CLINICAL MEDICINE NEWS
ПЕРЕДОВАЯ СТАТЬЯ
In October 2020, the Russian Ministry of Health approved clinical guidelines for the management of patients with myocarditis. The aim of this review was to highlight controversial and open issues without unambiguous answer or those that were not described in the paper. The review highlights the objective factors that complicate the development of practical guidelines for the management of this category of patients. Comments on the definition and classification of inflammatory heart diseases are given. The approaches to the diagnosis of patients with suspected myocarditis are discussed. Particular attention is paid to the decision-making strategy in selecting optimal therapy in patients with documented myocarditis and the role of endomyocardial biopsy.
ORIGINAL ARTICLES
Aim. To evaluate the informative value of biomarkers (cardiac troponin l (cTnl), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-brain natriuretic peptide (NTproBNP), stimulating growth factor (ST2)) as laboratory markers of myocardial ischemia-reperfusion injury in patients with ST-segment elevation acute coronary syndrome (STEACS) undergoing endovascular revascularization.
Material and methods. The study included 115 patients with STEACS who underwent endovascular myocardial revascularization. To identify the informative value of biomarkers, the levels of cTnl, NTproBNP, hsCRP, sST2 were analyzed at baseline, as well as after reperfusion therapy on the 2nd (cTnl) and 5th (sST2, hsCRP, NTproBNP) days. Contrast-enhanced cardiac magnetic resonance imaging was performed 5 days after endovascular intervention.
Results. Microvascular obstruction was detected in 54 patients (47%), of which 24 (44%) patients had a combination of microvascular obstruction and myocardial hemorrhage. ln 61 cases (53%), no microvascular damage was registered. lt was found that with an increase in the threshold initial NTproBNP levels >590 pg/ml, the odds ratio (OR) of myocardial reperfusion injury was 12,2 (95% confidence interval (CI), 4,81-30,92, p<0,001). In addition, we analyzed biomarker levels in the early period after myocardial infarction, at which threshold values of reperfusion injury parameters were established as follows: for cTnI >8,1 ng/ml, OR=7,17 (95% CI, 3,11-16,53, p=0,001); for hsCRP >14 mg/L, OR=12,71 (95% CI, 5,03-32,08, p=0,001); for NTproBNP >334 pg/ml, OR=11,8 (95% CI, 4,88-28,59, p=0,001); for sST2 >41 ng/ml, OR=7,17 (95% CI, 3,11-16,53, p=0,001). According to multivariate analysis, predictors of microvascular injury were the initial NTproBNP values, as well as the cTnI, hsCRP, and sST2 values in the early postinfarction period (sensitivity — 89,5%, specificity — 83,3%).
Conclusion. Thus, the initial NTproBNP, as well as cTnI, hsCRP, sST2 values after percutaneous coronary intervention are more informative for assessing the risk of microvascular damage.
Aim. To assess the prognostic role of a decrease in longitudinal strain and an increase in the left ventricular sphericity index as predictors of NYHA class III heart failure (HF) progression, requiring hospitalization in a cohort of patients with noncompaction cardiomyopathy (NCM) in combination with dilated cardiomyopathy (DCM).
Material and methods. We examined 90 patients with a combination of NCM and DCM aged 18 to 72 years (median age, 41 years; men — 73; women — 17), who, in addition to conventional echocardiographic and magnetic resonance imaging (MRI) characteristics, were studied for two-dimensional strain and global longitudinal strain (GLS) parameters and left ventricular sphericity index (SI) using cardiac MRI. The endpoints included NYHA class III HF progression, requiring hospitalization.
Results. During the follow-up period (median follow-up, 36 (6; 152) months) in 59 of 90 (65,5%) patients with NCM in combination with DCM, symptoms progressed to NYHA class III HF, requiring hospitalization. Multivariate analysis showed following independent risk factors for HF-related hospitalization: a decrease in GLS <10% (hazard ratio (HR), 5,1; 95% confidence interval (CI), 1,6-16,7, p<0,007) and an increase in SI >0,5 (HR, 9,0; 95% CI, 2,2-37,8, p<0,003) .The 3-year event-free survival rate for patients with one risk factor (GLS, %<10 and SI <0,5; GLS, %>10 and SI >0,5) was 79,2±16,9% and 64,4±24,6%, respectively, while for the group with two risk factors (GLS, %<10 and SI>0,5) — 12,3%.
