
Scientific and practical peer-reviewed journal for cardiologists and internists "Rational Pharmacotherapy in Cardiology" has been coming out since 2005 with the support of the Russian Society of Cardiology and the National Medical Research Center for Therapy and Preventive Medicine. Editor-in-chief of the Journal is Prof. Sergey A. Boytsov, MD, PhD, Academician of the Russian Academy of Sciences, Director of the National Medical Research Center of Cardiology named after Academician E.I. Chazov
The "Rational Pharmacotherapy in Cardiology" Journal is a national edition with issued 6 times per year. The Journal is recommended for the publication of the results of master’s and doctor’s dissertations according to the List of editions of the State Commission for Academic Degrees and Titles. It is distributed by subscription and for free at special events.
The Editorial Board consists of leading Russian and international scientists in the field of cardiology, preventive cardiology, internal medicine, clinical pharmacology and preventive pharmacotherapy, including 44 Doctors of Science and 9 Academicians and corresponding members of the Russian Academy of Sciences , and National Academies of Sciences.
The Journal mainly contains original study articles, scientific reviews, lectures, analysis of clinical practice. The Journal highlights the problems of early diagnosis, primary and secondary prevention of cardiovascular diseases, associated conditions, effective pharmacotherapy, and current questions of experimental and clinical pharmacology.
All manuscripts are published for free. They are subject to a thorough scientific expertise: double-blind review, plagiarism check, multi-stage editing. Authors are required to submit a statement of disclosure of conflict of interest associated with the publication. Reviewers are experts on the subject of peer-reviewed material. In each issue the best original articles are translated and published in Russian and English languages.
The Journal has website (www.rpcardio.com) in English and Russian where the full texts of published materials for all years are available in open access. The Journal is also available in open access on the website of the Scientific Electronic Library (SEL) and has a high impact factor of the Russian Science Citation Index (RSCI). Full-text electronic versions of all published materials are also available on the website of the Russian Scientific Electronic Library CyberLeninka and international open access website DOAJ. Published materials are presented in the international electronic databases Scopus, Web of Science, EMBASE, Ulrich's Periodicals Directory.
HAC: 140105 Cardiology, 140306 Pharmacology, Clinical Pharmacology.
Science Index (2020) – 1,595
The two-year impact factor of the RSCI, taking into account citations from all sources, 2020 - 1,342
Scopus (2020) - 0,8
(Pharmacology (medical) - Q3, 25 percentile)
Cardiology and Cardiovascular Medicine - Q4, 22 percentile)
Current issue
ORIGINAL STUDIES 
Aim. To assess the association of hypertension with the severe forms and fatal outcomes of Coronavirus disease 2019 (COVID-19).
Material and Methods. This retrospective cohort study involved adult patients (≥18 years old), admitted to the University hospital №4 of Sechenov University (Moscow, Russia) between 08 April 2020 and 19 November 2020 with clinically diagnosed or laboratory-confirmed COVID-19. The cohort included 1637 patients. The primary outcome was all-cause in-hospital mortality. The secondary outcomes included intensive care unit admission (ICU) and invasive ventilation. Multiple logistic regression was performed to assess the independent association between risk factors and endpoints.
Results. A total of 1637 patients were included in the study. 51.80% (n=848) of the subjects were males. The median age was 59.0 (48.0; 70.0) years and 55.90% (n=915) had pre-existing diagnosis of hypertension. Patients with hypertension had significantly more severe lung injury based on chest CT scan findings as well as lower oxygen saturation (SрO2). More of them were admitted to ICU and placed on invasive ventilation. The hypertension group also had higher mortality. Age, hypertension, glucose, C-reactive protein and decreased platelet count were independently associated with mortality, hypertension having the strongest association (OR 1.827, 95% CI 1.174-2.846, p=0.008). Age, hypertension, neutrophil count, platelet count, glucose, and CRP were independently associated with ICU admission, with hypertension having the strongest association (OR 1.595, 95% CI 1.178-2.158, p=0.002). Age, hypertension, glucose, CRP and decreased platelet count were independently associated with invasive ventilation, with hypertension having the strongest association (OR 1.703, 95% CI 1.151-2.519, p=0.008).Based on the multiple logistic regression models, odds of death, ICU admission, and invasive ventilation were higher in the hypertension group as compared to the group without hypertension.
