Chronic Heart Failure in Children: Clinical Guidelines

List of Abbreviations

MRA – mineralocorticoid receptor antagonist

ARB – angiotensin receptor blocker

ARNI – angiotensin receptor-neprilysin inhibitor

BB – beta-blocker

CHD – congenital heart disease

BMI – body mass index

ACEI – angiotensin-converting enzyme inhibitor

SGLT2i – sodium-glucose cotransporter 2 inhibitor

LV – left ventricle

MRI – magnetic resonance imaging

RV – right ventricle

RAAS – renin-angiotensin-aldosterone system

SNS – sympathoadrenal system

HF – heart failure

CRT – cardiac resynchronization therapy

HT – heart transplantation

EF – ejection fraction

FC – functional class

CHF – chronic heart failure

HFpEF – heart failure with preserved ejection fraction

HFrEF – heart failure with reduced ejection fraction

HFmrEF – heart failure with mildly reduced ejection fraction

ECG – electrocardiography

ECMO – extracorporeal membrane oxygenation

PM – pacemaker

EchoCG – echocardiography

GLS – global longitudinal strain

NYHA – New York Heart Association

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

*** – medical device implanted in the human body when providing medical care within the framework of the state guarantee program for free medical care to citizens

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

Terms and Definitions

Heart failure (HF) is a clinical syndrome characterized by typical symptoms (dyspnea, tachycardia, fatigue, leg and foot edema) and signs (elevated jugular venous pressure, pulmonary rales, peripheral edema) caused by an abnormality in cardiac structure and/or function, leading to reduced cardiac output and/or increased cardiac filling pressure at rest or during exertion.

Acute heart failure (AHF) is a life-threatening condition characterized by a rapid onset or sharp worsening of HF symptoms/signs up to the development of pulmonary edema or cardiogenic shock, requiring urgent therapeutic measures.

Chronic heart failure (CHF) is a condition characterized by a gradual increase in HF symptoms/signs, long-standing and typically progressive, up to the development of "decompensation".

HF decompensation is a condition characterized by a pronounced exacerbation of symptoms/signs of chronic heart failure.

Systolic HF is HF caused by impaired ventricular contractility.

Diastolic HF is HF caused by impaired ventricular relaxation function.

Chronic heart failure with reduced left ventricular ejection fraction (HFrEF) is HF with markedly reduced left ventricular contractility (LVEF < 40%).

Chronic heart failure with mildly reduced left ventricular ejection fraction (HFmrEF) is HF with moderately reduced left ventricular contractility (LVEF 41–49%).

Chronic heart failure with preserved left ventricular ejection fraction (HFpEF) is HF with preserved left ventricular contractility (LVEF ≥ 50%).

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Heart failure (HF) is a syndrome developing as a result of impaired cardiac filling and/or emptying capacity, occurring in conditions of imbalance between vasoconstrictor and vasodilator neurohormonal systems, accompanied by inadequate perfusion of organs and systems and manifested by complaints: dyspnea, weakness, palpitations, and fatigue and, upon progression, fluid retention in the body (edematous syndrome) [1].

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

The causes of CHF in children are diverse, depend on age, and differ fundamentally from those in adults (Table 1). Thus, in newborns and infants, the main causes of HF are congenital heart defects (CHD). In 78% of children with CHD, HF disappears after CHD correction [2,3].

In preschool and school age, the causes of HF are idiopathic and inflammatory heart diseases: infective endocarditis, myocarditis, cardiomyopathies, primary pulmonary hypertension, pericarditis. Recently, the number of myocardial lesions in systemic connective tissue diseases and vasculitis, especially Kawasaki disease, has also been increasing. In addition, diseases causing chronic myocardial overload due to its increased intensive work (tachyarrhythmias) or increased peripheral vascular resistance (arterial hypertension) are important [4,5].

The main causes of heart failure with reduced ejection fraction (HFrEF) in children, i.e., systolic HF, are myocarditis and cardiomyopathy with a dilated phenotype. In such patients, pathological remodeling of the left ventricle (LV) develops with its dilation and altered geometry (the LV becomes spherical), accompanied by impaired LV myocardial contractility. These changes in children progress rapidly. It is hypothesized that several pathophysiological mechanisms are involved in this process. The first is myocardial injury leading to cardiomyocyte death (e.g., inflammation, toxic agents, genetically determined process, etc.). The second is a systemic response to decreased LV systolic function, characterized by increased activity of vasopressor systems: the sympathoadrenal system (SAS), the renin-angiotensin-aldosterone system (RAAS), endothelin, vasopressin, and cytokines. Activation of the RAAS and SAS leads to peripheral vasoconstriction, sodium and fluid retention, which increases the load on the LV and also exerts a direct toxic effect on the myocardium, stimulating fibrosis and apoptosis, which leads to further cardiac remodeling and impaired function. In addition to myocardial injury, the activation of neurohumoral systems also has a detrimental effect on other organs — blood vessels, kidneys, muscles, bone marrow, lungs, and liver, forming a pathophysiological "vicious" cycle and leading to many clinical manifestations of CHF, including myocardial electrical instability. Clinically, all these changes are associated with the development and progression of CHF symptoms and lead to impaired quality of life, reduced physical activity of patients, and HF decompensation requiring hospitalization. Intervening in these two key processes (myocardial injury and neurohumoral system activation) forms the basis of CHF treatment [1,6].

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is significantly less understood in both adults and children, due to the heterogeneity, complexity of diagnosis, and treatment of this condition. This type of HF is primarily caused by impaired left ventricular (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. The mechanical properties of the myocardium, which are characterized by elasticity, compliance, and stiffness, affect LV filling during diastole and atrial systole. Myocardial hypertrophy, fibrosis, or infiltration increases its stiffness, leading to a sharp rise in LV filling pressures. In addition, LV compliance depends on the level of preload. LV compliance decreases during its dilatation. Depending on the severity of diastolic disorders, three types of LV filling are distinguished: delayed relaxation, pseudonormalization, and restriction. The severity of clinical manifestations of diastolic HF and patient prognosis are primarily determined by the severity of diastolic dysfunction. The prognosis of patients with HFpEF depends on the cause of the disease and the severity of diastolic dysfunction [1,6].

The epidemiology and etiology of HFpEF differ from those of systolic HF. The main causes of HFpEF in children include hypertrophic and restrictive cardiomyopathies, constrictive pericarditis, hydropericardium, thyrotoxicosis, infiltrative diseases, metastatic myocardial lesions, and others.

Table 1. Causes of heart failure in children

1.3 Epidemiology of the Disease or Condition

The exact prevalence of chronic heart failure (CHF) in children in Russia is unknown due to a lack of relevant studies. According to available data, the incidence of CHF in the pediatric population ranges from 0.87/100,000 (UK and Ireland) to 7.4/100,000 (Taiwan) [7]. In a large population-based study, the prevalence of CHF among the pediatric population of Spain (6 months – 14 years) was 0.08% [8].

