Atrial Fibrillation and Flutter: Clinical Guidelines

List of Abbreviations

AAD – antiarrhythmic drugs. (Class IA AAD – ATC C01BA Antiarrhythmic drugs, class IA; Class IB AAD – ATC C01BB Antiarrhythmic drugs, class IB; Class IC AAD – ATC C01BC Antiarrhythmic drugs, class IC; Class III AAD – ATC C01BD Antiarrhythmic drugs, class III)

AAT – antiarrhythmic therapy

VKA – vitamin K antagonists

AH – arterial hypertension

OAC – anticoagulant therapy

ACE – angiotensin-converting enzyme

ATC – Anatomical Therapeutic Chemical classification system

aPTT – activated partial thromboplastin time

WPW – Wolff-Parkinson-White (syndrome/phenomenon), see also WPW

ГКМП – hypertrophic cardiomyopathy

AP – accessory pathway

ЕОК – European Society of Cardiology

CHD – coronary heart disease

IS – ischemic stroke

CrCl – creatinine clearance

CT – computed tomography

LV – left ventricle

INR – international normalized ratio

MRI – magnetic resonance imaging

MS – medical service

NSAIDs – non-steroidal anti-inflammatory and antirheumatic drugs

OAC – oral anticoagulants (according to the ATC classification: vitamin K antagonists – B01AA, direct thrombin inhibitors – B01AE, and direct factor Xa inhibitors – B01AF)

ACS – acute coronary syndrome

DOAC – direct oral anticoagulants (according to the ATC classification: direct thrombin inhibitors and direct factor Xa inhibitors)

DM – diabetes mellitus

HF – heart failure

CRT – cardiac resynchronization therapy

TIA – transient ischemic attack

AFL – atrial flutter

TEC – thromboembolic complications

LAA – left atrial appendage

LVEF – left ventricular ejection fraction

AF – atrial fibrillation

CHF – chronic heart failure

CKD – chronic kidney disease

PCI – percutaneous coronary intervention / coronary stenting

TEE – transesophageal echocardiography (transesophageal echocardiography A04.10.002.001, intraoperative transesophageal echocardiography A04.10.002.005)

HR – heart rate

ECG – electrocardiogram

PM – pacemaker (139070 – Implantable dual-chamber rate-responsive pacemaker***, 210180 – Implantable single-chamber rate-responsive pacemaker***, 233950 – Implantable triple-chamber (biventricular) pacemaker***, 334620 – Implantable dual-chamber rate-responsive pacemaker, 1.5T/3T MRI-conditional***))

APRE – episodes of rapid atrial rhythm

EchoCG – echocardiography

β-blockers – beta-blockers

NYHA – New York Heart Association

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

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

# – medicinal product for medical use used inconsistently with the indications for use, contraindications, routes of administration, and doses contained in the instructions for use of the medicinal product

Terms and Definitions

Antiplatelet agents – according to the ATC classification, antiplatelet drugs except heparin B01AC

Evidence-based medicine – the conscientious, explicit, and judicious use of current best evidence (clinical research results) in making decisions about the care of individual patients [1].

Disease – a disorder of bodily function, working capacity, and ability to adapt to changing environmental and internal conditions arising from the impact of pathogenic factors, accompanied by alterations in the body's protective, compensatory, and adaptive reactions and mechanisms [2].

Platelet P2Y₁₂ receptor inhibitors – according to the ATC classification: clopidogrel** B01AC04, prasugrel B01AC22, ticagrelor** B01AC24

Instrumental diagnostics – diagnostics utilizing various devices, apparatuses, and instruments to examine a patient.

Interventional treatment – instrumental treatment methods aimed at achieving long-term maintenance of sinus rhythm, heart rate control, or prevention of cardioembolic complications, performed using catheters advanced into the heart chambers via major vessels (endovascularly).

Outcome – any possible result arising from exposure to a causal factor, preventive or therapeutic intervention, or all established changes in health status resulting from an intervention [3].

Cardioversion (restoration of sinus rhythm) resulting from external electrical cardioversion (defibrillation) – A16.10.018.001, intravenous drug administration, continuous intravenous drug administration – A11.12.003, or prescription of drugs for heart and pericardial diseases – A25.10.001

Catheter ablation – a minimally invasive surgical procedure that achieves the destruction of arrhythmogenic zones or pathological conduction pathways using radiofrequency (endovascular radiofrequency ablation of cardiac conduction pathways and arrhythmogenic zones), cryoablation (endovascular cryoablation of cardiac conduction pathways and arrhythmogenic zones), or other forms of energy.

Conflict of interest – a situation in which a medical or pharmaceutical worker, in the exercise of their professional activities, has a personal interest in obtaining material gain or other advantage, either personally or through a representative, which influences or may influence the proper performance of their professional duties due to a contradiction between the personal interest of the medical or pharmaceutical worker and the interests of the patient [2].

Clinical trial – any investigation conducted in human subjects intended to discover or verify the clinical and/or pharmacological effects of investigational products, and/or to identify any adverse reactions to investigational products, and/or to study absorption, distribution, metabolism, and excretion with the object of ascertaining their safety and/and efficacy. The terms "clinical trial" and "clinical study" are synonymous [4].

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

Medicinal products – pharmacological agents in the form of dosage forms used for the prevention, diagnosis, and treatment of diseases, rehabilitation, and the preservation, prevention, or termination of pregnancy [5].

Medical intervention – types of medical examinations and/and medical manipulations performed by a medical worker or other employee authorized to carry out medical activities in relation to a patient, affecting their physical or mental state and having a preventive, diagnostic, therapeutic, rehabilitative, or research focus, as well as artificial termination of pregnancy [2].

Medical worker – an individual who has medical or other education, works in a medical organization whose job (official) duties include the performance of medical activities, or an individual who is an individual entrepreneur directly engaged in medical activities [2].

Mechanical heart valve prosthesis – mechanical bileaflet aortic valve prosthesis***, mechanical bileaflet mitral valve prosthesis***

Acute coronary syndrome – a term denoting any group of clinical signs or symptoms suggesting acute myocardial infarction or unstable angina

Parenteral anticoagulants – according to the ATC classification, the heparin group B01AB

Patient – an individual to whom medical care is provided or who applies for medical care regardless of the presence of a disease and their condition [2].

Oral anticoagulants – according to the ATC classification: vitamin K antagonists – B01AA, direct thrombin inhibitors – B01AE, and direct factor Xa inhibitors – B01AF

Clinical Practice Guidelines Development/Update Working Group – a team of specialists working together and in coordination to develop or update clinical practice guidelines and bearing joint responsibility for the results of this work.

Condition – bodily alterations arising from the impact of pathogenic and/or physiological factors and requiring medical care [2].

Syndrome – a stable set of several symptoms with a unified pathogenesis [6].

Stent – drug-eluting stent (coronary artery drug-eluting stent, fully bioresorbable***, coronary artery stent eluting a drug with a bioresorbable polymer coating***, coronary artery drug-eluting stent with a non-bioresorbable polymer coating***) and/or bare-metal stent (synonym: bare-metal coronary stent***)

Structural heart disease – a concept including coronary artery disease (CAD), all types of cardiomyopathies (dilated, hypertrophic, restrictive, arrhythmogenic right ventricular cardiomyopathy), hemodynamically significant valvular and congenital heart defects, as well as the presence of marked left ventricular (LV) hypertrophy. The definition of "CAD" is presented in the clinical guidelines "Stable Coronary Artery Disease", "Non-ST-Segment Elevation Acute Coronary Syndrome", and "ST-Segment Elevation Acute Myocardial Infarction".

The definition of "marked LV hypertrophy" corresponds to hypertrophy with an LV wall and/or interventricular septum thickness of ≥14 mm based on imaging methods (echocardiography, cardiac magnetic resonance imaging). At the same time, in the absence of convincing scientific data, the working group believes that the physician has the right to make an independent decision regarding this definition.

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

Thrombolysis – intravenous administration of drugs for thrombolytic therapy – A11.12.003.002

Level of Evidence (LoE) – the degree of certainty that the found effect of a medical intervention is true [7].

Grade of Recommendation (GoR) – the degree of certainty in the reliability of the intervention's effect and that following the recommendations will bring more benefit than harm in a specific situation [7].

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

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Atrial fibrillation (AF) is the most common type of supraventricular tachyarrhythmia with chaotic electrical activity of the atria at a rate of 350–700 per minute (with the absence of a P wave on the ECG), precluding their coordinated contraction and typically resulting in an irregular ventricular rhythm.

Atrial flutter (AFL) is a supraventricular tachyarrhythmia characterized by atrial activation at a rate of 250–350 per minute ("flutter waves" with the absence of an isoelectric line on the ECG) due to a macro-re-entry process around a specific anatomical or functional obstacle (typically involving the tricuspid valve).

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

AF is a complexly organized arrhythmia whose development mechanisms are diverse and complement each other. The triggering mechanism of the cardiac rhythm disorder can be cardiac and extracardiac pathologies leading to arrhythmogenic transformation of the atrial myocardium, initiation of the arrhythmia, and the triggering of a cascade of electrical and neurohumoral changes that contribute to its maintenance [8–10].

The development and persistence of AF and AFL, like any sustained cardiac rhythm disorder, are impossible without a trigger that initiates the arrhythmia and a substrate that maintains it. In most cases, the development of a sustained paroxysm occurs against the background of structural remodeling of the atrial myocardium.

In most cases, determining the exact etiology of AF is not possible. Along with this, there are a number of associated clinical conditions that are markers of an increased risk of developing cardiac rhythm disorders. These include:

• Acquired or congenital structural pathologies of the myocardium, pericardium, valve apparatus, and/or great vessels [11].

• Arterial hypertension (AH); increases the risks of developing not only AF, but also stroke and thromboembolic complications.

• Coronary artery disease (CAD); detected in 20% of patients with AF [12, 13]. The pathogenetic mechanism is partly due to ischemia of atrial cardiomyocytes.

• Clinically overt heart failure (HF) NYHA functional class II–IV (NYHA) [12, 13]. AF occurs in 30–40% of patients with HF NYHA class III–IV.

• Thyroid dysfunction. In recent epidemiological studies, hyperthyroidism or hypothyroidism in patients with AF was diagnosed quite rarely, but not only overt disorders but also subclinical thyroid dysfunction may also contribute to the development of arrhythmia [12, 13].

• Age. According to numerous clinical studies, the risk of developing AF increases in individuals over 40 years of age. Age is also one of the key factors in stratifying the risk of thromboembolic complications.

• Overweight and obesity; observed in 25% of patients with AF [13]. According to recent studies, there is a direct correlation between the thickness and volume of epicardial adipose tissue and the risk of developing AF. Possible pathophysiological mechanisms include the inflammatory effect of epicardial adipose tissue on the atrial myocardium [14, 15].

• Diabetes mellitus (DM) is noted in 20% of patients with AF and may contribute to atrial damage.

• Obstructive sleep apnea syndrome, especially in combination with AH, DM, and structural heart disease, can be a pathogenetic factor for AF, as apnea causes an increase in atrial pressure, atrial size, or changes in the state of the autonomic nervous system.

Given such a variety of risk factors and associated clinical conditions, the treatment of patients with AF requires a multidisciplinary approach and should be aimed, among other things, at correcting risk factors and concomitant pathology. The modern concept of dynamic monitoring and management of patients with AF is well represented within the AF-CARE framework.

C (comorbidity and risk factor management) – management of comorbid conditions and risk factors;

A (avoid stroke and thromboembolism) – prevention of stroke and thromboembolic complications.

R (reduce symptoms by rate and rhythm control) – reduction of arrhythmia symptoms through heart rate or rhythm control.

E (evaluation and dynamic reassessment) – dynamic monitoring.

The AF-CARE concept implies the need for an individualized approach and a multifactorial characterization of arrhythmia in each patient at a specific point in time. This approach makes it possible to track how the patient, their arrhythmia, and concomitant diseases change over time and to take comprehensive steps aimed at preventing the progression of AF and the development of complications. Thus, the modern approach to the management of a patient with AF should include the correction of concomitant comorbid pathology, medical and interventional treatment aimed at symptom control and the prevention of thromboembolic events, and regular dynamic monitoring.

1.3 Epidemiology of the Disease or Condition

The estimated prevalence of AF in the adult population ranges from 2% to 4% [16]. Due to the active search for undiagnosed forms of arrhythmia and the improvement in life expectancy of the population as a whole, a 2.3-fold increase in the prevalence of AF is expected by 2060 [17–20]. According to available data, AF is more frequently detected in men than in women and in non-Caucasian patient cohorts compared to Caucasians [20].

Statistical data describing the prevalence of AF in the Russian population are sketchy and very sparse due to the lack of a general database registry. According to the EPOCHA-CHF epidemiological study, the prevalence of AF in a representative sample of the European part of the Russian Federation was 2.04%, or 2,040 patients per 100,000 population [22]. At the same time, the prevalence of AF among respondents aged 20 to 29 years is low (0.1%), increases with age, and reaches its maximum value in the group aged 80 to 89 years (9.6%). Comorbidity increases the risk of AF presence, especially in the presence of four and five comorbid conditions.

Also, according to the Stress, Aging and Health in Russia cohort study, in individuals older than 55 years, the prevalence of AF is 6.65%, while the incidence of AF increases from 2.4% in men and 2.1% in women aged 55 to 64 years to 10% and 12.8% at age ≥75 years, respectively [21].

1.4 Features of Coding the Disease or Condition

I48.0 – Paroxysmal atrial fibrillation

I48.1 – Persistent atrial fibrillation

I48.2 – Chronic atrial fibrillation

I48.3 – Typical atrial flutter. Atrial flutter type I

I48.4 – Atypical atrial flutter. Atrial flutter type II

I48.9 – Unspecified atrial fibrillation and atrial flutter

1.5 Classification of the disease or condition

According to the classic arrhythmia classification, which takes into account the course and duration of the heart rhythm disorder, 5 types of AF/AFL are distinguished:

1. First diagnosed – AF/AFL that has not been diagnosed previously, regardless of the duration of the arrhythmia or the presence and severity of related symptoms.

2. Paroxysmal – self-terminating, in most cases within 48 hours. Some AF/AFL paroxysms may last up to 7 days. Episodes of AF terminated by cardioversion within 7 days should be classified as paroxysmal AF/AFL.

3. Persistent – AF lasting for more than 7 days, including episodes terminated by cardioversion or pharmacologically after 7 days or more.

4. Long-standing persistent – a prolonged episode of AF/AFL lasting more than 1 year, provided that a rhythm control strategy is chosen.

5. Permanent – a form of AF/AFL where the patient and physician have made a joint, agreed decision not to attempt sinus rhythm restoration. Accordingly, interventional procedures aimed at rhythm control are, by definition, not required. However, if the decision is reconsidered in favor of a rhythm control strategy, the arrhythmia should be reclassified depending on the duration of the AF/AFL.

Comment: in addition, recently, with the advancement of interventional and surgical treatment technologies for AF/AFL, an additional variant of the arrhythmia has begun to be distinguished – the early persistent form of AF, which implies the presence of a heart rhythm disorder lasting from 7 days to 3 months. The importance of identifying this form of heart rhythm disorder is based on the expected outcomes of the planned treatment and available data confirming the potential success of both antiarrhythmic therapy and interventional procedures [23, 24].

According to H. Wells' classification (1979), two types of AFL are distinguished:

Typical flutter (Type I). Observed in 90% of patients. It is characterized by the propagation of a macro re-entry wave counterclockwise (most frequently) or clockwise (significantly less frequently) around the tricuspid valve. A characteristic feature of this type of AFL is the obligatory re-passage of the excitation wave through the so-called cavotricuspid isthmus.

Atypical flutter (Type II). Atypical AFL includes all other types of atrial macro re-entry that do not involve the cavotricuspid isthmus area in the re-entry circuit.

1.6 Clinical presentation of the disease or condition

The clinical presentation of AF can vary from palpitations, dyspnea, chest discomfort, sleep disorders, drowsiness, fatigue, and psychosocial disorders to the complete absence of any symptoms [25–28].

For the correct selection of treatment tactics and the most favorable outcome, the arrhythmia in each individual patient should be characterized in a clearly structured manner. For this purpose, it is advisable to use the 4S-AF scheme (Stroke risk, Symptom severity, Severity of AF burden, Substrate severity), which describes 4 domains associated with AF:

1. stroke risk stratification (according to the CHA2DS2-VASc scale);

2. assessment of symptom severity;

3. assessment of disease burden (duration, frequency of development, and spontaneous termination of AF paroxysms);

4. assessment of the severity of the arrhythmogenic substrate (age, cardiovascular disease risks and comorbidities, atrial dilation/dysfunction/fibrosis).

ESC IIaC (LoE C, GoR 5)

• In patients with AF, it is recommended to evaluate AF-related symptoms (including weakness, fatigue, exertional dyspnea, palpitations, chest pain) using the modified EHRA symptom scale before and after initiating treatment to assess AF burden and treatment efficacy [30, 31].

ESC I C (LoE C, GoR 4)

Comment: The modified EHRA classification is presented in Table P1 of Appendix G1.

ESC I C (LoE C, GoR 4)

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition:

To establish the diagnosis of AF, it is necessary to have a registered episode of arrhythmia in 12 leads or a recording of ≥30 seconds duration on single- or multi-lead ECG recording devices with characteristic features:

• Absolutely irregular RR intervals (not recorded in cases of a combination of AF and 3rd-degree AV block [Frederic syndrome]).

• Absence of distinct P waves on the ECG. In individual leads – most frequently in lead V1 – some regular atrial electrical activity is occasionally detected.

• The duration of the atrial cycle (if determined), i.e., the interval between two consecutive atrial activations (f-waves), is usually variable and less than 200 ms, which corresponds to an atrial rate of more than 300 beats per minute.

Characteristic ECG criteria for AFL are:

• Regular atrial rhythm (F waves with a cycle of less than 240 ms) at a rate of 250–350 per minute with identical or varying RR intervals. In some cases, the ventricular rate may vary significantly (usually, a fixed AV conduction ratio from 4:1 to 2:1 is observed, rarely 1:1).

• The presence of F waves that, in typical AFL, have a "sawtooth" curve appearance, particularly visible in the inferior leads (II, III, aVF).

Comment: In many patients, the diagnosis of AF is straightforward, and the arrhythmia manifests with typical symptoms accompanied by characteristic ECG changes on a standard 12-lead ECG recording. Diagnosis becomes more challenging in the context of asymptomatic episodes or AF detected during prolonged electrocardiographic monitoring.

The duration of the arrhythmia recorded during prolonged electrocardiographic monitoring required to establish a diagnosis of AF is not strictly defined.

The generally accepted standard for diagnosing AF is an arrhythmia recording on a 12-lead ECG of 10 seconds or more, while the consensus recommendation requires an arrhythmia duration of 30 seconds or more on single- or multi-lead ECG devices.

2.1 Complaints and Anamnesis

Symptoms in AF/AFL are quite non-specific and may occur in other supraventricular arrhythmias and other cardiovascular pathologies. The most frequent ones include: palpitations, dyspnea, chest discomfort, sleep disorders, drowsiness, fatigue, and psychosocial disorders. In a number of patients, there is a complete absence of any symptoms, and the first manifestation of AF may be an ischemic stroke (IS) or transient ischemic attack (TIA).

• Patients with suspected AF require a comprehensive medical and family history taking to assess familial predisposition and the presence of risk factors for AF/AFL development [32, 33].

ESC IB (LoE B, GoR 2)

Comment: Individuals undergoing screening should be informed about the clinical significance of AF and the need for treatment if arrhythmia is detected. If screening is positive, it is recommended to provide a structured diagnostic scheme to confirm the diagnosis of AF and prescribe optimal therapy.

2.2 Physical Examination

• All patients with AF are recommended to undergo resting pulse palpation to detect asymptomatic AF/AFL paroxysms [34, 35]

RSC IC (LoE C, GoR 5)

• In all patients with AF, it is recommended to perform a thorough physical examination, determine anthropometric data to identify overweight/obesity, and detect comorbidities [36].

RSC IC (LoE C, GoR 5)

2.3 Laboratory Diagnostics

Laboratory diagnostic methods are not required to verify the diagnosis of AF/AFL; however, a detailed examination of the patient, including laboratory tests, is necessary for all patients with documented AF/AFL if there are indications for long-term anticoagulant therapy (ACT). This issue will be discussed in more detail in Section 2.5.1, "Evaluation of patients with AF before prescribing anticoagulant therapy."

In addition, a set of laboratory tests is necessary to exclude concomitant extracardiac pathology in patients before initiating pharmacotherapy and at various stages of treatment.

• All patients with AF/AFL are recommended to undergo a general (clinical) urinalysis, a complete blood count (CBC) with assessment of hemoglobin and hematocrit levels, red blood cell, white blood cell, and platelet counts, and erythrocyte sedimentation rate as part of the initial evaluation, upon admission to the hospital, and during follow-up to determine the activity level of comorbid conditions [37].

RSC IC (LoE C, GoR 5)

• All patients with AF/AFL are recommended to undergo a general therapeutic biochemical blood test (levels of potassium, sodium, glucose, creatinine, total protein, urea, uric acid, total bilirubin, direct and indirect bilirubin in the blood, and determination of aspartate aminotransferase and alanine aminotransferase activity in the blood) as part of the initial evaluation, upon admission to the hospital, and during follow-up to determine the activity level of comorbid conditions [37].

RSC IC (LoE C, GoR 5)

• All patients with AF/AFL are recommended to have a blood thyroid-stimulating hormone (TSH) test to evaluate thyroid function as part of the initial evaluation, and during follow-up in patients receiving Amiodarone** therapy, to clarify thyroid function status [37].

RSC I C (LoE C, GoR 5)

Comment: blood thyroid-stimulating hormone (TSH) testing is also recommended for patients with AF/AFL if the nature of the arrhythmia changes: increased frequency of paroxysms, ineffectiveness of previously effective rate-control therapy in persistent/permanent forms, etc.

• Patients with AF/AFL and clinical presentation of HF are recommended to consider testing for N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the blood as part of the initial evaluation upon admission to the hospital for mortality risk stratification [37].

RSC IC (LoE C, GoR 5)

• All patients with AF/AFL are recommended to undergo a coagulogram (screening hemostasis test) (activated partial thromboplastin time (APTT), determination of the international normalized ratio (INR)) as part of the initial evaluation, upon admission to the hospital, and subsequently during follow-up to diagnose hemostatic disorders and predict bleeding risk [37].

RSC IC (LoE C, GoR 5)

• All patients with AF/AFL scheduled for interventional or surgical treatment, patients with moderate or severe anemia, and those with suspected bleeding are recommended to undergo ABO blood grouping, Rhesus factor (Rh0/D antigen) testing, C, c, E, e, C^w, K, k antigen phenotyping, and anti-erythrocyte antibody screening upon admission to the hospital for the selection of compatible donor blood in case a decision is made to transfuse red blood cells or fresh frozen plasma [37].

RSC IC (LoE C, GoR 5)

• All patients with AF/AFL are recommended to undergo hepatitis B virus surface antigen (HbsAg) testing in the blood, hepatitis C virus antibody testing in the blood, Treponema pallidum antibody testing in the blood, human immunodeficiency virus HIV-1 IgM and IgG antibody testing in the blood, and human immunodeficiency virus HIV-2 IgM and IgG antibody testing in the blood as part of the initial evaluation upon admission to the hospital to rule out association with HIV infection, hepatitis, or syphilis [37].

RSC IC (LoE C, GoR 5)

2.4 Instrumental Diagnostics

• To confirm the presence of AF, all patients with suspected AF are recommended to undergo electrocardiography [38, 39, 628].

ESC IB (LoE C, GoR 5)

• Patients older than 65 years are recommended to undergo ECG recording for AF screening during routine check-ups for comorbid cardiac conditions every 12 months [40-44, 628]

ESC IB (LoE B, GoR 3)

• Performing ECG screening at least once every 12 months is recommended for individuals aged ≥75 years or those at high risk of stroke to detect AF [44-46, 628].

ESC IIa (LoE B, GoR 3)

• Patients receiving antiarrhythmic therapy are recommended to undergo 12-lead ECG recording at least once every 12 months to evaluate treatment safety and efficacy [34, 628].

RSC IC (LoE C, GoR 5)

ESC IB (CQR A, LOR 2)

Comment: An atrial high-rate episode (AHRE) is an event meeting programmed or preset criteria, recorded by the atrial lead of intracardiac devices that allow automatic continuous monitoring of atrial rhythm and store tracking data. AHREs recorded by such devices must be visually verified because some may be artifacts. To exclude such artifacts, the duration of an AHRE is generally required to be ≥5 minutes. When AHRE or subclinical AF is detected, it is recommended to check the electrograms/ECG traces for artifacts or other causes of false detection. Long episodes of AHRE/subclinical AF (at least 5–6 min) are associated with a high risk of clinical AF [48, 49], ischemic stroke [48, 50], major adverse cardiovascular events [51], and cardiovascular death [52]. In selected patients with prolonged AHRE episodes (≥24 h) and high and very high risk of ischemic stroke, continuous OAC therapy may be considered (those with a history of ischemic stroke and/or age ≥75 years, CHA2DS2-VASc ≥3 points (≥2 points in males), and additional risk factors not accounted for in CHA2DS2-VASc, such as CKD, elevated biomarker levels, or spontaneous echo contrast on transthoracic echocardiography (TTE) in a dilated left atrium).

• Long-term electrocardiographic monitoring (Holter ECG monitoring) is recommended for symptomatic patients to assess the adequacy of heart rate control and clarify the relationship between AF episodes and symptoms [53].

RSC IC (LoE C, GoR 5)

• All patients with AF are recommended to undergo echocardiography to assess cardiac structure and function [54, 629].

RSC IC (LoE C, GoR 5)

• Patients with TIA or ischemic stroke are recommended to undergo screening via resting ECG followed by electrocardiographic monitoring (Holter ECG monitoring) for at least 72 hours to detect AF [31, 33].

