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Rational Pharmacotherapy in Cardiology

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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

Vol 18, No 3 (2022)
View or download the full issue PDF (Russian)

ORIGINAL STUDIES 

236-241 2001
Abstract

Aim: The aim of this meta-analysis and systematic review was to evaluate the possible connection between AF and VTE.

Material and methods. Atrial fibrillation (AF) and atrial flutter (AFL) contribute to intra-atrial blood stasis which leads to thrombus formation with its embolization. There is some evidence that AF can be a risk factor for deep vein thrombosis (DVT) and pulmonary embolism (PE). The following databases were searched: PubMed (MEDLINE), EMBASE, Google Scholar, the Cochrane Central Register of Controlled Trials. The time frame for conducting a systematic literature search ranged from January 1, 1990 to November 1, 2021. The diagnosis of atrial fibrillation had to be confirmed by using ECG. The diagnosis of VTE could be made with Doppler imaging, ventilation/perfusion scan, CT angiography, venography, angiography or autopsy. Only the three studies with 102192 patients meeting the requirement were included in the meta-analysis.

Results. The prevalence of DVT and PE were assessed using incidence rate ratios (IRR) method of the inverse variance random effects model and its 95% confidence interval (CI). The significant association between atrial fibrillation and pulmonary embolism was found (IRR, 4.18 95% Cl 1.958.98). Also there is obvious association between DVT and AF (IRR, 2.97 95% Cl 2.18-4.03).

Conclusion. It can be concluded that the increased risk of developing VTE is associatedwith concomitant AF.

242-250 1303
Abstract

Aim. Research of the association of heart rate variability (HRV) with the level of psychosocial stress (PS) and other indicators of the risk of cardiovascular diseases in a sample of 41-44-year-old men living in Moscow.

Material and methods. A total of 299 men aged 41-44 years were examined. The study included a clinical examination and a survey using a standard questionnaire. The categorization of risk factors (RF) for cardiovascular diseases (CVD) was carried out in accordance with generally accepted criteria The psychosocial stress was assessed using the Reeder scale. Depending on the psychosocial stress level, all surveyed men were divided into 3 groups by terciles: group 1 (3,28-4,0 points) – mild stress, group 2 (2,71-3,14) – moderate stress, group 3 (1,28-2,57) – severe stress. The analysis of HRV was performed on the basis of a short recording of an electrocardiogram using the original software package.

Results. Nonparametric ANOVA showed that the mean [M (95% CI)] values of the HRV time domain (SDNN, rMSSD and the state of regulatory reserves) were lower in the group of men with high PS compared with the group with low PS [25.3 ms (20.9-29.7) versus 40.5 ms (30.7-50.3), p=0.007; 29.5 ms (24.6-34.3) versus 49.5 ms (36.7-62.3), p=0.030; and 46.7 (44.7-48.6) versus 49.7 (48.1-51.4), p=0.019; respectively]. On the contrary, the mean values [M (95% CI)] of the integral indicators of HRV (SI and IVR) were higher in the group of men with high PS [635.8 c.u. (556.2-715.4) versus 488.9 (423.8-554.1), p=0.005; 1172.6 (1045.1-1300.1) versus 904.7 (790.0-1019.4), p=0.003; respectively]. The results of correlation and multiple regression analysis confirmed that these HRV indicators are statistically significantly associated not only with PS, but also with other indicators (age, waist / hip ratio, diastolic blood pressure). However, their predictive value turned out to be low, and the proportion of the explained variance of HRV indices ranged from 2.5 to 13.1%.

Conclusion. The weakening of the autonomous regulation of the heart rate with a decrease in the activity of the parasympathetic link, the activation of the central circuit of regulation with the prevalence of sympathetic influences, a decrease in the functional reserves of the heart rate regulation system are associated with an increase in the level of PS and other indicators of the risk of cardiovascular diseases.

251-260 1890
Abstract

Aim. To perform a comparative analysis of indicators of transthoracic echocardiography (TE), to establish echocardiographic predictors and their predictive role in the occurrence of stable ventricular tachyarrhythmia (VT) paroxysms in patients with nonischemic chronic heart failure (HF) and cardioverter-defibrillator (ICD) implanted for primary prevention of sudden cardiac death.

