Rational Pharmacotherapy in Cardiology

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Vol 17, No 3 (2021)
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362-368 458

Aim. To analyze prevalence of cardiovascular risk factors in the Kemerovo region based on the results of epidemiological studies (2013 and 2016).

Material and methods. The study was based on two large epidemiological studies of the Kemerovo region: on 2013, «The epidemiology of cardiovascular diseases and their risk factors in the Russian Federation» and on 2016, «The prospective study of urban and rural epidemiology: study of the influence of social factors on chronic non-infectious diseases in low, middle and high income countries». In the study we analyzed cardiovascular risk factors using identical questionnaires, functional, anthropometric, biochemical means and measured on identical scales. As a result, we analyzed the prevalence of smoking, diabetes mellitus, overweight and obesity, abdominal obesity, hypercholesterolemia and hypertriglyceridemia, high levels of low-density lipoprotein (LDL).

Results. Univariate analysis indicates that in the sample of 2016, compared to the sample of 2013, the prevalence of smoking is statistically significantly lower, as well as the proportion of participants with high cholesterol levels, but not taking lipid-lowering drugs. In contrast, the prevalence of diabetes, hypercholesterolemia and hypertriglyceridemia is higher. In women, the frequency of abdominal obesity on 2016 is lower than on 2013: at 35-44 age group odds ratio (OR) =0.67 with 95% confidence interval (CI) 0.44-1.03, at 45-54 age group OR =0.47 with 95% CI 0.31-0.72, 55-65 age group OR =0.49 with 95% CI 0.30-0.79. A high incidence of diabetes, hypercholesterolemia and hypertriglyceridemia is characteristic mainly of older women (55-65 age group): accordingly, OR =1.96 with 95% CI 1.19-3.22, OR =1.42 with 95% CI 1,02-1.97, OR =1.51 at 95% CI 1.08-2.12. In the 45-54 age group of men, they smoked statistically significantly less often on 2016 compared to 2013, OR =0.59 with 95% CI 0.36-0.96. The prevalence of overweight and obesity in both samples is the same: for women, the OR for overweight in different age groups is within 0.74-0.87, for men - within 0.95-1.78; for obesity OR in women is from 0.70 to 0.79, in men - from 1.03 to 1.34.

Conclusion. A significant advantage of the study is the analysis of changes in prevalence in age and gender groups, which showed significant differences in the dynamics of men and women in different age categories for a number of risk factors. Analysis of the dynamics of the prevalence of cardiovascular risk factors makes it possible to assess the effectiveness of state and regional policies in the field of health protection and, first of all, "risk groups” that require closer attention, development and implementation of targeted health-saving technologies.

369-375 448

Aim. To study the prevalence of musculoskeletal disorders in patients with stable coronary artery disease (CAD).

Material and methods. Patients with stable CAD (n=387) were included in the study. The subjects were admitted to the hospital for planned myocardial revascularization (ages of 50-82). The median age was 65 [59;69] years. Most of the sample consisted of males - 283 (73.1%). 323 (83.5%) patients had arterial hypertension (AH), 57.1% - history of myocardial infarction, and a quarter of the patients had type 2 diabetes mellitus (DM). The study of musculoskeletal system included the identification of sarcopenia in accordance with The European Working Group on Sarcopenia in Older People (EWGSOP, 2019); verification of osteopenia/osteoporosis according to the WHO criteria (2008); diagnosing osteosarcopenia in case of sarcopenia and osteopenia/osteoporosis coexistence.