Conclusion. Global longitudinal strain characteristics according to 2D Strain echocardiography and SI according to cardiac MRI are associated with adverse events in NCM and DCM combination and can be used to identify patients with a high risk of HF progression to NYHA class III, requiring hospitalization.
Aim. To study the efficacy and safety of mycophenolate mofetil (MM) in combination with corticosteroids in the treatment of lymphocytic myocarditis in comparison with a standard combination of corticosteroids and azathioprine.
Material and methods. The study included 46 patients aged 18 years and older with severe and moderate lymphocytic myocarditis (men, 34; women 12; mean age, 53,5±13,0 years). The diagnosis was verified using endomyocardial biopsy. Symptom duration averaged 9,5 [4; 20.25] months. All patients had class 3 [2,75; 3] heart failure (HF). The main group included 29 patients who received MM 2 g/day, including six patients — instead of azathioprine, which was canceled due to cytopenia (n=3) or insufficient effect (n=3). The comparison group included 17 patients who received azathioprine 150 [100; 150] mg/day. Patients of both groups also received methylprednisolone at a starting dose of 24 [24; 32] and 24 [24; 24] mg/day and standard HF therapy. In 7/2 patients, the parvovirus B19 genome was detected in the myocardium. In all cases, an increase in anticardiac antibody titers was evidence of immune activity. The average follow-up period was 24 [12; 54] months (at least 6 months).
Results. The groups were completely comparable in age, initial characteristics and standard drug therapy. In both groups, a comparable significant increase in the ejection fraction (EF) was noted as follows: from 31,2±7,6 to 44,7±8,3% and from 29±9,1 to 46±11,9% (p<0,001). An excellent response to treatment (an increase in EF by 10% or more) was noted in 68,2% and 66,7% of patients, a good response (by 9-5%) — in 27,3% and 14,3%, a poor response (an increase in less than 5% or a decrease in EF) — in 4,5% and 19,0%, respectively. In both groups, we noted the same significant (p<0,01) decrease in pulmonary artery systolic pressure (36,3±12 to 28,1±6,1 mm Hg in the MM group and from 44,1±8,5 to 30,7±12,1 mm Hg in the azathioprine group), left ventricular (LV) end-diastolic dimension (from 6,4±0,6 to 6±0,7 cm and from 6,2±0,5 to 5,8±0,6 cm), LV end-diastolic volume (from 188,7±55,2 to 178,8±57,1 ml and from 167,8±47,5 to 163,3±61,8 ml), LV end-systolic volume (from 130,3±44,1 to 98,4±32 ml and from 118,1±39 to 94,1±46 ml), left atrial volume (from 98,3±30,3 to 86,7±32,6 ml and from 105±27,4 to 91,2±47,3 ml, p<0,05), as well as mitral regurgitation grade. The incidence of deaths was 2 (6,9%) and 2 (8,7%), transplantation — 1 (3,4%) and 1 (4,3%) patients, death+transplantation end point — 3 (10,3%) and 2 (11,8%) without significant differences between the groups. The presence of the parvovirus B19 genome did not affect the results of treatment. The incidence of infectious complications was comparable in both groups (in one case, MM was completely canceled), no new cytopenia cases were noted during the follow-up period.
Conclusion. In patients with moderate and severe virus-negative (except for parvovirus B19) lymphocytic myocarditis, the combination of moderate-dose corticosteroids with mycophenolate mofetil 2 g/day is at least no less effective than the standard regimen of immunosuppressive therapy. There was a tendency towards a more pronounced decrease in anticardiac antibody titers in combination with better tolerance (no cases of cytopenia) in MM group. MM in combination with corticosteroids can be recommended as an alternative treatment regimen for lymphocytic myocarditis.
Endomyocardial biopsy (EMB) is the method of choice for diagnosing a wide range of myocardial diseases.
Aim. To assess the rationale for diagnostic EMB in children and adults.
Material and methods. Morphological and statistical analysis of 2803 diagnostic EMBs in adults (n=811) and children (n=83), including those in heart transplantation (n=1909), was carried out.