ESC IB (LoE C, GoR 4)

• In patients with cryptogenic stroke, it is recommended to consider additional electrocardiographic monitoring using non-invasive monitors or implantable cardiac monitors*** (loop recorders) to detect asymptomatic AF [55].

RSC IIa (LoE B, GoR 2)

• Contrast-enhanced computed tomography of the left atrium and pulmonary veins (LA CT) is recommended to be considered in selected AF patients to evaluate LA anatomy (e.g., prior to cardiac left atrial appendage occluder implantation or catheter ablation), and to rule out intracardiac thrombosis as an alternative to transesophageal echocardiography when the procedure cannot be performed prior to catheter ablation or cardioversion [56, 57].

RSC IIa (LoE A, GoR 1)

2.5 Other Procedures

Before prescribing any antithrombotic agent, patients must undergo evaluation aimed at ruling out anemia, assessing liver and kidney function, and identifying potential sources of bleeding. Special attention should be paid to erosive and ulcerative gastrointestinal lesions, liver diseases, urolithiasis, inflammatory genitourinary diseases, chronic hemorrhoids, malignancies, uterine myomas, and aneurysms of the aorta and its branches, including intracranial arteries. All patients with hematuria are indicated to undergo ultrasound of the kidneys and urinary tract to rule out urolithiasis, tumors, inflammatory diseases, etc. Women with a history of abnormal uterine bleeding are indicated for an obstetrician-gynecologist consultation/examination to rule out dysfunctional bleeding and tumors as the cause of bleeding. Patients with refractory hypertension or diabetes mellitus are indicated for an ophthalmologist consultation/examination. In complex cases, the decision to prescribe antithrombotic agents should be made by a multidisciplinary team of specialists in relevant fields.

• All patients prior to the initiation of oral anticoagulants are recommended to undergo a complete blood count (CBC) to rule out anemia and thrombocytopenia [58-65]

RSC IC (LoE B, GoR 2)

Comment: The use of oral anticoagulants in patients with thrombocytopenia and anemia is presented in Appendix A3, Table P6.

• All patients are recommended to undergo blood tests for aspartate aminotransferase, alanine aminotransferase, total bilirubin, and total protein before prescribing oral anticoagulants to rule out liver disease [58, 59, 61–63, 65].

RSC IC (LoE C, GoR 5)

Comments: Severe liver disease/liver cirrhosis increases the risk of bleeding due to the development of coagulopathy. In the presence of liver cirrhosis, its severity must be assessed using the Child-Pugh score, which includes both clinical factors (presence of encephalopathy and ascites) and laboratory parameters (total bilirubin, albumin, INR). The Child-Pugh scale is provided in Appendix G1, Table P2. It is important to remember that all direct oral anticoagulants (DOACs) are contraindicated in patients with Child-Pugh class C liver cirrhosis. The prescription of rivaroxaban** is contraindicated in patients with Child-Pugh class B liver cirrhosis. Apixaban**, dabigatran etexilate**, and edoxaban may be used with caution in patients with class B cirrhosis. The use of vitamin K antagonists (VKAs) in patients with severe liver disease and associated coagulopathy is challenging due to the baseline elevation of INR and difficulties in its subsequent assessment; therefore, prescribing VKAs to patients with severe liver disease is contraindicated [66-68].

• All patients are recommended to undergo a blood creatinine test with creatinine clearance calculation using the Cockcroft-Gault formula before prescribing oral anticoagulants to select the optimal oral anticoagulant and determine the DOAC dose [58, 59, 61–65].

ESC IА (LOCR B, LOE 2)

Comments: in general clinical practice, the CKD-EPI formula is used to calculate the glomerular filtration rate. However, in randomized trials with direct oral anticoagulants (DOACs), renal function was evaluated using the Cockcroft-Gault formula, based on which drug dose adjustments were made and contraindications to DOAC administration were determined.

• All patients are recommended to have their baseline INR determined prior to prescribing oral anticoagulants to rule out impaired hepatic synthesis of clotting factors [58, 61-63, 65, 69].

RSC IC (LoE B, GoR 2)

• All patients are recommended to undergo a general (clinical) urinalysis (to rule out hematuria and albuminuria) before prescribing oral anticoagulants [58, 61-63, 65].

RSC IC (LoE C, GoR 5)

• All patients with a history of gastrointestinal bleeding, erosive and ulcerative lesions of the esophagus, stomach, or duodenum, as well as symptoms of dyspepsia, are recommended to undergo esophagogastroduodenoscopy to rule out peptic ulcer exacerbation, acute erosions, or other pathology associated with an increased risk of bleeding [58, 65, 70, 71].

RSC IC (LoE C, GoR 5)

Comments: Patients diagnosed with iron deficiency anemia who have no obvious sources of bleeding should be evaluated for the need for colonoscopy to rule out bowel diseases as potential sources of bleeding [70-72].

• Patients who have suffered a stroke within the previous 8 weeks, as well as those with pronounced residual neurological deficits and no neuroimaging data to rule out the hemorrhagic nature of the stroke and vascular malformations, are recommended to undergo computed tomography (CT) of the brain and/or magnetic resonance imaging (MRI) of the brain and magnetic resonance angiography of intracranial vessels [58, 73-75].

RSC IC (LOCR C, LOE 4)

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

3.1 Conservative Treatment

3.1.1 Recommendations for stroke and systemic thromboembolism prevention in patients with atrial fibrillation

A major problem for patients with AF is the high risk of ischemic stroke (IS) and systemic thromboembolism, which are most often of cardioembolic origin due to thrombus formation in the left atrial appendage, and less frequently in the left atrial cavity. Of all thromboembolic complications in patients with AF, more than 90% are accounted for by IS. Among ischemic strokes, cardioembolic stroke has the most unfavorable prognosis due to high mortality and the development of permanent disability.

3.1.1.1 Main provisions on the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation

• All patients with AF are recommended to have their risk of thromboembolic complications (TECs) (IS, TIA, and systemic thromboembolism) assessed using the CHA₂DS₂-VASc score [58, 65, 76–79].

ESC IA (LOCR C, LOE 4)

Comments: The CHA₂DS₂-VASc score is presented in Table P3 of Appendix G1.

Since 2024, European experts have proposed using the following for TEC risk stratification: the CHA₂DS₁-VA score (an equivalent of CHA₂DS₃-VASc, which excludes female sex as a risk factor). From the experts' perspective, female sex is not an independent risk factor, but rather an age-dependent risk modifier. Indeed, to date, European countries have seen a significant decrease in the incidence of stroke in patients with AF, gender differences no longer reach statistical significance, and women and men now receive anticoagulation with equal frequency. The FinACAF registry, conducted in a European population, showed that as of 2007, the CHA2DS2-VASc score outperformed CHA2DS2-VA in predicting stroke risk, but as of 2018, it no longer did. Russian experts do not have data on such a dramatic decrease in strokes in the Russian Federation as in Europe. According to the Russian EPOCH-CHF registry (2022), patients in Russia are younger and sicker, the prevalence of AF in women is 1.5 times higher than in men, and only 24% of patients receive anticoagulant therapy. In addition, ESC experts recommend using a score validated in the relevant population (CHA₂DS₂-VA as one of the options, not the only one). In the Russian Federation, the CHA₂DS₈-VA score has not been validated.

The prescription of anticoagulant therapy based on the CHA₂DS₂-VA score has not been evaluated in any randomized trial; ESC recommendations for its use in 2024 are based solely on expert opinion.

Finally, in the guidelines approved by the Russian Ministry of Health in November 2024 (NSTE-ACS; STEMI, Stable CAD), it is recommended to use the CHA₂DS₂-VASc score. To avoid contradictions, including during the evaluation of physicians' work by insurance companies and in the assessment of treatment quality control, Russian experts decided to continue using the CHA₂DS₄-VASc score, at least until the next guideline revision.

• All patients with AF/AFL are recommended to undergo bleeding risk assessment prior to initiating antithrombotic therapy. It is recommended to actively search for modifiable and non-modifiable bleeding risk factors in order to identify patients at high risk of bleeding [58, 60, 65, 79–83].

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

Comments: The purpose of identifying patients at high risk of bleeding is primarily not to withhold oral anticoagulants, but to determine an individual management regimen that includes measures to correct modifiable risk factors and monitor therapy safety.

To assess bleeding risk, several scales have been proposed, of which the most widely used is the HAS-BLED score (presented in Table P4 of Appendix G1). A HAS-BLED score ≥3 indicates a high risk of bleeding. Nevertheless, a calculated high bleeding risk should not be the sole limitation to prescribing oral anticoagulants. First and foremost, the patient should be evaluated to identify potential sources of bleeding and correct modifiable risk factors, and in the presence of non-modifiable factors, the drug best suited to the patient's clinical characteristics (comorbidities, stroke risk, preferred dosing regimen) should be chosen.

A table listing modifiable and non-modifiable bleeding risk factors is presented in Table P1 of Appendix A3.

• Long-term administration of oral anticoagulants for the prevention of TECs is recommended for male patients with a CHA₂DS₂-VASc score ≥2 and female patients with a CHA₃DS₄-VASc score ≥3 [61, 62, 63–89].

ESC IA (LoE B, GoR 2)

• The prescription of oral anticoagulants for the prevention of TECs is recommended for men with CHA₂DS₂-VASc = 1 and women with CHA₃DS₄-VASc = 2, taking into account individual patient characteristics and preferences [77, 90–94].

ESC IIaB (LoE B, GoR 2)

Comments: The decision to prescribe oral anticoagulants in this category of patients should be made based on an individual risk/benefit assessment. It should be borne in mind that the main advantage of oral anticoagulants, according to randomized clinical trials, has been demonstrated primarily in patients at high risk of thromboembolic events (CHA₂DS₂-VASc ≥2 in men and CHA₂DS₂-VASc ≥3 in women). The true incidence of stroke and systemic embolism in male patients with a CHA₂DS₂-VASc score of 1 varies significantly, ranging from 0.5 to 2.8% per year, which, along with the assessment of individual bleeding risk, must be taken into account when deciding on anticoagulant therapy in this category of patients. Appendix B, Table P1 presents an algorithm designed to simplify the decision-making process for prescribing oral anticoagulants to this category of patients. 

• The prescription of oral anticoagulants for the prevention of thromboembolic events is recommended for all patients with hypertrophic cardiomyopathy, regardless of their CHA₂DS₂-VASc score [563].

ESC IB (LoE A, GoE 3)

• The prescription of oral anticoagulants for the prevention of thromboembolic events is recommended for all patients with amyloidosis, regardless of their CHA₂DS₂-VASc score [630, 631]

ESC IB (LoE C, GoE 4)

• When VKA therapy is prescribed, it is recommended to achieve the maximum time in the therapeutic range (TTR) for INR values within the therapeutic range (2.0–3.0), which should be regularly evaluated [95-103].

ESC IA (LoE B, QoE 3)

Comments: during the titration of an individual warfarin** dose, it is necessary to monitor the INR value every 3 days until two consecutive similar INR values within the target range are obtained. This indicates that the therapeutic anticoagulation range has been reached. Subsequently, INR monitoring should be performed once every 4–6 weeks. In the event of excessive hypocoagulability, a change in the warfarin** dose, or the initiation of concomitant therapy that may affect the INR level, its value must be determined within 4–5 days to confirm that the INR remains within the therapeutic range.

The algorithm for selecting the therapeutic dose of warfarin** is given in Appendix B, Table P2 [103].

An effort should be made to maintain the INR within the target range of 2.0–3.0 in all patients (including elderly patients). The optimal time in the therapeutic range (TTR) for INR values is considered to be ≥70%. Previously accepted INR values of 1.6–2.2 for elderly patients are currently considered unjustifiably low due to a twofold increase in the risk of stroke at INR values <2.0.

Lower INR values within the target range (2.0–2.5) should be targeted when warfarin** is used in combination with antithrombotic drugs (antiplatelet agents other than heparins B01AC) (acetylsalicylic acid*** and/or clopidogrel**) or when therapy is resumed after bleeding.

Comments: Algorithms for switching between oral anticoagulants are presented in Appendix B, Table P3 [65].

• In patients with AF (excluding patients with mechanical heart valve prostheses or moderate/severe mitral stenosis) who have not previously received anticoagulant therapy, the recommended first-line drugs are apixaban**, dabigatran etexilate**, rivaroxaban**, or edoxaban (in the absence of contraindications) [61-63, 104-108].

ESC IA (LoE A, GoR 1)

• Patients with AF are recommended to be prescribed the full dose of apixaban** (5 mg twice daily), dabigatran etexilate** (150 mg twice daily), rivaroxaban** (20 mg once daily), or edoxaban (60 mg once daily) as providing maximum protection against stroke (except for special indications) [61-63, 106, 108, 109].

RSC IA (LoE B, GoE 1)

Comments: when prescribing NOACs, one should strive to prescribe the full dose of the drugs, restricting the use of reduced doses to special indications:

1) apixaban**: 2.5 mg twice daily in patients with CKD and a creatinine clearance of 15–29 ml/min, or if the patient has 2 or more of the following criteria: age ≥80 years, body weight ≤60 kg, or blood creatinine concentration ≥133 µmol/l;

2) dabigatran etexilate**: 110 mg twice daily in patients older than 80 years, as well as in cases of concomitant use of verapamil**; at the physician's discretion, based on the individual ratio of thrombotic and bleeding risks, the dose may be reduced in case of an increased risk of bleeding (especially gastrointestinal bleeding), in patients with a creatinine clearance of 30–50 ml/min, and in patients aged 75–80 years.

3) rivaroxaban**: 15 mg once daily at a creatinine clearance of 15–49 ml/min;

4) edoxaban: 30 mg once daily if one of the following criteria is met: creatinine clearance 15–49 ml/min, body weight ≤60 kg, concomitant use of strong P-glycoprotein inhibitors (cyclosporine**, erythromycin, ketoconazole).

Comment: The decision on the need for anticoagulant therapy and the choice of a specific drug in patients with stage V CKD (with creatinine clearance <15 ml/min or on regular dialysis) should be made individually by a multidisciplinary team of specialists, based on the balance of thrombosis and bleeding risks. Patients in this category are characterized by a very high risk of both thrombotic and bleeding complications. The advisability of anticoagulant therapy in stage V CKD patients has not been proven in RCTs, and the results of observational studies are contradictory. Data on optimal oral anticoagulants and their doses are based on established clinical practice and pharmacokinetic studies; comparative RCTs have not been completed or lack sufficient statistical power.

In the Russian Federation, the only oral anticoagulant approved for patients with stage V CKD (CrCl <15 ml/min, or on regular dialysis) is warfarin**. Recently, the results of small studies have emerged indicating that apixaban** and rivaroxaban** are at least non-inferior to warfarin** in terms of the efficacy-safety ratio in patients with stage 5 CKD.

• If, during warfarin** therapy, INR values are frequently outside the target range (time in therapeutic range ≤70%), the recommended treatment is apixaban**, dabigatran etexilate**, rivaroxaban**, or edoxaban (if there are no contraindications) [61-63, 100, 101, 110, 111].

ESC IIaA (LoE A, GoE 1)

Comments: Algorithms for switching between oral anticoagulants are presented in Appendix B, Table P3 [65].

ESC IIIB (LoE C, GoE 4)

• Antiplatelet agents (acetylsalicylic acid**, clopidogrel**) are not recommended for the prevention of stroke and systemic embolism in patients with AF [82, 85, 112].

ESC IIIA (LoE B, GoE 1)

• For patients with AF and moderate or severe mitral stenosis, or with a mechanical heart valve prosthesis, only VKAs are recommended for the prevention of thromboembolic events [61-63, 114–120].

ESC IB (LoE B, GoR 2)

Comments: if warfarin** is prescribed to patients with moderate or severe mitral stenosis, the therapeutic INR range is 2.0–3.0.

In patients with a mechanical heart valve prosthesis***, the target INR is determined by the position and type of the prosthesis, as well as the presence of additional risk factors for thromboembolic events. AF is one such additional risk factor, which dictates higher target INR values. Accordingly, when a modern bileaflet mechanical prosthesis*** is implanted in a patient with AF, the target INR is 3 (acceptable range 2.5–3.5) regardless of the prosthesis position (mitral/tricuspid or aortic) [121]

The duration of warfarin** therapy in patients with non-rheumatic AF after mitral bioprosthetic valve implantation*** / aortic bioprosthetic valve implantation*** is 3 months, after which NOACs may be prescribed.

• Apixaban**, dabigatran etexilate**, rivaroxaban**, and edoxaban are not recommended for the prevention of thromboembolic events in patients with mechanical heart valve prostheses*** [61-63, 87, 115, 120, 122-124].

ESC IIIB (LoE C, GoE 4)

• Apixaban**, dabigatran etexilate**, rivaroxaban**, and edoxaban are not recommended for the prevention of thromboembolic events in patients with moderate and severe mitral stenosis [61-63, 87, 122–124].

ESC IIIC (LoE B, GoE 1)

3.1.1.2 Stroke and Systemic Thromboembolism Prevention During Cardioversion

Restoration of sinus rhythm in patients with AF can be complicated by stroke or systemic thromboembolism. The incidence of such complications averages 5-7%, whereas prophylactic anticoagulant therapy can reduce this risk to less than 1%. Anticoagulant therapy should be administered according to general guidelines in patients with a first episode of AF, including those precipitated by triggers such as pulmonary embolism, sepsis, major surgery, or myocardial infarction. It should be borne in mind that NOACs are at least as effective in preventing thromboembolic complications of cardioversion as warfarin**. When NOACs are used for pharmacological support during cardioversion, the patient must be thoroughly informed about the importance of treatment adherence.

The risk of normalization-related thromboembolism largely depends on the duration of the AF episode. This parameter is the primary determinant of the anticoagulant support strategy for cardioversion.

The algorithm for antithrombotic support of cardioversion is presented in Table P4 of Appendix B.

• When cardioversion is planned, all patients not receiving oral anticoagulants are recommended to promptly initiate therapy with a rapid-onset oral anticoagulant (apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban, or #enoxaparin sodium** or unfractionated heparin sodium**). #Enoxaparin sodium** and heparin sodium** should be used in doses approved for the treatment of venous thrombosis (therapeutic doses of heparin and its derivatives are given in Table P3 of Appendix A3) [125-129].

ESC IB (LoE C, GoR 4)

Comments: among all low-molecular-weight heparins (ATC code B01AB Heparin group), preference is given to #enoxaparin sodium**, as data from small randomized trials (ACUTE II and ACE) are available for it [127, 128]. For #dalteparin sodium, only observational studies and a Japanese randomized trial using a reduced dose are available [129]. If a patient not receiving anticoagulant therapy has an indication for emergency cardioversion due to hemodynamic instability (acute left ventricular failure, pulmonary edema) or acute myocardial ischemia, administration of heparin sodium** or #enoxaparin sodium** should be initiated as soon as possible at doses approved for the treatment of venous thrombosis (Table P3, Appendix A3).

• If the duration of the AF episode is 48 hours or more, or if the duration of the rhythm disturbance is unknown, it is recommended to administer anticoagulant therapy for at least 3 weeks prior to cardioversion. For this purpose, oral anticoagulants are recommended: apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban, or warfarin** (INR 2.0-3.0). Initiation of warfarin** therapy should be combined with treatment with heparin sodium** or #enoxaparin sodium** at doses recommended for the treatment of venous thrombosis (Table P3, Appendix A3) until the INR reaches the target range. Anticoagulant therapy is indicated regardless of the CHA₂DS₂-VASc score and the method of sinus rhythm restoration (pharmacological or electrical) [125, 126, 130, 131].

ESC IB (LoE B, GoR 2)

Comments: in most cases, the duration of treatment with heparin sodium** or #enoxaparin sodium** during warfarin** titration should be at least 5 days. However, if the target INR is reached earlier, the duration of treatment with heparin sodium** or #enoxaparin sodium** may be shortened.

Despite 3 weeks of oral anticoagulant therapy, whenever technically feasible, transesophageal echocardiography (TEE) should preferably be performed prior to cardioversion, especially in patients at high risk for thromboembolic events and in cases of suspected patient non-adherence to NOAC therapy.

• If cardioversion is planned for an AF episode of less than 48 hours' duration in a patient not receiving anticoagulant therapy, it is recommended to immediately initiate a rapid-onset oral anticoagulant (apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban) or the administration of heparin sodium** or #enoxaparin sodium**. #Enoxaparin sodium** and heparin sodium** should be used at doses approved for the treatment of venous thrombosis (Table P3, Appendix A3) [125, 130-134].

ESC IB (CGR B, LOR 3)

Comments: NOACs should be administered at least 2-4 hours before cardioversion. If apixaban** is chosen for antithrombotic support of cardioversion and sinus rhythm restoration is planned 2-4 hours after the first dose, the first dose of apixaban** should be increased to 10 mg, followed by the standard dose of 5 mg twice daily (if criteria for dose reduction are met, a loading dose of 5 mg and a maintenance dose of 2.5 mg twice daily should be used). If a loading dose is not administered, cardioversion may be performed only after taking 5 standard doses of apixaban** [135].

• As an alternative to prolonged anticoagulation prior to cardioversion, it is recommended to rule out thrombus in the left atrium (LA) and LA appendage using TEE or, if TEE is not feasible, contrast-enhanced CT of the LA and pulmonary veins against the background of a pre-established therapeutic level of anticoagulation [125, 135].

ESC IB (LoE B, GoR 2)

• If TEE / contrast-enhanced CT of the LA and pulmonary veins reveals a thrombus in the LA appendage or cavity, cardioversion is not recommended [125, 135].

ESC IB (LoE B, GoR 2)

Comments: if cardioversion is delayed due to detected LA appendage or cavity thrombosis, follow-up TEE to assess thrombus dynamics is advisable after 3-4 weeks of oral anticoagulant treatment.

• If repeat TEE / contrast-enhanced CT of the LA reveals no thrombus, it is recommended to perform cardioversion and continue anticoagulant therapy [125, 135].

ESC IB (LoE B, GoR 2)

Comments: if a thrombus persists on repeat transesophageal echocardiography/contrast-enhanced CT of the LA, cardioversion must not be performed. Alternative management strategies, such as ventricular rate control, should be considered. There is no evidence base to guide the optimal antithrombotic therapy strategy in patients with persistent thrombus in the left atrial appendage or cavity. Persistence of a thrombus after 3-4 weeks of oral anticoagulants does not always mean treatment failure; in some cases, additional time and compliance assessment are required. To date, there is no evidence of efficacy for switching oral anticoagulants (switching from one NOAC mechanism of action to another, switching to VKAs or low-molecular-weight heparins [ATC code B01AB Heparin group]).

• In patients with an AF episode duration of less than 48 hours, it is recommended to consider early cardioversion without prior TEE / contrast-enhanced CT of the LA and pulmonary veins [135].

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

Comments: recently, accumulating evidence indicates that the risk of thromboembolic events begins to rise after the first 12 hours of AF. When technically feasible, it is advisable to perform TEE / contrast-enhanced CT of the LA even for paroxysms lasting less than 48 hours in patients at high risk for cardioversion-related thromboembolic events (CHA₂DS₂-VAS_C ≥2 in men, ≥3 in women, and/or AF episode duration >12 hours) [136].

• Following cardioversion, it is recommended to continue anticoagulant therapy for at least 4 weeks. If heparin and its derivatives were initially prescribed, it is recommended to switch the patient to oral anticoagulants [130, 132].

ESC IB (LoE C, GoR 4)

Comments: the incidence of stroke/thromboembolic events in patients with an AF paroxysm of less than 24 hours and low thromboembolic risk (CHA₂DS₂-VASc score of 1 for women, 0 for men) is quite low. For such patients, withholding anticoagulation for 4 weeks post-cardioversion may be considered on an individual basis [137]. This approach is based on expert opinion and has not been validated in randomized trials. If the decision is made to withhold oral anticoagulants after cardioversion, anticoagulation should still be administered prior to the procedure.

• Four weeks after cardioversion, it is recommended to decide on the need for continuous oral anticoagulant therapy based on the thromboembolic risk assessed using the CHA₂DS₂-VASc score. In patients with a high thromboembolic risk (2 or more points for men, 3 or more points for women on the CHA₂DS₂-VASc score), as well as in patients with a history of intracardiac thrombus, oral anticoagulant therapy is recommended to be continued indefinitely – even if sinus rhythm is maintained after cardioversion [130, 138].

ESC IB (LoE C, GoR 4)

• When performing cardioversion in patients with atrial flutter, the same anticoagulation regimen is recommended as in patients with atrial fibrillation [139].

ESC IC (LoE B, GoR 3)

• Apixaban**, dabigatran etexilate**, rivaroxaban**, and edoxaban are not recommended for anticoagulant support of cardioversion in patients with mechanical heart valve prostheses [61–63, 87, 115, 131].

ESC IIIC (LoE B, GoR 2)

Comments: DOACs are not recommended for anticoagulant support of cardioversion in patients with moderate-to-severe or severe mitral stenosis due to the lack of relevant evidence.

3.1.1.3 Secondary stroke prevention in patients with atrial fibrillation and atrial flutter

• In patients receiving oral anticoagulators who develop symptoms of acute stroke, it is recommended to perform neuroimaging (brain computed tomography and/or brain magnetic resonance imaging) to determine the stroke type, assess its size and localization [58, 65, 140–146].

RSC IIaB (LoE C, GoR 4)

Comments: Brain CT/MRI in patients with acute stroke symptoms helps rule out hemorrhagic stroke or intracranial hemorrhage, hemorrhagic transformation of ischemic stroke during anticoagulant therapy, and assesses the volume and localization of the necrosis/ischemia lesion, which determines the timing for starting/resuming oral anticoagulant therapy. In patients with severe or moderate stroke and a large ischemic lesion, serial neuroimaging is recommended when deciding to resume anticoagulant therapy to rule out hemorrhagic transformation.

• If symptoms of acute stroke develop in patients receiving oral anticoagulators, it is recommended to temporarily interrupt drug administration for a period determined by a multidisciplinary board, which may include a cardiologist, neurologist, and radiologist [142–144, 147, 148].

