[Chronic kidney disease and chronic heart failure: impact on prognosis and choice of pathogenetic therapy].

AIM: To evaluate the impact of a decrease in glomerular filtration rate (GFR) on the prognosis of patients with chronic heart failure (CHF), to analyze real clinical practice regarding the frequency of prescribing pathogenetic therapy for CHF, achieving target dosages depending on the gradation of GFR in patients included in the CHF Register of the Tyumen region. MATERIALS AND METHODS: The analysis included medical data of 4077 patients (1662 men and 2415 women) with NYHA class I-IV CHF who underwent examination and treatment in medical organizations of the Tyumen region for the period from January 2020 to May 2023. Criteria for inclusion in the register: proven heart failure. Chronic kidney disease (CKD) was assessed by GFR calculated using the CKD-EPI formula (ml/min/1.73 m2). The primary end point was defined as death from all causes. RESULTS: GFR<60 ml/min/1.73 m2 was recorded in 34.6% of patients, more common in women (40.2 and 26.6%, respectively; p<0.001). When dividing patients into phenotypes according to LVEF, no statistically significant differences were found in the distribution of patients according to GFR. In patients with HFrEF and HFpEF GFR<45 ml/min/1.73 m2 was associated with an increased risk of meeting the endpoint. Analysis of prescribed pathogenetic therapy showed that in patients with HFrEF, the frequency of prescription of ACE inhibitors, â-blockers and MRA decreased (p=0.023, 006 and 0.01, respectively), and ARNI, on the contrary, increased with a decrease in GFR (p=0.026). In patients with HFpEF, a similar trend towards a decrease in the frequency of prescription of ACEIs and MCBs with a decrease in GFR (p<0.001) remained, but it was compensated by an inversely proportional increase in the frequency of prescription of ARBs (p<0.001). 100% of the target dosage is achieved in more than 90% of patients taking MRA across the entire LVEF range. While for â-blockers and ARNI/ACE/ARB the percentage of patients receiving the full therapeutic dosage of drugs is significantly lower. When analyzing target dosages of pathogenetic drugs, gradations of achieved doses were distributed evenly throughout the entire range of GFR. CONCLUSION: GFR<60 ml/min/1.73 m2 occurs in every 3 patients with CHF across the entire range of LVEF. A decrease in GFR worsens the prognosis of patients with both HFrEF and HFpEF, increasing in direct proportion with the severity of the stage of CKD. Inclusion of patients in the monitoring program within the framework of the CHF service allows the treatment to be significantly brought closer to optimal drug therapy, at the same time, certain efforts are required to overcome difficulties with titration to target dosages.

[Anthracycline-induced Heart Failure: Treatment and Recovery Prospects].

The article presents a clinical case of heart failure associated with the anthracycline-containing antitumor therapy in a breast cancer patient with an initially low risk of developing cardiovascular complications.

[Creation of registers as one of the mechanisms for improving medical care for patients with chronic heart failure. Problem state].

The annual mortality of patients with clinically pronounced symptoms of chronic heart failure in the Russian Federation reaches 26-29%, i.e., from 880 to 986 thousand patients with heart failure die in the country in one year, which is comparable to the population of a large city. Providing care for patients with heart failure places a heavy burden on the country's health care system, making a significant contribution to mortality rates, hospitalization rates, including readmissions, which in turn requires considerable costs. The article presents an overview of registry studies that are devoted to assessing the effectiveness of diagnostics, the completeness of examinations, as well as the adequacy of ongoing drug treatment.

[Effects of sacubitril/valsartan in patients with cancer therapy-related heart failure].

