prosthetic MV thrombosis, suture dehiscence, etc.). To do this, physicians in these specialties must be well acquainted with the "auscultatory melody" of a normally functioning prosthetic mitral valve and its changes during dysfunction.

When auscultating a mechanical artificial valve installed in the mitral position, the opening and closing clicks of the working occluder element of the prosthesis should be clearly audible. Often these clicks are heard upon examining the patient before starting auscultation. The closing click occurs 0.06 to 0.13 seconds after the aortic component of the second heart sound. This interval may increase with bradycardia. Sometimes, during careful auscultation, a soft systolic murmur (grade 1) can be heard at the apex of the heart. This is a murmur of hemodynamically tolerated and clinically insignificant transprosthetic regurgitation, which exists in installed mechanical valve prostheses due to their design features: during their manufacture, a slight gap is created between the leaflets of the occluder element. This is done because there is a possibility that with tight closure, there is a risk of leaflet sticking and closure of the mitral prosthesis.

A decrease in the loudness of clicks during a patient's routine visit, especially if the prosthesis was recently implanted, should raise concern, even in the absence of symptoms. The auscultation of harsh murmurs at the apex of the heart in the projection of the prosthesis (systolic, e.g., in paravalvular leak, early mesodiastolic – in prosthesis thrombosis) should be a reason for immediate referral of the patient for an echocardiographic (EchoCG) study [15].

Auscultation of a biological MV prosthesis does not reveal such a loud sound of the working valve and, at normal function, practically does not differ from the sounds of a working native valve. However, one of the disadvantages of biological artificial valves is their lower wear resistance. Therefore, the hearts of patients with an installed biological artificial MV should be auscultated more frequently, at every physician visit. Usually, biological prosthesis dysfunction presents with a harsh systolic murmur [16]. However, fusion of biological prosthesis leaflets has also been described [17]; in such a case, dysfunction may manifest as a murmur of mitral stenosis – an early mesodiastolic murmur.

2.3 Laboratory Diagnostics

• In all patients with MR, it is recommended to perform a complete (clinical) urinalysis and a complete (clinical) blood count with hemoglobin level assessment, hematocrit evaluation, red blood cell, leukocyte, and platelet count, and erythrocyte sedimentation rate determination as part of the initial examination, during follow-up at least once a year and upon hospital admission, as well as in case of surgical treatment if necessary in the pre- and/or postoperative period [12, 18, 19].

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

ESC/ACC IIaC (LoE C, LoD 5)

ESC/ACC IIaC (LoE C, LoD 5)

• All patients with MR admitted to the hospital for surgical treatment are recommended to undergo an assessment of acid-base status and blood gases (pH, BE, pCO2, PO2, Lac-analysis of capillary/arterial/venous samples) to evaluate the severity of hypoxemia and the degree of metabolic disorders, a coagulogram (exploratory hemostasis screening) (activated partial thromboplastin time, prothrombin time, prothrombin index), blood D-dimer concentration determination, blood fibrinogen level testing, and blood antithrombin III activity determination. Determination of the international normalized ratio (INR) to predict the risk of perioperative bleeding and blood loss volume. Determination of ABO blood groups. Determination of the Rh blood group (Rh factor) D antigen. Phenotyping for C, c, E, e, Cw, K, k antigens and screening for anti-erythrocyte antibodies. Determination of Hepatitis B virus surface antigen (HbsAg) in the blood. Determination of antibodies to Hepatitis C virus in the blood. Determination of antibodies to Treponema pallidum in the blood. Determination of IgM and IgG antibodies to Human immunodeficiency virus HIV 1 in the blood, and determination of IgM and IgG antibodies to Human immunodeficiency virus HIV 2 in the blood to rule out association with HIV infection and hepatitis, as well as in cases of surgical treatment when necessary in the pre- and/or postoperative period [12, 13, 18, 20, 23, 166-171]

ESC/ACC IIaC (LoE C, LoD 5)

Comments: performing a complete (clinical) blood count for all patients with MR during dispensary follow-up and prior to surgical treatment is important for detecting anemia and ensuring its timely correction [166, 167].

A number of studies have demonstrated a correlation between serum BNP levels and prognosis in MR. Detecting an increase in BNP concentration can serve as an additional factor when choosing the optimal timing for mitral valve intervention. Conversely, a low BNP level has a high negative predictive value and can be useful in confirming that patients are asymptomatic [21, 22, 24], which dictates the need for this study.

2.4 Instrumental Diagnostics

2.4.1. Non-invasive Diagnostic Methods

• All patients with suspected MR and those under dispensary observation with an established diagnosis are recommended to undergo resting electrocardiography (ECG) with recording, analysis, description, and interpretation of electrocardiographic data (12-lead ECG), as well as when necessary in the event of surgical treatment in the pre- and/or postoperative period [2].

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

Comments: resting ECG recording, analysis, description, and interpretation of electrocardiographic data in 12 leads can be used to detect AF, the occurrence of which is a Class IIa indication for MV repair in primary MR [12]; scar changes that may suggest secondary MR [25, 26]; as well as left bundle branch block and QRS complex duration greater than 0.14 s, which may be an indication for resynchronization therapy in patients with secondary MR [26].

• Patients with suspected MR and those under dispensary observation with an established diagnosis are recommended to undergo targeted chest X-ray to diagnose the primary condition, rule out other heart and large vessel diseases, as well as extra-cardiac pathology (pathology of other mediastinal organs, lungs, pleura), assess the pulmonary circulation status, and detect pulmonary congestion, as well as in case of surgical treatment when necessary in the pre- and/or postoperative period [2].

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

Comments: Targeted chest X-ray allows the detection of cardiomegaly (cardiothoracic ratio greater than 50%) as a consequence of LV dilation in long-standing MR; venous congestion or pulmonary edema in acute MR; and calcifications in the MV projection area as a potential cause of MR [1, 2].

• All patients with MR or suspected MR and those under dispensary observation with an established diagnosis are recommended to undergo transthoracic echocardiography (TTE) to identify the mechanisms and severity of MR, assess LV function, the extent of regional wall motion abnormalities, dimensions of other cardiac chambers, and pulmonary artery pressure, as well as in case of surgical treatment when necessary in the postoperative period [2, 12, 13, 28, 29].

ESC IA (LoE C, GoR 5)

Comments: Transthoracic echocardiography is the primary diagnostic method for MR, identifying its mechanisms, confirming the diagnosis of heart valve disease, assessing severity and disease prognosis, and selecting the timing and methods of treatment [2, 12, 13, 28, 29]. Transthoracic echocardiography is performed in all patients with suspected MR. Echocardiographic criteria for diagnosing MR are presented on pages 11 and 12 in the MR severity classification table.

Assessment of regurgitant volume and effective regurgitant orifice area (EROA) is performed based on the proximal isovelocity surface area (PISA) method. A volume greater than 60 mL or an effective orifice area greater than 0.4 cm2 indicates severe MR. However, it must be borne in mind that Doppler methods for calculating ERO using PISA may underestimate MR severity due to the crescentic shape of the regurgitant orifice, and multiple parameters must be used to determine the degree of MR [12, 13, 28, 30]. Visual assessment of MR severity based on the depth of the jet penetration into the LA cavity is not a criterion that can be used to determine MR severity.

