home Auditorium 8 Clinical guidelines for heart failure. Clinical recommendations: Chronic heart failure Treatment of CHF recommendations

Clinical guidelines for heart failure. Clinical recommendations: Chronic heart failure Treatment of CHF recommendations

3.1.1 The main goals of treating a patient with chronic heart failure.

In the treatment of each patient with CHF, it is important to achieve not only the elimination of the symptoms of CHF (shortness of breath, swelling, etc.), but also to reduce the number of hospitalizations and improve the prognosis. Reducing mortality and the number of hospitalizations are the main criteria for the effectiveness of therapeutic interventions. As a rule, this is accompanied by a reversal of LV remodeling and a decrease in natriuretic peptide (NUP) concentrations.
For any patient, it is also extremely important that the treatment allowed him to achieve elimination of the symptoms of the disease, improve the quality of life and increase his functionality, which, however, is not always accompanied by an improvement in the prognosis of the patient with CHF. However, the hallmark of modern effective pharmacotherapy is the achievement of all designated treatment goals.

3,1,2 Therapy recommended for all patients with symptomatic heart failure and reduced left ventricular ejection fraction.

Angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (β-blockers) and aldosterone antagonists (mineralocorticoid receptor antagonists, MRAs) are recommended for the treatment of all patients with symptomatic heart failure (FC II-IV) and reduced LV ejection fraction.

Two large randomized trials (CONSENSUS and SOLVD-Treatment Branch), as well as a meta-analysis of smaller studies, have convincingly proven that ACE inhibitors increase survival, reduce the number of hospitalizations, improve functional class and quality of life in patients with CHF, regardless of the severity of the clinical manifestations of the disease. The results of three other large randomized trials (SAVE, AIRE, TRACE) demonstrated the additional effectiveness of ACE inhibitors and a reduction in mortality in patients with LV systolic dysfunction/CHF symptoms after acute myocardial infarction (AMI). In turn, the ATLAS study showed that treatment of patients with high doses of ACE inhibitors has an advantage over low-dose therapy and reduces the risk of death/hospitalization with long-term use in patients with CHF. In addition, the SOLVD-Prophylaxis arm clinical trial demonstrated that ACEIs may delay or prevent the development of CHF symptoms in patients with asymptomatic LV dysfunction.
ACE inhibitors in addition to β-blockers are recommended for all patients with symptomatic heart failure and reduced LV ejection fraction to reduce the risk of hospitalization due to HF and death.
Strength of Recommendation Level I (Level of Evidence A).
ACE inhibitors are recommended for patients with asymptomatic LV systolic dysfunction and a history of myocardial infarction to prevent the development of HF symptoms.
Strength of Recommendation Level I (Level of Evidence A).
ACE inhibitors are recommended for patients with asymptomatic LV systolic dysfunction without a history of myocardial infarction to prevent the development of HF symptoms.

The following ACE inhibitors are registered for use in Russia: zofenopril, captopril**, quinapril, lisinopril**, perindopril**, ramipril, spirapril, trandolapril, fosinopril, cilazapril, enalapril**.
They are recommended for the use of ACE inhibitors, which have the most significant evidence base for CHF.
Strength of Recommendation Level I (Level of Evidence A).
Comments. Table 9 shows the doses of ACE inhibitors that have the most significant evidence base for CHF.
Table 9. Recommended drugs and doses.
Practical aspects of the use of ACE inhibitors in patients with CHF-HFEF are presented in Appendix D1.
The results of several large randomized controlled trials (CIBIS II, MERIT-HF, COPERNICUS, USCP) have convincingly proven that beta-blockers increase survival, reduce the number of hospitalizations, improve the functional class of CHF and quality of life when added to standard therapy (diuretics, digoxin** and ACE inhibitors) in patients with stable mild and moderate CHF, as well as in patients with severe CHF. In the SENIORS study, which differed significantly in design from the above-mentioned studies (elderly patients, some of them with preserved left ventricular systolic function, longer follow-up period), the effect of nebivolol was slightly less pronounced compared to previous protocols, however it is impossible to compare them directly. Another large clinical trial, COMET, showed a significant benefit of carvedilol** compared to short-acting metoprolol tartrate** in reducing the risk of death in patients with CHF (long-acting sustained-release metoprolol succinate** was used in the MERIT-HF trial ).
Beta blockers in addition to ACEIs are recommended for all patients with stable symptomatic heart failure and reduced LV ejection fraction to reduce the risk of hospitalization due to HF and death.
Strength of Recommendation Level I (Level of Evidence A).
Comments. Today, it is generally accepted that ACE inhibitors and β-blockers, due to their mechanism of action, complement each other’s effects, and therapy with these groups of drugs should begin as early as possible in patients with CHF and reduced LVEF. In addition to the positive effects of ACE inhibitors, β-blockers have a much more pronounced effect on LV remodeling and LVEF. β-ABs also have an anti-ischemic effect, are more effective in reducing the risk of sudden death, and their use leads to a rapid reduction in mortality in patients with CHF from any cause.
β-ABs are recommended for patients after a MI and the presence of LV systolic dysfunction to reduce the risk of death and prevent the development of HF symptoms.
Strength of recommendation level I (Level of certainty of evidence B).
Prescribing β-AB is not recommended in the presence of symptoms of decompensation (persistence of signs of fluid stagnation, increased pressure in the jugular vein, ascites, peripheral edema). If β-blockers have already been prescribed before the onset of symptoms of decompensation, continuation of therapy is recommended, if necessary, in a reduced dose.
Level of Recommendation Strength IIA (Level of Evidence A).
Comments. If there are symptoms of severe hypoperfusion, it is possible to completely cancel β-AB therapy, followed by its mandatory resumption when the condition stabilizes before discharge from the hospital.
Beta-blockers recommended for CHF and their dosages are presented in Table 10.
Table 10. Drugs and dosages.
Practical aspects of the use of beta-blockers in patients with CHF-HFEF are presented in Appendix D2.
The RALES study showed that the use of spironolactone** to standard therapy (ACE inhibitors, β-blockers, diuretics, digoxin**) reduces the number of hospitalizations and improves the clinical condition of patients with CHF (III-IV class), in 2010 the results of the EMPHASIS-HF study were convincing showed that the addition of eplerenone to standard therapy for patients with CHF II or higher of any origin reduces the number of hospitalizations, reduces overall mortality and mortality due to CHF. Previously, the data from these clinical trials were confirmed by the results of the EPHESUS (eplerenone) study in patients with AMI complicated by the development of CHF and LV systolic dysfunction.
MCAs are recommended for all patients with class II-IV CHF and LVEF ≤ 35% who remain symptomatic of heart failure despite treatment with ACE inhibitors and beta-blockers to reduce the risk of hospitalization due to HF and death.
Strength of recommendation level I (Level of evidence certainty A) .
Comments. When using AMKR in combination with ACEIs/ARBs and beta-blockers, the most dangerous is the development of severe hyperkalemia ≥ 6.0 mmol/l, which occurs in everyday clinical practice much more often than in the studies conducted.
AMCR should be prescribed both during inpatient treatment and on an outpatient basis, if they have not been prescribed previously.
Recommended doses:
Starting dose Target dose.
Spironolactone** 25 mg once 25-50 mg once.
Eplerenone 25 mg once, 50 mg once.
Practical aspects of the use of AMCR in patients with CHF-HFEF are presented in Appendix D3.

3,1,3 Therapy recommended for selected groups of patients with symptomatic heart failure and reduced left ventricular ejection fraction.

Unlike other treatments, the effect of diuretics on morbidity and mortality in patients with CHF has not been studied in long-term studies. However, the use of diuretics eliminates symptoms associated with fluid retention (peripheral edema, shortness of breath, pulmonary congestion), which justifies their use in patients with CHF regardless of LVEF.
Diuretics are recommended to improve symptoms of heart failure and increase physical activity in patients with signs of fluid retention.

Diuretics are recommended to reduce the risk of hospitalization due to HF in patients with symptoms of fluid retention.

Comments. Diuretics cause rapid improvement in the symptoms of CHF, unlike other treatments for CHF.
Only diuretics are able to adequately control fluid status in patients with CHF. Adequacy of control (optimal “dry” weight of the patient – euvolemic state) largely ensures the success/failure of therapy with β-blockers, ACE inhibitors/ARBs and AMCR. In the case of relative hypovolemia, the risk of developing decreased cardiac output, hypotension, and deterioration of renal function increases significantly.
The optimal dose of a diuretic is considered to be the lowest dose that ensures the patient is maintained in a state of euvolemia, etc.; when daily intake of a diuretic drug ensures balanced diuresis and constant body weight.
In patients with CHF, diuretics should be used only in combination with β-blockers, ACE inhibitors/ARBs, and AMCRs.
Diuretics recommended for the treatment of CHF are presented in Table 11.
Table 11. Doses of diuretics most often used in the treatment of patients with CHF.

Diuretic	Initial dose		Usual daily dose
Loop diuretics
Furosemide**	20-40mg		40-240mg
Torasemide	5-10mg		10-20mg
Bumetanide*	0.5-1mg		1-5mg
Ethacrynic acid	25-50mg		50-250mg
Thiazide diuretics
Bendroflumethiazide*	2.5 mg		2.5-10mg
Hydrochlorothiazide**	12.5-25mg		12.5-100mg
Metolazone*	2.5 mg		2.5-10mg
Indapamide**	2.5 mg		2.5-5 mg
Potassium-retaining diuretics
	+ ACEI/ARB	- ACEI/ARB	+ ACEI/ARB	- ACEI/ARB
Amiloride*	2.5 mg	5mg	5-10mg	10-20mg
Triamterene^	25mg	50mg	100mg	200mg

Note: * - the drug is not registered and is not used in the Russian Federation; ^ - used only in combination with hydrochlorothiazide 12.5 mg.
Practical aspects of the use of diuretics in patients with CHF-HFEF are presented in Appendix D4.
A new class of therapeutic agents that simultaneously influence both the activity of the RAAS and the activity of the natriuretic peptide system (NUP). The first drug in this class was LCZ696, in which it was possible to combine 2 subunits consisting of the molecules valsartan (angiotensin receptor blocker) and sacubitril (neprilysin inhibitor). Accordingly, blockade of angiotensin receptors reduces the activity of the RAS, and inhibition of neprilysin leads to a slowdown in the degradation of NUP and bradykinin. As a result of this dual mechanism of action, systemic vasoconstriction is reduced, fibrosis and hypertrophy of the heart and blood vessels are reduced, diuresis and natriuresis are increased, and vasodilatory effects prevail against the development of maladaptive LV remodeling.
To date, one large randomized trial (PARADIGM-HF) has been conducted to evaluate the long-term effects of sacubitril/valsartan compared with the ACE inhibitor enalapril** on morbidity and mortality in outpatients with symptomatic HF (FC II-IV) and reduced LVEF ≤ 40% ( study adjusted to ≤35%) who had elevated NUP concentrations and HF hospitalizations within a year. An important criterion for inclusion in the study was the introductory period, in which the ability of patients to tolerate the required doses of the study drugs was tested (enalapril** 10 mg 2 times a day, LCZ696 200 mg 2 times a day). The study was stopped early (median follow-up 27 months), and the risk reduction in CV death/HF hospitalization (primary endpoint) was 20% in the sacubitril/valsartan group (97/103 mg twice a day). day) compared with enalapril** (10 mg 2 times/day), which made it possible to include this group of drugs in modern recommendations for the treatment of patients with HF with reduced LVEF.
Valsartan + Sacubitril is recommended instead of an ACE inhibitor in outpatients with reduced LVEF and persistent symptoms of HF despite optimal therapy with ACE inhibitors, beta-blockers and MCBs to reduce the risk of hospitalization due to HF and death.
Recommendation strength level I (evidence level B).
Comments. Despite the superiority of sacubitril/valsartan over enalapril** in the PARADIGM-HF study, questions remain regarding the safety profile of this new class of drugs, especially important when used in clinical practice. One of the most important is the risk of developing hypotension at the beginning of treatment, especially in elderly patients over 75 years of age (the development of hypotension in 18% in the sacubitril/valsartan group versus 12% in the enalapril group**), although this did not lead to an increase in the frequency of patient withdrawal from treatment. research. The development of angioedema was rare (0.4% and 0.2%, respectively), which may be partly due to the presence of a run-in period. Also, the issue of the effect of Valsartan + Sacubitril on the degradation of beta-amyloid has not been fully resolved, which requires continued monitoring and safety assessment over a long period.
The recommended starting dose of Valsartan + Sacubitril is 49/51 mg 2 times a day, the target dose is 97/103 mg 2 times a day.
Today, the use of ARBs is recommended for patients with CHF and reduced LVEF ≤ 40% only in case of intolerance to ACE inhibitors (CHARM-Alternative, VAL-HeFT and VALIANT).
Strength of recommendation level I (Level of certainty of evidence B).
ARBs are not recommended in patients with symptoms of heart failure (class II-IV), despite treatment with ACE inhibitors and β-blockers.

Comments. In this case, in addition to ACE inhibitors and β-blockers, it is recommended to add the MCR antagonist eplerenone or spironolactone. This prescribing algorithm is based on the results of the EMPHASIS-HF clinical trial, which demonstrated a much greater reduction in morbidity/mortality with eplerenone compared with the same effect of ARBs in the Val-HeFT and CHARM-Added trials, as well as the RALES and EMPHASIS-HF protocols , in which both AMKRs were able to reduce mortality from any cause in patients with CHF, in contrast to ARBs (studies with the addition of ARBs “on top” of ACEIs and β-blockers). Additional prescription of an ARB is possible only if a patient with CHF, for some reason, has intolerance to AMCR, and symptoms of HF persist despite selected therapy with ACE inhibitors and β-blockers, which will require subsequent strict clinical and laboratory monitoring.
ARBs are recommended to reduce the risk of HF hospitalization and CV death in patients with symptomatic HF who are unable to tolerate ACEIs (patients should also take beta-blockers and MCBs).
Strength of recommendation level I (Level of certainty of evidence B).
Comments. By “intolerance” to ACE inhibitors one should understand the presence of individual intolerance (allergy), the development of angioedema, cough. Impaired renal function, the development of hyperkalemia and hypotension during treatment with ACE inhibitors are not included in the concept of “intolerance” and can be observed in patients with CHF with the same frequency both when using ACE inhibitors and ARBs.
ARBs are recommended in selected patients with symptoms of HF who are taking beta-blockers and are unable to tolerate AMCR.
Level of Recommendation Strength IIb (Level of Evidence C).
“Triple” blockade of the RAAS (combination of ACEI + MCR antagonist + ARB) is not recommended for use in patients with CHF due to the high risk of developing hyperkalemia, deterioration of renal function and hypotension.