Results. At the initial screening of sarcopenia in accordance with EWGSOP, clinical signs (according to the Strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) questionnaire) were detected in 41.3% of cases, but further examination (dynamometry, quantitative assessment of skeletal muscle) confirmed this diagnosis only in 19.9% of patients with CAD. Among the examined patients with CAD a low T-score according to DEXA was found in 53 (13.7%) of cases, and osteopenia was diagnosed 10 times more often than osteoporosis (90.6% vs. 9.4%). Furthermore, due to combination of low bone density (osteopenia/osteoporosis) and reduced muscle mass and strength (sarcopenia), osteosarcopenia was verified in one patient. Thus, the study revealed the prevalence of particular types of musculoskeletal disorders in 105 (27.1%) patients with stable CAD. The most common type of musculoskeletal disorder was sarcopenia - 52 cases (13.4%); osteopenia/osteoporosis was detected in 28 patients (7.2%), osteosarcopenia in 25 (6.5%). The most pronounced clinical manifestation of sarcopenia and osteopenia/osteoporosis, reflected by a higher score on the SARC-F questionnaire, low handgrip strength, small area of muscle tissue, low musculoskeletal index, as well as low values of bone mineral density, were observed in patients with osteosarcopenia. Patients with osteopenia/osteoporosis did not differ significantly from patients without musculoskeletal conditions in most parameters, with the exception of the T-score, the average SARC-F score, and muscle strength in men. The conducted correlation analysis revealed not only the relationship between the parameters of musculoskeletal function, but also their association with age, duration of AH, CAD, and type 2 DM.

Conclusion. Several types of musculoskeletal disorders were found in a third of patients with CAD. Sarcopenia was revealed to be the most frequent type of musculoskeletal disorder.

376-385 897

Aim. To assess the duration of the anticoagulant treatment of venous thromboembolism (VTE) in various categories of patients in real clinical practice through survey of practitioners, as well as correspondence of the duration with current clinical guidelines.

Material and methods. Data obtained from electronic survey of practicing surgeons as part of a commercial brand assessment (Brand Adoption Monitor) was studied. Survey was carried out by the "Validata” analytical agency at the request and with the financial support of Bayer. Inpatient and outpatient vascular surgeons, as well as general outpatient surgeons were invited to complete the electronic questionnaire. The number of interviewed specialists was 100: 50 inpatient vascular surgeons and 50 outpatient specialists, among whom the share of vascular surgeons (phlebologists, angi-ologists) was about 20%. The study was completed in 20 cities of Russia with a population of at least 200,000 people from all federal districts except the North Caucasus and the Republic of Crimea. The selection criteria for participants were: work experience in the specialty ≥3 years, work experience at the current organization >6 months, ≥5 patients with VTE during in the last month.

Results. In total, 104 doctors were surveyed during the period from December 11, 2019 to January 20, 2020, of which 50 were inpatient vascular surgeons and 54 were from outpatient setting. According to the survey of vascular surgeons in hospitals, 75% (6 [5;10]) of patients were hospitalized with a primary episode of VTE and 25% (2 [1;4]) with a recurrent thrombotic event. In an outpatient surgeon, 27.5% (3 [2;5]) of patients were treated in an outpatient setting without hospitalization, 34.7% (3 [2;5]) came to an appointment immediately after discharge from the hospital and 38.8% (2 [1;4]) were a repeat visit regarding a previous VTE. Most often, surgeons observed episodes of clinically unprovoked VTE in 27.3% of cases, thrombotic events provoked by major transient risk factors were 12.2%, event provoked by small transient risk factors were 13.3% and events provoked by small persistent risk factors were 12.6%, while cancer-associated thrombosis represented 13.5%. Most surgeons chose to prescribe anticoagulant therapy beyond 3 months. About half of the specialists prescribed therapy for a year or longer for cancer-associated thrombosis and recurrent VTE. When treating the first episode of clinically unprovoked VTE, about half of the respondents chose anticoagulation for a period of 3 to 6 months. About 60% of specialists prescribed anticoagulant therapy for a period of 3 to 6 months to patients with minor transient or persistent risk factors and patients with VTE provoked by major transient risk factor (trauma or surgery).

Conclusion. Correspondence of the duration of anticoagulant therapy in real clinical practice with the international clinical guidelines varies within 450% range and, on average, does not exceed 30%. This discrepancy was both in situations when the duration of therapy was lower than recommended, but also in situations when treatment extension would not have been recommended.