Conclusion. Hypertension can be an independent predictor of severe COVID-19 and adverse outcomes, namely death, ICU admission, and invasive ventilation in hospitalized patients.
Aim. To study associations between arterial stiffness and bone mineral density in postmenopausal women.
Material and methods. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation. The Bone mineral density (BMD) of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry.
Results. A significant correlation of PWV with age, duration of menopause was revealed, a more pronounced correlation was noted with blood pressure (BP), maximum IMT thickness. There was no significant correlation between PWV and BMD. AI showed a statistically significant but weak negative correlation with the HN (rs=0.12, p<0.05); a more pronounced negative correlation was obtained for BMD (rs=0.16, p<0.01). For indicators characterizing the degree of bone mass increased, there is a significant correlation with age (rs=-0.4, p<0.01), weight (rs=0.4, p<0.01), Quetelet index (rs=0.3, p<0.01) and the presence of AP (rs=-0.12, p<0.05). According to the results of multivariate regression analysis, the most significant predictors of arterial stiffness were indicators reflecting obesity and diastolic BP. The relationship between BMD and age-adjusted vascular stiffness was not statistically significant.
Conclusion. In our study, postmenopausal women have increased arterial stiffness, suggesting a higher risk of cardiovascular disease. The relationship between bone mineral density and vascular wall stiffness was insignificant. To a greater extent, arterial stiffness depended on age, increased blood pressure, and the presence of atherosclerotic changes.
NOTES FROM PRACTICE 
Aim. To study the perioperative dynamics of myocardial injury biomarkers high-sensitivity cardiac troponin I (hs-cTnI), ischemia-modified albumin (IMA) and soluble ST2 (sST2) when taking nicorandil in lung cancer patients with concomitant coronary heart disease (CHD) undergoing surgical lung resection.
Material and methods. The study included 54 patients (11 women and 43 men) with non-small cell lung cancer and concomitant stable CHD who underwent lung resection in the volume of lobectomy or pneumonectomy. Patients were randomly assigned to the nicorandil group (oral administration 10 mg BID for 7 days before and 3 days after surgery; n=27) and the control group (n=27). In the study groups, the perioperative dynamics of hscTnI, IMA and sST2, determined in the blood before and 24 and 48h after surgery, were compared. We calculated the incidence of acute myocardial injury in the groups, which was diagnosed in cases of postoperative hs-cTnI increase of more than one 99th percentile of the upper reference limit. The associations of nicorandil intake and acute myocardial injury were evaluated.
Results. The groups were comparable in gender, age, basic clinical characteristics, as well as baseline levels of myocardial injury biomarkers. After the intervention, both samples showed an increase in the hs-cTnI and sST2 levels and a decrease in IMA concentration (all p<0.02 for related group differences). In the nicorandil group, in comparison with the control one, 48h after surgery, we found lower mean levels of hs-cTnI [16.7 (11.9;39.7) vs 44.3 (15.0;130.7) ng/l; p<0.05) and sST2 [62.8 (43.6;70.1) vs 76.5 (50.2;87.1) ng/ml; p<0.05), concentration increase rates of hs-cTnI [14.8 (0.7;42.2) vs 32.5 (14.0;125.0) ng/l; p<0.01) and sST2 [24.4 (10.3;42.4) vs 47.4 (17.5;65.3) ng/ml; p<0.05), as well as highest concentrations for the entire postoperative period of hs-cTnI [30.7 (12.0;53.7) vs 79.0 (20.3;203.3) ng/L, p<0.01] and sST2 [99.8 (73.6;162.5) vs 147.8 (87.8;207.7) ng/mL; p<0.05]. The serum IMA decreased when taking nicorandil to a greater extent [-8.0 (-12.6; -2.0) vs -2.7 (-6.0; +5.5) ng/ ml; p<0.01] 24h after surgery. Acute myocardial injury was diagnosed in 7 people in the nicorandil group (25.9%) and in 15 in the control one (55.6%; pχ2=0.027). The adjusted odds ratio of acute myocardial injury when taking nicorandil was 0.35 (95% confidence interval 0.15-0.83, p=0.017).