Results. In 231 (28%) cases, adults were diagnosed with myocarditis, of which in 6 patients — granulomatous, in 5 — eosinophilic and in 6 — lymphocytic-macrophage myocarditis after coronavirus infection. In children, myocarditis was found in 22 cases (27%). Arrhythmogenic right ventricular dysplasia took the second place in detection rate in children and adults. Immunohistochemical study revealed viral envelope protein 1 (VP1) antigen of enteroviruses in one third of myocarditis cases, and in half — other cardiotropic viruses. Dotted dystrophin expression was observed in myocarditis. A correlation was established between the perforin expression and myocarditis presence (Pearson χ2=27,8; Fisher's exact test=27,3; p=0,01).
Conclusion. Analysis of diagnostic EMB results confirmed its rationale in adults and children not only for heart transplantation, but also for identifying cardiac pathology, including for myocarditis diagnosis. It has been shown that immunohistochemical study with antiviral antibodies can be considered as an alternative method for detecting viral infection. An immunohistochemical analysis for perforin and dystrophin can be recommended as additional morphological markers of myocarditis.
Aim. To compare the effectiveness of standard heart failure therapy with and without combined immunosuppressive therapy in patients with documented lymphocytic myocarditis (LM) based on data from actual clinical practice.
Material and methods. This observational study included 70 patients with documented LM, 40% (n=28) of whom received immunosuppressive therapy. All patients underwent standard echocardiographic and laboratory investigations, endomyocardial biopsy with histological, immunohistochemical and molecular genetic analysis. Contrast-enhanced cardiac magnetic resonance imaging was performed in 74% of patients. All patients received standard therapy for heart failure at baseline.
Results. The groups did not differ in demographic and echocardiographic characteristics. The appointment of immunosuppressive therapy was accompanied by an increase in ejection fraction by 12,2% compared to 6,4% (p=0,02). There were no significant differences in combined endpoints (survival and the need for heart transplantation) depending on therapy regimen (log-rank p=0,97).
Conclusion. The prognosis of patients with chronic LM depends on the process activity, the severity of impaired hemodynamics and ventricular arrhythmias, as well as on the presence of persistent viral infection. Compliance with patient selection algorithm before prescribing immunosuppressive therapy is associated with the improvement in myocardial global contractility.
Aim. To assess right heart condition in patients with coronavirus disease 2019 (COVID-19) pneumonia.
Material and methods. One hundred and five patients with COVID-19 pneumonia were divided into 3 groups depending on the involvement of lung parenchyma: group I — 0-25%, II — 25-50%, III — 50-75%. The clinical status of patients was assessed using the NEWS2 and SHOKS-COVID scales. A complete blood count and biochemical blood tests were performed to determine the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I. Echocardiography was performed to assess the right heart structural, hemodynamic and functional parameters.
Results. In patients with COVID-19 pneumonia, with an increase in lung parenchyma involvement, the intensity of systemic inflammatory response increased: C-reactive protein, group I — (4 [1,9; 35] mg/l), in III — (70,5 [33; 144] mg/l) (pI-III=0,012); myocardial stress marker level increased: NT-proBNP, group I — 77 [48; 150] ng/l, group III — 165 [100; 287] ng/l (pI-III=0,047). The dependence of NT-proBNP on C-reactive protein level was revealed (r=0,335, p=0,03). Intergroup comparison did not reveal significant differences between the main right heart functional parameters: TAPSE, Tei index (PW and TDI), FAC of the right ventricle (RV) (p>0,05). However, differences in the tricuspid annular peaks were found as follows: group I — 0,14 [0,12; 0,14] m/s, group II — 0,14 [0,12; 0,15] m/s, group III — 0,16 [0,14; 0,17] m/s (pI-II=0,012, pI-III=0,014) and RV global longitudinal strain: group I — 19,63±7,72%, group III — 27,4±5,93% (pI-III=0,014). The relationship between the RV global longitudinal strain and SHOKS-COVID score was confirmed (r=0,381; p=0,024).
Conclusion. Patients with COVID-19 pneumonia showed no signs of right heart dysfunction. The development of RV hyperfunction was noted. Most likely, this is a compensatory mechanism in response to acute RV afterload. NT-proBNP increase under conditions of an inflammatory response may indicate myocardial stress. The results obtained allow to expand our understanding of the right heart condition in patients with COVID-19 pneumonia.