1.4 Features of Coding the Disease or Condition

I50.0 - Congestive heart failure

I50.1 - Left ventricular failure

I50.9 - Heart failure, unspecified

I42.0 - Dilated cardiomyopathy

I42.8 - Other cardiomyopathies

I42.9 - Cardiomyopathy, unspecified

P29.0 - Neonatal cardiac failure

Q24.8 - Other specified congenital malformations of heart

1.5 Classification of the disease or condition

By LV ejection fraction [1] (Table 2):

• HFrEF — less than 40%,

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

• HFpEF — 50% or greater.

Table 2. Classification of heart failure by left ventricular ejection fraction

(a) Signs may be absent in the early stages of HF (especially in HFpEF) and in patients receiving optimal treatment.

(b) For the diagnosis of HFmrEF, the presence of other signs of structural heart disease (e.g., left atrial enlargement, LV hypertrophy, or echocardiographic measures of impaired LV filling) makes the diagnosis more likely.

(c) For the diagnosis of HFpEF: the greater the number of abnormalities, the higher the probability of HFpEF.

To determine the severity of CHF, a classification based on the stage of heart disease and functional class (FC) is used. In older children, the National Classification of CHF Stages can be used (Table 3)

Table 3. National Classification of CHF Stages

In international pediatric practice, the modified classification (scoring scale) by ROSS R.D. (2002) [9] is widely used (Tables 3(a) and 3(b)).

Table 3(a) Modified Classification (Scale) by ROSS R.D. (2002)

Table 3(b) Modified Classification (Scale) by ROSS R.D. (2002)

To determine the functional class (FC) of CHF in children under 7 years of age, the Ross R.D. FC classification (1987) is used; for those over 7 years of age, the NYHA (New York Heart Association) classification is used (Table 4).

Table 4. Classification of CHF FC by Ross R.D. (1987) and NYHA

1.6 Clinical presentation of the disease or condition

Diagnosis of CHF in children can be challenging due to the nonspecificity of symptoms and their varying severity—ranging from minimal manifestations occurring only during physical exertion to severe dyspnea at rest [5,10] (Table 5). The cause of dyspnea in CHF is pulmonary congestion, which leads to increased pressure in the pulmonary veins and capillaries.

Edema can be of cardiac or non-cardiac origin (renal pathology, chronic venous insufficiency, acute deep vein thrombosis, lymphedema, and other causes). The physician's task when evaluating a patient with edema is to confirm or exclude its cardiac origin. It is necessary to consider the clinical features of edema in HF, the identification of systemic venous hypertension, and the presence of signs of organic heart disease. In HF, edema is located in the most dependent parts of the body (lower extremities, and as HF progresses, scrotal, abdominal, and lumbar edema) and is symmetrical.

Table 5. Symptoms of CHF in Children

In infants during the first year of life, the earliest symptoms are dyspnea, initially appearing upon exertion (feeding); as the disease progresses, dyspnea occurs at rest, accompanied by restlessness, sweating, decreased appetite (often requiring gavage feeding), growth restriction, and failure to thrive [4,5,11]. Peripheral edema may not be visible due to the high tissue hydrophilicity in young children. Hepatosplenomegaly is frequently detected.

In older children and adolescents, the earliest symptoms are dyspnea, fatigue, and decreased exercise tolerance, which progress as the disease courses. Nonspecific but characteristic symptoms may include dyspeptic phenomena: nausea, vomiting, bowel motility disorders caused by inadequate blood supply to the GI tract and blood stasis in mesenteric vessels. Dyspnea in the early stages of CHF is associated with physical exertion; as the disease progresses, dyspnea occurs at lower levels of exertion, subsequently leading to orthopnea, coughing in the recumbent position, and related sleep disturbances [4].

Physical examination reveals pallor, dyspnea with chest retractions, nasal flaring, tachycardia, precordial bulge, leftward displacement of the relative cardiac dullness borders, muffled heart sounds, heart murmurs, accentuation of the 2nd sound in the pulmonary artery projection (characteristic of pulmonary hypertension), and gallop rhythm [4,12].

When signs of right ventricular CHF develop in children, signs of systemic venous congestion appear: distended veins, especially jugular veins, epigastric pulsation due to right ventricular (RV) hypertrophy or volume overload, hepatomegaly with tenderness upon palpation, and occasionally moderate splenomegaly [4,12].

In older children and adolescents in the decompensated stage, peripheral edema appears (on the feet, then ankles, shins, and in bedridden patients in the sacral region, usually worsening by evening), followed later by hydrothorax and ascites [4].

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.

3. Evidence of systolic and/or diastolic dysfunction (instrumental and/or laboratory).

2.1 Complaints and Anamnesis

• When interviewing the patient and/or the child's parents to identify clinical manifestations of heart failure, it is recommended to pay attention to the presence of fatigue, excessive sweating, decreased appetite, dyspnea (a feeling of lack of air during physical exertion, then at rest, worsening in the supine position), and palpitations in the child [4,12,68].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: these complaints should be the basis for suspecting CHF in a child, while at the same time they may also be caused by extracardiac pathology.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: the presence of congenital heart disease (CHD) in a child, previous surgical intervention for CHD, inflammatory myocardial disease, the presence of heart disease, or cases of sudden death in first-degree relatives increase the likelihood of HF in the patient. Abnormal development may indicate a possible genetic pathology that may include cardiac anomalies. Short stature may indicate a long-standing cardiac problem. Infectious diseases can act both as an etiological factor of heart failure and contribute to an increase in the child's metabolic demands, thereby helping to uncover the underlying condition. In individuals with a history of congenital heart disease, a complete review of all medical records and imaging studies is required [81].

2.2 Physical Examination

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: the most common clinical signs and symptoms detected during physical examination in children are presented in Table 6. Special attention should be paid to height and weight characteristics (lag in physical development), body temperature (affects heart rate and respiratory rate), respiratory rate (RR), and heart rate (HR). Perform auscultation of the heart and lungs, measure resting blood pressure, and assess for the presence of peripheral edema and hepatosplenomegaly.

Table 6. Characteristic clinical signs of CHF in children

2.3 Laboratory Diagnostics

LOD 2, GOR A

Comments: natriuretic peptides are biological markers of CHF. The test allows for: effective screening for heart failure—a normal natriuretic peptide level in untreated patients provides grounds to exclude CHF; assessing the severity of CHF, disease dynamics, and the effectiveness of ongoing therapy.