Conclusion. Taking nicorandil in patients with lung cancer and concomitant CHD who underwent surgical lung resection is associated with a lower postoperative increase in hs-cTnI and sST2 and a reduced risk of acute myocardial injury, which may indicate the cardioprotective effect of nicorandil under acute surgical stress conditions.
Aim. To study the levels of pro-inflammatory biomarkers in patients with obstructive and non-obstructive coronary artery disease (CAD), to identify possible differences for diagnosing the degree of coronary obstruction.
Material and methods. The observational study included two groups of patients: with non-obstructive (main group, coronary artery stenosis <50%; n=30) and obstructive (comparison group, hemodynamically significant coronary artery stenosis according to the results of coronary angiography; n=30) CAD. The levels of interleukin-1β (IL-1β) and interleukin 6 (IL-6) were measured in plasma using enzyme immunoassay.
Results. IL-6 levels were significantly higher in patients with obstructive CAD (p=0.006) than in patients with non-obstructive CAD. There were no significant differences in the level of IL-1β in both groups (p=0.482). When constructing the ROC curve, the threshold value of IL-6 was 26.060 pg/ml. At the level of IL-6 less than this value, CAD was diagnosed with hemodynamically insignificant stenoses of the coronary arteries.
Conclusion. The results of this study confirm that in patients with different types of coronary artery lesions, there are differences in the activity of the inflammation process in the arterial wall. IL-6 was higher in the obstructive lesion group, and IL-1β levels did not differ between groups. Thus, it can be assumed that hemodynamically significant obstruction of the coronary arteries develops as a result of highly active inflammation of the vascular wall. Given the presence of a proven biological basis and the available data on the effectiveness of monoclonal antibodies to IL-1β, one cannot exclude their possible benefit in a cohort of patients with CAD and hemodynamically insignificant stenoses.
Aim. Assessment of impact of the duration of preoperative antimicrobial therapy (AMT) on the sensitivity of microbiological examination and polymerase chain reaction (PCR) of blood/tissues of resected valves in operated patients with infective endocarditis (IE).
Materials and methods. 52 operated patients with active IE were included prospectively (Duke criteria, 2015). All patients underwent microbiological examination of blood before admission to the cardiac surgery hospital, as well as parallel simultaneous microbiological examination and PCR of blood/tissues of excised valves, followed by Sanger sequencing. The duration of preoperative treatment was calculated from the first day of AMT according to IE diagnosis to the day of surgery.
Results. The causative agent of IE was established in 84.6% (n=44) patients by means of complex etiological diagnosis. A significant decrease in the sensitivity of microbiological examination of venous blood was revealed when performed in the period before and after hospitalization to a surgical hospital (up 44.2% to 17.3%, p<0.05). When comparing microbiological examination of blood/tissues of resected valves and PCR of blood/tissues of resected valves, molecular biological methods demonstrated the greatest sensitivity, with a great advantage when examining the tissues of resected valves (17.3% and 19.2% vs. 38.5% and 75.0%, respectively; p<0.001). The microbiological examination of venous blood performed at an early date before admission to the cardiac surgery hospital was comparable in sensitivity to the PCR blood test performed at a later date after prolonged AMT, and significantly less sensitive in relation to the PCR of resected valve tissues [44.2% and 38.5% (p>0.05) vs. 75.0% (p<0.05)]. In course of AMT 1-28 days, there were comparable results of microbiological examination with PCR blood examination and significantly better results of PCR of resected valve tissues [31.0% and 34.5% and 41.4% (p>0.05) vs 72.4% (p<0.001), respectively], and with AMT ≥ 29 days, microbiological examination of any biological material was negative in all patients, and PCR of blood/tissues of resected valves retained high sensitivity (0% and 0% vs. 34.8% and 78.3%, respectively; p<0.01).
Conclusion. Long-term preoperative AMT significantly reduced the sensitivity of microbiological examination of resected valve blood/tissue in operated patients with IE, whereas PCR of resected valve blood/tissue was highly sensitive even with preoperative AMT for more than 29 days.