RSC IIaB (LoE C, GoR 4)

Comments: the first days following an acute ischemic stroke are characterized by an increased risk of both recurrent ischemic events and hemorrhagic complications due to blood-brain barrier disruption within the ischemic lesion. The feasibility of using oral anticoagulators in the first days of ischemic stroke is determined by balancing these risks. The larger the size of the cerebral infarction lesion, the higher the risk of hemorrhagic transformation.

Patients with a recent ischemic stroke were not previously included in RCTs; therefore, expert consensus on the timing of oral anticoagulant resumption is based on observational registry data and clinical judgment. For a long time, the clinical approach predominated (Table P5 of Appendix B), where the risks of hemorrhagic transformation (and consequently the timing of anticoagulation initiation) were assessed based on the severity of neurological deficit (the Diener rule). Thus, in patients with TIA, experts consider it acceptable not to interrupt anticoagulant therapy, whereas in patients with ischemic stroke, the drug interruption period ranged from 3–4 to 12–14 days depending on the neurological deficit severity determined by the National Institutes of Health Stroke Scale (NIHSS) score (Table P5 of Appendix G1) [147, 148]. For moderate and severe strokes, repeat neuroimaging is required to rule out hemorrhagic transformation.

Currently, an approach focused on the characteristics of the cerebral infarction lesion is beginning to dominate, placing neuroimaging results at the forefront. For example, from a neuroimaging perspective, a lesion is considered large if it involves the entire supply territory of one or more cerebral arteries (anterior, middle, or posterior). A detailed classification of stroke lesion sizes is provided in the ELAN study design description.

To date, several randomized trials (TIMING [564], ELAN [565], START [566], OPTIMAS [567]) and a number of observational studies [643] have been completed, demonstrating that earlier resumption of DOACs is at least non-inferior to the classical delayed resumption approach. For instance, in one of the largest studies, ELAN, resuming DOACs within the first 48 hours for small and medium-sized lesions and within 6–7 days for large ischemic stroke lesions was non-inferior to the "standard" approach at 1 month of follow-up, and showed superiority at 3 months regarding the composite endpoint of recurrent ischemic stroke, systemic embolism, major extracranial hemorrhage, symptomatic intracranial hemorrhage, and vascular death.

Thus, the decision on the timing of anticoagulant resumption should be made individually, taking into account the severity and stability of neurological status, the size and location of the infarction lesion, the presence and type of hemorrhagic transformation, and additional risk factors shifting the balance toward a recurrent ischemic or hemorrhagic event [568].

• In patients with atrial fibrillation, it is not recommended to prescribe heparin and its derivatives immediately after an ischemic stroke [569].

ESC IIIB (LoE B, GoR 1)

• In patients with atrial fibrillation and acute ischemic stroke, prior to initiating or resuming oral anticoagulant therapy, it is recommended to prescribe acetylsalicylic acid** (in the absence of contraindications) to reduce the risk of recurrent ischemic stroke and death [149, 150, 649–652].

ESC IIaB (LoE B, GoR 2)

• In patients with atrial fibrillation and acute ischemic stroke occurring during anticoagulant therapy, systemic thrombolysis is not recommended [151–154].

ESC IIIC (LoE C, GoR 4)

Comments: Thrombolysis may be considered in patients taking warfarin** if the INR does not exceed 1.7. In patients taking DOACs, thrombolysis is possible if at least one condition is met: 1) more than 48 hours have passed since the last DOAC dose and renal function is not impaired, 2) the drug is not detected in plasma, 3) parameters reflecting the anticoagulant activity of DOACs are within reference ranges. Quantitative assessment of anticoagulant activity for apixaban**, rivaroxaban**, and edoxaban can be performed by measuring anti-Xa activity; for dabigatran etexilate**, by measuring ecarin clotting time and/or diluted thrombin time (according to ATX – laboratory monitoring of drug therapy (direct anticoagulators) B03.005.007). The closest assay to those mentioned for assessing the anticoagulant activity of dabigatran etexilate** is the determination of thrombin time (its normal level rules out dabigatran etexilate** activity) and/or aPTT (its normal level rules out supratherapeutic, but not therapeutic, activity of dabigatran etexilate**) [136]. Some experts believe that if no more than 12 hours have passed since DOAC intake, thrombolysis should not be performed even with low drug concentration/low anticoagulant activity parameters, as their effect may not have reached its peak yet.

A table of parameters that should be evaluated before administering a reversal agent to terminate the effect of DOACs is presented in P4 of Appendix A3. In patients receiving dabigatran etexilate**, the possibility of thrombolysis should be discussed after inhibiting the anticoagulant effect of dabigatran etexilate** via intravenous administration of its specific reversal agent, idarucizumab.

Another reperfusion therapy option in acute stroke may be thrombectomy, performed primarily in patients showing signs of occlusion of the intracranial internal carotid artery or proximal middle cerebral artery on neuroimaging. Thrombectomy yields the greatest benefit within the first 6 hours and can be performed up to 24 hours in selected patient categories. Indications for the intervention depending on stroke severity, ischemic lesion size, lesion location, and time from symptom onset are outlined in the Clinical Guidelines for Stroke Management.

The number of patients taking oral anticoagulants included in relevant studies is small. Available data indicate that prior anticoagulant therapy per se is not a contraindication to thrombectomy. However, the potential for an increased risk of reperfusion-related bleeding must be taken into account [156, 157].

• In AF patients who have suffered an ischemic stroke or TIA while on anticoagulant therapy, it is recommended to assess and optimize treatment adherence [158].

RSC IC (CGR C, LOR 5)

Comments: currently, there are no data confirming the efficacy of switching from one DOAC to another in a patient who has suffered an ischemic stroke while on anticoagulant therapy. It is necessary to correct other stroke risk factors (smoking cessation, achieving target blood pressure, LDL-C, and glycemia levels, etc.).

• For patients with a history of stroke, it is recommended to prescribe DOACs rather than warfarin** (in the absence of contraindications) [100, 159, 160].

ESC IA (CGR B, LOR 1)

• The prescription of combined therapy with oral anticoagulants and antiplatelet agents in AF patients for the purpose of secondary prevention of ischemic stroke or TIA is not recommended [161-169].

ESC IIIB (CGR B, LOR 2)

• In AF patients with a high risk of ischemic stroke who have suffered an intracerebral hemorrhage, it is recommended to consider resuming oral anticoagulant therapy (preferably DOACs) in the absence of contraindications, based on a multidisciplinary decision, provided that the cause of the hemorrhage has been eliminated and risk factors corrected [74, 75, 170-172].

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

Comments: the decision to resume anticoagulant therapy in an AF patient after an intracerebral hemorrhage should be made by a multidisciplinary team consisting of a neurologist, cardiologist, neurosurgeon, and radiologist. The patient and their family members must be informed about the risks and benefits of resuming oral anticoagulant therapy.

In a patient who has suffered a hemorrhagic stroke, the risk of a subsequent ischemic stroke is often higher than that of a recurrent hemorrhagic event. Observational studies have shown that resuming anticoagulant therapy is associated with a reduced risk of recurrent stroke and lower mortality [74]; randomized controlled trial data are currently insufficient. However, the individual benefit-risk profile of resuming versus withholding anticoagulant therapy may vary. The risk of recurrent intracerebral hemorrhage depends, inter alia, on the location, cause, and severity of the index hemorrhage. Thus, the risk of hemorrhage recurrence is lower if the index event was associated with trauma and the hemorrhage had a subdural or epidural location. If the initial hemorrhage had a lobar or subarachnoid location, the risk of recurrence is higher. From a practical standpoint, assessing the risk of spontaneous hemorrhage recurrence relies primarily on the presence of tomographic signs of cerebral amyloid angiopathy. Factors increasing the risk of recurrent intracerebral hemorrhage are listed in Table P2 of Appendix A3.

According to the expert consensus of various professional societies, the optimal timing for resuming anticoagulant therapy ranges from 2 to 8 weeks after the hemorrhage; in patients at the highest risk of thromboembolic events (mechanical heart valve prostheses, rheumatic valve disease), this period may be shortened to 1-2 weeks [570].

In patients with non-valvular AF following an intracerebral hemorrhage, DOACs may be preferred over VKAs. When resuming anticoagulant therapy in such patients, combinations with antiplatelet agents should be avoided whenever possible; for those receiving VKAs, the INR should be maintained within 2-2.5, with the time in therapeutic range (TTR) being at least 70%. DOACs should be prescribed at the lowest effective doses for stroke and systemic embolism prevention. Blood pressure levels must be monitored, and alcohol intake, which significantly increases the risk of intracerebral hemorrhage, should be avoided.

Comments: in patients with a history of intracerebral hemorrhage for whom a decision has been made not to resume oral anticoagulant therapy due to an uncorrectable cause of a life-threatening hemorrhagic complication, implantation of a cardiac occluder*** in the left atrial appendage (LAA) is recommended [173-175]. It should be remembered that the standard management protocol for patients with a cardiac occluder*** involves a period of antithrombotic therapy (antiplatelet agents and/or oral anticoagulants) following device implantation, which carries a risk of recurrent bleeding.

Optimal tactics for thromboembolic event prevention in patients with atrial fibrillation who have suffered an intracranial hemorrhage (timing of anticoagulant therapy resumption, prognosis after cardiac occluder implantation***) are currently being investigated in randomized controlled trials.

Comments: The prognostic significance of hemorrhagic transformation depends on its type according to the ECASS classification (hemorrhagic infarction or parenchymal hematoma) and the presence of symptoms. Hemorrhagic transformation is an increasingly common phenomenon due to the widespread adoption of reperfusion therapy. Accumulated data [565, 571] indicate that the presence of hemorrhagic infarction (i.e., petechial imbibition) may not require delaying anticoagulant therapy. Patients with parenchymal hematomas were not included in RCTs; in their case, the question of anticoagulant therapy should be decided individually depending on the size of the hematoma, signs of midline shift, and dynamics according to computed tomography.

3.1.1.4 Prevention of bleeding during anticoagulant therapy. Management of patients with acute bleeding occurring during anticoagulant therapy. Antithrombotic treatment in patients with atrial fibrillation and flutter after previous hemorrhagic complications

Bleeding remains the main hazard of oral anticoagulant therapy. Active identification and elimination of bleeding sources, correction of bleeding risk factors, and a rational approach to choosing the antithrombotic therapy regimen help reduce the risk of hemorrhagic complications.

The management algorithm for patients with AF in the event of hemorrhagic complications is presented in Table P6 of Appendix B.

Randomized clinical trials have demonstrated the advantages of DOACs over warfarin** in terms of the development of intracranial hemorrhages [40-42], making DOAC therapy preferable to warfarin**. Apixaban**, dabigatran etexilate** at a dose of 110 mg twice daily, and edoxaban reduced the risk of major bleeding compared with warfarin** [61, 62, 110, 176-177]. The use of rivaroxaban**, dabigatran etexilate** at a dose of 150 mg twice daily, and edoxaban 60 mg once daily was associated with an increased risk of gastrointestinal bleeding compared with warfarin** [61, 63, 178, 179].

No direct comparative randomized trials have been conducted between DOACs, which precludes making strict recommendations regarding the choice of a specific DOAC in terms of its safety profile. The preferred strategy is not the choice of a specific DOAC, but the maximal correction of risk factors and elimination of potential bleeding sources (e.g., a bleeding ulcer or polyp in a patient with gastrointestinal bleeding).

Proton pump inhibitors reduce the risk of upper gastrointestinal bleeding in patients receiving oral anticoagulants (both warfarin** and DOACs) [182, 183]. It is advisable to consider the prophylactic administration of these drugs to patients at high risk for gastrointestinal bleeding. The risk of gastrointestinal bleeding can be assessed using the algorithm recommended by the European Society of Cardiology since 2015 [572, 627]; in patients with comorbid coronary artery disease, for example, the domestic REGATA scale [573] can be used (Table P6 of Appendix G1).

• All patients with AF are recommended to undergo regular assessment of bleeding risk factors with the aim of their maximal correction [60, 65, 79-83].

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

Comment: Modifiable and non-modifiable bleeding risk factors are presented in Table P1 of Appendix A3.

• All patients with arterial hypertension and AF are recommended to achieve the target blood pressure level, which helps reduce the risk of bleeding [165, 184, 185].

ESC IIaB (LoE C, GoR 4)

ESC IIa C (LoE C, LoR 4)

• Routine determination of genetically determined sensitivity to warfarin** is not recommended [189-192].

ESC IIIB (LOCE B, LOE 1)

Comments: Genotyping for warfarin sensitivity** may be advisable in selected patients at high risk of bleeding who have no alternative to warfarin therapy**.

• If bleeding occurs during oral anticoagulant therapy, it is recommended to assess the severity of bleeding, identify the source, and determine how long ago it started [34, 58, 65].

RSC IC (CGR C, LOR 5)

• If bleeding develops in patients receiving anticoagulant therapy, it is recommended to test the total blood hemoglobin level, assess the hematocrit, test the platelet count in the blood, and test the blood creatinine level with calculation of creatinine clearance using the Cockcroft-Gault formula. [58, 61–63, 65]

ESC IIaB (LOCE C, LOE 5)

• If bleeding develops in patients taking VKAs, recommends determination of INR [58, 61–63, 65, 193].

ESC IIaB (LOCE B, LOE 2)

• If bleeding develops in patients taking DOACs, it is recommended to ascertain the time of the last dose intake [58, 65, 194].

ESC IC (LoE C, GoR 5)

Comments: Laboratory tests characterizing the anticoagulant activity of DOACs are advisable if severe bleeding has developed and the administration of reversal agents for DOACs is being discussed. In life-threatening bleeding, measures to reverse the anticoagulant effect of the drugs should be carried out without waiting for the results of the corresponding coagulological tests. The test results can be used subsequently to assess the dynamics of the clinical situation.

A list of parameters that are advisable to evaluate prior to administering a DOAC reversal agent is provided in Table F4 of Appendix A3.

Menadione sodium bisulfite**, available on the domestic pharmaceutical market, is a precursor of vitamin K2, the effect of which develops very slowly; therefore, the administration of menadione sodium bisulfite** for the treatment of acute bleeding associated with VKAs is ineffective. The preferred approach is the administration of coagulation factor II, VII, IX and X concentrate in combination [Prothrombin complex]**, which contains the coagulation factors whose synthesis is blocked by VKAs, as well as proteins C and S.

• In patients with AF presenting with symptoms of acute clinically significant bleeding, it is recommended to discontinue oral anticoagulant therapy until the cause of bleeding is eliminated [58, 65].

ESC IC (LoE C, GoR 5)

• In patients receiving dabigatran etexilate** in the event of life-threatening bleeding or the need for emergency surgery, it is recommended to administer idarucizumab [194, 195].

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

Comments: for patients receiving dabigatran etexilate**, if idarucizumab is unavailable, dialysis/hemodialysis may be considered. For all DOACs in the absence of specific antidotes, coagulation factor II, VII, IX and X concentrate in combination [Prothrombin complex]**, preferably activated, can be used [653, 654]. Neutralization of the anticoagulant effect of the drugs does not exclude the need for standard measures to achieve hemostasis.

• All patients with AF who have experienced an episode of clinically significant bleeding during oral anticoagulant therapy are recommended to have an evaluation of the feasibility of resuming anticoagulant therapy involving all relevant specialists [189-192].

ESC IIa B (CGR C, LOR 4)

Comments: The decision to resume anticoagulant therapy should be made by a multidisciplinary team based on a comparison of the risk and expected severity of recurrent bleeding with the risk of thromboembolism. The concilium should evaluate all options for anticoagulant treatment and other interventions for stroke prevention, and determine the tactics for maximum correction of risk factors for bleeding and stroke. To date, observational study data have accumulated showing that discontinuation of anticoagulant therapy after bleeding is associated with an increased risk of thromboembolic events and mortality. In most cases, resumption of anticoagulant therapy is associated with a more favorable prognosis [200, 201, 574]. The timing for resuming anticoagulant therapy after bleeding is determined individually. In the case of a remediable source of bleeding, the use of an oral anticoagulant may be resumed after the appropriate intervention. Following gastrointestinal bleeding, as a rule, oral anticoagulant therapy can be resumed after 7 days [200].

If the multidisciplinary team decides not to resume anticoagulant therapy, implantation of a cardiac occluder*** in the left atrial appendage may be considered. It should be borne in mind that the standard management protocol for patients with a cardiac occluder*** involves a period of antithrombotic therapy (antiplatelet agents and/or oral anticoagulants) after device implantation, which is associated with the risk of recurrent bleeding.

Minor bleedings require only temporary discontinuation of oral anticoagulants (VKAs until INR drops <2.0, and DOACs for 1 day). It is important to explain to the patient the importance of adherence to therapy and the unreasonableness of refusing anticoagulant therapy even in the event of recurrent minor bleedings.

Comment: in patients with recent bleeding, the prescription of apixaban** 5 mg twice daily or dabigatran etexilate** at a dose of 110 mg twice daily may be considered as agents having an advantage over warfarin** according to randomized clinical trials and real-world clinical practice studies [61, 62].

3.1.1.5 Combination therapy with oral anticoagulants and platelet aggregation inhibitors in patients with atrial fibrillation and flutter who have suffered acute coronary syndrome and/or undergone percutaneous coronary interventions

In the Russian Federation, the prevalence of AF in acute coronary syndrome (ACS) reaches 18%, of which almost a quarter have this rhythm disorder detected for the first time [202, 203]. Approaches to prescribing anticoagulant therapy in concomitant coronary artery disease do not fundamentally differ from standard ones and are based on thromboembolic risk stratification, including in patients with an episode of AF newly diagnosed in the acute phase of ACS (even if this episode was single). Patients with ACS/PCI are indicated for dual antiplatelet therapy to reduce the risk of thrombotic complications, including stent thrombosis. On the other hand, antiplatelet therapy (even dual) is insufficient to reduce the risk of stroke in AF, which is the rationale for prescribing so-called triple antithrombotic therapy in patients with a combination of these diseases. In turn, this approach is associated with a substantial increase in the risk of major and fatal bleeding. A compromise tactic is to minimize the duration of combined antithrombotic therapy (both triple and dual) as much as the risk of thrombotic complications allows.

The 'baseline' strategy of combined antithrombotic therapy (in patients with low stent thrombosis risk and no high bleeding risk) is the administration of triple antithrombotic therapy for up to 7 days, followed by discontinuation of acetylsalicylic acid** and continuation of dual therapy for up to 12 months after ACS and up to 6 months after elective PCI. Depending on the individual ratio of ischemic/hemorrhagic complication risks, the duration of combined antithrombotic therapy may vary.

The risk of hemorrhagic complications can be assessed using various scales: HAS-BLED, ARC-HBR (Table 10 of Appendix G1), PRECISE-DAPT (Table 11 of Appendix G1), and the Russian ORACLE scale (Table 7 of Appendix G1) [575]. At the same time, the calculated risk of hemorrhagic complications should not be the sole determining factor, since at least half of AF patients with coronary artery disease simultaneously belong to the high-risk category for both stroke and bleeding.

Comment: The algorithm for choosing the antithrombotic therapy regimen after PCI in patients with AF is presented in Table F7 of Appendix B.

• In patients with AF and indications for combined antithrombotic therapy, it is recommended to prefer apixaban**, dabigatran etexilate**, rivaroxaban**, edoxaban rather than warfarin** [161, 204-208].

ESC IA (LOCE B, LOE 1)

ESC IIb B (LoE B, GoR 2)

Comments: In the absence of contraindications, full-dose NOACs are recommended (apixaban** 5 mg twice daily; dabigatran etexilate** 150 mg twice daily; rivaroxaban** 20 mg once daily, edoxaban 60 mg once daily). Standard dose-reduction criteria are used for all NOACs as part of combination therapy.

When using rivaroxaban** in patients at high bleeding risk, it should be kept in mind that the 15 mg dose is preferable to 20 mg for long-term treatment concurrently with one or two antiplatelet agents.

When using dabigatran etexilate** in patients at high bleeding risk, it should be kept in mind that the 110 mg dose is preferable to 150 mg for long-term treatment concurrently with one or two antiplatelet agents.

It should be remembered that the main measures to increase the safety of combined antithrombotic therapy are not the choice of a reduced NOAC dose, but the correction of bleeding risk factors, as well as the minimization of the duration of multicomponent therapy.

• If the patient is receiving a VKA in combination with antiplatelet agents, it is recommended to maintain the INR in the lower limit of the therapeutic range of 2.0-2.5 [204, 206, 209–212].

ESC IIaB (LOCE B, LOE 2)

• In all patients undergoing PCI with stent implantation, periprocedural administration of acetylsalicylic acid** is recommended [204-206].

ESC IC (RR S, ELD 5)

Comment: periprocedural administration refers to taking acetylsalicylic acid** prior to PCI in a loading dose followed by administration after PCI for ≤7 days.

• Ticagrelor** and prasugrel are not recommended for use as part of triple antithrombotic therapy in combination with acetylsalicylic acid** and an oral anticoagulant [213-215].

ESC IIIC (LoE B, GoE 1)

Comments: Prasugrel and ticagrelor** as part of multicomponent antithrombotic therapy have been little studied. The trial designs of RE-DUAL PCI, PIONEER-AF, ENTRAST-AF PCI, and AUGUSTUS allowed the choice of platelet P2Y₁₂ receptor inhibitor at the discretion of the attending physician. Prasugrel was prescribed in no more than 1% of trial participants, and ticagrelor** was received by 4% to 12% of patients. A meta-analysis of 4 trials showed that the use of prasugrel or ticagrelor** is associated with a 30% increase in the rate of major and clinically relevant bleeding without benefits in the rate of ischemic events [216].

The drug of choice in combined antithrombotic therapy (both triple and dual) is clopidogrel**. Dual therapy with a NOAC and ticagrelor**/prasugrel can be considered only in patients with ACS, a high risk of coronary thrombosis, and a low bleeding risk in whom triple therapy based on a NOAC or VKA would otherwise be justified.

When prescribing a combination of ticagrelor** and dabigatran etexilate**, one should keep in mind the pharmacokinetic interaction (the concentration of dabigatran etexilate** when coadministered with ticagrelor** increases by 24-65%). Administration of a loading dose of ticagrelor** is advisable no earlier than 2 hours after taking dabigatran etexilate** [136].

• Following successful PCI in patients with ACS and a low risk of stent thrombosis, or if the bleeding risk outweighs the risk of stent thrombosis, it is recommended to limit the duration of triple antithrombotic therapy (oral anticoagulants combined with acetylsalicylic acid** and platelet P2Y12 receptor inhibitors, preferably clopidogrel**) to 7 days, followed by discontinuation of acetylsalicylic acid** and continuation of dual therapy for up to 12 months regardless of stent type [204-206, 208].

ESC IA (CGR B, LOR 1)

• Following successful elective PCI in patients with a low risk of stent thrombosis, or if the bleeding risk outweighs the risk of stent thrombosis, it is recommended to limit the duration of triple antithrombotic therapy (oral anticoagulants combined with acetylsalicylic acid** and clopidogrel**) to 7 days, followed by discontinuation of acetylsalicylic acid** and continuation of dual therapy for up to 6 months regardless of stent type [204-206, 208].

ESC IA (CGR B, LOR 1)

Comments: Extension of triple therapy (oral anticoagulant, acetylsalicylic acid**, and clopidogrel**) beyond 7 days should be considered both in patients with ACS and after elective PCI in the presence of additional risk factors for ischemic events/stent thrombosis and a low bleeding risk.

Risk factors for stent thrombosis include: suboptimal stent positioning or residual dissection, stenting of the left main coronary artery/proximal left anterior descending artery/sole patent artery, stent length >60 mm, bifurcation 2-stent technique, treatment of chronic total occlusions, multivessel stenting, prior stent thrombosis on adequate dual antiplatelet therapy, diabetes mellitus, CKD.

The risk of ischemic events is higher in patients with a history of prior ACS episodes, multivessel coronary disease, concomitant peripheral atherosclerosis, early manifestation (before 45 years), and aggressive course of CAD (appearance of a new lesion within 2 years). For formalized assessment of ischemic risk in patients with stable CAD, the approach developed based on the REACH registry results [217] can be used, as well as the SYNTAX score (Table P8 of Appendix G1) [218]. In patients with ACS, the GRACE score (Table P9 of Appendix G1) can be used.

Arguments in favor of shortening the duration of combined antithrombotic therapy include the presence of a high bleeding risk and a low atherothrombotic risk. Bleeding risk can be assessed, inter alia, using various scales: HAS-BLED (Table P4 of Appendix G1), ARC-HBR (Table 10 of Appendix G1), PRECISE-DAPT (Table 11 of Appendix G1), and the Russian ORACLE scale (Table 7 of Appendix G1) [576].

Before discharge from the hospital, it is necessary to provide the patient with detailed recommendations regarding antithrombotic therapy, indicating specific timeframes for discontinuing certain drugs. Bleeding and ischemic risk is a dynamic indicator and should be regularly reassessed. Accordingly, perceptions of the optimal duration of combined antithrombotic therapy for a specific patient may change.

The regimen for multicomponent therapy in a patient with AF after elective PCI is presented in Table P7 of Appendix B.

• In patients with ACS who did not undergo coronary stenting, dual antithrombotic therapy with an oral anticoagulant and a single antiplatelet agent is recommended for up to 12 months [204, 206].

ESC IIa (RR B, ELD 2)

Comment: combined antithrombotic therapy in patients with ACS and AF receiving conservative management was studied only in the AUGUSTUS trial, in which the follow-up period did not exceed 6 months. The 12-month duration of combination therapy was extrapolated from randomized trials in which patients with ACS and AF underwent PCI and the follow-up period was at least 12 months. Based on the available evidence, it is preferable to use clopidogrel** as the antiplatelet agent. Apixaban** 5 mg twice daily is safer than warfarin**, at least for 6 months after ACS [204, 206].

It should be remembered that the transition to a combination of an oral anticoagulant and clopidogrel** is carried out after the completion of the initial ACS treatment period, which involves the use of dual antiplatelet therapy and a parenteral anticoagulant.

• Transition to oral anticoagulant monotherapy is recommended 6 months after elective PCI and 12 months after PCI performed for ACS [164, 208, 211, 219–220].