ARBs recommended for use in patients with CHF are presented in Table. 12.
Table 12. Angiotensin receptor blockers:
Practical aspects of the use of ARBs in patients with CHF-HFEF are presented in Appendix D5.
The use of ivabradine** is recommended only for patients with sinus rhythm, EF ≤ 35%, symptoms of class II-IV CHF and heart rate ≥ 70 per minute. , who are necessarily on selected therapy with recommended (or maximum tolerated) doses of β-AB, ACE inhibitors/ARBs and MCR antagonists.
Level of strength of recommendation IIa (Level of evidence B).
Comments. The mechanism of action of ivabradine** is to reduce heart rate due to selective inhibition of the ion current in the If channels of the sinus node without any effect on the inotropic function of the heart. The drug is effective only in patients with sinus rhythm. It has been shown that in patients with sinus rhythm, EF ≤ 35%, symptoms of FC II-IV CHF and heart rate ≥ 70 per minute. , despite therapy with recommended (or maximum tolerated) doses of β-blockers, ACE inhibitors/ARBs and MCR antagonists, addition of ivabradine** to treatment reduces the number of hospitalizations and mortality due to CHF. In addition, in the case of β-blocker intolerance, in the same category of patients, the use of ivabradine** in addition to standard therapy reduces the risk of hospitalization due to CHF.
The use of ivabradine** is recommended to reduce the risk of hospitalization due to HF and mortality due to CV causes in patients with symptoms of HF and LVEF ≤35%, sinus rhythm, resting heart rate ≥ 70 beats/min, who are on therapy with ACE inhibitors (ARBs) and AMCRs who are unable to tolerate or have contraindications to beta-blockers 120].
Level of confidence of recommendations II a (Level of certainty of evidence C).
Comments. The recommended initial dose of ivabradine** is 5 mg x 2 times a day, followed by an increase after 2 weeks to 7.5 mg x 2 times a day. In elderly patients, it is possible to adjust the dose of ivabradine** downward.
To date, the use of cardiac glycosides (CG) in patients with CHF is limited. Of the existing drugs, digoxin** is recommended; the effectiveness and safety of other SGs (for example, digitoxin**) for CHF have not been sufficiently studied. Prescribing digoxin** to patients with CHF does not improve their prognosis, but reduces the number of hospitalizations due to CHF, improves symptoms of CHF and quality of life [121-126]. The use of digoxin** in some cases can only complement therapy with β-blockers, ACE inhibitors/ARBs, MCR antagonists and diuretics.
Digoxin** is recommended for the treatment of patients with class II-IV CHF and reduced LVEF ≤ 40% (DIG study, meta-analysis data) with sinus rhythm, with persistent symptoms of HF despite therapy with ACE inhibitors, beta-blockers and MACR to reduce the risk of hospitalization due to HF and for any reason.

Comments. In such patients, it is necessary to take a balanced approach to its prescription, and it is preferable to use it if the patient has severe heart failure III-IVFC, low LVEF (< 25%) в сочетании с наклонностью к гипотонии. Оптимальной дозой дигоксина** для лечения больных ХСН считается 0,125-0,25мг/сутки. При длительном лечении необходимо ориентироваться на концентрацию дигоксина** в крови, которая должна находиться в безопасных пределах . Оптимальной концентрацией у больных ХСН является интервал от 0,8нг/мл до 1,1нг/мл (< 1,2нг/мл). Доза дигоксина** должна быть уменьшена (контроль концентрации) при снижении СКФ, у пожилых больных и женщин . Из-за вероятности развития желудочковых аритмий, особенно у больных с гипокалиемией, необходим жесткий контроль электролитов крови, функции почек, ЭКГ.
The use of digoxin** to control heart rate in patients with symptoms of CHF and the presence of tachyform atrial fibrillation (AF) (see Chapter 3,1,7).
The use of omega-3 PUFA esters is recommended in selected patients with class II-IV CHF, LVEF ≤ 40%, who are on standard therapy with β-blockers, ACE inhibitors/ARBs, MCR antagonists and diuretics to reduce the risk of death and hospitalization for cardiovascular reasons.
Level of Strength of Recommendation IIb (Level of Evidence B).
Comments. The evidence base for CHF is not significant. A small additional effect of omega-3 polyunsaturated fatty acids (PUFAs) was shown to reduce the risk of death and hospitalization due to cardiovascular (CV) causes in patients with class II-IV CHF, LVEF ≤ 40%, on standard β-blocker therapy , ACE inhibitors/ARBs, MCR antagonists and diuretics in the GISSI-HF study. There was no effect on hospitalizations due to CHF. The effect was confirmed by the results of the GISSI-Prevenzione protocol in patients after myocardial infarction, but not by data from the OMEGA clinical trial.
Due to the lack of evidence, peripheral vasodilators are currently not indicated for the treatment of patients with CHF. An exception is the combination of nitrate and hydralazine, which may improve prognosis, but only when used in African Americans (V-HeFT-I, V-HeFT-II and A-HeFT studies).
Therapy with hydralazine and isosorbide dinitrate is recommended to reduce the risk of death and hospitalization due to heart failure in African American patients with LVEF ≤35% or LVEF ≤45% in the presence of dilated LV and III-IV HF, despite therapy with ACEIs, beta-blockers, and MCBs. .
Level of strength of recommendation II a (Level of certainty of evidence B).
Therapy with hydralazine and issorbide dinitrate is recommended in rare cases to reduce the risk of death in symptomatic patients with HF with reduced LVEF who are unable to tolerate (or have contraindications to) ACE inhibitors or ARBs.
Level of Strength of Recommendation IIb (Level of Evidence B).

3,1,4 Therapy not recommended (no proven positive effect) for symptomatic patients with heart failure and reduced left ventricular ejection fraction.

Statin therapy is not recommended for patients with CHF.

Comments. The benefit of statins in patients with CHF has not been proven. The CORONA and GISSI-HF studies, which observed patients with FC II-IV CHF, ischemic and non-ischemic etiology, with LVEF ≤ 40%, on standard therapy with β-blockers, ACE inhibitors/ARBs and MCR antagonists, did not reveal any additional effect of rosuvastatin on the prognosis . At the same time, treatment with rosuvastatin in patients with CHF was relatively safe. Therefore, if statin treatment was prescribed to a patient with coronary artery disease before the development of symptoms of CHF, statin therapy can be continued.
The use of indirect anticoagulants is not recommended in patients with CHF and sinus rhythm.

Comments. According to the results of the WARCEF study, the use of indirect anticoagulants does not affect the prognosis and morbidity of patients with CHF in sinus rhythm compared with placebo and aspirin, unlike patients with AF.
Direct renin inhibitors (as an additional therapy to ACEIs/ARBs, β-blockers and MCR antagonists) are not recommended for the treatment of any group of patients with CHF.
Level of Strength of Recommendation III (Level of Evidence B).
Comments. The results of completed studies with aliskiren (ASTRONAUT - patients after decompensation of CHF, high risk; ALTITUDE - patients with diabetes mellitus, stopped early) indicate the absence of an additional positive effect of direct renin inhibitors on the prognosis and hospitalization of patients with CHF, as well as an increased risk of developing hypotension, hyperkalemia and renal dysfunction, especially in patients with diabetes mellitus.

3,1,5 Therapy, the use of which can be dangerous, and is not recommended for patients with chronic heart failure of functional class II-IV and reduced left ventricular ejection fraction.

Thiazolidinediones (glitazones are not recommended for patients with CHF), as they cause fluid retention, and therefore increase the risk of decompensation.
Strength of Recommendation Level III (Level of Evidence A).
Most BMCCs (dilithiazem, verapamil**, short-acting dihydropyridines) are not recommended for use in heart failure due to the presence of a negative inotropic effect, which contributes to the development of decompensation in patients with heart failure.
Strength of recommendation level III (Level of certainty of evidence C).
Comments. The exceptions are felodipine and amlodipine**, which do not affect the prognosis of patients with CHF (PRAISE I and II studies; V-HeFT III).
The use of NSAIDs and COX-2 inhibitors is not recommended for CHF, since NSAIDs and COX-2 inhibitors provoke sodium and fluid retention, which increases the risk of decompensation in patients with CHF.
Level of Strength of Recommendation III (Level of Evidence B).
“Triple” blockade of the RAAS in any combination: ACE inhibitor + AMCR + ARB (or direct renin inhibitor) is not recommended in the treatment of patients with CHF due to the high risk of developing hyperkalemia, deterioration of renal function and hypotension.
Strength of recommendation level III (Level of certainty of evidence C).
Class I antiarrhythmics are not recommended for patients with CHF, as they increase the risk of sudden death in patients with LV systolic dysfunction.
Strength of Recommendation Level III (Level of Evidence A).

3,1,6 Features of treatment of patients with chronic heart failure and ventricular arrhythmias.

It is recommended to correct factors that provoke ventricular arrhythmias (correction of electrolyte disturbances, discontinuation of medications that provoke ventricular arrhythmias, revascularization for ventricular tachycardia caused by ischemia).

It is recommended to optimize the doses of ACE inhibitors (or ARBs), beta-blockers, MACRs and Valsartan + Sacubitril for patients with CHF-HFEF.

Implantation of an ICD (implantable cardioverter defibrillator) or CRT-D (cardiac resynchronization therapy - defibrillator) is recommended for a certain group of patients with CHF-HFEF (see Chapter 6).
Strength of Recommendation Level I (Level of Evidence A).
To make treatment decisions for recurrent episodes of VA in patients with an ICD (or those for whom ICD implantation is not possible), it is recommended to consider several options, including risk factor management, optimization of CHF therapy, amiodarone**, catheter ablation, and CRT (cardiac resynchronization therapy). .
Level of Strength of Recommendation IIa (Level of Evidence C).
Routine administration of antiarrhythmic drugs is not recommended for patients with CHF and asymptomatic VAs for safety reasons (CHF decompensation, proarrhythmic effect or death).
Strength of Recommendation Level III (Level of Evidence A).
The use of antiarrhythmic drugs IA, IC classes and dronedarone is not recommended in patients with systolic CHF for the prevention of paroxysms of ventricular tachycardia.
Strength of Recommendation Level III (Level of Evidence A).
Comments. Amiodarone** (usually in combination with a beta-blocker) can be used to prevent symptomatic VAs, but it should be taken into account that such therapy may have the opposite effect on prognosis, especially in severe patients with CHF-HFEF.

3,1,7 Features of treatment of patients with chronic heart failure and atrial fibrillation.

Regardless of LVEF, all patients with CHF and atrial fibrillation (AF), especially in the case of a newly registered episode of AF or paroxysmal AF, should do the following:
identify potentially correctable causes (hypo- or hyperthyroidism, electrolyte disturbances, uncontrolled hypertension, mitral valve defects) and provoking factors (surgery, respiratory tract infection, exacerbation of asthma/chronic obstructive pulmonary disease, acute myocardial ischemia, alcohol abuse) that determine the basic tactics patient management;
assess the risk of stroke and the need for anticoagulant therapy;
assess the frequency of ventricular contractions and the need for their control;
evaluate symptoms of AF and CHF.
For more detailed information, please refer to the Guidelines for the management of patients with AF.
Treatment with ACE inhibitors, ARBs, beta blockers, and MCR antagonists may reduce the incidence of AF, unlike ivabradine**. CRT does not have a significant effect on the incidence of AF.
Amiodarone** reduces the incidence of AF, is used for pharmacological cardioversion, helps maintain sinus rhythm in most patients after cardioversion, and can be used to control symptoms in patients with paroxysmal AF if beta-blocker therapy is ineffective.
Recommendations for the initial treatment of patients with chronic heart failure and atrial fibrillation with a high frequency of ventricular contractions in an acute or chronic situation.
Emergency electrical cardioversion is recommended if AF has resulted in hemodynamic instability, to improve the patient's clinical condition.
Recommendation Strength I (Evidence Level C).
For patients with class IV CHF, in addition to the treatment of AHF, intravenous bolus administration of amiodarone** or digoxin** is recommended in most patients to reduce the ventricular rate (VFR).

For patients with class I-III CHF, oral beta-blockers are safe and recommended as first-line therapy to control heart rate, provided that the patient is euvolemic.
Strength of Recommendation Level I (Level of Evidence A).
For patients with CHF class I-III, digoxin** is recommended in case of high heart rate despite taking beta blockers, or in cases where the use of beta blockers is impossible or contraindicated.
Level of Strength of Recommendation IIa (Level of Evidence B).
Catheter ablation of the AV node is recommended in selected cases to control rate and improve symptoms in patients resistant to or unresponsive to intensive pharmacologic rhythm or rate control therapy, given that these patients become pacemaker dependent.

Treatment with dronedarone to control heart rate in patients with CHF is not recommended. Strength of Recommendation Level III (Level of Evidence A).
Electrical cardioversion or drug cardioversion with amiodarone** is recommended in patients with persistent symptoms of CHF despite optimal medical treatment and adequate heart rate control to improve the patient's symptoms/clinical status.
Level of Recommendation Strength IIb (Level of Evidence B).
Radiofrequency ablation of AF is recommended to restore sinus rhythm and improve symptoms in patients with persistent symptoms and/or signs of heart failure despite optimal medical treatment and adequate control of heart rate to improve symptoms/clinical status.
Level of Recommendation Strength IIb (Level of Evidence B).
Amiodarone** is recommended before (and after) successful electrical cardioversion to maintain sinus rhythm.
Level of Recommendation Strength IIb (Level of Evidence B).
Dronedarone is not recommended for rhythm control because it increases the risk of cardiovascular hospitalization and death in patients with class III-IV.
Strength of Recommendation Level III (Level of Evidence A).
Class I antiarrhythmic drugs are not recommended for patients with CHF, as they increase the risk of death.
Strength of Recommendation Level III (Level of Evidence A).

3,1,8 Features of the prevention and treatment of thromboembolic complications in patients with heart failure.

The examination of a patient with CHF should include measures to identify possible sources and risk factors for the development of thromboembolic complications (TEC). An assessment of renal function (creatinine clearance or glomerular filtration rate) is also required, the impairment of which is an additional risk factor for TEC and requires dose adjustment of a number of antithrombotic drugs.
Prevention of venous TEC is recommended for patients hospitalized with acute HF or severe decompensated CHF (FC III or IV), as well as if CHF is combined with additional risk factors (see Table 13), who do not receive anticoagulants for other indications.
Strength of Recommendation Level I (Level of Evidence A).
Comments. In the absence of contraindications, the means of choice include subcutaneous administration of anticoagulants - unfractionated heparin (5000 units 2-3 times / day; APTT monitoring is not required), enoxaparin (40 mg 1 time / day).
The duration of drug prophylaxis for venous VTE should be from 6 to 21 days (until restoration of full motor activity or until discharge, whichever comes first). In patients with bleeding, a high risk of bleeding, or other contraindications to the use of anticoagulants, mechanical methods of preventing venous TEC (compression stockings or intermittent pneumatic compression of the lower extremities) should be used. The widespread use of objective methods for diagnosing deep vein thrombosis (compression ultrasonography of the veins of the lower extremities and others) in patients who do not have symptoms of venous thrombosis is not recommended.
Table 13. Risk assessment and determination of indications for prophylaxis of venous TEC in hospitalized non-surgical patients - prevention is appropriate if the score is ≥4.

