Chronic heart failure recommendations. Clinical practice guidelines for heart failure

GBOU VPO "RNIMU them. N.I. Pirogov "Ministry of Health of the Russian Federation

department of Polyclinic Therapy, Faculty of General Medicine

head department - prof. I.I. Chukaeva

HEART FAILURE

d.m.s. Professor

Larina Vera Nikolaevna

HCp: //eurheartj.oxfordjournals.org/content/ early / 2016/05/19 / eurheartj.ehw128

New terminology for patients with LVEF 40-49%

“Heart Failure with mid-range ejection fraction - HFmrEF

reduced, intermediate and preserved LVEF

New algorithm for diagnosing HF in non-acutely onset outpatients based on the possible presence of HF

Combined diagnostic and treatment algorithm acute HF,

Prevention of progression of heart failure or prevention of death before clinical symptoms of heart failure appear

Indications for appointment new combined

the drug sacubitril / valsartan (sacubitril / valsartan),

the first in a class of Angiotensin II receptor inhibitors (type 1) neprilisin inhibitor

Change in indications for cardioresynchronization therapy

The concept of early appointment of adequate therapy simultaneously with the diagnosis of acute heart failure, which corresponds to the concept of "time to therapy", is already

existing in acute coronary syndrome

Key points

Definition

New classification of CHF with reduced LVEF (HFrEF) / CHF

with preserved LVEF (HFpEF)

HF diagnostics (in general)

Based on the presence / absence of stagnation / hypoperfusion

Definition of heart failure

Heart failure -clinical syndrome,characterized bytypical symptoms(shortness of breath, swelling of the ankles, fatigue ...) that may be accompanied

signs (increased pressure in the jugular veins, wheezing in the lungs,

peripheral edema ...),caused by structural and / or functional changes in the heart, leading to:

ü The current definition of HF limits itself to stages where HF symptoms are already present,

ü Before the onset of symptoms, the patient may have structural or functional changes in the heart (systolic or diastolic LV dysfunction) - “precursors” of heart failure.

ü "precursors" are associated with poor prognosis

ü determining the cause of cardiac origin - the main point when making a diagnosis of HF -essential for the choice of therapy

Key points

Definition

New classification of CHF with reduced LVEF (HFrEF) / CHF

with preserved LVEF (HFpEF)

HF diagnostics (in general)

(NT-pro) BNP cut-off border

Diagnosis of CHF with preserved LVEF

Assessment of diastolic dysfunction

  Combined algorithm for diagnosis and treatment of acute heart failure,based on the presence / absence of stagnation / hypoperfusion

New classification of CHF with reduced LVEF (HFrEF) / CHF with preserved LVEF (HFpEF)

The main terminology used to describe HF is based on the measurement of LVEF.

Patients with HF have a wide range of LVEF:

Reduced (EF<40%, СН со сниженной ФВ ЛЖ – HFrEF

Normal (LVEF ≥50%, HF with preserved LVEF - HFpEF

Gray zone (LVEF from 40% to 49%)

Separation of HF patients by EF- the disease is based on different etiological factors, patients differ in demographic indicators, concomitant pathology, response to therapy.

New classification of CHF with reduced LVEF (HFrEF) / CHF with preserved LVEF (HFpEF)

The diagnosis of HF with preserved LVEF is more difficult than with reduced EF.

patients with heart failure and preserved LVEF usually have:

Normal LV dimensions;

Thickening of the LV wall and / or enlargement of the LA as a sign of increased filling pressure (often meets);

Diastolic dysfunction (most patients),which is considered as one of the causes of HF in these patients.

However, most patients with decreased LVEF (formerly called systolic heart failure)also have diastolic dysfunction, while mild systolic dysfunction is present in some patients with preserved LVEF.

Federal clinical guidelines for chronic heart failure contain up-to-date information on the etiology, pathogenesis, clinic, classification, 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 the leading specialists of the Russian Federation in the field of pediatric cardiology, contain scientific and practical data corresponding to modern global trends in the management of patients with chronic heart failure.

Torasemide: 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 the treatment arterial hypertension (AH) and edema syndrome, mainly in patients with chronic hearty insufficiency (CHF). The most widely used thiazide (or thiazide-like) diuretics are hydrochlorothiazide in Europe and chlorthalidone in the United States, which have been used in the treatment of hypertension since the late 1950s. of the last century, as well as indapamide, which has joined them in recent years. According to new recommendations European Society of Hypertension / European Society of Cardiology 2013, diuretics, along with drugs blocking the renin-angiotensin system (RAS), β-blockers (BAB) and calcium channel blockers (CCB), are first-line drugs for the treatment of hypertension.

In the early 60s. last century in clinical loop diuretics - furosemide, and then ethacrynic acid, which got their name from the site of application of the action - along the thick part of the ascending knee of Henle's loop, entered the practice. In this segment of the ascending knee of Henle's loop, from 20 to 30% of the filtered sodium chloride is reabsorbed, which is 2-3 times more than after taking thiazide diuretics. These drugs have found wide application in the treatment of edematous syndrome in various diseases, especially in CHF. Furosemide and ethacrynic acid cause a more pronounced diuretic effect than thiazide diuretics, but this effect is more short-lived. After the introduction or ingestion of these loop diuretics (approximately within 2-6 hours after a single dose), the excretion of sodium ions in the urine increases significantly, however, 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" is caused by a number of intra- and extrarenal mechanisms for maintaining water-electrolyte balance under conditions insufficient intake of sodium chloride into the body, and further promotes the activation of RAS.

The pronounced excretion of sodium ions (the diuretic effect of short-acting loop diuretics), occurring within several hours a day, is compensated by a significant retention of sodium ions after the end of their diuretic action (i.e., for most of the day). The "rebound phenomenon" is an explanation for the fact that when taken 1 r. / 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 should be prescribed 2-3 r. / Day. Studies have shown that furosemide and bumetanide, when given once or twice a day, usually not enough effective as antihypertensive drugs. The decrease in blood pressure when prescribing furosemide 2 r. / Day is less than hydrochlorothiazide when taking 1 r. / Day. These data have led to the fact that short-acting loop diuretics are not recommended for widespread use in patients with hypertension, and their application limited to cases in the background chronic renal insufficiency .