Material and Methods. A prospective study was carried out, which included 166 patients with nonischemic HF at the age of 54 (49; 59) years with the left ventricle ejection fraction (LV EF) ≤35% and an ICD implanted. The observation time was 24 months. The primary endpoint was the first-ever stable paroxysm of VT (lasting for ≥30 seconds), detected in the «monitor» zone of VT, or paroxysm of VT, which required ICD therapy.  A total of 34 TE indicators were evaluated. Chi-square, Fischer, Manna-Whitney, single-factor logistic regression (LR), and multi-factor LR were used for data processing and analysis and for predictive modelling. Model accuracy was estimated using 4 metrics: ROC curve area (AUC), sensitivity, specificity and diagnostic efficiency.

Results. During the two-year observation, 32 patients (19.3%) had a primary endpoint. The average time of occurrence of a stable VT episode was 21.6±0.6 months (95% confidence interval [CI] 20.5-22.8 months). The value of LV end-systolic dimension was the only parameter independently associated with VT (odds ratio 2.8 per unit increase, 95% CI 1.04-7.5; p=0.042). The complex analysis of echocardiographic indicators made it possible to identify 5 factors with the greatest predictive potential, which are linearly and nonlinearly related to occurrence of VT. These included the LV end-diastolic and end-systolic volumes, LV mass, index of relative LV wall thickness, upper-lower size of the right atrium. The metrics of the best predictive model were: AUC – 0.71 0.069 with 95% CI 0.574-0.843; specificity 50%, sensitivity 90.9%; diagnostic efficiency 57.1%.

Conclusion. The study made it possible to evaluate the possibilities of the results of TE in predicting the probability of VT occurrence in patients with nonischemic HF and reduced LV EF. Predictive indicators have been identified that can be used to stratify the arrhythmic risk in the exposed cohort of patients.

261-267 1380
Abstract

Aim. The aim of the study was to evaluate the incidence and predictors of acute kidney injury (AKI) associated with transcatheter aortic valve implantation (TAVI).

Material and methods. 50 patients (39 women, 11 men) aged 76 (71; 80) years who underwent TAVI were examined. One day after TAVI, blood creatinine level was determined by the Jaffe method and troponin I by a highly sensitive method (hs-cTnI). Acute kidney injury (AKI) was diagnosed according to the KDIGO criteria (2012). The following hospital complications were evaluated: cases of cardiac death, intraoperative myocardial infarction (MI), stroke and transient ischemic attack, permanent pacemaker implantation, recurrent paroxysms of atrial fibrillation.

Results. History of MI had 22% of patients, percutaneous coronary intervention – 38%, hypertension – 98%, chronic kidney disease – 48%, diabetes mellitus – 24%, class II NYHA of chronic heart failure (CHF) – 52%, NYHA class III – 46%, NYHA class IV – 2%. The risk of operational mortality according to EuroSCORE II was 6.3±5.4%. AKI after TAVI was registered in 6 (12%) patients (1 grade AKI – 8%, 2 grade – 2%, 3 grade – 2%). Parameters associated with AKI after TAVI were higher CHF NYHA class (p=0,020), high hs-cTnI level (p=0,013), intraoperative MI (p=0.035). The predictor of AKI after TAVI was high hs-cTnI level (odds ratio 4.0, 95% confidence interval 1.0-16.1). Among patients with AKI after TAVI in compare with patients without AKI, the cumulative frequency of cardiac death, MI, strokes and transient ischemic attacks, implantation of a permanent pacemaker, the proportion of people with paroxysmal atrial fibrillation during the hospital stay was 5,8 times higher (66.7% vs 11.4% respectively, p=0.001).

Conclusion. AKI after TAVI was present in 12% of patients. The predictor for AKI development was an increase in hs-cTnI level after TAVI implantation. The hospital prognosis after TAVI is worse in patients with postoperative AKI. 

268-273 1278
Abstract

Aim. To evaluate the impact of a mobile application usage on the self-care skills, quality of life, adherence to treatment, as well as the psychological characteristics of comorbid patients with stable coronary heart disease.

Material and methods. The study will include patients over 18 years of age with an established diagnosis of ischemic heart disease, exertional angina pectoris I-IV CCS functional class, who have the technical ability to use the mobile application "B2Doc: Angina" on their smartphone. This mobile application contains main components of recommendations for the management of coronary heart disease and monitoring of patient’s well-being. The program is based on the previously developed and validated questionnaire of the self-care ability of patients with coronary artery disease. The mobile application includes advice of the day, tracking the dynamics of angina pectoris symptoms, blood pressure and pulse, a medication diary as well as educational material about coronary heart disease. The study will assess quality of life: general (SF-36) and angina-related (Seattle Angina Questionnaire), self-care skills using the Self-Care of Coronary Heart Disease Inventory questionnaire. The primary endpoints will be cardiovascular events (cardiovascular death, acute myocardial infarction, acute cerebrovascular accident, hospitalization with unstable angina or decompensated chronic heart failure) and death from all causes. Endpoints will be evaluated in 1, 3, 6 and 12 months after discharge.