Aim. To determine the concentration of blood fibrotic and inflammatory biomarkers in patients with atrial fibrillation (AF) associated with metabolic syndrome (MS) components.
Material and methods. The study included 646 patients aged 35-65 years: patients with AF and MS (n=142), those with AF and without MS (n=113), those with MS and without AF (n=175) and the control group consisted of healthy subjects without cardiovascular and metabolic diseases (n=107). All participants underwent anthropometric and laboratory investigations. Profibrogenic (aldosterone, galectin-3, TGF-beta1, CTGF) and proinflammatory (CT-1, IL-6) factors were determined in serum and plasma by ELISA. Statistical analysis was performed using IBM SPSS Statistics software (version 22.0).
Results. The highest concentrations of fibrotic and inflammatory biomarkers were found in patients with AF in combination with MS. In MS patients without AF, the concentration of aldosterone, galectin-3, TGF-beta1, CTGF, CT-1, and IL-6 was also higher than in healthy subjects. The levels of aldosterone, CT-1 and IL-6 in patients with AF were higher in the presence of three or more MS components, while the highest values of these parameters were found in patients with five MS components. The lowest concentrations of galectin-3, CTGF, and CT-1 in patients with AF were found in patients without MS components, and in the presence of even 1 MS component, they were significantly higher. Correlation analysis made it possible to establish a stronger relationship between aldosterone and TGF-betal with systolic blood pressure (p=0,493, p<O,O001 and p=0,530, p<O,O001), and CT-1, CTGF and IL-6 in a greater degree correlated with waist circumference (p=0,563, p<0,0001; p=0,626, p<0,0001; p=0,480, p<O,O001). The concentrations of galectin-3 and CTGF were more positively correlated with an increase in the number of MS components. In patients with AF and hypertension (HTN), but without abdominal obesity (AO), higher values of aldosterone (108,1±70,3 pg/ml and 89,3±32,2 pg/ml, p=0,003) and TGF-beta1 (3680,1±1863,3 pg/ml and 1968,1±1611,5 pg/ml, p=0,015) in serum than in AF patients without HTN and without AO. In the group of patients with AF and AO, but without HTN, higher concentrations of IL-6 (2,9±0,7 pg/ml and 1,9±0,6 pg/ml, p=0,001) and CTGF (162,9±92,2 pg/ml and 116,3±63,4 pg/ml, p=0,0001).
Conclusion. It can be assumed that hypertension through the aldosterone system and TGF-beta1, as well as abdominal obesity through the cytokine system CT-1 and IL-6 activate various mechanisms and pathways for myocardial remodeling. Integral molecules galectin-3 and CTGF mediate their interactions, in particular in patients with a combination of several MS components and contribute to a higher AF risk.
Idiopathic recurrent pericarditis (IRP) and adult-onset Still's disease (AOSD) are polygenic autoinflammatory diseases, in the pathogenesis of which pro-inflammatory cytokines from the interleukin-1 superfamily play a central role.
Aim. To compare serum concentrations of proinflammatory cytokines and glycosylated ferritin (GF) in patients with IRP and AOSD during an exacerbation.
Material and methods. The study included 15 patients with AOSD, 15 — IRP. The diagnosis of AOSD was established using the Yamaguchi criteria (1992). IRP was diagnosed in accordance with the 2015 European Society of Cardiology on the diagnosis and management of pericardial diseases. Blood sampling from all patients was carried out during the recurrence period prior to the anti-inflammatory therapy initiation. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), procalcitonin, total ferritin and GF was assessed. The results obtained were compared with levels of biochemical parameters, high-sensitivity C-reactive protein (CRP), as well as with white blood cell (WBC) and neutrophil counts.
Results. The median age in the AOSD group was 28 years, and the IRP — 55 years. An increase WBC count >10*109/L was detected in 10 and 9 patients in the AOSD and IRP groups, respectively. The concentration of CRP was increased in all patients and did not differ in the study groups (p=0,836).
The highest values of ferritin and GF levels were found in the AOSD group (1416 ng/ml vs 408 ng/ml, p=0,008) and (12% vs 33,9%, p=0,067), respectively. In both groups, increased concentrations of IL-6 and IL-18 were determined. In the AOSD group, the concentration of IL-18 was higher than in the IRP group (2114 pg/ml vs 161,5 pg/ml, p<0,001). IL-6 concentrations in the study groups did not differ (33,9 pg/ml vs 24,9 pg/ml, p=0,4). IL-1β serum concentration in all subjects corresponded to normal values.