Level of Proof 5, Grade of Recommendation C

- complete blood count (hemoglobin, red blood cells, platelets, white blood cells, hematocrit);

- acid-base balance and blood gas analysis;

- serum C-reactive protein level;

- serum iron, transferrin, and blood ferritin levels;

- blood electrolyte levels (sodium, potassium, chlorides, calcium, magnesium);

- blood creatinine, urea, and glomerular filtration rate (calculated parameter);

- blood glucose level;

- total and direct bilirubin levels in the blood;

- activity of aspartate aminotransferase, alanine aminotransferase, creatine kinase, creatine kinase-MB, and lactate dehydrogenase in the blood;

- total protein and albumin levels in the blood;

- blood levels of thyroid-stimulating hormone, free triiodothyronine (FT3), and free thyroxine (FT4);

- coagulogram (exploratory hemostasis screening): prothrombin, prothrombin index, thrombin time, international normalized ratio (INR), fibrinogen, activated partial thromboplastin time.

Comment: in the presence of factors predisposing to thrombosis (arrhythmias, prosthetic valves, significant cardiac chamber dilation, sharp decrease in contractility, history of thromboembolism, signs of left ventricular thrombosis), testing blood levels of D-dimer and soluble fibrin monomer complexes (SFMC) is indicated.

If signs of iron deficiency anemia are detected, further treatment of this condition should be carried out in accordance with the clinical guidelines for "Iron deficiency anemia".

LMR 3, LGR B

2.4 Instrumental Diagnostics

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: there are no specific signs unique to CHF, but in the presence of a completely normal ECG, CHF is unlikely.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: detection of chronic tachyarrhythmias or prolonged tachycardia paroxysms requires ruling out an arrhythmogenic origin of CHF.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Level of Proof 5, Grade of Recommendation C

Comments:

The following must be mandatory evaluated during the initial or follow-up examination:

- Assessment of cardiac anatomy and great vessels (presence of intracardiac shunts, blood flow obstruction);

- Measurement of left ventricular (LV) and right ventricular (RV) wall thicknesses;

- Measurement of LV end-diastolic and end-systolic dimensions, end-diastolic volume, and end-systolic volume, with determination of the standard deviation of the parameter from the mean for the given height-weight parameter (z-score) [21];

- Determination of LV ejection fraction using the biplane method of disks (Simpson's method, normal in young children > 55%, in older children > 50%); Since methods for calculating EF by Teichholz and fractional shortening are based on linear dimensions, they are currently not recommended for clinical use because they can yield inaccurate results in patients with regional left ventricular wall motion abnormalities;

- Determination of right ventricular function: measurement of tricuspid annular plane systolic excursion (TAPSE) (normal in adults > 20 mm, in children depends on age) and/or measurement of right ventricular fractional area change [22,23];

- Assessment of pressure in the right heart chambers;

- Assessment of left and right atrial dimensions;

- Assessment of heart valve function (aortic, pulmonary, mitral, tricuspid);

- Assessment of LV diastolic function.

Additional studies during echocardiography:

- Assessment of left ventricular global longitudinal strain (GLS) reflects the averaged degree of left ventricular systolic shortening along the long axis [24].

GLS has higher sensitivity in assessing left ventricular systolic function compared to EF, and therefore can be used to detect early changes in LV contractility.

- Transesophageal echocardiography may be recommended for patients with complex congenital and acquired heart defects, suspected infective endocarditis, and intracardiac thrombosis [25].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: normal heart dimensions do not exclude the presence of diastolic HF. The presence of pulmonary venous congestion is a criterion for CHF severity, and the dynamics of these changes serve as a marker of therapy efficacy.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: Cardiac MRI is an accurate method for assessing heart chamber dimensions and volumes, myocardial mass, RV and LV function, blood flow velocity and volume in large vessels, myocardial structure, perfusion defects, and areas of necrosis and/or fibrosis. MRI is informative in assessing cardiac morphology and function in patients with cardiomyopathies (especially apical HCM and non-compaction cardiomyopathy). It is recommended that the study be performed and its results interpreted by specialists with experience in cardiac imaging and the evaluation of myocardial diseases.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Level of Evidence (LE) 4, Grade of Recommendation (GR) C

Comments: Cardiopulmonary exercise testing (cardiopulmonary exercise testing with spiroergometry) is preferred. This method has age limitations. A cycle ergometer or treadmill is used during the study. The child's subjective reaction, ECG changes, blood pressure, and peak oxygen consumption are evaluated. The results are compared with normative values appropriate for age, gender, and body surface area [33]. In routine practice, the 6-minute walk test serves as an alternative to the cardiopulmonary exercise test [34].

2.5 Other Procedures

No other additional diagnostic studies are indicated for children with CHF.

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

Treatment goals:

• Improvement in well-being;

• Reduction in the severity of heart failure manifestations;

• Improvement in quality of life;

• Improvement in prognosis.

Principles of chronic heart failure management:

• Addressing the etiological factor;

• Reducing the demands on cardiac output (restriction of physical activity, maintaining thermal comfort, reducing peripheral vascular resistance);

• Targeting the myocardium (increasing myocardial contractility, reducing afterload, regulating circulating blood volume);

• Correction of homeostasis disorders and prevention/treatment of complications (correction of electrolyte balance and acid-base status, elimination of neurohormonal shifts, correction of iron deficiency anemia, prevention and treatment of thromboembolic syndrome);

• Heart rate regulation and treatment of cardiac arrhythmias and conduction disturbances.

3.1. Conservative management

General management measures for CHF are usually similar and do not depend on the underlying causes of CHF.

3.1.1. Lifestyle and dietary therapy

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: Complete restriction of physical activity is highly undesirable as it promotes deconditioning and a reduction in the adaptive mechanisms of the cardiovascular system. Reduction of physical activity in an infant can be achieved by stopping breastfeeding and switching to expressed breast milk from a bottle, or tube feeding if necessary.

In CHF, the replenishment of energy losses against the background of daily nutrient intake restriction becomes an acute problem. Patients with NYHA functional class III-IV CHF exhibit marked structural remodeling of the small intestinal mucosa, manifested by increased collagen deposition within it, as well as villous atrophy, leading to morphofunctional disorders [35]. This results in increased energy demands, reduced food intake, and macronutrient and micronutrient malabsorption.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: Assessment of physical development can be performed using "WHO Anthro", WHO "AnthroPlus 2009" software, WHO, Geneva, Switzerland.

Table 7. Classification of malnutrition

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: Restriction of fluid intake relative to physiological needs (Table 8) should be determined by the severity of myocardial dysfunction and the clinical manifestations of heart failure.

Table 8. Physiological fluid requirements in children by age [37].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

3.1.2. Therapy recommended for patients with systolic CHF

Level of Proof 5, Grade of Recommendation C

Comments: Currently, the same drug classes are used to treat CHF in children as in adults.