In the 80s. XX century in clinical practice has a new loop diuretic - torasemide . Torasemid characterized by high bioavailability and a longer lasting effect, which leads to 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 anti-aldosterone 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 knee of Henle's loop, where it inhibits the Na + / K + / 2Cl- transport system. The drug enhances the excretion of sodium, chlorine and water, without significantly affecting the 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 most of the phosphates and bicarbonates are reabsorbed. Torasemid does not affect the proximal tubules, causes less loss of phosphates and bicarbonates, as well as potassium in the urine.

Torasemide after oral administration 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 persons. The half-life of torasemide in healthy individuals is 4 hours; it practically does not change with CHF and chronic renal insufficiency... Compared with furosemide, the sodium and diuretic effect of torasemide occurs later and lasts much longer. The duration of the diuretic action of furosemide with intravenous administration is on average 2-2.5 hours and torasemide - about 6 hours; when taken orally, the effect of furosemide lasts about 4-6 hours, torasemide - more than 12 hours. Torasemide is removed from the 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 practice in our country appeared the original delayed-release torasemide - Britomar. 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 with the usual form of release of the drug. The drug is released for a longer 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. Sustained-release torasemide for long-term application does not cause changes in the level of potassium in the blood, does not have a noticeable effect on the level of calcium and magnesium, indicators of the glycemic and lipid profile. The sustained-release drug does not interact with anticoagulants (warfarin, phenprocoumon), cordial glycosides or organic nitrates, BAB, ACE inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs) II, CCA and spironolactone. It should be noted that the simultaneous application with diuretics, ACE inhibitors, and especially antagonists of mineralocorticoid receptors (MCR), prevents the development of electrolyte disturbances in the vast majority of cases.

Chronic heart 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 in patients with CHF, the effectiveness and clinical the need for this class of drugs for the treatment of patients with decompensation hearty activities beyond any doubt. Diuretics cause a rapid decrease in the symptoms of CHF associated with fluid retention (peripheral edema, shortness of breath, pulmonary congestion), in contrast to other treatments for CHF. In accordance with the algorithm for the treatment of systolic CHF in recommendations European Society of Cardiology 2012 diuretics are prescribed regardless of the 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 most important of the six goals in the treatment of CHF.

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

According to current clinical recommendations... the use of torasemide in comparison with other diuretics has a number of additional advantages. It should be noted that torasemide is more safe and tolerated than furosemide. Torasemide is the first loop diuretic that affects the progression of heart failure and the course of pathological processes in the myocardium. Experts identify antialdosterone and antifibrotic effects, proven in experimental and clinical studies. In a study by B. Lopes et al. it was shown that torasemide in comparison with furosemide leads to a decrease in the volume fraction of collagen and reduces the development of fibrosis. In one of the Russian studies, the effect of torasemide on left ventricular remodeling and the ability to normalize the ratio of indicators of collagen synthesis and breakdown was proved.

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 torasemide therapy, the functional class of circulatory insufficiency improved significantly more often, cardiovascular and general mortality significantly decreased. According to the results of the study, American experts came to the conclusion that torasemide is the drug of choice among diuretics in the treatment of congestive heart failure. In the Russian multicenter study, DUEL torasemide, in comparison 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 efficacy of long-acting torasemide and furosemide in patients with CHF II-III FC, edema syndrome and increased levels of natriuretic peptides (NP) on the degree of decrease in the concentration of NT-proBNP. 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 as a diuretic (Britomar, Takeda pharmaceutical company), the second - furosemide. Dose titration was carried out according to the standard scheme, depending on the severity of the edema syndrome. Treatment and observation lasted 3 months. the average dose of sustained-release torasemide 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 torasemide group, there was a trend towards a more significant improvement in the quality of life (p \u003d 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 of using torasemide in CHF. In patients with CHF, the usual starting dose of the drug is 2.5-5 mg 1 r. / Day, which, if necessary, is increased to 20-40 mg until an adequate diuretic response is obtained.

As noted earlier, diuretics belong to the first line of antihypertensive drug groups in the treatment of patients with hypertension. According to new American recommendations... they remain a priority drug for blood pressure control in all patients, if patients do not have clinical situations or conditions for preferential administration of any of the classes of antihypertensive drugs. All this indicates a significant position of diuretics both in mono- and especially in combination therapy of hypertension. Diuretics as a class have become nearly ideal remedies when a second drug is needed, since they potentiate the action 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-scale long-term clinical trials that have shown efficacy not only in controlling blood pressure, but also in reducing the risk of cardiovascular complications when using most of them. In many studies in recent years, the effectiveness of diuretics has been compared 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 manifested in the ASCOT study (when attached to BAB atenolol), as well as to possible electrolyte metabolism disorders (hypokalemia).

Other diuretics (loop diuretics) are usually prescribed instead of thiazides if serum creatinine reaches 1.5 mg / dL in a hypertensive patient or the 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 efficacy

and safety of torasemide

Most studies evaluating the effectiveness of torasemide were carried out back in the 90s. XX century In a 12-week double-blind study in 147 hypertensive patients, torasemide at doses of 2.5-5 mg / day was significantly superior in antihypertensive activity to placebo. Diastolic blood pressure returned to normal 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 of the studies, the natriuretic, diuretic and antihypertensive effects of torasemide in daily doses of 2.5 to 5 mg are 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 at a dose of 40 mg 2 rubles / day Torasemide reduced the serum potassium concentration to a much 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. treatment caused the same decrease in systolic and diastolic blood pressure. There was no significant effect of torasemide on serum potassium, magnesium, uric acid, glucose and cholesterol concentrations. In this study, the chlorthalidone group experienced significant reductions in blood potassium levels and significant increases in uric acid, glucose and cholesterol levels.

In a 12-week, randomized, double-blind study, the effects of 2.5 mg torasemide and 2.5 mg indapamide were compared in 66 hypertensive patients with grade 1 and 2 BP. Doses of drugs were doubled if, after 4 weeks, DBP remained above 100 mm Hg. Art. Both diuretics caused the same and significant decrease in DBP, with the maximum decrease observed after 8-12 weeks. after starting therapy. Doubling of the diuretic dose was required for 9 (28%) of 32 patients receiving torasemide, and 10 (29%) of 32 patients taking indapamide. DBP decreased<90 мм рт. ст. к концу исследования у 94% больных, получавших торасемид, и у 88% больных, принимавших индапамид .