In primary MR, due to LV volume overload, LVEF is overestimated; an EF greater than 60% is considered normal [12, 13]. A decrease in EF to 60% or less, as well as an increase in left ventricular end-systolic dimension of more than 40 mm, indicates LV systolic dysfunction [31-37].

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

ESC IIIA (LoE C, LoR 5)

Comments: TEE should not be used for routine or serial evaluation of MR when transthoracic echocardiographic visualization is adequate. Transesophageal echocardiography is particularly informative when infective endocarditis is suspected as a potential cause of MR. Transesophageal echocardiography, especially three-dimensional TEE, provides a complete anatomical understanding of the MV structure prior to surgery and allows for surgical planning. It should be taken into account that anesthesia prior to surgery may alter the severity of MR because a reduction in pre- and afterload leads to a decrease in regurgitation volume. The use of transesophageal echocardiography to evaluate the results of MV reconstructive surgery makes it possible to identify major complications—left ventricular inflow tract obstruction due to a reduced MV annulus diameter and left ventricular outflow tract obstruction due to systolic anterior motion (SAM) of the MV leaflets [12, 13, 38, 39].

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

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

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

Comments. Cardiac computed tomography is used in patients with MR during the preoperative preparation period or when there are absolute contraindications to MRI. The diagnostic value of contrast-enhanced cardiac CT is significantly inferior to cardiac MRI [13; 23].

ESC IIa C (CUA RSC, LOE 5)

• The use of stress tests (exercise ECG, exercise echocardiography, pharmacological stress echocardiography, or myocardial scintigraphy) may be recommended in case of discrepancy between symptoms and severity of mitral regurgitation (MR), to assess patient symptoms and exercise tolerance [12, 13, 39, 40, 41].

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

Comments: Contrast-enhanced cardiac MRI provides high accuracy in determining LV and RV volumes, LV ejection fraction, MR volume, and zones of fibrosis and akinesia. However, since symptoms in MR mainly occur during exertion, performing exercise echocardiography or pharmacological stress echocardiography makes it possible to objectify symptoms when previous examination results are doubtful. An increase in MR volume and/or pulmonary artery pressure, and their measurement during a stress test help explain the emerging symptoms and determine indications for surgery [41–43].

ESC/RCS IIa C (CUA RSC, LOE 5).

2.4.2 Invasive Diagnostic Methods

• Coronary angiography is recommended for all patients with MR to detect hemodynamically significant coronary artery stenoses before open surgical, transcatheter, or hybrid interventions in the following situations: age over 40 years, history and/or symptoms of CAD, signs of myocardial ischemia, decreased LV EF <50%, one or more risk factors for CAD and/or post-radiation injury [12, 13, 26].

ESC IA (LoE C, GoR 5)

Comments: in patients with MR who have risk factors for CAD (e.g., older age, hypercholesterolemia, or hypertension), or when MR is suspected to be of ischemic origin (myocardial infarction or presumed ischemia), coronary angiography should be performed before surgery [26, 28].

Cardiac ventriculography and/or hemodynamic measurements are indicated when non-invasive data on the severity of MR, LV function, or the need for surgical intervention are uninformative or contradictory [26, 44].

Women with early fertility and hormonal status disorders have a higher probability of developing significant atherosclerotic changes in the coronary vessels [45–48].

ESC/RCS IIb B (CUA C, LOE 5).

Comments: Right heart catheterization may be considered if elevated estimated systolic pulmonary artery pressure is detected by transthoracic echocardiography in the presence of severe tricuspid regurgitation [12].

2.5 Other Procedures

Other diagnostic examinations for the diagnosis of MR are not provided; expansion of diagnostic examinations is possible at the physician's discretion depending on the clinical situation and the patient's condition.

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

3.1. Conservative management

• Therapy with peripheral vasodilators (nitroprusside derivatives) may be recommended to maintain hemodynamics in patients with acute severe MR [12, 13, 19, 49].

ESC IIaB (Level of Evidence C, Quality of Evidence 5)

Comments: in acute severe MR, the role of drug therapy is limited and aimed primarily at stabilizing hemodynamics during preparation for surgery [50].

In acute MR combined with acute heart failure, organic nitrates and diuretics are used to reduce LV filling pressure. #Sodium nitroprusside dihydrate reduces afterload and regurgitation fraction. The drug is administered as an intravenous infusion at an initial dose of 0.3 mcg/kg/min, with a maintenance dose of 3–5 mcg/kg/min [172]. Inotropic agents (C01CA Adrenergic and dopaminergic agents) and intra-aortic balloon counterpulsation are used for hypotension and hemodynamic instability [20].

• Drug therapy for systolic dysfunction may be recommended for patients with severe primary MR and an ejection fraction of less than 60% if surgery is not planned [12, 13, 20].

ESC IIa B (CUA C, LOE 5)

Comments: Drug therapy for systolic dysfunction should consist of standard heart failure therapy and include angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs), diuretics (C03E Diuretics in combination with potassium-sparing diuretics), valsartan/sacubitril** (angiotensin II receptor antagonists in combination with other agents), C03D Aldosterone antagonists and other potassium-sparing agents, and sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins). Beta-blockers may be prescribed if necessary, provided there are no severe hemodynamic disturbances or other contraindications [51–59].

At the same time, the use of vasodilators (ACE inhibitors) is not indicated in normotensive asymptomatic patients with severe MR and normal LV systolic function, because preload reduction leads to decreased LV filling, increases mitral leaflet prolapse, and worsens MR severity [13].

• Heart failure drug therapy is recommended for all patients with severe secondary MR [12, 13, 20].

ESC IA (LoE C, SoR 5)

Comments: Therapy for secondary MR must include standard heart failure drug therapy—diuretics, ACE inhibitors or ARBs, C03D Aldosterone antagonists and other potassium-sparing agents, valsartan/sacubitril** (angiotensin II receptor antagonists in combination with other agents), sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins), and/or ivabradine—which helps improve both symptoms and patient prognosis. Beta-blockers may be prescribed if necessary, provided there are no severe hemodynamic disturbances or other contraindications [19, 53–59].

• Cardiac resynchronization therapy is recommended for symptomatic patients with severe secondary MR and a broad QRS complex greater than 0.14 s [12, 13, 20].

ESC IA (LoE C, SoR 5)

Comments: Cardiac resynchronization therapy helps reduce the severity of secondary MR by improving LV function and mitral leaflet coaptation in patients with a broad QRS complex greater than 0.14 s (most commonly associated with complete left bundle branch block), LV systolic dysfunction, and NYHA functional class III–IV heart failure [60].

3.2. Surgical treatment

Currently, the following types of surgical interventions are used for the treatment of MR:

1) mitral valve repair under cardiopulmonary bypass;

2) mitral valve replacement under cardiopulmonary bypass;

3) transcatheter edge-to-edge mitral valve repair.

Indications for Surgical Treatment of MR:

ESC/RCS none (CUA C, LOE 3)

ESC IB (CUA C, LOE 3)

ESC IB (CUA C, LOE 3)

ESC IB (CUA C, LOE 5)

Comment: Patients should be referred to surgical centers with extensive experience in mitral valve repair. Mitral valve replacement for MR should be performed when valve-sparing surgery is not feasible.