386-393 379

Aim. Assess the two-year survival rate of patients who have undergone acute cerebral circulation disorder, depending on their commitment to visiting the district polyclinic before and after discharge from the hospital.

Material and methods. The outpatient part of the REGION-M register included 684 patients attached to the Moscow City Polyclinic №64, discharged from the Moscow City Clinical Hospital n.a. F.I. Inozemtsev of from 01.01.2012 to 04.30.2017 with a confirmed diagnosis of acute cerebral circulation disorder (cerebral stroke / transient ischemic attack).

Results. Of the entire cohort, 83.2% of patients and 84.2% after hospital discharge attended the clinic during the year before the development of reference acute cerebral circulation disorder. Patients who attended the clinic before and after the reference stroke were older, more likely to have diabetes, comorbid disease and disability. For 22 months of follow-up, mortality was 28.8% (197 out of 684 people). Among those who applied and did not apply to the clinic before the reference acute cerebral circulation disorder, the difference in mortality tended to be reliable (27.4% versus 35.7%, p <0.1), while mortality was almost twice as low among patients who applied to the clinic at least 1 time after discharge (25.7%) than among patients who did not apply after discharge - 45.4%, p<0.0001. When adjusting for sex and age (the relative risk of death for them was 1.009, 95% confidence interval 1.005-1.01 2, p<0.0001 ), the statistical validity of reducing the risk of death was maintained when patients were committed to visiting the clinic after discharge - the relative risk of death 0.366 (95% confidence interval 0.269-0.500, p<0.0001 ).

Conclusion. Lower mortality among those who visited the district polyclinic after undergoing stroke confirms the important role of medical observation in the posthospital period. At the same time, there is a reserve in improving the long-term prognosis of the lives of patients who have suffered a cerebral stroke or transient ischemic attack, due to greater coverage of patients with medical supervision in the clinic.

394-400 348

Aim. Analysis of drug-induced bradiarrhythmia (DIB) causes and predisposing factors, followed by the development of recommendations for practitioners on its prevention.

Material and methods. The register included consistently all cases of hospitalization at the Regional Vascular Center (Ryazan) due to DIB in 2017 (n=114), 2018 (n=167), and retrospectively in 2014 (n=44). In total, 325 cases were reported: men - 26.1%, age 76.0 [68.0; 82.0] years; patients >65 years - 83.7%, and patients >75 years - 57.9%. The dose of medications with bradycardic action (BCA) taken the day before was known in 227 cases (69.8%), which allowed us to analyze the correctness of the intake regime in these cases.

Results. The excess of a single and / or daily medication dose (absolute overdose, AOD) occurred only in 10.6% of cases and was associated with the patient's attempt to cope with the deterioration of the disease or an acute clinical situation on their own. In other cases, there was no formal violation of the Instructions, but there was an inhibition of the heart's conducting system activity, characteristic of an overdose of medication (the so-called "relative” overdose, ROD). It was due to the summation/potentiation of BCA of several medications or changes in the medication pharmacokinetics. There were no differences in the clinical and demographic characteristics of patients and the provision of medical care in the groups with AOD and ROD (p>0.05). The exception was a high frequency of bradycardia <40 beats / min in AOD group (75.0% vs 49.8%, p=0.019) and, as a result, - management in the conditions of the Intensive Care Unit (66.7% vs 39.9%, p=0.012). Frequency of pre-admission receiving medications in AOD and ROD groups also did not differ (p>0.05): beta-blockers - an average of 64.3%, antiarrhythmic drugs with BCA- 41.0%, cardiac glycosides 25.1% (frequency each of these medicationsin DIB cases over the 5-year period has not changed), an agonist of the 11-imidazoline receptors - moxonidine (12.3%, its frequency has increased 8.9 times in 5 years, p=0.004), non-dihydropyridine calcium antagonists - 7.9% (decrease frequency over 5 years 4.0 times, p=0.002), other - 16.7%. In 56.8% of cases, medications with BCA were used in combination. At admission, a decrease in glomerular filtration rate (GFR) <45 ml/min/1.73 m2 was registered in 56.8% of cases, <30 ml/min/1.73 m2 - in 31.8%, <15 ml/min/1.73 m2 -in 10.9% (differences between groups with p>0.05). Hospital lethality in the AOD group is 4.2%, in the ROD group- 5.4% (p>0.05).