Risk factor	Point
Active cancer (metastasis and/or chemotherapy or radiotherapy< 6 месяцев назад)	3
History of venous thromboembolism (with the exception of superficial vein thrombosis)	3
Limited mobility (bed rest with toilet access for ≥3 days) due to limitations of the patient or as prescribed by a doctor	3
Known thrombophilia (antithrombin, protein C or S defects, factor V Leiden, prothrombin G20210A mutation, antiphospholipid syndrome)	3
Trauma and/or surgery ≤1 month ago	2
Age ≥70 years	1
Cardiac and/or respiratory failure	1
Myocardial infarction or ischemic stroke	1
Acute infection and/or rheumatological disease	1
Obesity (BMI ≥30 kg/m2)	1
Continued use of hormone replacement therapy or oral contraceptives	1

BMI-body mass index.
Prosthetic heart valves.
In the presence of a mechanical prosthetic heart valve in a patient with CHF, it is recommended to use a vitamin K antagonist indefinitely (for life) under the control of the international normalized ratio (INR), as monotherapy or in combination with low doses of acetylsalicylic acid** (75-100 mg/day) .
Strength of Recommendation Level I (Level of Evidence A).
Comments. The target INR depends on the type of prosthesis, its position, the presence of additional risk factors for TEC and the simultaneous use of acetylsalicylic acid. Indefinitely long-term (lifelong) use of a vitamin K antagonist under INR control is also indicated in the presence of a biological prosthetic heart valve in patients with reduced LVEF (.
The use of new oral anticoagulants (apixaban, rivaroxaban**, dabigatran**, edoxaban (the drug is not registered and not used in the Russian Federation)) is not recommended.

Heart defects.
Patients with hemodynamically significant mitral valve disease and the presence of a thrombus in the left atrium, previous arterial thromboembolism or atrial fibrillation are recommended to receive a vitamin K antagonist indefinitely (for life) with a target INR of 2-3.
Strength of Recommendation Level I (Level of Evidence A).
Comments. A similar approach can be used if there is a marked increase in the diameter of the left atrium (55 mm).
Atrial fibrillation.
Patients with atrial fibrillation and rheumatic heart valve disease (primarily mitral stenosis) are recommended to receive a vitamin K antagonist indefinitely (for life) with a target INR of 2-3.
Strength of Recommendation Level I (Level of Evidence A).
The use of new oral anticoagulants (apixaban, rivaroxaban**, dabigatran**, edoxaban (the drug is not registered and not used in the Russian Federation)) in patients with at least moderate mitral valve stenosis is not recommended.
Level of Recommendation Strength II I (Level of Evidence B).
To establish the risk of thromboembolic complications and the risk of developing hemorrhagic complications, it is recommended to use the CHA2DS2-VASc and HAS-BLED scales, respectively.
Recommendation Strength I (Evidence Level B).
Comments. The need for stroke prevention and arterial thromboembolism in non-valvular atrial fibrillation is determined by the sum of points on the CHA2DS2-VASc scale.
Scale C H A 2 DS 2. VASc - Congestive heart failure (chronic heart failure), Hypertension (Arterial hypertension), Age (age over 75 years), Diabetes mellitus (diabetes mellitus), Stroke (history of stroke/TIA/systemic embolism), Vascular disease (vascular disease ), Age (age 65–74 years), Sex category - (female).
HAS scale. BLED - Hypertension (Arterial hypertension), Abnormal renal-liver function (impaired kidney and/or liver function), Stroke (stroke), Bleeding history or predisposition (bleeding history or predisposition), Labile international normalized ratio (labile INR level ), Elderly (65 years) (age over 65 years), Drugs or alcohol concomitantly (use of certain medications or alcohol).
Therapy with oral anticoagulants for the prevention of thromboembolic complications is recommended for all patients with paroxysmal or persistent/permanent AF with a score of 2 or more on the CHA2DS2-VASc scale, in the absence of contraindications and regardless of the chosen patient management strategy (heart rate control and rhythm control).
Strength of Recommendation Level I (Level of Evidence A).
Comments. Moreover, depending on the characteristics of a particular patient, availability, vitamin K antagonists with a target INR can be selected, and in case of non-valvular atrial fibrillation, the absence of severe renal failure and other contraindications, new oral anticoagulants - apixaban at a dose of 5 mg 2 times a day (if present) at least two out of three factors - age 80 ≥ years, body weight ≤ 60 kg, creatinine ≥ 133 µmol/l, creatinine clearance 15-29 ml/min - the dose should be reduced to 2.5 mg 2 times / day); dabigatran etexilate** [199] at a dose of 110 or 150 mg 2 times a day (with caution if creatinine clearance is 30-49 ml/min, contraindicated if creatinine clearance is below 30 ml/min), age ≥80 years, moderate decrease in renal function (CrCl 30-50 ml/min), simultaneous use of P-glycoprotein inhibitors, or a history of gastrointestinal bleeding may increase the risk of bleeding, therefore, in patients with one or more of these risk factors, at the discretion of the physician, a reduction in the daily dose is possible up to 110 mg 2 times/day; rivaroxaban** [200] at a dose of 20 mg 1 time / day (with creatinine clearance< 50-30 мл/мин доза должна быть уменьшена до 15 мг 1 раз/сут).
In patients with CHF and non-valvular AF who have indications for anticoagulant therapy based on the CHA2DS2-VASc scale, it is recommended to prescribe new oral anticoagulants, but not warfarin, due to a lower risk of stroke, hemorrhagic intracranial complications and death, despite the higher risk of gastrointestinal bleeding.
Level of Recommendation Strength I Ia (Level of Evidence B).

3,1,9 Management of patients with chronic heart failure and concomitant pathology.

The presence of concomitant pathology in a patient with CHF may influence the characteristics of its management. This is due to several reasons. Firstly, the presence of damage to other organs in a patient with CHF may be a significant unfavorable prognostic factor. Secondly, the drug therapy required may adversely affect either the course of CHF or concomitant diseases. Finally, when several groups of drugs are taken in combination, serious drug-drug interactions may occur. A serious argument is also the fact that very often randomized clinical trials did not specifically study the combination of CHF and diseases of other organs and systems. This leads to a lack of evidence-based information on the management of such patients, and very often treatment algorithms are based only on the opinions of experts on this problem. It should be noted that all general approaches to diagnosis and treatment apply to the management of such groups of patients, with the exception of the special situations described below.
Arterial hypertension.
Arterial hypertension is currently one of the main etiological factors of CHF. It has been proven that antihypertensive therapy significantly improves the outcomes and symptoms of CHF.
ACE inhibitors (if intolerant, ARBs), beta-blockers or MCBs (or a combination) are recommended for lowering blood pressure as first, second and third line therapy, respectively, due to their proven effectiveness in patients with reduced LVEF (reducing the risk of death and hospitalization due to CH).
Strength of Recommendation Level I (Level of Evidence A).
Comments. This therapy is also safe in patients with CHF with preserved LVEF.
Thiazide diuretics (or loop diuretics, if the patient is already taking thiazide diuretics) are recommended to enhance antihypertensive therapy in case of insufficient antihypertensive effectiveness of the use of ACE inhibitors (ARBs instead of ACEIs, but not together!), beta blockers and AMCRs in patients with CHF.
Strength of recommendation level I (level of evidence certainty C).
The use of amlodipine** is recommended to enhance antihypertensive therapy in case of insufficient antihypertensive effectiveness of the use of ACE inhibitors (ARBs instead of ACE inhibitors, but not together!), beta blockers, MACRs and diuretics in patients with CHF.
Strength of Recommendation Level I (Level of Evidence A).
The use of felodipine is recommended to enhance antihypertensive therapy in case of insufficient antihypertensive effectiveness of the use of ACE inhibitors (ARBs instead of ACE inhibitors, but not together!), beta blockers, MACRs and diuretics in patients with CHF.
Level of Recommendation Strength IIa (Level of Evidence B).
Most BMCCs (dilithiazem, verapamil**, short-acting dihydropyridines) are not recommended for patients with CHF.
Strength of recommendation level III (Level of certainty of evidence C).
Comments. BMCCs have a negative inotropic effect, which contributes to the development of decompensation of CHF.
Moxonidine is not recommended for patients with CHF.
Level of Strength of Recommendation III (Level of Evidence B).

Federal clinical guidelines for chronic heart failure contain modern information about the etiology, pathogenesis, clinical picture, classification, and diagnosis of this syndrome. The general (strategic) principles of non-drug, drug and surgical treatment are presented, taking into account a differentiated approach to therapy. The recommendations summarize the experience of leading specialists of the Russian Federation in the field of pediatric cardiology and contain scientific and practical data that corresponds to modern global trends in the management of patients with chronic heart failure.

Torsemide: recommendations for clinical use in chronic heart failure and arterial hypertension

Karpov Yu.A.

Diuretics are among the most widely used cardiovascular drugs. This popularity is due to their high effectiveness in treating arterial hypertension(AH) and edematous syndrome, mainly in patients with chronic cardiac insufficiency(CHF). The most widely used thiazide (or thiazide-like) diuretics are hydrochlorothiazide in Europe and chlorthalidone in the USA, which have been used in the treatment of hypertension since the late 50s. last century, as well as indapamide, which has joined them in recent years. According to new recommendations According to the European Society of Hypertension/European Society of Cardiology 2013, diuretics, along with drugs that block the renin-angiotensin system (RAS), β-blockers (BABs) and calcium channel blockers (CCBs), are considered first-line drugs for the treatment of hypertension.

In the early 60s. last century in clinical Loop diuretics came into practice - furosemide, and then ethacrynic acid, which received their name from the site of action - along the thick part of the ascending limb of the loop of Henle. In this segment of the ascending limb of the loop of Henle, 20 to 30% of filtered sodium chloride is reabsorbed, which is 2-3 times more than after taking thiazide diuretics. These drugs have found widespread application in the treatment of edema syndrome in various diseases, especially CHF. Furosemide and ethacrynic acid cause a more pronounced diuretic effect than thiazide diuretics, but this effect is more short-term. After administration or oral administration of these loop diuretics (approximately 2-6 hours after a single dose), the excretion of sodium ions in the urine increases significantly, but after the cessation of the diuretic effect of the drugs, the rate of excretion of sodium ions decreases to a level below the initial level. The described “rebound phenomenon”, caused by a number of intra- and extrarenal mechanisms for maintaining water and electrolyte balance under conditions insufficient the entry of sodium chloride into the body, which further contributes to the activation of the RAS.

The pronounced excretion of sodium ions (the diuretic effect of short-acting loop diuretics), which occurs for several hours a day, is compensated by a significant retention of sodium ions after the end of their diuretic effect (i.e., for most of the day). The “rebound phenomenon” is an explanation for the fact that when taken once a day, loop diuretics (furosemide) usually do not increase the daily excretion of sodium ions and do not have a significant antihypertensive effect. To remove excess sodium ions from the body, loop diuretics must be prescribed 2-3 times a day. Studies have shown that furosemide and bumetanide, when administered once or twice a day, usually not enough effective as antihypertensive drugs. The decrease in blood pressure when furosemide is administered 2 times a day is less than that of hydrochlorothiazide when taken 1 time per day. These data led to the fact that short-acting loop diuretics were not recommended for widespread use in patients with hypertension, and their application limited to cases against the background chronic renal insufficiency .

In the 80s XX century V clinical practice, a new loop diuretic has appeared - torasemide . Torasemide characterized by high bioavailability and a longer lasting effect, which determines a number of favorable pharmacodynamic properties of the drug. Unlike furosemide, a short-acting diuretic, for torasemide the “rebound phenomenon” is not characteristic, which is associated not only with its longer duration of action, but also with its inherent antialdosterone activity (blockade of aldosterone receptors on the membranes of epithelial cells of the renal tubules) and a decrease in aldosterone secretion in the adrenal glands (experimental data).

Like other loop diuretics, torasemide acts on the inner surface of the thick segment of the ascending limb of the loop of Henle, where it inhibits the Na+/K+/2Cl- transport system. The drug enhances the excretion of sodium, chlorine and water without having a noticeable effect on glomerular filtration rate, renal blood flow or acid-base balance. It has been established that furosemide additionally affects the proximal convoluted tubules of the nephron, where the majority of phosphates and bicarbonates are reabsorbed. Torasemide has no effect on the proximal tubules, causes less loss of phosphates and bicarbonates, as well as potassium in the urine.

After oral administration, torasemide is rapidly absorbed with a maximum concentration after 1 hour. The bioavailability of the drug is higher than that of furosemide (80% versus 53%), and it remains high in the presence of concomitant diseases and in elderly and senile people. The half-life of torasemide in healthy individuals is 4 hours; it practically does not change with CHF and chronic renal insufficiency. Compared to furosemide, the sodium and diuretic effects of torasemide occur later and last much longer. The duration of the diuretic effect of furosemide when administered intravenously is on average 2-2.5 hours and torsemide - about 6 hours; when taken orally, the effect of furosemide lasts about 4-6 hours, torasemide - more than 12 hours. Torsemide is removed from the blood circulation, undergoing metabolism in the liver (about 80% of the total amount), and is excreted in the urine (about 20% of the total amount in patients with normal kidney function).

Recently in clinical In practice, the original slow-release torasemide, Britomar, appeared in our country. The prolonged form of torasemide provides a gradual release of the active substance, reducing fluctuations in the concentration of the drug in the blood, compared to the usual form of release of the drug. The drug substance is released over a longer period of time, due to which diuresis begins approximately 1 hour after taking the drug, reaching a maximum after 3-6 hours, the effect lasts from 8 to 10 hours. This allows you to achieve additional clinical benefits in treatment. Long-term release torasemide application does not cause changes in blood potassium levels, does not have a noticeable effect on calcium and magnesium levels, glycemic and lipid profiles. The slow-release drug does not interact with anticoagulants (warfarin, phenprocoumon), cordial glycosides or organic nitrates, beta blockers, ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs) II, CCBs and spironolactone. It should be noted that simultaneous application with diuretics, ACE inhibitors, and especially mineralocorticoid receptor antagonists (MCRs), prevent the development of electrolyte disturbances in the vast majority of cases.

