Heart failure: Clinical Guidelines

List of Abbreviations

AH – arterial hypertension

BP – blood pressure

ACE – angiotensin-converting enzyme

ARB – angiotensin II receptor blockers (syn. angiotensin II antagonists)

CCB – calcium channel blockers

LBBB – left bundle branch block

RBBB – right bundle branch block

CHD – congenital heart disease

SCD – sudden cardiac death

LVH – left ventricular hypertrophy

LVDD – left ventricular diastolic dysfunction

DHF – diastolic heart failure

DCM – dilated cardiomyopathy

VA – ventricular arrhythmia

VT – ventricular tachycardia

VES – ventricular extrasystoles

ACEI – angiotensin-converting enzyme inhibitors (syn. ACE inhibitors)

CHD – coronary heart disease

ICD – implantable cardioverter-defibrillator^***

ИМ – myocardial infarction

SGLT2i – sodium-glucose cotransporter 2 inhibitors

CTI – cardiothoracic ratio

CABG – coronary artery bypass grafting

LV – left ventricle

LVAD – left ventricular assist device

LA – left atrium

LDL – low-density lipoproteins

INR – international normalized ratio

MCS – mechanical circulatory support

MRI – magnetic resonance imaging

MSCT – multislice computed tomography

NSAIDs – nonsteroidal anti-inflammatory drugs

LCX – circumflex artery

ADHF – acute decompensated heart failure

AMI – acute myocardial infarction

ACS – acute coronary syndrome

OMT – optimal medical therapy

RR – relative risk

AHF – acute heart failure

SPECT – single-photon emission computed tomography

RV – right ventricle

LAD – left anterior descending artery

PET – positron emission tomography

RAAS – renin-angiotensin-aldosterone system

RCTs – randomized controlled trials

RFA – radiofrequency ablation

SBP – systolic blood pressure

SNS – sympathoadrenal system

DM – diabetes mellitus

GFR – glomerular filtration rate

HF – heart failure

CRT – cardiac resynchronization therapy

CRT-D – cardiac resynchronization therapy-defibrillator

CRT-P – cardiac resynchronization therapy-pacemaker

TSH – thyroid-stimulating hormone

TEC – thromboembolic complications

LAE – left atrial enlargement

EF – ejection fraction

LVEF – left ventricular ejection fraction

FC – functional class

AF – atrial fibrillation

CKD – chronic kidney disease

COPD – chronic obstructive pulmonary disease

CHF – chronic heart failure

HFmrEF – heart failure with mildly reduced LVEF

HFrEF – heart failure with reduced LVEF

HFpEF – heart failure with preserved LVEF

CRF – chronic renal failure

CVP – central venous pressure

PCI – percutaneous coronary intervention

HR – heart rate

ECG – electrocardiography

ECMO – extracorporeal membrane oxygenation

EchoCG – echocardiography

BNP – brain natriuretic peptide

β-blockers – beta-blockers

HbA1c – glycated hemoglobin

NT-proBNP – N-terminal pro-B-type natriuretic peptide

NYHA – New York Heart Association

Terms and Definitions

Chronic heart failure (CHF) is a clinical syndrome characterized by current or previous symptoms (dyspnea, fatigue, ankle and foot swelling) and signs (elevated jugular venous pressure, pulmonary rales, peripheral edema) resulting from a structural and/or functional cardiac abnormality that leads to a reduction in cardiac output and/or elevated intracardiac filling pressures at rest or during stress, and/or elevated natriuretic peptide levels.

Pre-heart failure – a state characterized by the absence of current or past symptoms and signs of CHF, but with evidence of structural and/or functional cardiac abnormalities and/or elevated brain natriuretic peptide levels.

Risk of CHF development refers to the presence of conditions and diseases associated with a high risk of developing CHF.

Acute HF (AHF) is a life-threatening condition characterized by the rapid onset or worsening of HF symptoms and/or signs, potentially leading to pulmonary edema or cardiogenic shock, and requiring urgent medical intervention and typically rapid patient hospitalization.

Acute decompensation of HF is a condition characterized by a rapid and pronounced worsening of CHF symptoms and/or signs.

Systolic CHF – HF characterized by a marked reduction in left ventricular (LV) contractility.

Diastolic CHF – HF primarily caused by impaired LV relaxation.

CHF with reduced LV ejection fraction (HFrEF) – CHF with LVEF ≤ 40%.

CHF with mildly reduced LV ejection fraction (HFmrEF) – CHF with LVEF = 41–49%.

CHF with preserved LV ejection fraction (HFpEF) – CHF with LVEF ≥ 50%.

The term "chronic circulatory failure" was introduced by A.L. Myasnikov and is essentially synonymous with chronic heart failure, but was used exclusively in our country. Today, it is not recommended as a replacement for the term CHF.

1. Brief information on the disease or condition

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

There are numerous causes of CHF (Table 1).

In the Russian Federation (RF), the main causes of CHF are arterial hypertension (AH) and coronary artery disease (CAD) [1, 2].

Their combination occurs in half of the patients [3].

CAD is the cause of systolic CHF in two-thirds of cases, frequently coexisting with diabetes mellitus (DM) and AH [1, 2]. Other causes of systolic CHF include viral infections, alcohol abuse, chemotherapy, left-sided chest radiation therapy, and "idiopathic" dilated cardiomyopathy [3, 4].

Other causes of CHF include various valvular heart diseases (4.3%) and myocarditis (3.6%) [3, 5].

Approximately half of HF patients have preserved LVEF, and its prevalence relative to HFrEF continues to increase by 1% per year [6, 7]. Patients with HF and an LVEF of 41% to 49% are categorized as having HFmrEF. Retrospective analyses of randomized controlled trials (RCTs) in patients with HFrEF and HFpEF that included patients with an LVEF ranging from 40% to 50% have shown that these patients respond well to therapies used for patients with an LVEF ≤ 40% [8–11].

The epidemiology and etiology of HFpEF differ from those of systolic CHF. Patients with HFpEF are older, with a higher proportion of women and individuals with obesity [3, 12].

Rarer causes of HFpEF include hypertrophic and restrictive cardiomyopathies, constrictive pericarditis, hydropericardium, thyrotoxicosis, infiltrative diseases, metastatic myocardial lesions, and other conditions that restrict myocardial relaxation.

In patients with LV systolic dysfunction, changes occurring in cardiomyocytes and the extracellular matrix following myocardial injury (e.g., myocardial infarction (MI) or myocarditis) lead to pathological ventricular remodeling with dilatation, altered geometry (the LV becomes more spherical), and impaired contractility. Over time, these changes progress, although HF symptoms may not be prominent early in the disease. Two pathophysiological mechanisms are thought to be involved. First, there are novel events leading to cardiomyocyte death (e.g., recurrent MI). However, further cardiac remodeling can also occur in the absence of overt recurrent myocardial injury.

Table 1. Causes of chronic heart failure

Secondly, a systemic response to decreased LV systolic function occurs. Patients experience increased activity of pressor systems: the sympathoadrenal system, the renin-angiotensin-aldosterone system (RAAS), the endothelin system, vasopressin, and cytokines. Activation of the RAAS and the sympathetic nervous system is of key importance. These neurohumoral factors not only cause peripheral vasoconstriction, sodium and fluid retention, and consequently an increased hemodynamic load on the LV, but also exert a direct toxic effect on the myocardium, stimulating fibrosis and apoptosis, which leads to further cardiac remodeling and impaired function. In addition to myocardial damage, the activation of neurohumoral systems adversely affects other organs as well—blood vessels, kidneys, muscles, bone marrow, lungs, and liver—forming a pathophysiological "vicious circle" and leading to many clinical manifestations of HFrEF, including myocardial electrical instability. Clinically, all these changes are associated with the development and progression of HFrEF symptoms and lead to a deterioration in quality of life, a decrease in patients' physical activity, decompensation of HF requiring hospitalization, and death resulting from both cardiac "pump" failure and the emergence of life-threatening ventricular arrhythmias. It must be emphasized that the severity of HFrEF symptoms does not always correlate with LVEF. Treatment for HFrEF is specifically based on targeting these two key processes (myocardial damage and activation of neurohumoral systems). The cardiac reserve in patients with HFrEF also depends on atrial contraction, the synchrony of LV function, and the interaction between the right ventricle (RV) and the LV. The development of atrial fibrillation (AF) or left bundle branch block (LBBB) can lead to acute decompensation of heart failure (ADHF) [13-16].

The most common cause of HFmrEF is CAD (50–60% of cases). Similar to HFrEF, a large proportion of patients with HFmrEF are men. AF and extracardiac comorbid conditions (obesity, DM, smoking, toxic exposures, etc.) are less common in patients with HFmrEF than in those with HFpEF [17-19].

The majority of patients with HFpEF are elderly individuals with multiple extracardiac comorbidities: obesity, hypertension, type 2 diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and anemia [20-22].

It is believed that all these comorbidities, along with advanced age, induce and maintain a chronic low-grade, low-intensity proinflammatory status in the body, as a result of which proinflammatory cytokines trigger systemic endothelial dysfunction, including in the coronary microcirculation, which is fraught with the development and progression of diastolic dysfunction. Specific causes of HFpEF include amyloidosis, hemochromatosis, restrictive cardiomyopathies, and diseases associated with isolated RV involvement.

The pathophysiology of HFpEF is less understood due to both the heterogeneity of this condition and the complexity of its diagnosis [16, 23-27].

In HFpEF, the main pathophysiological changes are impaired LV relaxation and compliance, where endothelial dysfunction of the coronary microcirculation, resulting from chronic inflammation, plays a key role [28-30].

As a rule, such HFpEF is based on impaired LV diastolic function, i.e., its inability to fill adequately without an increase in mean pulmonary venous pressure. LV diastolic function depends on both myocardial relaxation and its mechanical properties. LV myocardial relaxation is an active process dependent on the functioning of the cardiomyocytes' sarcoplasmic reticulum. Impaired active relaxation is one of the earliest manifestations of myocardial dysfunction in most cardiovascular diseases [28-30].

The mechanical properties of the myocardium, which are characterized by elasticity, compliance, and stiffness, affect LV filling during diastasis and atrial systole. Myocardial hypertrophy, fibrosis, or infiltration increases its stiffness, leading to a sharp rise in LV filling pressure. In addition, LV compliance also depends on the level of preload. LV compliance decreases with its dilation. Depending on the severity of diastolic abnormalities, three types of LV filling are distinguished: delayed relaxation, pseudonormalization, and restriction. The severity of clinical manifestations of HFpEF and patient prognosis are primarily determined by the severity of diastolic dysfunction [31-37].

1.3 Epidemiology of the Disease or Condition

According to Russian epidemiological studies, the prevalence of HF in the Russian Federation increased from 6.1% to 8.2% over a 20-year follow-up [3].

Prior to the 1990s, 60–70% of patients with HF died within 5 years. Modern therapy has reduced both the number of repeated hospitalizations due to HF decompensation and mortality [3, 13, 19, 38]. Nevertheless, in the Russian Federation, the average annual mortality rate among patients with NYHA functional class (FC) I–IV HF is 6%, and among patients with clinically overt HF, it is 12% [37]. According to the EPOCHA-HF study, the prognosis for patients is unfavorable: for NYHA FC I–II HF, the median survival time is 8.4 (95% confidence interval [CI]: 7.8–9.1) years, and for NYHA FC III–IV HF, it is 3.8 (95% CI: 3.4–4.2) years [3].

HFpEF is no less severe a disease than HFrEF: according to observational studies, the 5-year survival rate for this form of HF is 50%, and the risk of repeated hospitalizations exceeds 50% within the first 6 months after discharge from the hospital [7, 39].

The prognosis of patients with HFpEF depends on the cause of the disease and the severity of diastolic dysfunction [35, 36, 40].

For our country, HFpEF carries greater medical and social significance than in Western countries: according to the latest outpatient clinic registry, 78% of patients with HF have preserved LVEF [41].

1.4 Features of Coding the Disease or Condition

I50.0 - Congestive heart failure

I50.1 – Left ventricular failure

I50.9 – Heart failure, unspecified

1.5 Classification of the disease or condition

By LVEF (Table 2):

• HF with reduced EF (40% or less) (HFrEF)

• HF with mildly reduced EF (41% to 49%) (HFmrEF)

• HF with preserved EF (50% or more) (HFpEF)

Table 2. Characteristics of heart failure according to left ventricular ejection fraction.

Note.

^a - symptoms may be absent in the early stages of HF or in patients receiving diuretic therapy.

^b – in the diagnosis of HFmrEF, the presence of evidence of structural heart disease (e.g., increased left atrial (LA) size, LV hypertrophy (LVH), or echocardiographic signs of impaired LV filling) makes the diagnosis more likely.

^c – concentric LVH (LV mass index ≥95 g/m² in women and ≥115 g/m² in men; relative wall thickness index >0.42); LA enlargement (volume index >34 ml/m² in sinus rhythm and >40 ml/m² in AF); resting Doppler E/e' ratio >9; N-terminal pro-B-type natriuretic peptide (NT-proBNP) / brain natriuretic peptide (BNP) level >125/35 pg/ml in sinus rhythm or >365/105 pg/ml in AF; pulmonary artery systolic pressure (PASP) >35 mmHg or tricuspid regurgitation velocity >2.8 m/s. The diagnostic accuracy of HFpEF will be higher when more of these features are present in the patient.

During therapy, LVEF may increase in some patients with HF. According to expert consensus, the group of patients with HF with improved LVEF includes those who meet the following three criteria: 1) have a history of reduced LVEF ≤40%; 2) have an absolute improvement in LVEF ≥10% compared to baseline; 3) have a repeat LVEF measurement ≥40% [42, 43].

By HF stages - Russian Society of Cardiology 2023 expert classification [44–46]:

Pre-stage of heart failure: absence of symptoms and signs of HF in the present and past. Presence of evidence of structural and/or functional cardiac damage and/or elevated brain natriuretic peptide levels.

Stage 1. Clinically overt heart failure: presence of symptoms and signs of HF in the present or past caused by impaired cardiac structure and/re function.

Stage 2. Advanced, clinically severe heart failure: severe symptoms and signs of HFrEF/HFpEF, recurrent hospitalizations for HF despite attempts to optimize HF therapy or intolerance to HF therapy.

Comments: Of particular importance is not only the treatment of patients with already established HF, but also its primary prevention, i.e., preventing or delaying the onset of the first symptoms of HF. Special attention should be paid to the early stages of the cardiovascular continuum, those diseases and conditions in which the risk of developing HF is particularly high: hypertension, obesity, IHD, AF, cardiomyopathies, DM, CKD, COPD, anti-tumor therapy. Identifying a group of patients in whom the risk of developing HF is considered high or very high is critical for implementing preventive strategies that reduce cardiovascular risks, including the risk of developing HF, informing patients about prognosis, and increasing motivation to adhere to recommendations. Primary prevention strategies for HF in patients at high risk of its development are presented in Section 5, and strategies for preventing HF symptoms in patients with pre-HF are presented in Section 3.1.2.2.

Threshold values of cardiac structural and functional abnormalities that allow diagnosing pre-HF in the absence of symptoms and/or signs of HF are presented in Sections 2.4.2.1 and 2.4.2.2 (Table 4).

Stages of development and progression of HF with additional explanations are presented in Appendix A3-1.

By functional class:

• Class I. No limitation of physical activity: ordinary physical activity does not cause undue fatigue, dyspnea, or palpitations. The patient tolerates increased exertion, but it may be accompanied by dyspnea and/or delayed recovery.

• Class II. Slight limitation of physical activity: comfortable at rest, but ordinary physical activity results in fatigue, dyspnea, or palpitations.

• Class III. Marked limitation of physical activity: comfortable at rest, but less than ordinary physical activity causes symptoms.

• Class IV. Inability to carry on any physical activity without discomfort; symptoms of HF are present at rest and increase with minimal physical activity.

Examples of diagnosis formulation:

1. Primary: Essential hypertension, Stage II. Risk 3 (high). Dyslipidemia. LV hypertrophy. Diastolic dysfunction. Pre-stage of heart failure.

2. Primary: IHD: exertional angina, FC 3. LV systolic dysfunction. Pre-stage of heart failure.

3. Primary: IHD: post-infarction cardiosclerosis (prior myocardial infarction in 2019).

Complications: HFmrEF, Stage 1. FC 2. Pulmonary hypertension, WHO FC 1.

4. Primary: Genetically determined familial dilated cardiomyopathy.

Complications: HFrEF, Stage 2. FC 4. Bilateral hydrothorax, ascites, anasarca.

1.6 Clinical presentation of the disease or condition

The clinical presentation of HF includes typical symptoms (dyspnea, orthopnea, paroxysmal nocturnal dyspnea, reduced exercise tolerance, fatigue, ankle edema) and signs (elevated jugular venous pressure, hepatojugular reflux, gallop rhythm, leftward displacement of the apex beat) caused by structural and/or functional abnormalities of the heart [47-51].

Nevertheless, the diagnosis of HF, especially in early stages, can be challenging because these symptoms and signs are nonspecific and can be caused by a variety of conditions other than HF.

According to a meta-analysis by Mant J. et al., dyspnea is the only symptom with high sensitivity (89%), but it has low specificity (51%). Clinical signs with relatively high specificity include orthopnea (89%), peripheral edema (72%), elevated jugular venous pressure (70%), cardiomegaly (85%), heart murmurs (99%), and hepatomegaly (97%), but the sensitivity of these signs is low, ranging from 11% (heart murmurs) to 53% (edema) [48].

The most common reasons for patients with HF to seek medical attention are complaints of dyspnea and peripheral edema [47, 48].

Dyspnea is the most common symptom of HF, but it is also observed in many other diseases [48].

It is particularly difficult to interpret and differentiate in the elderly, patients with obesity, and pulmonary diseases [49, 52].

The cause of dyspnea in HF is pulmonary congestion, which leads to increased pressure in the pulmonary veins and capillaries. Dyspnea in the early stages of HF is associated with physical exertion (the severity of dyspnea increases with exertion). As the condition progresses, exercise tolerance deteriorates: dyspnea occurs at lower levels of physical activity, fatigue increases, exercise tolerance decreases, and orthopnea eventually develops.

Edema can be of cardiac or non-cardiac origin (renal pathology, chronic venous insufficiency, acute deep vein thrombosis, lymphedema, and other causes) [53].

The primary task when evaluating a patient with edema is to confirm or rule out its cardiac origin. The following features help accomplish this task: clinical characteristics of edema in HF, identification of systemic venous hypertension, and signs of organic heart disease. In HF, edema is symmetrical and localized in the most dependent parts of the body (lower extremities; as HF worsens, scrotal, abdominal, and lumbar edema may occur).

Signs of venous hypertension include elevated central venous pressure in the jugular veins, hepatojugular reflux, edema, and hepatomegaly. Distention and pulsation of the jugular veins is a characteristic and most specific sign of elevated central venous pressure. However, jugular vein distension can also occur due to non-cardiac causes such as tumors, scars, venous thrombosis, and respiratory disorders. Hepatomegaly is a classic sign of RV failure (congestive hepatomegaly) [48].

Therefore, palpation of the liver must be performed in all patients. In hepatic congestion due to RV failure, there is marked distention of the jugular veins during liver palpation (positive hepatojugular reflux / Plesch sign). A patient with HF may also have less typical symptoms and less specific signs, which are presented in Table 3.

2. Diagnostics, medical indications and contraindications for diagnostic methods

To establish a diagnosis of HF, the following criteria must be met:

1. Characteristic complaints

2. Clinical signs confirming their presence (in doubtful cases, response to diuretic therapy)

3. Evidence of LV systolic and/or diastolic dysfunction

4. Measurement of natriuretic peptides (to rule out the diagnosis of HF).

The diagnostic algorithm for HF is presented in Appendix B1.

2.1 Complaints and Anamnesis

• When interviewing the patient, it is recommended to inquire about complaints of fatigue, dyspnea, leg edema, and palpitations.

ESC IC (LoE A, GoR I) [47-50]

Comments. These complaints should prompt the physician to suspect HF in the patient. However, all the aforementioned "classic" complaints may also be caused by non-cardiac conditions.

• When taking the medical history, it is recommended to assess whether the patient has heart pathology leading to functional or structural changes.

ESC IC (LoE A, GoR I) [47-50]

Comments. A long history of hypertension, prior myocardial infarction, or inflammatory myocardial disease significantly increases the likelihood of HF in a patient with the above complaints. Conversely, the absence of a history of heart disease minimizes the chance of HF in the patient.

2.2 Physical Examination

• Physical examination of the patient is recommended to detect symptoms and clinical signs caused by sodium and water retention.

ESC IC (LoE A, GoR I) [47-51]

The most common symptoms and signs detected on physical examination are presented in Table 3. It should be noted that the aforementioned symptoms and clinical signs may also occur in other diseases/conditions.

Table 3. Characteristic clinical signs and symptoms of heart failure.

ᵃ This symptom of severe HF corresponds to dyspnea when leaning forward [54]

To determine the severity of clinical symptoms in patients with HFrEF/HFpEF, the clinical status rating scale is used (Appendix G1).

2.3 Laboratory Diagnostics

• All patients with a suspected diagnosis of CHF are recommended to have blood levels of brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured [55–63].

ESC IB (CQR A, LOR 2)

Comments. Natriuretic peptides are biological markers of CHF, the levels of which are also used to monitor treatment efficacy. A normal natriuretic peptide level in untreated patients practically rules out cardiac damage, making a diagnosis of CHF unlikely. With a gradual (non-acute) onset of symptoms, NT-proBNP and BNP values below 125 pg/mL and 35 pg/mL, respectively, indicate the absence of CHF.

• All patients are recommended to undergo a complete blood count (determining red blood cell, platelet, and leukocyte counts, and hematocrit evaluation) to rule out comorbidities and determine the CHF management strategy [64].

ESC IC (CQR B, LOR 3)

• All patients with CHF are recommended to undergo a complete blood count (determining red blood cell, platelet, and leukocyte counts, and hematocrit evaluation) dynamically in an inpatient and/or outpatient setting [64].

ESC IC (CQR B, LOR 3)

• All patients with CHF are recommended to have blood ferritin levels and transferrin saturation assessed to determine the management strategy [64–67].

ESC IC (CQR A, LOR 2)

• All patients with CHF are recommended to have blood ferritin levels and transferrin saturation assessed dynamically in an inpatient and/or outpatient setting [64–67]

ESC IC (CQR A, LOR 2)

• All patients are recommended to undergo a biochemical blood test to rule out comorbidities and determine the CHF management strategy: blood sodium and potassium levels, blood creatinine level and glomerular filtration rate (GFR) (calculated parameter), total protein and albumin levels in the blood, blood glucose level, blood triglyceride level, blood cholesterol level and blood lipoprotein levels, alkaline phosphatase activity in the blood, gamma-glutamyltransferase activity in the blood, aspartate aminotransferase activity and alanine aminotransferase activity in the blood [68–73].

ESC IC (LoE A, LoR 3)

• All patients with CHF are recommended to undergo a biochemical blood test dynamically in an inpatient and/or outpatient setting: blood sodium and potassium levels, blood creatinine level and GFR (calculated parameter), total protein and albumin levels in the blood, blood glucose level, blood triglyceride level, blood cholesterol level and blood lipoprotein levels, alkaline phosphatase activity in the blood, gamma-glutamyltransferase activity in the blood, aspartate aminotransferase activity and alanine aminotransferase activity in the blood [68–73].