Aim. The analysis of the experience of using PCSK9 inhibitors (alirocumab) in patients with very high cardiovascular risk, аccording to long observations in real clinical practice.
Material and methods. In study evaluated the data for 31 people (23 men and 8 women, the average age of those surveyed was 59.4±5.8 years) of very high cardiovascular risk with atherogenic dyslipidemia and no achievement of the target lipid levels. Alirokumab was administered in a dose of 150 mg subcutaneously once every 2 weeks in the day hospital of a multidisciplinary clinic. The primary endpoint was reached the target level of low density lipoprotein cholesterol (HS-LDL) level and/or reduce HS-LDL levels by 50% or more. Liver tests, level of creatinine and glycemia were studied to assess safety; side effects studied/
Results. The long-term use of alirocumab (on average 7,5±2,3 months) is well tolerated without adverse reactions and withdrawal syndrome, in the day hospital of a multidisciplinary clinic. 90% of patient have achieved either a target level of HS-LDL less than 1.4 mmol/l or a reduction in HS-LDL by 50% or more. The remaining third of patients achieved both target levels. It can be distinguished a group of patients with a good response to the medication, in the first months of administration of alirokumab.
Conclusion. The results of conducting an efficiency assessment for use of the alirocumab in a dose of 150 mg subcutaneously within two weeks showed that this therapy has the high efficacy and good tolerability without any adverse reactions, in the day hospital of a multidisciplinary clinic.
PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY 
Aim. To assess adherence to the recommended therapy at the stage of outpatient follow-up and its impact on long-term outcomes in patients after acute myocardial infarction based on the materials of the prospective PROFILE-IM registry.
Material and methods. The PROFILE-IM register included 160 patients who applied to one of the polyclinics in Moscow after a myocardial infarction. The combined endpoint (CE) included death from any cause, cardiovascular events (nonfatal myocardial infarction, nonfatal cerebral stroke), emergency hospitalizations for cardiovascular diseases, significant cardiac arrhythmias. Patients' adherence to therapy was assessed using the original questionnaire "Scale of Adherence of the National Society of Evidence-based Pharmacotherapy" (NODF) and a direct standardized patient survey by a doctor about taking medications. Visits to the doctor were carried out every two months, data from the first year of patient follow-up are presented.
Results. In a personal interview with a doctor, the ratio of the proportion of committed, partially committed and non-committed patients did not change significantly over the entire follow-up period, while the proportion of committed patients was 81-85%. The "NODF Adherence Scale" showed that the proportion of non-committed patients was about 10 times higher than with direct patient responses to the doctor, and the proportion of non-committed and partially committed patients remained high at all stages of follow-up (respectively 28% and 10% at the beginning of the study, 18% and 10% at the end of the study). Among the main factors of non-commitment, there was a decrease in the importance of forgetfulness and an increase in factors such as fear of side effects of medications, doubt about the need for long-term use of medications and well-being. A direct relationship of adherence with the male sex, the presence of hypertension, a feedback relationship with alcohol consumption was revealed. The risk of CE in non-committed patients was higher compared to the group of committed and partially committed patients (p<0.01).
Conclusion. The proportion of non-committed and partially committed patients remained high at all stages of follow-up. There was a direct relationship between adherence to therapy with the male sex, the presence of hypertension in the anamnesis, and a feedback relationship with alcohol consumption. Low adherence to therapy significantly increased the risk of cardiovascular events.
ASSOCIATED PROBLEMS OF CARDIOLOGY 
The term "microbiota" refers to the microbial community occupying a specific habitat with defined physical and chemical properties and forming specific ecological niches. The adult intestinal microbiota is diverse. It mainly consists of bacteria of Bacteroidetes and Firmicutes types. The link between the gut microbiota and cardiovascular disease (CVD) is being actively discussed. Rapid progress in this field is explained by the development of new generation sequencing methods and the use of sterile gut mice in experiments. More and more data are being published about the influence of microbiota on the development and course of hypertension, coronary heart disease (IHD), myocardial hypertrophy, chronic heart failure (CHF) and atrial fibrillation (AF). Diet therapy, antibacterial drugs, pro- and prebiotics are successfully used as tools to correct the structure of the gut microbiota of the macroorganism. Correction of gut microbiota in an experiment on rats with coronary occlusion demonstrates a significant reduction in necrotic area. A study involving patients suffering from CHF reveals a significant reduction in the level of uric acid, highly sensitive C-reactive protein, and creatinine. In addition to structural and laboratory changes in patients with CVD when modifying the microbiota of the gut, also revealed the effect on the course of arterial hypertension. Correction of gut microbiota has a beneficial effect on the course of AF. We assume that further active study of issues of influence and interaction of gut microbiota and macroorganism may in the foreseeable future make significant adjustments in approaches to treatment of such patients.