ESC IA (CGR B, LOR 1)

Comments: in individual cases, in patients with a very high risk of thrombotic events and an acceptable bleeding risk, it may be considered to continue dual therapy with an oral anticoagulant and a platelet aggregation inhibitor (ATC B01AC Antiplatelet agents, excluding heparin) (clopidogrel** or acetylsalicylic acid**) after 6 months following elective PCI and 12 months following PCI for ACS. Conversely, in patients with a high bleeding risk and absence of high ischemic risk, shortening the dual therapy period may be considered in individual cases.

• In patients receiving oral anticoagulants, it is recommended to use radial access for PCI to reduce the risk of hemorrhagic complications [655-657, 670].

ESC IIa A (RR B, ELD 2)

3.1.1.6 Management of Patients with Atrial Fibrillation and Flutter and Stable Coronary Artery Disease Receiving Conservative Therapy

• Patients with stable coronary artery disease receiving conservative treatment, concomitant atrial fibrillation, and a high risk of thromboembolic events are recommended monotherapy with an oral anticoagulant [164, 220, 221].

RSC IB (LoE B, GoR 2)

Comment: The evidence base for the benefits of oral anticoagulant monotherapy compared to combination therapy with oral anticoagulants and antiplatelet agents in patients with stable coronary artery disease receiving conservative treatment is limited to three open-label randomized trials – OAC-ALONE [221], AFIRE [220], and EPIC-CAD [576], as well as cohort studies, including the large Danish Registry [164]. The OAC-ALONE study was terminated prematurely and lacked sufficient statistical power to confirm the hypothesis that monotherapy is non-inferior to combination therapy regarding ischemic events. The total incidence of major bleeding and thromboembolic events did not differ between the groups. The AFFIRE trial was conducted in Japan, comparing reduced-dose rivaroxaban** 15 mg monotherapy with combination therapy of rivaroxaban** + one antiplatelet agent. In the monotherapy group, the incidence of major bleeding was 41% lower, and the incidence of ischemic events was 28% lower. However, it remains unclear to what extent these study results can be extrapolated to other patient populations. The EPIC-CAD study demonstrated that edoxaban monotherapy is associated with a reduced incidence of the composite endpoint comprising all-cause death, major ischemic, and hemorrhagic events. Finally, the Danish Registry, as well as a meta-analysis of 6 observational/cohort studies including data from the Danish Registry and the OAC-ALONE trial, showed that oral anticoagulant monotherapy is associated with a reduced incidence of major bleeding without an increased risk of ischemic events [222].

None of these studies separately evaluated patients with low and high risks of ischemic events. Perhaps in individual patients at the highest risk of ischemic events and without a high bleeding risk, the prescription of combination therapy with an oral anticoagulant and acetylsalicylic acid** or clopidogrel** may be considered.

• In patients with stable coronary artery disease receiving conservative treatment, atrial fibrillation, and a high risk of thromboembolic events, it is recommended to prefer apixaban**, dabigatran etexilate**, rivaroxaban**, or edoxaban over warfarin** [223].

ESC I A (LoE B, GoR 1)

3.1.1.7 Anticoagulant therapy and invasive procedures

Until recently, any invasive procedure implied discontinuing anticoagulant therapy for the duration of the procedure followed by its subsequent resumption. Later, the tactic of "bridging therapy" became widespread, where a short-acting parenteral anticoagulant (heparin sodium**, #enoxaparin sodium**, #nadroparin calcium) is prescribed during the discontinuation of the oral agent, with the subsequent resumption of the oral drug [230, 632]. It should be emphasized that routine use of "bridging therapy" in all patients increases the bleeding risk. A differentiated approach based on assessing the ratio of thrombotic to hemorrhagic risks in a particular patient appears optimal. Thus, the majority of interventions with a low predicted bleeding risk can be performed without discontinuing anticoagulant therapy, while interventions with a moderate or high bleeding risk require temporary cessation of anticoagulants. "Bridging therapy" is necessary only for patients with a very high risk of thromboembolic events.

• In patients with atrial fibrillation receiving oral anticoagulants, it is recommended to evaluate the risk and clinical significance of potential perioperative bleeding, patient-related risk factors for hemorrhagic complications, and the risk of thrombotic complications upon oral anticoagulant withdrawal before an invasive procedure [34].

RSC IC (LoE C, GoR 5)

Comments: The risk of bleeding in the perioperative period depends both on the characteristics of the surgical intervention and on comorbid conditions determining the overall hemorrhagic risk for a specific patient.

A brief classification of major invasive procedures according to bleeding risk is presented in Table F5 of Appendix A3. Any validated scales can be used to assess the overall risk of hemorrhagic complications for a specific patient [59, 60, 64, 224]. The HAS-BLED scale is most commonly used (Table F4 of Appendix G1). The optimal approach is to assess the full spectrum of major risk factors for hemorrhagic complications (Table F1 of Appendix A3). Special attention should be paid to such factors as bleeding in the preceding 3 months, thrombocytopenia or thrombocytopathy (e.g., due to uremia), concomitant use of antiplatelet agents or other drugs/dietary supplements associated with impaired platelet function, bleeding during a similar procedure in the past, and a history of bleeding during "bridging therapy". If possible, the elective procedure should be postponed until maximum correction of all modifiable bleeding risk factors in the individual patient is achieved.

• Most minor invasive procedures (tooth extraction, root canal procedures, minor dermatological surgeries, cataract removal), as well as certain invasive cardiac procedures (coronary angiography and PCI via the radial approach, pacemaker implantation, catheter ablation for atrial flutter/fibrillation), are recommended to be performed without discontinuing anticoagulant therapy [225-229].

RSC IA (LoE B, GoR 2)

Comments: if the patient is taking warfarin**, it is advisable to perform an elective invasive procedure against the background of INR at the lower limit of the therapeutic range (2-2.5) without switching to heparin and its derivatives. To do this, it is necessary to determine the INR a few days before the procedure and, if necessary, adjust the dose of the drug, or skip 1-2 doses before the procedure. On the day of the procedure, the INR must also be assessed, then, on the evening of the surgery day or the next morning, provided adequate hemostasis, warfarin** therapy should be resumed at the patient's usual maintenance dose, without using a loading dose.

If PCI is planned and the patient is taking a DOAC, the morning dose on the day of the procedure should be skipped. The endovascular procedure should be performed with administration of a full dose of a parenteral anticoagulant (most often unfractionated heparin**, targeting the appropriate activated clotting time). DOAC therapy can be resumed after the effect of the parenteral anticoagulant has worn off.

• Routine use of "bridging therapy" during oral anticoagulant discontinuation due to an invasive procedure increases the risk of perioperative bleeding and therefore is not recommended [225, 230, 231].

ESC IC (LoE B, LoR 2)

Comments: The use of "bridging therapy" should be strictly limited to specific indications determining a very high risk of thromboembolic events (mechanical heart valve, stroke/TIA <3 months ago, CHA₂DS₂-VASc score ≥7 points). In patients with a moderately high risk of thromboembolic events (CHA₂DS₂-VASc score – 5-6, stroke/TIA ≥3 months ago), the use of "bridging therapy" may be considered in case of an acceptable risk of hemorrhagic complications.

"Bridging therapy" involves discontinuing the oral anticoagulant (primarily warfarin**) and switching to heparin and its derivatives at doses used for the treatment of venous thrombosis. High-bleeding-risk surgery in patients taking warfarin** can be performed when the INR is below 1.5. Postoperatively, parenteral anticoagulation can be resumed as soon as stable hemostasis is established (optimally within 12–24 hours after surgery, though this may be extended to 48–72 hours following major procedures and in high-bleeding-risk cases). In the absence of bleeding, administration of a VKAs at the previously established maintenance dose should also be resumed. Parenteral anticoagulation can be discontinued once the INR reaches the target range (unfractionated heparin** therapy is usually administered for at least 5 days). In patients with a mechanical heart valve, therapeutic anticoagulation must be resumed within the first 24 hours postoperatively. Fondaparinux sodium is not routinely used for bridging therapy, but this option may be considered in patients with a history of heparin-induced thrombocytopenia.

Due to their rapid onset of action and predictable offset, DOACs rarely require bridging therapy. If a decision is made to temporarily interrupt DOAC therapy, the duration of discontinuation should be determined by the bleeding risk of the surgical procedure and renal function (Table P7 of Appendix A3). DOACs can be resumed 12–48 hours postoperatively, guided by the achievement of effective hemostasis and the risk of thromboembolism.

3.1.2 Treatment strategies for patients with atrial fibrillation and atrial flutter

Drug therapy

For the management of patients with AF and AFL, two alternative therapeutic strategies are recommended:

1) restoration (if necessary) and maintenance of sinus rhythm for as long as possible using pharmacological and interventional antiarrhythmic treatments, the so-called "rhythm control";

2) reduction of ventricular rate in the presence of persistent AF/AFL, the so-called "rate control", involving the use of heart rate-lowering drugs and refraining from antiarrhythmic treatment per se.

• The "rhythm control" strategy is recommended for patients with AF/AFL and a short history of AF/AFL (less than 12 months from diagnosis) and concomitant cardiovascular diseases [232].

RSC IA (LoE B, GoR 2)

Comment: For a long time, the "rate control" and "rhythm control" strategies in the treatment of patients with AF were considered equivalent; however, data from the EAST-AFNET 4 trial demonstrated the benefits of choosing the "rhythm control" strategy in patients with a recent history of AF and concomitant cardiovascular diseases. These benefits include a lower incidence of adverse outcomes (composite endpoint: cardiovascular death, stroke, ACS, hospitalization for worsening heart failure). According to a meta-analysis by S. Han et al., early selection of the "rhythm control" strategy compared to the "rate control" strategy contributed to a reduction in the risk of death (both all-cause and cardiovascular), stroke, and HF-related hospitalizations [183].

In all other situations, the choice of AF treatment strategy is determined individually, depending on the nature of the arrhythmia, severity of clinical manifestations, presence of comorbidities, tolerance to various drug groups, and with the mandatory consideration of the attending physician's opinion and the patient's preference. Antiarrhythmic treatment aimed at "heart rhythm control" does not eliminate the need for parallel "rate control", as there is always a possibility of AF recurrence, which should not occur with an excessively high ventricular rate [233, 234].

Recently, evidence has emerged that interventional procedures compared to medical therapy may improve the prognosis of patients with AF [235].

3.1.2.1 Heart Rate Control

Heart rate (HR) control is one of the main objectives in the treatment of patients suffering from AF and/or AFL, regardless of the chosen therapeutic strategy. The choice of a long-term HR control tactic is recommended as a first-line treatment strategy for patients with asymptomatic and oligosymptomatic AF and/or AFL, as well as an equivalent alternative to long-term antiarrhythmic treatment for patients with symptomatic AF/AFL in case of failure of previous preventive antiarrhythmic treatment attempts (Section 3.1.4) and in chronic AF (Tables P10 and P11 of Appendix A3) [236, 237].

In AF/AFL presenting with severe symptoms, to eliminate these clinical manifestations, intravenous or oral administration of drugs that slow atrioventricular conduction is advisable: beta-blockers (β-blockers) or non-dihydropyridine calcium channel blockers with a direct effect on cardiomyocytes (hereinafter referred to as direct-acting cardiac calcium channel blockers) (verapamil**, #diltiazem). Doses of the heart rate-lowering drugs most commonly used in the treatment of patients with AF/AFL are listed in Tables P10 and P11 of Appendix A3 [238, 239, 633-636].

The occurrence of severe hemodynamic instability during AF/AFL, despite the use of heart rate-lowering drugs, is an indication for emergency electrical cardioversion followed by consideration of the "rhythm control" strategy (see also Section 3.1.2.2).

3.1.2.1.1 Pharmacological Agents for Heart Rate Control

Patients with permanent AF or AFL (i.e., those in whom sinus rhythm restoration is not planned) are not recommended to use class I and III antiarrhythmic drugs (AADs) on a continuous basis (with the exception of amiodarone**) [236, 237, 240].

• For ventricular rate control during AF or AFL, the use of β-blockers, digoxin**, direct-acting cardiac calcium channel blockers (verapamil**/#diltiazem), or a combination of β-blockers and digoxin** is recommended [233, 234, 236, 237, 633-636].

ESC IA (LOCE B, LOE 1)

Comments: The list of drugs recommended for ventricular rate control in AF/AFL, along with their standard therapeutic doses, is presented in Tables P10 and P11 of Appendix A3. In case of insufficient effect of rate-lowering drugs and their combinations, as well as the impossibility of long-term medication use, the possibility of non-pharmacological treatment methods (catheter ablation/atrioventricular junction modification with pacemaker implantation - PM / cardiac resynchronization therapy (CRT)) should be considered, see also Section 3.2.4.

3.1.2.1.2 Selection of Drug for Heart Rate Control

• The individual choice of a drug and its daily dose for ventricular rate control in AF/AFL should be guided by achieving target HR values: in the complete absence of arrhythmia symptoms, the resting ventricular rate should be no more than 110 bpm; in the presence of symptoms associated with arrhythmia, no more than 80 bpm (also at rest) [241, 242].

ESC IIaB (LOCE B, LOE 2)

Comments: Management algorithms for patients using the "rate control" strategy are presented in Tables P8 and P9 of Appendix B. Before recording an ECG to evaluate the efficacy of rate-lowering therapy, a 3-minute rest period is required. Individual control of the efficacy and safety of such treatment (there is a risk of clinically significant bradycardia, especially at night) should be performed using Holter ECG monitoring. In patients with a high level of physical activity (predominantly young patients), the efficacy of the prescribed therapy should be assessed using exercise stress testing on a cycle ergometer or treadmill. In certain categories of patients, it is advisable to monitor electrocardiographic data for a longer period (more than 24 hours) to evaluate the efficacy and safety of the rate control strategy.

• β-Blockers, digoxin**, #diltiazem, or verapamil** are recommended for HR control in AF or AFL in patients with normal or moderately reduced LV systolic function (LV ejection fraction [EF] ≥40%) [243-245, 633-636].

ESC IB (LoE B, GoR 2)

Comments: β-Blockers (preferably long-acting cardioselective ones) are the cornerstone of therapy aimed at HR control in persistent AF/AFL. Management algorithms for patients using the "rate control" strategy are presented in Tables P8 and P9 of Appendix B. Doses of rate control drugs are specified in Tables P10 and P11 of Appendix A3.

• β-Blockers and digoxin** are recommended for HR control in AF/AFL in patients with reduced LV systolic function (LV EF <40%) [244-246].

ESC IB (LoE B, GoR 2)

Comments: in sedentary patients (elderly individuals with reduced physical activity) when β-blockers are contraindicated or ineffective, digoxin** monotherapy may be prescribed to reduce HR in AF/AFL.

Digoxin** monotherapy is rarely used due to the delayed onset of its therapeutic effect and a smaller reduction in HR during physical activity compared to β-blockers. Digoxin** can cause life-threatening adverse effects, so it should be used with caution, especially in patients with hepatic and renal impairment. Low-dose digoxin** (≤0.25 mg daily), corresponding to a serum digoxin concentration of 0.5 to 0.9 ng/mL, is associated with the best efficacy and safety profile [244, 245, 247, 248, 562]

• The use of combinations of various drugs affecting HR in AF or AFL is recommended in cases where target HR values cannot be achieved using a single medicinal product [238, 242, 243, 249].

ESC IB (LoE B, GoR 2)

Comments: the most effective and safe combination of drugs for ventricular rate control in AF or AFL is a combination of β-blockers and digoxin**. The combination of nondihydropyridine calcium channel blockers with direct cardiac effects (verapamil**/#diltiazem) and β-blockers is not recommended, as it may lead to dangerous mutual potentiation of their negative chronotropic and inotropic effects. Co-administration of digoxin** and verapamil**, as well as digoxin** and amiodarone**, is not recommended due to an increased risk of digitalis toxicity.

• In case of inefficacy or inability to use other rate-controlling drugs, including their combinations, as well as in patients with unstable hemodynamics due to recurrent paroxysms of AF/AFL or significantly reduced LVEF, it is recommended to consider amiodarone** for heart rate control in AF/AFL [250, 251].

ESC IIb B (LoE B, GoR 2)

Comments: 1) clinical manifestations of hemodynamic instability during AF/AFL are an indication for emergency external electrical cardioversion; amiodarone** can be used only if external electrical cardioversion is unavailable, ineffective, or the arrhythmia recurs; 2) the possibility of sinus rhythm restoration with amiodarone** must be taken into account; 3) drug dosages are given in Tables P10 and P11 of Appendix A3. 4) The use of amiodarone** is more preferable within the rhythm control strategy. 5) an alternative to amiodarone** for rate control in persistent AF or AFL is non-pharmacological rate control methods (catheter ablation/AV junction modification with pacemaker/cardiac resynchronization therapy device implantation in AF/AFL, as well as catheter ablation of the cavotricuspid isthmus in typical AFL, see also section 3.2.4.).

3.1.2.2 Sinus rhythm restoration

• Emergency external electrical cardioversion is recommended in AF complicated by acute hemodynamic instability (symptomatic hypotension, syncope/presyncope, signs of acute myocardial ischemia, pulmonary edema/acute heart failure – HF) for immediate restoration of sinus rhythm [137, 158, 252–259].

ESC IB (LoE C, GoR 4)

Comments: In this clinical scenario, AF poses an immediate threat to the patient's life and requires prompt cardioversion. The complete algorithm for AF cardioversion is presented in Table P10 of Appendix B.

• Sinus rhythm restoration to relieve clinical manifestations of AF is recommended in case of poor subjective tolerance of the arrhythmia, inability to achieve adequate ventricular rate control, and in situations where adequate ventricular rate control is not accompanied by clinical improvement (e.g., severe AF symptoms persist or clinical manifestations of HF develop) [135, 256, 259-265].

ESC IB (LoE B, GoR 2)

Comments: Many AF paroxysms can terminate spontaneously within several hours; therefore, when a patient presents with a recent-onset paroxysm and no hemodynamic instability, initial administration of rate-controlling drugs will help improve the patient's condition and may avoid the need for pharmacological or external electrical cardioversion. Since electrolyte imbalance is one of the factors provoking AF (e.g., due to intestinal infection, alcohol intoxication, or diuretic use), IV administration of potassium preparations may be advisable at this stage (in the absence of contraindications such as severe renal failure, hyperkalemia, etc.). In situations where AF is caused by a transient and potentially reversible factor (high fever, thyrotoxicosis, alcohol intoxication, etc.), treating the underlying condition may also contribute to spontaneous restoration of sinus rhythm. Pharmacological or external electrical cardioversion is inappropriate in such cases due to the high risk of early AF recurrence before the cause is eliminated (normalization of thyroid status, reduction of body temperature, etc.).

• For elective rhythm restoration in patients with AF, it is recommended to use pharmacological or external electrical cardioversion [266].

ESC IIaC (LoE B, GoR 2)

Comments: The choice of rhythm restoration method is made taking into account the clinical presentation of the disease (duration of the arrhythmia episode, use of antiarrhythmic drugs, anamnestic data on previously safe and effective rhythm restoration methods, presence of organic heart disease), physician and patient preferences. Electrical cardioversion (direct current cardioversion) is a highly effective method that allows rapid restoration of sinus rhythm, although AF recurrences may occur after rhythm restoration. Drugs used for sinus rhythm restoration not only terminate AF but also prevent early recurrences of arrhythmia. Most class I and III antiarrhythmic drugs (except for 4-nitro-N-[(1RS)-1-(4-fluorophenyl)-2-(1-ethylpiperidin-4-yl)ethyl]benzamide hydrochloride) are effective only for recently developed arrhythmia episodes (duration less than 48 hours).

The recommended algorithm for AF cardioversion is presented in Table P10 of Appendix B. Dosages of drugs used for AF termination (pharmacological cardioversion) are presented in Table P12 of Appendix A3. The tactics of anticoagulant therapy during AF/AFL cardioversion are discussed in Section 3.1.1.2.

3.1.2.2.1. Oral class IC antiarrhythmic drugs for sinus rhythm restoration ("pill-in-the-pocket")

• For patients with infrequent AF paroxysms who are not taking maintenance antiarrhythmic therapy (AAT) (Section 3.1.2.3), without concomitant structural heart disease or CAD, provided the arrhythmia duration is <48 hours, a single self-administered oral dose of #flecainide at 200–300 mg or #propafenone** at 450–600 mg may be recommended for sinus rhythm restoration (Table P12 of Appendix A3) [267–269, 577].

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

Comment: Preliminary safety assessment of this treatment in a hospital setting is required. This approach is not recommended for atrial flutter paroxysms.

3.1.2.2.2 Electrical cardioversion

• Elective external electrical cardioversion for arrhythmia termination is recommended in case of inefficacy of antiarrhythmic drugs (AADs), contraindications to their use, or when the attending physician and the patient prefer this method of rhythm restoration (Table P10 of Appendix B) [259, 263, 270].

ESC IC (RR S, ELD 5)

• Pre-administration of amiodarone**, sotalol**, or propafenone** is recommended to be considered to increase the efficacy of external electrical cardioversion and prevent AF recurrence [252, 260, 262, 271–273].

ESC IIaB (LOCE B, LOE 2)

• Emergency external electrical cardioversion is recommended for arrhythmia termination if a high ventricular rate is refractory to pharmacological control and is accompanied by persistent angina or other manifestations of myocardial ischemia, severe hypotension, or manifestations of HF (Table P10 of Appendix B) [257, 258, 274].

ESC IC (RR S, ELD 5)

3.1.2.2.3 Pharmacological cardioversion

Not in ESC guidelines (Level of Evidence 3, Grade of Recommendation B)

• I.v. administration of propafenone** is recommended for cardioversion of AF lasting up to 48 hours in patients with no contraindications to the drug (Table P12 of Appendix A3) [275, 276].

ESC I A (CGR B, LOR 2)

Comments: In patients with AF and structural heart disease (post-infarction cardiosclerosis, reduced LV systolic function, LVEF 40% or less with any manifestations of HF, as well as LV myocardial hypertrophy (LVH) with a wall thickness greater than 14 mm according to echocardiography), the use of propafenone** for sinus rhythm restoration is not recommended due to the high risk of arrhythmogenic effects of this drug in this category of patients.

• I.v. administration of procainamide** is recommended for cardioversion of AF lasting up to 48 hours in patients with no contraindications to the drug (Table P12 of Appendix A3) [277–282].

ESC I C (Level of Evidence B, Grade of Recommendation 2)

Comments: In patients with AF and structural heart disease (post-infarction cardiosclerosis, reduced LV systolic function, LVEF 40% or less – with any manifestations of HF, as well as LV myocardial hypertrophy exceeding 14 mm according to echocardiography), procainamide is not recommended** for sinus rhythm restoration due to the high risk of proarrhythmic action of this drug.

• I.v. administration of amiodarone** is recommended for cardioversion of AF in patients with no contraindications to the drug [276, 283–285].

ESC I A (RRR B, LOR 1)

Comments: Amiodarone** can also be used in patients with AF and structural heart disease, including severe chronic HF with low LVEF (Table A3-P12). It should be noted that rhythm restoration usually occurs at a later time.

• I.v. administration of 4-nitro-N-[(1RS)-1-(4-fluorophenyl)-2-(1-ethylpiperidin-4-yl)ethyl]benzamide hydrochloride is recommended for cardioversion of AF of any duration, including persistent and long-standing persistent forms of arrhythmia, in patients with no contraindications to the drug [286-293; 653-654, 671-672].

ESC not specified (LoE B, GoR 2)

Comments: The drug can also be used as an alternative to elective electrical cardioversion. The administration regimen and dose are presented in Table A3-P12.

3.1.2.2.4 Other methods of sinus rhythm restoration

• Frequent and ultrafast atrial pacing (see comment) is recommended for terminating AFL, but not AF [294-300].

ESC I C (LoE C, GoR 4)

Comments: Atrial pacing at a rate exceeding the atrial rate (overdrive pacing) to terminate any form of AFL can be achieved using a transesophageal pacing system (MOH A17.10.002.001 Transesophageal cardiac pacing), implanted devices (PM***, ICD***, CRT devices [MOH A23.10.002 Programming of a permanent implantable antiarrhythmic device]), as well as via temporary transcutaneous pacing / temporary external pacing (provided central venous access is available and a temporary single-chamber PM is inserted; MOH A17.10.002 Cardiac pacing). This method is ineffective for terminating AF. The anticoagulation management strategy during the termination of any form of AFL is determined by the same principles as during AF termination (Section 3.1.1.2).

3.1.2.3 Pharmacological prevention of atrial fibrillation and atrial flutter

The basic principles and efficacy criteria for pharmacological AAT of AF can be formulated as follows:

1) The goal of AAT is to reduce AF symptoms.

2) The efficacy of AAT aimed at maintaining sinus rhythm is low.

3) Effective AAT leads to a reduction rather than a complete disappearance of AF recurrences.

4) If one AAD proves ineffective, a clinically acceptable result may be achieved with another drug.

5) Arrhythmogenic or extracardiac side effects of antiarrhythmic drugs (AADs) are quite common.

6) Safety, rather than efficacy, should primarily determine the choice of AAD [139].

In light of recent clinical trial data, maintaining sinus rhythm in patients with AF and concomitant cardiovascular disease can improve their long-term prognosis, positively influence the rate of adverse outcomes, and is currently the preferred treatment strategy for patients with a short history of AF/AFL (<12 months from diagnosis). Prescribing medical antiarrhythmic therapy (AAT) approximately doubles the likelihood of maintaining sinus rhythm compared to placebo; thus, the efficacy of prophylactic AAT is modest and inferior to catheter ablation. Unlike ablation, AAT carries a potential risk of arrhythmogenic action, but lacks the risks of surgery [158, 237, 260, 301–304].

• Long-term medical AAT is recommended for rhythm control in patients with symptomatic recurrent paroxysmal AF, persistent AF after cardioversion, as well as in patients following AF/AFL ablation during the first 3 months or indefinitely (as part of a hybrid approach) [260, 305, 306].