ESC IC (LoE A, LoR 3)

• All patients with CHF and DM are recommended to have glycated hemoglobin levels measured in the blood [74].

ESC IC (LoE B, GoR 3)

• All patients are recommended to have blood thyroid-stimulating hormone levels measured to rule out comorbidities and determine the CHF management strategy [75].

ESC IC (CQR C, LOR 45)

• All patients are recommended to undergo a general urinalysis to rule out comorbidities and determine the CHF management strategy [76].

ESC IC (CQR C, LOR 2)

2.4 Instrumental Diagnostics

2.4.1. Electrocardiography

• All patients with CHF are recommended to undergo 12-lead electrocardiography (ECG) with assessment of heart rhythm, heart rate (HR), QRS complex morphology and duration, presence of atrioventricular and ventricular conduction disturbances (LBBB, right bundle branch block), myocardial scars, and myocardial hypertrophy. A diagnosis of CHF is unlikely in the presence of an entirely normal ECG [77–81].

ESC IC (CQR A, LOR 2)

2.4.2. Echocardiography

• All patients with suspected HF are recommended to undergo echocardiography (EchoCG) to assess cardiac structure and function in order to confirm the diagnosis and establish the HF phenotype [82–85].

ESC IC (LoE B, GoR 3)

• Patients with an established diagnosis of HF are recommended to undergo EchoCG to assess the heart valve apparatus, RV function, and pulmonary artery pressure in order to identify individuals with valvular abnormalities suitable for surgical/invasive correction [86].

ESC IC (RR S, ELD 5)

• Patients when planning and undergoing interventions/treatment with potential cardiotoxic effects are recommended to undergo EchoCG to assess cardiac structure and function [87].

ESC IC (CQR C, LOR 5

• Patients with CHF are recommended to undergo repeat EchoCG to assess cardiac structure and function in the following clinical situations:

— in case of worsening HF symptoms or after a major cardiovascular event;

— patients with HF receiving guideline-directed medical therapy at maximally tolerated doses before deciding on the use of implantable devices;

— patients whose treatment involves interventions with potential cardiotoxic effects [87].

ESC IC (RR S, ELD 5)

Comments. Other imaging modalities are indicated only in cases where:

• the diagnosis is unclear (e.g., due to suboptimal image quality on transthoracic EchoCG);

• a rare cardiac disease or an extracardiac cause of the patient's symptoms and clinical signs is suspected;

• a more detailed assessment of the cause of HF is required (e.g., perfusion scintigraphy or angiography if CAD is suspected, or myocardial biopsy in certain infiltrative cardiomyopathies).

2.4.2.1. Assessment of left ventricular systolic function

• In patients with CHF, it is recommended to use the biplane disk summation technique (Simpson's method) determining LV volumes in the four-chamber and two-chamber views to calculate LVEF [88–90].

ESC IC (CQR B, LOR 2)

Comments. Patients who are being evaluated for cardiac resynchronization therapy (CRT), implantable cardioverter-defibrillator (ICD) placement, or continuation of interventions/treatment with potential cardiotoxic effects, and whose EchoCG showed borderline LVEF values, are recommended to undergo more accurate methods of assessing LV contractility (three-dimensional EchoCG, contrast-enhanced EchoCG, cardiac magnetic resonance imaging (MRI)) for a more precise evaluation of LV contractility [91–94].

• Patients in whom EchoCG quality proved unsatisfactory (visualization <80% of the LV endocardium) are recommended to undergo contrast-enhanced EchoCG, which provides better visualization of the endocardium and more accurate assessment of LV volumes [95, 96].

ESC IC (CQR C, LOR 4

• In patients at high risk of developing HF, especially when using interventions with potential cardiotoxic effects, as well as in suspected HFpEF it is recommended to assess myocardial deformation—left ventricular (LV) global longitudinal strain (GLS)—to detect early (subclinical) changes in LV contractility [97–101].

ESC IC (CQR B, LOR 1

Comments. Global longitudinal strain (GLS) reflects the average magnitude of LV systolic shortening along the long axis. GLS is characterized by greater sensitivity and reproducibility in assessing LV systolic function compared to EF [97–101].

A GLS <16% indicates a decrease in LV systolic function, while GLS values from -16 to -18% are considered borderline [102].

Reduced GLS is detected in 50–60% of patients with HFpEF despite preserved LVEF [103, 104].

Such discrepancy between GLS and LVEF in patients with HFpEF is explained by the fact that EF predominantly reflects circumferential shortening of the ventricle (its thickening), whereas GLS reflects longitudinal shortening of the ventricle. Furthermore, in concentric LVH, which is so characteristic of HFpEF, the ventricular volume is usually reduced, meaning that even a minor stroke volume may be associated with normal/supernormal EF. Therefore, when assessing true LV contractility in patients with HFpEF, it is better to rely on GLS rather than EF [105].

Methods for calculating LV EF using Teichholz or Quinones formulas, as well as calculating fractional shortening, are based on linear measurements and can yield inaccurate results, primarily in patients with regional LV wall motion abnormalities; therefore, they are not currently recommended for clinical use. Other indicators of LV systolic function include the peak systolic velocity of the lateral mitral annulus measured by tissue Doppler imaging, mitral annular plane systolic excursion (MAPSE), and the LV wall motion score index, though they are rarely used in clinical practice.

Signs of systolic dysfunction (LV EF <50% and/or GLS <16%) in the absence of symptoms/signs of HFrEF allow for the diagnosis of pre-stage HF.

2.4.2.2. Assessment of left ventricular diastolic function

It is believed that the majority of HFpEF cases are based on impaired left ventricular diastolic function, and its thorough assessment is the key to the correct diagnosis of this form of HF. None of the ultrasound parameters possesses such high accuracy that the state of diastolic function could be judged solely on the basis of its value; the results of all studies should always be taken into account, including Doppler, 2D, and, whenever possible, 3D imaging data.

• All patients with suspected HF are recommended to undergo echocardiography with assessment of diastolic function to determine the severity of structural and functional abnormalities, assess prognosis, and choose treatment tactics [106].

ESC IC (CQR C, LOR 5

Comments. When assessing LV diastolic function, the primary focus should be on the ratio of early diastolic to atrial systolic mitral inflow velocities (E/A). If the E/A ratio is ≤0.8 and the E wave velocity is ≤50 cm/s, the LV filling pressure is normal and the patient has mild diastolic dysfunction (grade I, or impaired relaxation). If the E/A ratio is >2, the LV filling pressure is significantly elevated, and the patient has severe diastolic dysfunction (grade III, or restrictive filling). In all other cases, three other criteria for elevated LV filling pressure are evaluated: 1) average E/e' >14; 2) indexed LA volume (>34 mL/m²); 3) peak tricuspid regurgitation velocity >2.8 m/s (reflecting the degree of pulmonary artery pressure elevation; Fig. P2). If at least two criteria are met, it indicates moderate diastolic dysfunction (grade II, or pseudonormalization). If no more than one criterion is met, the patient should be classified as having grade I diastolic dysfunction. It should be kept in mind that an E/A ratio ≥2 can be observed in healthy young individuals (however, their e′ parameter will be within the normal range (Appendix B2, Fig. P2).

Table 4. Structural and functional abnormalities associated with diastolic dysfunction / elevated LV filling pressure [107, 108]

¹ -[107, 109]

The presence of at least one of the criteria listed in Table 4 in the absence of symptoms and/or signs of HF allows for the diagnosis of pre-stage HF.

Diagnostic scores HFA–PEFF or H2FPEF can be used to assess the probability of HFpEF (Appendix G3) [108, 110–112].

2.4.3. Targeted chest X-ray

• Targeted chest X-ray is recommended for patients with HF to detect alternative pulmonary diseases, pulmonary hemodynamics disorders, and cardiomegaly [79, 113].

ESC IC (CQR A, LOR 2)

Comments. The results of the chest X-ray require correlation with the clinical picture and ECG data. In patients with newly presenting symptoms of HF, chest X-ray can be used to identify other causes of HF symptoms (lung tumors, interstitial lung diseases) and to detect cardiomegaly (cardiothoracic ratio >50%); in patients with established HF, it is used to detect pulmonary hemodynamics disorders (venous and arterial pulmonary hypertension), pleural effusion, and pulmonary edema.

2.4.4. Coronary angiography

• Coronary angiography is recommended for patients with HF and CCS angina refractory to medical therapy, presence of symptomatic ventricular arrhythmias (VA), or after cardiac arrest, in order to establish the diagnosis of CAD and assess its severity [114].

ESC IB (CQR A, LOR 2)

• Coronary angiography may be recommended for patients with HF who have an intermediate-to-high pre-test probability of CAD and/or myocardial ischemia according to stress tests, and who are considered suitable candidates for coronary revascularization, to address the issue of potential myocardial revascularization [115–117].

ESC IIbB (LoE A, LoR 2)

2.4.5. Radionuclide diagnostics

• Single-photon emission computed tomography (SPECT) of the myocardium is recommended for patients with HF and CAD to assess ischemia and determine myocardial viability [118, 119].

ESC IIaB (LOCE B, LOE 2)

• 99mTc-Pyrophosphate myocardial scintigraphy (V09BA03 Technetium (99mTc) pyrophosphate) is recommended for patients with HFpEF to identify transthyretin cardiac amyloidosis [120–123].

ESC IIaB (LOCE B, LOE 2)

2.4.6. Transesophageal echocardiography

• Patients with HF and AF in whom restoration of sinus rhythm is planned are recommended to undergo transesophageal echocardiography to rule out left atrial appendage thrombosis [124].

ESC IC (CQR C, LOR 5

Comments: Transesophageal echocardiography is not used for routine diagnosis of HF; it is typically resorted to in patients with complex acquired heart disorders (especially mitral valve pathology and prosthetic valve dysfunction), suspected aortic dissection, infective endocarditis, and in certain categories of patients with congenital heart defects.

2.4.7. Stress echocardiography (exercise/pharmacological)

• Patients with HFrEF and CAD are recommended to undergo stress echocardiography with dobutamine infusion** to diagnose viable myocardial tissue when deciding on revascularization [125–127].

ESC IC (LoE B, LoR 2)

• Patients with HF and suspected severe aortic stenosis who present with a low transvalvular pressure gradient due to LV systolic dysfunction are recommended to undergo stress echocardiography [128–131].

ESC IC (LoE B, LoR 3

• Patients with symptomatic HFpEF and mild LV diastolic dysfunction or inconclusive resting evaluation results are recommended to undergo diastolic transthoracic stress echocardiography with graded physical exercise (or a diastolic stress test, DST) to assess changes in filling pressure during exercise, which helps confirm or refute the diagnosis of HFpEF [110, 132–134].

ESC IC (CQR B, LOR 1

Comments. Supine cycle ergometry is commonly used as physical exercise during the DST; the E/e′ ratio and tricuspid regurgitation velocity are used to assess the dynamics of filling pressure during exercise (parameters that sufficiently reflect filling pressure dynamics). If the Doppler E/e′ ratio exceeds 14 during the DST (combined with or without an increase in tricuspid regurgitation velocity >3.4 m/s), it indicates an increase in LV filling pressure and points to the presence of HFpEF in the patient [110].

The diagnosis of HFpEF cannot be established solely on the basis of an isolated increase in tricuspid regurgitation velocity (i.e., without a corresponding increase in the E/e′ ratio), since a significant isolated rise in pulmonary artery pressure may be associated with occult pulmonary arterial hypertension [135].

In patients with normal EF who already have elevated LV filling pressure at rest (i.e., grade II–III diastolic dysfunction), the diagnosis of HFpEF is unquestionable; however, such patients may undergo a stress test to detect stress-induced myocardial ischemia and assess exercise tolerance [132].

2.4.8. Computed tomography coronary angiography

• Coronary computed tomography angiography is recommended for patients with HF and low or intermediate probability of CAD to detect stenosing coronary artery disease [136–138].

ESC IIaB (LOCE B, LOE 2)

Comments. Computed tomography coronary angiography is the most informative non-invasive method for assessing coronary artery patency, characterized by high spatial resolution and high scanning speed. The method has a high negative predictive value, which makes it possible to rule out the diagnosis of coronary artery disease in patients with low and/or intermediate disease risk [139, 140].

2.4.9. Magnetic resonance imaging of the heart and great vessels

Cardiac and great vessel MRI encompasses various techniques that allow detailed information on cardiac morphology, intracardiac hemodynamics, ventricular function, blood flow velocity and volume in large vessels, and myocardial structure to be obtained in a single examination, even without contrast administration. The use of contrast agents significantly expands the capabilities of the method. Images obtained immediately after contrast administration allow evaluation of the first pass of the agent through the myocardium and detection of perfusion defects as well as areas of microvascular obstruction. Post-contrast images reveal areas of necrosis and/or fibrosis; such images can detect even small areas of contrast enhancement, making it possible to study not only the left ventricle, but also the right ventricle and the atrial myocardium. The presence and severity of fibrous changes not only assist in establishing the correct diagnosis but also determine the prognosis of patients with certain cardiomyopathies.

There are absolute contraindications to MRI (MR-incompatible pacemakers, ICDs, resynchronization devices, cerebral vascular metallic devices, presence of metal in the orbits), as well as a number of relative contraindications (claustrophobia, certain metal implants, hyperthermia, inability to remain still during the scan). It should be remembered that intravascular (including intracoronary) stents, most artificial valves, and certain types of artificial pacemakers are not contraindications to MRI. Gadolinium-based contrast agents are generally well tolerated by patients; however, their use in patients with severe renal impairment (GFR <30 mL/min/m²) is only possible in cases of serious clinical necessity. Recent studies indicate the need for restricted use of linear gadolinium-based contrast agents (only as second-line agents) due to data regarding the potential deposition of gadolinium molecules in brain tissue. The use of linear gadolinium-based contrast agents is prohibited in patients with decreased renal function [141-146].

• Cardiac and great vessel MRI is recommended in patients with uninformative echocardiography to assess cardiac anatomy and function, systolic and diastolic dysfunction, and left ventricular ejection fraction [147-152].

ESC IB (LoE B, GoR 2)

Comments. Cardiac MRI is the gold standard for assessing cardiac chamber sizes and volumes, myocardial mass, and contractile function. Cardiac MRI is an accurate method for assessing the right heart, right ventricular dimensions, and right ventricular ejection fraction. MRI is informative in assessing cardiac morphology and function in patients with cardiomyopathies (especially apical hypertrophic cardiomyopathy and left ventricular non-compaction) and complex congenital heart disease. MRI is a non-invasive alternative to echocardiography.

ESC IIaB (LOCE B, LOE 2)

ESC IIaB (LoE B, GoR 1)

Comments. Contrast-enhanced cardiac MRI allows evaluation of myocardial structure based on the distribution of the gadolinium-based contrast agent in the myocardium. Contrast enhancement occurs in myocardial regions with damaged cardiomyocyte membranes. Images obtained immediately after contrast administration allow evaluation of the first-pass perfusion through the myocardium and detection of perfusion defects as well as areas of microvascular obstruction. Late gadolinium enhancement images (obtained 10–20 minutes after injection) reveal areas of necrosis and/or fibrosis. Such images can detect even small areas of contrast uptake (spatial resolution up to 1 g), making it possible to evaluate not only the left ventricle, but also the right ventricle and atrial myocardium. The cause of cell membrane integrity loss is determined by the localization and spatial characteristics of the enhancement foci: transmural and subendocardial enhancement in regions corresponding to coronary artery territories is typical for ischemic injury, whereas subepicardial, intramural, and patchy enhancement is typical for non-ischemic injury. Performing specialized sequences such as T2 mapping and T1 mapping (both with and without contrast enhancement) provides information on diffuse myocardial changes (amyloid, glycogen, or iron deposition, diffuse fibrosis) that cannot be obtained using other non-invasive imaging modalities. The presence and extent of fibrous changes not only assist in making the correct diagnosis but also determine the prognosis of patients with certain cardiomyopathies. Furthermore, contrast-enhanced MRI allows not only the detection of myocardial fibrosis in patients with heart failure of ischemic and non-ischemic etiology, but also its quantification: determining the extent of scar tissue and its heterogeneity. Both parameters affect the achievement of clinical efficacy of the implanted device. Scar localization must be considered during lead implantation, as placing the lead in the scar area reduces the potential benefit of cardiac resynchronization therapy. Further research into the clinical efficacy of contrast-enhanced MRI prior to resynchronization device implantation may allow contrast-enhanced cardiac MRI to be recommended for patients with worsening heart failure symptoms despite adequate medical therapy before deciding on resynchronization device implantation [179-190].

2.4.10. Right heart catheterization

• Right heart catheterization (transvenous cardiac catheterization) is recommended in patients with advanced heart failure as part of the evaluation for heart transplantation and/or mechanical circulatory support (MCS) [191, 192].

ESC IC (RR S, ELD 5)

• Right heart catheterization (transvenous cardiac catheterization) is recommended in patients in whom heart failure is considered to be caused by constrictive pericarditis, restrictive cardiomyopathy, congenital heart disease, or high-output heart failure [192].

ESC IIaC (LoE C, GoR 5)

ESC IIaC (LoE C, GoR 5)

• Right heart catheterization (transvenous cardiac catheterization) may be considered in selected patients with heart failure with preserved ejection fraction to confirm the diagnosis [193-195].

ESC IIbC (LoE C, GoR 5)

2.5 Other Procedures

2.5.1. Stress tests

Exercise stress testing is recommended to assess functional status, treatment efficacy, candidacy for heart transplantation, and prescription of cardiac rehabilitation.

6-minute walk test

• In routine clinical practice, the 6-minute walk test is recommended to assess exercise tolerance [110, 196] (Appendix G2).

ESC IIaC (LoE A, GoR 2)

Cardiopulmonary exercise testing

Cardiopulmonary exercise testing (CPET) evaluates ventilation and gas exchange during graded physical exercise (peak oxygen consumption index, anaerobic threshold). Patients with heart failure exhibit a reduced anaerobic threshold and peak oxygen consumption.

• CPET is recommended in patients with advanced heart failure as part of the evaluation for heart transplantation and/or MCS [197-199].

ESC IC (RR S, ELD 5)

• CPET is recommended in patients with heart failure to optimize exercise prescription [197-199].

ESC IIaC (LoE C, GoR 5)

• CPET is recommended in patients with heart failure to identify the cause of unexplained dyspnea and/or exercise intolerance [197-199].

ESC IIaC (LoE C, GoR 5)

2.5.2. Endomyocardial biopsy

• Endomyocardial biopsy should be considered in patients with rapidly progressive heart failure despite standard therapy when there is a likelihood of specific cardiac involvement that can only be confirmed by histological findings, in order to guide subsequent disease-specific therapy [200, 201].

ESC IIaC (LoE C GoR 5)

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

3.1. Conservative management

3.1.1. Main objectives of treatment for patients with chronic heart failure:

-reduction of heart failure symptoms (dyspnea, edema, etc.),

-improvement in quality of life,

-reduction in hospitalization rates,

-improvement in prognosis.

Reduction in mortality and the number of hospitalizations is the primary criterion for the efficacy of therapeutic interventions. As a rule, this is accompanied by the reversal of LV remodeling and a decrease in natriuretic peptide concentrations.

For any patient, it is also extremely important that the treatment allows them to achieve symptom relief, improves their quality of life, and enhances functional capacity, although this is not always accompanied by an improved prognosis in patients with HFrEF. Nevertheless, a hallmark of modern effective pharmacotherapy is the achievement of all specified treatment goals.

3.1.2. Therapy Recommended for Patients with Symptomatic Heart Failure with Reduced Left Ventricular Ejection Fraction

• ACE inhibitors/valsartan+sacubitril**, beta-blockers (beta-blockers), aldosterone antagonists, dapagliflozin**/empagliflozin** (sodium-glucose cotransporter 2 inhibitors) are recommended as part of a four-drug combination therapy for the treatment of all patients with symptomatic HFrEF (≤40%) to reduce heart failure-related hospitalizations and death [202-213].

ESC no (LoE A, GoR 2)

3.1.2.1. Angiotensin II Receptor Antagonists in Combination with Other Drugs (valsartan+sacubitril**)

• Valsartan+sacubitril** is recommended for all patients with symptomatic HFrEF in the absence of contraindications to reduce the risk of heart failure hospitalization and death [203, 214].

ESC IB (Level of Reliable Evidence A, Level of Clinical Evidence 2)

• Initiation of therapy with valsartan+sacubitril** instead of ACE inhibitors/ARBs is recommended in patients with HFrEF hospitalized due to heart failure decompensation, after hemodynamic stabilization, for further reduction of the risk of heart failure hospitalizations and death [203].

ESC IIaB (Level of Reliable Evidence B, Level of Clinical Evidence 2)

Comments. The recommended starting dose of valsartan+sacubitril** in stable heart failure is 49/51 mg twice daily, and the target dose is 97/103 mg twice daily. In patients who have not previously received ACE inhibitor or angiotensin II receptor blocker (ARB) therapy, or who received low doses of these drugs, therapy with valsartan+sacubitril** should be initiated at a dose of 25.7/24.3 mg twice daily with slow titration [214].

When initiating therapy during heart failure decompensation after hemodynamic stabilization, the initial dose of valsartan+sacubitril** is 24/26 mg twice daily [203].

Switching to valsartan+sacubitril** should be performed no earlier than 36 hours after the last dose of an ACE inhibitor.

Practical aspects of using valsartan/sacubitril** in patients with HFrEF are outlined in Appendix A3-2.

3.1.2.2. ACE inhibitors

• ACE inhibitors are recommended for all patients with symptomatic HFrEF in the absence of contraindications to reduce the risk of heart failure hospitalization and death [202, 215-217].

ESC IA (LoE A, GoR 2)

• ACE inhibitors are recommended for patients with asymptomatic left ventricular systolic dysfunction and a history of myocardial infarction for the prevention of heart failure symptoms [218].

ESC IA (Level of Reliable Evidence A, Level of Clinical Evidence 2)

• ACE inhibitors are recommended for patients with asymptomatic left ventricular systolic dysfunction without a history of myocardial infarction to prevent the development of heart failure symptoms [219].

ESC IB (Level of Reliable Evidence A, Level of Clinical Evidence 2)

Comment: Asymptomatic left ventricular systolic dysfunction in patients with or without a history of myocardial infarction falls under the pre-heart failure stage, and prescribing ACE inhibitors is considered a strategy to prevent the onset of heart failure symptoms.

The following ACE inhibitors are used to treat heart failure: captopril**, quinapril, lisinopril**, perindopril**, ramipril**, spirapril, fosinopril, enalapril** and others (Table 5).

Table 5. Doses of ACE inhibitors for the treatment of patients with HFrEF [202, 215-221].

! The use of #enalapril** at an initial dose of 2.5 mg twice daily does not correspond to the dosing regimen specified in the drug's instructions for use; however, the clinical efficacy and safety of this regimen were demonstrated in the SOLVD RCT with a 12-year patient follow-up period, and therefore this dosing regimen is recommended for use [202].

Practical aspects of using ACE inhibitors in patients with HFrEF are outlined in Appendix A3-3.

Beta-blockers (beta-blockers) are recommended for all patients with stable symptomatic HFrEF in the absence of contraindications to reduce the risk of heart failure hospitalization and death [210-212, 222].