ESC IIa B (CUA C, LOE 3)

ESC IIa B (CUA C, LOE 3)

ESC IIbB (LoE C, GoR 5)

ESC IB (CQR A, LOR 2)

ESC IB (CQR A, LOR 2)

ESC IIaC (LoE C, GoR 5)

• Transcatheter edge-to-edge mitral valve repair (TEER) for severe primary mitral regurgitation is recommended for symptomatic patients who meet echocardiographic criteria for the procedure and are evaluated by the Heart Team as inoperable or at high risk for standard surgery [12].

ESC IIbB (Level of Evidence C, Grade of Recommendation 5)

• Transcatheter edge-to-edge mitral valve repair (TEER) for chronic severe secondary mitral regurgitation in symptomatic patients with coronary artery disease is recommended when the Heart Team considers these patients unsuitable for surgical correction based on their individual characteristics (and in the presence of persistent severe MR) [12, 77].

ESC IIaC (Level of Evidence C, Grade of Recommendation 5)

• Transcatheter edge-to-edge mitral valve repair (TEER) for chronic severe secondary mitral regurgitation without concomitant coronary artery disease or other cardiac pathology is recommended for symptomatic patients who cannot undergo surgery but whose criteria suggest a high probability of a favorable response to the intervention [12, 78–80].

ESC IIaB (LOCE A, LE 2)

• In high-risk symptomatic patients who are ineligible for surgery and do not meet criteria suggesting an increased likelihood of response to TEER, it is recommended to consider heart transplantation, left ventricular assist device implantation, or alternative transcatheter valve interventions, where feasible [12].

ESC IIbC (LoE C, GoR 5)

ESC IIIB (LoE C, GoR 5)

ESC IIIB (LoE C, GoR 5)

Comments: Mitral valve repair is performed when the valve anatomy is suitable for this type of surgery, and in the presence of surgical expertise and appropriate equipment. This procedure preserves the patient's native valve and avoids the risks associated with lifelong anticoagulation therapy required for prosthetic valves (except in patients with atrial fibrillation) or risks related to prosthesis dysfunction in the late postoperative period. Furthermore, preservation of the mitral apparatus results in better postoperative LV function and survival compared to non-sparing approaches [60, 81]. The improvement in postoperative function is attributed to the fact that the mitral apparatus is an integral part of the LV, significantly supporting its normal geometry, volume, and function. However, mitral valve repair is technically more demanding than valve replacement, may require longer cardiopulmonary bypass times, and is not always successful. Valve morphology and surgical experience are critical for the success of the repair. Rheumatic disease with calcification limits the feasibility of this technique even for experienced surgeons [82]. The reoperation rate after mitral valve repair is similar to that after mitral valve replacement. In patients undergoing repair, the reoperation rate due to severe recurrent MR is 7–10% at 10 years [83–86]. Approximately 70% of recurrent MR is believed to result from the initial surgery, and 30% from disease progression [83]. The reoperation rate is lower in patients whose initial operation was performed on a diseased posterior leaflet compared to those with disease involving both leaflets or the anterior leaflet [85].

Mitral valve repair is advisable in patients with severe symptomatic MR and depressed LV function to preserve LV function at preoperative levels. Mitral valve replacement with destruction of subvalvular structures can lead to deterioration of LV function or even fatal LV dysfunction postoperatively. On the other hand, in a relatively asymptomatic patient with severe regurgitation and preserved LV function, valve repair may be the method of choice to prevent left ventricular dysfunction resulting from prolonged volume overload. However, a failed mitral valve repair necessitates valve replacement, which in such patients is a complication in itself, as the risk of prosthesis-related complications outweighs the risk of volume overload when initially deferring surgery in favor of a watchful waiting strategy.

Therefore, a "prophylactic" operation in an asymptomatic patient with MR and normal LV function requires careful selection of the medical center and surgeon to ensure a high likelihood of a successful reconstructive outcome.

Mitral valve replacement with preservation of the chordal apparatus has certain advantages. The procedure guarantees postoperative mitral valve competence, preservation of annular-papillary continuity and thus LV function, and increases postoperative survival compared to mitral valve replacement with excision of the valvular apparatus [87–89]. The disadvantages include the risk of damage to native valvular tissue and the subsequent need for anticoagulation therapy.

Mitral valve replacement involving the removal of the mitral apparatus should be performed only if preservation is impossible due to severe structural alteration (e.g., in rheumatic heart disease).

The choice of the prosthesis type (mechanical or biological) is the result of balancing the risk of bleeding/thromboembolism associated with mechanical valves against the risk of structural valve deterioration associated with biological prostheses. Age, lifestyle, and patient preferences must be taken into account. Bioprostheses should be considered in patients at high risk of bleeding, when life expectancy is less than the durability of the bioprosthesis, and in women planning pregnancy. A bileaflet mechanical mitral prosthesis is preferred for patients under 65 years of age in the absence of additional bleeding risk factors, while bioprostheses are preferred for patients over 70 years of age. In patients aged 65 to 70 years, either type of prosthesis is acceptable [90–92].

In most cases, based on diagnostic findings, an experienced surgeon can accurately determine the type of upcoming procedure. The goals of reconstructive surgery on the mitral valve include restoring leaflet coaptation function, achieving and stabilizing the optimal annular size, and creating adequate coaptation area and optimal leaflet coaptation height. Various techniques are used for this, including leaflet resection, chordal replacement, and annuloplasty. The most favorable lesion type for a successful mitral valve repair is non-rheumatic posterior leaflet prolapse [93]. Involvement of the anterior leaflet, both leaflets, as well as a rheumatic etiology and mitral annular or leaflet calcification reduce the likelihood of successful repair, necessitating innovative approaches for chordal apparatus correction [94–99].

Given the more favorable prognosis (left ventricular survival and function), cardiologists are advised to refer patients for mitral valve repair to surgical centers with experience in performing this procedure [64].

The use of video-assisted minimally invasive approaches or robot-assisted surgery in highly specialized centers contributes not only to the correction of the defect, but also to a reduction in surgical trauma and faster patient rehabilitation.

Symptomatic patients with normal left ventricular function: surgery is indicated for patients with overt signs of heart failure despite normal LV function parameters (ejection fraction >60% and end-systolic dimension <40 mm), as well as for patients with moderate HF symptoms and severe MR, especially if mitral valve repair rather than replacement is feasible. When repair is not feasible, mitral valve replacement with preservation of the subvalvular apparatus is the method of choice.

Asymptomatic and symptomatic patients with left ventricular dysfunction: the timing of surgery for asymptomatic patients is controversial, but currently, most experts conclude that mitral valve surgery is indicated upon the appearance of echocardiographic signs of LV dysfunction. These include: an LV ejection fraction of no more than 60% and/or an LV end-systolic dimension of at least 40 mm. Surgery performed at this time will likely prevent further deterioration of LV function and prolong life [66]. It must be emphasized that, unlike the timing of aortic valve replacement for aortic regurgitation, in patients with chronic MR, the LV ejection fraction should not drop below normal values [62, 66, 100–102]. Postoperative survival is more closely correlated with LV ejection fraction than with end-systolic dimension [62, 66, 103, 104]. Preoperative EF and LV end-systolic dimension directly correlate with postoperative LV function and the severity of heart failure [61, 66, 103, 105]. Mitral valve surgery may also be recommended for symptomatic patients with manifestations of LV systolic dysfunction (ejection fraction no more than 60% and/or end-systolic dimension at least 40 mm).