Longer observations of the efficacy of torasemide were also carried out. A 24-week randomized study investigated the effects of 2.5 mg torasemide and 25 mg hydrochlorothiazide in combination with 50 mg triamterene in duplicate doses after 10 weeks. with insufficient decrease in DBP in 81 patients with hypertension. In both groups, the same and significant reduction in blood pressure was obtained, although the antihypertensive effect of the combination of diuretics was somewhat 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 efficacy 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 indicators 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 of enalapril and 12-25 mg of hydrochlorothiazide in combination with 10 mg of 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 efficacy to thiazide diuretics (hydrochlorothiazide, chlorthalidone and indapamide), however, it causes hypokalemia much less frequently. Unlike other loop and thiazide diuretics, long-term treatment with torasemide does not require control over the content of electrolytes, uric acid, glucose and cholesterol. Thus, torasemide in low doses is an effective antihypertensive drug, which, when taken 1 r. / Day, causes a long 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 the parameters of purine, carbohydrate and lipid metabolism. When treating with torasemide, repeated laboratory monitoring of biochemical parameters is less often required, which reduces the overall cost of treating hypertension.

Comparison of the clinical effects of conventional torasemide and the form of the drug with prolonged release of the drug showed that the latter had no less effect on the decrease in DBP, and the degree of decrease in SBP was also similar for both drugs.

Scheme of using torasemide for the treatment of hypertension. The drug is recommended at an initial dose of 5 mg 1 r. / Day. If the target BP (<140/90 мм рт. ст. для большинства больных) не было достигнуто за 4 нед. то в соответствии с recommendations the doctor may increase the dose to 10 mg 1 p. / day or add an antihypertensive drug of another group to the treatment regimen, preferably from the group of drugs blocking the RAS (ACE inhibitors or ARBs), or CCBs. Sustained-release tablets are prescribed orally 1 p. / Day, usually in the morning, regardless of food intake.

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

Conclusion

Torasemide is a loop diuretic recommended for patients with CHF and hypertension. In the treatment of patients with CHF, the drug is not inferior in terms of the diuretic effect of furosemide, additionally has antialdosterone and antifibrotic effects. The drug can be successfully used in case of impaired renal function and impaired absorption of furosemide in patients with severe heart failure. In hypertension, torasemide lowers blood pressure when applied 1 r. / Day at a dose of 5-10 mg for 4 weeks; if necessary, can be used in combination with drugs blocking ASD. There is evidence of efficacy in the treatment of women with hypertension in the postmenopausal period in combination with an ACE inhibitor. Torasemide therapy is well tolerated and rarely leads to metabolic and electrolyte disturbances.

Literature

1.2013 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) // J. Hypertens. 2013. Vol. 31 (7). P. 1281-1357.

2. Blizzard V.I. Handbook of Clinical Pharmacology of Cardiovascular Medicines, 3rd ed. M. 2005.1527 p.

3. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 // Eur. Heart J. 2012. Vol. 33. P. 1787-1847.

4. Brater D.C. Leinfelder J. Anderson S.A. Clinical pharmacology of torasemide, a new loop diuretic // Clin. Pharmacol. Ther. 1987. Vol. 42. P. 187-192.

5. Britomar. Monograph. Ferrer Internationale, 2011.26 p.

7. Lopez B. Querejeta R. Gonzales A. et al. Effects of loop diuretics on myocardial fibrosis and collage type I turnover in chronic heart failure // J. Am. Coll. Cardiol. 2004. Vol. 43 (11). P. 2028-2035.

8. Ageev F.T. Zhubrina E.S. Gilyarevsky S.R. et al. Comparative efficacy and safety of long-term use of torasemide in patients with compensated heart failure. Influence on markers of myocardial fibrosis // Heart failure. 2013. No. 14 (2). S. 55-62.

9. Cosin J. Diez J. TORIC investigators. Torasemide in chronic heart failure: results of the TORIC study // Eur. J. Heart Fail. 2002. Vol. 4 (4). P. 507-513.

10. Mareev V.Yu. Vygodin V.A. Belenkov Yu.N. Diuretic therapy Effective doses of oral diuretics torasemide (diuver) and furosemide in the treatment of patients with exacerbation Chronic Heart Failure (DUEL-CHF) // Heart failure. 2011. No. 12 (3). S. 3-10.

11. Zhirov I.V. T.V. Goryunova Osmolovskaya Yu.F. and other Place of slow-release torasemide in the treatment of CHF // BC. 2013.

12. Go A.S. Bauman M.A. Sallyann M. et al. AHA / ACC / CDC Science Advisory An Effective Approach to High Blood Pressure Control // Hypertension. 2013. Nov. 21.

13. Achhammer I. Metz P. Low dose loop diuretics in essential hypertension. Experience with torasemide // Drugs. 1991. Vol. 41 (Suppl. 3). P. 80-91.

14. Baumgart P. Torasemide in comparison with thiazides in the treatment of hypertension // Cardiovasc. Drugs Ther. 1993. Vol. 7 (Suppl. 1). P. 63-68.

15. Spannbrucker N. Achhammer I. Metz P. Glocke M. Comparative study on the hypertensive efficacy of torasemide and indapamide in patients with essential hypertension // Drug. Res. 1988. Vol. 38 (1). P. 190-193.

16. Achhammer I. Eberhard R. Comparison of serum potassium levels during long-term treatment of hypertension patients with 2.5 mg torasemide o.d. or 50 mg triamterene / 25 mg hydrochlorothiazide o.d. // Prog. Pharmacol. Clin. Pharmacol. 1990. Vol. 8.P. 211-220.

17. Tkacheva O.N. Sharashkina N.V. Novikova I.M. and others. The use of a loop diuretic torasemide in the combined treatment of hypertension in postmenopausal women // Consilium Medicum. 2011.T.13 (10). S. 54-59.

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 Tung, Gary S. Frances, David A. Morrow, L. Christine Newby, Christopher P. Cannon, Robert L. Jess, Alan H. B. Wu6, Alan B. Storrow, Robert G. Christenson

NACB committee members

The chairman... Robert G. Christenson

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

The entire relationship of Committee members 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 views of the authors and members of the Committee and do not represent the official position of the National Academy of Clinical Biochemistry (NACB). The National Academy of Clinical Biochemistry is the academy of the American Association of Clinical Chemistry.

A. Conditions for determining markers in heart failure.

B. Background and definition of terms.

B. Conversion and determination of brain-type natriuretic peptide (NPMT) and amino-terminal precursor of brain-type natriuretic peptide (pro-NPMT).