ESC IA (LoE A, GoR 2)

Comments. Beta-blocker therapy should be initiated as early as possible in patients with HFrEF. Beta-blockers also have anti-ischemic effects, are more effective in reducing the risk of sudden cardiac death (SCD), and their use leads to a rapid reduction in all-cause mortality in patients with heart failure.

• Beta-blockers are recommended for patients after a myocardial infarction and with left ventricular systolic dysfunction to reduce the risk of death and prevent the development of heart failure symptoms [223].

ESC IB (LoE A, GoR 2)

• In patients with heart failure decompensation, if beta-blockers were already prescribed before the onset of decompensation symptoms, continuation of therapy is recommended, if necessary at a reduced dose, to improve prognosis [211].

ESC IIaA (Level of Reliable Evidence B, Level of Clinical Evidence 2)

Comments. If symptoms of severe hypoperfusion are present, complete discontinuation of beta-blocker therapy is possible, followed by its mandatory resumption once the condition stabilizes [211, 224].

Beta-blockers recommended for heart failure and their dosages are presented in Table 6.

Table 6. Doses of beta-blockers recommended for the treatment of patients with HFrEF.

Practical aspects of beta-blocker use in patients with HFrEF are detailed in Appendix A3-4.

3.1.2.3. Aldosterone antagonists

Aldosterone antagonists are recommended for all patients with symptomatic HFrEF in the absence of contraindications to reduce the risk of heart failure hospitalization and death [213, 225].

ESC IA (LoE A, GoR 2)

Comments. When aldosterone antagonists are used in combination with ACE inhibitors/ARBs and beta-blockers, the most significant risk is the development of severe hyperkalemia ≥6.0 mmol/L, which occurs significantly more often in routine clinical practice than in clinical trials [226].

Aldosterone antagonists should be prescribed both during inpatient treatment and in the outpatient setting if not previously prescribed; initial and target doses are presented in Table 7.

Table 7. Doses of aldosterone antagonists for the treatment of patients with HFrEF

Practical aspects of using aldosterone antagonists in patients with HFrEF are detailed in Appendix A3-5.

3.1.2.4. Dapagliflozin**/empagliflozin** (sodium-glucose cotransporter 2 inhibitors)

• Dapagliflozin**/empagliflozin** are recommended for all patients with symptomatic HFrEF, regardless of the presence or absence of diabetes mellitus and in the absence of contraindications, to reduce the risk of heart failure hospitalization and death [207–209].

ESC IC (Level of Evidence A, Grade of Recommendation 1)

Comments. For the treatment of patients with HFrEF, dapagliflozin** and empagliflozin** are used in fixed doses of 10 mg once daily.

Practical aspects of using sodium-glucose cotransporter 2 inhibitors in patients with HFrEF are detailed in Appendix A3-6.

3.1.2.5. Diuretics

Unlike other therapeutic agents, the effect of diuretics on morbidity and mortality in patients with heart failure has not been studied in long-term trials. Nevertheless, the use of diuretics relieves symptoms associated with fluid retention (peripheral edema, dyspnea, pulmonary congestion), which justifies their use in patients with heart failure regardless of LVEF [227–232].

• Diuretics are recommended to improve heart failure symptoms in patients with signs of fluid retention [227].

ESC IB (Level of Evidence A, Grade of Recommendation 1)

• The administration of diuretics is recommended to reduce the risk of heart failure hospitalization in patients with symptoms of fluid retention [227].

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

Comments. Diuretics cause a rapid regression of heart failure symptoms, unlike other heart failure therapies.

The optimal diuretic dose is considered to be the lowest dose that maintains the patient in a state of euholemia, i.e., when daily diuretic intake provides balanced diuresis and stable body weight. In patients with heart failure, diuretics should be used in combination with beta-blockers, ACE inhibitors/valsartan+sacubitril**/ARBs, and aldosterone antagonists (in the absence of contraindications to these drug classes).

Diuretics recommended for the treatment of heart failure are presented in Table 8.

Table 8. Doses of diuretics most frequently used in the treatment of patients with heart failure

Comments: diuretic doses may be increased to maximum values according to the product labeling.

Practical aspects of using diuretics in patients with HFrEF are detailed in Appendix A3-7.

• The use of ARBs is recommended in patients with HFrEF only in case of intolerance to valsartan+sacubitril**/ACE inhibitors to reduce the risk of heart failure hospitalization and death [204, 205, 233–235].

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

ARBs recommended for use in patients with heart failure are presented in Table 9.

Table 9. Doses of angiotensin II receptor blockers recommended for the treatment of patients with HFrEF

Practical aspects of ARB use in patients with HFrEF are detailed in Appendix A3-8.

3.1.2.7. If-channel inhibitors (other drugs for heart conditions)

• Ivabradine** is recommended for patients with symptomatic HFrEF in sinus rhythm and a heart rate (HR) ≥70 bpm who are receiving optimal medical therapy (OMT) including recommended (or maximally tolerated) doses of beta-blockers, to reduce HF-related hospitalizations and mortality [236-239].

ESC IIaB (LoE B, GoR 2)

Comments. The mechanism of action of ivabradine** consists in reducing HR due to selective inhibition of the If ionic current in the sinus node without any effect on the inotropic function of the heart. The drug is active only in patients in sinus rhythm. It has been shown that in patients in sinus rhythm, LVEF ≤35%, symptoms of HF NYHA classes II-IV, and HR ≥70 bpm despite therapy with recommended (or maximally tolerated) OMT doses, the addition of ivabradine** to treatment reduces the composite endpoint of HF-related hospitalizations and mortality. In addition, in case of beta-blocker intolerance, the use of ivabradine** in addition to standard therapy in this same category of patients reduces the risk of HF-related hospitalizations [237].

• Ivabradine** is recommended to reduce the risk of HF-related hospitalizations and cardiovascular mortality in patients with symptomatic HFrEF in sinus rhythm and an HR ≥70 bpm receiving OMT who are unable to tolerate or have contraindications to beta-blockers [238].

ESC IIaC (LoE B, GoR 2)

Comments. The recommended starting dose of ivabradine** is 5 mg twice daily, followed by an increase after 2 weeks to 7.5 mg twice daily. In elderly patients, downward dose adjustment of ivabradine** is possible [237-239].

The use of cardiac glycosides in patients with HF is limited. Of the existing drugs, digoxin** is recommended; the efficacy and safety of other cardiac glycosides in HF have not been sufficiently studied. The prescription of digoxin** to patients with HF does not improve their prognosis; however, it reduces the number of HF-related hospitalizations, the severity of HF symptoms, and improves quality of life [240-246].

In a number of cases, the use of digoxin** can only complement therapy with beta-blockers, ACE inhibitors/valsartan+sacubitril**/ARBs, aldosterone antagonists, dapagliflozin**/empagliflozin**, and diuretics.

ESC IIb B (LoE B, GoR 2)

Comments. Digoxin^** prescription should be approached with caution, and it is preferably used when the patient has severe HF NYHA classes III-IV, low LVEF (<25%) combined with a tendency toward hypotension. The optimal dose of digoxin** for the treatment of patients with HF is considered to be 0.125-0.25 mg/day. During long-term treatment, it is necessary to monitor blood levels of digoxin**, which should be within safe limits [243, 244].

The optimal concentration in patients with HF is the range from 0.8 ng/mL to 1.1 ng/mL (<1.2 ng/mL). The dose of digoxin** should be reduced (with concentration monitoring) in case of decreased GFR, in elderly patients, and in women [245].

Due to the likelihood of ventricular arrhythmias and atrioventricular conduction disturbances, monitoring of blood electrolytes, renal function, and ECG is necessary.

The principles of using digoxin** for HR control in patients with symptoms of HF and tachyarrhythmic atrial fibrillation are outlined in section 3.1.6.

3.1.3. Therapy Not Recommended (Positive Effect Not Proven) in Patients with Symptomatic Heart Failure and Reduced Left Ventricular Ejection Fraction

• The prescription of oral anticoagulants (OACs) (vitamin K antagonists, direct thrombin inhibitors, direct factor Xa inhibitors) to patients with HF and sinus rhythm, in the absence of other indications, is not recommended due to the lack of an effect on mortality [247-249].

ESC IIIA (LoE A, GoR 1)

• Direct renin inhibitors (as an add-on therapy to HF OMT) are not recommended for the treatment of any group of patients with HF [250, 251].

ESC III B (LoE A, GoR 2)

Comments. The results of studies (ASTRONAUT – patients after HF decompensation, high risk; ALTITUDE – patients with diabetes mellitus, terminated prematurely) indicate that direct renin inhibitors lack additional positive effects on the prognosis and hospitalizations of HF patients, and also increase the risk of hypotension, hyperkalemia, and renal dysfunction, especially in patients with diabetes mellitus [250, 251].

3.1.3.3. Pain management in chronic heart failure

Patients with HF do not require specific analgesia.

3.1.4. Therapy the Use of Which May Be Dangerous and Is Not Recommended for Patients with Chronic Heart Failure of NYHA Functional Classes II-IV and Reduced Left Ventricular Ejection Fraction

• Thiazolidinediones are not recommended for patients with HF, as they cause fluid retention and thereby increase the risk of decompensation [252-254].

ESC IIIA (LoE A, GoR 1)

• Most nondihydropyridine calcium channel blockers (syn. calcium antagonists, calcium channel blockers) (diltiazem, verapamil**, short-acting dihydropyridines) are not recommended for use in HF due to their negative inotropic effect, which contributes to the development of decompensation in patients with HF [255].

ESC IIIC (LoE A, GoR 2)

Comments. Exceptions are felodipine and amlodipine**, which do not affect the prognosis of patients with HF (PRAISE I and II; V–HeFT III trials) [256-258]..

• The use of nonsteroidal anti-inflammatory drugs (NSAIDs) or type 2 cyclooxygenase (COX-2) inhibitors (other nonsteroidal anti-inflammatory and antirheumatic drugs) is not recommended in HF, as NSAIDs and COX-2 inhibitors provoke sodium and fluid retention, which increases the risk of decompensation in patients with HF [259].

ESC IIIB (LoE C, GoR 4)

• Class I antiarrhythmic drugs (antiarrhythmic drugs class Ia, antiarrhythmic drugs class Ib, antiarrhythmic drugs class Ic) are not recommended for patients with HF, as they increase the risk of SCD in patients with LV systolic dysfunction [260, 261].

ESC IIIA (LoE A, GoR 2)

3.1.5. Features of Treatment of Patients with Chronic Heart Failure and Ventricular Rhythm Disorders

• Patients with HF are recommended to correct factors provoking or worsening the course of ventricular arrhythmias (correction of electrolyte disturbances, discontinuation of drugs provoking ventricular arrhythmias) for the purpose of treating and preventing arrhythmias [213, 262-264].

ESC IIaC (LoE C, GoR 5)

• Patients with HF and worsening ventricular arrhythmias are recommended to undergo coronary revascularization (cardiopulmonary bypass coronary artery bypass grafting, coronary artery stenting, percutaneous transluminal coronary angioplasty with coronary artery stenting) to improve disease prognosis [117, 265-267].

ESC IIaC (LoE B, GoR 3)

• Patients with HFrEF and ventricular rhythm disorders are recommended optimization of doses of ACE inhibitors/valsartan+sacubitril**/ARBs, beta-blockers, aldosterone antagonists to reduce the risk of SCD [212-214, 225, 268, 269].

ESC IA (LoE B, GoR 2)

Comments. If a patient is on ACE inhibitor or ARB therapy, the presence of ventricular rhythm disorders is an additional reason to switch to valsartan+sacubitril**, since according to the PARADIGM-HF study, treatment with valsartan+sacubitril** compared to enalapril reduced the risk of SCD [264].

• Patients with HFrEF, LVEF ≤35%, receiving OMT, are recommended implantation of an ICD^*** or CRT-D (cardiac resynchronization therapy defibrillator) for the purpose of preventing SCD [270-276].

ESC IA (LoE A, GoR 1)

• Routine prescription of Class I and III antiarrhythmic drugs is not recommended for patients with HF and asymptomatic ventricular arrhythmias for safety reasons (HF decompensation, proarrhythmic effect, or death) [277, 278].

ESC IIIA (CoE B, LOE 2)

Comments. In patients with HF and CRT, frequent premature ventricular contractions (PVCs) (more than 5-10% of the total number of QRS complexes per day) require the prescription of antiarrhythmic treatment or catheter ablation, as their presence can lead to a decrease in the percentage of biventricular pacing to less than 92% and, thus, reduce the effectiveness of CRT [279].

• For patients with heart failure with reduced ejection fraction (HFrEF), amiodarone^** administration is recommended in addition to beta-blocker therapy for the treatment of recurrent symptomatic sustained monomorphic ventricular tachycardia (VT) [280].

ESC IIaB (LoE B, GoR 2)

Comments. However, it should be noted that such therapy does not reduce the incidence of sudden cardiac death or patient mortality.

• For patients with ischemic heart failure and recurrent symptomatic sustained episodes of monomorphic VT or ICD*** shocks delivered for monomorphic VT despite ongoing amiodarone** therapy, catheter ablation (radiofrequency ablation of arrhythmogenic zones, cryoablation of arrhythmogenic zones) is recommended [281].

ESC IB (LoE B, LoR 2)

• For patients with unexplained reduction of LVEF, symptoms of heart failure, no structural heart disease on cardiac MRI, and frequent, predominantly monomorphic premature ventricular contractions (PVCs), catheter ablation (radiofrequency ablation of arrhythmogenic zones, cryoablation of arrhythmogenic zones) is recommended to restore left ventricular function [282-288].

ESC IC (LoE B, GoR 2)

Comment: Frequent PVCs are defined as a PVC burden of more than 10% based on 24-hour (Holter) ECG monitoring. Frequent PVCs in patients with no structural heart disease on cardiac MRI can be a cause of cardiomyopathy presenting with reduced LVEF and symptoms of heart failure (so-called PVC-induced cardiomyopathy) [282, 283].

• For patients with heart failure and left ventricular dysfunction resulting from frequent and predominantly monomorphic PVCs, medical antiarrhythmic therapy is recommended when catheter ablation is undesirable, carries a high risk, or has proven ineffective, with the aim of restoring left ventricular function [289, 290].

ESC IIaC (LoE B, GoR 2)

• For patients with non-ischemic left ventricular systolic dysfunction, cardiac MRI with late gadolinium enhancement is recommended to assess the risk of ventricular arrhythmias, clarify their etiology, and evaluate the risk of sudden cardiac death [291-293].

ESC IIaB (LoE A, GoR 2)

• For patients with non-ischemic left ventricular systolic dysfunction and syncope, invasive electrophysiological study (endocardial electrophysiological study) is recommended when standard evaluation fails to determine the cause of syncope [294, 295].

ESC IIaC (LoE B, GoR 2)

• The use of class IA and IC antiarrhythmic drugs is not recommended in patients with systolic heart failure for the treatment and prevention of ventricular arrhythmias [260, 278, 296].

ESC IIIA (LoE A, GoR 1)

• In patients with heart failure with reduced ejection fraction due to coronary artery disease and recurrent episodes of symptomatic sustained VT despite ongoing therapy with beta-blockers, aldosterone receptor antagonists, and ACE inhibitors/ARBs/sacubitril/valsartan**, as well as in cases of electrical storm when amiodarone is ineffective or not tolerated^**, catheter ablation (radiofrequency ablation of arrhythmogenic zones, cryoablation of arrhythmogenic zones) is recommended to suppress ventricular arrhythmias [276, 280, 297, 298].

ESC IB (LoE A, GoR 1)

Comments. The number of ventricular arrhythmias, the type of termination (antitachycardia pacing or endocardial defibrillation), potential side effects of amiodarone**, and patient preference should be taken into account.

• When arrhythmias are refractory to medical therapy, catheter ablation (radiofrequency ablation of arrhythmogenic zones, cryoablation of arrhythmogenic zones) may be recommended in selected patients with non-ischemic heart failure to gain control over VT or prevent recurrent ICD shocks [299-303].

ESC IIbB (LoE B, GoR 3)

• For patients with ischemic heart failure and LVEF ≥40% for the treatment of hemodynamically well-tolerated sustained monomorphic VT, catheter ablation (radiofrequency ablation of arrhythmogenic zones, cryoablation of arrhythmogenic zones) achieving established procedural efficacy criteria at an experienced center is recommended as an alternative to ICD implantation*** [304, 305].

ESC IIaC (LoE A, GoR 3)

• Catheter ablation (radiofrequency ablation of arrhythmogenic zones, cryoablation of arrhythmogenic zones) at specialized centers is recommended for patients with non-ischemic cardiomyopathy and recurrent symptomatic sustained monomorphic VT or ICD*** shocks for monomorphic sustained VT when antiarrhythmic drug therapy is ineffective, contraindicated, or not tolerated [299, 306-308].

ESC IIaC (LoE A, GoR 3)

3.1.6. Specifics of Management of Patients with Heart Failure and Atrial Fibrillation

• Regardless of LVEF, for all patients with heart failure and atrial fibrillation (AF), especially in cases of newly diagnosed AF or paroxysmal AF, it is recommended to:

— identify potentially reversible causes (hypo- or hyperthyroidism, electrolyte disturbances, uncontrolled hypertension, mitral valve disease) and triggers (surgery, respiratory infection, asthma/COPD exacerbation, acute myocardial ischemia, alcohol abuse) that dictate the primary management strategy;

— assess stroke risk and the need for anticoagulant therapy;

— assess ventricular rate and the need for rate control;

— assess symptoms of AF and heart failure [309-313].

ESC IC (LoE C, GoR 5)

• To assess the risk of thromboembolic events (TE) in patients with AF, it is recommended to use the CHA2DS2-VASc score [314-316].

ESC IA, (LoE B, GoR 3)

Comments. The need for stroke and arterial thromboembolism prevention in non-valvular AF is determined by the CHA2DS2-VASc score.

• Long-term oral anticoagulant (OAC) therapy for the prevention of thromboembolic events is recommended for all patients with paroxysmal or persistent/permanent AF and heart failure who have a CHA2DS2-VASc score of 2 or more for men and 3 or more for women [317-320].

ESC IA (LoE A, LoR 2)

• Long-term OAC therapy for the prevention of thromboembolic events is recommended for all patients with paroxysmal or persistent/permanent AF and heart failure who have a CHA2DS2-VASc score of 1 or more for men and 2 or more for women [321, 322].

ESC IIaB (LoE B, GoR 2)

Comment: Treatment should be tailored individually, taking into account clinical benefit and patient preferences.

• For patients with heart failure and AF, when choosing between direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs), the use of DOACs is recommended due to a lower risk of stroke, intracranial hemorrhage, and death, except for patients with moderate-to-severe mitral stenosis or a mechanical mitral valve prosthesis, for whom VKAs are recommended [318, 319, 323-325].

ESC IA (LoE A, GoR 1)

3.1.6.2. Prevention of Atrial Fibrillation in Patients with Heart Failure

• For patients with heart failure, therapy with ACE inhibitors/sacubitril/valsartan**/ARBs, beta-blockers, aldosterone antagonists, dapagliflozin**/empagliflozin** is recommended, including to reduce the incidence of AF [126, 233, 326-329].

ESC IA (LoE A, GoR 1)

• Amiodarone** is recommended for patients with heart failure and AF for pharmacological cardioversion [330-333].

ESC IIaC (LoE B, GoR 2)

• The use of amiodarone^** is recommended in patients with paroxysmal AF when beta-blocker therapy is ineffective for symptom control [330-333].

ESC IIaC (LoE B, GoR 2)

3.1.6.3. Recommendations for Initial Treatment of Patients with Heart Failure and Atrial Fibrillation with Rapid Ventricular Response in Acute or Chronic Settings

• Emergency electrical cardioversion is recommended for all patients with heart failure if AF has led to hemodynamic instability, in order to improve the patient's clinical condition [334, 335].

ESC IC (LoE C, GoR 5)

Comments. Hemodynamic instability is defined as a significant drop in blood pressure accompanied by presyncope/syncope or acute decompensated heart failure.

• Intravenous bolus administration of amiodarone** is recommended for patients with acute heart failure in addition to acute heart failure treatment to reduce ventricular rate [336, 337].

ESC IIaB (LoE B, GoR 2)

Comments. The optimal heart rate during AF is 80 to 100 bpm at rest, although in some cases a heart rate up to 110 bpm may be acceptable [334, 335, 338, 339].

• For patients with heart failure NYHA class I-III who are euvolemic, oral beta-blocker therapy is recommended as first-line therapy for rate control [340].

ESC IIa (RR B, ELD 2)

Comments. In patients with heart failure and AF, beta-blockers do not improve prognosis compared to other rate-control drugs [262].

• For patients with HFrEF, digoxin** is recommended when the heart rate remains high despite the use of beta-blockers, or when beta-blockers cannot be prescribed for heart rate control [341, 342].

ESC IIaB (Level of Evidence A, Grade of Recommendation 1)

Comments. The optimal heart rate in patients with AF and HFrEF is unknown. The initial strategy is to reduce the heart rate to less than 100-110 bpm, with a stricter reduction (less than 80 bpm at rest) if symptoms related to high heart rate persist. Digoxin** has a narrow therapeutic window. The target serum concentration of digoxin** should not exceed 1.2 ng/mL.

• Atrioventricular node catheter ablation (creation of an artificial atrioventricular block followed by pacemaker implantation) with simultaneous implantation of a pacemaker*** or cardiac resynchronization therapy device (three-chamber implantable cardioverter-defibrillator***, three-chamber implantable pacemaker (biventricular)***) or conduction system pacing may be recommended in selected cases for heart rate control and symptom improvement in patients in whom rhythm control cannot be achieved via AF catheter ablation, or in patients unresponsive to intensive pharmacological heart rate control therapy [343-346].

ESC IIbB (Level of Evidence A, Grade of Recommendation 1)

Comment: it must be taken into account that these patients become pacemaker-dependent.

• Atrioventricular node catheter ablation (creation of an artificial atrioventricular block followed by pacemaker implantation) is recommended for patients with AF and ongoing CRT who have an insufficient (less than 90-95%) percentage of biventricular pacing in order to achieve heart rate control and symptom reduction [279, 347-351].

ESC IIaB (LoE B, GoR 2)

3.1.6.4. Recommendations for rhythm control in patients with atrial fibrillation, symptomatic HFrEF, and left ventricular systolic dysfunction in the absence of acute decompensation

• Electrical cardioversion or pharmacological cardioversion with amiodarone**, if a rhythm control strategy is chosen, may be recommended in patients with persistent HFrEF symptoms despite OMT and adequate heart rate control, to improve symptoms and clinical status [331, 352].

ESC IIb B (LoE B, GoR 2)

• Pulmonary vein ostia isolation (radiofrequency ablation of arrhythmogenic zones, cryoablation of arrhythmogenic zones, thoracoscopic isolation of arrhythmogenic zones) is recommended for patients with HFrEF and paroxysmal or persistent AF when paroxysms cause hemodynamic instability, worsening of HFrEF, or unpleasant symptoms despite the use of recommended pharmacotherapy for clinical symptom improvement [353-355].

ESC IIaB (Level of Evidence A, Grade of Recommendation 1)

Comments. Pulmonary vein ostia ablation is less likely to be successful in patients with long-standing AF and significant right or left atrial dilatation.