The management strategy for patients with MR, heart failure symptoms, and marked LV dysfunction remains controversial. The question is whether a patient with MR has such profound LV dysfunction that the likelihood of its recovery after surgery is minimal. Often in such situations, it is difficult to differentiate between primary cardiomyopathy with secondary MR and primary MR with secondary myocardial dysfunction. In the latter case, if mitral valve repair is possible, the indications and contraindications for surgery must be carefully weighed. Even if LV dysfunction is very severe and irreversible, surgery will likely reduce symptom severity and prevent further deterioration of LV function. Mitral valve replacement should only be performed if the subvalvular apparatus can be preserved. Modification of mitral valve geometry using a support ring in severe LV dysfunction and significant MR can be successful in patients with primary myocardial disease [106–111], although the prognosis in this case is comparable to aggressive medical therapy including beta-blockers and cardiac resynchronization [112–115]; however, no prospective randomized trials have been conducted on this matter.

Asymptomatic patients with normal left ventricular function: as previously noted by us, mitral valve surgery in asymptomatic patients with severe MR and normal LV function can preserve LV size and function, and prevent the complications of chronic severe MR [116]. However, there are no randomized trials proving the validity of this approach. Studies indicate that asymptomatic patients with severe MR and normal LV function have a high probability of developing symptoms and/or LV dysfunction, necessitating surgery within 6–10 years [116-117]. Two recent studies evaluated the risk of sudden death in asymptomatic patients with severe MR and normal LV function [111-112]. In the first retrospective study, where MR severity was assessed by Doppler echocardiography, 198 patients with an effective regurgitant orifice area greater than 40 mm² had a 4% annual risk of cardiac death over a mean follow-up of 2.7 years [116]. In the second study, 132 patients were followed for five years, during which the indications for surgery were the development of heart failure symptoms, LV dysfunction (ejection fraction less than 60%), LV dilation (LV end-systolic dimension greater than 45 mm), atrial fibrillation, or pulmonary hypertension. There was only one cardiac death in an asymptomatic patient, but this patient refused surgery, which was indicated upon the onset of LV dilation [117].

Mitral valve repair is frequently performed in hemodynamically stable patients with recently acquired severe MR, such as due to chordal rupture. Surgery is also recommended for asymptomatic patients with chronic MR presenting with new-onset atrial fibrillation, provided the likelihood of successful valve repair is high.

Thus, cardiologists are strongly advised to refer asymptomatic patients with severe MR and normal LV function who are candidates for mitral valve repair to surgical centers specializing in valve-sparing procedures (if there is greater than a 90% probability of successful valve repair at a center specializing in this procedure).

Endovascular treatment of MR poses complex challenges because this condition is driven by multiple distinct etiologies, and each individual device typically addresses only one of the mechanisms. Transcatheter mitral valve repair (TMVR) using a mitral valve leaflet clip is a minimally invasive treatment option for MR. Two randomized trials (COAPT and MITRA-FR) [12, 77, 71–73] evaluated its safety and efficacy in patients with severe MR and HF symptoms persisting despite medical therapy who were not deemed suitable candidates for surgery by the Heart Team. The procedure demonstrated safety and effective reduction of MR for up to 3 years [78]. However, in the MITRA-FR trial [12, 71, 73, 77], transcatheter edge-to-edge repair had no impact on the primary composite endpoint of all-cause mortality or heart failure hospitalization at 12 months and 2 years compared with medical therapy alone (in accordance with chronic heart failure guidelines). In the COAPT trial [72], transcatheter edge-to-edge repair significantly reduced the primary endpoint of cumulative heart failure hospitalizations as well as several pre-specified secondary endpoints, including all-cause mortality at 2 years. The conflicting results of these two trials have sparked considerable debate. The discrepancy may be partly explained by differences in trial design, patient selection, echocardiographic assessment of MR severity, background medical therapy, and technical factors.

Other transcatheter mitral interventions aside from TMVR, such as transcatheter mitral valve replacement devices, are currently the subject of intensive research, but clinical data remain limited.

Selection of Mitral Valve Prosthesis Type

• Mechanical mitral valve replacement (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, poor treatment adherence, as well as geographical, social, and occupational conditions) [12].

ESC IC (RR S, ELD 5)

• Mitral valve replacement 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) [12].

ESC IC (LoE C, GoR 5)

• Mitral valve replacement with a mechanical prosthesis (mechanical bileaflet mitral valve prosthesis***) is recommended for patients already receiving anticoagulant therapy due to an implanted mechanical heart valve prosthesis in another position [12].

ESC IIaC (LoE C, GoR 5)

• Mitral valve replacement with a mechanical prosthesis (mechanical bileaflet mitral valve prosthesis***) is recommended for patients younger than 65 years [12, 118].

ESC IIa B (CUA C, LOE 5)

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

Comments: The choice of the type of implanted prosthesis (mechanical or biological) is the result of weighing the risks of bleeding/embolism associated with a mechanical prosthesis against the risk of degenerative changes in bioprosthetic valves. A mechanical prosthesis is preferred for patients under 65 years of age in the absence of additional bleeding risk factors. For patients with mitral regurgitation aged 65 and older, either type of prosthesis is acceptable, taking into account the risk of bleeding, the patient's social status (living in a rural area, difficulties with INR monitoring), expected patient compliance with anticoagulant therapy (B01A: Antithrombotic agents), the presence of comorbid conditions (severe CHF, AF) requiring anticoagulants (B01A: Antithrombotic agents), as well as patient preferences [12, 13, 90-92].

ESC IIb C (LoE C, LoR 5)

Comments: Risk factors for thromboembolic events include atrial fibrillation, a history of unprovoked proximal deep vein thrombosis and/or symptomatic pulmonary embolism, hypercoagulable states, and antiphospholipid antibodies.

• Mitral valve replacement with a biological prosthesis (mitral valve bioprosthesis***) is recommended with the patient's written informed consent, in the presence of contraindications or the inability to undergo long-term anticoagulant therapy (high risk of hemorrhagic complications, comorbid conditions, lack of treatment adherence, low accessibility of therapy, personal preferences, lifestyle, and occupation), as well as in patients with a life expectancy shorter than the expected durability of the bioprosthesis [12].

ESC IC (RR S, ELD 5)

• Mitral valve replacement with a biological prosthesis (mitral valve bioprosthesis***) is recommended in the event of reoperation due to thrombosis of a mechanical mitral valve prosthesis despite adequate anticoagulant therapy [12].

ESC IC (RR S, ELD 5)

ESC IIaC (LoE C, GoR 5)

ESC IIaC (LoE C, GoR 5)

ESC IIb B (LoE C, LoR 3)

Indications for Reoperation

ESC IB (LoE A, GoE 3)

ESC IIa C (LoE C, LoR 2)

Comments: Emergency valve replacement is performed for obstructive prosthetic valve thrombosis in critically ill patients without contraindications to surgery. Treatment of non-obstructive thrombosis of a mechanical prosthesis in the mitral position depends mainly on the occurrence of a thromboembolic event and thrombus size. Vitamin K antagonists (VKAs) and/or unfractionated heparin (B01AB: Heparin group) are used as first-line drugs to achieve optimal anticoagulation in non-obstructive thrombosis [12; 122].