II. USE OF LABORATORY MARKERS

FOR A BASIC 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 OF HEART DYSFUNCTION

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

B. Approaches to screening for cardiac dysfunction.

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

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

Literature

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

A. Conditions for the determination of laboratory markers in heart failure

The past decade has revolutionized the definition of a number of laboratory markers and approaches to the diagnosis and treatment of heart failure. The medical community hopes that significant advances in the understanding of currently available cardiac markers will improve the identification of heart failure options and the individualization of treatment for these conditions, and more. However, as with most new diagnostic methods, despite the promising results of key trials, there are many challenges in the clinical setting.

The material discussed in this guideline relates to the definition of NPMT, pro-NPMT, and cardiac troponin in relation to the identification, risk stratification, and treatment of heart failure, including therapeutic indications for adults (over 18 years of age). Together with the accompanying document " Practical guidelines of the National Academy of Clinical Biochemistry and the Committee for Standardization of Markers of Heart Damage at the International Federation of Clinical Chemistry: Analytical Problems of Determining Biochemical Heart Failure " These recommendations are aimed at the proper use of the results of these tests by physicians and laboratory personnel. The Committee believes that disseminating these guidelines to clinicians and laboratory staff should improve their understanding and, ultimately, patient care and treatment outcomes for heart failure. Although it is difficult to specify in such a situation, the manual is intended as a short guide that can be useful in specific situations. The Committee considers that gaining and disseminating knowledge about the determination of natriuretic peptides is a major challenge in the application of the results of such assays. For this reason, there are plans to disseminate these guidelines widely. The committee believes this will help educate users about the advantages and disadvantages of defining NPMT and pro-NPMT. For example, in terms of cost, the direct cost of analyzing an NPMT or pro-NPMT is approximately US $ 50 (2007 exchange rate). There is evidence, albeit somewhat conflicting, that the use of the NPMT definition generally reduces the cost of treating heart failure without increasing patient risk. The costs were considered by the committee in developing the recommendations, but are considered moderate in relation to the overall cost of treating heart failure, and this view 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 identification of biochemical markers (such as NPMT or pro-NPMT) is not important per se and should be used and interpreted in the broader clinical context, taking into account the accompanying factors. When used correctly, the health benefits of testing will far outweigh the side effects and risks associated with obtaining information on NPMT and pro-NPMT levels. The use of cardiac troponin results in connection with population-based studies of heart failure is also discussed, mainly 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 disorder in the heart that results in impairment of the ability of the ventricles to fill or expel blood. The importance of this problem, which affects 2–3% of the US population, is constantly growing along with the 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 of the population, as well as a noticeable increase in the number of people who have survived myocardial infarction. According to the most conservative estimates, 50% of cases of heart failure are of ischemic origin, in 75% of cases hypertension is the main etiological factor. The cost of heart failure is estimated at $ 100 billion in Europe and the United States, with 70% of the cost in the United States being hospitalized.

The diagnosis of heart failure at the patient's bedside is based on clinical signs and symptoms, rather than on the basis of any test results. However, a significant proportion of patients turn to a cardiologist after a general practitioner mistakenly made a diagnosis other than heart failure. In this regard, the definition of biomarkers in heart failure has three important goals: 1) to find out the possible (and probably 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.

In the last ten years, it has been shown that natriuretic peptides, especially NPMT and its amino-terminal propetide pro-NPMT, are highly informative in confirming or refuting the diagnosis of heart failure, as well as in determining the delayed risk. In addition, several new cardiac, inflammatory and metabolic biomarkers have begun to be mentioned in the literature, such as natriuretic peptide type C, endothelin-1, C-reactive protein, cardiac troponin, apelin, myotrophin, urotensin-II, adrenomedullin and the middle fragment of proadrenomedullin, cardiotropin -1, urocortin, soluble ST2 receptor, myeloperoxidase (MPO), copeptin, growth differentiation factor-15 (GDF-15), lymphocytic kinases of G-protein coupled receptors (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 currently known or studied for clinical diagnosis, treatment and risk stratification of heart failure

Standard laboratory markers

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, edema, etc.), but also to reduce the number of hospitalizations and improve the prognosis. Reducing mortality and 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 the concentration of natriuretic peptides (NP).
For any patient, it is also extremely important that the treatment allowed him to achieve the 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. Nevertheless, the hallmark of modern effective pharmacotherapy is the achievement of all the indicated treatment goals.