• Amiodarone** may be recommended for patients with HFrEF and AF if a rhythm control strategy is chosen before (and after) successful electrical cardioversion to maintain sinus rhythm and reduce clinical symptoms [330-333].

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

Comments. It should be considered that, according to the AF-CHF data, the rhythm control strategy using amiodarone** showed no advantages over the rate control strategy. It is recommended to start therapy with beta-blockers with or without the addition of digoxin^**, and if ineffective, consider rhythm control using amiodarone** or catheter ablation. In case of severe paroxysms and patient reluctance to remain in AF, therapy with amiodarone** may be initiated. Adverse effects associated with amiodarone** should be considered, as well as the fact that the drug may negatively affect patients with LVEF <35% and NYHA functional class III-IV [278, 356].

• Class I antiarrhythmic drugs are not recommended for patients with HFrEF because they increase the risk of death [260, 277, 278].

ESC IIIA (LoE A, GoR 1)

3.1.7. Management of patients with heart failure with preserved ejection fraction and comorbid conditions

The presence of comorbidities in a patient with HFrEF can influence their management. This is due to several reasons. First, target organ damage in a patient with HFrEF may be a significant adverse prognostic factor. Second, the required drug therapy may adversely affect either the course of HFrEF or the concomitant diseases. Finally, concurrent use of multiple drug classes may lead to serious drug-drug interactions. Another serious argument is that randomized controlled trials very often did not specifically investigate the combination of HFrEF and diseases of other organs and systems. This has led to a lack of evidence base for the management of such patients, and treatment algorithms have very often been based solely on expert opinion. It should be noted that all general approaches to diagnosis and treatment are applied to the management of such patient groups, except for special situations described below.

Arterial hypertension

Hypertension is one of the main etiological factors of HFrEF. It has been proven that antihypertensive therapy significantly improves outcomes and symptoms of HFrEF.

• ACE inhibitors (or ARBs in case of intolerance) or sacubitril/valsartan**, beta-blockers, or aldosterone antagonists (or a combination) are recommended to lower blood pressure due to their proven efficacy in patients with HFrEF (reduction of mortality and HFrEF hospitalization risks) [202, 210, 213-217, 219, 357].

ESC IA (LoE A, LoR 2)

Comments. This therapy is also safe in patients with HFpEF and HFmrEF.

• Thiazide or loop diuretics are recommended to potentiate antihypertensive therapy when the combination of an ACE inhibitor/sacubitril/valsartan**/ARB, beta-blocker, and aldosterone antagonist has insufficient antihypertensive efficacy in patients with HFrEF and hypertension [358-360].

ESC IA (Level of Evidence A, Grade of Recommendation 1)

• Amlodipine** may be recommended in patients with HFrEF and hypertension to potentiate antihypertensive therapy when the combination of an ACE inhibitor/sacubitril/valsartan**/ARB, beta-blocker, aldosterone antagonist, and diuretics has insufficient antihypertensive efficacy [256, 258].

ESC IIbA (Level of Evidence A, Grade of Recommendation 2)

• Felodipine may be recommended in patients with HFrEF and hypertension to potentiate antihypertensive therapy when the combination of an ACE inhibitor/sacubitril/valsartan**/ARB, beta-blocker, aldosterone antagonist, and diuretics has insufficient antihypertensive efficacy [256].

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

Comments. Amlodipine** and felodipine do not affect the prognosis of patients with heart failure and are effective drugs for treating hypertension.

• Diltiazem and verapamil** are not recommended for patients with HFrEF due to their negative inotropic effect and the risk of worsening HFrEF [255].

ESC IIIC (Level of Evidence A, Grade of Recommendation 2

Comments. Clinical studies of verapamil** in heart failure are practically non-existent due to its well-known negative inotropic effect and manufacturer warnings [255].

• Moxonidine** is not recommended for patients with HFrEF due to an increased risk of death [361].

ESC IIIB (Level of Evidence A, Grade of Recommendation 2

• Alpha-blockers are not recommended for blood pressure reduction in patients with HFrEF and hypertension due to potential neurohormonal activation, fluid retention, and worsening clinical symptoms [362-364].

ESC IIIA (Level of Evidence A, Grade of Recommendation 2

Dyslipidemia

• Initiation of lipid-lowering therapy with HMG-CoA reductase inhibitors in patients with NYHA functional class II-IV HFrEF is not recommended, as it does not affect prognosis unless patients have other indications for these drugs [365, 366].

ESC IIIA (Level of Evidence A, Grade of Recommendation 2

Comments. According to major randomized controlled trials in patients with HFrEF, the use of HMG-CoA reductase inhibitors does not lead to improved prognosis. At the same time, such therapy is safe, and its continuation may be considered in patients already receiving it.

Exertional angina

• Beta-blockers are recommended as first-line antianginal drugs in patients with HFrEF and exertional angina due to their ability not only to reduce angina symptoms but also to lower the risk of HFrEF-related hospitalizations and death [210, 212, 357, 367].

ESC IA (Level of Evidence A, Grade of Recommendation 2

• In case of insufficient efficacy of beta-blockers (upon reaching the maximum dosage) or their intolerance in patients with HFrEF in sinus rhythm (heart rate ≥70 bpm), ivabradine** is recommended to be added to therapy for antianginal purposes as a recommended heart failure treatment [236, 239, 368].

ESC IIaB (Level of Evidence B, Grade of Recommendation 2

• Trimetazidine is recommended for patients with HFrEF who continue to experience angina pectoris despite therapy with beta-blockers and/or ivabradine**, as an effective agent that is safe in heart failure [369-371].

ESC IIaA (LoE A, GoR 1)

Comments. There is evidence that trimetazidine has an additional beneficial effect of improving LV function and exercise tolerance in patients with HFrEF and CAD who are receiving beta-blocker therapy.

• Ranolazine may be recommended for patients with HFrEF who continue to experience angina pectoris despite therapy with beta-blockers and/or ivabradine**, as an alternative to trimetazidine [372].

ESC IIbC (LoE B, GoR 2)

Comments. Ranolazine is an effective antianginal agent, but its safety in heart failure is unknown.

• Oral or transdermal organic nitrates may be recommended for patients with HFrEF who continue to experience angina pectoris despite therapy with beta-blockers and/or ivabradine** [373-376].

ESC IIbB (LoE A, GoR 2)

Comments. Organic nitrates are effective antianginal agents that are safe in HFrEF.

• Nicorandil may be recommended for patients with HFrEF who continue to experience angina pectoris despite therapy with beta-blockers and/or ivabradine**, as an alternative to organic nitrates [377].

ESC IIbC (LoE C, GoR 5)

Comments. Nicorandil is an effective agent for the treatment of angina, but its safety in heart failure is unknown.

• Amlodipine** or felodipine may be recommended for patients with HFrEF who continue to experience angina pectoris despite therapy with beta-blockers and/or ivabradine**, as effective antianginal agents that are safe in HFrEF [256, 258].

ESC IIbB (LoE A, GoR 2)

• The administration of diltiazem and verapamil** is not recommended in patients with HFrEF due to their negative inotropic effect and the risk of worsening HFrEF [255].

ESC IIIC (LoE A, GoR 4)

• It is recommended to consider coronary revascularization (coronary artery stenting, on-pump coronary artery bypass grafting, percutaneous transluminal coronary angioplasty with stenting) in patients with HFrEF to relieve symptoms of effort angina (or equivalent) in those with a coronary anatomy suitable for revascularization despite OMT including antianginal drugs [378].

ESC IIaA (LoE B, GoR 2)

• In patients with HFrEF and CAD, it is recommended to consider myocardial revascularization (on-pump coronary artery bypass grafting, coronary artery stenting, percutaneous transluminal coronary angioplasty with coronary stenting) after a careful assessment of the individual risk/benefit ratio, taking into account coronary anatomy (proximal stenoses >90% of major vessels, left main or left anterior descending artery stenosis), comorbidities, life expectancy, and patient preference [379].

ESC IIbC (LoE B, GoR 2

Diabetes mellitus

The same medications, including beta-blockers, are used to treat patients with heart failure and diabetes mellitus. The risk of hypoglycemia and other side effects associated with their use has been greatly exaggerated.

• Dapagliflozin** and empagliflozin** are recommended for patients with HFrEF and type 2 diabetes mellitus to reduce the risk of heart failure hospitalization and cardiovascular death [207-209, 380].

ESC IA (LoE A, GoR 1)

• Metformin** is recommended for patients with heart failure and type 2 diabetes mellitus for glycemic control, in the absence of contraindications [381-384].

ESC IIaC (LoE C, GoR 4)

Comments. Metformin** is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) and hepatic impairment due to the risk of lactic acidosis.

• Thiazolidinediones are not recommended for the management of hyperglycemia in patients with NYHA class II-IV heart failure, as these drugs cause fluid retention and increase the risk of heart failure exacerbations [252-254, 385].

ESC IIIA (LoE A, GoR 1)

• The dipeptidyl peptidase-4 inhibitor saxagliptin** is not recommended for the treatment of diabetes mellitus in patients with heart failure or at increased risk of developing it, as it leads to an increased risk of heart failure hospitalization [386].

ESC IIIB (LoE A, GoR 2)

• The dipeptidyl peptidase-4 inhibitors sitagliptin** and linagliptin** may be recommended for the treatment of type 2 diabetes mellitus in patients with heart failure, as they are safe in heart failure and do not affect the risk of heart failure hospitalization [387-389].

ESC IIbB (LoE A, GoR 2)

• Glucagon-like peptide-1 receptor agonists may be recommended for the treatment of type 2 diabetes mellitus in patients with heart failure, as they are safe in heart failure and do not affect the risk of heart failure hospitalization [390-398].

ESC IIbA (LoE B, GoR 1)

Table 10. Recommended drugs for the treatment of type 2 diabetes mellitus in patients with HFrEF

Chronic obstructive pulmonary disease

Diagnosing COPD in patients with heart failure is difficult due to overlapping symptoms and signs and the challenge of interpreting spirometry data. At the same time, there is overdiagnosis of COPD and bronchial asthma in patients with heart failure. The presence of chronic bronchial obstruction is not a contraindication for prescribing beta-blockers in heart failure.

• In patients with heart failure and COPD, it is recommended to use cardioselective beta-blockers (bisoprolol**, metoprolol** [extended-release/extended-action tablets], nebivolol) for heart failure treatment, as they pose a lower risk of bronchial obstruction [399-403].

ESC IIaA (LoE A, GoR 1)

Comments. Initiation and titration of cardioselective beta-blockers must be carried out under strict medical supervision. The onset of cough requires ruling out both a COPD exacerbation, ACE inhibitor intolerance, and heart failure decompensation.

• In patients with HFrEF and sinus rhythm with pronounced bronchial obstruction where beta-blockers cannot be prescribed or target doses cannot be reached, and with a heart rate >70 bpm, it is recommended to add ivabradine** to the therapy for heart failure management [404].

ESC IIaC (LoE B, GoR 2)

Renal failure

Decreased eGFR is not only an independent adverse prognostic factor but also a contraindication to certain medications. Practical aspects of drug administration are outlined in Appendices A3.

Anemia and iron deficiency

To diagnose anemia, hemoglobin and red blood cell counts in a complete blood count should be evaluated; to confirm iron deficiency, serum ferritin concentration and transferrin saturation should be assessed.

• The administration of erythropoiesis-stimulating agents (epoetin alfa**) is not recommended for the treatment of anemia in patients with heart failure, as they do not improve clinical outcomes but increase the incidence of thromboembolic events [405].

ESC IIIB (LoE A, GoR 2)

• The administration of oral iron preparations to patients with HFrEF and iron deficiency (serum ferritin <100 mcg/L, or ferritin levels between 100-299 mcg/L with a transferrin saturation <20%) without anemia is not recommended due to their ineffectiveness [406].

ESC none (LoE B, GoR 2)

• Intravenous ferric carboxymaltose^** is recommended for patients with symptoms of heart failure, left ventricular ejection fraction <45%, and iron deficiency (serum ferritin <100 mcg/L, or ferritin levels between 100-299 mcg/L with transferrin saturation <20%) to alleviate heart failure symptoms, improve functional capacity, and enhance quality of life in patients with heart failure [407-411].

ESC IIaA (LoE A, GoR 2)

• Intravenous ferric carboxymaltose** is recommended for symptomatic patients with heart failure, left ventricular ejection fraction <50%, recent hospitalization for heart failure, and iron deficiency (serum ferritin <100 mcg/L, or ferritin levels between 100-299 mcg/L with transferrin saturation <20%) to reduce the risk of heart failure-related hospitalizations [408, 409, 412-415].

ESC IIaB (LoE A, GoR 1)

Comments. The drug dose is calculated individually based on the baseline hemoglobin and body weight values of the patient (Table 11).

Table 11. Calculation of the cumulative dose of ferric carboxymaltose** in patients with HFmrEF and iron deficiency [405].

Gout and arthritis

• Allopurinol** is recommended for patients with HF as uric acid-lowering therapy [416].

ESC not specified (LoE B, GoR 2)

Comment. In the CARES trial, the use of allopurinol** in patients with cardiovascular diseases and gout was associated with a lower risk of cardiovascular and all-cause mortality compared with febuxostat. However, there is no evidence that uric acid-lowering therapy favorably affects LV function, HF symptoms, and prognosis [416].

• NSAIDs are not recommended for use in patients with HF due to an increased risk of HF decompensation and worsening renal function [417].

No ESC recommendation (LoE C, QoE 4)

Comment. The risk of adverse effects depends on the duration of therapy, type, and dose of NSAIDs.

• For an acute gouty attack in a patient with HF, colchicine is recommended as it has fewer adverse effects compared with NSAIDs [418].

No ESC recommendation (LoE B, QoE 1)

The safety of drugs used to treat rheumatoid arthritis and other systemic connective tissue diseases in patients with HF has not been established. High doses of tumor necrosis factor-alpha (TNF-alpha) inhibitors and systemic glucocorticoids may worsen the course of HF and should be used with caution.

Amyloidosis

• In patients with HF and confirmed transthyretin amyloid cardiomyopathy with mutations in the transthyretin gene (variant-type transthyretin amyloid cardiomyopathy), tafamidis is recommended to regress symptoms, reduce HF-related hospitalizations, and improve clinical outcomes [419-421].

ESC IB (LoE B, GoR 2)

• In patients with HF and wild-type transthyretin amyloid cardiomyopathy, tafamidis is recommended to reduce symptoms, reduce HF-related hospitalizations, and improve clinical outcomes [419-422].

ESC IB (LoE B, GoR 2)

Comment: Cardiac amyloidosis is an infiltrative cardiomyopathy characterized by the accumulation of a protein with a specific fibrillar structure—amyloid—in cardiac tissues. More than 95% of all cases of cardiac amyloidosis are associated with amyloid formation from two precursor proteins: immunoglobulin light chains (AL amyloidosis) and transthyretin (ATTR amyloidosis or transthyretin amyloid cardiomyopathy). Differential diagnosis of these two forms of amyloidosis is a key task for the clinician, as management approaches differ fundamentally depending on the precursor protein. Currently, the cascade diagnostic algorithm is based on a non-biopsy approach; echocardiography, cardiac MRI, and bone scintigraphy with osteotropic radiopharmaceuticals are used as diagnostic tools. Thus, to rule out AL amyloidosis, it is necessary to determine parameters characterizing plasma cell dyscrasia:

- presence of a monoclonal protein (immunoglobulin/light chain) in serum/urine determined by capillary electrophoresis/immunofixation;

- elevated concentration of one of the free immunoglobulin light chains (involved chain) in serum and/or urine (nephelometric method) with an abnormal κ/λ ratio;

- increased number of plasma cells in the myelogram (usually 5% to 10% according to aspiration biopsy data).

Depression

Up to 20% of patients with HF have clinically significant depression. The presence of depression is associated with poorer clinical status and prognosis of the patient [423].

• For the treatment of depressive episodes in patients with HF, tricyclic antidepressants (non-selective monoamine reuptake inhibitors) (amitriptyline**, imipramine**, clomipramine**) and neuroleptics (antipsychotics) (haloperidol** and other typical antipsychotics) are not recommended due to their high cardiotoxicity [424-426].

ESC IIIA (LoE C, QoE 5)

• Sertraline** and escitalopram may be recommended for the treatment of depressive episodes in patients with HF [427, 428].

ESC IIb B (LoE B, GoR 2)

Comments. Sertraline** and escitalopram have demonstrated safety in patients with HF in clinical trials.

3.1.8. Management of patients with heart failure in special populations

In recent years, numerous evidence has been obtained regarding certain differences in the pathogenesis, mechanisms of development, clinical symptoms, and response to HF treatment depending on gender, age, and ethnic characteristics. It should also be taken into account that in RCTs, many representatives of special groups did not constitute a representative sample [429], and only subgroup analysis results or cohort studies are available [430].

Nevertheless, there is currently no basis for a differentiated approach to treatment based on the patient's gender, age, race, and ethnicity.

• Uniform standards for HF treatment are recommended in patients with HF regardless of the patient's gender, age, race, and ethnicity [429, 430].

ESC IA (LoE B, QoE 3)

Comments. It is known that women are more likely to develop cough while taking ACE inhibitors, which leads to more frequent use of ARBs [429, 431-433].

3.1.9. Management of patients with HFmrEF and HFpEF

Treatment of patients with HFmrEF

• In patients with HFmrEF and signs of fluid retention, diuretics are recommended to improve the clinical symptoms of HF [227].

ESC IC (LoE A, QoE 1)

• In patients with HFmrEF, dapagliflozin**/empagliflozin** is recommended to reduce the risk of hospitalization for HF and death [434, 435].

ESC IA (LoE A, QoE 2)

• In patients with HFmrEF, it is recommended to consider the use of sacubitril+valsartan** to reduce the risk of hospitalization for HF and death [10, 436, 437].

ESC IIaB (LoE B, QoE 2)

• In patients with HFmrEF, ACE inhibitors/ARBs, beta-blockers approved for HFrEF, and aldosterone antagonists may be recommended to reduce the risk of hospitalization for HF and death [9, 438, 439].

ESC IIbC (LoE B, QoE 3)

• In patients with HFmrEF, the use of digoxin^** should be considered following the same principles and rules as in the treatment of patients with HFrEF [440].

No ESC recommendation (LoE B, QoE 2)

Treatment of patients with HFpEF

• Patients with HFpEF and congestion are recommended diuretics to eliminate congestion and reduce the severity of symptoms and signs of heart failure [227, 441].

ESC IB (LoE A, QoE 1

• In patients with HFpEF, dapagliflozin**/empagliflozin** is recommended to reduce the risk of hospitalization for HF and death [434, 435].

ESC IA (LoE A, QoE 2)

• In patients with HFpEF in euvolemic status who have pronounced functional limitations and severe LV diastolic dysfunction, diuretics are recommended to improve the clinical symptoms of HF [193].

ESC IIaB (LoE B, QoE 2)

• In patients with HFpEF, valsartan/sacubitril** is recommended to reduce the risk of HF hospitalization and death [436, 437].

ESC IIaB (LoE B, QoE 2)

• In patients with HFpEF and an NT-proBNP level >360 pg/mL, mineralocorticoid receptor antagonists are recommended to reduce the risk of cardiovascular death, HF hospitalization, and cardiac arrest [442, 443].

ESC IIaC (Level of Evidence B, Certainty of Evidence 2)

• In patients with HFpEF, ACE inhibitors/ARBs or mineralocorticoid receptor antagonists may be considered to reduce the risk of HF hospitalization [442, 444, 445].

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

• In patients with HFpEF and sinus rhythm, beta-blockers may be recommended to reduce the risk of HF hospitalization [431, 446, 447].

ESC IIbB (Level of Evidence B, Certainty of Evidence 2)

Comments. There is limited evidence that ACE inhibitors and ARBs reduce symptom severity and improve functional class in HFpEF [442, 444]. The ability of beta-blockers and mineralocorticoid receptor antagonists to reduce symptom severity in HFpEF has not been proven [438, 448, 449].

Data on the efficacy of ACE inhibitors and ARBs regarding the risk of HFpEF exacerbations are highly contradictory [444, 450]. Beta-blockers appear to be ineffective in patients with atrial fibrillation; the effect of digoxin^** on the risk of hospitalization in this patient category has not been studied [10, 442, 444, 445]. Beta-blockers may be prescribed to patients with HFpEF if there are additional indications.

3.2. Surgical treatment

3.2.1. Revascularization in patients with heart failure

• Coronary artery bypass grafting is recommended as the preferred method of myocardial revascularization in patients with heart failure who are suitable for surgery, particularly if they have diabetes mellitus and in patients with multivessel disease [378, 451-453].

ESC IIaB (LOCE B, LOE 2)

• In patients with heart failure undergoing left ventricular assist device implantation, myocardial revascularization (on-pump coronary artery bypass grafting, coronary artery stenting, transluminal balloon coronary angioplasty with stenting) may be recommended [454, 455].

ESC IIbC (LoE C, GoR 5)

Comments. Concomitant coronary artery bypass grafting during left ventricular assist device implantation increases the risk of perioperative death and should be performed only in strictly selected patients at reference centers [454]. Myocardial revascularization for right ventricular ischemia may be recommended during left ventricular assist device implantation [455].

• Coronary revascularization (on-pump coronary artery bypass grafting, coronary artery stenting, transluminal balloon coronary angioplasty with stenting) may be recommended to improve prognosis in patients with HFrEF and coronary artery disease with coronary anatomy suitable for revascularization, but only after careful individual risk-benefit assessment, including the location of coronary lesions (i.e., proximal stenosis of a large-diameter vessel >90%, hemodynamically significant left main coronary artery stenosis, or proximal left anterior descending artery stenosis), comorbidities, and life expectancy [117, 379].

ESC IIb C (LoE A, GoR 2)

• Percutaneous coronary intervention (PCI) (transluminal balloon angioplasty and coronary artery stenting) may be recommended as an alternative to coronary artery bypass grafting based on a multidisciplinary team decision, taking into account coronary anatomy, comorbidities, and surgical risk [456].

ESC IIb C (LoE B, GoR 3)

Comments. In a large registry including 4,616 patients with HFrEF and multivessel coronary artery disease, mortality was comparable (mean follow-up 2.9 years) after coronary artery bypass grafting and PCI (using everolimus-eluting stents). Despite comparable mortality, PCI was associated with a higher risk of myocardial infarction, particularly in patients with incomplete and repeat revascularization. Coronary artery bypass grafting was associated with a higher risk of stroke. Thus, PCI may be considered as an alternative to coronary artery bypass grafting if complete myocardial revascularization can be achieved. The choice between PCI and coronary artery bypass grafting should be based on a careful assessment of coronary anatomy, expected completeness of revascularization, comorbidities (diabetes mellitus, chronic kidney disease), severity of heart failure and left ventricular systolic dysfunction, patient preferences, clinical data, and multidisciplinary consultations involving a cardiologist, cardiac surgeon, and endovascular specialist.

3.2.2. Recommendations for the Treatment of Valvular Heart Disease in Patients with Chronic Heart Failure

Aortic Stenosis

The prognosis of heart failure in patients with severe aortic stenosis is extremely poor. There is no medical therapy proven to improve prognosis in such patients. Treatment is aimed at symptom relief, but even if effective, surgical treatment of the valve lesion should not be delayed. It should be kept in mind that the use of vasodilators in these patients carries a risk of hypotension.