AIM: To evaluate the effect of Sacubitril/Valsartan (S/V) on the functional status, systolic and diastolic function of the left ventricle (LV), tolerability of therapy and to determine predictors of its effectiveness in patients with cancer therapy-related heart failure (СTRHF). MATERIALS AND METHODS: Forty patients 58 [46; 65.5] years of age with HF associated with anthracycline-containing cancer therapy were enrolled. Clinical examination, echocardiography, and assessment of potassium and creatinine levels were performed at baseline and after 6 months of S/V therapy. RESULTS: NYHA functional class (FC) improvement was observed in 22 (64.7%) patients. Radiation therapy (RT) decreased (OR 0.091; 95% CI 0.01-0.83; p=0.03) while baseline low LV EF increased (OR 9.0; 95% CI 1.78-45.33; p=0.008) the odds of FC improvement. LV EF increased from 37.3 [30; 42.5] % to 45 [38; 48] % (p<0.0001) and exceeded 50% in 7 (20.6%) patients. The odds of LV EF recovery increased when S/V therapy was initiated ≤1 year after anthracycline therapy (OR 10.67; 95% CI 1.57-72.67; p=0.0016) and decreased in patients with the history of RT (OR 0.14; 95% CI 0.02-0.89; p=0.0037) and in patients over 58 years (OR 0.07; 95% CI 0.01-0.68; p=0.022). LV diastolic function improvement included E/e' descent from 13.6 [10; 18.3] to 8.9 [6.9; 13.7] (p=0.0005), and decrease in diastolic dysfunction grade in 18 (45%) patients (p=0.0001). No significant change in serum potassium (4.45 [4.2; 4.8] versus 4.5 [4.3; 4.8]; p=0.5) and creatinine (75.4 [67.6; 85.1] versus 75.5 [68.2; 98.3]; p=0.08) levels were observed. CONCLUSION: S/V therapy is associated with improvement of EF, systolic and diastolic LV function, demonstrates a favorable tolerability profile in patients with СTRHF. Lack of RT and low baseline LV EF increased the odds of LV EF improvement; lack of RT, early (≤1 year) start of treatment after discontinuation of anthracycline therapy, and age <58 years increased the odds of LV EF recovery.

[Heart Failure With Low and Preserved Left Ventricular Ejection Fraction - are These Two Different Independent Diseases or One Disease, but at Different Stages of its Progression? How Does This Affect the Choice of Therapy and Its Effectiveness?]

The article discusses the question of whether it is possible to conclude that any heart failure (HF), throughout the entire range of left ventricular ejection fractions (LVEF), is a single holistic disease, based on the "external" similarity of treatments for reduced (HFrEF) and preserved (HFpEF) LVEF, and that positioning HFpEF and HFrEF as separate independent diseases is not valid.

[What is "normal left ventricular ejection fraction" and its relationship with the pathogenesis and effectiveness of the treatment of heart failure].

The article focuses on modern views on the role and place of left ventricular ejection fraction (LV EF) in determining the status of cardiovascular patients (primarily patients with heart failure) in the algorithm for their diagnosis, treatment, and prediction of the outcome. Conclusions and recommendations on the use of LV EF in patients with chronic heart failure (CHF) are the following: 1) LV EF remains a familiar and convenient instrumental indicator not so much of myocardial contractility as of hemodynamics in general. Assessment of LV EF is useful for selection and ranking of CHF patients whereas the LV EF dynamics is useful for assessing the quality of their management. 2) In the entire population of cardiovascular patients, the "normal" LV EF (mortality nadir) is in the range of 60-65%. 3) LV EF demonstrates a U-shaped relationship with prognosis: in cardiovascular patients with LV EF below the mortality nadir, the relationship is inversely proportional, and above the mortality nadir, it is directly proportional. The question of the boundary between "normal" and "reduced" LV EF in terms of CHF syndrome remains open, but obviously, this boundary is most likely within the range of 50 to 60%. 4) LV EF determines the effectiveness of CHF treatment, but this rule is not applicable to all LV EF ranges and not to all classes of drugs.

[Prospects for use of Vericiguat in HFrEF: Implications of VICTORIA Trial Results. Advisory Board Summary].