The main principles of treatment for HFrEF are:

- Prescription of the 3 main drug classes to reduce RAAS and SNS activity: ACE inhibitors/ARBs/ARNI, MRAs, beta-blockers;

- Prescription of diuretics is recommended for patients with congestive symptoms to improve clinical status, although their effect on the prognosis of CHF patients has not been studied;

- The use of cardiac glycosides in patients with CHF is limited. Of the existing drugs, digoxin is recommended; the efficacy and safety of other cardiac glycosides in CHF have not been sufficiently studied. The administration of digoxin does not improve survival;

- Long-term use of positive inotropic agents in patients with CHF is contraindicated as it leads to increased mortality.

Medicines for the treatment of HFrEF can be divided into two main categories according to the level of evidence (Table 9, Table 10) [41].

Medicinal products for the treatment of patients with CHF are used in accordance with the classification and rating of benefit or efficacy, as well as the level of evidence. Medical treatment of patients with CHF cannot be intermittent and implies lifelong drug therapy when the cause of CHF cannot be eliminated.

Table 9. Drugs for the treatment of HFrEF

Table 10. Pharmacological treatment of patients with HFrEF (< 40%) and HFmrEF (41–49%). Drugs proven to reduce the risk of death and hospitalization specifically in CHF and used in all patients

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comment:

ACE inhibitor prescribing algorithm:

- ACE inhibitors are prescribed in the absence of absolute contraindications (bilateral renal artery stenosis and angioedema) and in the presence of normal laboratory parameters (potassium, creatinine);

- selection of therapy is carried out in a specialized inpatient setting with blood pressure monitoring, starting from a low dose with its gradual titration to the therapeutic dose (Table 11);

- arterial hypotension is not a contraindication to the prescription of ACE inhibitors;

- prescribing minimum doses of ACE inhibitors is better than omitting them; one should strive to achieve the target dose;

- monitoring of blood biochemistry (urea, creatinine, potassium) 1–2 weeks after the start of ACE inhibitor dose titration.

If a cough specifically related to the prescription of an ACE inhibitor occurs (the cough stops when the ACE inhibitor is discontinued and returns when therapy is resumed), the ACE inhibitor should be replaced with an ARB.

In case of acute renal impairment (an increase in creatinine concentration by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within 48 hours; or an increase in creatinine concentration by ≥ 1.5 times compared to baseline (if known, or presumed to have occurred within the preceding 7 days); or urine output < 0.5 mL/kg/hour for 6 hours), it is necessary to discontinue all drugs with potential nephrotoxic effects and potassium-sparing diuretics, switch the patient to an ACE inhibitor with a dual elimination pathway (liver-kidney) — #ramipril**, and reduce the ACE inhibitor dose by half [42].

Table 11. Starting and therapeutic doses of ACE inhibitors used for the treatment of children with CHF [42]

In children under 18 years of age, the use of drugs in this group is off-label.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Table 12. Starting and therapeutic doses of ARBs used for the treatment of children with CHF [42]

Comment: the principles of prescribing ARBs are similar to the principles of prescribing ACE inhibitors.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comment: it is recommended to prescribe the drug #valsartan + sacubitril** at a low starting dose when the patient's clinical condition is stable. Switching to #valsartan + sacubitril** is carried out no earlier than 36 hours after taking the last dose of an ACE inhibitor.

If patients have previously taken ACE inhibitors/ARBs, it is recommended to prescribe #valsartan + sacubitril** at an initial dose of 1.6 mg/kg (max. 50 mg) twice daily, followed by gradual titration to the therapeutic dose of 3.1 mg/kg twice daily [82,83]. If the patient has not previously taken ACE inhibitors/ARBs or has taken them in a non-therapeutic dose, it is recommended to initiate therapy at a dose half the usual recommended starting dose [83].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments:

Algorithm for prescribing BBs:

- BBs are prescribed in the absence of contraindications (bronchial asthma, symptomatic bradycardia, second-degree or higher atrioventricular block) and in a stable patient condition (without intravenous inotropic support, without signs of severe congestion);

- initiation of therapy with a low dose, with a gradual increase in dose under the control of blood pressure and heart rate, urine output, and body weight dynamics;

- prescribing minimum doses of beta-blockers is better than not prescribing them at all, but one should strive to reach the target dose.

In the first days of treatment and during beta-blocker dose titration, transient disorders may develop: hypotension, bradycardia, worsening of heart failure, which requires their timely management. If heart failure symptoms increase, the diuretic dose should be increased and/or the beta-blocker dose temporarily reduced; if bradycardia occurs, the dose should be reduced or heart rate-lowering drugs (e.g., digoxin, amiodarone) should be discontinued. Once the patient's condition stabilizes, dose titration to target therapeutic levels should be continued.

For infants and young children, a twice-daily dosing regimen of the beta-blocker is preferred; individual hypersensitivity to the drug is also possible – in such situations, a lower dose of the beta-blocker may be required.

Table 13. Starting and therapeutic doses of beta-blockers used in the treatment of children

Information on the titration algorithm for ACE inhibitors and beta-blockers in infants can be found in Appendix B [43].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments:

Algorithm for MRA prescription:

- the drug is prescribed provided there is no hyperkalemia and significant renal dysfunction;

- blood potassium and creatinine levels are monitored at 1, 4, 8, and 12 weeks, 6, 9, and 12 months, and every 6 months of treatment thereafter;

- in the event of hyperkalemia (increase in blood potassium level > 5.5 mmol/L), the MRA dose must be halved with continuous monitoring of blood biochemical parameters; in case of hyperkalemia ≥ 6.0 mmol/L, MRA must be discontinued, and continuous monitoring of blood electrolytes must be performed;

- in case of acute kidney injury (increase in creatinine concentration by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within 48 hours; or increase in creatinine concentration ≥ 1.5-fold from baseline (if known or presumed to have occurred within the prior 7 days); or urine output < 0.5 mL/kg/h for 6 hours), the MRA dose must be halved with continuous monitoring of blood biochemical parameters; with a further increase in blood creatinine, aldosterone antagonists must be discontinued, with continuous monitoring of blood electrolytes and treatment of the condition.

If gynecomastia develops during MRA therapy in male patients or menstrual irregularities in female patients, it is recommended to switch spironolactone to the selective aldosterone antagonist #eplerenone (for children over 4 years of age: 0.5 mg/kg/24 h, up to a maximum of 25 mg/24 h) [42].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comment: the main indication for prescribing #dapagliflozin** is type 2 diabetes mellitus; however, the results of the DAPA-HF trial in the adult population demonstrated that the administration of #dapagliflozin** in patients with CHF and reduced myocardial contractility without diabetes mellitus was accompanied by a reduction in the risk of cardiovascular death and heart failure hospitalizations. Currently, dapagliflozin is included in the European guidelines for the treatment of chronic heart failure in patients with preserved and reduced EF [39]. In the pediatric population of patients with CHF, one observational study on the efficacy of #dapagliflozin** has been published to date, according to which the drug proved effective and safe and demonstrated that the addition of dapagliflozin to therapy was accompanied by a significant decrease in natriuretic peptide levels and an increase in EF. The drug is prescribed orally at a dose of 0.1-0.2 mg/kg/24 h once daily, max. 10 mg/24 h [45,83].