• Aortic valve intervention—either transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR)—is recommended for patients with heart failure and severe high-gradient aortic stenosis (valve area ≤1 cm² (or ≤0.6 cm²/m²), peak velocity ≥4 m/s, mean transvalvular gradient ≥40 mm Hg) to reduce mortality and improve symptoms [457].

ESC IB (CQR A, LOR 2)

Comment. Patients with heart failure and low-flow, low-gradient aortic stenosis (aortic valve area ≤1 cm², peak velocity <4 m/s, mean transvalvular gradient <40 mm Hg, and indexed stroke volume ≤35 mL/m²) require evaluation to clarify the severity of stenosis (dobutamine stress echocardiography** and/or multidetector computed tomography). When high-gradient severe aortic stenosis is suspected (valve area <1 cm², mean pressure gradient >40 mm Hg), other conditions (i.e., anemia, hyperthyroidism, arteriovenous shunts) must be ruled out before performing aortic valve replacement.

ESC IC (LoE B, GoR 3)

Comment. Aortic valve replacement is recommended for patients with a life expectancy of more than 1 year. Several studies have shown that TAVI is non-inferior to SAVR in reducing clinical events (mortality and disabling stroke) in patients at high and intermediate surgical risk. In some randomized controlled trials, the mean age of low-risk patients was >70 years, and the follow-up period was limited to 2 years. Therefore, SAVR is recommended for patients aged under 75 years and at low surgical risk (STS-PROM or EuroSCORE II <4%), whereas TAVI is indicated for patients aged over 75 years or at high surgical risk (STS-PROM or EuroSCORE II >8%). In all other cases, the choice between TAVI and SAVR should be made through multidisciplinary discussion by a cardiologist, cardiac surgeon, and endovascular specialist, weighing the risks and benefits of each procedure according to age, life expectancy, individual patient preferences, and other clinical and anatomical features.

SAVR is recommended for patients younger than 75 years and at low surgical risk (STS-PROM/EuroSCORE II <4%) or operable patients who are unsuitable for transfemoral TAVI.

TAVI is recommended for patients older than 75 years or at high surgical risk (STS-PROM/EuroSCORE II >8%).

• Balloon aortic valvuloplasty (transluminal balloon aortic valvuloplasty, transluminal balloon valvuloplasty of aortic valve stenosis) may be recommended for patients with severe symptoms of acute heart failure (cardiogenic shock) as a bridge to SAVR or TAVI, or for patients with severe heart failure as a bridge to recovery or destination therapy [460, 461].

ESC IIbC (Level of Evidence B, Certainty of Evidence 3)

Aortic Regurgitation

Severe aortic regurgitation can cause progressive LV dilatation followed by its dysfunction and HF. Medical therapy, including ACE inhibitors, may improve HF symptoms in patients with severe aortic regurgitation. Beta-blockers and ivabradine should be used with caution as they prolong diastole and may worsen aortic regurgitation.

• Surgical aortic valve replacement (cardiopulmonary bypass aortic valve replacement) is recommended for patients with severe aortic regurgitation and heart failure symptoms regardless of LVEF [462-466].

ESC IA (LoE A, GoR 3)

Comment. In cases of high or prohibitive surgical risk, TAVR can be used to treat aortic regurgitation [467].

Mitral Regurgitation

• Surgical treatment, preferably mitral valve repair (cardiopulmonary bypass mitral valve repair, subvalvular mitral apparatus reconstruction), is recommended for patients with severe primary mitral regurgitation and heart failure symptoms [468-471].

ESC IB (LoE A, GoR 2)

• Transcatheter mitral valve repair may be recommended for patients with severe primary mitral regurgitation and heart failure symptoms if surgery is contraindicated or the surgical risk is high [472, 473].

ESC IIbB, (LoE C, GoR 2)

• Transcatheter edge-to-edge mitral valve repair is recommended to be considered in carefully selected patients with secondary mitral regurgitation who are not eligible for surgery and do not require coronary revascularization, who have heart failure symptoms despite OMT, and who meet the criteria (LVEF 20-50%, LVESD <70 mm, PASP <70 mmHg, absence of moderate to severe RV dysfunction or severe truncal/tricuspid regurgitation, absence of hemodynamic instability) to reduce HF hospitalization rates [474].

ESC IIaC (LoE B, GoR 2)

• Patients with HF and severe secondary mitral regurgitation who have an indication for myocardial revascularization are recommended to undergo single-stage coronary artery bypass grafting and surgical mitral valve replacement [475].

ESC IIaC (LoE C, GoR 5)

• Transcatheter edge-to-edge mitral valve repair may be recommended in carefully selected patients with severe secondary mitral regurgitation, not eligible for surgery and not requiring coronary revascularization, with severe HF despite OMT who do not meet the criteria for reducing HF hospitalizations (LVEF 20-50%, LVESD <70 mm, PASP <70 mmHg, absence of moderate to severe RV dysfunction or severe truncal/tricuspid regurgitation, absence of hemodynamic instability) to alleviate HF symptoms [476].

ESC IIbC (Level of Evidence B, Certainty of Evidence 3)

Comments: Heart transplantation or left ventricular assist device implantation should also be considered in patients with severe secondary mitral regurgitation who are ineligible for surgery and do not require coronary revascularization.

Tricuspid regurgitation

Treatment of HF with tricuspid regurgitation includes diuretics and neurohormonal blockers, as well as transcatheter or surgical intervention. A multidisciplinary heart team, including HF specialists, should be involved in the evaluation and treatment planning.

• Tricuspid valve intervention (cardiopulmonary bypass mitral and tricuspid valve replacement, cardiopulmonary bypass mitral valve replacement and tricuspid valve repair, cardiopulmonary bypass tricuspid valve replacement and mitral valve repair, mitral and tricuspid valve annuloplasty, cardiopulmonary bypass aortic, mitral, and tricuspid valve replacement, cardiopulmonary bypass mitral and tricuspid valve replacement with aortic valve repair, cardiopulmonary bypass mitral valve replacement, tricuspid valve repair, and aortic valve repair, cardiopulmonary bypass tricuspid valve replacement, aortic valve repair, and mitral valve repair, cardiopulmonary bypass aortic valve replacement with mitral and tricuspid valve repair, cardiopulmonary bypass aortic and mitral valve replacement with tricuspid valve repair) is recommended for patients with severe tricuspid regurgitation undergoing concurrent left-sided heart surgery [477-481].

ESC IB (LoE A, GoR 3)

• Tricuspid valve intervention (cardiopulmonary bypass mitral and tricuspid valve replacement, cardiopulmonary bypass mitral valve replacement and tricuspid valve repair, cardiopulmonary bypass tricuspid valve replacement and mitral valve repair, mitral and tricuspid valve annuloplasty, cardiopulmonary bypass aortic, mitral, and tricuspid valve replacement, cardiopulmonary bypass mitral and tricuspid valve replacement with aortic valve repair, cardiopulmonary bypass mitral valve replacement, tricuspid valve repair, and aortic valve repair, cardiopulmonary bypass tricuspid valve replacement, aortic valve repair, and mitral valve repair, cardiopulmonary bypass aortic valve replacement with mitral and tricuspid valve repair, cardiopulmonary bypass aortic and mitral valve replacement with tricuspid valve repair) is recommended to be considered in patients with moderate tricuspid regurgitation and tricuspid annular dilatation undergoing concurrent left-sided heart surgery, and in symptomatic patients with isolated severe tricuspid regurgitation [477, 479-483].

ESC IIaB (LoE A, GoR 3)

Comment. Surgery for isolated TR is associated with high in-hospital mortality (8.8%), although these data may have been influenced by advanced-stage HF. Transcatheter techniques are potential treatment options for tricuspid regurgitation. Preliminary results show a reduction in tricuspid regurgitation symptoms and HF severity with a low complication rate. Further prospective studies are needed to demonstrate the prognostic impact of these treatments in patients with HF.

3.3. Other treatment

3.3.1. Cardiac resynchronization therapy

• CRT is recommended for patients with symptomatic HF, sinus rhythm, QRS duration ≥150 ms, LBBB QRS morphology, and LVEF ≤35% despite OMT to improve symptoms, reduce morbidity and mortality [349, 484-494].

ESC IA (LoE A, GoR 1)

• CRT is recommended for patients with symptomatic HF, sinus rhythm, QRS duration ≥150 ms, non-LBBB QRS morphology, and LVEF ≤35% despite OMT to alleviate symptoms, reduce morbidity and mortality [349, 484-494].

ESC IIaB (LoE B, GoR 1)

• CRT is recommended for symptomatic patients with HF, sinus rhythm, QRS duration 130-149 ms, LBBB QRS morphology, and LVEF ≤35% despite OMT to improve symptoms and reduce morbidity and mortality [489, 495].

ESC IIaB (Level of Evidence A, Grade of Recommendation 1)

• CRT may be recommended for patients with HF symptoms, sinus rhythm, QRS duration 130-149 ms, non-LBBB QRS morphology, and LVEF ≤35% despite OMT to alleviate symptoms and reduce morbidity and mortality [489, 495].

ESC IIbB (LoE B, GoR 1)

• In all HFrEF patients with an indication for ventricular pacing due to high-grade atrioventricular block, including those with AF and regardless of HF NYHA class, CRT is recommended instead of right ventricular pacing to prevent HF progression [346, 496, 497].

ESC IA (LoE A, GoR 1)

• In patients with AF, QRS duration ≥130 ms, LBBB, LVEF ≤35%, and NYHA class III-IV HF despite OMT, CRT is recommended only when full biventricular capture can be achieved or restoration of sinus rhythm is anticipated to improve the clinical course of HF [344, 350, 498, 499].

ESC IIaC (Level of Evidence A, Grade of Recommendation 2)

• In HFrEF patients with implanted pacemakers^*** or ICDs^*** who experience worsening of existing heart failure due to a high percentage of right ventricular pacing despite OMT, CRT may be recommended to improve the course of chronic heart failure [344, 346, 349, 496, 500-503].

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

• CRT is not recommended in patients with heart failure and a QRS duration <130 ms in the absence of indications for ventricular pacing due to high-grade atrioventricular block, as it does not improve life expectancy [489, 504-506].

ESC IIIA (LoE A, GoR 1)

• Early implantation of a CRT device with or without a defibrillator function (CRT-P/CRT-D) may be recommended in selected patients with acute anterior STEMI complicated by acute heart failure and atrioventricular block to reduce symptom severity [507].

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

Use of alternative physiological pacing methods – His bundle pacing

• For patients with indications for CRT and an unsuccessful attempt at coronary sinus lead implantation, left ventricular epicardial lead implantation or His bundle pacing (dual-chamber pacemaker implantation) is recommended [508-511].

ESC IIaB (CoE B, LOE 2)

• His bundle pacing combined with backup ventricular lead implantation (dual-chamber pacemaker implantation) may be recommended as an alternative to CRT in patients with supraventricular arrhythmias and rapid ventricular response as part of a "pace-and-ablate" strategy, even in cases with a "narrow" QRS complex [508, 512-514].

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

• His bundle pacing (dual-chamber pacemaker implantation) may be recommended as an alternative to right ventricular pacing in patients with atrioventricular block, an LVEF >40% (HFmrEF), and an anticipated high percentage of right ventricular pacing [515, 516].

ESC IIbC (Level of Evidence A, Grade of Recommendation 3)

3.3.2. Indications for implantable cardioverter-defibrillator implantation***

• In patients with heart failure who have had an episode of ventricular tachycardia or ventricular fibrillation occurring more than 48 hours after acute myocardial infarction, not related to reversible causes, and resulting in hemodynamic instability, an ICD*** ^{is recommended} when life expectancy is greater than 1 year with good functional status, to reduce the risk of sudden cardiac death and all-cause mortality [270-273].

ESC IA (LoE B, QoE 3)

Comments. The decision to implant a device should be made based on the patient's quality of life, LVEF (it is not established whether survival improves when LVEF is ˃35%), and the absence of other comorbidities that could lead to death within the next year.

• An early LVEF assessment prior to hospital discharge is recommended for all patients with acute myocardial infarction to stratify the risk of sudden cardiac death [517, 518].

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

• In patients hospitalized for acute myocardial infarction with an LVEF ≤40% detected before hospital discharge, a repeat LVEF assessment is recommended after 6–12 weeks to identify indications for primary prevention of sudden cardiac death [518-520].

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

• An ICD^*** is recommended for patients with ischemic left ventricular systolic dysfunction, an LVEF <35%, symptomatic NYHA class II–III heart failure, and receiving OMT, with an expected survival of more than 1 year in good functional status, to reduce the risk of sudden cardiac death and all-cause mortality [521-523].

ESC IA (LoE A, GoR 1)

• ICD implantation^*** is recommended for patients with ischemic left ventricular systolic dysfunction, an LVEF <30%, and symptomatic NYHA class I heart failure on OMT, to reduce the risk of sudden cardiac death and all-cause mortality [521].

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

• ICD implantation*** is recommended for patients with nonsustained ventricular tachycardia, ischemic left ventricular systolic dysfunction, an LVEF ≤40%, and on OMT, when sustained monomorphic ventricular tachycardia is induced during diagnostic endocardial electrophysiological testing, to reduce the risk of sudden cardiac death [524].

ESC IIaB (Level of Evidence B, Grade of Recommendation 2

• ICD implantation*** is recommended for patients with ischemic heart failure, an LVEF ≥40%, and hemodynamically well-tolerated sustained monomorphic ventricular tachycardia when catheter ablation has failed or is undesirable, for the prevention of sudden cardiac death [525].

ESC IIaC (LoE B, GoR 3)

• An ICD^*** is recommended for patients with non-ischemic left ventricular systolic dysfunction, an LVEF <35%, symptomatic NYHA class II–III heart failure, a survival prognosis of more than 1 year in good functional status, and receiving OMT, to reduce the risk of sudden cardiac death and all-cause mortality [356, 526].

ESC IIaA (LoE B, GoR 2)

• ICD implantation^*** may be recommended for patients with NYHA class IV heart failure refractory to medical therapy only if the patient is a candidate for CRT, left ventricular assist device implantation, or heart transplantation [527-529].

ESC IIbC (Level of Evidence A, Grade of Recommendation 1)

• Prior to ICD^*** replacement due to battery depletion, a reassessment of the patient's functional status and indications for sudden cardiac death prevention is recommended to determine treatment goals, patient needs, and clinical status [530-534].

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

• Patients with non-ischemic left ventricular systolic dysfunction are recommended to undergo cardiac MRI with late gadolinium enhancement to assess the risk of ventricular arrhythmias, their etiology, and the risk of sudden cardiac death [291-293].

ESC IIaB (Level of Evidence A, Grade of Recommendation 1)

• Genetic testing for mutations in the *LMNA*, *PLN*, *RBM20*, and *FLNC* genes is recommended for patients under 50 years of age with heart failure, non-ischemic cardiomyopathy, and atrioventricular conduction disturbance to determine indications for sudden cardiac death prevention [535-539].

ESC IB (LoE B, LoR 3)

• Genetic testing for mutations in the *LMNA*, *PLN*, *RBM20*, and *FLNC* genes is recommended for risk stratification in patients with early-onset sporadic non-ischemic cardiomyopathy or suspected hereditary disease to determine indications for sudden cardiac death prevention [535-539].

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

• ICD implantation*** is recommended for patients with heart failure, non-ischemic cardiomyopathy, and a pathogenic *LMNA* mutation if the predicted 5-year risk of life-threatening ventricular arrhythmias is >10%, in the presence of nonsustained ventricular tachycardia, reduced LVEF <50%, or atrioventricular conduction disturbance [540-542].

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

Comment: The 5-year risk score for life-threatening arrhythmias includes the patient's sex, LVEF, atrioventricular conduction abnormalities, presence of nonsustained ventricular tachycardia (>3 ventricular complexes with heart rate >120 bpm on 24-hour Holter monitoring), and non-missense mutations (insertions, deletions, truncating mutations, or splice-site mutations). LMNA-risk VTA calculator (lmna-risk-vta.fr) [540].

• Subcutaneous implantable cardioverter-defibrillators are recommended as an alternative to conventional transvenous ICDs^*** in selected heart failure patients without pacing needs, no requirement for antitachycardia pacing for ventricular arrhythmias, and no indications for CRT, for the prevention of sudden cardiac death [543].

ESC IIaB (LoE B, GoR 2)

Comments. Such devices may be the preferred option for patients with difficult transvenous access or when ICD removal is required due to infection. These devices should not be implanted in patients requiring pacing or CRT. Furthermore, these devices lack the capability to terminate arrhythmias using antitachycardia pacing.

3.3.3. Other implantable devices for heart failure treatment

3.3.3.1. Cardiac contractility modulation therapy

• Cardiac contractility modulation (dual-chamber pacemaker implantation) is recommended for patients with left ventricular systolic dysfunction, an LVEF of 25–45%, NYHA class II–III heart failure, and a narrow QRS complex (<130 ms) to improve exercise tolerance, enhance quality of life, and alleviate heart failure symptoms [544-549].

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

3.3.3.2. Implantation of circulatory support systems and left ventricular assist devices as an alternative to heart transplantation

• The use of left ventricular assist device (LVAD) implantation as an alternative to heart transplantation may be recommended in patients with severe heart failure (NYHA functional class III-IV) as a bridge to heart transplantation, as an alternative to heart transplantation in patients with contraindications (age, comorbidities), or in patients with potentially reversible myocardial diseases (e.g., peripartum cardiomyopathy) with a high probability of reverse cardiac remodeling and restoration of myocardial contractility [550-559].

ESC IIbB (LoE A, GoR 2)

Comments. Multicenter randomized controlled trials confirm the clinical benefits of using implantable LVADs as an alternative to heart transplantation and in the management of severe heart failure, demonstrating significantly superior survival rates and a substantial reduction in adverse events compared to patients receiving optimal medical therapy (OMT).

4. Medical Rehabilitation and Sanatorium-Resort Treatment

ESC IA (LoE A, GoR 1)

Comments. Cardiac rehabilitation consists of three phases during which patient routing is implemented. Cardiac rehabilitation starts as early as possible, is carried out on a scheduled basis after diagnosis establishment (at the first contact with the patient) or in the chronic course of the disease regardless of disease duration, provided the patient's clinical state is stable, there are medical indications for specific rehabilitation methods, and is based on a patient-centered approach. The presence of contraindications to physical exercise does not restrict patients' participation in cardiac rehabilitation programs and does not preclude the use of other physical rehabilitation methods.

Medical rehabilitation (cardiac rehabilitation) programs for patients with heart failure should last from 8 to 36 weeks with a training frequency of 2 to 7 times per week (depending on the rehabilitation phase), with the majority of the programs being implemented in the outpatient rehabilitation setting [568].

ESC IA (LoE A, GoR 1)

• The outpatient phase of cardiac rehabilitation for patients with clinically stable heart failure is recommended to be conducted in-person, remotely (at home using digital and mobile health tools), or in a blended format to reduce the risk of hospitalization, improve functional status, enhance quality of life, and improve prognosis [569, 571-577].

ESC IA (LoE A, GoR 1)

Comments. Cardiac rehabilitation under outpatient and home monitoring conditions using telemedicine and digital health technologies is considered a way to increase patient coverage with rehabilitation, improve adherence to lifestyle modifications, rehabilitation, and pharmacotherapy [578, 579]. The efficacy of home-based cardiac rehabilitation is comparable to that in a healthcare facility setting [575, 577, 580].

ESC IA (LoE A GoR 2)

Comments. Medical rehabilitation (cardiac rehabilitation) programs for patients with heart failure should be carried out by an MDRT consisting of a physical and rehabilitation medicine physician, cardiologist / general practitioner / primary care physician (depending on local capabilities), physical rehabilitation specialist, nutritionist, medical psychologist (psychotherapist), physical rehabilitation nurse, and a social worker (if available) [568, 581].

Considering that patients with heart failure have an extremely high risk of cardiovascular complications and death, as well as the need to adjust pharmacotherapy during the stages of medical rehabilitation, the physical and rehabilitation medicine physician must either hold a specialty certificate in Cardiology, or undergo advanced training in Cardiology, or the MDRT implementing the medical rehabilitation (cardiac rehabilitation) program for this category of patients must include a cardiologist, or if unavailable, a general practitioner or primary care physician with experience in managing heart failure patients [586].

The MDRT determines the patient's individual rehabilitation program, provides ongoing medical monitoring, and delivers the package of rehabilitation interventions.

Comments. To assess the patient's clinical status, exercise capacity, level of functioning and disability, and the impact of personal and environmental factors, it is recommended to use standardized and valid diagnostic methods and assessment tools based on the International Classification of Functioning, Disability and Health (ICF) [588-590] (www.icf-research-branch.org/download/category/12-cardiovascularandrespiratoryconditions). In patients with heart failure, according to indications, it is recommended to determine nutritional status using standardized questionnaires, cognitive function status (e.g., using the Montreal Cognitive Assessment [MoCA]); in patients aged ≥60 years, to screen for frailty and assess fall risk (using the Short Physical Performance Battery, the Timed Up and Go test, and the Morse Fall Scale) in order to individualize the rehabilitation program [569, 571, 590, 591]. A comprehensive cardiac rehabilitation program is presented in Appendix A3-9.

ESC IA (LoE C, GoR 5)

• As part of cardiac rehabilitation programs, it is recommended to assess psychosocial cardiovascular risk factors, including anxiety and depressive states using standardized questionnaires. If clinically significant disorders are identified, consultation with a clinical psychologist / psychotherapist / psychiatrist is recommended, along with psychopharmacotherapy if necessary [595, 596].

ESC IIaC (LoE C, GoR 5)

Comments. To identify symptoms of anxiety/depression, it is recommended to use the Hospital Anxiety and Depression Scale (HADS).

ESC IIaB (LoE B GoR 3)

Comments. In patients with HF, CPET is primarily recommended to determine risk and prognosis [198, 199, 571]. CPET is also the gold standard for prescribing cardiac rehabilitation and determining its effectiveness [198, 599].

Contraindications to exercise testing and physical training: acute coronary syndrome (ACS), severe angina pectoris, life-threatening cardiac arrhythmias, uncontrolled hypertension, symptomatic hypotension, active endocarditis, myocarditis and pericarditis, acute HF (with hemodynamic instability), symptomatic aortic valve stenosis, severe obstructive hypertrophic cardiomyopathy, advanced atrioventricular block, intracardiac thrombus, acute systemic diseases [198].

ESC IA (LoE A, GoR 1)

Comments. Contraindications to physical training: progression of HF with decreased exercise tolerance or dyspnea at rest in the preceding 3–5 days, angina attacks and pronounced ischemia at very low physical exertion (<2 metabolic equivalents, <50 Watts), uncontrolled diabetes mellitus, recent thromboembolism and/or thrombophlebitis, new-onset atrial fibrillation/atrial flutter (AFL). The risk of complications during physical training increases with a weight gain of >1.8 kg in the preceding 1–3 days, dobutamine** inotropic support, a decrease in systolic blood pressure (SBP) after exercise, complex ventricular arrhythmias at rest or occurring during physical exertion, NYHA class IV HF, heart rate ≥100 bpm at rest, and comorbid conditions limiting exercise tolerance [198].