ESC I B (LoE B, LoR 2)

Comment: The choice of Class IC or Class III AADs for the prevention of AF/AFL is recommended to be made taking into account the presence and severity of structural heart disease, the patient's comorbid background (presence of renal or hepatic impairment), the risk of arrhythmogenic action, and the spectrum of extracardiac adverse effects of the drug [236, 307].

• For more successful maintenance of sinus rhythm, in addition to prescribing Class IC or Class III AADs, it is necessary to control risk factors for cardiovascular complications (HF, hypertension, diabetes mellitus, body mass index, sleep apnea syndrome, etc.) and potential triggering factors for AF, such as stress, alcohol, physical overload, electrolyte disturbances, and thyrotoxicosis [274, 308-320].

ESC IIaB (LoE C, GoR 4)

• All patients receiving long-term AAT are recommended to undergo an annual examination including 12-lead ECG, 24-hour Holter ECG monitoring, and echocardiography to confirm compliance with the criteria for safe AAD selection [260, 321–327, 628, 629].

ESC IIaC (LoE C, GoR 5)

• Patients receiving long-term AAT are recommended regular monitoring of PQ, QRS, and QT intervals and heart rate using electrocardiography (ECG) and 24-hour Holter ECG monitoring to assess the potential risk of proarrhythmic effects of Class IC or Class III AADs and to timely detect clinically significant conduction disturbances and/or sinus node dysfunction caused by the drug [260, 322-327, 628].

ESC IB (LoE B, GoR 2)

Comments: at the start of treatment (first 3 days), daily ECG monitoring is recommended to establish the adequacy of the individual dose selection. When using amiodarone**, such monitoring is additionally recommended at 1 and 4 weeks. Long-term AAT is not recommended in patients with a QT interval >500 ms or sinus bradycardia <50 bpm at rest, or with episodes of 2nd–3rd degree sinoatrial block or 2nd–3rd degree atrioventricular block without prior pacemaker implantation***.

3.1.2.3.1 Drugs for the prevention of atrial fibrillation and atrial flutter recommended for patients without identified structural heart disease

• In patients without structural heart disease, medical prevention of AF recurrences should be initiated with beta-blockers, especially when the arrhythmia is clearly associated with mental or physical stress. In this way, a rate-control effect on heart rate during AF can also be achieved [249, 328].

ESC IB (LoE B, GoR 2)

Comments: the algorithm for the prevention of AF and AFL recurrences is presented in Table P11 of Appendix B.

• Class IC AADs (flecainide, propafenone**, lappaconitine hydrobromide** and its prolonged-release formulation, diethylaminopropionylethoxycarbonylaminophenothiazine) are recommended for the prevention of recurrent symptomatic AF (paroxysmal and persistent, post-cardioversion) in patients without structural heart disease, any form of CHD, and CHF [181, 321, 329–338, 348-349, 351, 578, 639-642]

ESC IА (LOCR B, LOE 2)

Comments: Medicinal products should not be unreasonably prescribed at doses lower than recommended, as in this situation they will not prevent the occurrence of paroxysms but will cause adverse effects. To prevent the potential transformation of AF into AFL with a high ventricular response rate, in the absence of contraindications, it is advisable to combine Class IC AADs with beta-blockers. In a specific category of patients with very severe symptoms of AF who have no structural heart disease, consideration may be given to prescribing combination antiarrhythmic therapy. It should be noted that clinical studies evaluating the efficacy and safety of this approach have not been conducted; combination therapy may only be prescribed in a specialized inpatient setting with mandatory safety monitoring.

Propafenone**, flecainide, diethylaminopropionylethoxycarbonylaminophenothiazine, lappaconitine hydrobromide**, and its prolonged-release dosage form slow down the depolarization process in all cardiac structures—in working myocardial cells and the conduction system—without affecting repolarization. Thus, these drugs may contribute to the formation of conditions for the emergence of arrhythmias via a reentry mechanism in both the atria and the ventricles. When using class IC antiarrhythmic drugs (AADs), careful monitoring of the PR interval and QRS complex duration on the ECG is required. An increase in the duration of the QRS interval on the ECG by 25% or more compared to baseline or >120 ms indicates the risk of a proarrhythmic effect, which can manifest as both the development of blocks at various levels of the cardiac conduction system and the occurrence of reentry ventricular arrhythmias, such as monomorphic ventricular tachycardia and ventricular extrasystoles. The drugs have a negative inotropic effect. The algorithm for the prevention of AF and AFL recurrences is presented in Table P11 of Appendix B.

ESC IIbA (CoE B, LOE 2)

Comment: Sotalol** is a class III AAD that slows repolarization and possesses non-selective β-blocker properties (for this reason, it is contraindicated in bronchopulmonary diseases). In terms of efficacy in preventing AF recurrence, it is inferior to amiodarone**. It should be noted that data from a regularly updated Cochrane review indicate an increase in overall mortality in patients receiving sotalol** compared with those receiving placebo or no antiarrhythmic therapy [181]. The drug carries a dose-dependent risk of torsades de pointes ventricular tachycardia (>2%). The proarrhythmic effect of sotalol** is associated with QT interval prolongation, which requires monitoring the dynamics of this parameter on the ECG. If the QTc interval increases to 500 ms or more, sotalol** should be discontinued or its dose reduced. The risk of a proarrhythmic effect is higher in women, patients with LV dysfunction, heart failure, marked LV hypertrophy (LV myocardial thickness ≥14 mm according to echocardiography), severe bradycardia, renal dysfunction, hypokalemia, or hypomagnesemia (Table P13 of Appendix A3).

• The prescription of amiodarone** for the purpose of preventing AF recurrence in patients without structural heart disease is recommended only if β-blockers, propafenone**, flecainide, lappaconitine hydrobromide** and its prolonged-release dosage form, diethylaminopropionylethoxycarbonylaminophenothiazine**, and sotalol** cannot be used or are ineffective, and catheter ablation is unfeasible or ineffective [303, 328, 341–343].

ESC IB (CoE B, LOE 1)

Comments: the algorithm for the prevention of AF and AFL recurrences is presented in Table P11 of Appendix B.

3.1.2.3.2 Medications for the prevention of atrial fibrillation and atrial flutter recommended for patients with detected structural heart pathology

• Amiodarone** is recommended for the prevention of recurrent symptomatic AF in patients with structural heart pathology, including CHF and LVH with a wall thickness greater than 14 mm [262, 304, 307, 344–347].

ESC IB (CoE A, LOE 1)

Comments: Amiodarone** is the most effective drug for the prevention of AF. It is a class III AAD; the main mechanism of its antiarrhythmic action is the slowing of repolarization in myocardial cells and the cardiac conduction system. In addition, the drug possesses the electrophysiological properties of all four classes of antiarrhythmic agents. The main antiarrhythmic effect of the drug is additionally enhanced by blocking thyroid hormone synthesis. Unlike most other class I and class III AADs, it can be prescribed to patients with organic heart disease, including chronic heart failure. The risk of polymorphic ventricular tachycardia of the torsades de pointes type during treatment with amiodarone** is lower (0.5%) than with other class III AADs, which is due to the blockade of multiple types of ion channels. However, due to this risk, it is recommended to monitor the duration of the QT interval on the ECG during the amiodarone** loading period (up to 4 weeks). An extension of this interval beyond 500 ms requires a dose reduction or discontinuation of the drug. Amiodarone** causes various extracardiac side effects (hypo- and hyperthyroidism, hepatitis, pneumonitis, pulmonary fibrosis, keratopathy, photosensitivity), especially with prolonged use, which makes its prescription justified only when other class I and III AADs are ineffective or contraindicated. Due to the drug's pharmacokinetic features, a long loading period is required (Table P13 of Appendix A3).

• For the purpose of preventing AF recurrence in patients with CAD, it is recommended to consider prescribing sotalol** [262, 307, 338].

ESC IIbA (CoE A, LOE 1)

• The prescription of amiodarone** for the prevention of AF is recommended for patients with CAD when sotalol** is ineffective/contraindicated and/or catheter ablation is unfeasible/ineffective [262, 303, 338, 341, 342].

ESC IA (LOCE B, LOE 1)

Comments: All patients prior to prescribing amiodarone** are advised to undergo a chest X-ray and thyroid status evaluation (blood test for thyroid-stimulating hormone (TSH) levels, thyroid ultrasound).

If signs of thyroid hyperfunction are detected, amiodarone** therapy is contraindicated. Thyroid hypofunction should be medically corrected and is not an absolute contraindication to its prescription. During amiodarone** therapy, thyroid status monitoring is required after 3 months, and thereafter at least once every 6 months (blood serum free thyroxine (FT4) level testing and blood thyroid-stimulating hormone (TSH) level testing, if necessary—an appointment (examination, consultation) with an endocrinologist), and testing for hepatospecific enzyme levels (determination of blood alanine aminotransferase activity, determination of blood aspartate aminotransferase activity).

During ongoing amiodarone** therapy, an annual chest X-ray is indicated, along with respiratory function testing every 6 months (Methodological Guidelines A12.09.001 Testing of unforced respiratory volumes and flows). In case of clinical manifestations in the absence of significant changes on the chest X-ray, it is advisable to perform multislice computed tomography of the lungs (Methodological Guidelines A06.09.008.001), and if necessary—an initial appointment (examination, consultation) with a pulmonologist.

To prevent the development of photosensitivity, it is recommended to avoid sun exposure or use special sunscreen products.

An annual initial appointment (consultation) with an ophthalmologist (Methodological Guidelines B01.029.001), followed by subsequent follow-up visits (Methodological Guidelines B01.029.002), is necessary to detect significant corneal deposits or visual impairment.

• The prescription of class IC AADs is not recommended for patients with CAD, signs of structural heart disease, heart failure, an LVEF reduction to 40% or less, or LVH with a wall thickness greater than 14 mm according to echocardiography, because drugs of this group can potentiate life-threatening ventricular arrhythmias, possess a negative inotropic effect, and exert a significant suppressive effect on the cardiac conduction system [321, 338, 348–351].

ESC IIIA (CoE B, LOE 2)

3.2 Surgical and interventional treatment of atrial fibrillation and atrial flutter

• Catheter ablation of paroxysmal AF is recommended for patients who have symptomatic AF recurrences while receiving antiarrhythmic therapy (beta-blockers, nondihydropyridine calcium channel blockers with direct cardiac effects, amiodarone**, propafenone**, lappaconitine hydrobromide** and its prolonged-release dosage form, diethylaminopropionylethoxycarbonylaminophenothiazine, sotalol**, flecainide) and who prefer further rhythm control. The procedure should be performed in an experienced center by a physician who has received appropriate training [352–356].

ESC IA (LoE B, GoR 2)

• Catheter ablation of persistent AF is recommended for patients who have symptomatic AF recurrences while receiving antiarrhythmic therapy (beta-blocker, nondihydropyridine calcium channel blocker with direct cardiac effects, amiodarone**, propafenone**, lappaconitine hydrobromide** and its prolonged-release dosage form, diethylaminopropionylethoxycarbonylaminophenothiazine, sotalol**, flecainide) and who prefer further rhythm control. The procedure should be performed in an experienced center by a physician who has received appropriate training [352–356].

ESC IIaB (CoE B, LOE 2)

Comments: Catheter ablation is not considered a life-prolonging method or a procedure that reduces the risk of stroke.

• Catheter ablation of AF is recommended as a first-line therapy for the prevention of AF recurrence and symptom improvement in selected patients with symptomatic paroxysmal AF as an alternative to antiarrhythmic drug therapy, taking into account patient preference and the risk-benefit ratio. The procedure should be performed in an experienced center by a properly trained physician [353-356].

ESC IIaB (LOCE B, LOE 2)

Comments: Patient selection must be performed with particular care to achieve good long-term outcomes of the procedure in both paroxysmal and persistent AF.

• As a catheter-based treatment for AF, it is recommended to perform antral pulmonary vein isolation using radiofrequency energy (including contact force-sensing catheters), cryoablation, or pulsed field ablation, including the use of three-dimensional mapping navigation systems [357-360, 579-581].

ESC IB (LoE B, GoR 2)

Comments: Primary isolation of the pulmonary vein ostia should be performed using radiofrequency ablation, cryoablation, and pulsed field ablation. The choice of the pulmonary vein isolation technique depends on the anatomy of the left atrium, the equipment available at the clinic, the level of training of the specialist, and the surgeon's primary method of choice. Currently, there is no convincing evidence of the efficacy of additional left atrial lesions (linear ablations, ablation of fragmented components, and ganglionated plexi), despite encouraging results of left atrial posterior wall isolation in persistent forms of arrhythmia in some studies

No ESC recommendation (LoE B, GoR 2)

• Catheter ablation for AF is recommended in symptomatic patients with AF and heart failure with reduced left ventricular ejection fraction to improve symptoms and cardiac pump function when arrhythmia-induced cardiomyopathy is suspected as the cause of heart failure [361-366].

ESC IIaC (LoE B, GoR 1)

• Catheter ablation for AF is recommended in symptomatic patients with heart failure and reduced left ventricular ejection fraction to improve survival in chronic heart failure, reduce heart failure-related hospitalizations, and decrease the rate of progression to persistent arrhythmia in paroxysmal AF [367, 368].

ESC IA (LoE B, GoR 2)

Comments: The procedure may have low efficacy in patients with NYHA functional class III–IV heart failure, normosystolic form of AF, and extremely low LVEF <20% who are receiving optimal medical therapy.

• Catheter ablation for AF is recommended as a preferred strategy over pacemaker implantation*** in patients with AF and concomitant sinus bradycardia [369, 370].

ESC IIaC (LoE C, GoR 4)

Comments: following the catheter procedure, it is recommended to evaluate sinus node function and, if organic sinus node disease criteria are present, consider pacemaker implantation after the surgery.

ESC IIaB (LOCE B, LOE 2)

Comments: The choice of the repeat pulmonary vein or left atrial isolation technique depends on the equipment available at the clinic, the specialist's training level, and the surgeon's primary method of choice.

• Catheter ablation of the cavotricuspid isthmus with intraoperative achievement of bidirectional conduction block is recommended for the treatment of typical atrial flutter in patients with ineffective antiarrhythmic drug therapy or as a first-line therapy based on patient preference, regardless of the flutter type (first-detected, paroxysmal, persistent, long-standing persistent), duration, and severity of atrial remodeling [371-374].

ESC IB (LoE C, GoR 4)

Comments: when performing catheter ablation of atypical atrial flutter, it is recommended to use non-fluoroscopic mapping navigation, including high-density mapping, to increase procedural efficacy.

• Catheter ablation of the typical atrial flutter substrate (cavotricuspid isthmus) is recommended for the prevention of atrial flutter recurrences as part of an AF ablation procedure if it has been previously documented or detected during the AF ablation [372, 373].

ESC IIaB (LoE C, GoR 4)

ESC IIa A (LoE B, GoR 1)

ESC IIa A (LoE B, GoR 1)

ESC IIb B (LoE B, GoR 1)

• Minimally invasive surgical treatment is recommended to be considered as a treatment option for patients with symptomatic persistent AF or following failed catheter ablation. Decisions for such patients should be made by an AF Heart Team including cardiovascular surgeons and cardiologists [378, 382, 384, 386, 387, 389].

ESC IIaC (LoE B, GoR 3)

• Patients with AF and a CHA2DS2-VASc score ≥2 who have undergone thoracoscopic ablation or hybrid treatment with concomitant left atrial appendage resection are recommended to continue oral anticoagulation therapy to reduce the risk of thromboembolic events [374, 595].

ESC I C (LoE B, GoR 2)

• Concomitant surgical isolation of arrhythmogenic zones, preferably the Maze procedure and its cryomodification, is recommended for patients with AF undergoing mitral valve surgery to restore sinus rhythm and improve the long-term outcomes of the intervention. Decisions for such patients should be made by an AF Heart Team including cardiovascular surgeons and cardiologists [374, 390, 596-603].

ESC IA (LoE A, GoR 1)

Comment: The classical Maze procedure, which has undergone a series of modifications, is currently performed using alternative energy sources—bipolar radiofrequency and cryoablation. Performing a modified Maze IV procedure using bipolar radiofrequency and/or cryoablation is an effective method for the concomitant treatment of atrial fibrillation during surgical correction of mitral valve disease [598, 602].

• Patients with AF are recommended to undergo concomitant surgical ablation or the Maze procedure during cardiac surgery (CABG and/or aortic valve surgery, congenital heart disease correction) to restore sinus rhythm and improve long-term outcomes. Decisions for such patients should be made by an AF Heart Team including cardiovascular surgeons and cardiologists [374, 604-609].

ESC IIa B (LoE C, GoR 4)

Comment: Favorable results and high efficacy of the Maze V procedure for the correction of concomitant AF during simultaneous CABG and aortic valve surgery have been demonstrated [626]. Given its technological features, it can be considered optimal for use in combination with CABG. The advantages of this technique include performing the entire radiofrequency ablation phase on a beating heart without opening the left heart chambers, which reduces myocardial ischemia time and provides complete electrophysiological control when creating transmural linear ablation zones and restoring sinus rhythm. Freedom from arrhythmia without antiarrhythmic therapy after CABG combined with Maze V at 12-, 24-, and 36-month follow-up was 91%, 88%, and 77%, respectively [611].

When performing open cardiac surgery (CABG), to prevent the development of postoperative atrial fibrillation, it is advisable to consider performing prophylactic epicardial radiofrequency ablation of the pulmonary vein ostia combined with AAT (amiodarone**). Decisions regarding such patients should be made by an AF multidisciplinary team including cardiovascular surgeons and cardiologists [612-615].

• For the prevention of postoperative AF following cardiac surgery, perioperative oral therapy with beta-blockers is recommended [389, 391].

ESC IB (CoE A, LOE 1)

• In hemodynamically significant postoperative AF, restoration of sinus rhythm using external electrical or pharmacological cardioversion is recommended [158].

ESC IC (LoE C, GoR 5)

Comments: The hemodynamic significance of the arrhythmia, especially in the early postoperative period, always requires emergency measures.

• Following cardiac surgery in patients with AF, individual stroke and bleeding risk is recommended to be considered when making decisions regarding long-term anticoagulant therapy [76, 377, 389, 391].

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

Comments: Decisions on continuing systemic anticoagulant therapy after a surgical procedure should be based on thromboembolic risk stratification rather than on the efficacy of the procedure performed.

• In symptomatic postoperative patients with AF, administration of class IC or class III antiarrhythmic drugs is recommended with the aim of restoring/maintaining sinus rhythm [158].

ESC IIaC (LoE C, GoR 5)

Comments: Prophylactic antiarrhythmic therapy is recommended after surgical procedures. This reduces the number of recurrences in the early postoperative period.

• In patients at high risk of developing AF in the postoperative period, evaluating the appropriateness of prophylactic amiodarone** before and after surgery is recommended [392].

ESC IIaA (LeveL of Evidence B, Grade of Recommendation 1)

Comments: prophylactic antiarrhythmic therapy, including amiodarone** therapy (in the absence of contraindications), is indicated after surgical procedures. This reduces the number of recurrences inulatory the early postoperative period.

• In patients with AF without hemodynamic instability, ventricular rate control and oral anticoagulant therapy are recommended [393].

ESC IIaB (LoE B, GoR 2)

• Following surgical resection or closure of the left atrial appendage (LAA) in patients with AF and high thromboembolic risk, continuation of anticoagulant therapy indefinitely is recommended [383, 394].

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

Comments: Decisions on continuing systemic anticoagulant therapy after a surgical procedure should be based on stroke risk stratification rather than on the efficacy of the procedure performed.

• Surgical closure or resection of the LAA is recommended for patients with AF undergoing open or thoracoscopic cardiac surgery [395].

ESC IIaB (LOCE B, LOE 2)

• Creation of an iatrogenic atrioventricular block followed by pacemaker implantation (service code A16.10.019.003) for heart rate control is recommended if the ventricular rate is not controlled by medical therapy, recurrences of AF cannot be prevented with antiarrhythmic therapy, or the latter causes serious side effects, while catheter or surgical ablation of AF is contraindicated, has proven ineffective, or its possibility has been rejected [396, 397].

ESC IIaB (LOCE B, LOE 2)

Comments: This recommendation should be considered as a last resort (not applied routinely) in centers performing catheter pulmonary vein isolation and minimally invasive surgical interventions for AF,

• Creation of an iatrogenic atrioventricular block followed by biventricular pacemaker implantation (three-chamber [biventricular] implantable pacemaker***) is recommended for a specific group of patients with permanent AF and indications for cardiac resynchronization therapy (NYHA functional class III-IV heart failure despite optimal medical therapy, LVEF ≤35%) [398-401].

ESC IIaB (LOCE B, LOE 2)

Comments: The appropriateness of the procedure should be considered in non-responders to resynchronization in whom a high heart rate during AF prevents effective biventricular pacing, some time after implantation.

• Creation of an iatrogenic atrioventricular block is recommended for a specific group of non-responders to resynchronization in whom a high ventricular rate during AF prevents effective biventricular pacing, and amiodarone** is ineffective or contraindicated [158].

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

Comments: beta-blockers or their combination with digoxin** can be effectively used to reduce the spontaneous rhythm rate, taking into account clinical limitations and complications associated with amiodarone**.

• Biventricular pacing is recommended for patients with any form of AF, severely depressed LV function (LVEF ≤35%), and severe heart failure (NYHA functional class III-IV) after creation of an iatrogenic atrioventricular block [158].

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

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

Comments: Such treatment should not be performed without prior attempts at medical therapy or catheter/surgical AF ablation for rhythm and/or ventricular rate control in patients with AF.

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

• Before catheter ablation of AF, anticoagulant therapy is recommended to prevent thromboembolic complications [158, 227, 356, 402, 403].

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

Comments: according to the opinion of several expert societies, the minimum required period of anticoagulant therapy prior to ablation in patients at high risk of thromboembolic events is 3 weeks [616].

• To prevent periprocedural thromboembolic complications, performing catheter ablation of AF without discontinuing anticoagulant therapy is recommended [404, 405].

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

Comments: in patients receiving DOAC therapy at target doses, performing catheter ablation without discontinuing oral anticoagulant therapy is well-founded. If the patient is receiving a once-daily DOAC, it is advisable to postpone the dose to the evening to reduce the risk of bleeding.

Omitting the morning dose of the drug on the day of AF/AFL catheter ablation with resumption 3-5 hours after the procedure is also well-founded (at the discretion of centers performing catheter AF ablation). The algorithm for anticoagulant therapy during catheter ablation for AF is presented in Table P12, Appendix B.

• Before performing catheter ablation of AF, it is recommended to perform transesophageal echocardiography (TEE) of the heart to rule out atrial thrombosis, even if the patient has received anticoagulant therapy for 3 weeks or more [160, 235, 365, 411, 412]. In patients unable to undergo TEE, it is recommended to use intracardiac echocardiography and/or contrast-enhanced CT of the left atrium and pulmonary veins to detect atrial thrombosis [406-413]. Atrial imaging should be performed no more than 48 hours before ablation.

ESC IIaC (Level of Evidence B, Grade of Recommendation 1)

Comments: Atrial thrombosis (including the appendages) is a contraindication for catheter ablation. Currently, there are many options for visualizing the atria; the strongest evidence base has been accumulated for transesophageal echocardiography (TEE), but there is also sufficient convincing data on the feasibility of using contrast-enhanced computed tomography (CT) of the left atrium and pulmonary veins, as well as intracardiac echocardiography.

• During AF catheter ablation, administration of unfractionated heparin** is recommended before or immediately after transseptal puncture. The recommended activated clotting time (ACT) should be maintained at least 300–350 seconds [406, 407, 414–422].

ESC IB (LoE B, GoR 2)

ESC IIaB (LoE C, GoR 4)

• Following AF catheter ablation, systemic anticoagulation therapy with warfarin** or DOACs is recommended for at least 2 months, regardless of the presence or absence of thromboembolic risk according to the CHA₂DS₂-VASc score [424, 425].

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

• In patients who have undergone AF ablation, the prescription of oral anticoagulants is recommended in accordance with the anticoagulation guidelines for patients with AF, regardless of the procedural success [158, 402].

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

• Decisions on continuing systemic anticoagulation therapy for more than 2 months after catheter ablation are based on stroke risk stratification rather than the procedural success [158, 402].

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

• Patients with risk factors for stroke and systemic embolism (CHA₂DS₂-VASc $\ge 2$ points for men, CHA₂DS₃-VASc $\ge 3$ points for women) are recommended long-term anticoagulation therapy, regardless of the success of the ablation [426].

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

• In patients who missed doses of oral anticoagulants prior to ablation, resumption is recommended 3–5 hours after ablation [174, 389, 427–430].

ESC IIa C (Level of Evidence A, Grade of Recommendation 2)

Comments: The decision to continue systemic anticoagulation therapy 3–5 hours after ablation should be made after confirming the absence of pericardial effusion using echocardiography or other significant bleeding.

• For patients in whom a decision to discontinue anticoagulation therapy has been made based on their beliefs and preferences, it is recommended to consider prolonged and frequent Holter heart rhythm monitoring to detect potential AF recurrences [158, 628].

ESC IIb C (LoE C, LE 5)

3.2.6.1 Left Atrial Appendage Endovascular Occlusion

• In patients with AF at moderate or high risk of thromboembolic events ($ ext{CHA}_2 ext{DS}_2 ext{-VASc} \ge 2$) and a contraindication to long-term oral anticoagulation therapy, it is recommended to consider left atrial appendage (LAA) endovascular occlusion [431–435].

ESC IIb B (Level of Evidence 1, Grade of Recommendation B)

• In selected groups of patients with AF (Table P9, Appendix A3) at moderate or high risk of stroke and at high risk of major bleeding on OACs, it is recommended to consider LAA endovascular occlusion as an alternative to oral anticoagulant therapy [173, 431–433, 617].