Conclusion. The main reasons of DIB are excess of the recommended dose, unrecorded summation/potentiation of BCA of several medications, and / or changes in the medication pharmacokinetics. Predisposing factors are self-medication of patients with worsening cardiovascular disease or acute clinical situations (e.g., hypertensive crisis), taking multiple medications with BCA, accession of heart disease, manifested by bradyarrhythmia, decrease in GFR, elderly and senile age.

401-407 336

Aim. To study the features of the use of thrombolytic therapy (TLT) in normotensive patients with pulmonary embolism (PE) in real clinical practice in Russian hospitals.

Material and Methods. From 04/1 5/2018 to 04/15/2019 patients hospitalized with a diagnosis of PE consistently were included in the Russian multicenter observational prospective register "SIRENA” (RusSIan REgistry of pulmoNAry embolism).

Results. For 12 months in the registry was included 609 patients with a lifetime confirmed diagnosis of PE. TLT was performed in 152 patients with PE (25.0%), of which only 51 (33.8%) were indicated as "high risk" (shock or hypotension). In 101 not high risk patients, the indications for TLT were: severe shortness of breath/respiratory failure - 19 (18.8%), massive venous thrombosis - 7 (6.9%), signs of massive/submassive PE - 10 (9.9%), intermediate-high risk - 14 (13.9%), suspicion of acute coronary syndrome with ST segment elevation - 3 (2.9%), high pulmonary hypertension -2 (2.0%). The other 46 (45.5%) non-high-risk patients had no clear indication of the reasons for TLT in their medical history. To study the features of management of patients with not high-risk PE who received TLT (group 1), a selection of pairs of patients from the "SIRENA” registry, comparable in gender and age, in a ratio of 1:1 of patients with not high-risk PE who did not perform TLT (group 2). Hospital mortality was 4 (4%) patients in the TLT group and 6 (5.9%) patients in group 2 (р=0,748). Logistic regression analysis showed that floating blood clot in the veins of the lower extremities, syncopes in the debut of PE, respiratory rate over 22 per minute were independent clinical factors that significantly influence the doctor's decision to perform thrombolysis, and probability of completion TLT decreased in the presence of a history of bleeding, chronic kidney disease, surgery in the previous 12 months, increase in the size of the right atrium on EchoCG (statistical significance of the model x2=51.574; p<0.001). The development of bleeding during hospitalization was recorded only in 10 (9.9%) patients of group 1, including severe (3 stage on the BARC scale) in 2 patients. Patients without TLT more often developed an acute heart failure (25.9% vs. 8.5%, p=0.043).

Conclusion. In real clinical practice, there is a high frequency of TLT in patients with not high-risk PE. Floating blood clot in the veins of the lower extremities, syncope in the debut of PE, respiratory rate over 22 per minute were independent clinical factors that significantly influence the doctor's decision to perform thrombolysis.


408-413 336

Aim. To study the level of serum biomarkers of endothelial dysfunction and myocardial stress in patients with various types of hypertrophic cardiomyopathy (HCM).