Physical training can be performed in an individual format and/or in organized groups in a medical institution, and/or at home after training and mastering the program. A home-based physical training program is effective and safe in patients with stable HFrEF [560, 572-575, 577, 605-607].

The physical rehabilitation program includes: a set of therapeutic gymnastics with breathing exercises, inspiratory muscle training, regular moderate-intensity dynamic physical exertion, interval training, and low/moderate-intensity strength training (Appendix 1). During controlled physical training in patients with HF, it is recommended to monitor the patient's condition (complaints, clinical symptoms), provide continuous or intermittent control of heart rate, blood pressure, and ECG (in patients at high risk for complications), and assess exercise tolerance using the Borg rating of perceived exertion scale and Borg dyspnea index; the "Talk Test" can be used [198, 569, 608].

Comments. When prescribing a training regimen, it is recommended to use the FITT model, covering frequency, intensity, time, and type of exercise. Training frequency: 2–7 times a week. The main regimen is continuous moderate-intensity aerobic training, but at the start of rehabilitation, especially in high-risk patients, low-intensity interval training may be used. Exercise intensity: moderate (at the start of rehabilitation, 40% of peak oxygen uptake (VO2 peak) with subsequent gradual increase to 50–60% VO2 peak. Subsequently, provided there is good tolerance, an increase in intensity to 65–90% of VO2 peak can be considered. Exercise duration: should gradually increase from 15 to 30, then 45–60 minutes. To increase muscle strength and exercise tolerance, 2–3 strength training sessions per week can be added to aerobic training with an initial intensity of <30% of one-repetition maximum and a gradual increase in load up to 40–60% of one-repetition maximum. In addition to aerobic and strength exercises, flexibility, coordination, balance exercises, and breathing exercises can be additionally used if necessary (especially in the presence of comorbid respiratory pathology) [568].

• Patients with clinically stable HFrEF, low risk of complications, and good exercise tolerance, given their capabilities and desire, can be recommended high-intensity interval training [569, 605, 609-611].

ESC IA (LoE A, GoR 1)

Comments. When prescribing this type of training, it is recommended to assess all potential risk factors and the safety of this physical intervention [612].

• Patients with clinically stable HFrEF, if able and willing, may be recommended to include low/moderate-intensity strength training in their physical rehabilitation program to preserve/prevent muscle mass loss, increase and/or maintain muscle strength, and increase physical performance [569, 605, 613-616].

ESC IIbA (LoE B, GoR 1)

Comments. Strength training is prescribed in addition to well-tolerated aerobic physical training.

ESC IIaB (LoE B, GoR 1)

Comments. Breathing exercises, including those using training devices, increase respiratory muscle strength (especially inspiratory muscles), physical performance, alleviate HF symptoms, and improve quality of life, especially in patients with baseline inspiratory muscle weakness [569, 605, 618-621].

• Breathing exercises with and without breathing trainers are recommended for patients with NYHA class IV HF to initiate physical rehabilitation [569, 616-619].

ESC IIaB (LoE B, GoR 1)

Comments. In patients with severe HF who are unable to fully participate in traditional physical rehabilitation programs in the presence of inspiratory and peripheral muscle weakness, neuromuscular electrical stimulation of the diaphragm and/or lower limb muscles can be considered as an alternative method to increase muscle strength, physical performance, and improve quality of life, provided there are no contraindications, taking into account the patient's physical and cognitive functions and the alignment of this method with the specific patient's rehabilitation goals (as indicated) [622, 623].

5. Prevention and Dispensary Observation

• Follow-up in primary care is recommended for stable patients receiving optimal treatment for long-term monitoring, evaluation of treatment efficacy, disease progression, and treatment adherence [624, 625].

ESC IC (Level of Evidence A, Grade of Recommendation 1)

Comments. It is believed that in most cases of HF, follow-up monitored by general practitioners is quite sufficient, provided the latter have appropriate knowledge and experience in managing such patients. However, if a patient, despite taking standard therapy for HF, continues to have certain symptoms, a cardiologist should be involved in their management. Currently, the most effective management scheme for a patient with HF appears to be based on close interaction between the general practitioner and the cardiologist. It is of great importance to familiarize patients and their families with the main aspects of the disease course, treatment methods, main indications for therapy, dosing principles and expected effects of drugs, as well as potential side effects. Equally important is training patients in skills to monitor disease symptoms and timely recognize impending decompensation. The need for daily weighing should be explained, which allows patients to independently adjust the dose of diuretics.

ESC IA (LoE A, GoR 1)

Comments. Outpatient management of patients with CHF should involve a multidisciplinary approach with the participation of cardiologists, general practitioners, specialists in related fields, and nurses. It is necessary to schedule regular patient visits to the physician to monitor clinical and laboratory parameters, optimize drug therapy, detect signs of disease progression early, and foster patient adherence to treatment. The frequency of visits depends on the severity of the disease; additionally, elderly patients may benefit from more frequent specialist visits.

In patients without clinical manifestations of CHF but with a high risk of developing it, several preventive strategies have proven effective. The management of cardiovascular diseases and conditions associated with a high risk of CHF is carried out in accordance with current clinical guidelines (see Section 1.4. Comments on the CHF classification).

• Patients with arterial hypertension are recommended antihypertensive treatment to prevent or delay the onset of HF and to prevent hospitalizations due to CHF [627–630].

ESC IA (LoE A, GoR 1)

Comment. The SPRINT study demonstrated a 38% reduction in the risk of developing CHF in the intensive blood pressure control group compared to the standard approach [631].

• Patients with a high risk of cardiovascular disease or with established cardiovascular disease are recommended statin therapy to prevent or delay the onset of HF and to prevent hospitalizations due to CHF [627, 628, 632].

ESC IA (CURL B, LOR 2)

• Patients with diabetes mellitus and a high risk of cardiovascular disease or established cardiovascular disease are recommended SGLT2 inhibitors (canagliflozin, dapagliflozin**, empagliflozin**) to prevent hospitalizations due to CHF [627, 628, 633–635].

ESC IA (LoE A, GoR 2)

ESC IC (LoE B, GoR 2)

Management strategies for patients at high risk of CHF should be maintained at the pre-HF stage.

Dispanserization (active clinical monitoring) of patients with CHF is regulated by Order of the Russian Ministry of Health No. 168n dated March 15, 2022, "On Approval of the Procedure for Conducting Dispanserization of Adults." In accordance with this order, dispanserization is established within 3 working days after: 1) diagnosis establishment during outpatient medical care; 2) receipt of the discharge summary from the inpatient medical record following the provision of inpatient medical care.

Appendix No. 1 to the Procedure for Dispensary Observation of Adults, approved by Order of the Russian Ministry of Health No. 168n dated March 15, 2022, states that dispensary observation by a general practitioner is carried out for CHF stage 1–2a, NYHA class I–II NYHA and LVEF ≥40%, excluding combinations with DM and/or CKD stage 4 and above. The minimum frequency of dispensary visits (examinations, consultations) is at least 2 times a year.

Comments: Due to the update of the CHF classification, prior to making amendments to Order N 168n, the patient profile for dispanserization by a general practitioner or cardiologist is determined based on the NYHA functional class and LVEF.

• For patients with HFmrEF and HFpEF undergoing dispanserization, it is recommended to monitor the following health indicators: weight (body mass index), waist circumference, smoking status; blood pressure, heart rate; general clinical and biochemical blood tests (with estimated GFR at least once a year); red blood cell count, hemoglobin level (complete blood count) at least once a year; for patients receiving warfarin therapy, international normalized ratio (at least twice a year); NT-proBNP level (at least once every 2 years); absence of signs of disease progression based on ECG (at least once a year); absence of signs of pulmonary congestion according to chest X-ray (at least once a year); absence of signs of disease progression based on echocardiography – LVEF (at least twice a year); absence of life-threatening cardiac arrhythmias according to ECG monitoring (at least once a year) [640].

No ESC guideline (LoE C, GoR 5)

Appendix No. 2 to the Procedure for Conducting Dispanserization of Adults, approved by Order of the Ministry of Health of the Russian Federation No. 168n dated March 15, 2022, states that dispanserization by a cardiologist is carried out for the following diseases, conditions, and functional disorders: CHF stage 2B–3 and/or with LVEF <40% and/or NYHA functional class III–IV, CHF stage 1–2a, NYHA functional class I–II, and LVEF ≥40% combined with diabetes mellitus and/or CKD stage 4 and 5. The minimum frequency of dispanserization visits (examinations, consultations) is at least twice a year.

Comments: Due to the update of the CHF classification, prior to making amendments to Order N 168n, the patient profile for dispanserization by a general practitioner or cardiologist is determined based on the NYHA functional class and EF.

• For patients with HFrEF undergoing dispanserization, it is recommended to monitor the following health indicators: weight (body mass index), waist circumference, smoking status; blood pressure, heart rate; general clinical and biochemical blood tests (with estimated GFR) at least twice a year; complete blood count (at least twice a year); for patients receiving warfarin therapy, international normalized ratio (at least twice a year); NT-proBNP (at least once every 2 years); ECG (at least once a year); chest X-ray (at least once a year); echocardiography (at least twice a year); ECG monitoring (at least once a year) [640].

No ESC guideline (LoE C, GoR 5)

6. Organization of Medical Care

Indications for hospitalization in a medical organization (emergency, inpatient):

• To reduce the risk of all-cause and cardiovascular mortality and prevent the risk of sudden cardiac death, hospitalization is recommended for patients with decompensated HF, hemodynamic instability, and life-threatening arrhythmias [641–648].

ESC IC (LoE B, GoR 3)

Comments. Life-threatening conditions in HF decompensation include pulmonary edema (whether resolved or unresolved at the pre-hospital stage), cardiogenic shock, marked decrease in exercise tolerance, hypotension (SBP <90 mm Hg) and high risk of acute left ventricular failure, hypertension (SBP >180 mm Hg) or paroxysmal arrhythmias with signs of decompensation in at least one circulatory loop, respiratory rate >25 breaths/min, heart rate <40 or >130 bpm, life-threatening arrhythmias, or the need to double IV loop diuretics without an adequate diuretic response, as well as the need for intubation, symptoms of hypoperfusion, oxygen saturation (SpO2) <90% (despite oxygen therapy), and use of accessory respiratory muscles.

• Presence of any of the following signs: respiratory rate >25 breaths/min; use of accessory respiratory muscles; pulmonary edema; heart rate <50 bpm, heart rate >130 bpm; second- or third-degree atrioventricular block; SBP <90 mm Hg; blood oxygen saturation <90% despite oxygen administration; signs of hypoperfusion (oliguria, cold extremities, altered mental status) [649].

ESC IC (LoE C, GoR 5)

• Criteria for transferring a patient from the intensive care unit to the cardiology department: resolution of pulmonary edema; absence of signs of hypoxemia; presence of adequate diuresis; absence of inotropic support for the preceding 6 hours [649].

ESC IC (LoE C, GoR 5)

Indications for discharging a patient from a medical organization (inpatient facility):

• Patients with CHF whose symptoms of HF decompensation have resolved and whose hemodynamic parameters have stabilized, as confirmed by clinical, instrumental, and laboratory data, are recommended discharge from the inpatient facility for continued monitoring and treatment in the outpatient setting [626, 650–653].

ESC IC (LoE A, GoR 1)

• Stable hemodynamics; absence of electrolyte disturbances; absence of CHF decompensation manifestations such as edema, orthopnea, jugular venous distension; decreased NT-proBNP levels; absence of significant ascites; absence of signs of fluid accumulation in body cavities; stable renal function over the preceding 24 hours on oral diuretic therapy [649].

ESC IC (LoE C, GoR 5)

System of medical care for patients with CHF.

ESC IC (LoE A, GoR 3)

Comments. This form of medical care makes it possible to reduce the main costs of managing patients with CHF, with a significant decrease in the number of hospitalizations and the cost of outpatient medical support. Currently, priority is given to the tactic of more thorough preparation for discharge after CHF decompensation, followed by monitoring by a cardiologist specializing in CHF at a specialized outpatient CHF center, along with home monitoring via active visits (nursing care) and telephone or telemedical monitoring [625, 651, 661-666].

ESC IA (LoE A, LoR 1)

Comments. An effective model for treating patients with CHF is the establishment of a CHF center. A large number of meta-analyses, which included from 9 to 53 RCTs (12,356 patients), have shown that only patient management through "seamless" follow-up by a multidisciplinary team in both inpatient and outpatient settings by cardiologists in cooperation with visiting nurses can reduce both the risks of all-cause mortality and rehospitalization by 20%. Strategies utilizing only telephone contact with recommendations to visit the attending physician in case of worsening condition reduced the number of HF-related hospitalizations, but did not affect mortality or all-cause hospitalizations. The system of inpatient medical follow-up combined with outpatient monitoring by cardiologists helps maintain higher treatment adherence, which is confirmed by a reduced risk of readmissions and lower risks of all-cause and cardiovascular mortality [658].

Indications for consultation of a patient in a tertiary medical organization to address the issues of heart transplantation and implantation of mechanical circulatory support devices:

• Severe and persistent symptoms of HFrEF/HFpEF (NYHA class III or IV); LVEF ≤30%, refractory to therapy; isolated RV failure or inoperable valvular disorders; or congenital pathology; or persistently high (or rising) BNP or NT-proBNP levels and severe diastolic dysfunction or structural LV pathology according to the definition of HFmEF or HFpEF.

• Episodes of pulmonary or systemic congestion requiring high doses of intravenous diuretics (or diuretic combinations), or episodes of low cardiac output requiring inotropic or vasoactive agents, or malignant arrhythmias leading to an unplanned visit or hospitalization within the past 12 months.

• Marked limitation of physical activity with the inability to walk >300 m during the 6-minute walk test or peak oxygen consumption (pVO2) <12-14 ml/kg/min of cardiac origin [649].

ESC none (LoE C, GoE 5)

7. Additional Information

7.1. Factors influencing the outcome of a disease or condition

High mortality from CHF is primarily due to cardiovascular causes, including the progression of CHF. Readmissions for acute decompensated heart failure (ADHF) are the strongest predictor of death [672, 673].

According to the OPTIMIZE-HF registry, 29.9% of patients with reduced LVEF and 29.2% with an LVEF ≥40% are readmitted within 90 days of discharge [674].

The main non-cardiac causes of CHF decompensation are infections, non-adherence to drug therapy, failure to follow fluid and salt restrictions, alcohol abuse, intake of NSAIDs, corticosteroids, and drugs with negative inotropic or cardiotoxic effects.

Infections. Up to 38% of CHF decompensations requiring hospitalization are caused by various infectious diseases, including respiratory infections in 15.3–20% of cases [675, 676].

The hospitalization rate for patients with CHF increases significantly during seasonal influenza [677].

Furthermore, the presence of a respiratory infection, including pneumonia, is a predictor of poor outcomes in patients with decompensated CHF [676, 677].

Given the link between these conditions, there is reason to believe that targeting respiratory infections can influence the course of CHF. This primarily applies to influenza and pneumococcal infection, for which inexpensive and accessible vaccines are available. To date, there are no completed RCTs investigating the efficacy of such immunization in patients with CHF. Nevertheless, the results of most observational studies indicate a positive effect of influenza and pneumococcal vaccination [678–681].

In the largest Danish national cohort study, which included 134,048 patients with CHF, annual influenza vaccination was associated with a 19% reduction in the risk of both cardiovascular and all-cause mortality. The effect was most pronounced when vaccination was administered at the beginning of the influenza season (September–October) [681].

Data on the effect of pneumococcal vaccination on the course of HF are even scarcer. No RCTs have been conducted either. A meta-analysis published in 2020, which included 7 observational studies, reported that pneumococcal vaccination was associated with a 22% reduction in the risk of death in patients with cardiovascular diseases, including HF, or at very high risk of developing them. In conclusion, the authors emphasized that due to the study design, as well as a serious risk of bias in three of the included studies, the level of certainty of the results is reduced [682].

• Influenza and pneumococcal vaccination are recommended for all HFrEF/HFpEF patients (in the absence of contraindications) to reduce the risk of death [678-682].

ESC not stated (CGR B, LOR 3)

NSAID intake. NSAIDs, by blocking the compensatory increased synthesis of prostaglandins in patients with HF, increase vascular resistance and decrease renal blood flow, glomerular filtration, and natriuresis [683, 684].

These mechanisms cause sodium and fluid retention, which increases the risk of HF decompensation [259, 685].

A meta-analysis of observational studies published in 2016 confirmed the negative impact of NSAIDs on the course of CHF. The maximum increase in the risk of CHF decompensation was observed with the use of non-selective NSAIDs; with COX-2 inhibitors, this increase was smaller and did not reach statistical significance. At the same time, the authors emphasized that such a difference could be due to a statistical error owing to the small number of studies involving COX-2 inhibitors [686].

Water and salt regimen. Conducted studies have not confirmed the necessity of strict restriction of water and salt intake [687-691].

At the same time, the design and statistical power of the studies do not allow for formulating clear recommendations with an indication of class and level of evidence. Nevertheless, patients with CHF should monitor their fluid intake volume (1.5–2 liters per day) and salt intake (no more than 6 g of salt per day).

Alcohol. Alcohol is strictly prohibited only for patients with alcoholic cardiomyopathy. For all other patients with CHF, alcohol restriction is presented as a general recommendation—no more than 20 ml of pure alcohol per day for men and 10 ml for women [692].

7.2. Advanced (end-stage, severe) heart failure

Advanced (end-stage, severe) HF is a stage in the course of HF where clinical symptoms persist or progress despite maximal therapy. At this stage, the frequency of patient hospitalizations and cardiovascular mortality sharply increase. In the vast majority of patients, advanced HF develops against the background of reduced LVEF, although this is not mandatory.

Criteria for advanced HF are presented in Table 12 [693].

Table 12. Criteria for advanced heart failure (components from all items must be present) [693]

• In patients with advanced HF and persistent congestion, in the absence of contraindications, doubling the dose of loop diuretics and/or adding thiazide diuretics to the treatment regimen may be recommended to reduce clinical symptoms [441, 694].

ESC IIbC (CARR B, LE 2)

• In patients with advanced HF and resistance to diuretic therapy, blood ultrafiltration may be recommended to reduce clinical symptoms [695, 696].

ESC IIbC (CARR A, LE 2)

• In patients with advanced HF, it is recommended to consider the possibility of outpatient follow-up in specialized HF clinics [697, 698].

ESC IIbC (CARR C, LE 2)

• In patients with severe HF who are ineligible for heart transplantation or left ventricular assist device implantation, inotropic agents may be recommended to reduce clinical symptoms [699, 700].

ESC IIbC (CARR B, LE 2)

• Patients with severe HF are recommended to consult a cardiovascular surgeon to address the feasibility of heart transplantation or ventricular assist device implantation [701].

ESC IIaA (GPP A, LoE 2)

• Patients with severe HF are recommended to consult a palliative care specialist [702].

ESC IIaB (LoE B, GoR 1)

7.3. Acute decompensated heart failure

AHF is a clinical syndrome characterized by the rapid onset or worsening of symptoms and signs typical of impaired cardiac function. AHF is a life-threatening condition requiring immediate medical intervention and, in most cases, emergency hospitalization. Acute decompensated heart failure (ADHF) refers to the rapid escalation of clinical manifestations (dyspnea, severity of arterial hypoxemia, onset of arterial hypotension) that prompts urgent medical care and emergency hospitalization in a patient already suffering from chronic heart failure.

7.3.1. Clinical Manifestations, Classification, and Pathogenesis of Acute Heart Failure / Acute Decompensated Heart Failure

The clinical manifestations of ADHF are diverse, but generally fall into two main patterns: signs of congestion and/or hypoperfusion.

Signs of pulmonary congestion occur due to elevated pulmonary capillary pressure and vary in clinical severity from weakness and fatigue to a full-blown picture of pulmonary edema. Typical signs also include orthopnea, paroxysmal nocturnal dyspnea, moist non-sonorous rales upon auscultation of both lungs, and characteristic chest X-ray findings. Signs of systemic congestion include neck vein distension, hepatomegaly, hepatojugular reflux, gastrointestinal congestion symptoms, bilateral peripheral edema, and ascites. Rapidly progressive systemic congestion may be accompanied by pain in the right upper quadrant due to liver capsule distension.

Signs of congestion (especially pulmonary congestion) do not always indicate fluid accumulation (fluid overload). They may result from rapid blood redistribution due to changes in vascular tone.

Signs of hypoperfusion are the result of low cardiac output and vary in clinical severity from weakness and fatigue to a full-blown picture of shock (cold and clammy extremities, oliguria, confusion, weak pulse volume). Hypoperfusion is often combined with arterial hypotension, but may also occur in patients with SBP >90 mm Hg.

In a patient with ADHF, signs of congestion and hypoperfusion may occur either separately or simultaneously, changing over the course of treatment.

CHF decompensation is usually preceded by a period of gradual worsening of clinical manifestations with progressive fluid retention in the body. However, with the sudden addition of a triggering factor (e.g., a rapid increase in BP, onset of tachyarrhythmia, myocardial ischemia), ADHF can develop in patients with compensated CHF who do not have significant fluid retention.

The presence of ADHF does not necessarily indicate a low LVEF. With similar clinical manifestations of ADHF, LVEF may be reduced (≤40%), mildly reduced (LVEF 41–49%), or even preserved (>50%). Regardless of the clinical presentation of AHF/ADHF, the predominance of left ventricular diastolic dysfunction cannot be ruled out. These circumstances should be taken into account when choosing treatment modalities, in particular when deciding on the use of positive inotropic drugs.

• In patients with AHF/ADHF, it is recommended to use the clinical hemodynamic profile assessment scale, expanded to account for the combination of congestion and hypoperfusion signs, including for guiding the initial treatment of AHF/ADHF [703].

ESC IIaB (GPP B, LoE 3) (GPP C, LoE 3) (Table 13).

Table 13. Clinical severity classification of acute decompensation of CHF

7.3.2. Diagnosis of acute decompensated heart failure

• In all patients with suspected ADHF, it is recommended to take a medical history and perform a physical examination to assess the severity of the condition [704].

ESC IC (GPP B, LoE 3)

• In patients with ADHF, it is recommended to assess the presence and severity of dyspnea, the ability to lie flat (presence of orthopnea), use of accessory muscles of respiration, respiratory rate, severity of hypoxemia (cyanosis), determine systolic and diastolic blood pressure, assess heart rate and rhythm, body temperature, presence and severity of peripheral hypoperfusion signs (cold skin, weak pulse volume, lethargy, adynamia), and presence and severity of excessive fluid accumulation and congestion (moist non-sonorous pulmonary rales, neck vein distension, bilateral peripheral edema, hepatomegaly, ascites, hydrothorax, hydropericardium) to verify the diagnosis and determine the severity of the condition [704].

ESC IC (GPP B, LoE 3)

• Targeted chest radiography is recommended for all patients with ADHF to detect pulmonary venous congestion, pleural effusion, verify pulmonary edema, and perform differential diagnosis [705].

ESC IC (LoE B, LoR 3

• Echocardiography is recommended for patients with ADHF within the first 24–48 hours of hospitalization to identify underlying heart diseases, the mechanism of ADHF development, and for differential diagnosis [706–710].