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

Angiotensin converting enzyme (ACE) inhibitors, beta-blockers (β-AB) and aldosterone antagonists (mineralocorticoid receptor antagonists, AMKR) 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-Therapeutic Branch), as well as a meta-analysis of smaller studies, have convincingly proved that ACE inhibitors increase survival, reduce the number of hospitalizations, improve FC and the quality of life of CHF patients, regardless of the severity of the clinical manifestations of the disease. The results of three other large randomized trials (SAVE, AIRE, TRACE) have demonstrated additional efficacy of ACE inhibitors and reduced mortality in patients with LV systolic dysfunction / CHF symptoms after acute myocardial infarction (AMI). In turn, the ATLAS study showed that the treatment of patients with high doses of ACE inhibitors has an advantage over low-dose therapy and reduces the risk of death / hospitalization during long-term use in patients with CHF. In addition, in the clinical trial SOLVD-Prophylactic branch, it was shown that ACE inhibitors can delay or prevent the development of CHF symptoms in patients with asymptomatic LV dysfunction.
ACE inhibitors in addition to β-AB are recommended for all patients with symptomatic heart failure and reduced LV ejection fraction to reduce the risk of hospitalization due to heart failure and death.
Strength of recommendation I (Evidence level 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 I (Evidence level 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 **.
Recommended for the use of ACE inhibitors, which have the most significant evidence base in CHF.
Strength of recommendation I (Evidence level 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-sEFV are described in Appendix D1.
The results of several large randomized controlled trials (CIBIS II, MERIT-HF, COPERNICUS, USCP) have convincingly proved that beta-blockers increase survival, reduce 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 significantly differed in design from the aforementioned studies (elderly patients, some of them with preserved left ventricular systolic function, a longer follow-up period), the effect of nebivolol was somewhat less pronounced than in previous protocols, however it is impossible to compare them directly. Another large clinical trial, COMET, showed a significant advantage of carvedilol ** compared to short-acting metoprolol tartrate ** in reducing the risk of death in patients with CHF (metoprolol succinate ** long-acting sustained release drug was used in the MERIT-HF study ).
Beta-blockers in addition to ACE inhibitors are recommended for all patients with stable symptomatic heart failure and reduced LV ejection fraction to reduce the risk of hospitalization due to heart failure and death.
Strength of recommendation I (Evidence level A).
Comments.Today, it is generally accepted that ACE inhibitors and β-ABs, by virtue of 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. Complementing the positive effects of ACE inhibitors, β-ABs 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 decrease in mortality in patients with CHF for any reason.
β-ABs are recommended for patients after MI and with LV systolic dysfunction to reduce the risk of death and prevent the development of HF symptoms.
Strength of recommendation I (Evidence level B).
The appointment of 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-ABs have already been prescribed before the onset of symptoms of decompensation, continued therapy is recommended, if necessary, in a reduced dose.
Strength of recommendation IIA (Evidence level A).
Comments.In the presence of symptoms of severe hypoperfusion, a complete cancellation of β-AB therapy is possible, 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.Preparations and dosages.
The practical aspects of the use of beta-blockers in patients with CHF-CFV are set out in Appendix D2.
RALES studies have shown that the use of spironolactone ** to standard therapy (ACE inhibitors, β-AB, diuretics, digoxin **) reduces the number of hospitalizations and improves the clinical condition of patients with CHF (III-IV FC), in 2010 the results of the EMPHASIS-HF study are convincing showed that the addition of eplerenone to the standard therapy of patients with CHF II and higher of any genesis reduces the number of hospitalizations, reduces overall mortality and mortality due to CHF. Earlier, the data of these clinical trials were confirmed by the results of the EPHESUS study (eplerenone) in patients with AMI, complicated by the development of CHF and LV systolic dysfunction.
AMCR is recommended for all patients with CHF II-IV FC 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 heart failure and death.
Strength of recommendation I (Evidence level A).
Comments.When AMCR is used in combination with ACE inhibitors / ARBs and beta-blockers, the most dangerous development is severe hyperkalemia ≥ 6.0 mmol / L, which occurs in everyday clinical practice much more often than in the studies conducted.
AMKR should be prescribed both during inpatient treatment and on an outpatient basis, if not previously prescribed.
Recommended doses:
Initial dose Target dose.
Spironolactone ** 25 mg single dose 25-50 mg single dose.
Eplerenone 25 mg single dose 50 mg single dose.
Practical aspects of the use of AMCR in patients with CHF-cEF are set out in Appendix D3.

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

Unlike other therapies, the effect of diuretics on the morbidity and mortality of CHF patients has not been studied in long-term studies. Nevertheless, the use of diuretic drugs removes the 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 HF symptoms and increase physical activity in patients with signs of fluid retention.

Diuretics are recommended to reduce the risk of hospitalization for heart failure in patients with symptoms of fluid retention.

Comments.Diuretics cause a rapid improvement in the symptoms of CHF, in contrast to other treatments for CHF.
Only diuretics are able to adequately control the water 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-AB, ACE inhibitors / ARBs, and AMCR. In the case of relative hypovolemia, the risk of developing a decrease in cardiac output, hypotension, and deterioration of renal function significantly increases.
The optimal dose of a diuretic is considered to be the lowest dose that maintains the patient in a state of euvolemia, etc. when the daily intake of a diuretic provides balanced diuresis and constant body weight.
In patients with CHF, diuretics should be used only in combination with β-AB, ACE inhibitors / ARBs, AMKR.
Diuretics recommended for the treatment of CHF are presented in Table 11.
Table 11.Doses of diuretics most commonly used in the treatment of CHF patients.

Diuretic	Initial dose		Usual daily dose
Loop diuretics
Furosemide **	20-40mg		40-240mg
Torasemid	5-10mg		10-20mg
Bumetanide *	0.5-1mg		1-5mg
Ethacrynic acid	25-50mg		50-250mg
Thiazide diuretics
Bendroflumethiazide *	2.5mg		2.5-10mg
Hydrochlorothiazide **	12.5-25mg		12.5-100mg
Metolazone *	2.5mg		2.5-10mg
Indapamide **	2.5mg		2.5-5mg
Potassium-retention diuretics
	+ ACE-I / ARB	- ACE inhibitors / ARBs	+ ACE-I / ARB	- ACE inhibitors / ARBs
Amiloride *	2.5mg	5mg	5-10mg	10-20mg
Triamteren ^	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.
The practical aspects of the use of diuretics in patients with CHF-cEF are set out in Appendix D4.
A new class of therapeutic agents that simultaneously affect the activity of the RAAS and the activity of the natriuretic peptide (NP) system. The first drug in this class was LCZ696, in which it was possible to combine 2 subunits consisting of valsartan (angiotensin receptor blocker) and sacubitrile (neprilisin inhibitor) molecules. Accordingly, blockade of angiotensin receptors reduces RAS activity, and inhibition of neprilysin slows down the degradation of NP and bradykinin. As a result of this dual mechanism of action, systemic vasoconstriction decreases, fibrosis and hypertrophy of the heart and blood vessels decrease, urine output and natriuresis increase, and vasodilating effects, directed against the development of maladaptive LV remodeling, prevail.
To date, there has been one large randomized study (PARADIGM-HF) evaluating the long-term effects of sacubitril / valsartan versus an ACE inhibitor enalapril ** on the morbidity and mortality of outpatients with symptomatic HF (FC II-IV) and decreased LVEF ≤ 40% ( in the course of the study, correction was carried out to ≤35%), who had increased concentrations of NP and hospitalization due to heart failure during the year. An important criterion for inclusion in the study was the introductory period, in which the patients' ability to tolerate the required doses of the study drugs was tested (enalapril ** 10mg 2 times / day, LCZ696 200mg 2 times / day). The study was stopped early (average follow-up period was 27 months), and the reduction in the risk of death due to CV causes / hospitalizations due to heart failure (main study endpoint) was 20% in the group of patients taking sacubitrile / valsartan (97 / 103mg 2 times / day) compared with enalapril ** (10mg 2 times / day), which made it possible to include this group of medicinal pre-drugs in modern recommendations for the treatment of patients with HF with reduced LVEF.
Valsartan + Sakubitril is recommended instead of an ACE inhibitor in outpatients with reduced LVEF and persisting HF symptoms, despite optimal therapy with ACE inhibitors, beta-blockers and AMCR to reduce the risk of hospitalizations due to HF and death.
Strength of recommendation I (Evidence level B).
Comments.Despite the superiority of sacubitril / valsartan over enalapril ** in the PARADIGM-HF study, questions remain related to the safety profile of the new class of drugs, which are especially important when used in clinical practice. One of the most important is the risk of hypotension at the beginning of treatment, especially in elderly patients over 75 years of age (hypotension in 18% in the sacubitril / valsartan group versus 12% in the enalapril group **), although this did not lead to an increase in the patient's withdrawal rate from research. The development of angioedema was rare (0.4% and 0.2%, respectively), which could be partly due to the presence of an introductory period. Also, the issue with the influence of Valsartan + Sakubitril on the degradation of beta-amyloid has not been fully resolved, which requires continued monitoring and safety assessment in a long period.
The recommended starting dose is Valsartan + Sakubitril 49 / 51mg 2 times a day, the target dose is 97 / 103mg 2 times a day.
To date, 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 I (Evidence level B).
ARBs are not recommended in patients with symptoms of HF (FC II-IV) despite treatment with ACE inhibitors and β-AB.