POINT OF VIEW 
The experience of managing patients with COVID-19 around the world has shown that, although respiratory symptoms predominate during the manifestation of infection, then many patients can develop serious damage to the cardiovascular system. However, coronary artery disease (CHD) remains the leading cause of death worldwide. The purpose of the review is to clarify the possible pathogenetic links between COVID-19 and acute coronary syndrome (ACS), taking into account which will help to optimize the management of patients with comorbid pathology. Among the body's responses to SARS-CoV-2 infection, which increase the likelihood of developing ACS, the role of systemic inflammation, the quintessence of which is a "cytokine storm" that can destabilize an atherosclerotic plaque is discussed. Coagulopathy, typical for patients with Covid-19, is based on immunothrombosis, caused by a complex interaction between neutrophilic extracellular traps and von Willebrandt factor in conditions of systemic inflammation. The implementation of a modern strategy for managing patients with ACS, focused on the priority of percutaneous interventions (PCI), during a pandemic is experiencing great difficulties due to the formation of time delays before the start of invasive procedures due to the epidemiological situation. Despite this, the current European, American and Russian recommendations for the management of infected patients with ACS confirm the inviolability of the position of PCI as the first choice for treating patients with ACS and the undesirability of replacing invasive treatment with thrombolysis.
Pulmonary hypertension and right heart dysfunction often complicate the course of chronic heart failure. At the same time, the addition of these pathological conditions significantly increases the frequency of hospitalizations and worsens survival prognosis. That is why the assessment of the unfavorable outcome’s risk in the group of such patients is extremely important. This problem draws an interest for a more detailed study, considering the fact that the most convenient, accessible and minimally invasive prognosis marker has still being searched for nowadays. In this review article, which is based on the analysis of literature over the past 20 years dedicated to the problem of pulmonary hypertension and chronic heart failure, right ventricular-arterial coupling, has been considered as a relatively new parameter and as an example of one of these prognostic markers. This parameter can be assessed by echocardiography examination and our article describes several options of calculating it, including one of the most popular and valuable ratio of tricuspidal anular plane systolic excursion to the systolic pulmonary artery pressure (TAPSE/sPAP).
Mitral valve prolapse (MVP) has long been the subject of intense discussions regarding the prognosis and follow-up tactics. In most cases, this condition has a benign prognosis. However, recent autopsy and follow-up studies have shown risks of developing sudden cardiac death (SCD) in some subgroups of patients who have this clinical phenomenon. The proposed literature review uses the population of patients with MVP with the highest probability of developing life-threatening ventricular tachyarrhythmias. Patients with the presence of a complex of changes, including bicuspid MVP, negative T waves in the inferior and lateral leads on a standard 12-lead electrocardiogram (ECG), and a special anatomical phenomenon called mitral annular disjunction (MAD), are at high risk of developing ventricular ectopias and VSS. A reflection of the high risk of SCD in such patients is the increase of ventricular ectopy according to Holter monitoring. The presence of a bicuspid MVP and the MAD phenomenon, which is a separation of the line of attachment of the posterior mitral leaflet from the basal inferior wall segment towards the atrial wall, determines the presence of a special form of MVP, the so-called arrhythmogenic MVP. Hence, in most cases MVP has a benign prognosis. However, patients with the aforementioned ar- rhythmic MVP signs must be given particular attention and annual follow-up including ECG control, Holter monitoring and echocardiographic examination of the heart to reduce the risk of ventricular tachyarrhythmias and SCD development.