ESC IC (GPP B, LoE 3)

Comments. In patients with ADHF presenting with shock, suspected acute intracardiac hemodynamic disturbance, or aortic dissection, echocardiography is recommended immediately to identify underlying heart diseases, the mechanism of ADHF development, and for differential diagnosis.

• Transthoracic lung ultrasound is recommended in patients with ADHF in the early stages after hospitalization for the rapid detection of interstitial edema and hydrothorax [711, 712].

ESC IIaC (GPP B, LoE 2

• A 12-lead ECG is recommended for all patients with ADHF as soon as possible to detect rhythm and conduction disorders and rule out ACS [713, 714].

ESC IC (LoE B, LoR 3

Comments. Of utmost importance is the detection of acute myocardial ischemia indicating the need for urgent interventions to restore coronary blood flow in patients with ACS, as well as tachy- or bradyarrhythmias contributing to the onset of ADHF. Patients with ADHF and suspected ACS are indicated for coronary angiography to diagnose this condition.

• In patients with ADHF, determining blood oxygen saturation via arterial blood gas analysis (acid-base and blood gas analysis) is recommended only when oxygenation cannot be rapidly assessed using pulse oximetry or when an accurate assessment of arterial oxygen and carbon dioxide partial pressure is required (particularly in the presence of an arterial catheter in patients with cardiogenic shock) to determine the severity of the condition [715].

ESC IC (GPP C, LoE 5)

• In patients with pulmonary edema or chronic obstructive pulmonary disease complicated by ADHF, it is recommended to use venous blood to determine pH, carbon dioxide partial pressure, and lactate concentration (acid-base and blood gas analysis) [715].

ESC IIaC (GPP C, LoE 5)

• In patients with ADHF and signs of hypoperfusion, the use of venous blood to determine lactate concentration (acid-base and blood gas analysis) may be recommended [715].

ESC IIbC (GPP C, LoE 5)

• Invasive hemodynamic assessment via pulmonary artery catheterization for the diagnosis of ADHF is not recommended for all patients [715].

ESC IIIC (GPP C, LoE 5)

• Performing invasive hemodynamic assessment is recommended only in hemodynamically unstable patients when it is necessary to identify the mechanism of decompensation [715].

ESC IIbC (GPP C, LoE 5)

• Arterial or central venous catheterization for diagnostic purposes is not recommended in patients with ADHF [715].

ESC IIIC (GPP C, LoE 5)

• For all patients, determination of blood creatinine levels (with calculation of creatinine clearance or GFR) is recommended to detect damage to other organs and body systems and determine potential management tactics [716].

ESC IA (CURL B, LOR 2)

• For all patients, performing a complete blood count, determination of blood urea (or residual nitrogen), potassium, sodium, glucose, bilirubin, and liver enzymes (aspartate aminotransferase and alanine aminotransferase) is recommended to detect damage to other organs and body systems and determine potential management tactics [717–719].

ESC IC (LoE C, SoR 5)

Comments. It is extremely important to rule out, as early as possible, those causes of acute decompensated heart failure (ADHF) that require a specific treatment strategy. In this regard, when pulmonary embolism (PE) is suspected, it is advisable to determine the blood D-dimer concentration, and when a septic condition is suspected, to determine the blood procalcitonin concentration [720].

• In all patients with ADHF and suspected ACS upon hospital admission, for the purpose of diagnosing this condition and assessing prognosis, the determination of cardiac troponin T or I concentrations in the blood may be recommended [721-723].

ESC IIbB (RRR A, LOC 3)

Comments. In ADHF, this parameter is almost always elevated, which objectively complicates the diagnosis of acute myocardial infarction (MI) and by no means always indicates the presence of acute MI [721-723].

• In all patients with newly onset dyspnea as early as possible after hospitalization, it is recommended to determine blood levels of natriuretic peptides – BNP or NT-proBNP to confirm the diagnosis of ADHF [724-726].

ESC IA (LoE A, LoR 2)

Comments. This test is recommended to differentiate ADHF from non-cardiac causes of dyspnea, assess the severity of ADHF and its prognosis upon hospitalization, and evaluate the prognosis of ADHF by changes in the levels of these biomarkers before discharge. It should be noted that reduced levels of natriuretic peptides may be observed in a number of patients with end-stage decompensated HF, obesity, extremely rapid progression of clinical symptoms, and right ventricular failure. Conversely, extremely high levels of natriuretic peptides can be determined in atrial fibrillation and severe renal dysfunction [725].

• In patients with suspected ADHF, it is recommended to use the following blood natriuretic peptide levels to exclude the diagnosis of ADHF: BNP <100 pg/mL, NT-proBNP <300 pg/mL [724-727].

ESC IA (LoE A, GoR 1)

Comments. A blood BNP concentration >400 pg/mL; NT-proBNP >450 pg/mL in patients younger than 55 years, >900 pg/mL in patients aged 55-75 years, and >1800 pg/mL in patients older than 75 years points in favor of ADHF [725, 728].

• In patients with ADHF during hospitalization prior to hospital discharge, to reduce the severity of clinical symptoms and decrease the risk of readmissions, it is recommended to identify potential iron deficiency, defined as a serum ferritin concentration <100 ng/mL or a serum ferritin concentration of 100–299 ng/mL and transferrin saturation <20% [408]

ESC IIaB (RRR C, LOC 3)

7.3.3. Biomarkers for prognostic assessment or additional risk stratification in ADHF patients

• Risk stratification may be recommended for patients with ADHF early in the disease course, at various stages of inpatient treatment, and at discharge to determine the patient's management approach, make decisions regarding the feasibility of in-hospital transfer, and determine the timing of safe discharge to outpatient care [62, 703, 724, 729-731].

ESC IIbB (RRR A, LOC 3)

• Determination of BNP or NT-proBNP concentrations in patients with ADHF to determine prognosis is recommended upon admission, at discharge, and at the outpatient stage of medical care [62, 703, 724, 729-731].

ESC IA (LoE A, GoR 3)

Comments. A decrease in BNP/NT-proBNP levels by discharge is associated with lower mortality and readmission rates over the next 6 months. The prognostic value of BNP immediately upon hospital admission is small [62, 703, 724, 729-731].

7.4. Treatment of acute decompensated heart failure

7.4.1. Inpatient treatment goals for acute heart failure

7.4.1.1. Stages of acute decompensated heart failure management

The stages of ADHF treatment are presented in Table 14.

Table 14. Stages of treatment for acute decompensated heart failure

7.4.1.2. Approaches to initial management of acute decompensated heart failure

• In patients with ADHF after hospitalization, to improve clinical outcomes, it is recommended to initiate as soon as possible and simultaneously carry out clinical evaluation, examination, and treatment [715].

ESC IC (CQR C, LOR 5

• During the initial assessment of patients with ADHF, to improve clinical outcomes, in addition to prompt diagnosis and differential diagnosis, it is recommended to identify factors provoking and/or aggravating ADHF, as well as comorbidities and life-threatening conditions [715].

ESC IC (RRR C, LOC 5)

• In patients with ADHF, to improve clinical outcomes, therapeutic intervention targeting factors provoking and/or aggravating the course of ADHF, as well as life-threatening comorbidities and conditions, is recommended to be carried out as quickly as possible along with the elimination of clinical manifestations of ADHF [715].

ESC IC (RRR C, LOC 5)

• In patients with ADHF with blood oxygen saturation <90% according to pulse oximetry or arterial blood partial pressure of oxygen <60 mmHg, oxygen therapy is recommended to correct hypoxemia [733].

ESC IC (RRR C, LOC 5

Comments. If necessary, the oxygen concentration in the inspiratory mixture can be increased to up to 100%. During oxygen therapy, it is recommended to monitor blood oxygen saturation using pulse oximetry and avoid hyperoxia, especially in patients with COPD.

• In patients with ADHF and respiratory failure (respiratory rate >25 breaths/min, blood oxygen saturation <90% by pulse oximetry), as well as in pulmonary edema, to reduce the severity of respiratory distress and decrease the need for mechanical ventilation with endotracheal intubation, prompt initiation of non-invasive ventilation (NIV) performed against the background of spontaneous breathing is recommended [733-736].

ESC IIaB (RRR A, LOC 1)

Comments. NIV is understood as respiratory support without endotracheal intubation, tracheal catheterization, or tracheostomy, where the patient-ventilator interface is achieved using tightly fitted nasal and facial masks. Continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP) is recommended as NIV methods in ADHF. In patients with hypercapnia and acidosis (typically having COPD) who have indications for assisted ventilation, BiPAP is recommended for inspiratory support. The use of CPAP/BiPAP is not recommended in arterial hypotension.

If necessary, the oxygen concentration in the inspiratory mixture can be increased to up to 100%. During NIV, blood pressure and blood oxygen saturation should be monitored using pulse oximetry, striving to avoid hyperoxia, especially in patients with COPD.

• In patients with cardiac or respiratory arrest, coma, progressive consciousness disorders, progressive worsening of respiratory failure with increasing hypoxemia (arterial blood partial pressure of oxygen <60 mmHg or 8.0 kPa), hypercapnia (arterial blood partial pressure of carbon dioxide >50 mmHg or 6.65 kPa) and acidosis (pH <7.35) during NIV, the need for airway protection, persistent hemodynamic instability, agitation or NIV intolerance with worsening respiratory failure, as well as the impossibility of a tight mask seal, to improve clinical outcomes, endotracheal intubation with mechanical ventilation is recommended [737].

ESC IC (CQR C, LOR 5

• Routine placement of a urinary catheter in patients with ADHF to monitor urine output is not recommended [738].

ESC IIIC (GPP C, LoE 5)

• In patients with AHFS and signs of fluid accumulation (fluid overload) without marked arterial hypotension and signs of hypoperfusion, prompt intravenous administration of loop diuretics is recommended to improve the clinical status [739-743].

ESC IC (TR = B, LE = 2)

• In patients with AHFS, when fluid accumulation (fluid overload) is not suspected and the only mechanism of decompensation appears to be acutely arising blood redistribution (e.g., hypertensive crisis in patients without prior history of HF, impaired LV contractility, or valvular heart disease), intravenous furosemide** is not recommended [739].

• ESC IB (TR = C, LE = 3) In patients with AHFS and SBP >110 mm Hg without signs of hypoperfusion, intravenous administration of peripheral vasodilators may be recommended to relieve symptoms (primarily dyspnea) and reduce pulmonary congestion [744-747].

ESC IIbB (TR = A, LE = 1

Comments. When fluid retention is not suspected and there is no arterial hypotension (e.g., in the presence of hypertension at admission in previously compensated patients), the use of peripheral vasodilators is recommended, and extreme caution should be exercised in choosing the diuretic dose (or avoiding them altogether).

• In patients with AHFS and AF/AFL, beta-blockers are recommended to control tachysystole [748].

ESC IIaB (TR = B, LE = 3

Comments. The use of beta-blockers in AHFS requires caution, especially in patients with arterial hypotension, signs of marked fluid accumulation, or low LVEF. Ideally, the decision to use beta-blockers should be made after confirming the absence of marked LV systolic dysfunction.

• In patients with AHFS and AF/AFL for the control of tachysystole when beta-blockers are contraindicated, insufficiently effective, or cannot be used in the appropriate dose, intravenous digoxin** is recommended to control tachysystole [748].

ESC IIaC (LoE B, GoR 3)

• In patients with AHFS and AF/AFL for the control of tachysystole when beta-blockers are contraindicated, insufficiently effective, or cannot be used in the appropriate dose, intravenous amiodarone** should be considered to control tachysystole [749-751].

ESC IIbC (CARR A, LE 2)

• In patients with AHFS and reduced LVEF, it is recommended to maintain (or initiate) treatment that has a favorable effect on prognosis to improve clinical outcomes [752-754].

ESC IC (RRR C, LOC 5)

• In patients with CHF and LVEF £40%, the administration of specific (target) doses of certain beta-blockers (bisoprolol**, carvedilol**, or metoprolol** (extended-release tablets) in CHF, carvedilol or metoprolol** in MI), ACE inhibitors, and in a subset of patients, aldosterone antagonists (spironolactone** or eplerenone) is recommended to improve prognosis [755].

ESC IC (LoE B, LoR 3

Comments. In patients with AHFS presenting with hyperkalemia (blood potassium concentration >5.5 mmol/L) or severe renal impairment, discontinuation, temporary cessation, or dose reduction of drugs affecting the RAS is necessary to improve clinical outcomes. In patients with AHFS, after stabilization of hemodynamic parameters and improvement of renal function, it is recommended to resume (или initiate) therapy with drugs affecting the RAS with gradual titration up to target doses (or, if unsuccessful, to the maximum tolerated dose in the given patient) to improve clinical status.

• In patients with AHFS with SBP <85 mm Hg and/or HR <50 bpm, discontinuation, temporary cessation, or dose reduction of beta-blockers is recommended to improve clinical outcomes [756].

ESC IIaC (TR = B, LE = 3

• In patients with AHFS and LVEF £40% who were previously treated with sacubitril/valsartan**, continuation of sacubitril/valsartan** is recommended in the absence of contraindications to improve clinical outcomes [203, 757].

ESC IIaB (TR = A, LE = 2)

• In patients with AHFS and LVEF £40% after hemodynamic stabilization (SBP >100 mm Hg), initiation of sacubitril/valsartan** dose titration should be considered to improve clinical outcomes [203, 757].

ESC IIaB (TR = A, LE = 2)

• In patients with AHFS after hemodynamic stabilization (SBP >100 mm Hg), initiation of empagliflozin** therapy should be considered to improve clinical outcomes [758, 759].

ESC IIaB (TR = A, LE = 2

7.4.1.3. Assessment of a patient with acute heart failure decompensation during hospitalization. Criteria for stabilization and discharge

• In patients with AHFS, monitoring of respiratory rate, blood oxygen saturation via pulse oximetry, heart rate, cardiac rhythm, non-invasive blood pressure, daily body weight measurement, and meticulous fluid intake and output charting are recommended during the hospital stay to improve clinical outcomes [738, 760].

ESC I C (LoE C, GoR 4)

Comments. The intensity and choice of monitoring methods should depend on the patient's severity. In the early stages of treatment, the following may be required:

- ECG monitoring;

- evaluation of direct venous and arterial pressure and cardiac output (invasively or non-invasively) in patients with persistent arterial hypotension following treatment initiation;

- evaluation of pulmonary artery wedge pressure in patients with arterial hypotension and hypoperfusion during treatment when right and left ventricular dysfunction is noted, or when ultrasound findings do not match clinical manifestations;

- evaluation of acid-base balance in patients with respiratory failure or hemodynamic instability;

- evaluation of blood lactate concentration in patients with arterial hypoxemia or hemodynamic instability (at baseline and every 1-2 hours in the early stages of treatment).

In patients with hemodynamic instability, suspected life-threatening intracardiac hemodynamic disturbances, or aortic dissection, urgent echocardiography is recommended. Repeat echocardiography is not recommended unless there is a significant worsening of the patient's condition.

• In patients with AHFS during the hospital stay, daily assessment of signs related to fluid overload (dyspnea, pulmonary rales, peripheral edema, body weight) and the presence of hypoperfusion is recommended to improve clinical outcomes [738, 761-765].

ESC IC (TR = C, LE = 4)

• In patients with AHFS during the hospital stay, blood creatinine, urea, and electrolyte levels are recommended to be assessed at least once every 48 hours, and daily when intravenous therapy or agents affecting the RAS are used [738, 763, 764].

ESC IC (RR S, ELD 5)

Comments. More frequent laboratory evaluations may be required in severe cases. Renal function may be impaired upon admission and subsequently improve or worsen with diuretic therapy.

• In patients with AHFS, re-evaluation of blood natriuretic peptide concentrations is recommended prior to hospital discharge to determine prognosis [763, 765-767].

ESC IB (TR = C, LE = 5)

• In patients with AHFS prior to discharge, elimination of fluid accumulation (fluid overload) is recommended based on symptoms and signs of fluid retention, body weight trends, blood natriuretic peptide dynamics, hemoconcentration signs, and renal function to reduce the risk of rehospitalization and death [763, 765, 767-769].

ESC IB (TR = B, LE = 3)

• In patients with AHFS prior to discharge, determination of volume status via dielectric constant-based remote dielectric sensing (ReDS) is recommended to reduce the risk of readmissions [770, 771].

ESC not specified (LoE B, GoR 2)

• In patients with AHFS, the patient's response to treatment is recommended to be used as a determining factor for transfer between different hospital units to improve clinical outcomes [761].

ESC IIaB (TR = B, LE = 3)

• In patients with AHFS, parenteral administration of phosphocreatine is recommended after clinical stabilization to reduce clinical symptoms and improve quality of life [772-780].

ESC not stated (CGR B, LOR 3)

• In patients with recurrent episodes of AHFS, rapid discharge or overly rapid transfer to units with less intensive monitoring and patient care is not recommended to improve clinical status [781].

ESC IC (LoE B, GoR 3)

Comments. Prior to hospital discharge following treatment, it is necessary that the patient is hemodynamically stable, fluid accumulation has been resolved, and renal function and the patient's clinical status on oral therapy remain stable for at least the preceding 24 hours.

• To improve clinical outcomes in patients with AHF, it is recommended to conduct the first outpatient visit with a physician or other healthcare professional involved in the care of such patients within the first week after discharge (an alternative approach is a telephone call in the first 3 days and a visit within 2 weeks after discharge) [666].

ESC IB (LoE A, GoR 1)

• To improve clinical outcomes in patients with CHF after an episode of AHF, it is recommended to organize a specialized multidisciplinary team structure [782].

ESC IB (LoE A, GoR 1)

7.4.1.4. Treatment strategies for patients with acute decompensated heart failure aimed at reducing recurrence and improving survival

• In patients who have survived AHF, after hospital discharge, it is recommended to properly manage diseases and disorders that complicated AHF and/or could provoke a new episode of decompensation to improve clinical outcomes [766].

ESC IB (LoE B, GoR 3)

Comments. In patients who have survived AHF, after hospital discharge, it is recommended to maintain normal blood pressure in patients with hypertension, normovolemia in CHF, correct intracardiac hemodynamic disturbances, prevent tachyarrhythmia paroxysms or tachysystole episodes in persistent heart rhythm disorders (AF or atrial flutter), and provide adequate treatment for lung diseases and prevent recurrent episodes of pulmonary embolism to improve clinical outcomes.

• All patients with AHF before hospital discharge should be prescribed evidence-based oral medications to reduce the risk of readmissions and improve clinical outcomes: beta-blockers, ACE inhibitors (or ARBs in case of intolerance) or sacubitril/valsartan**; aldosterone antagonists (spironolactone** or eplerenone) and empagliflozin** [753, 783].

ESC IC (LoE B, GoR 3)

Comments. Dose titration can be initiated after hemodynamic stabilization and in the absence of other contraindications. In patients with AHF, if titration of these drugs was not completed during hospitalization, it should be continued in the outpatient setting, and appropriate prescriptions must be given upon discharge [756].

• All patients with AHF are recommended to visit an outpatient specialist within 7–14 days after hospital discharge to assess volume status, drug therapy tolerance, and medication dose titration in order to reduce the risk of readmissions and improve clinical outcomes [784, 785].

ESC IC (LoE A, GoR 3)

• In CHF patients with LVEF ≤40% and a history of AHF after hospital discharge, it is recommended to titrate beta-blockers, ACE inhibitors/sacubitril/valsartan** (or ARBs in case of intolerance), aldosterone antagonists (spironolactone** or eplerenone), and dapagliflozin**/empagliflozin** (sodium-glucose cotransporter 2 inhibitors) up to target doses to improve clinical outcomes [755, 786].

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

• In patients with CHF decompensation who were taking beta-blockers, it is recommended to continue treatment with this group of drugs to improve clinical outcomes, provided there is no severe bradycardia, high-grade atrioventricular block, symptomatic hypotension, or hypoperfusion [540, 786].

ESC IIaB (LoE A, GoR 3)

• In patients with CHF decompensation who were taking beta-blockers, in situations of temporary dose reduction or discontinuation of beta-blockers at the time of hospitalization, it is recommended to subsequently resume dose titration up to the target dose once the condition has stabilized to improve clinical outcomes [540, 786].

ESC IIaB (LoE A, GoR 3)

• Patients with AHF and LVEF <40% without contraindications may be recommended to receive empagliflozin** (a sodium-glucose cotransporter 2 inhibitor) to reduce the risk of readmissions [758, 759].

ESC IIbB (LoE A, GoR 2)

• In patients with AHF, to improve clinical symptoms and reduce the risk of readmissions after discharge, it is recommended to administer ferric carboxymaltose** (in case of iron deficiency, defined as serum ferritin <100 ng/mL or serum ferritin 100–299 ng/mL and transferrin saturation <20%) [408].

ESC IIaB (LoE B, GoR 2)

7.4.1.5. Medications used for the treatment of patients with acute decompensated heart failure

Narcotic analgesics.

• In patients with AHF, the routine use of narcotic analgesics to improve the clinical condition is not recommended [787, 788].

ESC IIIC (LoE A, GoR 3)

Comments. Natural opium alkaloids (opioids), such as morphine^**, have demonstrated the ability to reduce left ventricular end-diastolic pressure, afterload, heart rate, and dyspnea severity in small studies. The approach to prescribing narcotic analgesics in AHF should be individualized. Intravenous administration of morphine^** can be used with caution in patients with severe pain syndrome, severe dyspnea (usually in pulmonary edema), and agitation.

Peripheral vasodilators

• In patients with AHF and SBP >110 mmHg without signs of hypoperfusion, intravenous administration of peripheral vasodilators may be recommended to relieve symptoms (primarily dyspnea) and reduce pulmonary congestion [744].

ESC IIbB (TR = A, LE = 1

Comments. When administering peripheral vasodilators intravenously, careful monitoring of clinical symptoms, SBP values, and dose titration are recommended to avoid arterial hypotension [744]. In patients with ADHF and severe LVH, significant aortic stenosis, the use of peripheral vasodilators should be undertaken with extreme caution and is generally not recommended [745, 789, 790]. With continuous use of organic nitrates, the development of tolerance should be expected, requiring increased doses. Intravenous infusion of peripheral vasodilators should be performed; in individual cases (particularly in patients with pulmonary edema associated with very high BP), intravenous boluses of nitroglycerin at 1-2 mg may be used.

Table 15. Peripheral vasodilators recommended for the treatment of acute decompensated heart failure.

Diuretics

• In patients with AHF and signs of fluid accumulation (fluid overload) without severe hypotension and signs of hypoperfusion, prompt intravenous administration of loop diuretics is recommended to improve the clinical condition [741].

ESC IC (TR = B, LE = 2)

Comments. In addition to increasing salt and water excretion, loop diuretics have some vasodilating effect that helps reduce preload, which may be important in patients with acute pulmonary congestion/pulmonary edema. In patients who have not previously received loop diuretics, an initial intravenous dose of 20–40 mg of furosemide** is recommended. In patients chronically taking loop diuretics for the treatment of CHF, it is recommended to start treatment with an intravenous dose of furosemide** equivalent to the home dose or twice the home dose. The optimal frequency of intravenous administration of furosemide is 2–3 times a day (continuous intravenous infusion at an appropriate daily dose is also possible) [741].