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comment: diuretics are not among the main groups of drugs used for the pathogenetic treatment of CHF, but their use, along with reducing pre- and afterload, leads to an improvement in the functional state of internal organs. In patients with CHF, diuretics should be used in combination with beta-blockers, ACE inhibitors/ARBs, and MRAs. The doses of diuretics are determined individually, taking into account the child's age, stage of CHF, severity of edema syndrome, response to previously used doses, etc. (Table 14).

Diuretic prescription algorithm:

- therapy starts with a low effective dosage, which is gradually increased until symptoms disappear;

- once fluid congestion symptoms resolve and a stable body weight is achieved, the diuretic dose can be considered adequate in the absence of signs of renal impairment and dehydration;

- the goal of diuretic therapy is to achieve a state of euvolemia using the minimum diuretic dosage;

- once compensation is achieved, a fixed dose of diuretics is recommended, which may be adjusted based on body weight monitoring, fluid intake, and output results;

- during diuretic therapy, regular monitoring of blood pressure, potassium, sodium, creatinine, and urea levels is recommended;

- phenomena of CHF decompensation require increasing the diuretic dose due to the development of hypoperfusion and bowel wall edema, which leads to impaired drug absorption;

- in case of diuretic resistance or heart failure decompensation, switching to intravenous drug administration, adding additional diuretics or inotropic agents to the therapy is possible;

- the first-line drugs for heart failure therapy are loop or thiazide diuretics.

Table 14. Doses of diuretics most frequently used for the treatment of children with CHF [42]

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: thiazides are not recommended for patients with low blood pressure and a tendency to collapse reactions, as they produce the most pronounced hypotensive effect. Thiazides are ineffective when renal function is reduced.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: furosemide** produces a rapid, powerful, but short-lived diuretic effect; the drug's action begins in an hour and lasts 4-6 hours, while with intravenous administration, the effect occurs within 10-15 minutes and lasts from two to three hours. In concomitant renal failure, the dose of furosemide** is increased to up to 5 mg/kg/day. The drug has a quite pronounced withdrawal syndrome.

#Torasemide additionally possesses antialdosterone and antifibrotic activity. 10 mg of torasemide correspond to 40 mg of furosemide**. Use of the drug in children is off-label.

Table 15 presents potential disorders associated with the use of loop diuretics [4].

Table 15. Potential complications associated with the use of loop diuretics

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: clinical observations demonstrate the efficacy of #digoxin** in children with CHF by reducing symptoms, improving myocardial contractility, and decreasing neurohormonal activation (lower catecholamine levels and RAAS activity), which suggests that prescribing maintenance doses of #digoxin** is pathogenetically justified in children with systolic CHF.

Currently, in the treatment of CHF, it is recommended to use a maintenance dose of #digoxin**: 10–12 mcg/kg for infants, 8–10 mcg/kg for children over one year of age, and 0.125 mg for adolescents weighing less than 55 kg, at which its extracardiac neuromodulatory effect is fully manifested without pronounced proarrhythmic effects [4].

#Digoxin** in combination with diuretics is the initial treatment regimen for CHF caused by uncorrected congenital heart defects with volume overload and no outflow obstruction.

During therapy with #digoxin**, ECG monitoring is required (risk of arrhythmias).

Level of Reliable Evidence 2, Strength of Recommendation Grade B

Comments: #Ivabradine** reduces heart rate by selectively inhibiting ionic current in the If-channels of the sinus node without affecting myocardial inotropic function. The drug is effective only in patients with sinus rhythm. The drug may also be used in patients with sinus rhythm and symptoms of CHF NYHA class II-IV who have beta-blocker intolerance.

#Ivabradine** is prescribed at an initial dose of 0.1 mg/kg/day in 2 divided doses (maximum 10 mg/day in 2 divided doses), and the maximum dose is 0.3 mg/kg/day in 2 divided doses (maximum 15 mg/day in 2 divided doses) in children aged 6–18 years [42].

Level of Proof 5, Grade of Recommendation C

Comments: #Levosimendan** is a non-glycoside cardiotonic agent. The administration of levosimendan is indicated as a short-term treatment for acute decompensation of severe chronic heart failure (CHF) when standard therapy is ineffective and inotropic therapy is required. In patients with CHF, the positive calcium-dependent inotropic and vasodilating effects of #levosimendan** lead to increased myocardial contractility, reduced preload and afterload, without impairing diastolic function. It activates the ischemic myocardium in patients following percutaneous transluminal coronary angioplasty or thrombolysis. #Levosimendan** increases cardiac output, stroke volume, ejection fraction, and heart rate (HR), reduces systolic and diastolic blood pressure (BP), pulmonary capillary wedge pressure, right atrial pressure, and total peripheral vascular resistance. #Levosimendan** is administered as an infusion over 1 hour at a dose of 12 mcg/kg, followed by a continuous infusion at a dose of 0.1-0.2 mcg/kg/min for 24 hours [42].

Dobutamine** is a selective beta1-adrenoreceptor agonist that exerts a positive inotropic effect on the heart, moderately increases heart rate, increases stroke volume and cardiac output, decreases total peripheral resistance and pulmonary vascular resistance; at medium and high doses (7.5–10 mcg/kg/min), it increases heart rate and systemic blood pressure while decreasing ventricular filling pressure; at low doses (2–4 mcg/kg/min), it increases renal and coronary blood flow and improves myocardial oxygen supply. Considering the potential tachycardic and arrhythmogenic effects of the dobutamine** stimulant, the drug is used in short courses for stage III heart failure (НК III) under continuous blood pressure and ECG monitor control.

Dopamine** is an alpha-, beta1-, beta2-adrenergic agonist and dopamine receptor stimulant. The drug is administered as an infusion at a dose of 4 to 10 mcg/kg/min in cases of decompensated refractory heart failure to increase cardiac output, stabilize systemic blood pressure, and increase diuresis. Its action begins 5 minutes after the start of the infusion, with the maximum effect in 5-7 minutes.

Level of Proof 5, Grade of Recommendation C

Comment: #Amiodarone** (10 mg/kg/day in two divided doses, max. 200 mg x 2 times/day for 10 days, followed by a switch to 5 mg/kg/day in 1-2 divided doses) is effective against both supraventricular and ventricular arrhythmias, does not impair myocardial contractility, and exhibits peripheral vasodilator properties [12,84]. Off-label use in children.

#Sotalol** is prescribed at a dose of 2 to 6 mg/kg/day in 2-3 divided doses, considering its pronounced beta-blocking properties [12,84]. Off-label use in children.