Chronic cardiac failure

Currently, diuretics occupy one of the leading places in the treatment of CHF. Despite the fact that there is no data on their effect on the prognosis of patients with CHF, the effectiveness and clinical the need for this class of drugs for the treatment of patients with decompensation cardiac activities beyond any doubt. Diuretics cause a rapid reduction in the symptoms of CHF associated with fluid retention (peripheral edema, shortness of breath, pulmonary congestion), unlike other drugs for the treatment of CHF. In accordance with the treatment algorithm for systolic CHF in recommendations European Society of Cardiology 2012, diuretics are prescribed, regardless of functional class, to all patients with existing edema syndrome. Rational application diuretics can improve clinical symptoms and reduce the number of hospitalizations or achieve two of the six most important goals in the treatment of CHF.

Only with the help of diuretics can fluid status be adequately controlled in patients with CHF. Adequacy of control largely ensures the success of therapy with beta blockers, ACE inhibitors, ARBs and MCR antagonists. In the case of relative hypovolemia, the risk of developing decreased cardiac output, hypotension, and deterioration of renal function increases significantly. For the treatment of CHF, diuretics should be used only in combination with other drugs (blockers, RAS blockers, MCR antagonists). Table 1 presents diuretics and their doses for the treatment of CHF.

According to modern clinical recommendations. the use of torasemide compared to other diuretics has a number of additional advantages. It should be noted that torasemide has better safety and tolerability compared to furosemide. Torsemide is the first loop diuretic that affects the progression of heart failure and the course of pathological processes in the myocardium. Experts highlight antialdosterone and antifibrotic effects, proven in experimental and clinical studies. In a study by B. Lopes et al. It has been shown that torasemide, compared with furosemide, leads to a decrease in the volume fraction of collagen and reduces the development of fibrosis. One Russian study demonstrated the effect of torasemide on left ventricular remodeling and the ability to normalize the ratio of collagen synthesis and breakdown.

In the TORIC study, torasemide demonstrated the ability to better influence the prognosis of patients with CHF. This study analyzed the results of a 9-month comparative treatment with torasemide at a daily dose of 10 mg and furosemide 40 mg in patients with CHF. In the group of patients receiving torsemide therapy, the functional class of circulatory failure improved significantly more often, and cardiovascular and overall mortality significantly decreased. Based on the results of the study, American experts concluded that torasemide is the drug of choice among diuretics in the treatment of congestive heart failure. In the Russian multicenter study DUEL, torasemide, compared with furosemide, led to compensation faster, was more effective and caused fewer undesirable effects (0.3% versus 4.2% on furosemide), including metabolic and electrolyte ones.

Recently I.V. Zhirov et al. conducted a single-center, randomized, open-label study to determine the comparative effectiveness of long-acting torasemide and furosemide in patients with FC II-III CHF, edema syndrome and elevated levels of natriuretic peptides (NP) on the degree of reduction in NT-proBNP concentrations. The study included 40 patients with CHF II-III FC of ischemic etiology with LVEF less than 40%, divided into two equal groups by randomization in envelopes. The first group received long-acting torasemide (Britomar, Takeda pharmaceutical company) as a diuretic, the second group received furosemide. Dose titration was carried out according to a standard scheme depending on the severity of the edema syndrome. Treatment and observation lasted 3 months. the average dose of torasemide sustained release was 12.4 mg, furosemide - 54.2 mg. In both groups, during treatment, a significant improvement in exercise tolerance, an improvement in the quality of life of patients, and a decrease in the concentration of natriuretic hormones were observed. In the sustained-release torsemide group, there was a trend towards a more significant improvement in quality of life (p = 0.052) and a significantly more pronounced decrease in NT-proBNP levels (p<0,01). Таким образом, согласно данным этого исследования, торасемид замедленного высвобождения благоприятно влиял на течение и качество жизни пациентов с ХСН.

Scheme for the use of torasemide in CHF. In patients with CHF, the usual starting dose of the drug is 2.5-5 mg 1 time / day, which, if necessary, is increased to 20-40 mg until an adequate diuretic response is obtained.

As noted earlier, diuretics belong to the group of first-line antihypertensive drugs in the treatment of patients with hypertension. According to new American recommendations. they remain the drug of choice for blood pressure control in all patients, unless patients have clinical situations or conditions for preferential use of any of the classes of antihypertensive drugs. All this indicates a significant position of diuretics in both mono- and especially in combination therapy of hypertension. Diuretics as a class have become almost ideal when it is necessary to prescribe a second drug, since they potentiate the effect of drugs of all other classes. However, it should be noted that we are talking primarily about thiazide and thiazide-like diuretics (hydrochlorothiazide, bendroflumethiazide, chlorthalidone, indapamide, etc.). These diuretics have been studied in large, long-term clinical trials, demonstrating effectiveness not only in controlling blood pressure, but also in reducing the risk of cardiovascular complications with the use of most of them. In recent years, many studies have compared the effectiveness of diuretics with the effectiveness of newer groups of drugs - CCBs (INSIGHT, STOP-2 studies), ACE inhibitors (CAPPP, STOP-2), CCBs and ACE inhibitors (ALLHAT). Criticism of thiazide diuretics comes down mainly to negative metabolic disorders (lipid and carbohydrate metabolism), which was most clearly demonstrated in the ASCOT study (when combined with the beta-blocker atenolol), as well as possible disturbances of electrolyte metabolism (hypokalemia).

Other diuretics (loop diuretics) are usually prescribed instead of thiazide diuretics if the patient has hypertension serum creatinine reaches 1.5 mg/dL or glomerular filtration rate<30 мл/мин/1,73 м2 . Эти ограничения связаны главным образом с их кратковременным и относительно слабым антигипертензивным эффектом, что требовало их приема несколько раз в сутки, более слабым вазодилатирующим эффектом, а также выраженной активацией контррегуляторных механизмов, направленных на задержку солей и жидкости в организме. Как показали многочисленные клинические исследования по изучению эффективности и безопасности нового петлевого диуретика торасемида, препарат может наряду с тиазидными диуретиками использоваться для регулярного контроля АД при АГ.

Antihypertensive effectiveness

and safety of torasemide

Most studies assessing the effectiveness of torasemide were conducted back in the 90s. XX century In a 12-week double-blind study in 147 patients with hypertension, torasemide in doses of 2.5-5 mg/day was significantly superior to placebo in antihypertensive activity. Diastolic blood pressure normalized in 46-50% of patients receiving torasemide and 28% of patients in the placebo group. The drug was compared with various thiazide and thiazide-like diuretics, including in various combination therapy regimens. According to one study, the natriuretic, diuretic and antihypertensive effects of torasemide in daily doses of 2.5 to 5 mg were comparable to the effects of 25 mg of hydrochlorothiazide, 25 mg of chlorthalidone and 2.5 mg of indapamide per day and were superior to the effect of furosemide prescribed in a dose of 40 mg 2 times/day Torsemide reduced serum potassium concentration to a significantly lesser extent than hydrochlorothiazide and other thiazide diuretics, and practically did not cause disturbances in carbohydrate and lipid metabolism.

In another placebo-controlled study, 2.5 mg of torasemide and 25 mg of chlorthalidone per day compared with placebo for 8 weeks. treatments caused similar decreases in systolic and diastolic blood pressure. There was no significant effect of torasemide on serum concentrations of potassium, magnesium, uric acid, glucose and cholesterol. In this study, there was a significant decrease in blood potassium levels and a significant increase in uric acid, glucose, and cholesterol levels in the chlorthalidone group.

A 12-week, randomized, double-blind study compared the effects of torasemide 2.5 mg and indapamide 2.5 mg in 66 hypertensive patients with grade 1 and grade 2 elevations in blood pressure. Drug doses were doubled if DBP remained above 100 mmHg after 4 weeks. Art. Both diuretics caused similar and significant reductions in DBP, with the maximum reduction observed after 8–12 weeks. after starting therapy. Doubling the diuretic dose was required in 9 (28%) of 32 patients receiving torsemide and 10 (29%) of 32 patients receiving indapamide. DBP decreased<90 мм рт. ст. к концу исследования у 94% больных, получавших торасемид, и у 88% больных, принимавших индапамид .

Longer-term observations of the effectiveness of torasemide were also carried out. A 24-week randomized trial examined the effects of torasemide 2.5 mg and hydrochlorothiazide 25 mg in combination with triamterene 50 mg, doubling the doses after 10 weeks. with insufficient reduction in DBP in 81 patients with hypertension. Both groups achieved similar and significant reductions in blood pressure, although the antihypertensive effect of the diuretic combination was slightly more pronounced. Similar results were demonstrated in another study of the same duration with a similar design in 143 patients with hypertension. With the same antihypertensive effectiveness of torasemide and the combination of hydrochlorothiazide with triamterene (or amiloride), both types of therapy did not cause significant changes in either the concentration of electrolytes in the blood serum or indices of carbohydrate and lipid metabolism.

In the work of O.N. Tkacheva et al. studied the effect of torasemide 5-10 mg in combination with 10 mg enalapril and 12-25 mg hydrochlorothiazide in combination with 10 mg enalapril on electrolyte balance, carbohydrate, lipid and purine metabolism in women with uncontrolled hypertension in the postmenopausal period. There was a significant decrease in potassium and magnesium levels after 24 weeks. hydrochlorothiazide therapy by 11 and 24%, respectively (p<0,05), в то время как в группе торасемида статистически значимых изменений уровня калия и магния не было выявлено. Торасемид не оказывал влияния на углеводный, липидный и пуриновый обмен, тогда как в группе тиазидного диуретика было зарегистрировано достоверное повышение индекса инсулинорезистентности и уровня мочевой кислоты.

Consequently, torasemide in doses up to 5 mg/day, which are used in the treatment of hypertension, is comparable in antihypertensive effectiveness to thiazide diuretics (hydrochlorothiazide, chlorthalidone and indapamide), but is much less likely to cause hypokalemia. Unlike other loop and thiazide diuretics, long-term treatment with torasemide does not require monitoring of electrolytes, uric acid, glucose and cholesterol. Thus, torasemide in low doses is an effective antihypertensive drug, which, when taken 1 time per day, causes a long-term and uniform decrease in blood pressure throughout the day. Unlike all other loop and thiazide diuretics, torasemide rarely causes hypokalemia and has little effect on purine, carbohydrate and lipid metabolism. When treated with torasemide, repeated laboratory monitoring of biochemical parameters is less often required, which reduces the overall costs of treating hypertension.

A comparison of the clinical effects of conventional torasemide and the extended-release form of the drug showed that the latter had a non-inferior effect on reducing DBP, and the degree of reduction in SBP was also similar for both drugs.

Scheme for the use of torasemide for the treatment of hypertension. The drug is recommended in an initial dose of 5 mg 1 time / day. If the target blood pressure (<140/90 мм рт. ст. для большинства больных) не было достигнуто за 4 нед. то в соответствии с recommendations the doctor can increase the dose to 10 mg 1 time / day or add an antihypertensive drug of another group to the treatment regimen, preferably from the group of drugs that block the RAS (ACE inhibitors or ARBs), or CCBs. Extended-release tablets are prescribed orally 1 time per day, usually in the morning, regardless of meals.

In studies in patients with hypertension, extended-release torasemide slightly reduced potassium levels after 12 weeks. treatment. The drug had virtually no effect on biochemical indicators such as urea, creatinine and uric acid, and the incidence of gout was similar in the placebo group. In long-term studies, the administration of long-acting torasemide at doses of 5 and 20 mg over the course of a year did not cause significant changes in blood lipid levels compared to baseline values.

Conclusion

Torsemide is a loop diuretic that is recommended for patients with CHF and hypertension. When treating patients with CHF, the drug is not inferior in diuretic effect to furosemide, and additionally has antialdosterone and antifibrotic effects. The drug can be successfully used in cases of impaired renal function and impaired absorption of furosemide in patients with severe heart failure. For hypertension, torasemide reduces blood pressure when used 1 time per day at a dose of 5-10 mg for 4 weeks; if necessary, can be used in combination with drugs that block the RAS. There is evidence of effectiveness in the treatment of postmenopausal women with hypertension in combination with ACE inhibitors. Torsemide therapy is well tolerated and extremely rarely leads to metabolic and electrolyte disturbances.

Literature

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at the International Federation of Clinical Chemistry:

analytical problems of determining biochemical markers of acute coronary syndromes

“This document has been translated with permission of the National Academy of Clinical Biochemistry, Washington, DC, USA.

NACB is not responsible for the accuracy of the translation. Th e views presented are those of the authors and not necessarily those of the NACB.” Copyright © 2008 American Association for Clinical Chemistry and Terra Medica

W. G. Wilson Tang, Gary S. Francis, David A. Morrow, L. Christine Newby, Christopher P. Cannon, Robert L. Jess, Alan H. B. Wu6, Alan B. Storrow, Robert G. Christenson

Members of the NAKB committee

Chairman. Robert G. Christenson

Fred S. Apple, Christopher P. Cannon and Gary Francis, Robert L. Jess, David A. Morrow, L. Christine Newby, Ian Rawkild, Alan B. Storrow, W. G. Wilson Tang, Alan H. B. Wu

All Committee member relationships with industry can be found at http://www.aacc.org/AACC/members/nacb/LMPG/OnlineGuide/PublishedGuidelines/ACSHeart/heartpdf.htm. The materials in this publication express the opinions of the authors and committee members and do not represent the official position of the National Academy of Clinical Biochemistry (NACB). The National Academy of Clinical Biochemistry is an academy of the American Association of Clinical Chemistry.

A. Conditions for determining markers in heart failure.

B. Background and Definition of Terms.

B. Conversions and determination of brain-type natriuretic peptide (BPNP) and amino-terminal precursor of brain-type natriuretic peptide (pro-BPMT).

II. USE OF LABORATORY MARKERS

FOR INITIAL ASSESSMENT OF HEART FAILURE

A. Diagnosis of heart failure.

1. NPMT or pro-NPMT in the diagnosis of acute decompensated heart failure.

III. USE OF LABORATORY MARKERS IN SCREENING FOR HEART DYSFUNCTION

A. NPMT or pro-NPMT in screening for heart failure and cardiac dysfunction.

B. Approaches to screening for cardiac dysfunction.

IV. USE OF LABORATORY MARKERS IN CONTROL OF TREATMENT OF HEART FAILURE

A. Therapeutic monitoring under the control of the results of determining NPMT or pro-NPMT.

Literature

I. General overview of analytical problems in determining laboratory markers of heart failure

A. Conditions for determining laboratory markers in heart failure

In the last decade, a revolution has occurred in the identification of a number of laboratory markers and approaches to the diagnosis and treatment of heart failure. The medical community hopes that significant advances in understanding the currently available cardiac markers will lead to better identification of heart failure variants and individualization of treatment for these conditions and beyond. However, as with most new diagnostic methods, despite promising results from key trials, there are many challenges in the clinical setting.