Material and Methods. 48 patients with hypertrophic cardiomyopathy (27 men and 21 women) were examined, the mean age was 54±13 years. The patients were divided into two groups according to the course options: group 1 - symptomatic stable course (n=14); group 2 - progressive course of symptomatic HCM (n=34). In accordance with the assigned tasks, all patients underwent determination of biological markers of neurohumoral systems in blood serum using immunofluorescence assay analysis: N-terminal fragment of brain natriuretic peptide (NT-proBNP), von Willebrand factor (vWF), endothelin-1, E-selectin with subsequent evaluation and correlation of results with clinical and instrumental characteristics of patients. When performing echocardiography following parameters were assessed: dimensions of the heart chambers, the thickness of the interventricular septum, the thickness of the posterior wall of the left ventricle (LV), LV mass, LV mass index, the ratio between LV filling in diastole (peak E) and atrial systole (peak A)-(E/A), relative myocardial thickness index, left atrial volume index.

Results. Both groups showed increased levels of NT-proBNP and endothelin-1. E-selectin and vonWillebrand factor remained within the normal range. There was no statistically significant intergroup difference. There was a correlation between the level of the index of the relative myocardial thickness and the level of NT-proBNP (r=0.30; p=0.04). A correlation was found between the level of the vWF marker and the left atrial volume index (r=0.32; p=0.04). When assessing the association of indicators of intracardiac hemodynamics with other markers (E-selectin and endothelin-1, no statistically significant relationships were found.

Conclusion. In the course of the research, it was found that the high activity of endothelin-1 and NT-proBNP reflects endothelial dysfunction and myocardial stress in patients with HCM, especially in patients with a progressive variant of HCM. However, we did not find any changes in the levels of E-selectin and von Willebrand factor, as well as their intergroup differences. These results require additional studies to assess endothelial dysfunction in patients with HCM.

414-422 662

Aim. Determination of the possibility of reliable quantitative assessment of the coronary calcium index based on ultra-low-dose computed tomography (ultra-LDCT) which used in Moscow Lung Cancer Screening project.

Material and methods. The study included the results of 254 ultra-LDCT studies conducted as part of the Moscow lung cancer screening project. For compare the parameters of coronary calcium on different images used 16 pairs of ultra-LDCT images with a slice thickness of 1 mm and CT images with a slice thickness of 3 mm, performed without ECG synchronization, performed with an interval of less than 10 days, as well as 18 pairs of ultra-LDCT with a slice thickness of 1 mm and CT with ECG synchronization with a slice thickness of 3 mm, performed on the same day after execution. Analysis of DICOM 3.0 standard images was performed. Quantitative indicators of coronary calcium in patients from lung cancer screening were analyzed, a comparative analysis of the calcium index for Agatstone, Volume, Mass, and using the CAC-DRS scale (assessment of the degree of calcification by scores from 0 to 3 and the number of affected arteries from 0 to 4 points) was performed.

Results. Evaluation ultra-LDCT with a slice thickness in 1 mm and with a CT scan with slice thickness in 3 mm with and without ECG-synchronization for the presence of coronary calcium, and subsequent rating according to the index Agatston, Volume, Mass, as the total coronary calcium and for each coronary artery (right, left, left descending, left circumflex) received the complete data correlation (Pearson's - 1), with full correlation (Spearman's >0.9), with good rank correlations (>0,9). Compare qualitative (CAC-DRS V) and quantitative (CAC-DRS A) estimates on ultra-LDCT with CT with ECG synchronization in the same patients show a complete correlation of data was obtained (Pearson's formula - 1), with a complete correlation (Spearman's formula - 1).

Conclusion. Coronary calcium which detected in lung cancer screening subjects should be included in the overall decision-making process for further routing of patients (cardiologist, interventional surgeon, pulmonologist, therapist). Ultra-LDCT is a method that has high diagnostic accuracy in detecting and evaluating the prevalence of coronary calcium in comparison with standard CT with and without ECG synchronization, as demonstrated in our study. Evaluation of coronary calcium according to ultra-LDCT without ECG synchronization used in screening, preferably with a 1 mm slice thickness. Despite the fact that the gold standard is CT with ECG synchronization with a 3 mm slice thickness, the diagnostic significance of ultra-LDCT which used in lung cancer screening is high in relation to detecting coronary artery calcification.