LeveL of Evidence (LoE) 4, Grade of Recommendation (GoR) C

Level of Proof 5, Grade of Recommendation C

Level of Proof 5, Grade of Recommendation C

Comment: heparin sodium** is administered intravenously; the initial dose is 75-100 IU/kg IV bolus over 10 minutes; maintenance dose: infants aged 1-3 months - 25-30 IU/kg/h (800 IU/kg/day), infants aged 4-12 months - 25-30 IU/kg/h (700 IU/kg/day), children older than 1 year - 18-20 IU/kg/h (500 IU/kg/day) by continuous intravenous infusion, controlled by aPTT (prolonged 1.5-fold compared to baseline) [55].

Low molecular weight heparins (#enoxaparin sodium**) subcutaneously at a therapeutic dose: in children < 2 months, 1.5 mg/kg/dose every 12 hours; in children > 2 months, 1 mg/kg/dose every 12 hours; at a prophylactic dose: in children < 2 months, 0.75 mg/kg/dose every 12 hours; in children > 2 months, 0.5 IU/kg/dose every 12 hours, controlled by anti-Xa factor activity (target value 0.5-1 at 4-6 hours after subcutaneous administration) [55].

Warfarin** - initial dose 0.1-0.2 mg/kg/day monitored by INR every 1-3 days, aiming for a target value of 2.0-3.0 (2.5-3.5 for a mechanical mitral valve prosthesis). Before starting treatment, it is necessary to ensure the absence of high bleeding risk factors (coagulopathies, gastrointestinal ulcer lesions, etc.). After establishing the maintenance dose, continuous administration is continued with regular INR monitoring.

Level of Proof 5, Grade of Recommendation C

3.1.3. Therapy recommended for patients with diastolic HF

Level of Proof 5, Grade of Recommendation C

Comments: no studies have been dedicated to the treatment of diastolic heart failure in children; however, an analysis of previously conducted studies in the adult heart failure population demonstrates the ability of ACE inhibitors / ARBs / ARNI, beta-blockers, MRAs, and SGLT2 inhibitors to reduce mortality and the number of repeat hospitalizations in patients with heart failure with preserved ejection fraction.

Level of Proof 5, Grade of Recommendation C

3.2. Surgical treatment

3.2.1. Cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is performed by implantation of a biventricular pacemaker (233950 Implantable three-chamber pacemaker (biventricular)***); it improves the electromechanical pattern of myocardial activation, enhances systolic function, and promotes reverse remodeling of the LV, which is accompanied by an improvement in the HF functional class and a reduction in HF-associated mortality [64-67].

LeveL of Evidence (LoE) 4, Grade of Recommendation (GoR) C

• CRT may be recommended (A16.10.014.004 Implantation of a three-chamber pacemaker (resynchronization therapy), 233950 Implantable three-chamber pacemaker (biventricular)***) in symptomatic patients with a systemic RV, HF (Ross/NYHA HF functional class II-IV), receiving optimal medical therapy, with an LVEF < 35%, sinus rhythm with a wide QRS complex (intrinsic or paced) exceeding the upper limit of normal for age, and right bundle branch block morphology, in order to reduce symptom severity [66].

LeveL of Evidence (LoE) 4, Grade of Recommendation (GoR) C

• CRT may be recommended (A16.10.014.004 Implantation of a three-chamber pacemaker (resynchronization therapy), 233950 Implantable three-chamber pacemaker (biventricular)***) in symptomatic patients with a single ventricle, HF (Ross/NYHA HF functional class II-IV), receiving optimal medical therapy, with an LVEF < 35%, sinus rhythm with a wide QRS complex (intrinsic or paced) exceeding the upper limit of normal for age, and bundle branch block morphology, in order to reduce symptom severity [67].

LeveL of Evidence (LoE) 4, Grade of Recommendation (GoR) C

Comments: the best CRT results have been achieved in the group of patients with pacemaker-induced cardiomyopathy. The presence of the LV in the systemic position was an independent predictor of ventricular systolic function improvement during CRT. A predictor of CRT failure is the presence of dilated cardiomyopathy in the patient. CRT is effective when combined with other corrective or palliative cardiac surgery.

3.2.2. Implantable cardioverter-defibrillator implantation

Level of Evidence (LE) 4, Grade of Recommendation (GR) C

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Mechanical circulatory support devices

LeveL of Evidence (LoE) 4, Grade of Recommendation (GoR) C

Comments: patients with dilated and hypertrophic cardiomyopathy, congenital heart defects, and pacemaker-associated myocardial dysfunction (in the absence of response to CRT) may be considered as candidates for ventricular assist device implantation. Long-term circulatory support systems are not recommended in the presence of:

• irreversible renal, hepatic, or pulmonary dysfunction resulting from chronic diseases;

• active systemic infection;

• malignant neoplasms;

• severe neurological deficit;

• blood coagulation disorders;

• lack of social support / treatment adherence (rarely).

In all cases, the decision is made individually for each patient with a careful assessment of benefits and potential complications.

Extracorporeal membrane oxygenation

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: patient selection for ECMO is critically important.

Absolute contraindications to ECMO:

- chromosomal abnormalities with early lethality;

- severe neurological pathology;

- incurable malignant neoplasms.

Relative contraindications for ECMO:

- prolonged mechanical ventilation (> 14 days);

- neurosurgical procedures or intracranial hemorrhage within the last 7 days;

- chronic diseases with an unfavorable prognosis.

High-risk conditions for ECMO:

- pertussis pneumonia and disseminated herpesvirus infection;

- active cytomegalovirus infection;

- severe multiple organ failure;

- severe coagulopathy and thrombocytopenia.

In clinical practice, ECMO is frequently used as a method of circulatory support:

- following cardiac surgery, typically after surgical correction of congenital heart disease (CHD);

- during heart or lung transplantation;

- in myocarditis or graft rejection reaction.

Heart transplantation

Level of Evidence (LE) 4, Grade of Recommendation (GR) C

Comments: the main indications for HT in pediatric patients:

- end-stage myocardial diseases with systolic and/or diastolic dysfunction (e.g., cardiomyopathies, myocarditis);

- incurable congenital heart disease (especially patients with CHD with hemodynamics following Glenn/Fontan procedures);

- life-threatening arrhythmias refractory to medical therapy;

- incurable cardiac tumors causing blood flow obstruction or ventricular dysfunction;

- heart retransplantation;

- patients who cannot be weaned from mechanical circulatory support devices.

During the first year of life, the primary indication for HT is congenital heart disease, whereas in older children, it is dilated cardiomyopathy. First-year survival following transplantation is 90%. Five-year survival is 75%.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

The goal of rehabilitation is to assist patients and their families in obtaining information about the disease, acquiring self-management skills regarding dietary recommendations, physical activity, strict adherence to medication regimens, monitoring of CHF symptoms, and seeking medical care if they worsen. Patients should receive educational materials containing information on self-management, diet, weight control, physical activity, proper medication administration, etc.