Correlation analysis in the AOSD group revealed a direct relationship between the IL-18 and ferritin concentrations (rs=0,73, p=0,03).
Conclusion. The study established a similar pattern of changes in inflammatory biomarkers in patients with AOSD and IRI. The most informative marker of inflammation was IL-18.
Aim. To identify factors associated with long-term adverse cardiovascular events (CVEs) in patients with type 2 diabetes (T2D).
Material and methods. The study included 94 T2D patients aged 40 to 65 years with or without early symptoms of heart failure (HF). Patients underwent clinical and laboratory investigations, 6-minute walk test (6MWT), and echocardiography. Concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined. After 8,8±0,72 years of follow-up, the prevalence of following CVEs among patients were assessed: any-cause death, myocardial infarction, stroke, emergency myocardial revascularization, hospitalization due to decompensated HF. We assessed the relationship between the development of long-term CVEs in T2D patients and the initial characteristics using logistic regression model.
Results. Over a period of 8,8±0,72 years, CVEs occurred in 34 out of 88 (38,6%) patients with T2D. The baseline 6MWT values were lower in patients with CVEs (391,8±56,2 m vs 418,8±53,9 m, p=0,04). Stable coronary artery disease (55,9% vs 27,8%, p=0,008), early-stage HF (61,8% vs 27,8%; p=0,0016) were more common among patients with CVEs. Patients with CVEs had higher median initial NT-proBNP (46,9 pg/ml vs 24,2 pg/ml, p=0,01) and mean left atrial (LA) size (4,5±0,6 cm vs 4,19±0,5 cm, p=0,04) levels. The logistic regression established following factors associated with long-term CVEs in patients with T2D: NT-proBNP level (p=0,05), LA size (p=0,01), and 6MWT results (p=0,002).
Conclusion. The development of long-term CVEs in middle-aged T2D patients with or without early-stage HF is associated with an initially increased NT-proBNP levels, an increase in left atrial size, and a decrease in 6MWT values. Further prospective studies with larger samples are needed to identify other factors affecting outcome in patients with early signs of HF.
Aim. To develop predictive models of obstructive coronary artery disease (OPCA) in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) based on the predictive potential of cardiometabolic risk (CMR) factors.
Material and methods. This prospective observational cohort study included 495 patients with NSTE-ACS (median age, 62 years; 95% confidence interval [60; 64]), who underwent invasive coronary angiography (CAG). Two groups of persons were identified, the first of which consisted of 345 (69,6%) patients with OPCA (stenosis ≥50%), and the second — 150 (30,4%) without OPCA (<50%). The clinical and functional status of patients before CAG was assessed including 29 parameters. For data processing and analysis, the Mann-Whitney, Fisher, chi-squared tests and univariate logistic regression (LR) were used. In addition, for the development of predictive models, we used multivariate LR (MLR), support vector machine (SVM) and random forest (RF). The models was assessed using 4 metrics: area under the ROC-curve (AUC), sensitivity, specificity, and accuracy.
Results. A comprehensive analysis of functional and metabolic status of patients made it possible to identify the CMR factors that have linear and nonlinear association with OPCA. Their weighting coefficients and threshold values with the highest predictive potential were determined using univariate LR. The quality metrics of the best predictive algorithm based on an ensemble of 10 MLR models were as follows: AUC — 0,82, specificity and accuracy — 0,73, sensitivity — 0,75. The predictors of this model were 7 categorical (total cholesterol (CS) ≥5,9 mmol/L, low-density lipoprotein cholesterol >3,5 mmol/L, waist-to-hip ratio ≥0,9, waist-to-height ratio ≥0,69, atherogenic index ≥3,4, lipid accumulation product index ≥38,5 cm*mmol/L, uric acid ≥356 pmol/L) and 2 continuous (high density lipoprotein cholesterol and insulin resistance index) variables.
Conclusion. The developed algorithm for selecting predictors made it possible to determine their significant predictive threshold values and weighting coefficients characterizing the degree of influence on endpoints. The ensemble of MLR models demonstrated the highest accuracy of OPCA prediction before the CAG. The predictive accuracy of the SVM and RF models was significantly lower.