In September 2021, an online meeting of the Council of Experts was held. The proposed focus of discussion was publishing the results of an international prospective, randomized, double-blind, placebo-controlled study VICTORIA. The objective of the VICTORIA study was evaluation of the efficacy and safety of supplementing a standard therapy with vericiguat at a target dose of 10 mg twice a day as compared to placebo for prevention of cardiovascular death and hospitalization for heart failure (HF) in patients with clinical manifestations of chronic HF and left ventricular ejection fraction <45% who have recently had an episode of decompensated HF. The aim of the meeting was interpretation of the VICTORIA study results on efficacy and safety of vericiguat for a potential use in a Russian population of patients after a recent episode of decompensated chronic HF with reduced ejection fraction.

[Diastolic heart failure: 20 years later. Сurrent issues of pathoge-nesis, diagnosis and treatment of heart failure with preserved LVEF].

Relevant aspects of the pathogenesis, diagnosis, And treatment of heart failure with preserved LV EFThis review analyzes results of studies of the recent decade that focus on epidemiology, mechanisms of development, diagnostic methods, and treatments of heart failure with preserved ejection fraction (HFpEF). As expected, the prevalence of HFpEF continues to increase due to the growing contribution of comorbidities to the structure of causes for chronic heart failure (CHF), such as arterial hypertension with left ventricular hypertrophy, obesity, chronic kidney disease, as well as due to ageing of the population and decreased contributions of ischemic heart disease and myocardial infarction. Concomitant diseases are a source of low-intensity microvascular inflammation, which is currently assigned a role of a trigger mechanism eventually provoking energy deficiency, disorders of cardiomyocyte relaxation, and diffuse myocardial fibrosis. Both these processes lead to increased heart muscle rigidity and abnormally high left ventricular filling pressure (LVFP). High LVFP is associated with the development of pulmonary venous congestion and impairment of alveolar blood oxygenation, which form the clinical picture of HFpEF. Detecting high LVEF with tissue Doppler echocardiography by the E / e' value became the instrumental basis for the HFpEF diagnostics. Recognition of inflammation and fibrosis as the key pathogenetic factors marked the main vector of modern therapy for HFpEF (anti-inflammatory and antifibrotic). The best implementation of this vector became possible with the advent of drugs from the class of angiotensin receptor and neprilysin inhibitors (ARNI), sodium-glucose cotransporter type 2 (SGLT2) inhibitors, and aldosterone antagonists. However, the efficacy of such treatments is evident only with the LV EF <60-65% while at higher values, the efficacy substantially decreases. This limitation may result from the heterogenous nature of the disease and requires more advanced methods for verification of HFpEF clinical phenotypes. Among such methods, transcriptomic, metabolomic, and proteomic approaches are considered. With the use of capabilities of the "machine learning" and the artificial intelligence, these approaches can become a new frontier in research to represent an important step towards personalized medicine for patients with HFpEF.

[Remote electrocardiogram telemonitoring after endovascular interventions on the coronary arteries].

AIM: To evaluate the effectiveness of a new system for telemetric electrocardiogram (ECG) monitoring in patients after endovascular interventions (EI) on the coronary arteries (CA). MATERIALS AND METHODS: 168 patients with chronic ischemic heart disease who underwent EI on the CA on an outpatient basis, and during routine hospitalization, followed by telemetric ECG-monitoring after interventions were included. The monitoring was carried out using a three-channel telemetric recorder Astrocard HE3 (Russia), which provides continuous monitoring of 3-lead ECG for a long time. RESULTS: The telemetry was successfully performed in all 168 (100%) patients. In 165 (98%) patients, the quality of the recording was regarded as good, in 3 (2%) as satisfactory. There were no cases of disconnection of the device, no interruptions in recording. During the observation period, no life-threatening arrhythmia revealed. When comparing the telemetry results in different groups of patients, there were no significant differences in the incidence of arrhythmia. Patients with a history of percutaneous coronary interventions were questioned; according to which 92% of respondents reported that they felt more comfortable after the intervention followed by telemetric ECG-monitoring. CONCLUSION: Carrying out telemetric ECG-monitoring after EI on the CA improves the quality of observation after the procedure, promotes early discharge of patients, makes the intervention more comfortable and safe. The introduction of this technique into clinical practice will make it possible to more widely use the outpatient approach when carrying out EI, and to increase the turnover of specialized beds and the efficiency of the work of medical institutions.