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

Comments: Randomized controlled trials have demonstrated that LAA occlusion is non-inferior to warfarin** and DOACs in terms of efficacy and safety [431–434]. The latest meta-analysis involving 73,199 patients reached the same conclusion [435]. According to a prospective non-randomized study, patients deemed unsuitable for OAC who undergo implantation of a cardiac LAA occluder*** have a lower ischemic stroke risk relative to the calculated risk [173]. Prospective registries of LAA cardiac occluder*** implantation in patients who do not receive OAC for a prolonged period have shown a high procedural success rate, a low risk of serious procedure-related complications, and a low rate of ischemic stroke during follow-up [617, 618]. Based on these results, LAA occlusion is advisable in patients with non-valvular AF who have contraindications to long-term OAC due to an irreversible cause (Table P9, Appendix A3). Furthermore, it may be reasonable as an alternative to OAC based on patient preference after careful consideration of procedural risks and with the understanding that there is substantially more evidence supporting OAC.

3.2.6.2 Surgical Occlusion and Excision of the Left Atrial Appendage

Numerous observational studies indicate the feasibility and safety of surgical LAA occlusion/excision, but data from controlled studies are limited [394, 436]. A residual leak from the LAA or incomplete occlusion may be associated with an increased risk of stroke [437]. In most studies, LAA occlusion/excision was performed during other open-heart cardiac surgeries, and in recent years, also in combination with surgical AF ablation or as a standalone thoracoscopic procedure [395, 438]. A large randomized controlled trial involving LAA occlusion/excision during concomitant cardiac surgery has now been completed, demonstrating the clinical utility of this intervention in patients at high risk of thromboembolic events [437].

• Patients with AF undergoing cardiac surgery with a $ ext{CHA}₂ ext{DS}₂ ext{-VASc} \ge 2$ score are recommended surgical isolation/amputation of the left atrial appendage combined with ongoing anticoagulation therapy to reduce the risk of stroke and systemic embolism [428, 438, 439, 619–623].

No ESC recommendation (Level of Evidence 1, Grade of Recommendation A)

Comment: During cardiac surgery in patients with AF, simultaneous amputation of the left atrial appendage must be performed under the guidance of intraoperative transesophageal echocardiography [619, 621, 624].

3.3 Atrial fibrillation and atrial flutter in special patient categories

• Treatment of hypertension and rigorous blood pressure control are recommended for all patients with AF to prevent arrhythmia recurrences, ischemic, and hemorrhagic complications [430].

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

Comments: Hypertension is a major risk factor for ischemic stroke in AF. Uncontrolled high blood pressure increases the likelihood of ischemic stroke and hemorrhagic complications and may contribute to arrhythmia recurrences. Inhibition of the renin-angiotensin-aldosterone system can prevent myocardial structural remodeling and recurrent arrhythmia episodes [339].

• In patients with diagnosed AF and hypertension receiving antiarrhythmic drug therapy, it is recommended to prescribe ACE (angiotensin-converting enzyme) inhibitors / angiotensin II receptor blockers in combination with antiarrhythmic therapy to reduce the likelihood of AF recurrence [440–442].

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

Comments: Concomitant use of ACE inhibitors or angiotensin II receptor blockers and antiarrhythmic therapy may reduce the frequency of recurrent AF episodes after cardioversion compared to antiarrhythmic drugs alone [441, 442]. A meta-analysis of several studies demonstrated a lower risk of AF recurrence with antihypertensive therapy [443–445], although at least one controlled study failed to confirm the benefit of this treatment regimen [446]. It should also be noted that prescribing ACE inhibitors or angiotensin II receptor blockers without antiarrhythmic drug therapy does not reduce the likelihood of AF recurrence.

• Catheter ablation of an accessory pathway (AP) is recommended for patients with Wolff-Parkinson-White (WPW) syndrome and AF with rapid conduction over the AP to reduce the risk of sudden cardiac death [446–453].

ESC IB (LoE B, GoR 2)

Comments: To assess the risk of sudden cardiac death in patients with WPW syndrome and AF, one can rely on the shortest pre-excited R-R interval (less than 250 ms) or persistent AP conduction.

• Catheter ablation of the accessory pathway is recommended without delay for all patients who have survived sudden cardiac death [450].

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

Comments: Sudden cardiac death in WPW syndrome is most commonly caused by rapid conduction of AF/atrial flutter over the accessory pathway progressing to ventricular fibrillation. Catheter or surgical ablation of the accessory pathway is mandatory according to expert consensus.

• Asymptomatic patients with evidence of ventricular pre-excitation and AF are recommended close monitoring and, if necessary, catheter ablation of the accessory pathway [447, 451].

ESC IIaB (LoE B, GoR 2)

Comments: To decide on catheter ablation of the accessory pathway, an invasive cardiac electrophysiology study or transesophageal electrophysiological study can be performed to evaluate the antegrade effective refractory period of the accessory pathway.

• Urgent external electrical cardioversion for arrhythmia termination is recommended for patients with AF and ventricular pre-excitation syndrome in the presence of a high ventricular rate and hemodynamic instability [257, 258, 454].

ESC IB (LoE C, GoR 4)

• Intravenous procainamide** is recommended to restore sinus rhythm in patients with AF and ventricular pre-excitation syndrome, provided that AF is not accompanied by hemodynamic instability [452].

ESC IIA (LoE C, GoR 4)

• Intravenous propafenone** is recommended to restore sinus rhythm in patients with AF and ventricular pre-excitation syndrome, provided that AF is not accompanied by hemodynamic instability [452, 453].

ESC IIA (LoE B, GoR 2)

• Intravenous amiodarone** is not recommended for terminating AF/AFL in patients with WPW syndrome [455-458].

ESC IIIB (LoE C, GoE 4)

Comments: When administered intravenously, amiodarone** primarily exerts beta-blocker and calcium channel blocker effects; therefore, it does not significantly affect the refractoriness of the accessory pathway, but it can lower blood pressure and lead to hemodynamic instability.

• Class IC antiarrhythmic drugs may be considered, in the absence of contraindications, to prevent AF recurrence in patients with WPW syndrome when accessory pathway catheter ablation is ineffective, contraindicated, unfeasible, or declined by the patient [453, 459].

ESC IIb B (LoE B, GoR 2)

• Long-term oral amiodarone** therapy may be considered, in the absence of contraindications, to prevent AF recurrence in patients with WPW syndrome when accessory pathway catheter ablation is ineffective, contraindicated, unfeasible, or declined by the patient [460, 461].

ESC IIbB (LoE C, GoR 4)

• The use of verapamil*, #diltiazem, and digoxin**, as well as beta-blockers and intravenous amiodarone** for heart rate control in paroxysmal or persistent AF or AFL is not recommended in patients with WPW syndrome, as these drugs can enhance conduction via the accessory pathway (AP) [374, 454, 562, 633-636].

ESC IIIA (LoE C, GoR 5)

Comments: Catheter ablation of the accessory pathway is the treatment of choice for heart rate control in patients with WPW syndrome. Direct-acting cardiac selective calcium channel blockers and digoxin** can shorten the effective refractory period of the accessory pathway and lead to an increased ventricular rate. Beta-blockers do not significantly affect accessory pathway refractoriness, but they can lower blood pressure and lead to hemodynamic instability in the setting of AF. When administered intravenously, amiodarone** does not significantly affect accessory pathway refractoriness, but it can lower blood pressure and lead to hemodynamic instability.

• Lifelong anticoagulant therapy is recommended for all patients with hypertrophic cardiomyopathy (HCM) and AF, regardless of thromboembolic risk scores according to the CHA₂DS₂-VASc scale [462-465].

ESC IB (LoE C, GoR 4)

Comments: Observational data indicate a high risk of stroke in patients with HCM and AF, confirming the necessity of prescribing anticoagulant therapy

• Restoration of sinus rhythm via electrical or pharmacological cardioversion to improve symptoms is recommended for all patients with HCM and first-detected symptomatic AF [463].

ESC IB (LoE C, GoR 5)

Comments: This recommendation applies to all variants of first-detected symptomatic AF.

• Patients with hemodynamically stable AF and HCM are recommended to undergo heart rate reduction using β-blockers or #diltiazem/verapamil** [137, 463, 658-661]

Comments: Standard therapeutic doses of these drugs are presented in tables P10 and P11 of Appendix A3.

ESC IC (LoE C, GoR 5)

• Treatment of left ventricular outflow tract obstruction is recommended for patients with HCM and AF to reduce symptoms [464].

ESC IIaB (LOCE C, LOE 5)

• Administration of amiodarone** is recommended for patients with HCM and symptomatic recurrent AF to restore and maintain sinus rhythm [463, 465].

ESC IIaC (LoE C, GoR 4)

• Targeted genetic testing is recommended for patients with AF and suspected hereditary cardiomyopathies, based on clinical data, family history, and electrocardiographic phenotype [466, 467].

ESC IIaA (LoE C, GoR 4)

Comments: In recent years, genetic testing has assumed a major role in the verification of diagnosis and prognosis in patients with hereditary cardiomyopathies and channelopathies.

AF in patients with HF and preserved LVEF

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is difficult in patients with AF due to the complexity of differentiating symptoms related to arrhythmia from those of heart failure proper; in any case, correction of hypertension and myocardial ischemia is required. Echocardiography is a useful diagnostic method that allows the evaluation of signs of structural heart disease in the presence of symptomatic AF (left ventricular hypertrophy and/or diastolic dysfunction). A reduction in early diastolic myocardial velocity e’, recorded using tissue Doppler imaging, reflects impaired left ventricular relaxation, whereas the E/e’ ratio correlates with invasive measurements of left ventricular filling pressure [467-471]. Atrial natriuretic peptide levels are also applicable for diagnosing HFpEF [430], but this parameter tends to be elevated in the presence of AF, and optimal normal reference values have not yet been definitively established [472].

AF in patients with HF and mildly reduced LVEF

Heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) is a relatively new concept applied to patients with symptoms and signs of heart failure, a mild reduction in left ventricular ejection fraction (LVEF) down to 40–49%, elevated natriuretic peptide levels, and one or a combination of the following criteria: left ventricular hypertrophy, left atrial enlargement, or manifestations of diastolic dysfunction [473]. In AF, diagnosis is difficult because left atrial dilatation can occur in the setting of arrhythmia independently of concomitant heart failure, as can elevated natriuretic peptide concentrations. LVEF values in AF can be variable, while echocardiographic assessment is difficult due to reduced left ventricular systolic function during arrhythmia and cardiac cycle length variability. Therefore, further observations are required to develop specific treatment strategies for patients with AF and HFmrEF.

Prevention of AF development in patients with HF

Retrospective analyses of large randomized trials indicate a lower incidence of newly diagnosed AF in patients treated with ACE inhibitors/angiotensin II receptor blockers compared to the placebo group [474, 443, 445]. The reduction in AF incidence with ACE inhibitor/angiotensin II receptor blocker therapy is less evident in patients with heart failure and preserved ejection fraction [475]. In the absence of heart failure, the benefit of prescribing these drugs has not been demonstrated [476-478]. At the same time, β-blocker therapy in addition to ACE inhibitors/angiotensin II receptor blockers contributed to a 33% reduction in the adjusted risk of paroxysmal AF in patients with heart failure and systolic dysfunction, which underscores the necessity of prescribing β-blockers during sinus rhythm for prophylactic purposes [479]. The effectiveness of the aldosterone antagonist eplerenone has been proven; when used as part of combination therapy with ACE inhibitors/angiotensin II receptor blockers and β-blockers, a reduction in the incidence of AF was observed in patients with LVEF ≤35% and NYHA class II heart failure [480].

• Patients with diagnosed AF and heart failure with systolic dysfunction are recommended to initiate heart failure treatment at early stages [443, 445, 471-474].

RSC IA (LoE B, GoE 1)

• Patients with heart failure and reduced left ventricular ejection fraction are recommended to receive optimal medical therapy for heart failure in accordance with current clinical guidelines of the Russian Ministry of Health for the prevention of AF [443, 444, 474, 475, 481].

ESC IIA (LoE B, GoR I)

• In patients with AF and heart failure, achieving a heart rate target of less than 100–110 beats per minute is recommended [473, 482-488].

ESC IIaC (LoE B, GoR 2)

Comments: β-blockers, #diltiazem, verapamil**, and digoxin** are all acceptable options in heart failure with preserved ejection fraction, whereas β-blockers and digoxin** can be used in heart failure with reduced ejection fraction [662, 673].

Standard dosages of these drugs are presented in tables P10 and P11 of Appendix A3.

• In the absence of contraindications, elderly patients are recommended to undergo interventional procedures for the treatment of AF and AFL. The procedure is recommended to be performed in an experienced center by a physician who has received appropriate training [489].

RSC IIaC (LoE C, GoR 5)

Comments: It is advisable to take into account the anamnesis, arrhythmia pattern, presence of symptoms, and compliance of the patient with AF. Some studies have shown that advanced age is a predictor of complications during catheter ablation of AF and increases the risk of AF/AFL recurrence, death, and major adverse cardiac events.

• In elderly and senile patients, a comprehensive approach to AF treatment and individualized drug dosage selection with the assessment of comorbid conditions is recommended [158].

RSC IC (LoE C, GoR 5)

• External electrical cardioversion can be safely performed at all stages of pregnancy and is recommended for patients with hemodynamically significant AF if the risk of complications from ongoing AF is considered high for both mother and fetus [158]

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

Comments: Rhythm control should be considered the preferred strategy during pregnancy. Fetal heart rate should be monitored regularly after the procedure. Cardioversion should generally be preceded by anticoagulation.

• Anticoagulant therapy is recommended for pregnant women with AF if there is a high risk of thromboembolic events according to the CHA2DS2-VASc score [490].

ESC IB (LoE C, GoR 5)

Comments: Low-molecular-weight heparins (ATX B01AB Heparin group) are the drugs of choice during pregnancy. They can be used throughout the entire pregnancy. NOACs and fondaparinux sodium are not recommended, partly due to the lack of safety studies. VKAs must not be used in the first trimester of pregnancy and for 4 weeks prior to delivery; at other times, they should be used only in cases of absolute necessity when heparin and its derivatives cannot be used, and solely by decision of a medical board.

• The prescription of NOACs during pregnancy as well as during its planning is not recommended [158].

ESC IIIC (LoE C, GoR 5)

Comments: Currently, there is insufficient evidence regarding the safety of NOACs in pregnant women, despite the relative safety of these drugs compared to VKAs in the general patient cohort. The algorithm for prescribing anticoagulant therapy in comorbid conditions is presented in Table P13, Appendix B.

• Selective beta-blockers are generally safe and are recommended as first-line drugs in pregnant patients with AF. For acute heart rate control, intravenous administration of beta-blockers is recommended [158, 374, 663, 674].

ESC IB (LoE C, GoR 5)

Comment: Pharmacotherapy should be initiated at the lowest effective dose. It is recommended to check drugs and safety data before starting any new medication.

• If selective beta-blockers are ineffective in pregnant patients with AF, the use of digoxin** and #verapamil (40–80 mg 3 times daily for elective therapy or intravenously at a dose of 5–10 mg over 2 min for emergency indications) should be considered for heart rate control [158, 374, 674, 679].

ESC IB (LoE C, GoR 5)

• If beta-blockers are ineffective as a rhythm control strategy, it is recommended to consider prescribing sotalol**, flecainide, or propafenone** in pregnant patients with AF/AFL [674-677].

ESC IIaC (LoE C, GoR 5)

Comments: the use of the minimum effective therapeutic doses is recommended.

ESC IA (LoE B, GoR 2)

• Catheter ablation of the AF and AFL substrate is recommended for the prevention of arrhythmia recurrence in athletes [497, 498].

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

Comments: Catheter ablation is not considered a method that increases life expectancy or reduces the risk of stroke, but it can significantly improve quality of life.

ESC IIaC (LoE C, GoR 5)

• After taking oral formulations of propafenone**, patients are recommended to refrain from athletic exertion for as long as AF persists and further for up to two half-lives of the antiarrhythmic drug [267].

ESC IIaC (LoE C, GoR 3)

• Closure of atrial septal defects is recommended under the age of 40 to reduce the risk of AFL and AF [34, 499–504].

ESC IIaC (LoE B, GoR 3)

• In patients with a history of symptomatic atrial tachyarrhythmias and indications for surgical correction of an atrial septal defect, it is recommended to evaluate the feasibility of catheter ablation of AF during the surgical repair of the defect [158, 309, 374, 502, 503].

ESC IIaC (LoE C, GoR 5)

• The expediency of surgical treatment for AF (the Maze procedure) is recommended to be evaluated in patients with symptomatic AF scheduled for surgical correction of congenital heart disease [502, 504–506].

ESC IIaC (LoE C, GoR 4)

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

• Performing catheter ablation of atrial arrhythmias is recommended to be considered in specialized centers [158, 402].

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

• Before performing cardioversion in patients with congenital heart disease, it is recommended to consider preliminary transesophageal echocardiography (TEE) or, if not feasible, contrast-enhanced CT of the left atrium and pulmonary veins, combined with oral anticoagulant therapy for at least 3 weeks prior to the procedure [502, 504, 508, 509].

ESC IIbC (LoE C, GoR 4)

• Early surgical treatment is recommended for severe mitral regurgitation, preserved left ventricular ejection fraction, and newly diagnosed AF even in the absence of symptoms, especially if surgery is anticipated to be effective [510].

ESC IIaC (LoE B, GoR 2)

• Early mitral commissurotomy or replacement is recommended for asymptomatic patients with severe mitral stenosis, suitable valve anatomy, and newly diagnosed AF [510].

ESC IIaC (LoE B, GoR 2)

• In patients with ACS and AF, electrical cardioversion is recommended in case of hemodynamic instability, ischemia refractory to antianginal therapy, or inadequately controlled ventricular rate despite medical therapy [158].

ESC IC (LoE C, GoR 5)

• Intravenous administration of amiodarone** or beta-blockers is recommended for patients with AF and ACS to slow the ventricular rate [158].

ESC IC (LoE C, GoR 5)

• In the absence of clinical signs of heart failure, intravenous administration of nondihydropyridine calcium channel blockers (verapamil**) is recommended to reduce the ventricular rate [158].

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

• In patients with AF and ACS complicated by heart failure symptoms, intravenous administration of digoxin** should be considered to reduce the ventricular rate [158].

ESC IIb C (LoE C, LE 5)

ESC IIIB (LoE C, GoR 5)

ESC IIIB (CGR B, LOR 2)

• Glycemic control in diabetes mellitus is recommended for patients with diagnosed AF and diabetes to reduce the risk of thromboembolic events and improve the long-term prognosis of AF [313, 314, 511-515].

RSC IA (LoE B, GoR 2)

Comments: In patients with AF, a long history of diabetes mellitus appears to increase the likelihood of thromboembolic events, but does not affect the risk of bleeding during oral anticoagulant therapy. Intensive glycemic control does not affect the incidence of new-onset AF, whereas treatment with metformin** is associated with a reduced long-term risk of AF in this category of patients and likely helps reduce the risk of stroke [516].

• In patients with diabetes mellitus and AF, it is recommended to control all cardiovascular risk factors, including blood pressure and blood lipid levels [316, 511, 513-516].

ESC IC (LoE B, GoR 3)

• When AF occurs against the background of an acute respiratory infection or an exacerbation of chronic pulmonary disease, correction of hypoxemia and acidosis is recommended first and foremost [34, 317, 319, 327, 485, 517-522].

ESC IC (LoE C, GoR 4)

• Electrical cardioversion is recommended for patients with pulmonary diseases if the developed episode of AF causes hemodynamic instability [34, 317, 318, 517-522]

ESC IC (LoE B, GoR 3)

• In patients with chronic obstructive pulmonary disease, for ventricular rate control, it is recommended to use nondihydropyridine calcium channel blockers (verapamil** / #diltiazem) or, alternatively, selective beta-blockers or digoxin** [34, 317, 318, 319, 517-522, 633-636].

ESC IIaC (LoE B, GoR 3)

Comments: Standard therapeutic dosages of these drugs are presented in tables P10 and P11 of Appendix A3.

• The administration of non-selective beta-adrenomimetics and theophylline** is not recommended for patients with bronchospastic syndrome [34, 317, 318, 517-522].

ESC IIIC (LoE C, GoR 5)

ESC IIIC (LoE B, LoR 3)

• In patients with AF and a high probability of obstructive sleep apnea syndrome, it is recommended to perform additional diagnostic evaluation to verify the diagnosis [317, 318, 517-522].

ESC IIaB (LoE B, LoR 3)

Comments: Apnea causes an increase in atrial pressure, their size, and changes in the state of the autonomic nervous system. Timely correction of risk factors can improve long-term treatment outcomes in patients with AF.

• To reduce the frequency of AF recurrences and improve disease control, it is recommended to prescribe optimal therapy aimed at correcting obstructive sleep apnea [319, 519-522].

ESC IIaB (LoE B, LoR 3)

• To control ventricular rate in patients with AF against the background of thyrotoxicosis, it is recommended to use $\beta$-blockers, unless contraindicated [523].

RSC IIaC (LoE C, GoR 5)

Comments: In case of thyrotoxic crisis, their intravenous administration is possible; high doses of drugs may be required.

• If the use of $\beta$-blockers is impossible, for heart rate control in patients with AF and thyrotoxicosis, it is recommended to prescribe selective calcium channel blockers with a direct effect on the heart: #diltiazem or verapamil** [523, 633-636, 374, 669].

ESC IIaC (LoE C, GoR 5)

Comments: Standard therapeutic dosages of these drugs are presented in tables P10 and P11 of Appendix A3.

• If heart rhythm control is desired, thyroid function is recommended to be normalized prior to cardioversion, otherwise the probability of arrhythmia recurrence is high [523].

ESC IIaC (LoE C, GoR 5)

CKD is a frequently encountered comorbid condition in patients with AF; the prevalence of CKD worldwide continues to increase [524]. According to the ORBIT-AF registry, 30% of patients with AF have stage III, IV, or V CKD, and according to the domestic REKVAZA registry, approximately half of patients with AF have comorbid kidney pathology [525, 526]. There is a bidirectional interaction between AF and CKD: CKD predisposes to the development of AF, and the presence of AF is associated with deterioration of intrarenal hemodynamics, the risk of a further decrease in the glomerular filtration rate, and an increase in albuminuria [527]. Approximately one in five patients with CKD has newly diagnosed AF, and 50% of patients with AF have varying degrees of renal filtration function impairment. Compared to patients with only AF or CKD, patients with their combination have an increased risk of stroke and mortality due to an excessive risk of both TEAs and major bleeding, which makes risk stratification and treatment complex tasks [528].

• In all patients with AF, it is recommended to test blood creatinine levels or creatinine clearance (CrCl) using the Cockcroft-Gault formula in order to identify comorbid renal pathology and correctly select the dose of anticoagulant and antiarrhythmic drugs [58, 61-64, 65, 529].

ESC IA (LoE C, GoR 5)

Comments: The frequency of renal function monitoring in patients with AF receiving oral anticoagulants is presented in Section 5. Unlike the prescription of DOACs, where the choice of dose depends on the CrCl level, when choosing the dosage of AADs, there is no priority for the specified calculation formulas, since studies of this orientation have not been conducted [158]. Reduced renal filtration function may be important regarding the pharmacokinetics of the medications used. The main changes in drug pharmacokinetics in patients with CKD include bioavailability, volume of distribution, protein binding, drug metabolism, and excretion. These changes can lead to decreased elimination of drugs and/or their metabolites, increased sensitivity to drugs, an increased risk of side effects, and even loss of efficacy. For AADs eliminated by the kidneys, the most dangerous consequences of drug accumulation include toxic and arrhythmogenic effects with potential life-threatening complications [529]. When prescribing antiarrhythmic therapy in patients with AF and CKD, significant difficulties arise because assessing the impact of renal failure on the metabolism of a specific drug is complex due to the lack of a quantitative algorithm for predicting class-specific complications for AADs of various classes [530, 531].

• In patients with AF, when prescribing antiarrhythmic therapy, it is recommended to adjust the drug dose based on the glomerular filtration rate, taking into account the potential prolongation of the elimination half-life [58, 158].

RSC IC (CGR C, LOR 5)

Comments: Drug dosages in the treatment of AF and CKD must comply with the instructions. Tables P14 and P15 of Appendix A3 present the characteristics of drugs for maintaining sinus rhythm and controlling ventricular rate in AF and CKD. Patients without clear indications for rhythm control should default to a rate control strategy. At the same time, one should take into account the variability of symptoms and the potentially increased propensity to develop tachy-induced cardiomyopathy, the pharmacokinetics, and dialyzability of drugs used for rate control.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

• In patients with any form of AF, it is recommended to perform individual and group physical therapy sessions, including the use of exercise machines, with the aim of increasing their physical performance, quality of life, and cardiac function (LVEF) [532-535].

ESC IA (LOCE B, LOE 1)

Comments: Meta-analyses of analyzed randomized controlled trials have shown that as a result of physical training, patients with AF significantly improved exercise tolerance, LVEF, and scores on the “General Health” and “Vitality” scales of the SF-36 questionnaire (Table P12, Appendix G1). Available data also indicate an improvement in quality of life and LVEF, as well as a decrease in the severity of AF symptoms in the short term (up to 6 months) after exercise-based cardiac rehabilitation compared to no exercise control.

• In patients with AF, it is recommended:

  – three or more weekly sessions of moderate-intensity aerobic activity, such as walking, running, cycling, lasting at least 60 minutes for at least 3 months (optimally 6 months);

  – additionally including yoga and balance exercises in sessions to improve quality of life [532, 536-540].

ESC IA (LoE B, LoR 1)

Comments: Aerobic exercise and yoga have a positive effect on the emotional state of patients and help attenuate neurohormonal reactions to stress triggers [541, 542].

Moderate-intensity aerobic exercise for approximately 60 minutes every day for several months can reduce the risk of cardiovascular events. Sessions lasting 60 minutes compared to 120-minute exercises are accompanied by a higher level of patient adherence [543, 544].

• In patients with AF, in addition to physical training, it is recommended to implement educational programs with the aim of improving disease awareness, reducing cardiovascular hospitalization and cardiovascular death [512, 535, 545].