The material discussed in this guideline relates to the determination of NPMT, pro-NPMT and cardiac troponin in relation to the identification, risk stratification and treatment of heart failure, including treatment indications for adult patients (over 18 years of age). Together with the accompanying document " Practical guidelines of the National Academy of Clinical Biochemistry and the Committee for the Standardization of Markers of Heart Damage of the International Federation of Clinical Chemistry: analytical problems in determining biochemical heart failure" These recommendations are intended to promote the appropriate use of the results of these studies by clinicians and laboratory personnel. The committee believes that dissemination of these guidelines to clinicians and laboratory personnel should improve their understanding and, ultimately, patient care and outcomes in heart failure. Although specificity is difficult in this situation, the guide is intended to be a quick guide that may be useful in specific situations. The Committee believes that obtaining and disseminating knowledge about the determination of natriuretic peptides is a major challenge to the application of the results of such tests. For this reason, there are plans to disseminate these recommendations widely. The Committee believes that this will help educate users about the advantages and disadvantages of the NPMT and pro-NPMT definitions. For example, in terms of cost, the direct cost of an NPMT or pro-NPMT assay is approximately US$50 (2007 dollars). There is evidence, although somewhat conflicting, that the use of the NPMT definition generally reduces the costs of heart failure treatment without increasing the risk to patients. Costs were considered by the committee when developing the recommendations but were considered modest compared with the overall costs of treating heart failure, a view that is well documented.

It is important to emphasize that the value of the analysis results is that they complement clinical observations about the course of the disease. Thus, the determination of biochemical markers (such as NPMT or pro-NPMT) is not important in itself and should be used and interpreted in a broader clinical context, taking into account associated factors. When used correctly, the health benefits of testing will far outweigh the side effects and risks associated with obtaining NPMT and pro-NPMT level information. The use of cardiac troponin results in connection with population-based studies of heart failure is also discussed, primarily in relation to their role in risk stratification.

B. Background and Definition of Terms

Heart failure is a complex clinical syndrome that can result from any structural or functional abnormality in the heart that disrupts the ability of the ventricles to fill with or eject blood. This problem, which affects 2-3% of the US population, is growing in importance along with its associated costs. According to some authors, only 50% of such patients live longer than 4 years. The increasing prevalence of heart failure is a consequence of the aging population, as well as a marked increase in the number of people who survive myocardial infarction. According to the most conservative estimates, 50% of cases of heart failure are of ischemic origin, in 75% of cases the main etiological factor is hypertension. Costs associated with heart failure in Europe and the United States are estimated at $100 billion, with hospitalization accounting for 70% of costs in the United States.

A bedside diagnosis of heart failure is made based on clinical signs and symptoms rather than on the results of any tests. However, a significant proportion of patients turn to a cardiologist after a general practitioner has mistakenly made a diagnosis other than heart failure. In this regard, the identification of biomarkers in heart failure has three important goals: 1) to elucidate possible (and likely reversible) causes of heart failure; 2) confirm the presence or absence of heart failure syndrome; and 3) assess the severity of heart failure and the risk of its progression.

Over the past ten years, natriuretic peptides, especially NPMT and its amino-terminal propeptide pro-NPMT, have been shown to be highly informative in confirming or refuting the diagnosis of heart failure, as well as in determining long-term risk. In addition, several new cardiac, inflammatory and metabolic biomarkers have begun to be reported in the literature, such as C-type natriuretic peptide, endothelin-1, C-reactive protein, cardiac troponin, apelin, myotrophin, urotensin-II, adrenomedullin and proadrenomedullin middle fragment, cardiotropin -1, urocortin, soluble ST2 receptor, myeloperoxidase (MPO), copeptin, growth differentiation factor-15 (GDF-15), lymphocyte G-protein coupled receptor kinases (GRK-2), galectin-3, middle fragment and other circulating forms of natriuretic propeptide type A and many others. Their clinical significance remains to be established and confirmed (Table 3.1).

Table 3.1. Some laboratory markers known or currently being studied for the clinical diagnosis, treatment and risk stratification of heart failure

Standard laboratory markers

Natriuretic hormones
Study of blood natriuretic levels
hormones (BNP and NT-proBNP) are indicated to exclude
alternative causes of shortness of breath and determining the prognosis.
Diagnostically significant are:
BNP level
– more than 35 pg/ml,
NT-proBNP level
– more than 125 pg/ml
(class of recommendation IIa, level of evidence C).
Normal BNP and NT-proBNP levels exclude the diagnosis of HF!
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Scale for assessing the clinical condition of a patient with CHF (SCCS) (modified by Mareeva V. Yu.)

Symptom/sign
Quantity
points
Expressiveness
Edema
0 – no
1 – pasty
2 – swelling
3 – anasarca
SBP level
0 – more than 120 mm Hg. Art.
1 – 100–120 mm Hg. Art.
2 – less than 100 mm Hg. Art.
TOTAL
…
0 points – absence of clinical signs of HF.
I FC – less than or equal to 3 points;
II FC – from 4 to 6 points;
III FC – from 7 to 9 points;
IV FC – more than 9 points
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Scale for assessing the clinical condition of a patient with CHF (SCCS) (modified by Mareeva V. Yu.)

Heart failure with low EF
(HFrEF)
1. Symptoms ± Signs*
2. LVEF<40%

patients treated with diuretics
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Heart failure with low EF (HFrEF)

Heart failure with intermediate EF
(HFpEF)
1. Symptoms ± Signs*
2. LVEF 40-49%
3. Increase in NP level**

* - signs may not be observed in the early stages of heart failure and in

** - BNP >35 pg/ml and/or NT-proBNP >125 pg/ml.
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Heart failure with intermediate EF (HFpEF)

Heart failure with preserved EF
(HFpEF)
1. Symptoms ± Signs*
2. LVEF ≥50%
3. Increase in NP level**
4. At least one of the additional criteria:
a) appropriate structural change
(LV hypertrophy and/or LA dilatation)
b) diastolic dysfunction.
* - signs may not be observed in the early stages of heart failure and in
patients treated with diuretics;
** - BNP >35 pg/ml and/or NT-proBNP >125 pg/ml.
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Heart failure with preserved EF (HFpEF)

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Patients with HFpEF and HFpEF

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Patients with HFpEF and HFpEF

Treatment

Conservative treatment
Treatment goals: preventing the progression of CHF
(with FC I), reduction of symptoms, improvement of quality
life, inhibition and reverse development of remodeling
target organs, reducing the number of hospitalizations,
reduction in mortality.
An algorithm for managing patients with CHF is presented in
Appendix B.
All medicines for the treatment of CHF and decreased
LVEF can be divided into two main categories
according to the degree of evidence (Figure 1).
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Conservative treatment

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Basic drugs
influencing the prognosis of patients with CHF
ACE inhibitors
Used in maximum tolerated doses for everyone
patients with CHF I–IV class and with LVEF<40 % для снижения риска
death, re-hospitalization and improvement
clinical condition. Refusal to prescribe ACE inhibitors to patients
low and intermediate LVEF cannot be considered
justified if the SBP level is >85 mm Hg. and leads to
increased risk of death in patients with CHF (class
recommendations I level of evidence A).
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ACE inhibitors
ACE inhibitors have not yet proven their ability to improve prognosis
patients with HFpEF. However, due to improvement
functional status of patients and risk reduction
forced hospitalizations, ACEIs are indicated for everyone
patients with HFpEF (class of recommendations IIa, level
evidence B).
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The main drugs that affect the prognosis of patients with CHF

Starting
dose
Starting dose
for hypotension
2.5 x 2
1.25 x 2
10 x 2
20 x 2
6.25 x 3 (2)*
3.125 x 3 (2)
25 x 3 (2)
50 x 3 (2)
Fosinopril
5 x 1 (2)
2.5 x 1 (2)
10-20 x 1 (2)
20 x 1 (2)
Perindopril
2x1
1x1
4x1
8x1
Lisinopril
2.5 x 1
1.25 x 1
10 x 1
20 x 1
Ramipril
2.5 x 2
1.25 x 2
5x2
5x2
Spirapril
3x1
1.5 x 1
3x1
6x1
Trandolapril
1x1
0.5 x 1
2x1
4x1
5 x 1 (2)
2.5 x 1 (2)
10-20 x 1 (2)
40 x 1 (2)
7.5 x 1 (2)
3.75 x 1 (2)
15 x 1 (2)
30 x 1 (2)
A drug
Enalapril
Captoril
Quinapril
Zofenopril
Therapeutic Maximum
dose
dose
* - numbers in brackets indicate the possibility of different frequency of assignment
ACE inhibitors for CHF
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Dosages of ACE inhibitors for the treatment of CHF (mg × frequency of administration)

The main drugs that affect the prognosis of patients with CHF
ARA
Used in maximum tolerated doses in patients
CHF I–IV FC with LVEF<40 % для снижения комбинации риска
deaths and hospitalizations due to CHF with
intolerance to ACE inhibitors (class of recommendations IIa, level
evidence A).
ARAs have not been shown to improve the prognosis of patients with
HFpEF and with HFpEF. Use of the ARA candesartan in patients
with HFpEF and HFpEF may reduce hospitalization rates
(class of recommendations IIb, level of evidence B), and with
intolerance to ACE inhibitors in such patients, candesartan may
be the drug of choice (class IIa recommendations, level
evidence B).

The main drugs that affect the prognosis of patients with CHF

Dosages of ARAs recommended for prevention and
treatment of CHF (mg x frequency)
Starting
dose
Starting dose
for hypotension
Therapeutic
dose
Maximum
dose
Candesartan
4x1
2x1
16 x 1
32 x 1
Valsartan
40 x 2
20 x 2
80 x 2
160 x 2
Losartan a,b
50 x 1
25 x 1
100 x 1
150 x 1
A drug
Note: a - drugs whose higher doses have been demonstrated
reduction in morbidity and mortality compared to low ones, but no
Significant placebo-controlled RCTs and optimal doses have not been established;
b - this treatment did not show a decrease in cardiovascular and general
mortality in patients with HF or after AMI (did not impair the effectiveness
ongoing treatment).
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Dosages of ARAs recommended for the prevention and treatment of CHF (mg x frequency)

The main drugs that affect the prognosis of patients with CHF

A new therapeutic class of drugs has been developed,
acting on the RAAS and the neutral endopeptidase system
(ARNI). The first drug from this group is LCZ696, a substance
which consists of fragments of valsartan and sacubitril
(neprilysin inhibitor). Thanks to inhibition
neprilysin slows down the destruction of NP, bradykinin and
other peptides. Circulation of high concentrations of ANP and
BNP causes physiological effects through binding
with its receptors and increased production
cyclic GMF, thereby increasing diuresis, natriuresis,
causing relaxation of the myocardium and interfering with the processes
remodeling.
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The main drugs that affect the prognosis of patients with CHF
Neprilysin receptor antagonists (ARNIs)
In addition, ANP and BNP are secretion inhibitors
renin and aldosterone. Selective blockade of receptors
angiotensin II (AT1 subtype) reduces vasoconstriction,
sodium and water retention and myocardial hypertrophy.
Recent studies have shown long-term effects
sacubitril/valsartan versus ACE inhibitor (enalapril)
on the level of morbidity and mortality in outpatient
patients with symptomatic HFrEF EF ≤40%.

The main drugs that affect the prognosis of patients with CHF
Neprilysin receptor antagonists (ARNIs)
ARNI is recommended for patients with FC II-III CHF and LVEF<40%
stable course (without decompensation, administration of i.v.
or doubling the dose of oral diuretics and with SBP > 100
mmHg Art.), if ACE inhibitors (or ARAs) are tolerable. Translation
this category of patients on ARNI (at a dose of 100 mg x 2 times
no earlier than 36 hours after the last dose
ACEI (ARB), followed by dose titration to optimal
200 mg x 2 times a day) is produced for additional
reducing the risk of death and subsequent hospitalizations in
connection with worsening CHF (class of recommendations I,
level of evidence B).
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The main drugs that affect the prognosis of patients with CHF
Neprilysin receptor antagonists (ARNIs)
You can consider the use of ARNI in patients with CHF II-III
FC with LVEF<35% стабильного течения в качестве стартовой
therapy (instead of ACE inhibitors) to reduce the risk of death and
hospitalizations due to worsening CHF (class

Combination of two renin-angiotensin blockers
systems (excluding AMKR) is not recommended for treatment
patients with CHF due to a significant increase in serious
adverse events, including symptomatic
hypotension and deterioration of renal function (class of recommendations
III, level of evidence A).
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The main drugs that affect the prognosis of patients with CHF
Beta blockers
BBs are used in all patients with FC II–IV CHF and LVEF<40%
to reduce the risk of death and readmissions
together with ACE inhibitors (ARB) and AMKR (class of recommendations I, level
evidence A).
BABs are prescribed starting from 1/8 of the average therapeutic
dose, optimally after achieving the state
compensation, and slowly titrate to maximum
portable.
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The main drugs that affect the prognosis of patients with CHF
Beta blockers
Beta blockers can be prescribed to patients with HFpEF and HFpEF with
to reduce heart rate and severity of LVH.
The α-β adrenergic blocker carvedilol, in addition to reducing heart rate,
has a positive impact on performance
LV relaxation in patients with HFpEF (class of recommendations
IIb, level of evidence C).
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Dosages of BRB recommended for prophylaxis and
treatment of CHF (mg x frequency)
Starting dose
Therapeutic
dose
Maximum
dose
Bisoprolol
1.25 x 1
10 x 1
10 x 1
Metoprolol succinate
slow
release
12.5 x 1
100 x 1
200 x 1
Carvedilol
3.125 x 2
25 x 2
25 x 2
Nebivolol*
1.25 x 1
10 x 1
10 x 1
A drug
* - in patients over 70 years old
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Dihydropyridine BMCCs (amlodipine and felodipine) are not
influence the prognosis of patients with CHF.
These drugs can be prescribed against the background of the main
therapy for CHF for additional control of blood pressure, blood pressure
pulmonary artery and valve regurgitation (class
recommendations IIb, level of evidence B).
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Diuretics