ESC IC (LoE C, GoR 5)

ESC IIbB (LoE C, GoR 4)

ESC IIa C (LoE C, LoR 5)

ESC I C (LoE C, LoR 3)

ESC IIa B (LoE C, LoR 3)

Comments: Patients after mitral valve replacement undergo repeat surgical intervention on the mitral valve in the presence of a paravalvular leak associated with endocarditis or causing hemolysis, requiring repeated blood transfusions or leading to severe symptoms of heart failure. The decision on transcatheter or surgical closure of clinically significant paravalvular leaks should be made based on the patient's surgical risk, leak morphology, and the experience of the multidisciplinary/cardiac surgery team [12; 124].

ESC IB (Level of Evidence C, Grade of Recommendation 5)

ESC IB (Level of Evidence C, Grade of Recommendation 5)

Comments: Prosthetic valve infective endocarditis is the most severe form of infective endocarditis, occurring in 1-6% of patients with prosthetic valves, with an incidence of 0.3-1.2% per patient-year. Prosthetic valve infective endocarditis accounts for 10-30% of all cases of infective endocarditis and equally affects both mechanical and biological valve prostheses. Early prosthetic valve infective endocarditis is defined as that occurring within 1 year after surgery, and late as that occurring more than 1 year after surgery [125].

A surgical strategy is preferred for prosthetic valve IE of the mitral valve in high-risk subgroups: IE with severe prosthetic dysfunction, abscess, or persistent fever, and decompensated heart failure. Urgent surgery should be performed in the presence of uncontrolled local infection (abscess, pseudoaneurysm, fistula, enlarging vegetations) and in cases of infection caused by fungi or multidrug-resistant organisms. Emergency surgery is indicated only in cases of decompensated CHF with a refractory course leading to pulmonary edema or shock.

3.3. Other treatment

Anticoagulant Therapy After Surgical Treatment of Mitral Regurgitation

• To prevent thromboembolic complications in patients with atrial fibrillation and mitral regurgitation without a mechanical prosthesis (mechanical bileaflet mitral valve prosthesis***), direct oral anticoagulants (B01A: Antithrombotic agents) are recommended as anticoagulant therapy over VKAs [12, 13, 16].

ESC IA (LoE C, SoR 5)

ESC IB (CQR A, LOR 2)

Comment: High INR variability is a significant independent predictor of decreased survival after valve replacement. Currently, there is evidence that self-monitoring of INR reduces INR variability and the incidence of clinical events, including in patients with prosthetic valves; however, appropriate patient education and regular quality control are required. Nevertheless, for patients with unstable INR or complications related to anticoagulant therapy, anticoagulation monitoring should be performed in a clinical setting. Patients must be informed about the ongoing anticoagulant therapy, target INR values, and interactions of oral vitamin K antagonists with other drugs and food.

High thromboembolic risk factors include: left ventricular dysfunction, hypercoagulation, presence of atrial fibrillation, history of thromboembolism. Risk factors and target INR values for patients after mechanical mitral valve replacement (mechanical bileaflet mitral valve prosthesis***) are presented in Table 2.

Table 2. Risk factors and target INR values for patients after mechanical mitral valve replacement

ESC IIaC (LoE C, GoR 5)

ESC IIaC (LoE C, GoR 5)

ESC IC (LoE C, GoR 1)

• Direct oral anticoagulants (B01A: Antithrombotic agents) are recommended as preferred over vitamin K antagonists starting 3 months after biological mitral valve replacement in patients with atrial fibrillation [12, 13].

ESC IIaB (LoE C, GoR 5)

ESC IIbC (LoE C, GoR 5)

ESC IIb C (LoE C, GoR 5)

• In patients with a mechanical mitral valve prosthesis and implanted coronary stents who are at high ischemic risk (acute coronary syndrome or anatomical/procedural features) outweighing the bleeding risk, it is recommended to consider triple therapy including #acetylsalicylic acid** (75–100 mg/day), #clopidogrel** (75 mg/day), and a vitamin K antagonist for 14 to 30 days [12, 13, 155].

ESC IIa B (LoE C, GoR 5)

Comments: The addition of low doses (75–100 mg/day) of #acetylsalicylic acid** to vitamin K antagonist therapy may reduce the incidence of thromboembolic events at the cost of an increased bleeding risk [133]. Therefore, the addition of antiplatelet agents (B01AC Platelet aggregation inhibitors excluding heparin) to vitamin K antagonists should be performed in patients at very high risk for thromboembolic events when the benefits significantly outweigh the risks [158–160]. In patients who experience thromboembolic events despite target INR levels on vitamin K antagonists, low doses (75–100 mg/day) of #acetylsalicylic acid** should be added.

• In patients at high bleeding risk with implanted coronary stents*** and a mechanical mitral valve prosthesis (mechanical bileaflet mitral valve prosthesis***), it is recommended to consider a duration of triple therapy including #acetylsalicylic acid** (75–100 mg/day), #clopidogrel** (75 mg/day), and a vitamin K antagonist for 1 week, regardless of the stent type used and clinical presentation (acute coronary syndrome or stable coronary artery disease) [12, 155].

ESC IIa B (LoE B, GoR 3)

Comments: After discontinuing #acetylsalicylic acid** (75–100 mg/day), continue dual therapy, preferably including #clopidogrel** 75 mg/day and a vitamin K antagonist, with discontinuation of the antiplatelet agent (B01AC Platelet aggregation inhibitors excluding heparin) in high bleeding risk patients at 6 months and in low bleeding risk patients at 12 months, switching to vitamin K antagonist monotherapy.

• In patients with a mechanical MV prosthesis who require #acetylsalicylic acid** and/or #clopidogrel** in addition to VKA, the VKA dosage is recommended to be maintained in the lower part of the target INR therapeutic range (and the time should be >65-70% of the therapeutic range) [18, 159].

ESC IIa B (CUA C, LOE 5)

Analgesic Therapy in Adults

Perioperative pain management in the pre-, intra-, and postoperative periods is routine; the analgesic strategy is determined by the attending physician and anesthesiologist-resuscitologist depending on the scope of the surgical intervention.

• All patients with mitral regurgitation admitted to the hospital for surgical treatment are recommended to receive anxiolytics as part of premedication on the evening before surgery to ensure sedation and emotional stability and to reduce emotional stress. For premedication before transferring the patient to the operating room, opioids and/or benzodiazepine derivatives are used for sedation and emotional stability [178].

ESC class III (CoRE C, LOE 3)

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

• All patients with mitral regurgitation admitted to the hospital for surgical treatment are recommended to receive the following for intraoperative anesthesia: propofol**, benzodiazepine derivatives, halogenated hydrocarbons. Fentanyl** (for premedication before surgery), diazepam** (as part of preparation for surgery) [177, 178, 179].

ESC no (LoE A, GoR 2)

Comment. The following drugs are used for intraoperative anesthesia: midazolam**/diazepam**/propofol** and fentanyl**, sodium oxybate**; halogenated hydrocarbons in combination with intravenous fentanyl** in calculated dosages may be used. A multicenter randomized controlled trial revealed no differences in clinical outcomes between total intravenous anesthesia based on propofol** and fentanyl** versus combined anesthesia using halogenated gas anesthetics (N01AB Halogenated hydrocarbons) and fentanyl** during cardiac surgery [176].

• All patients with mitral regurgitation admitted to the hospital for surgical treatment are recommended to receive age-appropriate doses of opioids for analgesia in the early postoperative period [178].