ESC IB (LoE B, LoR 2)

• In patients who have undergone successful catheter ablation, it is recommended to conduct interdisciplinary cardiac rehabilitation programs lasting from 3 to 12 months, including physical exercise (including yoga classes), educational and psychological counseling with the aim of increasing physical performance, improving LVEF, reducing resting heart rate, and lowering anxiety levels [546-549].

ESC IA (LoE B, GoR 2)

• In patients who have undergone successful catheter ablation, it is recommended to prescribe physical training 1 month after surgical treatment [548, 549].

RSC IA (LoE B, GoR 2)

Comments: During a single-center, six-month randomized clinical trial comparing the results of an exercise-based cardiac rehabilitation program with clinical follow-up starting 4 weeks after catheter ablation, an increase in patients' physical performance was demonstrated without increasing the risk of AF recurrence.

Patients participated in a supervised exercise training program once or twice a week in a rehabilitation setting and were also instructed to perform unsupervised moderate-intensity walking for 30 minutes 2–3 times a week during the 6-month study period. The medically supervised exercise program combined moderate-intensity endurance training, such as stationary cycling or treadmill walking, with resistance training on weight machines at 40% to 60% of one repetition maximum [548].

There are isolated studies in which personalized exercise training programs were initiated in the inpatient setting immediately after surgery in the form of breathing exercises, a therapeutic exercise complex with energy expenditure calculations for each exercise, step training, and timed walking [550].

5. Prevention and Dispensary Observation

It is advisable to refer a patient with diagnosed or suspected AF for a consultation with a general practitioner or cardiologist for further evaluation, risk assessment, and treatment selection. The minimum initial evaluation should include 12-lead electrocardiography (ECG), echocardiography (EchoCG), complete blood count, routine blood chemistry, Holter ECG monitoring (multi-day monitoring if necessary), blood thyroid-stimulating hormone (TSH) level, and thyroid hormone testing (serum free thyroxine (fT4)).

Depending on the patient's condition, treatment goals, and comorbidities, further follow-up care may be provided by a general practitioner and cardiologist. The general practitioner's role is to monitor treatment efficacy, including the safety and effectiveness of anticoagulant therapy, maintain patient adherence to long-term therapy, and make timely referrals to specialists when indicated.

• As part of routine follow-up examinations it is recommended to include a 12-lead electrocardiogram (ECG) at least once a year in patients with AF (to exclude proarrhythmic effects of drugs, detect new rhythm and conduction disorders, ischemic changes, and signs of structural heart disease), assess renal function (with serum creatinine determination), and measure low-density lipoprotein cholesterol [34, 37, 628].

ESC – no (CURL C, LOR 5)

Patients receiving VKA therapy should have their INR levels monitored regularly. Holter ECG monitoring (to evaluate treatment efficacy, identify correlations between symptoms and arrhythmia episodes, or diagnose other significant rhythm and conduction disorders), EchoCG, and other tests may be performed as clinically indicated.

• Long-term electrocardiographic monitoring (Holter ECG monitoring) is recommended for patients with AF to assess treatment efficacy, identify correlations between symptoms and arrhythmia episodes, or diagnose other significant rhythm and conduction disorders [53].

RSC IC (LoE C, GoR 5)

• In the event of clinical deterioration or progression of the underlying cardiovascular disease during ongoing treatment, patients with AF are recommended an unscheduled visit (consultation) with a cardiologist to determine the scope of diagnostic tests, adjust therapy, and evaluate the need for hospitalization in a specialized department [37].

ESC – no (CURL C, LOR 5)

Catheter ablation of AF and/or atrial flutter does not alter the follow-up protocol for this group of patients.

• To improve treatment efficacy, lifelong follow-up with visits to a physician at least twice a year is recommended for the majority of patients with AF [551, 552].

ESC IIaB (LOCE B, LOE 2)

• During follow-up examinations of patients with AF, it is recommended to regularly assess the presence and progression of background diseases and risk factors in order to reduce the risk of complications [551, 552].

ESC IIaB (LOCE B, LOE 2)

Comments: Achieving control of comorbid conditions and managing modifiable risk factors improves prognosis in patients with AF and is a primary treatment goal. Key health targets include weight loss, alcohol cessation, moderate-intensity physical activity, sustained maintenance of target blood pressure levels, sustained compensation of heart failure, achievement of target low-density lipoprotein cholesterol levels in patients with concomitant coronary artery disease, glycemic control in patients with diabetes mellitus, optimal management of obstructive sleep apnea syndrome, etc. [308, 309, 553-555].

• All patients receiving VKA therapy are recommended to monitor their INR (Determination of the International Normalized Ratio (INR)) (targeting a therapeutic range of 2.0 to 3.0) with time in the therapeutic range (TTR) > 70% of observations. The algorithm for warfarin** dose adjustment is presented in Table P2 of Appendix B [97, 98].

ESC IB (CURL B, LOR 3)

Comments: The target INR range for patients receiving VKA monotherapy is 2.0–3.0. The target INR range for patients receiving a combination of VKAs and antiplatelet agents is 2.0–2.5. The time in therapeutic range (TTR), reflecting the percentage (%) of INR measurements within the therapeutic window, should be at least 70%.

• At each medical examination, it is recommended to assess treatment adherence and the adequacy of anticoagulation therapy in all patients with AF to reduce the risk of thromboembolic events, including stroke, as well as the risk of bleeding [556].

ESC IB (LoE B, GoR 2)

Comments: Routine INR monitoring is not recommended for patients receiving NOAC therapy; factors affecting drug and dose selection (creatinine clearance, age, weight, concomitant medications), liver function, hemoglobin levels, and platelet count are assessed dynamically.

ESC IB (CURL B, LOR 2)

Comments: Creatinine clearance for determining NOAC dosing should preferably be calculated using the Cockcroft-Gault formula, as this methodology was used in major clinical trials evaluating the efficacy and safety of NOACs. Based on the creatinine clearance value, the optimal NOAC and its correct dose must be selected.

• To improve treatment adherence, it is recommended to provide individualized counseling to patients with AF regarding their disease, treatment methods, and goals [557-559].

ESC IC (CURL B, LOR 3)

Comments: An adequate understanding of one's disease and the necessity of specific therapeutic measures can improve the clinical course of the disease and treatment outcomes. It is recommended to educate all patients with AF on action algorithms in case of clinical deterioration, including informing patients in accessible language about the initial symptoms of stroke and the importance of immediately calling a doctor if stroke or TIA is suspected.

• To exclude the proarrhythmic effects of drugs in patients with AF receiving antiarrhythmic or rate-control therapy, it is recommended to record, interpret, and describe a 12-lead electrocardiogram at least once a year [260, 262, 322, 325-327, 481, 560, 561, 628].

ESC IA (CURL B, LOR 2)

6. Organization of Medical Care

To improve the quality of medical care and select optimal management strategies, it is necessary to develop routing pathways for patients with AF at all stages of care, including primary health care (e.g., feldsher-midwife stations, central district hospitals) and specialized care, taking regional characteristics into account.

6.1 Indications for scheduled hospitalization

• Performing cardioversion when indicated (the approach to assessing thromboembolic risk and prescribing anticoagulant therapy is outlined in Section 3.1.1).

• Selection of rate-control therapy. The presence of rapid ventricular response must be documented on an ECG or during resting Holter ECG monitoring.

Adjustment of antiarrhythmic therapy.

• Worsening of heart failure in the setting of AF.

• Pacemaker implantation.

• Performing interventional and surgical procedures.

6.2 Indications for emergency hospitalization

• AF with hemodynamic instability (presyncopal or syncopal states, hypotension, signs of myocardial ischemia) regardless of the duration of the paroxysm and the form of AF, and/or AF with rapid ventricular response.

• AF paroxysm lasting up to 48 hours in cases of failed pharmacological cardioversion or contraindications to pharmacological cardioversion. In cases where rhythm restoration is not indicated (e.g., in previously identified minimally symptomatic AF paroxysms that do not affect hemodynamics and with established anticoagulant therapy), hospitalization may not be required.

• If there are indications (unstable hemodynamics, ventricular tachysystole, prior use of oral anticoagulants according to guidelines, or an AF episode lasting less than 48 hours), rhythm restoration or rate-control therapy may be performed by an ambulance crew at the pre-hospital stage.

6.3 Indications for hospital discharge

• An AF treatment strategy (rhythm control or ventricular rate control) has been selected and discussed with the patient.

• Thromboembolic risk assessment was performed, anticoagulant therapy was prescribed if necessary (Section 3.1.1), and the patient was informed about the importance of taking it. Replacing anticoagulant therapy with antiplatelet therapy is unacceptable.

• When performing cardioversion, anticoagulant therapy should be prescribed for at least 4 weeks in the absence of contraindications.

• Before prescribing anticoagulant therapy, an examination was performed, including a complete blood count (CBC), blood creatinine measurement with glomerular filtration rate calculation and creatinine clearance using the Cockcroft-Gault formula, blood glucose, potassium, sodium, and total bilirubin levels, and thyroid hormone status (thyroid-stimulating hormone [TSH] and serum free thyroxine [FT4]); these laboratory tests can be performed at both the inpatient and outpatient stages.

• If a VKA is used as the oral anticoagulant, INR monitoring (Determination of the International Normalized Ratio [INR]) was prescribed with instructions for subsequent outpatient measurements. If a rate-control strategy is chosen, adequate rate-lowering therapy was prescribed.

• Following ablation/surgical procedures, when indicated (Chapter 3.2.1), anticoagulant therapy should be prescribed for at least 8 weeks, and then indefinitely if stroke risk factors are present. The patient must be warned about the dangers of independently discontinuing the oral anticoagulant.

• A diagnostic workup for potential causes of AF was performed (exercise stress test or equivalent to rule out CHD, valvular heart disease, and thyroid disorders, as well as transient reversible causes such as electrolyte imbalances; these methods can be performed at either the inpatient or outpatient stages).

• Medicinal products were prescribed in accordance with the instructions for medical use, the pharmacotherapeutic group, and the route of administration and use.

6.4 Other organizational technologies

• During follow-up of patients with AF to optimize medical and anticoagulant therapy, it is advisable to:

• Perform thromboembolic and bleeding risk stratification at each patient medical encounter.

• Regularly record an electrocardiogram (ECG) to assess for potential signs of antiarrhythmic drug (AAD) overdose and rate-lowering therapy (assessment of PR interval and QT/QTc).

• Measure blood creatinine and glomerular filtration rate using the Cockcroft-Gault formula in patients on continuous anticoagulant therapy (Table P14 of Appendix A3).

• Regularly monitor INR levels (Determination of the International Normalized Ratio [INR]) to achieve the therapeutic anticoagulation range when a VKA is chosen as the anticoagulant.

• Conduct educational seminars for patients with AF to improve adherence to medical therapy.

• Consider ECG telemetry for patients with asymptomatic and mildly symptomatic AF.

• Use remote monitoring systems in patients with implanted pacemakers.

Use technologies that improve adherence to antiarrhythmic and anticoagulant therapy (medication reminder systems).

7. Additional Information

Improving patients' quality of life and preventing thromboembolic events are the primary goals of AF/AFL management. In addition to optimal antiarrhythmic and anticoagulant therapy, other important factors influencing the long-term prognosis of patients with AF include:

- correction of all modifiable risk factors (smoking, alcohol consumption, obesity, obstructive sleep apnea syndrome, electrolyte disturbances);

- treatment of comorbid conditions (CHD, CHF, diabetes mellitus, hypertension, CKD, thyroid disorders, obesity, obstructive sleep apnea syndrome).

Criteria for Evaluating the Quality of Medical Care

Quality of care criteria for primary health care in atrial fibrillation and flutter (ICD-10 codes I48.0, I48.1, I48.2, I48.3, I48.4, I48.9)

Quality of care criteria for specialized medical care in adults with atrial fibrillation and flutter (ICD-10 codes: I48.0, I48.1, I48.2, I48.3, I48.4, I48.9)

References

Appendix A1. Working Group Composition

Steering Committee of the Working Group:

Golitsyn S.P., MD, PhD, Professor (Moscow) – Co-chair, Russian Society of Cardiology

Goluhova E.Z., Academician of the RAS, MD, PhD, Professor (Moscow) – Co-chair, Russian Society of Cardiology, Association of Cardiovascular Surgeons of Russia

Mikhailov E.N., MD, PhD (Saint Petersburg) – Co-chair, Russian Society of Cardiology

Revishvili A.Sh., Academician of the RAS, MD, PhD, Professor (Moscow) – Co-chair, All-Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Pacing

Working Group Members:

Arakelyan M.G., PhD (Moscow), Russian Society of Cardiology

Vasilieva E.Yu., MD, PhD, Professor (Moscow), Russian Society of Cardiology

Davtyan K.V., MD, PhD, Professor (Moscow), All-Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Pacing

Drapkina O.M., Academician of the RAS, MD, PhD, Professor (Moscow), Russian Society of Cardiology

Drozdova L.Yu., PhD (Moscow), Russian Society of Cardiology

Kropacheva E.S., PhD (Moscow), Russian Society of Cardiology

Kuchinskaya E.A., PhD (Moscow), Russian Society of Cardiology

Layovich L.Yu., PhD (Moscow), Russian Society of Cardiology

Mironov N.Yu., PhD (Moscow), Russian Society of Cardiology

Mishina I.E., MD, PhD, Professor (Ivanovo), Russian Society of Cardiology

Panchenko E.P., MD, PhD, Professor (Moscow), Russian Society of Cardiology

Rzaev F.G., PhD (Moscow), All-Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Pacing

Tatarsky B.A., MD, PhD, Professor (Saint Petersburg), Russian Society of Cardiology

Utsumueva M.D. (Moscow), Russian Society of Cardiology

Shakhmatova O.O., PhD (Moscow), Russian Society of Cardiology

Shlevkov N.B., PhD (Moscow), Russian Society of Cardiology

Shector A.V., MD, PhD, Professor (Moscow), Russian Society of Cardiology

Andreev D.A., MD, PhD, Professor (Moscow), Russian Society of Cardiology

Artyukhina E.A., MD, PhD (Moscow), All-Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Pacing

Barbarash O.L., Corresponding Member of the RAS, MD, PhD (Kemerovo), Russian Society of Cardiology

Boqueria L.A., Academician of the RAS, MD, PhD, Professor (Moscow), Association of Cardiovascular Surgeons of Russia

Galyavich A.S., MD, PhD, Professor (Kazan), Russian Society of Cardiology

Duplyakov D.V., MD, PhD, Professor (Samara), Russian Society of Cardiology

Zenin S.A., MD, PhD (Novosibirsk), Russian Society of Cardiology

Irtyuga O.B., MD, PhD (Saint Petersburg), Russian Society of Cardiology

Kanorsky S.G., MD, PhD, Professor (Krasnodar), Russian Society of Cardiology

Lebedev D.S., MD, PhD, Professor (Saint Petersburg), Russian Society of Cardiology

Novikova N.A., MD, PhD, Professor (Moscow), Russian Society of Cardiology

Popov S.V., Academician of the RAS, MD, PhD, Professor (Tomsk), Russian Society of Cardiology

Serguladze S.Yu., MD, PhD (Moscow), Association of Cardiovascular Surgeons of Russia, All-Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Pacing

Filatov A.G., MD, PhD (Moscow), Association of Cardiovascular Surgeons of Russia, All-Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Pacing

Shlyakhto E.V., Academician of the RAS, MD, PhD, Professor (Saint Petersburg), Russian Society of Cardiology

Shubik Yu.V., MD, PhD, Professor (Saint Petersburg), Russian Society of Cardiology

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

Appendix A2. Methodology for Developing Clinical Guidelines

These guidelines are developed on the basis of the 2019 Russian Guidelines for the Diagnosis and Treatment of Atrial Fibrillation, the 2024 and 2020 European Society of Cardiology Guidelines for the Diagnosis and Treatment of Atrial Fibrillation, and the 2017 Guidelines of the All-Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Cardiac Pacing (VNOA) and the All-Russian Scientific Society of Cardiology (VNOK) on Electrophysiological Studies, Catheter Ablation, and the Use of Implantable Antiarrhythmic Devices.

The guidelines provide a summarized and systematic analysis of available clinical studies on the prevention, diagnosis, and treatment of patients with AF and AFL.

Target audience of these clinical guidelines:

1. Cardiologist.

2. General practitioner / Physician.

3. General practitioners (family physicians).

4. Cardiovascular surgeon.

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

In this regard, national guidelines were developed based on ESC guidelines, taking into account national specifics, diagnostic and treatment features, and the availability of certain medical care. For this reason, during the development of Russian clinical guidelines by the RSC, international classes of recommendation were used, allowing assessment of the necessity of a guideline statement and the levels of evidence for these classes (Tables 1/A2 and 2/A2).

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

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

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

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

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

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

Table 5/A2. Scale for assessing grades of recommendations (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and 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

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

2. Standard of medical care for patients with atrial fibrillation and atrial flutter (for specialized care delivery), approved by Order of the Ministry of Health of the Russian Federation No. 1622n dated December 28, 2012.

3. Order of the Ministry of Health of the Russian Federation No. 520n dated July 15, 2016, "On Approval of Criteria for Assessing the Quality of Medical Care."

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

Table P1. Risk factors for bleeding in patients with atrial fibrillation receiving anticoagulants

OAC – anticoagulant therapy, GCS – glucocorticosteroids, eGFR – estimated glomerular filtration rate, NSAIDs – nonsteroidal anti-inflammatory and antirheumatic drugs, INR – international normalized ratio, TTR – Time in Therapeutic Range

Table A2. Factors increasing the risk of recurrent intracerebral hemorrhage upon resumption of oral anticoagulants in atrial fibrillation patients

MRI – magnetic resonance imaging, ACS – acute coronary syndrome, PCI – percutaneous coronary intervention

Table A3. Therapeutic doses of unfractionated heparin** and #enoxaparin sodium** used in patients with atrial fibrillation [65, 128, 133, 664]

Table A4. Parameters to be evaluated prior to administration of a DOAC reversal agent

TT – thrombin time; PT – prothrombin time; aPTT – activated partial thromboplastin time;

Table A5. Classification of elective invasive procedures by bleeding risk

Table A6. Use of oral anticoagulants in patients with thrombocytopenia and anemia (modified from [136, 137]).

Comments: HIT – heparin-induced thrombocytopenia, OACs – oral anticoagulants, DOACs – direct oral anticoagulants, Plt – platelets

Table A7. Recommended discontinuation periods for direct oral anticoagulants prior to elective invasive/surgical procedures (excluding arrhythmia ablation)

CrCl– creatinine clearance.

Table A8. Recommended frequency of monitoring hemoglobin, renal, and hepatic function in patients on long-term direct oral anticoagulant therapy

Table A9. Situations where long-term anticoagulant therapy is contraindicated versus when it may be continued

Table A10. Dosages and oral administration regimens of heart rate control drugs in atrial fibrillation and atrial flutter

BB – beta-blockers

Notes:

a – [645], b – [562], c – [646], d – [647], e – [648], f – [665], g – [666], h – [667], i – [668]

Note: ¹ The individual dose of digoxin** is determined by the optimal serum drug concentration (0.5–0.9 ng/mL), ensuring the best balance of efficacy and safety.

² The drug may be prescribed if BBs, calcium channel blockers, and digoxin** are ineffective or contraindicated.

Table P11. Dosages and regimens of heart rate control drugs for atrial fibrillation and atrial flutter via IV administration

BB – beta-blockers

Table P12. Dosages and regimens of drugs for pharmacological cardioversion of atrial fibrillation and atrial flutter

Note:

a – [268], b – [267], c – [291], d – [678]

¹ – according to the E. Vaughan-Williams classification modified by D. Harrison.

Note: ¹ – according to the E. Vaughan-Williams classification modified by D. Harrison.

Abbreviations: AV – atrioventricular, i.v. – intravenous, CAD – coronary artery disease, LV – left ventricle, HF – heart failure, AF – atrial flutter, CHF – chronic heart failure, HR – heart rate, ECG – electrocardiogram.

Table P13. Oral drugs used to maintain sinus rhythm in patients with atrial fibrillation and atrial flutter

Note: ¹ – according to the E. Vaughan-Williams classification modified by D. Harrison.

Abbreviations: VKA – vitamin K antagonists, AV – atrioventricular, LVH – left ventricular hypertrophy, CAD – coronary artery disease, CrCl – creatinine clearance, LV – left ventricle, SA – sinoatrial, EF – ejection fraction, CHF – chronic heart failure, ECG – electrocardiogram, β-blockers – beta-adrenergic blockers.

Note 2 - Use of Sotalol** in patients with renal impairment

Since sotalol** is excreted primarily by the kidneys and its half-life is prolonged in renal failure, the dosing regimen (interval between doses) should be modified if CrCl is <60 mL/min, according to the table below.

Table P14. Characteristics of drugs for maintaining sinus rhythm in atrial fibrillation and atrial flutter and chronic kidney disease

CHF – congestive heart failure; CKD – chronic kidney disease; CrCl – creatinine clearance; LVEF – left ventricular ejection fraction; eGFR – estimated glomerular filtration rate; HD – hemodialysis.

Table P15. Characteristics of antiarrhythmic drugs for ventricular rate control in atrial fibrillation and atrial flutter and chronic kidney disease

eGFR – estimated glomerular filtration rate;

Notes:

a – [645]

b – [562]

c – [646]

g – [647]

d – [648]

Appendix B. Physician Action Algorithms

Table P1. Algorithm for decision-making on long-term anticoagulant therapy in patients with CHA2DS2-VASc = 1 for men and CHA2DS2-VASc = 2 for women (according to [625])

Notes: factors increasing the risk of thromboembolic events include the following: persistent/permanent atrial fibrillation, atrial fibrillation (not flutter), obesity, proteinuria (more than 150 mg per 24 hours or equivalent values), estimated glomerular filtration rate less than 45 ml/min, Nt-proBNP >1400 ng/L, positive troponin T or I, significant left atrial enlargement (transverse dimension ≥4.7 cm, volume ≥73 ml), decreased blood flow velocity in the left atrial appendage (less than 20 cm/s), ABC index. If the only non-sex-related thromboembolic risk factor included in CHA₂-DS₂-VASc is age over 65 years or diabetes mellitus, this is also an additional argument in favor of prescribing anticoagulants.

VKA – vitamin K antagonists, DOAC – direct oral anticoagulants

Table P2. Warfarin** dose titration algorithm (2.5 mg tablets)

Table S3. Algorithm for switching oral anticoagulants

A. Algorithm for patients receiving vitamin K antagonists

INR – international normalized ratio, DOAC – direct oral anticoagulants

B. Algorithm for patients receiving direct oral anticoagulants

INR – international normalized ratio, DOAC – direct oral anticoagulants

Table S4. Algorithm for anticoagulant therapy in patients with atrial fibrillation undergoing cardioversion

A. Algorithm for patients RECEIVING ORAL ANTICOAGULANTS for at least 3 weeks

ACT – anticoagulant therapy, LA – left atrium, OAC – oral anticoagulants, DOAC – direct oral anticoagulants, TEC – thromboembolic complications, AF – atrial fibrillation, TEE – transesophageal echocardiography.

Comment: performing TEE in these clinical situations is not mandatory but preferred. It is most appropriate to perform this study in patients at high risk of thromboembolic complications (and LA thrombosis, respectively), as well as in case of doubts regarding adherence to anticoagulant therapy. A protocol should be developed for each specific clinic, taking into account its technical capabilities and staff experience, regulating the use of TEE before cardioversion.

Note: early cardioversion is defined as cardioversion performed immediately upon seeking medical attention

B. Algorithm for patients NOT RECEIVING ORAL ANTICOAGULANTS for a minimum of 3 weeks

ACT – anticoagulant therapy, LA-left atrium, UFH – heparin sodium**, EN – #enoxaparin sodium**, OAC – oral anticoagulants, DOAC – direct oral anticoagulants, TEC – thromboembolic complications, AF – atrial fibrillation, TEE – transesophageal echocardiography.

Note: early cardioversion is defined as cardioversion performed immediately upon seeking medical attention

Comment: * – performing TEE in these clinical situations is not mandatory but preferred. It is most appropriate to perform this study in patients at high risk of thromboembolic complications (and LA thrombosis, respectively), as well as in case of doubts regarding adherence to anticoagulant therapy. A protocol should be developed for each specific clinic, taking into account its technical capabilities and staff experience, regulating the use of TEE before cardioversion.

Table S5. Decision-making algorithm for initiating or resuming oral anticoagulant therapy in a patient with ischemic stroke

A. Algorithm for stroke without hemorrhagic transformation according to neuroimaging

IS – ischemic stroke, CT – computed tomography, MRI – magnetic resonance imaging, BP – blood pressure, AH – arterial hypertension, TIA – transient ischemic attack, EchoCG – echocardiography.

Comments: minor neurological deficit – <8 points on the NIHSS scale, moderate neurological deficit 8-15 points on the NIHSS scale, severe (including moderately severe) neurological deficit >15 points on the NIHSS scale.

Table S6. Management algorithm for a patient with atrial fibrillation taking oral anticoagulants who develops bleeding

A. Bleeding in a patient taking warfarin**

B. Bleeding in a patient taking dabigatran etexilate**

C. Bleeding in a patient taking apixaban**, rivaroxaban** or edoxaban

INR – international normalized ratio, Plt – platelets, PCC – prothrombin complex concentrate (blood coagulation factors II, VII, IX and X in combination [Prothrombin complex]**), FFP – fresh frozen plasma.

Table S7. Selection of antithrombotic therapy regimen after PCI in patients with atrial fibrillation and indications for long-term anticoagulant therapy

ASA – acetylsalicylic acid**, iP2Y₁₂ – platelet P2Y12 receptor inhibitors, IHD – ischemic heart disease, PCI – percutaneous coronary intervention, ACS – acute coronary syndrome, OAC – oral anticoagulants

Table S8. Algorithm for long-term ventricular rate control in ASYMPTOMATIC atrial fibrillation or atrial flutter

AV – atrioventricular, CRT – cardiac resynchronization therapy device (233950 – Implantable triple-chamber (biventricular) pacemaker)***; AFL – atrial flutter, AF – atrial fibrillation, HR – heart rate (ventricular), PM – pacemaker

Table S9. Algorithm for long-term ventricular rate control in SYMPTOMATIC atrial fibrillation or atrial flutter

AV – atrioventricular, CRT – cardiac resynchronization therapy device ((233950 – Implantable triple-chamber (biventricular) pacemaker***); AFL – atrial flutter, AF – atrial fibrillation, HR – heart rate (ventricular), PM – pacemaker

Table S10. Algorithm for cardioversion of atrial fibrillation or atrial flutter paroxysm

Table S11. Algorithm for the prevention of atrial fibrillation or atrial flutter recurrence

BB – beta-blockers

Note: Class 1C – AAD according to the E. Vaughan-Williams classification modified by D. Harrison.