Atrial fibrillation (AF) is strongly associated with stroke risk, but an association by itself does not necessarily imply causation. The question remains whether AF is a risk factor for stroke and whether treatment that reduces the severity of AF will also reduce the burden of stroke. On the other hand, it is possible that AF is a risk marker associated with atrial insufficiency, in which structural and electrical atrial remodeling coexist, leading to the clinical manifestations of AF and the risk of stroke simultaneously. Atrial fibrillation and stroke are inextricably linked to the classic Virchow pathophysiology, which explains thromboembolism as blood stasis in a fibrillating left atrium. This concept has been reinforced by the proven efficacy of oral anticoagulants for the prevention of stroke in AF. However, a number of observations showing that the presence of AF is neither necessary nor sufficient for stroke cast doubt on the causal role of AF in vascular brain injury. The growing recognition of the role of atrial cardiomyopathy and the atrial substrate in the development of stroke associated with AF, as well as stroke without AF, has led to a rethinking of the pathogenetic model of cardioembolic stroke. A number of recent studies have shown that AF is a direct cause of stroke. Studies in which cardiac implantable devices have been used to collect data on pre-stroke AF do not appear to show a direct time relationship. The presence of AF is neither necessary nor sufficient for stroke, which casts doubt on the causal role of AF in cerebrovascular injury. Known risk factors for stroke in the presence of AF are also recognized risk factors for ischemic stroke, regardless of the presence of AF. The risk of stroke in patients with AF in the absence of risk factors differs little from that in patients without AF. This work is devoted to an attempt to answer the question whether AF is a marker or a risk factor for ischemic stroke.
CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY 
The pathogenetic mechanisms of arrhythmias, including high-grade ventricular arrhythmias (including non-sustained ventricular tachycardia), in patients with coronary heart disease may be different. Therefore, the characteristics of ventricular arrhythmias must be considered based on the totality of data, taking into account all the available features. The importance of a personalized approach to the management of a patient with coronary heart disease who had extensive myocardial infarction 18.5 years ago, followed by mammary coronary artery bypass grafting, aneurysmectomy and the development of heart failure with a low ejection fraction, in whom ventricular arrhythmias occurred against the background of a stable course of coronary disease , but after emotional stress, is reflected in this work. An extended examination, as well as a detailed study of the nature of ventricular arrhythmias, made it possible to determine the main provoking factor and select an individualized pathogenetic treatment with a good antiarrhythmic result that persists for several years of observation. Conducting mental tests and psychological questioning can be recommended for patients with coronary heart disease and chronic heart failure as an additional examination to assess the contribution of the psycho-emotional factor to arrhythmogenesis after excluding the ischemic and sympathetic nature of ventricular ectopia. It is incorrect to consider that all ventricular arrhythmias in patients with coronary heart disease are ischemic in nature, and in some clinical situations this statement is even erroneous.
An increase in life expectancy contributes to a steady growth of diseases of the cardiovascular system. In recent years, there has been a stable increase in the prevalence of rhythm disturbances in the population. Fibrillation and atrial flutter are among the most common causes of a decrease in the quality of life and an increase in mortality. However, the effectiveness of various methods of treatment is not absolute, and therefore the development and introduction of new antiarrhythmic drugs is particularly relevant. Thus, the use of a class III antiarrhythmic drug (niferidil) is of unconditional interest, and literature data describing the effectiveness of its use for the relief of atypical atrial flutter are extremely few. The article presents a case of successful relief of a persistent form of atypical atrial flutter in a 79-year-old patient using three consecutive intravenous injections of niferidil at a dose of 10 mcg/kg with a 15-minute interval in 19 hours after the start of therapy. The presented clinical case confirms the effectiveness of drug cardioversion with the use of niferidil and makes it possible to consider it as an alternative to electrical cardioversion in patients with atypical atrial flutter.
The review article discusses the safety issue of anticoagulant therapy in elderly patients with atrial fibrillation and high risk of bleeding. An evidence base is presented demonstrating the high safety of rivaroxaban in patients over 80 years of age, with a high risk of bleeding and cardiovascular complications, the presence of comorbid pathology, geriatric syndromes and chronic kidney disease (including in combination with anemia). The problem of low adherence to treatment in elderly patients and the possibility of solving it were separately considered.
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2022-06-14
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