423-428 342

Aim. To evaluate the relationship between albumin to creatinine ratio (ACR) in a single and 24-hours urine spots and chronic kidney disease (CKD) progression pace in patients with atrial fibrillation, CKD and diabetes mellitus.

Material and methods. 60 patients with atrial fibrillation (AF) and CKD were enrolled, study duration was 15 months. The patients were divided into two groups depending on the presence of DM. Total number of ACR tests was 170, dynamics of CKD progression was estimated with CKD-EPI formula for first visit and 15th month’s follow-up.

Results. The median score of CHA2DS2VASс scale was 4 [3;5]. The risk of hemorrhagic complications in both groups was low (median score 1 [1;1]. There is a strong statistically significant correlation between ACR in a single and 24-hours urine spots (p<0.001). No significant changes in kidney function within 15 months were found (GFR 53 [46;59] ml/min/1.73 m2 vs 50.5 [45.63] ml/min/1.73 m2 for patients with diabetes mellitus [DM] [p=0.94] and GFR 52.5 [46.58] ml/min/1.73 m2 vs 50 [44.58] ml/min/1.73 m2 for patients without DM [p=0.711]). When comparing the renal function of patients with and without DM after 15 months statistically significant differences were also not found (p = 0.510).

Conclusion. In respect that assessment of single sample ACR is much more practical and reliable, this method might replace traditional 24-hours urine assessment in future. However, due to the small sample size and the presence of wide discrepancies in individual cases, which can be associated with preanalytical errors in urine collection, large randomized clinical trials are needed to confirm the obtained data.

429-437 296

Aim. To study the impact of heart rate (HR) reduction with beta-blockers (BB) on left atrial (LA) function in hypertensive patients with paroxysmal or persistent mild symptomatic atrial fibrillation.

Material and methods. In this open prospective trial we randomly assigned patients with hypertension, sinus rhythm, elevated heart rate (≥70 bpm), and recurrent atrial fibrillation (EHRA 2A or less) to receive BB with a target HR of less or greater than 70 bpm for at least 4 months. All the patients underwent an echocardiogram [left atrial (LA) function was assessed as emptying fraction]and applanation tonometry at baseline and after 4 months. Primary endpoint was median LA emptying fraction (LAEF) measurement at the end of the study.

Results. 47 patients were randomized to group with a target HR of ≤70 bpm and 44 patients to >70 bmp. Among them 44 and 41 patients completed the study. Median follow up was 4.4 months. At the end of the study (4.5 months) median HR was 62 [60; 67] bmp in ≤70 group and 73 [72; 76] bpm in >70 group. Both groups received similar antihypertensive therapy and there were no intergroup differences in systolic and diastolic blood pressure. At the end of the study, patients in ≤70 group had significantly lower LAEF compared with >70 group (37% vs 42%; p=0.01). E’avg was lower and augmentation index was higher in ≤70 group as compared to >70. In regression analysis, after E’avg and augmentation index were included in the model, the association between LAEF and randomization group lost its significance.

Conclusion. Beta blockers treatment with strict HR reduction (≤70 bpm) significantly reduced LA function as compared to lenient target HR (>70 bpm).

438-443 324

Aim. To study short term effect of stent size and number on left ventricular mechanical dyssynchrony after elective percutaneous coronary intervention (PCI) to left anterior descending (LAD) artery.

Materials and methods. the study included 150 adult patients with LAD lesion treated with PCI using drug-eluting stent. Patients were evaluated pre PCI then 1 month and 3 months post PCI for evaluation of mechanical dyssynchrony using tissue synchronization image (TSI).