Expected results. We expect that the use of the mobile application "B2Doc: Angina" by patients will improve their self-care skills and quality of life, as well as increase awareness of the disease.

Conclusions. The use of the newly developed mobile application "B2Doc: Angina" is a potential tool for the prevention and treatment of coronary heart disease. It represents a promising solution for the rapid implementation and expansion of telemedicine practice. 

274-281 1971
Abstract

Aim. To study the effect of enhanced external counterpulsation (EECP) on the functional status, quality of life, structural and functional state of the vascular bed, and markers of glycemic control in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM).

Material and methods. A pilot prospective randomized study included 30 patients with CAD and DM. Using a random number generator, patients were randomized into 2 groups: EECP (n=15) and a comparison group (n=15). All patients (n=30) received optimal medical therapy (OMT) during 3 months of follow-up. Patients in the EECP group underwent a course of EECP (35 hours, cuff pressure: 220-280 mmHg) during the first 7 weeks of the study. At baseline and after 3 months of follow-up, patients in both groups underwent an assessment of clinical status, quality of life (based on the SF-36 questionnaire), as well as a 6-minute walk test to assess exercise tolerance. The dynamics of fasting glucose, postprandial glucose, insulin resistance index (HOMA-IR) and glycated hemoglobin were assessed. Photoplethysmography and applanation tonometry were performed to assess the state of the vascular bed.

Results. In the EECP group, after 3 months, there was a decrease in the frequency of angina attacks and an improvement in the functional class of angina according to the Canadian Cardiovascular Society (CCS) classification. A significant improvement in exercise tolerance was revealed [an increase in the 6-minute walking distance by 51 (35; 65) m, p<0.05], as well as an improvement in the physical and mental components of health according to the SF-36 questionnaire. A positive dynamics was shown in relation to the indicators of the state of both large vessels and the microvasculature (p>0.05), with the exception of the reflection index and the stiffness index (p<0.05). There was also a significant decrease in the HOMA-IR [-9.9% (-26.5; -4.0) vs 7.7% (-7.9; 13.8), p=0.004], as well as in the levels of fasting glucose [-10.5% (-15.8; -4.0) vs -2.7 (-8.3; 5.9), p=0.012] in the EECP group, compared with the OMT group.

Conclusion. EECP course therapy in addition to OMT has a positive effect on the functional status and quality of life of patients with CAD and DM. After 3 months of observation, there was noted a positive dynamics of the vascular state, as well as markers of glycemic control, and these changes were more pronounced in the EECP group. The results obtained may indicate the effectiveness of EECP as an add-on treatment for this group of patients.

NOTES FROM PRACTICE 

282-288 1378
Abstract

Aim. To study the dynamics of the lipid profile of hypertensive patients with dyslipidemia who underwent COVID-19.

Material and methods. Hypertensive patients with dyslipidemia who underwent COVID-19 [n=126; 58 men and 68 women; median age 60 (56.0; 65.5) years] examined. Patients were included into two groups: group 1 (n=64) received a single pill combination of lisinopril + amlodipine + rosuvastatin; 2 groups (n=62) continued the previous drug treatment. Clinical, demographic, office blood pressure (BP), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol, triglycerides, C-reactive protein (CRP) levels were assessed in all patients in 3 visits within 24 weeks.

Results. The groups did not differ in prior antihypertensive therapy (except for more frequent use of angiotensin II receptor blockers in group 2, p<0.05), lipid profile and blood pressure parameters at study entry. A decrease in systolic (by 9.5%) and diastolic blood pressure (by 12.1%) after 24 weeks was found in group 1 compared with 4.29% and 5.56%, respectively, in group 2 (p<0.05). A decrease in the level of total cholesterol by 14.5% and LDL-c by 31.4% after 24 weeks was found in group 1 compared with 11.2% and 9.7%, respectively, in group 2 (p<0.05). The level of CRP during the observation period decreased by 53.7% in group 1 versus 43.4% in patients of group 2 (p<0.05).