Slow calcium channel blockers (SCBCs)
For patients with HFrEF and HFpEF, calcium antagonists
verapamil and diltiazem are contraindicated (class
recommendations III, level of evidence C).
Prescribing verapamil and diltiazem in patients with HFpEF
to reduce heart rate can only be recommended in
case of intolerance to beta blockers and in the absence of pronounced
CHF, manifested, for example, by fluid retention, and EF
LV >50% (class of recommendation IIb, level of evidence C).
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Iron supplements
Intravenous use of trivalent drugs
iron should be considered in patients with CHF and
hemoglobin level<120 г/л для уменьшения симптомов и
improving exercise tolerance (class
recommendations IIa, level of evidence A).
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The use of statins has not proven to influence prognosis
patients with CHF, but led to a decrease in the number
hospitalizations for ischemic ethology.
Primary use of statins may be considered by
patients with CHF of ischemic etiology (class of recommendations
IIb, level of evidence A).
Primary prescription of statins for patients with CHF
non-ischemic etiology is not recommended (class
recommendations III, level of evidence B).
Previously prescribed statin therapy for patients with
ischemic etiology of CHF should be continued
(class of recommendation IIa, level of evidence B).
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Aspirin
Aspirin administration does not affect the prognosis of patients with CHF and
in some cases weakens the effect of fixed assets
treatment. Therefore, prescribing aspirin may be
considered only in patients who suffered ACS no more than 8
weeks ago and have undergone percutaneous procedures
intravascular effects (class of recommendations IIb,
level of evidence B).
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Cytoprotectors (trimetazidine MB)
Prescription of trimetazidine MB should be considered with
patients with CHF of ischemic etiology in addition to
the main means of treating decompensation for
elimination of symptoms, normalization of hemodynamics (and
increase in LVEF) and possible reduction in the risk of death and
readmissions (class IIA recommendations, level
evidence A).
Evidence of beneficial effects on symptoms and
There are currently no prognosis for other cytoprotectors.
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Peripheral vasodilators
Convincing data on the effect of vasodilators (including
including nitrates and their combination with hydralazine) are not present, and they
application may only be considered to eliminate
angina when other methods are ineffective (class
recommendations IIb, level of evidence B).
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Coenzyme Q-10
The use of coenzyme Q-10 in addition to basic products
treatment of CHF can lead to an increase in LVEF and elimination
symptoms and even, as shown in the relatively small
by volume of a randomized clinical trial,
reduce mortality. Therefore, the use of Coenzyme Q-10
can be considered as an addition to the main one
therapy for CHF (class of recommendations IIb, level of evidence
B).
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Treatment of patients with HFpEF and HFpEF
The pathophysiology of HFpEF and HFpEF is based on different
reasons, which include various associated
such as cardiovascular diseases (eg, AF, hypertension,
IHD, pulmonary hypertension) and other diseases, not
related to cardiovascular diseases (diabetes, chronic
kidney disease (CKD), iron deficiency anemia, COPD and
obesity). Unlike patients with HFrEF,
Hospitalization and death are more common in patients with HFpEF/HFpEF
not associated with cardiovascular diseases.
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Treatment of patients with HFpEF and HFpEF
There is still no proven treatment for patients with HFpEF and
HFpEF, which would reduce morbidity and mortality
these patients. Since these people are usually elderly
patients with severe symptoms and often have
low quality of life, an important goal of treating such
patients is to reduce symptoms and improve them
well-being.
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to symptoms
Diuretics generally relieve congestion if
such are present, thus reducing symptoms and
manifestations of heart failure. Diuretics have been shown to reduce
symptoms of HF regardless of LVEF (class I C).
There is no evidence that BB and AMCR reduce symptoms
HF in these patients.
There are conflicting data regarding
effectiveness of ACEIs and ARBs in such patients (proven
only the effectiveness of candesartan, assessed by
NYHA scale).
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Ivabradin

Impact of treatment in patients with HFpEF and HFpEF
for hospitalization
Some studies indicate that
nebivolol, digoxin, spironolactone and candesartan may
reduce the number of hospitalizations for HF in patients with
sinus rhythm.
For patients with AF, BBs are not effective, and digoxin is
the effect on hospitalization in these patients is not
studied.
The evidence supporting ARBs and ACEIs is inconclusive.
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Digoxin

Impact of treatment in patients with HFpEF and HFpEF
on mortality
According to studies, ACEIs, ARBs, BBs and AMCRs do not reduce
mortality in patients with HFpEF or HFpEF.
However, in older patients with HFrEF, HFpEF, or
HFpEF nebivolol reduced the combined endpoint
point mortality/hospitalization for cardiovascular disease, with no significant correlation between
effect of treatment and baseline EF.
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Digoxin

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Omega-3 polyunsaturated fatty acids (Omega-3 PUFA)

Drug treatment of HFpEF

Drugs
Class and level
ACE inhibitors
IIa B
RA antagonists
IIb B
- ARA intolerance to ACE inhibitors
(candesartan)
IIa B
Beta blockers
IIb C
- Nebivolol
IIa C
AMKR
IIa B
Diuretics
IIb C
BMCC (verapamil and diltiazem)
III C
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Oral anticoagulants (OAAC)

Drug treatment of HFpEF
To improve FC and reduce the risk of hospitalization
Drugs
Class and level
ACE inhibitors
IIa B
RA antagonists
IIa B
- ARA intolerance to ACE inhibitors
(candesartan)
IIa B
Beta blockers
IIb C
- Carvedilol
IIb C
AMKR
IIa B
Diuretics
IIb C
BMCC (verapamil and diltiazem)
IIb C
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Oral anticoagulants (OAAC)

Implantation of SRT and ICD

Drugs that do not affect the prognosis of patients with CHF and are used to improve symptoms

rhythm with HFrEF II–IV class with LVEF ≤35%, blockade
left PNH with a QRS complex duration of ≥150 ms with the aim
improving the clinical course of HF and reducing
mortality (class of recommendation I, level of evidence A).
Implantation of SRT/SRT-D is indicated for patients with sinus
rhythm with HFrEF II–IV class with LVEF ≤35%, blockade
left PNH with a QRS complex duration of 130–149 ms s
to improve the clinical course of the disease and
reduction in mortality (class of recommendations I, level
evidence B).
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Antiarrhythmics

Cardiac resynchronization therapy (CRT)
Implantation of SRT/SRT-D may be considered in
patients with HFrEF with LVEF ≤35%, II–IVFC with
the presence of blockade of the right LES or nonspecific
conduction disturbances with QRS duration ≥150ms
(class of recommendation IIb, level of evidence B).
Implantation of CRT/CRT-D is not indicated in patients with HFrEF II–
IV FC if they have a blockade of the right LES or
nonspecific conduction disorder with
QRS duration< 150 мс (класс рекомендаций III, уровень
evidence B).
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Slow calcium channel blockers (SCBCs)

Cardiac resynchronization therapy (CRT)
Implantation of SRT/SRT-D should be considered by
patients with HFrEF class II–IV, with permanent AF with
LVEF ≤35%, despite OMT, with QRS duration >130
ms, the presence of LBBB and completed or planned
radiofrequency catheter ablation of the AV node (class
recommendations IIa, level of evidence B), or when
pharmacological control of heart rate, which provides
more than 95% of imposed complexes (class of recommendations IIb,
level of evidence C) to reduce the risk of death and
improving the clinical course of heart failure.
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Slow calcium channel blockers (SCBCs)

Cardiac resynchronization therapy (CRT)
Implantation of SRT/SRT-D is contraindicated in patients with
HFrEF class II–IV with QRS duration<130 мс (класс
recommendations III, level of evidence A).
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Iron supplements

ICD is recommended for patients with expected
life expectancy more than 1 year for secondary
prevention of sudden cardiac death (SCD),
survivors of ventricular fibrillation or ventricular
tachycardia with unstable hemodynamics, or with loss
consciousnesses that occurred 48 hours after
myocardial infarction (MI), and also in the event that there is no
reversible causes of these rhythm disturbances
(grade of recommendation I, level of evidence A).
ICD is recommended for all patients with class II-III heart failure after
MI at least 40 days ago with LVEF ≤35%
for the purpose of primary prevention of SCD (class of recommendations
I, level of evidence A).
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HMG-CoA reductase inhibitors (statins)

Implantable cardioverter defibrillator (ICD)
ICD is recommended for all patients with FC II-III CHF
non-ischemic etiology with LVEF ≤35% with the aim
prevention of SCD (class of recommendations IIb, level
evidence A).
ICD can be recommended for patients with FC I CHF and EF
LV ≤30% with ischemic LV dysfunction after 40 days
after myocardial infarction and during
non-ischemic CHF to prevent the risk of sudden
cardiac death (class of recommendations I, level
evidence B) or with non-ischemic CHF (class
recommendations IIb, level of evidence B).
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Aspirin

Implantable cardioverter defibrillator (ICD)
ICD is not indicated for patients with class IV CHF that persists.
despite OMT, for which it is impossible to achieve
compensation and a favorable prognosis are not planned
heart transplantation, implantation of artificial left
ventricle and there are no indications for CRT (recommendation class III,
level of evidence C).
For patients with FC IV CHF awaiting diagnosis
artificial LV or heart transplantation,
ICD implantation is possible at the discretion of the team,
consisting of a cardiologist, electrophysiologist and
cardiac surgeon (class of recommendations IIb, level
evidence C).
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Transcript

3 Definition HF is a clinical syndrome caused by structural and/or functional pathology of the heart, which leads to a decrease in cardiac output and/or an increase in intracardiac pressure at rest or during exercise, which is characterized by typical symptoms (shortness of breath, peripheral edema and fatigue) and accompanied by characteristic signs (increased pressure in the jugular vein, wheezing, peripheral edema).

4 Criteria Classification Type of HF With reduced EF 1 Symptoms and signs With moderately reduced EF Symptoms and signs With preserved EF Symptoms and signs 2 LVEF<40% ФВЛЖ 40-49% ФВЛЖ 50% 3 1. BNP >35 pg/ml; NTproBNP>125 pg/ml 2. At least one additional. criterion: a. significant structural pathology (LVH and/or DLP) b. diastolic dysfunction 1. BNP > 35 pg/ml; NTproBNP>125 pg/ml 2. At least one additional. criterion: a. significant structural pathology (LVH and/or DLP) b. diastolic dysfunction

5 Recommendations for preventing the development or progression of HF before symptoms develop Recommendations Class Level Treatment of hypertension to prevent or delay the development of HF and increase life expectancy Statins for coronary artery disease or high risk, regardless of the presence of systolic dysfunction, to prevent or delay the development of HF and increase life expectancy Refusal smoking and reducing alcohol consumption I C Correction of other risk factors (obesity, dysglycemia) IIa C I I A A Empagliflozin should be considered in type II diabetes to prevent or delay the development of HF and increase life expectancy IIa B

6 Diabetes and Heart Failure Heart Failure: Subgroup Analysis Zinman B, et al New England Journal of Medicine Sep 2015, DOI: /NEJMoa

7 CKD or CHF lead to a vicious circle in which both organs are involved 1 Increased circulating blood volume Increased cardiac output Activation of compensatory mechanisms Increased peripheral resistance Increased blood pressure Slower natriuresis CKD Imbalance of nitric oxide and atomic oxygen Activation of the sympathetic nervous system Activation of the RAAS Inflammation Heart failure 1 Bongartz et al. Eur Heart J 2005;26:11. Cardiovascular lesions

8 Hospitalization for heart failure or CV death in patients with/without baseline heart failure Patients with hospitalization for heart failure or death from CVD (%) RR 0.63 (95% CI 0.51, 0.78) 7, 1 4.5 RR 0.72 (95% CI 0.50, 1.04) 20.1 Placebo 16.2 Empagliflozin 0 Patients without baseline heart failure Patients with baseline heart failure Cox regression analysis. CV, cardiovascular; RR, risk ratio; CI, confidence interval. Zinman B, et al New England Journal of Medicine Sep 2015, DOI: /NEJMoa

9 Hospitalization for heart failure or CV death: subgroup analysis Patients with event/analysed Empagliflozin Placebo RR (95% CI) Hospitalization for HF or CV death All patients 265/ /2333 0.66 (0.55, 0.79 ) Initial HF: No 190/ /2089 0.63 (0.51, 0.78) Initial HF: Yes 75/462 49/244 0.72 (0.50, 1.04) Hospitalization due to HF All patients 126/ /2333 0.65 (0.50, 0.85) Initial HF: No 78/ /2089 0.59 (0.43, 0.82) Initial HF: Yes 48/462 30/244 0.75 ( 0.48, 1.19) CV death All patients 172/ /2333 0.62 (0.49, 0.77) Initial HF: No 134/ /2089 0.60 (0.47, 0.77) Initial HF : Yes 38/462 27/244 0.71 (0.43, 1.16) Overall mortality All patients 269/ /2333 0.68 (0.57, 0.82) Initial HF: No 213/ /2089 0, 66 (0.54, 0.81) Initial HF: Yes 56/462 35/244 0.79 (0.52, 1.20) Cox regression analysis. HF, heart failure; CV, cardiovascular; RR, risk ratio; CI, confidence interval. Zinman B, et al New England Journal of Medicine Sep 2015, DOI: /NEJMoa In favor of empagliflozin In favor of placebo 0.25 0.50 1.00 2.00 4.00

10 Patients with events (%) 10 Cardiovascular death 38% risk reduction RR 0.62 (95% CI 0.49, 0.77) p< (через 48 месяцев) Плацебо 38% p< Эмпаглифлозин Эмпаглифлозин продемонстрирова л эффект ч/з 2 месяца ОР, отношение рисков Zinman B, Inzucchi SE et al., Cardiovasc Diabetol. 2014; 13:102

11 Patients with events (%) 11 Hospitalization for heart failure - 35% risk reduction RR 0.65 (95% CI 0.50, 0.85) p= (at 48 months) Placebo 35% p= Empagliflozin Empagliflozin demonstrated an effect w/w 1 -2 days Months RR, risk ratio Zinman B, et al New England Journal of Medicine Sep 2015, DOI: /NEJMoa

12 Frequency (%) Significant improvement in CV outcomes with empagliflozin RR: 0.86 (0.74-0.99) RR: 0.68 (0.57-0.82) RR: 0.62 (0.49- 0.77) RR: 0.65 (0.50-0.85) RR: 0.66 (0.55-0.79) -1.6% (p<0,04) ,1 10,5-2,6% (p<0,001) 8,3 5,7 3к-ЗНССЯ Общая смертность СС смерть Госпитализация изза сердечной недостаточности Плацебо (N=2333) -2,2% (p<0,001) 5,9 3,7-1,4% (p=0,002) 4,1 Эмпаглифлозин (N=4687) 2,7-2,8% (p<0,001) 8,5 5,7 Госпитализация изза сердечной недостаточности или СС смерть (за исключением фатального инсульта) ОР, отношение рисков. Указывается с 95% ДИ; САР; Снижение абсолютного риска. Zinman B, et al New England Journal of Medicine Sep 2015, DOI: /NEJMoa

13 Jardins new indication Indicated in patients with type 2 diabetes mellitus and high cardiovascular risk* in combination with standard cardiovascular therapy to reduce: overall mortality by reducing cardiovascular mortality; cardiovascular mortality or hospitalization for heart failure. High cardiovascular risk is defined as the presence of at least one of the following diseases and/or conditions: IHD (history of myocardial infarction, coronary artery bypass grafting, IHD with damage to one coronary vessel, IHD with damage to several coronary vessels); history of ischemic or hemorrhagic stroke; peripheral arterial disease (with or without symptoms). JARDINS instructions for medical use of the medicinal product Registration certificate: medicinal product

14 Recommendations of the European Society of Cardiology for the prevention of cardiovascular diseases, 2016 “In the absence of data from studies of other drugs in this group, the results obtained with empagliflozin cannot be considered a class effect” (regarding CV events).