The dose of furosemide** should be titrated taking into account urinary sodium concentration (an adequate response is defined as a urinary sodium level 2 hours after an intravenous bolus above 50–70 mEq/L) and/or urine output (at least 100-150 mL/h 6 hours after an intravenous bolus). If the response is insufficient, it is recommended to double the dose of furosemide** up to 400–600 mg or up to 1000 mg in patients with severe renal impairment, and additionally use a thiazide diuretic. During diuretic therapy, symptoms (severity of fluid retention, appearance of signs of hypoperfusion), patient body weight, urine output, blood pressure, presence of orthostatic hypotension, blood electrolyte and creatinine concentrations, and signs of hemoconcentration should be monitored to avoid electrolyte disturbances, severe renal function deterioration, and dehydration [694, 716].

The optimal diuretic therapy regimen and dosing approach have not yet been defined. Accordingly, in cases where early administration of diuretics is possible, it is recommended to use the minimum doses sufficient to achieve a clinical effect, taking into account renal function and previously used doses. After achieving the effect, it is recommended to gradually reduce the diuretic dose and, after eliminating fluid retention, use the lowest possible dose that prevents the recurrence of congestion.

• In patients with acute decompensated heart failure (ADHF) prior to the resolution of hypoperfusion signs, the use of diuretics is not recommended [716].

ESC IIIB (LOC B, LE Level 2)

• In patients with ADHF and edema that do not decrease with increasing doses of furosemide**, it is recommended to combine a loop diuretic with a thiazide diuretic to increase the efficacy of diuretic therapy [743, 791, 792].

ESC IIaB (LOC B, LE Level 2)

• In patients with ADHF and resistant edema despite increasing doses of loop diuretics, it is recommended to combine loop diuretics (furosemide** or torasemide) with thiazide diuretics to improve clinical symptoms, with particularly careful monitoring to prevent hypokalemia, hyponatremia, renal dysfunction, and hypovolemia [743, 791, 792].

ESC IIaB (LOC B, LE Level 2)

• In patients with ADHF and resistant edema against the background of increasing doses of loop diuretics, the addition of acetazolamide** may be recommended to improve clinical symptoms [793].

ESC IIbC (LOC A, LE Level 2)

Non-glycoside inotropic (cardiotonic) drugs

• In ADHF patients with left ventricular contractile dysfunction and arterial hypotension (SBP <90 mmHg) and/or signs of hypoperfusion in the presence of adequate ventricular filling pressures (absence of hypovolemia), short-term intravenous administration of non-glycoside inotropic (cardiotonic) drugs may be recommended to increase cardiac output, raise SBP, improve tissue perfusion, and maintain normal function of target organs [794].

ESC IIbC (GPP C, LoE 5)

Comments. The administration of non-glycoside inotropic drugs should be initiated at relatively low doses, gradually increasing the dose provided that ECG and blood pressure are carefully monitored to prevent potential adverse effects of therapy [794].

• In ADHF patients receiving beta-blockers, the intravenous administration of levosimendan** may be recommended, as it is preferable in this situation to dobutamine** and dopamine** to counteract the adverse effect of beta-adrenergic blockade leading to arterial hypotension and hypoperfusion [795].

ESC IIbC (LOC C, LE Level 2)

• In patients with ADHF without significant reduction in cardiac output leading to arterial hypotension and/or impaired organ perfusion, non-glycoside inotropic agents are not recommended for safety reasons [796-798].

ESC IIIA (LOC B, LE Level 1)

• In ADHF patients receiving non-glycoside inotropic drugs, particularly dobutamine** and dopamine**, ECG and blood pressure monitoring may be recommended to prevent the occurrence of cardiac arrhythmias [796-798].

ESC IIbB (LOC B, LE Level 3)

• In ADHF patients, when arterial hypotension is caused by hypovolemia and other potentially reversible causes (at least until these causes are corrected), the use of non-glycoside inotropic drugs, particularly levosimendan**, is not recommended [799].

ESC IIIA (LOC B, LE Level 2)

Comments. To prevent arterial hypotension when using levosimendan**, an intravenous bolus prior to the initiation of infusion is not recommended, nor is starting the drug in patients with uncorrected hypovolemia.

Table 16. Doses of non-glycoside inotropic agents

Vasopressor agents

• In patients with ADHF and cardiogenic shock, the use of vasopressor agents (preferably norepinephrine**) may be recommended to increase blood pressure and improve perfusion of vital organs [800-802].

ESC IIbB (LOC B, LE Level 2)

• In patients with ADHF receiving vasopressor agents, monitoring of ECG and blood pressure is recommended to prevent tachycardia, arrhythmias, and myocardial ischemia [803].

ESC IC (RRR C, LOC 5)

Table 17. Doses of vasopressor drugs

Digoxin**

• In patients with ADHF and atrial fibrillation/flutter with a heart rate >110 bpm, when restoration of sinus rhythm is impossible or unjustified, and beta-blockers are contraindicated or insufficiently effective, the use of digoxin** is recommended to reduce the ventricular rate [341, 342, 805].

ESC IIaB (LOC B, LE Level 1)

Comments. In these cases, the use of digoxin** is considered in patients with arterial hypotension and other contraindications to beta-blockers, as well as in addition to beta-blockers when their efficacy is insufficient. The usual initial dose of digoxin** is 0.25–0.5 mg intravenously (0.0625–0.125 mg in patients with moderate to severe renal impairment). The maintenance dose is not always obvious, especially in elderly patients, those with comorbid conditions, and other factors affecting its metabolism, which necessitates monitoring its blood concentration.

Calcium channel blockers

• In selected patients with ADHF and preserved left ventricular EF (≥50%) with absolute contraindications to beta-blockers, the use of non-dihydropyridine calcium channel blockers may be recommended for symptom control, provided there are no contraindications [750].

ESC IIbB (LOC B, LE Level 2)

Comments. The main indication for non-dihydropyridine calcium channel blockers is the control of tachyarrhythmia in atrial fibrillation/flutter.

7.4.2. Prevention of thromboembolic events

• In patients with ADHF not receiving anticoagulant or sodium heparin and heparin group drug therapy for other indications and having no contraindications to anticoagulants, subcutaneous injections of unfractionated heparin, low molecular weight heparins (sodium heparin and heparin group drugs), or the synthetic polysaccharide fondaparinux sodium are recommended for VTE prophylaxis [806].

ESC IA (LOC A, LE Level 1)

7.4.3. Non-pharmacological treatments for patients with acute decompensation of heart failure

• In patients with cardiogenic shock who fail to respond to pharmacotherapy, mechanical circulatory support (MCS) is recommended to improve clinical symptoms [807].

ESC IIaC (LOC C, LE Level 4)

Comments: The use of MCS can serve as a life-support measure until the causes of cardiogenic shock are clarified and further management is determined, prior to interventions capable of altering the clinical course and prognosis (correction of intracardiac shunt/structural defects, heart transplantation, etc.), as well as until clinical improvement occurs in cases where it is expected without additional invasive procedures. The determination of indications for MCS, selection of devices, and patient monitoring during treatment should be performed by an experienced multidisciplinary team taking into account the specifics of the individual clinical case [808-816].

• In patients with cardiogenic shock refractory to medical therapy, the use of intra-aortic balloon counterpulsation may be recommended to improve clinical symptoms while awaiting treatment for the underlying cause of cardiogenic shock (e.g., mechanical complications of myocardial infarction) or as a temporary measure prior to MCS or heart transplantation [817, 818].

ESC IIbC (LOC B, LE Level 2)

• Routine (mandatory) use of intra-aortic balloon counterpulsation is not recommended in patients with cardiogenic shock complicating myocardial infarction [817, 818].

ESC IIIB (LOC B, LE Level 2)

Criteria for Evaluating the Quality of Medical Care

Table 18. Quality of care criteria for primary health care provided to adults with chronic heart failure (ICD-10 codes: I50.0, I50.1, I50.9).

Table 19. Criteria for assessing the quality of specialized medical care provided to adults with chronic heart failure (ICD-10 codes: I50.0, I50.1, I50.9) 

References

Appendix A1. Working Group Composition

Presidium:

Galyavich A.S. (Kazan), Prof., Dr. Med. Sci.

Tereshchenko S.N. (Moscow), Prof., Dr. Med. Sci.

Uskach T.M. (Moscow), Prof., Dr. Med. Sci.

Working Group

Ageev F.T., Prof., Dr. Med. Sci.

Arutyunov G.P., Corr. Member RAS, Prof., Dr. Med. Sci.

Begrambekova Yu.L., Cand. Med. Sci.

Belenkov Yu.N., Academician RAS, Prof., Dr. Med. Sci.

Boytsov S.A., Academician RAS, Prof., Dr. Med. Sci.

Vasyuk Yu.A., Prof., Dr. Med. Sci.

Villevalde S.V., Prof., Dr. Med. Sci.

Vinogradova N.G., Dr. Med. Sci.

Garganeeva A.A., Prof., Dr. Med. Sci.

Gendlin G.E., Prof., Dr. Med. Sci.

Gilyarevsky S.R., Prof., Dr. Med. Sci.

Glezer M.G., Prof., Dr. Med. Sci.

Gotye S.V., Academician RAS, Prof., Dr. Med. Sci.

Grinshtein Yu.I., Prof., Dr. Med. Sci.

Dovzhenko T.V., Prof., Dr. Med. Sci.

Drapkina O.M., Academician RAS, Prof., Dr. Med. Sci.

Duplyakov D.V., Prof., Dr. Med. Sci.

Zhirov I.V., Dr. Med. Sci.

Zateyshchikov D.A., Prof., Dr. Med. Sci.

Zvartau N.E., Assoc. Prof., Cand. Med. Sci.

Irtyuga O.B., Assoc. Prof., Dr. Med. Sci.

Kobalava Zh.D., Corr. Member RAS, Prof., Dr. Med. Sci.

Koziolova N.A., Prof., Dr. Med. Sci.

Koroteev A.V., Prof., Dr. Med. Sci.

Libis R.A., Prof., Dr. Med. Sci.

Lopatin Yu.M., Corr. Member RAS, Prof., Dr. Med. Sci.

Mareev V.Yu., Prof., Dr. Med. Sci.

Mareev Yu.V., Cand. Med. Sci.

Matskeplishvili S.T., Corr. Member RAS, Prof., Dr. Med. Sci.

Mikhailov E.N., Dr. Med. Sci.

Nasonova S.N., Cand. Med. Sci.

Narusov O.Yu., Cand. Med. Sci.

Nedogoda S.V., Prof., Dr. Med. Sci.

Nedoshivin A.O., Prof., Dr. Med. Sci.

Ovchinnikov A.G., Dr. Med. Sci.

Orlova Ya.A., Prof., Dr. Med. Sci.

Perepech N.B., Prof., Dr. Med. Sci.

Pogosova N.V., Prof., Dr. Med. Sci.

Rimskaya E.M., Cand. Med. Sci.

Samko A.N., Prof., Dr. Med. Sci.

Saidova M.A., Prof., Dr. Med. Sci.

Sapelnikov O.V., Dr. Med. Sci.

Safiullina A.A., Cand. Med. Sci.

Sitnikova M.Yu., Prof., Dr. Med. Sci.

Skvortsov A.A., Dr. Med. Sci.

Skibitsky V.V., Prof., Dr. Med. Sci.

Stukalova O.V., Cand. Med. Sci.

Tarlovskaya E.I., Prof., Dr. Med. Sci.

Tereshchenko A.S., Cand. Med. Sci.

Chesnikova A.I., Prof., Dr. Med. Sci.

Fedotov P.A., Cand. Med. Sci.

Fomin I.V., Prof., Dr. Med. Sci.

Khasanov N.R., Prof., MD, DSc

Shevchenko A.O., Corresponding Member of the RAS, Prof., MD, DSc

Shaposhnik I.I., Prof., MD, DSc

Shariya M.A., MD, DSc

Shlyakhto E.V., Academician of the RAS, Prof., MD, DSc

Yavelov I.S., MD, DSc

Yakushin S.S., Prof., MD, DSc

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

Appendix A2. Methodology for Developing Clinical Guidelines

Since members of the Russian Society of Cardiology are also members of the European Society of Cardiology (ESC), all ESC guidelines are developed with the participation of Russian experts who co-author the European guidelines. Thus, the existing ESC guidelines reflect the consensus of leading Russian and European cardiologists. Therefore, the National Guidelines were developed on the basis of the ESC guidelines, taking into account national specifics, examination and treatment features, and the availability of medical care. For this reason, the text of these clinical guidelines simultaneously uses two grading scales for the reliability of evidence supporting guideline statements: ESC levels of evidence combined with levels of clinical evidence (LCE) and levels of evidence (LoE). ESC recommendation classes have also been added to assess the necessity of performing a recommendation statement (Tables P1, P2, P3, P4, P5).

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

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

Table P3. Scale for assessing levels of evidence (LoE) for diagnostic methods (diagnostic interventions)

Table P4. Scale for assessing levels of evidence (LoE) for prevention, treatment, and medical rehabilitation methods, including those based on natural healing factors (preventive, therapeutic, and rehabilitation interventions)

Table P5. Scale for assessing levels of clinical evidence (LCE) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural healing factors (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Special designations for medicinal products and medical devices.

** - the medicinal product is included in the list of vital and essential drugs for medical use

# - the medicinal product is used off-label

*** - the medical device belongs to devices implanted into the human body when providing medical care under the state guarantee program for free medical care to citizens.

Procedure for updating clinical guidelines.

The guideline update mechanism provides for their systematic review—at least once every three years or upon the emergence of new information on the management tactics of patients with this disease. The decision to update is made by the Russian Ministry of Health based on proposals submitted by professional medical non-profit organizations. The submitted proposals must take into account the results of a comprehensive assessment of medicinal products and medical devices, as well as the results of clinical approbation.

Appendix A3. Reference Materials

Appendix A3-1. Stages of development and progression of heart failure

Based on and modified from the classification by Heidenreich PA, et al. [627] and Bozkurt B. [42]

Appendix A3-2. Practical aspects of valsartan/sacubitril** use in patients with HFrEF

Prescription algorithm

• initiation of therapy is recommended with stable hemodynamics and a SBP of at least 90 mm Hg;

• in patients hospitalized due to decompensated heart failure, prescription is possible after condition stabilization and reduction of congestion; prescription must be completed before discharge from the hospital;

• blood potassium and creatinine levels must be checked before prescription;

• therapy should be initiated with low doses;

• starting dose may be reduced to 24/26 mg twice daily in patients with SBP 100-110 mm Hg, not previously treated with ACE inhibitors/ARBs, and GFR 30-60 mL/min/1.73 m²;

• titrate slowly, doubling the dose no more frequently than once every 2 weeks;

• always strive to achieve the target dose, or, if this is not possible, the maximum tolerated dose;

• monitor blood pressure and blood chemistry (urea, creatinine, potassium) 1-2 weeks after initiation and 1-2 weeks after final dose titration; further blood chemistry monitoring once every 4 months;

• patients should be informed about the goals of the recommended therapy and potential side effects, which may improve patient adherence to the prescribed therapy;

• discontinuation of valsartan/sacubitril*** for any reason may lead to a deterioration in the patient's clinical condition, which requires separate discussion with a cardiologist.

Contraindications:

• history of angioedema;

• previously identified bilateral renal artery stenosis;

• pregnancy and breastfeeding;

• GFR <30 mL/min/1.73 m²;

• symptomatic hypotension or SBP <90 mm Hg;

• allergic and other adverse reactions associated with the drug intake;

Use with caution / under the supervision of a cardiology specialist:

• significant hyperkalemia (potassium >5.0 mmol/L);

• administration of the drug at least 36 hours after ACE inhibitor discontinuation due to the risk of angioedema;

Drug interactions requiring special attention:

• potassium-sparing diuretics;

• aldosterone antagonists (spironolactone^**, eplerenone);

• NSAIDs (non-steroidal anti-inflammatory and antirheumatic drugs);

• sulfamethoxazole+trimethoprim**;

• high-potassium table salt substitutes;

• renin inhibitors.

Potential problems and solutions:

Asymptomatic hypotension:

Usually does not require changes in therapy.

Symptomatic hypotension:

• if dizziness, lightheadedness, weakness, and decreased blood pressure occur, it often resolves spontaneously, which requires an explanatory talk with the patient;

• if symptoms persist, the need for organic nitrates and other vasodilators should be reassessed;

• if there are no signs/symptoms of fluid congestion, consider reducing the diuretic dose;

• if these measures also fail to resolve the problem, consult a cardiologist.

Cough:

• cough may be not only a side effect of ACE inhibitors, but also of valsartan/sacubitril**, and may also be a symptom of HFrEF/HFpEF, associated with smoking, other lung diseases, including lung cancer;

• cough is also a symptom of pulmonary edema (especially if newly onset and worsening over a relatively short period of time);

• if you are sure that the cough is specifically related to the prescription of valsartan/sacubitril** (the cough stops when the drug is discontinued and returns again when therapy is resumed), its intensity must be assessed. In case of rare cough, therapy may be continued. In other cases, valsartan/sacubitril** should be replaced with an ARB.

Worsening of renal function:

• an increase in blood urea, creatinine, and potassium levels is possible after initiating therapy; however, if these changes are insignificant and asymptomatic, there is no need to modify the therapy;

• if potassium concentration increases to 5.5 mmol/L and eGFR decreases to 30 mL/min/1.73 m², the drug dose must be halved;

• if an excessive increase in blood urea, creatinine, and potassium concentration is observed after initiating therapy, all drugs with a potential nephrotoxic effect (e.g., NSAIDs) and potassium-sparing diuretics must be discontinued; in the absence of signs of hypervolemia, the reduction of the loop diuretic dose should be considered, especially for patients receiving dapagliflozin** or empagliflozin**;

• if previous measures are ineffective, halve the drug dose followed by monitoring of blood creatinine and potassium in 2 weeks; only thereafter consider reducing the dose/discontinuing aldosterone antagonists (cardiologist consultation);

• if the potassium level increases >6.0 mmol/L and eGFR further decreases, the drug should be discontinued and specialists (cardiologist, nephrologist) should be consulted;

• continue monitoring blood potassium and creatinine until they stabilize.

Appendix A3-3. Practical aspects of ACE inhibitor use in patients with HFrEF

ACE inhibitor prescribing algorithm:

• initiation of ACE inhibitor therapy is recommended with stable hemodynamics and an SBP of at least 85 mm Hg;

• start with low doses; if the patient is prone to hypotension, the starting dose may be halved;

• titrate slowly, doubling the dose no more frequently than once every 2 weeks;

• always strive to achieve the target dose, or, if this is not possible, the maximum tolerated dose;

• prescribing even minimal doses of ACE inhibitors is always better than not prescribing them at all;

• monitor blood pressure and blood chemistry (urea, creatinine, potassium) 1-2 weeks after initiation and 1-2 weeks after final dose titration; further blood chemistry monitoring once every 4 months;

• patients should be informed about the goals of the recommended therapy and potential side effects, which may improve patient adherence to the prescribed therapy;

• discontinuation of ACE inhibitor therapy for any reason may lead to a deterioration of the patient's clinical condition, which requires a separate discussion with a cardiologist.

Contraindications to prescribing:

• history of angioedema;

• dry cough and allergic reactions;

• previously identified bilateral renal artery stenosis;

• pregnancy.

Use with caution / under the supervision of a cardiology specialist:

• significant hyperkalemia (potassium >5.0 mmol/L);

• significant renal impairment (creatinine level >221 µmol/L or >2.5 mg/dL) or eGFR <30 mL/min/1.73 m²;

• symptomatic or pronounced asymptomatic arterial hypotension (SBP <90 mm Hg).

Drug interactions requiring special attention:

• potassium-sparing diuretics;

• aldosterone antagonists (spironolactone^**, eplerenone);

• ARBs;

• NSAIDs;

• sulfamethoxazole+trimethoprim**;

• high-potassium table salt substitutes;

• renin inhibitors.

Potential problems and solutions:

Asymptomatic hypotension:

Usually does not require changes in therapy.

Symptomatic hypotension:

• if dizziness, lightheadedness, weakness, and decreased blood pressure occur, it often resolves spontaneously, which requires an explanatory talk with the patient;

• if symptoms persist, the need for organic nitrates and other vasodilators should be reassessed; move the ACE inhibitor dose to the evening hours;

• in the absence of signs/symptoms of fluid congestion, consider reducing the diuretic dose;

• if these measures also fail to resolve the problem, consult a cardiologist.

Cough:

• cough may be not only a side effect of ACE inhibitors, but is also a symptom of HF, and may be associated with smoking, other lung diseases, including lung cancer;

• cough is also a symptom of pulmonary edema (especially if newly onset and worsening over a relatively short period of time);

• if you are sure that the cough is specifically related to the prescription of ACE inhibitors (the cough stops when ACE inhibitors are discontinued and returns again when therapy is resumed), its intensity must be assessed. In case of rare cough, therapy may be continued. In other cases, ACE inhibitors should be replaced with valsartan/sacubitril** or an ARB.

Worsening of renal function:

• an increase in blood urea, creatinine, and potassium levels is possible after initiating ACE inhibitor therapy; however, if these changes are insignificant and asymptomatic, there is no need to modify the therapy;

• after initiating ACE inhibitor therapy, an increase in creatinine level by 50% above baseline values, or up to 226 µmol/L (3.0 mg/dL), or a decrease in eGFR to 25 mL/min/1.73 m² is acceptable;

• an increase in potassium up to a level of ≤5.5 mmol/L is also acceptable;

• if an excessive increase in blood urea, creatinine, and potassium concentration is observed after initiating ACE inhibitor therapy, all drugs with a potential nephrotoxic effect (e.g., NSAIDs) and potassium-sparing diuretics must be discontinued; in the absence of signs of hypervolemia, the reduction of the loop diuretic dose should be considered; switch the patient to an ACE inhibitor with dual elimination (liver-kidney) – fosinopril, ramipril**;

• if previous measures are ineffective, halve the ACE inhibitor dose followed by monitoring of creatinine and potassium in 2 weeks; only thereafter consider reducing the dose/discontinuing aldosterone antagonists (cardiologist consultation);

• if potassium concentration increases >5.5 mmol/L, creatinine increases by more than 100% or up to 310 µmol/L (3.5 mg/dL), or eGFR decreases <20 mL/min/1.73 m², ACE inhibitor therapy should be discontinued and specialists (cardiologist, nephrologist) should be consulted;

• careful monitoring of blood biochemical parameters is necessary until they normalize.

Appendix A3-4. Practical aspects of beta-blocker use in patients with HFrEF

Prescribing algorithm:

• treatment must always be started with low doses;

• titrate slowly, doubling the dose no more frequently than once every 2 weeks;

• always strive to achieve the target dose, or, if this is not possible, the maximum tolerated dose;

• prescribing the lowest doses of beta-blockers is always better than having no beta-blocker therapy at all;

• it is necessary to regularly monitor heart rate, blood pressure, and clinical status (especially symptoms of fluid congestion, body weight);

• strict daily monitoring of the patient's weight is recommended – in case of a sudden increase, an immediate increase in diuretic dose is necessary until the patient reaches baseline body weight values;

Absolute contraindications:

• symptomatic bradycardia (HR <50 bpm);

• symptomatic hypotension (SBP <85 mm Hg);

• second-degree or higher atrioventricular block;

• severe obliterating atherosclerosis;

• allergies and other known adverse reactions associated with the drug.