ESC class III (CoRE C, LOE 3)

Comment. Medications used for postoperative pain management: first 24 hours after surgery – trimeperidine** or morphine** intramuscularly every 4–8 hours, NSAIDs (M01A Anti-inflammatory and antirheumatic products, non-steroids). When special dispensers are available, patient-controlled analgesia with fentanyl** is effective. If severe pain persists, trimeperidine**/morphine**/fentanyl** as indicated.

Use of nitric oxide in the postoperative period

• In the surgical treatment of mitral regurgitation in patients with precapillary pulmonary hypertension (mean pulmonary arterial pressure ≥20 mm Hg, pulmonary capillary wedge pressure ≤15 mm Hg), a pulmonary vascular resistance greater than 5 Wood units, and echocardiographic signs of right ventricular dysfunction, it is recommended to consider the use of inhaled nitric oxide in the intra- and postoperative periods [126].

ESC/RSC IIaB (LoE B, GoR 1).

Comments. Patients with pathological changes of the mitral valve are characterized by an increase in pulmonary circulation pressure (group 2 pulmonary hypertension, post-capillary pulmonary hypertension). Over time, such patients begin to show an increase in pulmonary vascular resistance, i.e., a precapillary component appears (reactive pulmonary hypertension). The performed surgical intervention on the mitral valve effectively relieves the post-capillary component of pulmonary hypertension. However, the increased pulmonary vascular resistance (precapillary component) continues to persist in the postoperative period, adversely affecting hemodynamic parameters, up to the development of RV dysfunction. The performed meta-analysis confirmed a significant improvement in clinical indicators—a reduction in the duration of mechanical ventilation and the length of stay in the intensive care unit with nitric oxide inhalation [126].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Medical rehabilitation programs for patients after surgical correction of mitral regurgitation are aimed at limiting psychological and physiological stress associated with prior cardiac surgery, reducing the risk of mortality and disability, modifying lifestyle, and improving cardiovascular function in order to maximize the possible quality of life of patients [127].

Cardiac medical rehabilitation is presented as a three-stage system within which patient routing is implemented (Appendix B, Figure 3) [128]. Medical rehabilitation care is provided to patients with mitral regurgitation on a scheduled basis after the diagnosis is established (at the first contact with the patient) or in the chronic course of the disease regardless of the timing of the disease, provided the patient's clinical state is stable, medical indications are present, and contraindications to certain rehabilitation methods are taken into account [12, 13].

When planning surgical correction of mitral regurgitation, patient preparation for effective recovery is recommended to begin in the preoperative period—at the prehabilitation stage—in order to inform the patient about the nature and scope of the surgical intervention, teach them to optimally perceive their well-being after surgery, and master the ability to correctly follow postoperative recommendations. Rehabilitation measures and methods are recommended to be applied taking into account the rehabilitation stage, as well as the clinical and physical state of the patient.

Cardiac rehabilitation is carried out by a multidisciplinary team of medical professionals to achieve optimal physical and psychosocial health of patients with mitral regurgitation, with the participation of partners, other family members, and caregivers [129].

No ESC guideline (LoE C, GoR 5)

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

No ESC guideline (LoE C, GoR 5)

Comments: most cardiac rehabilitation programs are implemented at the outpatient stage, which is preferably conducted in-person, remotely (at home using computer and telecommunication technologies), or in a blended format to increase patient coverage with rehabilitation measures and improve adherence to lifestyle changes, rehabilitation, and drug therapy [133-135].

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 and systematic analyses show that early mobilization improves physical function (the 6-minute walk test distance improved by 54 m) at discharge in patients after heart surgery [136].

A prospective RCT demonstrated that early initiation of cardiac rehabilitation improved postoperative functional capacity (6-minute walk test), reduced the duration of mechanical ventilation, oxygen therapy dependency, and hospital length of stay in patients undergoing elective cardiac surgery [137,138].

No ESC guideline (LoE C, GoR 5)

No ESC guideline (LoE C, GoR 5)

No ESC guideline (LoE C, GoR 5)

Comments: standardized and valid diagnostic methods and assessment tools according to the International Classification of Functioning, Disability and Health available for this purpose (www.icf-research-branch.org/download/category/12-cardiovascularandrespiratoryconditions) are used to assess the patient's clinical status, level of functioning and vital activity, and the influence of personal and environmental factors [130,142-144].

The International Classification of Functioning is a tool for describing disorders of organ and system functions and impairments in daily functions (self-care, communication, performance of professional and social roles) arising from a patient's disease/injury, taking into account the influence of environmental factors that may facilitate or hinder the patient's performance of the described functions.

No ESC guideline (LoE C, GoR 5)

No ESC guideline (LoE C, GoR 5)

Comments: The Hospital Anxiety and Depression Scale is presented in Appendix G1.

ESC IA (LoE C, GoR 5)

Comments: patient information and education are provided in any available format (individually, as part of rehabilitation counseling, and/or in the "School for Patients with Valvular Heart Disease") in person or online [131, 147].

ESC not specified (LoE C, GoR 4)

ESC not specified (LoE B, GoR 2)

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

In both patients with MR who have undergone surgery and those without surgical treatment, the physical rehabilitation program (in the absence of contraindications) includes medical gymnastics complexes with breathing exercises, inspiratory muscle training using breathing trainers (indicated) and other breathing techniques (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 level, heart rate, and ECG as indicated), and to assess the level of physical exertion using the Borg scale (Borg Rating of Perceived Exertion, BorgRPE) during training (Appendix G2) [131, 149].

ESC not stated (CGR B, LOR 3)

ESC not specified (LoE C, GoR 4)

Comment: indications for sanatorium-resort treatment include mitral regurgitation, stage I chronic heart failure (FC I-II) without prognostically unfavorable heart rhythm and conduction disturbances, without signs of process activity; mitral regurgitation in stage IIA chronic heart failure (FC II) without prognostically unfavorable heart rhythm and conduction disturbances, without signs of process activity, remission phase [152].

5. Prevention and Dispensary Observation

Active surveillance

ESC IB (Level of Evidence C, Grade of Recommendation 5)

• All patients receiving VKA therapy are recommended to perform self-monitoring of INR provided they have undergone appropriate training in a patient school and under medical supervision (remote monitoring of the laboratory parameter or regular doctor visits) [157].

ESC IB (GoR B, LoE 2)

• All patients with MR, as well as those after MV replacement, are recommended lifelong dispensary follow-up by a cardiologist to determine visit frequency, monitor compliance with prescribed recommendations, adjust therapy in a timely manner, assess the risk of cardiovascular complications, refer for additional examinations, sanatorium-resort treatment, and, if necessary, hospitalization [161, 162].

ESC IIA (GoR C, LoE 5).

ESC IA (LoE C, SoR 5)

ESC IA (LoE C, SoR 5)

Comments: Asymptomatic patients with mild MR, no LV dilatation or dysfunction, and no pulmonary hypertension may be followed up once a year and should be instructed to consult a physician immediately if their symptoms change. Annual echocardiography assessing LV dimensions and function as well as MR severity is not mandatory unless there is clinical evidence of MR progression. In patients with mild MR, echocardiography may be performed every 3–5 years. In patients with moderate MR, clinical evaluation, including echocardiography, should be performed annually or more frequently if new symptoms appear. If new symptoms develop, perform early transthoracic echocardiography (and transesophageal echocardiography if necessary) [12, 13, 28].