15 Recommendations of the European Society of Cardiology for the diagnosis and treatment of acute and chronic heart failure, 2016 In the “Diabetes mellitus” section, the SGLT2 inhibitor and the only representative of this class, empagliflozin, are mentioned for the first time. “Early use of an SGLT2 inhibitor in patients with T2DM and cardiovascular disease” is recommended (grade IIa recommendation and level of evidence B)

16 Recommendations for preventing the development or progression of HF before the development of symptoms Recommendations Class ACEI level in asymptomatic system. LV dysfunction after MI to prevent or delay the development of HF and increase the life expectancy of ACE inhibitors in asymptomatic system. LV dysfunction without a history of MI to prevent or delay the development of HF ACE inhibitors in chronic conditions. IHD without system LV dysfunction to prevent or delay the development of HF β-blockers in asymptomatic system. LV dysfunction after MI I B I I IIa A B A ICD in asymptomatic system. LV dysfunction (LVEF<30%) в течении как мин. 40 дней после ИМ ИКД I B

17 Diuretics to relieve symptoms and signs of stagnation ICD therapy for EF 35% despite OMT, VF/VT CHF with reduced EF Treatment with ACE inhibitors and β-blockers Persistence of symptoms and EF 35% Yes Add AMR No Resistance to ACEIs / ARBs Persistence of symptoms and EF 35% Yes Sinus rhythm with QRS 130 ms No Sinus rhythm with heart rate 70 per 1 min BRAIN instead of ACEI Resynchronization therapy Ivabradine Yes Digoxin or G+nitrates, surgery Persistence of symptoms No Without additional treatment. Reducing the dose of diuretics?

18 Additional treatment for FC II-IV and reduced EF Inhibitors of If-channels Ivabradine should be considered for symptoms of HF with EF 35% at SR and heart rate 70 per minute despite treatment with β-blockers and OMT Ivabradine should be considered for symptoms of HF with EF 35% with SR and heart rate 70 per minute with intolerance or contraindications to β-blockers in addition to other therapy IIa IIa B B

19 Additional treatment for FC II-IV and reduced EF Angiotensin receptor blockers, neprelysin Sacubitril/valsartan to replace ACEI if symptoms persist despite OMT I B

20 Recommendations for resynchronization therapy Recommendations Class Level PCT is indicated for symptoms of HF in sinus rhythm with LBBB and a QRS duration of more than 150 ms with an EF of 35% PCT should be considered for symptoms of HF in sinus rhythm and a QRS duration of more than 150 ms without signs of LBBB with an EF of 35 % PCT is indicated for symptoms of HF in sinus rhythm with LBBB and a QRS duration of ms with an EF of 35% PCT may be considered for symptoms of HF in sinus rhythm and a QRS duration of ms without signs of LBBB with an EF of 35% I IIa I IIb A B B B

21 Recommendations for resynchronization therapy Recommendations Class Level PCT should be considered in class III-IV CHF with AF and QRS duration 130 ms with EF 35% PCT can be considered in patients with implanted devices and long RV stimulation time. With the exception of patients with stable CHF. PCT is contraindicated when QRS duration is less than 130 ms IIa IIb III B B A

22 Prevention of SCD Recommendations Class Level of ICD for secondary prevention with a favorable prognosis within 1 year ICD for primary prevention in CHF II-III FC, EF 35% despite 3 months. OMT with a favorable prognosis within 1 year ICD is contraindicated in the first 40 days after MI III C ICD is contraindicated in patients with class IV CHF (NYHA) III B ICD can be considered for a short period if there is a high risk of SCD or during the preparatory phase before surgery I I IIb A A/B C

23 Treatment of patients with preserved or moderately reduced EF RECOMMENDATIONS Class Level Examination of patients and treatment of associated cardiovascular and other pathologies. Nebivalol for the elderly? Diuretics when congestion occurs to relieve symptoms and signs I I C B

24 Thank you for your attention!

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Diagnosis and treatment of chronic heart failure (according to the recommendations of the European Society of Cardiology for the diagnosis and treatment of acute and chronic heart failure 2016)

^ V.N. Larina, I.I. Chukaeva

Department of Polyclinic Therapy, Faculty of Medicine, Russian National Research Medical University named after N.I. Pirogov, Ministry of Health of the Russian Federation, Moscow

The article is devoted to the diagnosis and treatment of chronic heart failure based on the 2016 recommendations of the European Society of Cardiology for the diagnosis and treatment of acute and chronic heart failure.

Key words: chronic heart failure, left ventricular ejection fraction, systolic dysfunction, diastolic dysfunction, BNP, NT-proBNP.

Among the most important medical problems, heart failure (HF) plays a leading role due to its high prevalence and poor prognosis. Chronic heart failure (CHF) is detected in 2% (1-3%) of the population of developed countries, reaching 10% or more among people over 70 years of age. Every 6th patient over 65 years of age who seeks help from a primary care physician for dyspnea on exertion has undiagnosed HF, mostly with preserved left ventricular (LV) ejection fraction (EF). HF syndrome can be compared to an iceberg. The visible part of the iceberg is the identified cases of HF: most of these patients are observed and treated on an outpatient basis by internists and cardiologists. The huge invisible part of the iceberg is the undiagnosed cases of HF, the majority of these patients have asymptomatic LV dysfunction.

Every 3rd patient hospitalized in the therapeutic department of a multidisciplinary hospital notes:

Contact information: Larina Vera Nikolaevna, [email protected]

CHF of different functional classes. In a significant number of cases, hospitalization is due to the progression of heart failure due to low adherence to treatment, the presence of uncontrolled arterial hypertension (AH), cardiac conduction and rhythm disturbances, pulmonary infections, etc. Among patients with CHF, the 5-year survival rate is approximately 50%, and the 10-year survival rate is approximately 10%. Up to 70% of patients die within 5 years after the first hospitalization for CHF, and the presence of LV dysfunction is associated with an increased risk of sudden death.

Today, a number of issues remain that require multilateral analysis, despite certain advances in the study of epidemiology and pathogenesis, drug and surgical treatment, and prevention of HF. In this regard, the updated version of the ESC (European Society of Cardiology) and HFA (Heart Failure Association) recommendations for the diagnosis and treatment of acute HF and CHF, proposed by a group of experts in May 2016, is of great practical interest. . .

Class Definition Statement for use

I Evidence and/or general agreement that a particular treatment or procedure is useful, effective, or beneficial Recommended for use/indicated (should be prescribed)

II Conflicting data and/or differences of opinion regarding the benefit/effectiveness of a particular treatment or procedure

IIa Most evidence/opinion suggests benefit/effectiveness, but more research needed Consider (appropriate to prescribe)

IIb Evidence/opinion is less convincing on benefit/effectiveness. To clarify the feasibility of prescribing, additional research is needed. Application can be considered (can be prescribed)

III Evidence and/or general agreement that a particular treatment or procedure is not helpful or effective, and in some cases may be harmful. Not recommended (not prescribed)

Table 2. Confidence levels

Confidence level Data source

A Data obtained from multicenter randomized clinical trials or meta-analyses

B Data are from a single randomized clinical trial or a few large non-randomized trials.

C Consensus and/or small studies, retrospective studies, registry data

The clinical guidelines reflect current issues regarding the etiology, classification, diagnosis, treatment and prevention of HF, based on a standard gradation of evidence (Tables 1, 2), which will help practicing physicians and other healthcare professionals in choosing the right tactics for managing patients with HF .

1) the term “HF with a slight decrease in LVEF” (40-49%) was introduced;

3) an algorithm for diagnosing non-acute HF is presented;

4) an algorithm has been developed that combines the diagnosis and treatment of acute HF, based on the presence/absence of congestion/hypoperfusion;

5) data on preventing the progression of heart failure and prolonging the life of patients was revised;

6) indications for prescribing a combination drug containing the neprilysin inhibitor sacubitril and the angiotensin receptor-neprilysin inhibitor (ARNI) inhibitor valsartan have been determined;

7) the indications for cardiac resynchronization therapy for heart failure have been changed;

8) a concept of early therapy was proposed, simultaneously with the diagnosis of acute HF, similar to the existing concept for acute coronary syndrome.

The recommendations consist of 12 sections, which contain the definition, epidemiology, prevention, prognosis and diagnosis of HF, pharmacological treatment of HF with reduced and preserved LVEF, non-surgical types of interventions for HF with reduced LVEF, comorbid conditions.

Chronic heart failure

MV type Criteria

With decreased Symptoms ± signs*

LVEF LVEF<40%

With a slight Symptoms ± signs* decrease in EF LVEF 40-49%

Increasing the level of NUP**

b) diastolic dysfunction With preserved Symptoms ± signs*

LVEF >50%

Increasing the level of NUP**

At least one additional criterion:

a) structural heart disease: LV hypertrophy and/or left atrium enlargement;

b) diastolic dysfunction

* Symptoms may be absent in the initial stages of heart failure and when treated with diuretics. **BNP (brain natriuretic peptide -

brain NUP) >35 pg/ml and/or NT-proBNP (N-terminal fragment of NUP precursor) >125 pg/ml. Designations: NUP - natriuretic peptide.

treatments for HF, acute HF, heart transplantation, multidisciplinary management of patients with HF, including palliative care. The recommendations are available in full on the ESC website.

Definition of CH

Heart failure is a clinical syndrome with typical symptoms (shortness of breath, swelling of the ankles, fatigue), which may be accompanied by signs caused by structural and/or functional changes in the heart (increased pressure in the jugular veins, wheezing in the lungs, peripheral edema), leading to a decrease in cardiac function. and/or increased intracardiac pressure at rest or during exercise.

The definition of HF focuses the doctor's attention on the need and importance of identifying HF at the preclinical stage - the stage of asymptomatic structural and/or functional changes in the heart (systolic or diastolic dysfunction of the LV), which are considered as precursors of HF.

The need to identify HF at the preclinical stage is due to existing evidence linking precursors to HF with a poor prognosis and reduced mortality, especially

among patients with asymptomatic LV systolic dysfunction, with timely treatment.

Terminology and classification of heart failure

HFA experts suggested considering HF depending on the value of LVEF as follows (Table 3):

HF with preserved LVEF (>50%);

HF with a slight decrease in LVEF (40-49%);

recommendations, patients with LVEF 40-49% were included in the so-called “gray zone”, and in the current version they are proposed to be considered as patients with HF with “average” LVEF: “The average child in a family of heart failure: HF with EF 40-49 %..." . Experts believe that the allocation of patients with a slight decrease in LVEF into a separate group will serve as an incentive for a detailed study of the characteristics of the clinical picture, hemodynamic and neurohumoral status, as well as therapy.

The term “heart failure” in current recommendations is used in the presence of clinical symptoms according to the NYHA (New York Heart Association) classification, even if the patient has a medical history 3.201b|1

Table 4. Clinical symptoms and signs of HF

Symptoms Signs

Typical More specific

Shortness of breath Increased pressure in the jugular veins

Orthopnea Hepatojugular reflux

Paroxysmal nocturnal dyspnea III heart sound (gallop rhythm)

Decreased exercise tolerance Displacement of the apical impulse to the left

Fatigue, tiredness, increased time Systolic murmur

recovery after physical activity

Swelling of the ankles

Less typical Less specific

Night cough Weight gain (>2 kg/week)

Wheezing Weight loss (with progressive heart failure)

Feeling of bloating Heart murmur

Weight gain (>2 kg/week) Peripheral edema

Depression Wheezing in the lungs

Confusion (especially in older people) Dullness of sound in the lower lungs

Loss of appetite (pleural effusion)

Fainting (especially the elderly) Tachycardia

Dizziness Tachypnea

Palpitations Irregular pulse

Bendopnea* Cheyne-Stokes breathing

Hepatomegaly

Cachexia

Oliguria

Cold extremities

Low pulse pressure

* Bendopnea (shortness of breath when bending forward) is a new symptom of HF, described by T. T. a1. in 2014. Note. 2016 additions are in bold and symptoms that are not in the current guidelines compared to the 2012 version are in italics.

there are no symptoms if treatment is effective. In the absence of symptoms or signs of HF, including a history, but in the presence of reduced LVEF, the patient is considered to have asymptomatic LV systolic dysfunction.

Patients who have had HF for some period are considered to have CHF. If the patient remains stable for at least 1 month following treatment for symptomatic HF, the patient is considered to have stable HF. With an exacerbation of CHF, we should talk about decompensation of HF, which can occur either suddenly or gradually, often leading to hospitalization. New-onset (de novo) HF can manifest acutely or gradually. The term “congestive HF” has been proposed to be used to describe acute HF or CHF with signs of volume overload. Specified states

in most cases, they can occur in the same patient at different periods depending on the course of HF.

Diagnosis of HF

Experts point to the need to determine the cause of cardiac origin, which is decisive when diagnosing HF and choosing optimal therapy.

As a rule, myocardial damage is the leading cause of impaired systolic and/or diastolic ventricular function. Pathology of the valvular apparatus, pericardium, cardiac conduction and rhythm disturbances, hypertension and other causes also contribute to the development of heart failure (usually there are several causes). The etiology of HF in the latest version of the recommendations is described in sufficient detail and includes the consequences of myocardial diseases, volume overload and arrhythmias.

Chronic heart failure

Diagnosis requires the presence of symptoms and clinical signs typical of heart failure. ESC experts have made amendments to the list of symptoms and signs necessary to make a diagnosis of heart failure, in order to facilitate the work of a doctor in everyday practice. Clinical symptoms and signs typical of HF are given in Table. 4.

The recommendations provide a simple and detailed algorithm for diagnosing heart failure. If the presence of HF is suspected, it is necessary to evaluate the medical history, clinical symptoms, physical examination and electrocardiography (ECG). Heart failure is unlikely in the absence of an appropriate history, symptoms and signs of HF, as well as in the absence of virtually unchanged ECG. Abnormal ECG findings increase the likelihood of HF but have low specificity, so the use of ECG data is recommended to rule out HF rather than confirm it. If at least one of the above parameters is present (history, symptoms, ECG changes), it is recommended to determine the concentration of natriuretic peptides (NUP), especially in the case of CHF.

Patients whose LLP values are lower than recommended do not need echocardiography (EchoCG) to exclude possible diseases of cardiovascular origin. An increased level of NUP helps establish an initial working diagnosis and identify patients in need of subsequent studies.