CLINICAL CASE
Rhabdomyolysis is a very rare and most severe form of statin-induced muscle adverse event characterized by muscle pain, muscle necrosis with myoglobinemia and/or myoglobinuria with a very high risk of acute kidney injury and death. The article presents a case report of developing rhabdomyolysis in a middleaged female patient with hypertension, decompensated type 2 diabetes and albuminuria. A 60-year-old woman was admitted to the hospital for emergency indications with complaints of severe muscle weakness that began in the neck, which spread over several days to the upper and lower extremities, with a symptoms progression up to paresis. According to the appointment of a primary care physician, three months before hospitalization, the patient was switched from therapy with European generic brand-name rosuvastatin 20 mg to the Russian generic unbranded atorvastatin in the same dose (20 mg), which is not comparable in lipid-lowering effect. In a laboratory study, an increase in creatine phosphokinase level by 348 times (50462 U/L) of upper normal limit in combination with severe hypokalemia 1б7 mmol/L in the absence of renal dysfunction was recorded. Cancellation of statin, metformin and empagliflozin, intensive infusion therapy and treating electrolyte imbalance made it possible to prevent the development of acute renal damage, life-threatening arrhythmias and completely stop muscle complaints within a few days. The patient was discharged from the hospital on the 23rd day with reference clinical and laboratory values, including creatine phosphokinase.
This case emphasizes the importance of maintaining clinical suspicion regarding rhabdomyolysis in patients receiving statin therapy in the presence of risk factors (in this case, female sex, hyperglycemia, chronic kidney disease, concomitant therapy), as well as the relevance of timely diagnosis and treatment of this condition.
REVIEW
This article describes evolution of criteria for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The novel diagnostic criteria for ARVD/C published in 2020 are analyzed in detail, among which biventricular and leftdominant arrhythmogenic cardiomyopathy are identified for the first time. The need to develop novel criteria was fed on the accumulation of new data on ARVD/C, in particular, significant advances in magnetic resonance imaging technologies. The novel criteria retained high sensitivity and specificity in relation to traditional right ventricular disease form and became more sensitive in relation to the biventricular and left-dominant arrhythmogenic cardiomyopathy.
Nevertheless, the addition of left-dominant disease forms reduces the criteria specificity in general, since left ventricle involvement with a similar clinical performance can have different etiology that goes beyond the ARVD/C, even when mutations are detected in typical genes, which is demonstrated by case reports described in the article. Like the previous two versions, the novel criteria will be fully assessed only with a large sample of patients after their introduction into the routine cardiology clinical practice.
Despite the growing population of elderly people and long-livers every year, the treatment of acute coronary syndrome in these groups is not fully developed and is not regulated in clinical guidelines due to the lack of large randomized clinical trials. The article presents a literature review covering the following issues arising during clinical decision-making in the treatment of non-ST-segment elevation acute coronary syndrome in this group of patients: selection of invasive treatment strategy, scope of myocardial revascularization, appointment of dual antiplatelet therapy taking into account the bleeding risk, decreased renal function and senile asthenia. In addition, a case report of successful treatment of a 101-year-old female patient with non-ST-segment elevation myocardial infarction, who underwent percutaneous coronary intervention with stenting of infarct-related artery, was presented.
Perivascular adipose tissue (PVAT) is an active regulator of vascular homeostasis. In physiological conditions, it maintains normal function of vessels, releasing antiatherogenic, anti-inflammatory and vasodilating biologically active substances. Dysfunctional PVAT secretes pro-inflammatory cytokines and adipokines, which play an important role in the development of cardiovascular diseases. This review considers the PVAT function in health and disease, its contribution to the pathogenesis of atherosclerosis, hypertension, aortic aneurysm and vasculitis. In addition, novel methods of non-invasive PVAT assessment and potential strategies for targeted treatment of cardiovascular diseases are presented.
CLINICAL GUIDELINES
Russian Society of Cardiology (RSC)
With the participation: Eurasian Association of Therapists (EUAT), Society of Specialists in Heart Failure (OSSN), Russian Scientific Medical Society of Therapists (RNMOT), Russian Society of Pathologists, Russian Society of Radiologists and Radiologists (RSR)
Endorsed by: Research and Practical Council of the Ministry of Health of the Russian Federation
ISSN 2618-7620 (Online)