[Three ages of spironolactone. Evolution of views on spironolactone capabilities in the treatment of patients with heart failure.]

The article describes the history of the discovery of aldosterone and the creation of its antagonist, spironolactone. The effects of aldosterone associated with the stimulation of two types of receptors.  Long-term effect (nuclear or genomic) and fast - term (membrane). They are manifested not only by the influence on the water-salt metabolism and the volume of extracellular fluid, but also in the regulation of vascular tone and elasticity of the vascular wall and, most interestingly, the effect on cardiac remodeling. Early after its development  Spironolactone was considered as a medicine for water-salt metabolism regulation, diuresis and normalization of blood pressure. In the following period,  Spironolactone embraced a new area - systolic heart failure. The drug was considered not only to enhance safe diuresis, but also to eliminate the phenomenon of escape of the antialdosterone effect angiotensin-converting enzyme inhibitors. The change in the paradigm of heart failure towards the prevailing changes in her diastolic phenotype, which is based on excessive diffuse myocardial fibrosis, changed role of spironolactone in the treatment of heart failure. Currently, it is considered as an independent drug, due to its powerful antifibrotic effect, blocking which controls the whole complex of endo- and paracrine effects of aldosterone.

[Treatment of patients with heart failure and preserved ejection fraction: reliance on clinical phenotypes].

The article discusses the problem of improving the effectiveness of treatment of heart failure with preserved left ventricular ejection fraction (HFpEF). The relative "failure" of early studies with renin-angiotensin-aldosterone system inhibitors was largely due to the lack of understanding that patients with HFpEF represent a heterogeneous group with various etiological factors and pathogenetic mechanisms of the disease. Therefore, the so-called personalized approach should be used in the treatment of these patients. This approach is based on the identification of clearly defined disease phenotypes, each characterized by a set of demographic, pathogenetic, and clinical characteristics. Based on the literature and own experience, the authors consider four main phenotypes of HFpEF: 1) phenotype with brain natriuretic peptide "deficiency" syndrome associated with moderate/severe left ventricular hypertrophy; 2) cardiometabolic phenotype; 3) phenotype with mixed pulmonary hypertension and right ventricular failure; and 4) cardiac amyloidosis phenotype. In the treatment of patients with phenotype 1, it seems preferable to use the valsartan + sacubitril (possibly in combination with spironolactone) combination treatment; with phenotype 2, the empagliflozin treatment is the best; with phenotype 3, the phosphodiesterase type 5 inhibitor sildenafil; and with phenotype 4, transthyretin stabilizers. Certain features of different phenotypes overlap and may change as the disease progresses. Nevertheless, the isolation of these phenotypes is advisable to prioritize the choice of drug therapy. Thus, the diuretic treatment (preferably torasemide) should be considered in the presence of congestion, regardless of the HFpEF phenotype; the valsartan + sacubitril and spironolactone treatment is appropriate not only in the shortage of brain natriuretic peptide but also in the presence of concentric left ventricular hypertrophy (except for the amyloidosis phenotype); and the treatment with empagliflozin and statins may be considered in all situations where pro-inflammatory mechanisms are involved.

Epidemiology of atrial fibrillation in a representative sample of the European part of the Russian Federation. Analysis of EPOCH-CHF study.