An important aspect in the successful treatment of CHF is compliance with dietary and physical activity recommendations.

Rehabilitation measures should be aimed at maintaining cardiac and pulmonary function. Regular aerobic exercise is recommended for patients with heart failure (HF) to improve their functional status and HF symptoms. Contraindications to physical training include life-threatening cardiac arrhythmias, active myocarditis and pericarditis, progressive HF with decreased exercise tolerance or resting dyspnea in the preceding 3-5 days, severe heart valve stenoses, severe obstructive hypertrophic cardiomyopathy, intracardiac thrombosis, and acute systemic diseases.

Patients and family members should also receive clinical and psychological counseling and support to resolve problems, facilitate the patient's adaptation within the family and society, help maintain family bonds, and reorient family roles due to a family member's illness.

5. Prevention and Dispensary Observation

Prevention of chronic heart failure (CHF) consists of the early detection of diseases accompanied by the development of heart failure, and the prevention of worsening conditions in already diagnosed CHF. In case of clinical deterioration, hospitalization is required to adjust the ongoing therapy.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Comments: all patients with signs of CHF must be under dispensary follow-up (dispensary observation) by a local cardiologist. Dispensary follow-up is carried out for the primary disease in accordance with established timelines. If signs of CHF persist in patients after reaching 18 years of age, it is advisable to continue further dispensary follow-up with an adult cardiologist.

6. Organization of Medical Care

Medical care for children with CHF is provided in accordance with the following levels:

Level 1:

- provision of primary (including specialized cardiological) health care in outpatient settings;

- if signs of HF are detected, the child must be referred to a level 2 or 3 medical organization (inpatient facility);

- after the diagnosis of HF is established, the child must be under the dispensary follow-up of a pediatrician and pediatric cardiologist at their place of residence, taking into account the recommendations of level 2–3 specialists. The frequency of follow-up is determined based on the severity of HF;

- in case of clinical deterioration and/or development of complications, the child must receive a referral for hospitalization to a level 2–3 medical organization or be hospitalized on an emergency basis.

At level 1, a child with HF (functional class I–II in the absence of life-threatening arrhythmias) may be referred for rehabilitation if there are no medical contraindications.

Level 2:

- provision of specialized cardiological medical care, including primary specialized care;

- referral for examination and treatment in the presence of medical indications to level 3 medical organizations.

Level 3:

- provision of scheduled, urgent, and emergency specialized cardiological care, including high-tech medical care;

- preparation and referral for cardiac surgery or endovascular procedures.

Indications for emergency hospitalization in a medical organization (inpatient facility): CHF decompensation, hemodynamic instability, presence of life-threatening cardiac arrhythmias.

Life-threatening conditions in HF decompensation include cardiogenic shock, signs of hypoperfusion, signs of severe hypervolemia in one or both circulatory loops, life-threatening cardiac arrhythmias, and oxygen saturation (SpO₂) < 90%.

Indications for planned hospitalization in a medical organization:

- provision of specialized cardiological care requiring continuous medical supervision and performance of therapeutic procedures;

- conducting examinations in case of suspected HF and the need to prescribe or adjust HF therapy.

The duration of hospital stay depends on the severity of the condition and the stage of CHF, and typically is: for CHF stage IIB–III — 3–4 weeks, CHF stage IIB–A — 2–3 weeks, CHF stage IIA–I — 7–14 days. In a stable condition with circulatory insufficiency stage I and no need for therapy adjustment, stay in a day hospital setting is possible.

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

- relief of HF decompensation symptoms; stabilization of hemodynamic parameters, completion of necessary diagnostic measures; prescription of required drug therapy, its satisfactory tolerability, and the absence of significant side effects.

Rehabilitation of children with HF (functional class I–II in the absence of life-threatening arrhythmias) is carried out in specialized rehabilitation centers/departments in the absence of medical contraindications.

Sanatorium-resort treatment for children with HF (functional class I–II in the absence of life-threatening arrhythmias) is possible on the basis of specialized children's sanatoriums.

7. Additional Information

7.1. Factors influencing the outcome of a disease or condition

The prognosis of CHF is determined by the severity of the disease and the underlying condition that caused its development. According to the U.S. Pediatric Cardiomyopathy Registry, up to 50% of children with CHF die within 5 years. According to the British Heart Foundation, 34% of children with newly onset CHF due to myocardial injury require a heart transplant or die within the first year of follow-up.

7.2. Vaccine prophylaxis in children with CHF

Children with conditions accompanied by CHF should be considered an immunocompromised group. The close morphofunctional connection between the cardiovascular and bronchopulmonary systems (where acute bronchopulmonary diseases can complicate the course and outcome of heart failure) makes vaccination against pneumotropic infections mandatory once hemodynamic disorders are minimized, including during medical therapy for CHF.

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Level of trustworthiness of evidence (LTE) 5, Level of recommendation (LR) C

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Basargina E.N., MD, Professor (Moscow) – Chair of the Working Group, Member of the Association of Pediatric Cardiologists of Russia

Vasichkina E.S., MD (Saint Petersburg) – Member of the Association of Pediatric Cardiologists of Russia

Gandaeva L.A., Cand. Med. Sci. (Moscow) – Member of the Association of Pediatric Cardiologists of Russia

Zharova O.P., Cand. Med. Sci. (Moscow) – Member of the Association of Pediatric Cardiologists of Russia

Kovalev I.A., MD, Professor (Moscow) – Member of the Association of Pediatric Cardiologists of Russia

Koloskova N.N., MD (Moscow) – Member of the Russian Cardiological Society

Kotlukova N.P., MD, Professor (Moscow) – Member of the Association of Pediatric Cardiologists of Russia

Leontyeva I.V., MD, Professor (Moscow) – Member of the Association of Pediatric Cardiologists of Russia

Pervunina T.M., MD (Saint Petersburg) – Member of the Association of Pediatric Cardiologists of Russia

Ryabtsev D.V., Cand. Med. Sci. (Moscow) – Member of the Russian Cardiological Society

Trunina I.I., MD, Professor (Moscow) – Member of the Association of Pediatric Cardiologists of Russia

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

The clinical guidelines were developed by expert specialists of the All-Russian Public Organization "Association of Pediatric Cardiologists of Russia" based on the achievements of evidence-based medicine, domestic and foreign clinical experience in the treatment of chronic heart failure in children. The basis of this version of the clinical guidelines was formed by Russian and foreign fundamental guidelines and monographs on pediatric cardiology and cardiology, research results, and the latest versions of European and American guidelines. The sources for modern updates were journal publications in authoritative peer-reviewed journals included in Russian and foreign science citation indices.