Conclusion. The single pill combination of lisinopril/amlodipine/rosuvastatin in hypertensive patients with dyslipidemia who underwent COVID-19 led to an improvement in lipid profile and blood pressure control.

289-296 1352
Abstract

Aim. To study the association of nucleotide polymorphisms in platelet receptor and cytochrome P450 genes with the development of resistance to antiplatelet drugs in CHD patients.

Material and Methods. The study included 243 patients diagnosed with CHD after coronary artery bypass surgery (CABG), including 140 patients in the acetylsalicylic acid (ASA) treatment group and 103 patients in the dual antiplatelet therapy (DAT) group. All patients were tested for platelet aggregation using an optical aggregometer with inducers: 5 mM ADP and 1 mM arachidonic acid (AA). DNA samples were analyzed by allele-specific PCR for the presence of polymorphisms rs2046934, rs1126643, rs5918, rs6065, rs4244285 in the platelet receptor and cytochrome P450 genes.

Results. No statistically significant differences were found during comparison of the prevalence of the studied polymorphisms in the platelet receptor and cytochrome P450 genes between the groups of aspirin-sensitive and aspirin-resistant patients, as well as between the groups of clopidogrelsensitive and clopidogrel-resistant patients. No association between carriage of the minor and major alleles of the polymorphisms studied and the development of antiplatelet drug resistance was found. In the group of patients on ASA therapy, carriers of the C allele of the T1565C (rs5918) ITGB3 polymorphism had a higher rate of AA-induced platelet aggregation compared to carriers of the T allele (18,49±25,92 vs 10,43±17,34, р=0,004).

Conclusion. Polymorphisms of P2RY12 (rs2046934), ITGA2 (rs1126643), ITGB3 (rs5918), GP1BA (rs6065), CYP2C19*2 (rs4244285) genes are not associated with antiplatelet drug resistance in both patients on ASC therapy and on DAT. The presence of minor alleles of the rs2046934, rs1126643, rs6065, rs4244285 polymorphisms are not associated with increased platelet aggregation activity before CABG.However, in the group of patients on ASA therapy C-allele carriers of the rs5918 polymorphism of the ITGB3 gene had a higher rate of AA-induced platelet aggregation compared to T-allele carriers.

297-305 1359
Abstract

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.

Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.

Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p<0,05) and Tyr (r=-0,583, p<0,05), as well as the level of Phe with total cholesterol (r=-0,461, p<0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p<0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p<0,05), and the level of Tyr with LDL (r=0,349, p<0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).

Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY 

306-310 1299
Abstract

Aim. To assess adjusted pharmacotherapy for prescribing drugs of the main classes, according to clinical guidelines, and achieving target levels of lowdensity lipoprotein cholesterol (LDL-C) in patients with stable coronary heart disease (CHD).

Material and methods. Of the 73 patients included in the ALIGN study, 64 patients (53 males and 11 females; mean age 68,2±9,4 years) with stable coronary artery disease attended a second visit (3 months after the initial treatment adjustment). Prescribed drug therapy, its compliance with clinical guidelines, achievement of lipid profile and blood pressure (BP) targets were studied in all patients.

Results. An increase in the frequency of taking beta-blockers (p=0.002), lipid-lowering drugs (p=0.008) by patients was found during the second visit. The proportion of patients taking all 4 groups of drugs according to clinical guidelines (statins, antiplatelet agents, beta-blockers, angiotensinconverting enzyme inhibitors / angiotensin II receptor blockers) increased from 44% to 65.5% (p<0.001) after correction of therapy, as well as an increase in the proportion of patients taking 1 antianginal drug in the presence of exertional angina from 75% to 89% (p<0.001) was found. About 90% of hypertensive patients achieved the target level of systolic blood pressure (p<0.001). Achievement of the target level of cholesterol low density lipoprotein (<1.8 mmol/l) during the second visit was found in half of the patients (p=0.004).

Conclusion. Despite the initial correction of drug therapy by the staff of the cardiology department, the prescribed treatment for patients with stable coronary artery disease did not in all cases comply with clinical guidelines due to insufficient adherence of doctors and insufficient adherence of patients to prescribed medical recommendations.

Working group of the register PROFILE: Voronina V. P., Dmitrieva N. A., Komkova N. A., Zagrebelny A.V., Kutishenko N.P., Lerman O.V., Lukina Yu. V., Tolpygina S.N., Martsevich S.Yu.