Table S12. Anticoagulant therapy during catheter ablation for atrial fibrillation

Notes: * – considering catheter ablation without skipping the morning dose of apixaban** or dabigatran etexilate** is possible in patients with a very high risk of thromboembolic complications (CHA₂DS₂-VASc≥4), as well as in cases where the local protocol provides for the administration of heparin sodium** after transseptal puncture and/or routine use of protamine sulfate** before removing the sheath for the cardiac ablation system

ACT – activated clotting time, INR – international normalized ratio, IAS – interatrial septum, OAC – oral anticoagulants, DOAC – direct oral anticoagulants

Table S13. Algorithm for prescribing oral anticoagulants in comorbid conditions

Notes: R – recommended for use, C – use with caution, especially in the presence of additional bleeding risk factors or drug-drug interactions, Contraindicated – contraindicated

* criteria for prescribing a reduced dose of DOACs:

- for apixaban **: 2.5 mg twice daily if the patient has 2 or more of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine concentration ≥133 µmol/L, or CrCl 15–29 mL/min.

- for dabigatran etexilate **: 110 mg twice daily in patients older than 80 years, as well as in cases of concomitant verapamil ** use; at the physician's discretion based on the individual risk-benefit ratio for thrombotic and hemorrhagic complications, the dose may be reduced in case of an increased risk of bleeding (especially gastrointestinal bleeding), in patients with a creatinine clearance of 30–50 mL/min, and in patients aged 75–80 years.

- for rivaroxaban **: 15 mg once daily at a creatinine clearance of 15–49 mL/min;

- for edoxaban: 30 mg once daily in the presence of one of the following criteria: creatinine clearance of 15–49 mL/min, body weight ≤60 kg, concomitant use of strong P-glycoprotein inhibitors (cyclosporine **, erythromycin, ketoconazole).

Abbreviations: HIV – human immunodeficiency virus, CrCl – creatinine clearance, CKD – chronic kidney disease.

Appendix C. Patient Information

Atrial fibrillation and flutter (AF/AFL) are cardiac arrhythmias characterized by irregular electrical activity of the atria. Patients most frequently complain of a sensation of irregular or rapid heartbeat, potentially accompanied by shortness of breath, fatigue, and chest discomfort. If these symptoms have recently appeared, become more frequent, or progressed, seek medical attention immediately (optimally, call an ambulance). The irregularity of heartbeats leads to altered blood flow, which in turn can cause blood clots (thrombi) to form in the atria. The migration of thrombi via the bloodstream to blood vessels supplying the brain leads to ischemic stroke. The risk of stroke in patients with AF/AFL is five times higher compared to peers of the same age without arrhythmia. Key factors in preventing such complications are the timely detection of arrhythmia and the prescription of appropriate pharmacotherapy.

To reduce the risk of ischemic stroke, the physician may recommend therapy with blood-thinning medications—oral anticoagulants. According to their mechanism of action, these drugs block one of the clotting factors in the coagulation system and prevent thrombus formation at the earliest stage.

Depending on the type of arrhythmia, the patient and the attending physician may choose the most preferred management strategy for AF/AFL: rhythm control (taking medications to prevent arrhythmia episodes) or rate control. When choosing the latter, the drug dose is individually adjusted to help reduce the heart rate.

When pharmacotherapy is ineffective, interventional treatment methods for patients with AF/AFL are widely used—radiofrequency or cryoballoon catheter ablation, i.e., a procedure aimed at destroying the foci generating "aberrant" electrical impulses in the atria.

Regardless of the chosen treatment strategy, daily regular intake of oral anticoagulants and antiarrhythmic drugs as indicated is a mandatory condition for the successful treatment of patients with AF and AFL.

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

Appendix G1. Assessment scales, questionnaires, and other patient evaluation tools presented in the clinical guidelines

Table P1. Modified EHRA scale

Russian title: Modified EHRA scale.

Original title (if applicable): The modified European Heart Rhythm Association (mEHRA) symptom classification

Source (official developer website, validation publication):

Wynn GJ, Todd DM, Webber M, Bonnett L, McShane J, Kirchhof P, et al. The European Heart Rhythm Association symptom classification for atrial fibrillation: validation and improvement through a simple modification. Europace 2014;16:965–72. https://doi.org/10.1093/europace/eut395

Type (underline):

- rating scale

Purpose: scale for assessing the severity of symptoms associated with atrial fibrillation/flutter.

Content (template):

Key (interpretation): depending on the severity of arrhythmia symptoms, the patient is assigned a clinical manifestation class from I – no arrhythmia symptoms to IV – disabling symptoms.

Table P2. Child-Pugh scale for assessing the severity of liver cirrhosis

Russian title: Child-Pugh Score.

Original title (if applicable): Child-Pugh Score for Cirrhosis Mortality

Source (official developer website, validation publication):

Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646-9. doi: 10.1002/bjs.1800600817. PMID: 4541913.

Type (underline):

- rating scale

Purpose: Scoring system to assess the severity of liver cirrhosis and patient survival.

Content (template):

Key (interpretation): Severity grade based on the total score:

Class A <7 points

Class B 7-9 points

Class C >9 points

Table P3. Risk factors for stroke and systemic embolism in patients with atrial fibrillation and their point values (CHA₂DS₂-VASc score)

Russian title: CHA2DS2-VASc. Score for assessing the risk of thromboembolic events in patients with atrial fibrillation/flutter

Original title (if applicable): CHA2DS2-VASc

Source (official developer website, validation publication):

Olesen, Jonas Bjerring, et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. Bmj 342 (2011): d124.

Type (underline):

- rating scale

Purpose: clinical tool for predicting the risk of ischemic stroke and systemic thromboembolism in atrial fibrillation and flutter

Content (template):

Key (interpretation):

Notes: none

Table P4. Bleeding risk score HAS-BLED

Russian title: HAS-BLED. Score for assessing the risk of major bleeding in patients with atrial fibrillation.

Original name (if any): HAS-BLED score

Source (official developer website, validation publication): Pisters R, Lane DA, Nieuwlaat R, et al. "A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey." Chest. 2010;138(5):1093-1100.

Type (underline):

- rating scale

Purpose: assessment of major bleeding risk in patients with atrial fibrillation.

Content (template):

* First letters of English terms.

H – Hypertension, systolic BP >160 mm Hg. A – Abnormal renal and/or liver function: dialysis, kidney transplantation, or serum creatinine ≥200 µmol/L; chronic liver disease (e.g., cirrhosis) or biochemical evidence of significant hepatic derangement (e.g., bilirubin at least 2x the upper limit of normal in association with AST/ALT/alkaline phosphatase >3x the upper limit of normal, etc.). S – Stroke history. B – Bleeding history and/or predisposition, e.g., bleeding diathesis, anemia, etc. L – Labile INR: unstable/high INR or <60% of INR measurements within the target range. E – Elderly (age >65 years). D – Drugs/alcohol: concomitant use of antiplatelet agents, nonsteroidal anti-inflammatory and antirheumatic drugs (NSAIDs), or alcohol abuse.

Key (interpretation): 0-1 point: low bleeding risk. 2 points: moderate risk. ≥3 points: high risk, close monitoring and correction of modifiable risk factors required.

Table P5. National Institutes of Health Stroke Scale for assessing neurological deficit in stroke patients (NIHSS)

Russian title: NIHSS

Original title: National Institutes of Health Stroke Scale

Source: Adams, H. P., Davis, P. H., Leira, E. C., Chang, K-C., Bendixen, B. H., Clarke, W. R., Woolson, R. F., Hansen, M. D. (1999). Baseline NIH Stroke Scale score strongly predicts outcome after stroke: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology, 53, 126 -31.

Type (underline):

- rating scale

Purpose: to assess the severity of neurological deficit in stroke patients

Content:

1a. Level of consciousness. The investigator must assign a score even if assessment is difficult due to endotracheal intubation, language barrier, orotracheal trauma, or bandages. A score of 3 is given only if the patient has no motor response to painful stimuli (excluding protective reflexes). Ask the patient two or three general questions regarding the circumstances of their hospital admission. Based on the responses, evaluate the results. Remember that the patient should not be assisted.

0 = alert, responsive immediately to examination.

1 = drowsy, responsive to minor stimulation.

2 = stuporous, requires repeated stimulation to respond, or unresponsive requiring more intense stimulation to elicit a non-stereotypic motor response.

3 = comatose, response only via reflex motor acts, spontaneous movements, or complete unresponsiveness, atonia, areflexia.

1b. Level of consciousness. Questions. Ask the patient: "What month is it? How old are you?" Close but incorrect answers are not counted. Patients with aphasia and/or decreased level of arousal who cannot correctly answer the two questions receive 2 points. Patients unable to speak due to endotracheal intubation, orotracheal trauma, severe dysarthria, language barrier, or other reasons (excluding aphasia) receive 1 point. Only the first attempt is scored; verbal and non-verbal assistance from the physician is not permitted.

0 = correct answer to both questions.

1 = correct answer to one question.

2 = incorrect answer to both questions.

1c. Level of consciousness. Commands. The patient must be asked to close and open their eyes, then make a fist and release it with their non-paretic hand. If the patient's hand cannot be used for this item, another command may be substituted. If the patient cannot understand the command, the task may be demonstrated. Patients with trauma, amputation, or other physical defects should be evaluated using a single-step command. Only the first attempt is scored. Questions are also asked only once.

0 = both commands performed correctly.

1 = one command performed correctly.

2 = neither command performed correctly.

2. Gaze. Only horizontal eye movements are assessed. Evaluate voluntary or reflex (oculocephalic reflex) eye movements. Caloric testing is not permitted. If the patient has conjugate gaze deviation that can be overcome voluntarily or by eliciting the oculocephalic reflex, score 1. If the patient has an isolated paresis of eye muscles innervated by cranial nerves III, IV, or VI, score 1. Eye movements must be examined in all patients, including those with aphasia. Patients with ocular trauma, eye patching, pre-existing blindness, or other visual acuity or visual field disorders must be examined by eliciting the oculocephalic reflex. To detect partial gaze palsy, it is recommended to establish eye contact with the patient and move from side to side relative to the patient.

0 = normal.

1 = partial gaze palsy, overcome voluntarily or by eliciting the oculocephalic reflex.

2 = forced deviation of the eyes not overcome by eliciting the oculocephalic reflex.

3. Visual fields. Visual fields (upper and lower quadrants) are tested separately. If necessary, finger counting or sudden presentation of a visual stimulus (examiner's finger) in the visual field may be used. During testing, the patient should look at the examiner's face, but tracking finger movements can be considered a normal positive response. In unilateral blindness or enucleation, visual fields are assessed in the good eye. If there is a clearly demarcated visual field defect in the form of upper or lower quadrant hemianopia, score 1. If the patient is blind for any other reason, score 3. Simultaneous bilateral stimulation must also be performed. If this reveals a discrepancy (reduced field toward the affected eye), score 1, and use this result to answer question No. 11. Two points correspond to complete hemianopia, and any partial visual field loss, including quadrantanopia, corresponds to 1 point.

0 = normal.

1 = partial hemianopia.

2 = complete hemianopia.

3 = bilateral hemianopia (blindness, including cortical blindness).

4. Facial palsy. Using verbal and non-verbal techniques, ask the patient to show their teeth, raise their eyebrows, close their eyes, and squeeze their eyes shut. The examiner may demonstrate these commands. Assess the symmetry of the grimace in response to a noxious stimulus in patients who cannot understand you. If the patient has a facial bandage, orotracheal intubation, or other barriers, these should be removed (as much as possible) during the assessment.

0 = normal.

1 = minor paralysis, facial asymmetry in the form of flattening of the nasolabial fold, asymmetry when smiling.

2 = partial paralysis (partial or complete paralysis of the lower facial muscles).

3 = complete paralysis of the lower and upper facial muscles on one or both sides (complete absence of movement in the upper and lower facial muscles).

5a. Motor function in the upper extremity (left arm). Position the patient's limbs as follows: extend the arms (palms down) at an angle of 90° (if the patient is sitting) or 45° (if the patient is supine). Each limb is evaluated in turn, starting with the non-paretic arm. The examiner may demonstrate the maneuver in patients with aphasia. Application of noxious stimuli is not permitted. In the event of limb amputation or shoulder joint injury, the examiner must enter UN (untestable) in the appropriate box. Clearly count aloud to ten and demonstrate the count on your fingers so that the patient can see it. Start counting as soon as you release the patient's limb.

0 = limb holds the 90° or 45° position for 10 seconds without downward drift.

1 = limb drifts down before the full 10 seconds, but does not hit the bed or other support.

2 = limb cannot sustain the raised position (drifts down to the bed or other support within 10 seconds), but has some effort against gravity.

3 = limb falls to the bed with no effort against gravity, minimal movement is present.

4 = no active movement.

UN = limb amputation or shoulder joint injury.

5b. Motor function in the upper extremity (right arm).

6a. Motor function in the lower extremity (left leg). Position the limbs accordingly: at an angle of 30° in the supine position. The examiner may demonstrate the maneuver in patients with aphasia. Application of noxious stimuli is not permitted. Each limb is evaluated in turn, starting with the non-paretic leg. Only in the event of limb amputation or hip joint injury, the examiner must enter UN (untestable) in the appropriate box. Clearly count aloud to five and demonstrate the count on your fingers so that the patient can see it. Start counting as soon as you release the patient's limb.

0 = leg holds the 30° position for 5 seconds without downward drift.

1 = leg drifts down before the full 5 seconds, but does not hit the bed or other support.

2 = leg cannot sustain the raised position (drifts down to the bed or other support within 5 seconds), but has some effort against gravity.

3 = leg falls to the bed with no effort against gravity, minimal movement is present.

4 = no active movement.

UN = limb amputation or hip joint injury.

6b. Motor function in the lower extremity (right leg).

7. Limb ataxia. Unilateral cerebellar signs are assessed. The test is performed with eyes open. If there is any visual defect, testing should be conducted in the unaffected visual field. Ataxia is absent if the patient does not understand the task or is paralyzed. In case of joint injury or limb amputation, score UN (untestable). Ask the patient to perform finger-nose-finger, finger-to-finger, and heel-to-shin tests with both limbs. In case of blindness, the finger-to-finger test should be omitted. A patient with aphasia will often be able to perform the test normally if the examiner first moves the limb.

0 = absent.

1 = present in one limb.

2 = present in two limbs.

8. Sensory loss. Only sensory loss attributable to the current illness is considered. The examiner should test as many body areas of the patient as possible (face; arms, except hands; legs, except feet; trunk). Patients in a stupor and/or with aphasia are scored 1, and patients with brainstem stroke and bilateral sensory loss are scored 2. If the patient does not respond to external stimuli and has tetraplegia, a score of 2 is assigned, the same as for a coma.

0 = normal; no sensory loss.

1 = moderate sensory loss; the patient feels pinprick as less sharp or as dull on the affected side.

2 = severe to total sensory loss; the patient feels nothing (is not aware of being touched) in the face, arm, and leg.

9. Aphasia. The patient is asked to describe the attached picture, name the objects shown on a sheet of paper, and read sentences from the attached list. If the patient is blind, they must name objects placed in their hand, repeat something after the examiner, or say something spontaneously. An intubated patient should be asked to write their answers. A score of 3 should be given only if the patient is mute, follows no one-step commands, and answers no questions. Mild aphasia is scored 1. To correctly choose between 1 and 2, use the provided materials; it is assumed that a patient who misses more than 2/3 of the proposed items or performs a small number of simple commands will receive a score of 2. In a comatose state, a score of 3 is assigned.

0 = no aphasia; normal.

1 = mild to moderate aphasia.

2 = severe aphasia.

3 = mute, global aphasia.

10. Dysarthria. If the patient's condition is assessed as normal, they should be able to speak adequately, responding to the examiner's request to read something or repeat words from the attached list. If the patient shows signs of severe aphasia, articulation clarity is assessed during spontaneous speech. Only if the patient is intubated or has another physical barrier to speech, the patient's condition is scored 9, and the examiner must provide a clear written explanation of the reason why the patient's condition cannot be assessed. Do not tell the patient the reason for testing. Use the provided word list for all patients and do not tell them that you are testing speech clarity. As a rule, slurring of one or several words is considered normal. A score of zero is given to patients who read all words clearly. Patients suffering from aphasia or those who cannot read are assessed based on the quality of their spontaneous speech or repetition of words spoken aloud by the examiner. A score of 2 is given when the patient's speech is completely unintelligible or in patients who are mute.

0 = normal.

1 = mild to moderate dysarthria; the patient slurs at least some words and, at worst, can be understood with some difficulty.

2 = severe dysarthria; the patient's speech is so slurred as to be unintelligible in the absence of or out of proportion to any dysphasia, or is mute/anarthric.

UN = patient intubated or has other physical barrier to speech.

11. Extinction and inattention (previously termed "neglect"). Information obtained during the preceding tests is sufficient to detect neglect (inattention). If, due to a severe visual impairment, simultaneous bilateral visual stimulation cannot be performed, but the response to cutaneous stimuli is normal, the patient's condition is considered normal. If the patient has aphasia, but by all indications attentively follows the voice from both sides, their condition is considered normal. The presence of visual-spatial neglect, or anosognosia, is regarded as pathological. Since pathology is scored only when present, this item is always tested. It can be assumed that significant variation in examiners' opinions is possible when assessing this item, as all neurologists use somewhat differing methods to test for neglect. Therefore, to increase the reliability of the study, perform only simultaneous bilateral stimulation for visual and tactile stimuli. With unilateral extinction of stimuli in both modalities, score inattention as 2, and with unilateral extinction of a stimulus in a single modality as 1. If the patient is conscious but demonstrates any other pronounced type of neglect, score the level of inattention as 1.

0 = no abnormalities.

1 = depressed response (extinction, inattention) to simultaneous bilateral stimulation in one of the listed modalities (visual, tactile, auditory, spatial).

2 = marked unilateral extinction or extinction of stimuli in more than one modality; the patient does not recognize (fails to distinguish) their own hand or other landmarks on one side only.

Key (interpretation): maximum score is 42. Absence of neurological deficit corresponds to 0 points.

Notes: scale items must be scored in order. Instructing the patient is unacceptable, even if it contradicts routine clinical practice. The patient's first response is recorded. Only the patient's actual response is evaluated, not their (in your view) potential actions. All symptoms present in the patient must be noted, including those that may have resulted from prior strokes. To examine speech production, the patient is asked to describe events in a picture, name objects, and read sentences and words presented by the examining physician.

Table P6. REGATA scale for assessing the risk of upper gastrointestinal bleeding in patients with stable ischemic heart disease

Original title: REGATA scale

Source: official website of the developers https://regata-score.ru/, Komarov A.L., Shakhmatova O.O., Korobkova V.V., et al. Risk factors and outcomes of gastrointestinal bleeding in patients with stable ischemic heart disease: data from the REGATA-1 long-term antithrombotic therapy observational registry. Russian Journal of Cardiology. 2021;26(6):4465.

Type (underline):

- rating scale

Purpose: to assess the risk of upper gastrointestinal bleeding in patients with stable ischemic heart disease (including those receiving oral anticoagulants due to concomitant AF); developed on a domestic population.

Content:

Comment: * – clinically significant peripheral atherosclerosis is taken into account (arterial stenosis of 50% or more)

Key (interpretation): 0-3 points – low bleeding risk, 4 points or more – high risk of upper gastrointestinal bleeding

Notes: the scale assesses the risk of major and clinically relevant bleeding over a 2-year period

Table P7. Bleeding risk scale in patients with acute coronary syndrome ORACUL

Original title: ORACUL scale

Source: official website of the developer https://oracul.msk.ru/calculators/index, Brazhnik V.A., Minushkina L.O., Erlikh A.D., et al. Use of the ORACUL scale for assessing hemorrhagic risk in patients with acute coronary syndrome and atrial fibrillation. Rational Pharmacotherapy in Cardiology 2021;17(1):11-15.

Type (underline):

- rating scale

Purpose: assessment of bleeding risk in patients with acute coronary syndrome (including those with concomitant AF); developed on a domestic population.

Content:

Key (interpretation): 0-67 points – low bleeding risk, 68-107 points – moderate bleeding risk, 108-133 points – high bleeding risk, more than 133 points – very high bleeding risk

Notes: The ORACLE scale has demonstrated predictive value for both the in-hospital period and the subsequent 12 months after ACS.

The scale evaluated the risk of bleeding requiring any intervention by medical personnel (Bleeding Academic Research Consortium [BARC] types 2-5)

Table P8 SYNTAX score for assessing coronary artery disease severity

Russian name: SYNTAX score

Original name: SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score

Source: developer's original website https://syntaxscore.org/, Serruys P., Onuma Y., Garg S., et al. Assessment of the SYNTAX score in the Syntax study. EuroIntervention. 2009;5(1):50-56.

Type (underline):

- rating scale

Purpose: assessment of coronary artery disease severity to select the optimal revascularization strategy and to predict the risk of ischemic events in patients with coronary artery disease who underwent percutaneous coronary intervention (including those with concomitant AF)

Content: the score is calculated using an electronic calculator (https://syntaxscore.org/calculator/syntaxscore/frameset.htm)

Interpretation (key): 0-22 points – low risk of cardiovascular events, 23-32 – intermediate risk of cardiovascular events, >32 points – high risk of cardiovascular events.

Notes: originally developed to select the optimal revascularization strategy in patients with multivessel coronary artery disease or left main coronary artery disease, the scale subsequently demonstrated predictive value for long-term outcomes after PCI

Table P9. GRACE risk score for adverse outcomes in acute coronary syndrome GRACE

Russian name: GRACE score

Original name: GRACE (The Global Registry of Acute Coronary Events) risk score

Source: Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, et al.; Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003 Oct 27;163(19):2345-53. doi: 10.1001/archinte.163.19.2345.

Type (underline): rating scale.

Purpose: a standardized method for determining the in-hospital mortality risk level in patients with acute coronary syndrome based on a list of criteria present at admission (including in patients with concomitant AF).

Content

Interpretation (key): ≤108 points – low in-hospital mortality risk (<1%), 109-140 points – moderate (1-3%), ≥141 points – high (>3%)

Notes: to assess the long-term prognosis of patients with ACS (mortality, death and myocardial infarction at 1 year and 3 years), an updated version of the scale has been developed – GRACE 2.0 (https://gracescore.org/) [661]).

Even more accurate risk stratification is achieved using modified variants of the scale that take into account high-sensitivity troponin [662] (the original scale evaluated non-high-sensitivity troponin, creatine kinase, and the MB fraction of creatine kinase).

A version of GRACE 3.0 enhanced with artificial intelligence methods is also currently available (https://www.grace-3.com/).

Table P10. Academic Research Consortium for High Bleeding Risk (ARC-HBR) bleeding risk score

Russian title: ARC-HBR score

Original scale name: Academic Research Consortium for High Bleeding Risk

Source: Urban P, Mehran R, Colleran R, et al. Defining high bleeding risk in patients undergoing percutaneous coronary intervention: a consensus document from the Academic Research Consortium for High Bleeding Risk. Eur Heart J. 2019 Aug 14;40(31):2632-2653

Type (underline): rating scale.

Purpose: assessment of bleeding risk in patients who have undergone PCI (including those with concomitant AF)

Content:

Abbreviations: eGFR – estimated glomerular filtration rate, NSAIDs – nonsteroidal anti-inflammatory and antirheumatic drugs, PCI – percutaneous coronary intervention

Interpretation (key): bleeding risk is considered high if at least one major or two minor risk factors are present

Table P11. PRECISE-DAPT score for assessing bleeding risk in patients undergoing percutaneous coronary intervention and receiving dual antiplatelet therapy

Russian title: PRECISE-DAPT score

Original title: PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy score

Source: official developer website http://www.precisedaptscore.com/predapt/; Costa F, van Klaveren D, James S, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet. 2017 Mar 11;389(10073):1025-1034. doi: 10.1016/S0140-6736(17)30397-5.

Type (underline): rating scale.

Purpose: assessment of bleeding risk in patients undergoing percutaneous coronary intervention and receiving dual antiplatelet therapy, in order to determine the duration of combined antiplatelet therapy (including in combination with an oral anticoagulant in patients with AF);

Content: the score is calculated using a nomogram with an electronic calculator available on the original developer website (http://www.precisedaptscore.com/predapt/webcalculator.html).

Interpretation (key): ≥ 25 points – high bleeding risk, shortened duration of combined antiplatelet therapy is recommended; <25 points – low bleeding risk, standard duration of combined antiplatelet therapy is recommended

Table P12. SF-36 Quality of Life Questionnaire

Russian title: SF-36 Quality of Life Questionnaire

Original title: 36-Item Short Form Survey (SF-36)

Source: official developer website https://www.rand.org/health-care/surveys_tools/mos/36-item-short-form.html.

J. E. Ware Jr, C. D. Sherbourne. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection // Medical Care, 1992. 30(6)

Type (underline): rating scale.

Purpose: a non-specific questionnaire for assessing a patient's quality of life. The questionnaire reflects general well-being and the degree of satisfaction with aspects of human life affected by health status.

Content: the score is calculated using a nomogram with an electronic calculator available on the original developer website

Interpretation (key): the 36 items of the questionnaire are grouped into eight scales: physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning, and mental health. Each scale score ranges between 0 and 100, where 100 represents full health; all scales form two summary measures: mental and physical health.

Results are presented as scores across 8 scales, formulated such that a higher score indicates a higher level of quality of life.