Target audience for these clinical guidelines:

1. Pediatric cardiologist.

2. Pediatrician.

3. Cardiovascular surgeon.

4. General practitioner (family physician).

The development utilized the system of levels of evidence certainty (LEC) and levels of recommendation grades (LRG) for therapeutic, rehabilitative, preventive, and diagnostic interventions (Tables PA2-1, PA2-4, and PA2-2), introduced in 2018 by the Center for Healthcare Quality Assessment and Control of the Russian Ministry of Health.

Table PA2-1. Scale for assessing the levels of reliability of evidence (LRE) for diagnostic methods (diagnostic interventions)

Table PA2-1. Scale for assessing levels of evidence certainty (LEC) for methods of prevention, treatment, and rehabilitation (preventive, therapeutic, and rehabilitative interventions)

Table PA2-1. Levels of Clinical Effectiveness (LE) rating scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

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

Appendix A3. Reference Materials

1. Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, "On approval of the procedure and timeframe for the development of clinical guidelines, their revision, the standard template of clinical guidelines, and requirements for their structure, composition, and scientific validity of the information included in clinical guidelines."

2. Order of the Ministry of Health of the Russian Federation No. 440n dated October 25, 2012 "On approval of the Procedure for the provision of medical care in the field of 'pediatric cardiology'."

3. Order of the Ministry of Health of the Russian Federation No. 203n dated May 10, 2017 "On approval of criteria for assessing the quality of medical care."

4. Methodological recommendations for assessing the validity of evidence and clinical effectiveness of recommendations. FSBI "CECCMP" of the Russian Ministry of Health, 2018.

5. Decree of the Government of the Russian Federation No. 3053-r dated December 31, 2018 "On approval of the list of medical devices implanted in the human body when providing medical care under the state guarantee program of free medical care for citizens, as well as the list of medical devices dispensed upon prescriptions for medical devices when providing a set of social services."

6. Decree of the Government of the Russian Federation No. 2406-r dated October 12, 2019 "On approval of the list of vital and essential drugs, as well as lists of drugs for medical use and the minimum assortment of drugs required for the provision of medical care."

Appendix B. Physician Action Algorithms

Algorithm for prescribing ACE inhibitor and BB therapy in infants

On the first day, ACE inhibitor therapy is prescribed at 1/10 of the therapeutic dose; the next day, BBs are added, also starting at 1/10 of the therapeutic dose. Subsequently, the dose is increased every other day, adhering to the rule of alternating the dose-escalation days for ACE inhibitors and BBs. The patient's body weight, fluid intake and output, respiratory rate, heart rate, and presence of hepatomegaly are monitored daily. If necessary, the dose titration rate can be slowed down or accelerated [77].

Appendix C. Patient Information

Heart failure (HF) is a syndrome reflecting the heart's inability to maintain blood circulation adequate to the body's metabolic demands. HF is not an independent disease; it is a complication that develops in the course of various diseases/conditions affecting both the cardiovascular system and other organs and systems.

HF can be acute or chronic, left-sided or right-sided, systolic or diastolic. HF can develop in children of any age and sex.

Chronic heart failure (CHF) is a condition characterized by a gradual worsening of HF symptoms/signs, long-standing and typically progressive, up to the development of "decompensation".

In early childhood, CHF may be a manifestation of congenital heart defects or myocarditis; in older children, cardiomyopathies; and at any age, cardiac arrhythmias.

The main manifestations of HF include: increased fatigue, sweating, decreased appetite, shortness of breath (labored, frequent breathing), tachycardia (increased heart rate), and edema. In infants, the first symptoms may include poor weight gain, sweating during feeding, and prolonged feeding times. If such symptoms appear, it is necessary to consult a physician to rule out conditions accompanied by the development of HF. If cardiovascular pathology is suspected, the child undergoes a comprehensive examination after a medical evaluation to determine the nature of the pathology.

To clarify the diagnosis, laboratory and instrumental examinations may be required. Commonly prescribed laboratory tests include: complete blood count, urinalysis, blood chemistry with electrolyte levels, blood gas analysis, and natriuretic peptide. Instrumental diagnostic methods include: electrocardiogram, chest X-ray, and echocardiography.

If a disease is identified, the physician will recommend a treatment regimen that must be strictly followed. The scope of therapy depends on the severity of HF signs, its stage, and functional class. In some cases, hospitalization may be required for further evaluation and selection of therapy (in cases of severe/decompensated HF, intravenous medications and mechanical ventilation may be required).

The main and crucial aspects of CHF management include:

• Physical activity restriction. Bed rest is indicated only for patients with severe (stage 2B-3) HF until their condition stabilizes, followed by a gradual increase in physical activity. The permissible level of physical activity is determined individually for each patient, taking into account the underlying disease that led to heart failure. Children with CHF should not participate in sports, school physical education classes, or active recreation.

• Diet. Rational nutrition appropriate for the child's age is essential in the treatment of CHF. Monitoring fluid intake and output is important. For underweight children, specialized high-calorie products are indicated. For infants in their first year of life, partial substitution of formulas with high-calorie medical nutrition is possible.

• Pharmacotherapy: the scope of drug therapy is determined by the physician according to the underlying cause of CHF identified in the child. The goal of therapy is to reduce the workload on the heart. It is crucial to adhere to the medication schedule prescribed by the physician to increase treatment efficacy. It is extremely important to follow the dosages of all recommended HF medications! Missing doses or exceeding the specified dosages may lead to life-threatening complications!

• The main classes of drugs used to treat HF in children are angiotensin-converting enzyme inhibitors, beta-blockers, mineralocorticoid receptor antagonists, diuretics, and cardiac glycosides.

During the course of treatment, your child may undergo additional diagnostic examinations to detect significant cardiac arrhythmias, assess myocardial status, and identify vascular pathology.

It should be remembered that the treatment of CHF is long-term, continuous, and requires regular monitoring of the child's condition. In case of positive dynamics (for example, after surgical treatment of congenital heart disease or in favorable outcomes of myocarditis), a gradual withdrawal of therapy under the supervision of a cardiologist may be possible. Discontinuing therapy on one's own can lead to a deterioration of the child's condition.

An important prognostic indicator for patients with HF is left ventricular systolic function, which is assessed during an echocardiographic examination.

If pharmacotherapy for CHF is insufficiently effective, surgical treatment methods may be used. These include: cardiac resynchronization therapy (implantation of a pacemaker with specific characteristics) and mechanical circulatory support devices. If the aforementioned methods are ineffective, heart transplantation may be recommended.

CHF prevention consists of the early detection of diseases accompanied by the development of HF and the prevention of clinical worsening in patients with already diagnosed CHF.

All patients with signs of CHF must be under dispensary observation by a local cardiologist. Dispensary observation is carried out for the underlying disease in accordance with established timelines. If signs of CHF persist when patients reach 18 years of age, it is advisable to continue further dispensary observation with a cardiologist.

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

Not applicable.