POINT OF VIEW 

311-319 786
Abstract

Modern approaches to interpreting the results of randomized trials, which can reduce the distortion of information when they are presented to a wide range of doctors, are discussed in the article. Data on the role of taking into account multiple comparisons in the planning and analysis of large randomized clinical trials are given. The validity and approaches to using a hierarchical approach to assessing the statistical significance of indicators (“endpoints”) in cases where, in accordance with a pre-adopted study protocol, several indicators are supposed to be evaluated are considered in detail. Approaches to interpreting the p value as well as 95% confidence intervals are considered. Particular attention is paid to the interpretation of the components of the main combined indicator, since when interpreting just such data, the presentation of the results of the study and the manipulation of doctors' opinions may be distorted. This is especially true for data on mortality and mortality from complications of cardiovascular diseases. Modern approaches to the analysis of research results using methods other than the usual Kaplan-Meier analysis, in particular, the method based on the calculation of the "win ratio" are discussed. Data obtained in modern clinical studies are given as examples.

320-331 779
Abstract

The issue of antithrombotic therapy in patients with infective endocarditis has been studied for over 75 years. During that time studying of pathogenesis of the disease and its embolic complications, lead to the introduction of the concept of “immunothrombosis”. That mechanism allows infective agents (mostly bacteria) to be cloaked from the immune system and to multiply freely, leading to growth of vegetation, thus resulting in higher chance of fragmentation. Small-scale experimental and clinical studies on the correction of hemostatic disorders in infective endocarditis, that were performed in 20th century, didn’t show any significant results, that could affect clinical practice. However, reinterpretation of available data on coagulative system will allow to have elements of hemostasis as an application point in treating infective endocarditis. The article will discuss latest insights on the role of hemostasis system in pathophysisology of infective endocarditis, its effects on the development of the embolic complications, perspectives for diagnostics and treatment.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY 

332-341 766
Abstract

The article is devoted to modern ideas about the role of drug interactions as a factor affecting the efficacy and safety of the use of direct oral anticoagulants (DOACs) in clinical practice. Data on drug interactions of apixaban, rivaroxaban and dabigatran with the drugs most frequently used in patients with cardiovascular diseases are given. Drug interactions for DOACs, depending on concomitant use of drugs that are inhibitors or inducers of the CYP3A4 enzyme or P-glycoprotein enzymes, are determined by most of the drug interactions of DOACs are considered. The results of studies in which drug interactions of DOACs were assessed by changes in indicators such as the area under the concentration-time curve and the maximum or minimum concentration of drugs in the blood are discussed. The data presented in the article may be useful for accounting for drug interactions in the treatment of patients with DOACs in clinical practice, despite the current lack of reasonable dose adjustment rules depending on the majority of such interactions. The data presented in the article suggest that apixaban has the fewest number of clinically significant interactions among the DOACs available in Russia.

342-349 736
Abstract

Pulmonary hypertension is a severe and often rapidly progressive disease with a fatal outcome. Approved specific therapy with five classes of drugs – prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators and prostacyclin receptor agonists has significantly improved the prognosis of patients. An accessible and reproducible criterion of exercise tolerance – a distance walked in six-minute walk test (6MXD) – occupies one of the central places among the performance indicators (clinical, echocardiographic and hemodynamic) of specific pulmonary vasodilators. Reflecting the clinical severity of pulmonary hypertension and, according to some data, its long-term prognosis, the dynamics of 6MXD is an integral component of the combined primary endpoints of randomized controlled trials. In the CHEST-2019 recommendations, the dynamics of the 6MXD was used to standardize the randomized controlled trials. The 6MXD is indispensable for dynamic observation and decisionmaking on further treatment tactics 

350-358 654
Abstract

Heart rhythm disorders are one of the most urgent problems in cardiology. The first reports on the possibility of using drugs in the treatment of cardiac arrhythmias began to appear in the scientific literature from the middle of the 18th century. This pharmacotherapeutic direction has been developed since the second half of the 20th century, when new antiarrhythmic drugs began to be used in clinical practice. The introduction of new drugs and modern methods of treating arrhythmias into clinical practice has significantly improved the prognosis and quality of life of patients. Combination antiarrhythmic therapy, including antiarrhythmic drugs and radiofrequency ablation, seems to be the most promising and successful tactic for treating patients in the future. A historical review of the literature on the clinical use of antiarrhythmic drugs both in past years and at present is presented in the article.

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