If the normal NUP values are exceeded (BNP (brain natriuretic peptide) >35 pg/ml; NT-proBNP (N-terminal fragment of the NUP precursor) >125 pg/ml), echocardiography is indicated, which helps the doctor develop a further treatment plan patient with HF, monitor its effectiveness, and assess life prognosis. If it is impossible to determine LLP in routine practice for confirmation

Table 5. Reasons for increasing the level of LLP

Origin Causes

Cardiac HF

Acute coronary syndrome

Embolism of pulmonary branches

Myocarditis

LV hypertrophy

Hypertrophic or

restrictive cardiomyopathy

Heart valve pathology

Congenital heart defects

Atrial and ventricular

tachyarrhythmia

Heart bruise

Cardioversion

Surgical procedures

involving the heart

Pulmonary hypertension

Non-cardiac Older age

Ischemic stroke

Subarachnoid

hemorrhage

Kidney failure

Liver dysfunction

(mainly cirrhosis

liver with ascites)

Paraneoplastic syndrome

Chronic obstructive

lung disease

Severe infection, including

pneumonia and sepsis

Severe burns

Pronounced metabolic

and hormonal disorders

(for example, thyrotoxicosis,

diabetic ketoacidosis, etc.)

When interpreting LLP values, it is necessary to remember about other reasons leading to an increase in its level (Table 5).

The diagnostic algorithm for HF with reduced and preserved LVEF is the same. On average, serum concentrations of NUP are lower in HF with preserved LVEF than in HF with reduced LVEF. The negative predictive value for both gradual and acute onset of HF is the same and amounts to 0.94-0.98. However, the positive predictive value of the LLP level is lower as with gradual

If the diagnosis of HF is confirmed (based on all available data): determine the etiology and begin treatment

Rice. 1. Algorithm for diagnosing CHF. * Typical symptoms of heart failure. **Normal function and volumes of the ventricles and atria; other reasons for the increase in LLP levels should be assumed. IHD - coronary heart disease; MI - myocardial infarction.

Signs (±symptoms) of HF

Rice. 2. Algorithm for diagnosing HF with preserved LVEF. LVMI - indexed LV myocardial mass; IOLP - indexed left atrium volume; m - men; f - women; E is the rate of early diastolic filling of the LV transmitral flow, Ecp is the average rate of early diastolic displacement of the lateral and septal segments of the mitral valve annulus according to tissue myocardial Dopplerography.

HF with preserved LVEF (>50%) HF with a slight decrease in LVEF (40-49%)

Structural changes:

>115 g/m2 (m) >95 g/m2 (w)

Functional changes:

E"<9 см/с

Chronic heart failure

Implantation of a cardioverter-defibrillator is recommended to prevent sudden death and prolong life in patients: a) with asymptomatic LV systolic dysfunction (LVEF<30%) ишемического происхождения спустя не менее 40 дней после острого инфаркта миокарда; б) с бессимптомной дилатационной кардиомиопатией неишемического происхождения (ФВ ЛЖ <30%), получающих оптимальное медикаментозное лечение I B

Treatment for other risk factors for HF (obesity, impaired glucose tolerance) is recommended to prevent the development of HF IIa C

Designations: ACE inhibitors - angiotensin-converting enzyme inhibitors; IHD - coronary heart disease.

(0.44-0.57), and with acute (0.66-0.67) onset of heart failure. In this regard, experts emphasize that the definition of LLP is necessary not so much to confirm, but to exclude HF.

Thus, as the initial diagnostic tests when diagnosing HF, experts proposed determining the concentration of NUP, performing an ECG and EchoCG, in contrast to previous recommendations, in which EchoCG was in first place, ECG in second place, and laboratory indicators in third place.

The algorithm for diagnosing CHF is presented in Fig. 1.

To diagnose CHF with preserved LVEF and with a slight decrease in it, it is proposed to take into account the following 4 criteria:

1) clinical symptoms and/or signs typical of HF;

2) preserved LVEF (>50%), a slight decrease in LVEF (40-49%);

3) increased levels of BNP >35 pg/ml, NT-proBNP >125 pg/ml;

4) objective evidence of functional and/or structural changes in the heart according to echocardiography (Fig. 2).

Prevention of heart failure

Current recommendations pay special attention to measures to prevent the development and progression of clinically significant HF. To date, it has been proven that the occurrence of HF, as well as its progression, can be prevented using a set of measures aimed at changing the patient’s lifestyle as the leading factor determining the state of health and risk factors for the development of HF (Table 6).

Rice. 3. Algorithm for the treatment of CHF with reduced LVEF. CRT - cardiac resynchronization therapy; HR - heart rate. Here and in Fig. 4: AMCR - mineralocorticoid receptor antagonists; ARAs - angiotensin II receptor antagonists; BAB - P-blockers; ACEIs are angiotensin-converting enzyme inhibitors.

Timely, evidence-based treatment of asymptomatic LV systolic dysfunction, hypertension, prescription of statins to patients with a high and very high risk of developing coronary heart disease (CHD), regular physical activity and smoking cessation are of particular importance for preventing the occurrence of HF and prolonging life. patients.

Treatment of heart failure

Pathogenetically based pharmacological treatment is the leading

approach to the management of patients with HF and is aimed at improving the clinical condition and functional activity, quality of life, preventing hospitalizations and reducing mortality. Treatment tactics and groups of pharmacological drugs recommended for HF with reduced LVEF are presented in Fig. 3 and 4.

Angiotensin-converting enzyme inhibitors (ACEIs), mineralocorticoid receptor antagonists (MCRAs), and β-blockers (BABs) (Class I, Level A) remain the first-line drugs for the treatment of all patients with HF.

Rice. 4. Pharmacological treatment of CHF with reduced LVEF (ESC 2016). BMCC - slow calcium channel blockers; NSAIDs are non-steroidal anti-inflammatory drugs.

since there is substantial evidence of their beneficial effect on prognosis. When prescribed together, ACE inhibitors and beta blockers have a complementary effect at the beginning of treatment of patients with CHF with reduced LVEF (class I, level A). Diuretics are indicated for patients with heart failure in the presence of edema syndrome in order to reduce the severity of clinical symptoms and signs (class I, level B), while the drug and its dose are determined by the attending physician (Table 7).

The goal of diuretic therapy is to achieve and maintain a euvolemic state using the lowest available dose of diuretic, which is adjusted gradually according to the individual characteristics of the patient. Diuretics should always be prescribed in combination with ACE inhibitors (or antagonists).

angiotensin II receptors (ARA), beta blockers and AMCR in patients with reduced LVEF in the presence of signs of fluid stagnation. In some asymptomatic patients with euvolemia/hypovolemia, diuretic therapy may be (temporarily) discontinued. Patients can self-adjust diuretic doses by monitoring symptoms/signs of congestion and weighing themselves daily.

Angiotensin II receptor antagonists are prescribed to all patients with persistent symptoms (P-GU functional class according to OTNA) and LVEF<35% (несмотря на лечение ИАПФ/АРА или БАБ) с целью уменьшения выраженности клинических симптомов, риска госпитализаций по поводу СН и улучшения выживаемости.

If clinical symptoms of HF and LVEF persist<35% у амбулаторных

Table 7. Doses of diuretics (in mg) used in patients with HF

Diuretics Initial dose Daily dose

Loop diuretics*

Furosemide 20- -40 40- 240

Bumetanide 0.5- -1.0 1- 5

Torasemide 5- -10 10- 20

Thiazide diuretics**

Bendroflumethiazide 2.5 2.5- 10.0

Hydrochlorothiazide 25.0 12.5- 100.0

Metolazone 2.5 2.5- 10.0

Indapamide 2.5 2.5- 5.0

Potassium-sparing diuretics***

Spironolactone/eplerenone 25.0 50 50 200

Amiloride 2.5 5 10 20

Triamterene 25.0 50 100 200

* Oral or intravenous, doses should be adjusted according to volume overload/body weight, high doses may cause renal impairment and ototoxicity. ** Thiazide diuretics are not prescribed for glomerular filtration rate<30 мл/мин/1,73 м2, за исключением случаев совместного применения с петлевыми диуретиками. *** Из АМКР предпочтительно назначение спиронолактона/эплеренона. Амилорид и триамтерен не следует комбинировать с АМКР. Обозначения: АРА - антагонисты рецепторов ангиотензина II.

For patients taking an optimal dosage of ACEI/ARB + beta blocker + MACR, it is recommended to replace the ACEI with the drug sacubitril/valsartan in order to reduce the risk of hospitalization for HF and death (class I, level B).

This addition to the 2016 guidelines is based on the results of the PARADIGM-HF trial, which included 8442 patients with HF. When taking sacubitril/valsartan, there was a statistically significant reduction in the risk of death from cardiovascular failure or hospitalization for HF, as well as an improvement in overall survival compared with taking enala-pril. Sacubitril/valsartan belongs to a group of drugs with simultaneous blockade of neprilysin (neutral endopeptidase) and AT1 receptors of angiotensin II, which increases its antiproliferative effect on the cardiovascular system.

hospitalizations due to heart failure and cardiovascular death (class I, level B).

Ivabradine has been proposed to be considered as a drug of choice in patients with HF with LVEF<35%, синусовым ритмом с частотой сердечных сокращений >70 per 1 min and the presence of hospitalizations during the last year due to decompensation of HF in order to reduce mortality and the frequency of hospitalizations for HF (class IIa, level B). The European Medicines Agency has approved ivabradine for use in Europe in patients with CHF, LVEF<35%, синусовым ритмом с частотой сердечных сокращений >75 per 1 min, since its positive effect on the prognosis in this category of patients has been proven.

Hydralazine and isosorbide dinitrate may be recommended in patients with HF with reduced LVEF who are intolerant of ACEIs or ARBs (or have contraindications to their use) to reduce the risk of death (Class IIb, Level B).

Chronic heart failure

randomized clinical studies are presented in table. 8.

Cardiac glycosides, in particular digoxin, are indicated when clinical symptoms of HF and sinus rhythm persist despite treatment with ACE inhibitors/ARBs, beta blockers and MACRs, in order to reduce the risk of hospitalization both for HF and for other reasons (class IIb, level IN). Digoxin can also be recommended to patients with HF and reduced LVEF, combined with atrial fibrillation, in order to slow the ventricular rhythm when other treatment methods cannot be used.

ω3-polyunsaturated fatty acid supplements may be considered for clinically significant HF in addition to primary care to reduce the risk of hospitalization and death from cardiovascular causes (Class IIb, Level B).

It is not advisable to initiate statin therapy in most patients with HF, since their beneficial effect on the prognosis of patients with HF and reduced LVEF has not been established. If the patient is already taking statins for coronary artery disease and/or hyperlipidemia, continuation of this therapy is indicated.

Oral anticoagulants are not recommended for use due to the lack of evidence of their effect on morbidity/mortality in patients with HF without atrial fibrillation. If a patient is taking anticoagulants because of atrial fibrillation or a high risk of venous thrombosis, continued use of these medications is advisable.

Antiplatelet drugs, including acetylsalicylic acid, are not recommended for use in patients with heart failure without concomitant coronary artery disease due to the lack of significant evidence of a positive effect on prognosis.

Thiazolidines (class III, level A) and non-steroidal anti-inflammatory drugs (class III, level B) are not recommended

Table 8. Drug doses (in mg) in patients with HF with reduced LVEF

Drugs Starting dose Target dose

Captoril1 6.25*** 50***

Enalapril 2.5** 20**

Lisinopril2 2.5-5.0* 20-35*

Ramipril 2.5* 10*

Trandolapril1 0.5* 4*

Bisoprolol 1.25* 10*

Carvedilol 3.125** 25**, 4

Metoprolol succinate 12.5-25* 200*

Nebivolol 1.25* 10*

Candesartan 4-8* 32*

Valsartan 40** 160**

Losartan2, 3 50* 150*

Eplerenone 25* 50*

Spironolactone 25* 50*

Sacubitril/valsartan 49/51** 97/103**

Inhibitors of sinus node If channels

Ivabradine 5** 7.5**

* 1 per day. ** 2 times a day. *** 3 times a day. 1 Target therapeutic doses obtained in studies in patients who have suffered myocardial infarction are indicated. 2 Drugs have been identified where higher doses were superior to lower doses in reducing mortality/morbidity, but there is no definitive evidence on the optimal drug dose based on independent, randomized, placebo-controlled trials. 3 There was no effect of this treatment on cardiovascular or other mortality in patients with HF. 4 50 mg 2 times a day is recommended for patients weighing more than 85 kg.

recommended for use due to an increased risk of heart failure progression and hospitalization.

When choosing tactics for managing patients with HF with preserved LVEF, great importance is attached to timely screening

and treatment of concomitant pathologies of both cardiovascular and other origins (class I, level C), since at present there is no definitive drug therapy that can affect both morbidity and mortality in this type of heart failure. The main goal of treating such patients is to improve the clinical condition and quality of life, since in most cases this category of patients consists of people of the older age group.

The relevance of the presence of concomitant pathology is beyond doubt, since comorbidity can complicate the diagnosis of heart failure, worsen its course and reduce the quality of life of patients, change the effect of medications and reduce patient adherence to treatment. In this regard, the recommendations pay serious attention to the early detection of concomitant diseases and discuss some features of the management of patients with coronary artery disease, cachexia and sarcopenia, cancer, depression, stroke, diabetes mellitus, erectile dysfunction, gout, pathology of the musculoskeletal system, hypo- and hyperkalemia, hypertension, anemia, kidney, liver, lung diseases, obesity, obstructive breathing disorders during sleep.

The recommendations discuss the organization of a comprehensive multidisciplinary approach to patients with HF, including a plan for discharge of the patient from the hospital after decompensation of HF under further supervision of the attending physician, recommendations for lifestyle changes, physical training and other aspects.

Experts strongly recommend identifying patients with geriatric conditions, in particular frailty syndrome, in order to provide timely medical and psychosocial support to the patient and his close circle. Senile asthenia is associated with age and is associated with a decrease in physiological reserve and functions of many body systems, which can lead to disability and an unfavorable life prognosis.

Current guidelines emphasize palliative care. Traditionally, palliative care in the final period of life is provided mainly to cancer patients, but now the principles of providing this type of care have begun to extend to other long-term progressive diseases. Palliative care is based on an interdisciplinary approach; the patient himself, his family, and society are involved in the process of providing care.

The core concept of palliative care is to meet the patient's needs wherever they receive care, at home or in hospital. Steadily progressive decline in physical and cognitive functions, dependence on outside assistance in daily life, frequent hospitalizations, poor quality of life, cachexia, and clinical state close to death are priority indications for providing palliative care to patients with HF.

The list of references can be found on our website www.atmosphere-ph.ru

Diagnosis and Treatment of Chronic Heart Failure

(based on 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure) V.N. Larina and I.I. Chukaeva

The article deals with diagnosis and treatment of chronic heart failure based on 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.

Key words: chronic heart failure, left ventricular ejection fraction, systolic dysfunction, diastolic dysfunction, BNP, NT-proBNP.