Preoperative ejection fraction is an important predictor of postoperative survival in patients with chronic MR [160, 161]. Echocardiographic measurement of end-systolic dimension (or volume) is also useful as a criterion for timing MV surgery. End-systolic dimension, which may be less load-dependent than ejection fraction, should be less than 40 mm preoperatively to ensure normal postoperative LV function [33]. If patients develop clinical symptoms, surgery is indicated even if LV systolic function and dimensions are within normal limits [12, 13].

ESC/RSC IC (GoR C, LoE 5)

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

ESC/RSC IIaC (GoR C, LoE 5)

• In patients with MR and after mitral valve replacement, it is recommended to record, decode, describe, and interpret a resting electrocardiogram once a year at a follow-up visit and additionally upon the appearance of arrhythmias, as well as when prescribing or modifying treatments affecting intracardiac electrical conduction [2].

ESC IC (GoR C, LoE 5).

ESC/RSC none (GoR C, LoE 5)

ESC IIa B (GoR C, LoE 5)

Comments: The evaluation includes: 1) Transthoracic echocardiography; 2) 12-lead electrocardiography; 3) Targeted chest X-ray in 2 projections (anteroposterior and left lateral); 4) Complete blood count; 5) Biochemical blood test; 6) INR determination (in case of warfarin therapy).

• Following the initial postoperative evaluation, a patient with MR is recommended to be monitored and re-examined (with echocardiography) at 6 and 12 months, and then annually if the clinical course is uncomplicated [12, 13, 18]

ESC/RSC none (GoR C, LoE 5)

• To resolve the issue of referring patients with MR for echocardiography, transesophageal echocardiography, MRI, computed tomography, coronary angiography, and other imaging studies, it is recommended to conduct a cardiologist consultation/examination [12, 161, 162].

ESC IIaC (GoR C, LoE 5).

Comments: During the first doctor's visit after hospital discharge, if indicated, the following may be performed: ECG, EchoCG, targeted chest X-ray, complete blood count, levels of potassium, sodium, glucose, creatinine, total protein, urea, total bilirubin, TSH, CRP, and INR to assess renal and hepatic function and exclude inflammation. Serum total cholesterol, LDL-C, and TG testing to identify risk factors for concomitant atherosclerosis and, if necessary, adjust therapy. It is crucial not to miss symptoms of prosthetic valve dysfunction or worsening heart failure. If the patient underwent surgery for infective endocrinological conditions (infective endocarditis), the follow-up visit must be scheduled after completion of the antibiotic therapy course [162]. Dispensary follow-up of patients after mitral valve replacement should be performed 2–4 weeks after hospital discharge, then every 6 months, and subsequently annually. The main goals of dynamic follow-up after mitral valve replacement are monitoring INR during the dose-adjustment phase every 1–3 days, and then with an established dose every 3–4 weeks during a follow-up visit, adjusting the warfarin dose, dynamically monitoring prosthetic function for early diagnosis of abnormalities and detection of late postoperative complications, managing heart failure and cardiac arrhythmias, and monitoring ECG and EchoCG.

Patients after surgery do not become completely healthy individuals; severe heart disease persists, and the further course of the illness depends on many factors: left ventricular function, progression of unreplaced valve disease, pulmonary hypertension, and heart failure.

In the absence of complications and symptoms of disease progression, an annual examination is sufficient, and there is no need to perform all cardiological tests routinely; it is advisable to use them when indicated. EchoCG is prescribed to all patients with prosthetic valves when new murmurs are detected or changes occur in the patient's clinical status, when symptoms may indicate progressive valvular or ventricular dysfunction [163]. Each heart valve prosthesis is characterized by its own pressure gradient values. In addition, each type of valve prosthesis has specific features of paravalvular regurgitation. A number of other non-invasive studies can be performed to assess valve and ventricular function [164].

All patients must be informed about the prevention of infective endocarditis, which includes skin and dental hygiene, oral sanitation at least once a year, timely wound disinfection, and treatment of chronic foci of bacterial infection.

ESC IIa C (LoE C, LoR 5).

Follow-up visits for patients with a complicated disease course

ESC IA (LoE C, SoR 5)

Comments: Causes of left ventricular systolic dysfunction include: pre-existing left ventricular systolic dysfunction prior to surgery; perioperative myocardial injury; progression of unoperated valve pathology; complications associated with prosthetic valves; presence of comorbid pathology (CAD, arterial hypertension). Optimal medical therapy will prevent the progression of systolic dysfunction and the worsening of chronic heart failure symptoms in patients with both primary and secondary MR [50–55].

ESC I A (LoE C, LoR 4)

Comments: in patients with primary MR after surgical intervention, adequate risk factor correction is required to prevent the development of CAD and avoid repeat cardiac surgery. In ischemic MR, secondary prevention of CAD will prevent the progression of systolic dysfunction and the worsening of chronic heart failure symptoms [5, 20, 165].

6. Organization of Medical Care

Stages of medical care:

1. Primary healthcare level

2. Specialized outpatient care

3. Specialized inpatient medical care and/or high-tech inpatient care

4. Postoperative rehabilitation stage, dynamic follow-up

5. Type of medical care: specialized medical care, primary health care, emergency medical care

6. Conditions for providing medical care: inpatient, outpatient, outside a medical organization

7. Form of medical care: elective, emergency

Indications for elective hospitalization:

1) unclear diagnosis and the need for special investigative methods (use of diagnostic procedures that are impossible or impractical in an outpatient setting) to clarify the cause and severity of MR;

2) elective surgery for mitral valve replacement or repair;

Indications for emergency hospitalization:

1) acute MR complicated by the development of pulmonary edema, cardiogenic shock, unstable hemodynamics;

2) atrial fibrillation paroxysm;

3) decompensation of chronic heart failure against the background of primary or secondary chronic MR;

Indications for patient discharge from the hospital:

1) diagnosis of MR established using special diagnostic methods with determination of the cause and severity

2) completed mitral valve replacement or repair surgery with a finished postoperative observation period and management of perioperative complications

3) selected medical therapy in case of refusal of surgical intervention;

4) terminated atrial fibrillation paroxysm.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Bokeria L.A., Academician of RAS (Moscow), ACCS, Chair

2. Irtyuga O.B., MD, PhD (Saint Petersburg), RSC, Co-chair

3. Asatryan T.V., PhD (Moscow), ACCS, Secretary

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

5. Apkhanova T.V., 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)

6. Aronov D.M., MD, PhD, Professor (Moscow), RSC, RosOKR

7. Afanasyev A.V., MD, PhD (Novosibirsk), RSC, ACCS

8. Barbuhatti K.O., MD, PhD, Associate Professor (Krasnodar), ACCS

9. Belan I.A. (Krasnodar), RSC

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

11. Bogachev-Prokofiev A.V., MD, PhD (Novosibirsk), RSC, ACCS

12. Gareev D.A. (Saint Petersburg), RSC

13. Gendlin G.E., MD, PhD, Professor (Moscow), RSC

14. Gordeev M.L., MD, PhD, Professor (Saint Petersburg), RSC, ACCS

15. Golukhova E.Z., Academician of RAS (Moscow), RSC, ACCS

16. Demchenko E.A., MD, PhD (Saint Petersburg), RSC, RosOKR

17. Dzhordzhikiya R.K., MD, PhD, Professor (Kazan), ACCS

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

19. Isakov S.V., PhD (Saint Petersburg), RSC, ACCS

20. Karaskov A.M., Academician of RAS (Novosibirsk), ACCS

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

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

23. Malev E.G., MD, PhD (Saint Petersburg), RSC

24. Matskeplishvili S.T., MD, PhD, Professor (Moscow), RSC

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

26. Muratov R.M., MD, PhD, Professor (Moscow), ACCS

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

28. Sinitsyn V.E., MD, PhD, Professor (Moscow), All-Russian Public Organization for the Promotion of the Development of Diagnostic Radiology and Therapy "Russian Society of Roentgenologists and Radiologists"