Comments.In this case, in addition to ACE inhibitors and β-ABs, it is recommended to add the MCR antagonist eplerenone or spironolactone. This prescribing algorithm is driven by the results of the EMPHASIS-HF clinical trial, which showed a much greater reduction in morbidity / mortality with the use of eplerenone compared to the similar effect of ARBs in the Val-HeFT and CHARM-Added studies, as well as the RALES and EMPHASIS-HF protocols. , in which both AMCRs were able to reduce mortality for any reason in patients with CHF, in contrast to ARBs (studies with the addition of ARBs "on top" ACE inhibitors and β-AB). Additional prescription of ARBs is possible only if the patient with CHF, for some reason, has an intolerance to AMCR, and the symptoms of HF persist against the background of selected therapy with ACE inhibitors and β-AB, which will require subsequent strict clinical and laboratory control.
ARBs are recommended to reduce the risk of HF hospitalizations and CV deaths in symptomatic HF patients unable to tolerate ACE inhibitors (patients should also take beta-blockers and AMCRs).
Strength of recommendation I (Evidence level B).
Comments.Under "intolerance" ACE inhibitors should be understood - the presence of individual intolerance (allergies), the development of angioedema, cough. Renal dysfunction, the development of hyperkalemia and hypotension in the treatment of ACE inhibitors is not included in the concept of "intolerance" and can be observed in patients with CHF with the same frequency both with the use of ACE inhibitors and ARBs.
ARBs are recommended in selected patients with HF who are taking beta-blockers and unable to tolerate AMCR.
Strength of recommendation IIb (Evidence level C).
"Triple" blockade of RAAS (combination of ACE inhibitors + MCR antagonist + ARBs) is not recommended for use in patients with CHF due to the high risk of 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:
The practical aspects of the use of ARBs in patients with CHF-sEFV are described in Appendix D5.
The use of ivabradine ** is recommended only for patients with sinus rhythm, EF ≤ 35%, symptoms of CHF II-IV FC and a heart rate of ≥ 70 per minute. , necessarily being on the selected therapy with the recommended (or maximum tolerated) doses of β-AB, ACE inhibitors / ARBs and MCR antagonists.
Strength of recommendation IIa (Evidence level B).
Comments.The mechanism of action of ivabradine ** is to decrease heart rate due to selective inhibition of ion current in the If-channels of the sinus node without any effect on the inotropic function of the heart. The drug works only in patients with sinus rhythm. It was shown that in patients with sinus rhythm, EF ≤ 35%, symptoms of CHF II-IV FC and a heart rate of ≥ 70 per 1 min. despite therapy with the recommended (or maximum tolerated) doses of β-AB, ACE inhibitors / ARBs and MCR antagonists, adherence to ivabradine ** treatment reduces the number of hospitalizations and mortality due to CHF. In addition, in the case of β-AB intolerance, in the same category of patients, the use of ivabradine ** as a standard therapy reduces the risk of hospitalizations due to CHF.
The use of ivabradine ** is recommended to reduce the risk of hospitalizations 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 ACE inhibitors (ARB) and AMCR therapy who are unable to tolerate or have contraindications to the appointment of beta-blockers 120].
Strength of recommendation IIa (Evidence level C).
Comments.The recommended initial dose of ivabradine ** is 5 mg x 2 times a day, with a subsequent increase in 2 weeks to 7.5 mg x 2 times a day. In elderly patients, it is possible to adjust the dose of ivabradine ** towards its reduction.
To date, the use of cardiac glycosides (CG) in patients with CHF is limited. Of the existing drugs, digoxin ** is recommended, the efficacy and safety of other SGs (for example, digitoxin **) in CHF has not been studied enough. Prescribing digoxin ** to patients with CHF does not improve their prognosis, but reduces the number of hospitalizations due to CHF, improves CHF symptoms and quality of life [121-126]. The use of digoxin ** in some cases can only complement therapy with β-AB, ACE inhibitors / ARBs, MCR antagonists and diuretics.
Digoxin ** is recommended for the treatment of patients with CHF II-IV FC and decreased LVEF ≤ 40% (DIG study, meta-analysis data) with sinus rhythm, with persisting HF symptoms despite therapy with ACE inhibitors, beta-blockers and AMCR to reduce the risk of hospitalizations because of CH and for any reason.

Comments.In such patients, it is necessary to carefully approach its appointment, and it is preferable to use it if the patient has severe heart failure III-IV FC, low LV EF (< 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.
Use of digoxin ** for heart rate control in patients with symptoms of CHF and the presence of atrial fibrillation (AF) tachyform (see Chapter 3,1,7).
The use of omega-3 PUFA esters is recommended in some patients with CHF II-IV FC, LVEF ≤ 40%, who are on standard therapy with β-AB, ACE inhibitors / ARBs, MCR antagonists and diuretics to reduce the risk of death and hospitalizations for cardiovascular causes.
Strength of recommendation IIb (Evidence level B).
Comments.The evidence base for CHF is not significant. A small additional effect of omega-3 polyunsaturated fatty acids (PUFA) preparations was shown in terms of reducing the risk of death and hospitalization for cardiovascular (CV) causes in patients with CHF II-IV FC, LVEF ≤ 40%, who are on standard β-AB therapy , ACE inhibitors / ARBs, MCR antagonists and diuretics in the GISSI-HF study. No effect on hospitalization due to CHF was identified. The effect was confirmed by the results of the GISSI-Prevenzione protocol in patients after myocardial infarction, but not by the data from the OMEGA clinical trial.
Due to the lack of evidence base, 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 CHF in African American patients with LVEF ≤35% or LVEF ≤45% in the presence of dilated LV and FC III-IV HF despite therapy with an ACE inhibitor, beta-blockers and AMCR ...
Strength of recommendations IIa (Evidence level B).
Therapy with hydralazine and isorbide dinitrate is rarely recommended to reduce the risk of death in symptomatic HF patients with reduced LVEF who are unable to tolerate an ACE inhibitor or ARB (or are contraindicated).
Strength of recommendation IIb (Evidence level B).