Aim    To study true prevalence of atrial fibrillation (AF) in a representative sample from the European part of the Russian Federation; to describe characteristics of patients with AF; and to provide the frequency of anticoagulant treatment.Material and methods    Cross-sectional data of the EPOCH epidemiological study (2017) were used. Data were collected in 8 constituent entities of the Russian Federation; the sample size was 11 453 people. The sample included all respondents who had given their consent for participation and were older than 10 years. Statistical tests were performed in the R system for statistical data analysis.Results    The prevalence of AF in the representative sample from the European part of the Russian Federation was 2.04 %. The AF prevalence increased with age and reached a maximum value of 9.6% in the age group of 80 to 89 years. The AF prevalence among females was 1.5 times higher than among men. With age standardization, the AF prevalence was 18.95 and 21.33 per 1,000 people for men and women, respectively. The AF prevalence increased in the presence of concurrent cardiovascular diseases (CVDs) or diabetes mellitus as well as with an increased number of comorbidities in the same person and reached 70.3 and 60.0 % in patients with 4 and 5 comorbidities, respectively. Patients with AF had a greater number of comorbidities and higher CHA2DS2VASc scores (5.0 vs. 2.0, p<0.001) compared to patients with CVDs without AF. Only 22.6 % of patients with CVD and AF took anticoagulants. Only 23.9% of patients with absolute indications for the anticoagulant treatment received anticoagulants.Conclusion    The AF prevalence in the European part of the Russian Federation was 2.04 %; it increased with age and in patients with concurrent CVDs or diabetes mellitus. Most of AF patients (93.2 %) required a mandatory treatment with oral anticoagulants.

[Ð ossibility of using European (HFA-PEFF) and American (H2FPEF) algorithms for diagnosing heart failure with preserved ejection fraction in Russian clinical practice].

This article focuses on the significance of a unified approach to diagnosing heart failure with preserved left ventricular ejection fraction (HFpEF). The key hemodynamic index of HFpEF is increased left ventricular filling pressure (LVFP) and its noninvasive marker, the E / e' value obtained by tissue Doppler echocardiography (EchoCG). The modern verified algorithms for HFpEF diagnosis, HFA-PEFF and Н2FPEF, mandatorily take into account the E / e' value. However, the routing use of these algorithms in the Russian practice may be complicated since even among "advanced" specialists who are interested in heart failure, 38% of the interviewed do not use or do not know how to use tissue Doppler EchoCG or the algorithm for diagnosing HFpEF with E / e'. In addition to the obvious way of overcoming this problem by equipping respective medical facilities with ultrasonic apparatuses with tissue Doppler EchoCG software and educating physicians, a possibility of using simplified HFA algorithm without the E / e' value is being considered. However, such approach will inevitably lead to erroneous estimation of the probability of HFpEF and, at the best, to underestimation of this probability with ensuing mistakes in diagnosis and treatment. Simplifying the HFA-PEFF and H2FPEF algorithms by omitting one or more parameters is possible but this requires a special investigation to develop a new rating scale and actually a new algorithm, which, in turn, will require a new validation.

[Focus ultrasound for cardiology practice. Russian consensus document].

This document is a consensus document of Russian Specialists in Heart Failure, Russian Society of Cardiology, Russian Association of Specialists in Ultrasound Diagnostics in Medicine and Russian Society for the Prevention of Noncommunicable Diseases. In the document a definition of focus ultrasound is stated and discussed when it can be used in cardiology practice in Russian Federation.

Chronic heart failure in the Russian Federation: what has changed over 20 years of follow-up? Results of the EPOCH-CHF study.

Aim    To study the etiology and the dynamics of prevalence and mortality of CHF; to evaluate the treatment coverage of such patients in a representative sample of the European part of the Russian Federation for a 20-year period. Material and methods    A representative sample of the European part of the Russian Federation followed up for 2002 through 2017 (n=19 276); a representative sample of the population of the Nizhny Novgorod region examined in 1998 (n=1922).Results    During the observation period since 2002, the incidence of major CHF symptoms (tachycardia, edema, shortness of breath, weakness) tended to decrease while the prevalence of cardiovascular diseases has statistically significantly increased. During the period from 1998 through 2017, the prevalence of I-IV functional class (FC) CHF increased from 6.1 % to 8.2 % whereas III-IV FC CHF increased from 1.8 % to 3.1 %. The main causes for the development of CHF remained arterial hypertension and ischemic heart disease; the role of myocardial infarction and diabetes mellitus as causes for CHF was noted. For the analyzed period, the number of treatment components and the coverage of basic therapy for patients with CHF increased, which probably accounts for a slower increase in the disease prevalence by 2007-2017. The prognosis of patients was unfavorable: in I-II FC CHF, the median survival was 8.4 (95 % CI: 7.8-9.1) years and in III-IV FC CHF, the median survival was 3.8 (95 % CI: 3.4-4.2) years.