29. Skopin I.I., Corresponding Member of RAS, MD, PhD, Professor (Moscow), ACCS

30. Sukhova I.V., PhD (Saint Petersburg), RSC

31. Tarasov D.G., PhD (Astrakhan), ACCS

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

33. Uspensky V.E., MD, PhD (Saint Petersburg), RSC, ACCS

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

35. Khubulava G.G., Academician of RAS (Saint Petersburg), ACCS

36. Chernov I.I., PhD (Astrakhan), ACCS

37. Shlyakhto E.V., Academician of RAS (Saint Petersburg), RSC

38. Shneider Yu.A., MD, PhD (Kaliningrad), ACCS

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

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

The members of the Working Group confirmed the absence of financial support/conflict of interest. If a conflict of interest was reported, the working group member(s) were excluded from the discussion of sections related to the conflict of interest area.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the developed clinical guidelines:

• Cardiovascular surgeon

• Cardiologist

• Ultrasound Diagnostics Physician

• General Practitioner

• 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 guidelines includes publications indexed in the PubMed and Scopus databases. The literature search depth was 30 years.

Methods used to assess the quality and strength of evidence

• expert consensus;

• evaluation of the recommendation quality in accordance with the rating scheme (Table P1).

• evaluation of the evidence strength in accordance with the rating scheme (Table P2).

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, the development of national guidelines was based on the ESC guidelines, taking into account national specifics, examination and treatment characteristics, and the availability of certain types of medical care. For this reason, during the development of Russian clinical guidelines by the RSC, international classes of recommendation were used, which make it possible to assess the necessity of implementing a guideline statement and the levels of evidence for these classes (Tables P1 and P2).

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

In addition, a new system of evidence level (EL) and recommendation grade (RG) scales for therapeutic, rehabilitative, preventive, and diagnostic interventions (Tables P3, P4, and P5) was introduced in 2018 by the Center for Expertise and Quality of Medical Care of the Russian Ministry of Health. Thus, the text of clinical guidelines developed by RSC experts simultaneously utilizes two scales.

Table P1. Classes of recommendations according to the European Society of Cardiology (ESC) guidelines.

Table P2. Levels of evidence according to the European Society of Cardiology (ESC) guidelines.

Table P3. Scale for assessing levels of evidence (LE) for prevention, treatment, and rehabilitation methods (preventive, therapeutic, rehabilitative interventions)

Table P4. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table P5. Scale for assessing grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitative interventions)

Procedure for updating clinical guidelines.

The clinical guideline update mechanism provides for their systematic revision—at least once every three years—as well as upon the emergence of new evidence-based medicine data regarding 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 the Basics of Protecting the Health of Citizens in the Russian Federation (Federal Law No. 323-FZ of November 21, 2011)

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

3. "On Approval of the Procedure for Organizing Medical Rehabilitation for Adults" (Order of the Russian Ministry of Health No. 778n dated 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 dated 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)

Appendix A3-2. Contraindications to physical training in patients after surgical correction of mitral regurgitation

• 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 events, 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 mmHg).

• Angina attacks.

• A decrease in systolic BP ≥20 mmHg in response to physical exertion.

• Cardiac arrhythmias (high-grade extrasystoles or tachyarrhythmias) and conduction disorders (grade II–III 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.

A3-3. Fig. 4A. Etiology of mitral regurgitation.

Appendix B. Physician Action Algorithms

Fig. 1B. Algorithm for primary diagnosis and surgical treatment of MR

Note: ACG – acustocardiography.

Fig. 2B. Algorithm for patient examination after MR correction

Fig. 3B. Algorithm for patient routing with mitral regurgitation within the medical cardiac rehabilitation system.

Note: - possible patient movement during the provision of specialized and primary medical care, including medical rehabilitation;

MDRT – multidisciplinary rehabilitation team;

- participation of the MDRT in the medical rehabilitation process

Fig. 4B. Algorithm for using diagnostic imaging and instrumental methods in patients with mitral regurgitation

Appendix C. Patient Information

Mitral regurgitation – a valvular heart disease characterized by incompetence of the mitral valve, resulting in a portion of blood being pumped from the left ventricle back into the left atrium instead of the aorta during cardiac contraction. Mitral regurgitation of varying severity may be detected from the first years of life; functional mitral regurgitation, which is not a pathology, can be observed during adolescence. It can be either congenital or acquired.

Severe, significant mitral regurgitation may manifest as dyspnea on exertion and at rest, fatigue, and in advanced cases, lower extremity edema and cardiac arrhythmias.

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

• Follow-up with a local cardiologist is recommended at least once a year, strictly adhering to their prescriptions and appointments.

• Cardiologist follow-up in a specialized center is recommended at least once a year.

• For any invasive procedures (dental, cosmetic, and other procedures involving or carrying the risk of disrupting the integrity of the skin and mucous membranes), antibiotic prophylaxis is strictly recommended to prevent infective endocarditis.

• Cases of planned invasive procedures should be coordinated with the cardiologist supervising the patient at their place of residence.

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

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

• If the following symptoms occur or sharply progress, an urgent consultation with a cardiologist is recommended as soon as possible: fatigue, dyspnea, edema, abdominal distension, arrhythmias, syncope, neurological deficits (loss of vision, hearing, speech, limb numbness, paresis and paralysis, including transient ones), acute respiratory infections, fever of unknown origin.

Preparation for CT coronary angiography:

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

• Determination of blood creatinine.

• Inform the referring physician and radiologist about thyroid diseases, bronchial asthma, diabetes mellitus, iodine allergies, and intolerance to nitrates and beta-blockers.

• 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.

• Determination of blood creatinine.

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: Zigmond, A. S., & Snaith, R. P. (1983). "The Hospital Anxiety and Depression Scale". Acta Psychiatrica Scandinavica, 67(6):361–370. doi:10.1111/j.1600-0447.1983.tb09716.x

Type: rating scale

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

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 abnormal anxiety/depression; 11 points and above – abnormal anxiety/depression.

Explanation: Each HADS statement has 4 possible answers. The patient is asked to choose the answer that best describes how they have been feeling over the past 7 days; the scores are then summed up separately for each part.

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

Russian title: Original Borg Scale

Original title: Borg Rating of Perceived Exertion

Source:

Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14:377-381.

Borg G. Psychophysical scaling with applications in physical work and the perception of exertion. ScandJWorkEnvironHealth. 1990;16(Suppl 1):55–58.

Type: rating scale

Purpose: subjective assessment of physical exertion / training 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 exertion at all, 9 – very light (like walking slowly at one's own pace), 12 to 14 – somewhat hard (like walking fast or jogging); 15 and above – high intensity zone, like very fast running.