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

Statin therapy is not recommended for patients with CHF.

Comments.The benefits of statins in patients with CHF have not been proven. CORONA and GISSI-HF studies, in which patients with CHFII-IV FC, ischemic and non-ischemic etiology, with LVEF ≤ 40%, who were on standard therapy with β-AB, ACE inhibitors / ARBs and MCR antagonists, did not reveal an additional effect of rosuvastatin on the prognosis ... At the same time, treatment with rosuvastatin in CHF patients was relatively safe. Therefore, in the event that statin treatment was prescribed to a patient with coronary artery disease before the development of CHF symptoms, 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 study, the use of indirect anticoagulants in WARCEF does not affect the prognosis and morbidity of patients with CHF with sinus rhythm in comparison with placebo and aspirin, in contrast to patients with AF.
Direct renin inhibitors (as an adjunct therapy to ACE inhibitors / ARBs, β-AB and MCR antagonists) are not recommended for the treatment of any of the groups of CHF patients.
Strength of recommendation III (Evidence level B).
Comments.The results of the 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 CHF patients, as well as an increased risk of 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 II-IV functional class 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 III (Evidence level 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 CHF.
Strength of recommendation III (Evidence level C).
Comments.The exceptions are felodipine and amlodipine **, which do not affect the prognosis of patients with CHF (studies PRAISE I and II; V – HeFT III).
The use of NSAIDs and COX-2 inhibitors is not recommended in CHF, since NSAIDs and COX-2 inhibitors provoke sodium and fluid retention, which increases the risk of decompensation in CHF patients.
Strength of recommendation III (Evidence level B).
"Triple" blockade of RAAS in any combination: ACE inhibitors + AMKR + ARBs (or a direct renin inhibitor) are not recommended in the treatment of CHF patients due to the high risk of hyperkalemia, deterioration of renal function and hypotension.
Strength of recommendation III (Evidence level 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 III (Evidence level A).

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

Correction of factors provoking ventricular arrhythmias is recommended (correction of electrolyte disturbances, withdrawal of drugs provoking ventricular arrhythmias, revascularization in ventricular tachycardia caused by ischemia).

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

Implantation of an ICD (implantable cardioverter defibrillator) or CPT-D (cardiac resynchronization therapy - defibrillator) is recommended for a specific group of patients with CHF-sPF (see Chapter 6).
Strength of recommendation I (Evidence level A).
Several options are recommended to be considered when deciding on the treatment of recurrent VA episodes in patients with CDI (or those who cannot have ICD implantation), including risk factor correction, optimization of CHF therapy, amiodarone **, catheter ablation, and CRT (cardiac resynchronization therapy) ...
Strength of recommendation IIa (Evidence level C).
Routine administration of antiarrhythmic drugs is not recommended in patients with CHF and asymptomatic VA for safety reasons (CHF decompensation, proarrhythmogenic effect, or death).
Strength of recommendation III (Evidence level 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 III (Evidence level A).
Comments.Amiodarone ** (usually in combination with beta-blockers) can be used to prevent symptomatic VA, but it should be borne in mind that such therapy may have the opposite effect on the prognosis, especially in severe CHF-CFE patients.

3,1,7 Features of the 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 reported episode of AF or paroxysmal AF, should be performed:
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 main tactics patient management;
assess the risk of stroke and the need for anticoagulant therapy;
to assess the frequency of ventricular contractions and the need to control them;
assess the symptoms of AF and CHF.
For more information, refer to the Guidelines for the Management of Patients with AF.
Treatment with ACE inhibitors, ARBs, beta-blockers, and MCR antagonists can reduce the incidence of AF, in contrast to ivabradine **. CRT has no significant effect on the incidence of AF.
Amiodarone ** reduces the incidence of AF, is used for pharmacological cardioversion, in most patients it helps to maintain sinus rhythm 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 ventricular rate 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.
Strength of recommendation I (Evidence level C).
For patients with CHF IV FC, 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 CHF I-III FC, oral administration of beta-blockers is safe and is recommended as the first line of therapy to control PSR, provided that the patient is in a state of euvolemia.
Strength of recommendation I (Evidence level A).
For patients with CHF I-III FC class, digoxin ** is recommended in case of high RR, despite taking beta-blockers, or in the case when the appointment of beta-blockers is impossible or contraindicated.
Strength of recommendation IIa (Evidence level B).
AV nodal catheter ablation is recommended in selected cases to control heart rate and improve symptoms in patients refractory or unresponsive to intensive pharmacological therapy to control the rhythm or heart rate, given that these patients become dependent on a pacemaker.

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

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

Examination of a patient with CHF should include measures to identify possible sources and risk factors for the development of thromboembolic complications (TEO). It is also mandatory to assess renal function (creatinine clearance or glomerular filtration rate), the violation of which is an additional risk factor for feasibility studies and requires dose adjustment of a number of antithrombotic drugs.
Prevention of venous feasibility studies is recommended for patients hospitalized with acute HF or severe decompensated CHF (III or IV FC), 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 I (Evidence level A).
Comments.In the absence of contraindications, the means of choice include the subcutaneous administration of anticoagulants - unfractionated heparin (5000 U 2-3 times / day; control of APTT is not required), enoxaparin (40 mg 1 time / day).
The duration of medication prophylaxis for venous feasibility studies should be from 6 to 21 days (until full motor activity is restored 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 TEO (compression hosiery or intermittent pneumatic compression of the lower extremities) should be used. The widespread use of objective methods for the diagnosis of deep vein thrombosis (compression ultrasonography of the veins of the lower extremities and others) in patients without symptoms of venous feasibility study is not recommended.
Table 13.Risk assessment and determination of indications for prophylaxis of venous feasibility studies in hospitalized nonsurgical patients - prophylaxis is advisable with a score of ≥4.