[The use of diuretics in chronic heart failure. Position paper of the Russian Heart Failure Society].

The document focuses on key issues of diuretic therapy in CHF from the standpoint of current views on the pathogenesis of edema syndrome, its diagnosis, and characteristics of using diuretics in various clinical situations.

[The role of diastolic transthoracic stress echocardiography with incremental workload in the evaluation of heart failure with preserved ejection fraction: indications, methodology, interpretation. Expert consensus developed under the auspices of the National Medical Research Center of Cardiology, Society of Experts in Heart Failure (SEHF), and Russian Association of Experts in Ultrasound Diagnosis in Medicine (REUDM)].

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is associated with certain difficulties since many patients with HFpEF have a slight left ventricular diastolic dysfunction and normal filling pressure at rest. Diagnosis of HFpEF is improved by using diastolic transthoracic stress-echocardiography with dosed exercise (or diastolic stress test), which allows detection of increased filling pressure during the exercise. The present expert consensus explains the requirement for using the diastolic stress test in diagnosing HFpEF from clinical and pathophysiological standpoints; defines indications for the test with a description of its methodological aspects; and addresses issues of using the test in special patient groups.

[Empagliflozin and heart failure: position paper of the experts on the results of the online meeting and discussion of the EMPEROR-Preserved Trial].

At an international online expert meeting held on September 16, 2021, the results of the empagliflozin research program EMPA-REG Outcome, EMPEROR-Reduced and EMPEROR-Preserved were reviewed. We analyzed cardiovascular and renal outcomes during the treatment with empagliflozin in patients with chronic heart failure, regardless of the presence of type 2 diabetes mellitus. The positive results of the EMPEROR-Preserved study are updated and their significance for clinical practice is discussed. Several proposals have been adopted that will accelerate the introduction of empagliflozin therapy into practice in patients with heart failure and overcome clinical inertia.

[The Choice of Priorities in Contemporary Comparative Trials: Superiority vs non Inferiority. Causes and Effects].

The article compares two statistical approaches, which are commonly used in current comparative studies, a hypothesis that a drug is superior over another one (superiority) and a hypothesis that a drug is not inferior to another one in the efficacy and safety (non-inferiority). Using the example of specific studies, the difference between the methods and the tasks, for the solution of which one or another method should be applied, are shown. In order to prove the superiority in efficacy and safety of a new drug over an existing one, only a statistical approach that uses the "superiority" hypothesis is applicable. Studies using the "non-inferiority" hypothesis are generally used for comparing drugs, which are not considerably different in their efficacy, but the study drug has other advantages in the administration, storage, tolerability etc. The choice of statistical method is determined exclusively by the task of the study.

The Molecular and Cellular Mechanisms Associated with a Microvascular Inflammation in the Pathogenesis of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a severe disease with an often unfavorable outcome. The prevalence of HFpEF continues to increase, while effective treatment options remain elusive. All the medical strategies used to improve the outcome in a heart failure with reduced ejection fraction proved ineffective in HFpEF, which was probably due to the different mechanisms of development of these two types of heart failure and the diversity of the HFpEF phenotypes. According to the current paradigm of HFpEF development, a chronic mild pro-inflammatory state causes a coronary microvascular endothelial inflammation, with further myocardial fibrosis and diastolic dysfunction progression. This inflammatory paradigm of HFpEF has been confirmed with some evidence, and suppressing the inflammation may become a novel strategy for treating and managing HFpEF. This review summarizes current concepts about a microvascular inflammation in hypertrophied myocardium and provides a translational perspective of the anti-inflammatory and immunomodulatory approaches in HFpEF.