Risk factor	Score
Active cancer (metastases and / or chemotherapy or radiotherapy< 6 месяцев назад)	3
History of venous feasibility studies (excluding superficial vein thrombosis)	3
Restricted mobility (bed rest and going to the toilet for ≥3 days) due to patient restrictions or as directed by a physician	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
Heart and / or respiratory failure	1
Myocardial infarction or ischemic stroke	1
Acute infection and / or rheumatologic disease	1
Obesity (BMI ≥30 kg / m2)	1
Continued use of hormone replacement therapy or oral contraceptives	1

BMI-body mass index.
Heart valve prostheses.
In the presence of a mechanical prosthesis of the heart valve in a patient with CHF, it is recommended to use a vitamin K antagonist for an indefinitely long time (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 I (Evidence level A).
Comments.The target INR depends on the type of prosthesis, its position, the presence of additional risk factors for feasibility studies and the concomitant use of acetylsalicylic acid. Indefinitely long (lifelong) use of a vitamin K antagonist under INR control is also shown in the presence of a biological prosthesis of heart valves in patients with reduced LVEF (.
The use of new oral anticoagulants (apixaban, rivaroxaban **, dabigatran **, edoxaban (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, preceding arterial feasibility study or atrial fibrillation are recommended to receive a vitamin K antagonist with a target INR of 2-3 for an indefinite period (for life).
Strength of recommendation I (Evidence level A).
Comments.A similar approach can be used with a marked increase in the diameter of the left atrium (55 mm).
Atrial fibrillation.
Patients with atrial fibrillation who have rheumatic lesions of the valvular apparatus of the heart (primarily mitral stenosis) are recommended to receive a vitamin K antagonist with a target INR of 2-3 for an indefinite period (for life).
Strength of recommendation I (Evidence level 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 stenosis is not recommended.
Strength of recommendation II I (Evidence level 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.
Strength of recommendation I (Evidence level B).
Comments.The need for prevention of stroke and arterial feasibility studies in non-valvular atrial fibrillation is determined by the sum of the CHA2DS2-VASc scores.
Scale C H A 2 DS 2.VASc - Congestive heart failure, Hypertension, Age (over 75 years old), Diabetes mellitus, Stroke (history of stroke / TIA / systemic embolism), Vascular disease ), Age (65–74 years old), Sex category - (female).
HAS scale.BLED - Hypertension (Arterial hypertension), Abnormal renal-liver function (impaired renal and / or liver function), Stroke (past stroke), Bleeding history or predisposition (history of bleeding or predisposition), Labile international normalized ratio (labile INR ), Elderly (65 years) (over 65), Drugs or alcohol concomitantly (addicting certain drugs or alcohol).
Oral anticoagulant therapy for the prevention of thromboembolic complications is recommended for all patients with paroxysmal or persistent / permanent AF who have 2 or more points 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 I (Evidence level A).
Comments.At the same time, depending on the characteristics of a particular patient, availability, vitamin K antagonists with a target INR can be selected, and in the case of nonvalvular atrial fibrillation, the absence of severe renal failure and other contraindications, new oral anticoagulants - apixaban at a dose of 5 mg 2 times / day (if available at least two 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 / day (with caution when creatinine clearance is 30-49 ml / min, contraindicated when creatinine clearance is below 30 ml / min), age ≥80 years, moderate decrease in renal function (CC 30-50 ml / min), concomitant use of P-glycoprotein inhibitors, or an indication of 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 doctor, a decrease in the daily dose may be 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 nonvalvular 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 the lower risk of stroke, hemorrhagic intracranial complications and death, despite the higher risk of gastrointestinal bleeding.
Strength of recommendation I Ia (Evidence level 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 affect the features of its management. There are several reasons for this. First, the presence of other organ lesions in a patient with CHF may be a significant unfavorable prognostic factor. Secondly, the required drug therapy can adversely affect either the course of CHF or comorbidities. Finally, when several groups of drugs are taken together, serious drug interactions between drugs can be detected. A serious argument is also the fact that very often in randomized clinical trials the combination of CHF and diseases of other organs and systems has not been specifically studied. This leads to a lack of evidence-based information on the management of such patients, and very often treatment algorithms are based only on expert opinions on this issue. It should be noted that for the management of such groups of patients, all general approaches to diagnosis and treatment are used, with the exception of 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 (in case of intolerance - ARBs), beta-blockers or AMKR (or a combination) are recommended for lowering blood pressure as the first, second and third line of therapy, respectively, due to their proven efficacy in patients with reduced LVEF (reducing the risk of death and hospitalization due to CH).
Strength of recommendation I (Evidence level A).
Comments.This therapy is also safe in CHF patients 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 efficacy of ACE inhibitors (ARBs instead of ACE inhibitors, but not together!), Beta-blockers and AMKR in patients with CHF.
Strength of recommendation I (Evidence level C).
The appointment of amlodipine ** is recommended to enhance antihypertensive therapy in case of insufficient antihypertensive efficacy of ACE inhibitors (ARBs instead of ACE inhibitors, but not together!), Beta-blockers, AMCRs and diuretics in CHF patients.
Strength of recommendation I (Evidence level A).
The appointment of felodipine is recommended to enhance antihypertensive therapy with insufficient antihypertensive efficacy of ACE inhibitors (ARBs instead of ACE inhibitors, but not together!), Beta-blockers, AMCRs and diuretics in patients with CHF.
Strength of recommendation IIa (Evidence level B).
Most BMCCs (dilithiazem, verapamil **, short-acting dihydropyridines) are not recommended for patients with CHF.
Strength of recommendation III (Evidence level C).
Comments.BMCCs have a negative inotropic effect, which contributes to the development of CHF decompensation.
Moxonidine is not recommended for patients with CHF.
Strength of recommendation III (Evidence level B).

The new paper was published in the European Heart Journal and the European Journal of Heart Failure, and also presented at the European Heart Failure Congress 2016 and the 3rd World Congress on Acute Heart Failure.

Heart failure affects approximately 1–2% of the adult population in developed countries.

Regarding the latter, the authors of the document say that this is a big step forward against the background of a number of traditional antidiabetic drugs that are associated with an increased risk of worsening heart failure. In contrast, this SGLT2 inhibitor reduces the risk of hospitalization for heart failure in high-risk patients, although in fairness, it should be noted that there are no studies yet examining SGLT2 inhibitors in patients with already diagnosed heart failure.

Professor Ponikowski concluded the press release with the following conclusion: “Heart failure is becoming a disease that is preventable and treatable.