Results. Before revascularization mean left ventricular ejection fraction was 51.2±5.7 %, mean time to peak TSI was 213.6±10.9 ms; 1 month after PCI TSI improved significantly to 163.7±17.6 ms (p<0.001), 3 months after PCI showed more improvement to 120.7±26.9 ms (p<0.001). After 3m; 61 patients (40.7%) showed recovery to normal TSI value. The predictors of non-improvement of time to peak TSI after 3 months were diabetes mellitus (p=0.007), dyslipidemia (p=0.001) and stent length (p=0.001), number of stents (p=0.004). There were strong negative correlation between stent length and improvement of the time to peak TSI at 1 month (r=-0.352, p<0.001) and at 3 months (r=-0.509, p<0.001),and also with number of stent at 1 month (r= -0.173, p=0.034) and at 3 months (r=-0.499, p<0.001), but the correlation between stent diameter and improvement of the TSI wasn’t significant neither at 1 month nor at 3 months (r=0.055, p=0.504 and r= -0.018, p=0.827) respectively.

Conclusion. Increased number and length of the implanted stents were predictors to non-improvement of mechanical dyssynchrony, while stent diameter didn’t affects the recovery.

444-449 328

Aim. To study approaches to the treatment of chronic heart failure (CHF) with reduced and mid-range left ventricular ejection fraction (LVEF) in patients with arterial hypertension (AH) against the background of obstructive sleep apnea (OSA).

Material and methods. The study included 136 patients with CHF and AH. Inclusion criteria for the study: 1) moderate and severe OSA (with an apnea/hypopnea index of more than 15 per hour); 2) II-IV functional class of CHF according to NYHA; 3) the level of brain natriuretic peptide precursor (NT-proBNP) ≥125 pg/ml; 3) LVEF <50%; 4) the duration of hypertension is at least 2 years. Patients received drug therapy, including beta-blockers, mineralocorticoid receptor antagonists, diuretics, ACE inhibitors or angiotensin receptor inhibitors or valsartan/sacubitrile. After 12 months of followup, the patients were divided into 2 groups depending on the medication being administered. Group 1 included patients (n = 50) receiving therapy with valsartan/sacubitril, group 2 included patients (n = 86) receiving therapy without this drug. Effective CPAP-therapy also was registered in each group.

Results. In patients with CHF who received valsartan/sacubitril, disease progression was recorded in 28% of cases, while in patients who did not receive therapy with this drug, an unfavorable course of CHF was recorded in 42.8% (p = 0.001). In group 1, the NT-proBNP level significantly (p = 0.034) decreased by 34%, while in group 2, a significant (p = 0.002) increase in biomarker levels was revealed by 35.5%. In the group of patients receiving therapy with valsartan/sacubitril an increase in LVEF (p = 0.007) was revealed by 12.5%. In group 1, an increase in exercise tolerance was achieved in the form of a significant (p = 0.012) increase in the distance of the six-minute walk test by 18.2%, while in group 2, the six-minute walk distance decreased by 19.2% (p = 0.034). In the subgroup of patients receiving CPAP therapy in combination with valsartan/sacubitril therapy (n=8), LVEF increased by 11.6% (p = 0.043), the six-minute walk test distance increased by 29.7% (p = 0.046), and NT-proBNP decreased by 22.5% (p = 0.039), while in the group of patients who received only CPAP therapy (n=19).

Conclusion. The most significant slowdown in the rate of progression of CHF in patients with AH associated with OSA, an increase in exercise tolerance, as well as the most pronounced tendency to the reverse development of pathological echocardiographic changes in the myocardium when using valsartan/sacubitrile in drug therapy in combination with effective hardware CPAP therapy.

450-455 293

Aim. To study the morpho-functional parameters of the heart in convalescents of hemorrhagic fever with renal syndrome (HFRS) using echocardiography.

Material and methods. The study included 27 patients without any chronic diseases who had severe or moderate HFRS (the main group) within 3 weeks after their discharge from the infection diseases hospital. The reference group consisted of 19 patients comparable by age and gender, without any chronic diseases. Transthoracic echocardiography was the basic method of heart and hemodynamics investigation. The test was performed using tissue Doppler and non-Doppler assessment of left ventricle systolic deformation method (speckle-tracking method).

Results. Violation of longitudinal systolic deformation of the left ventricle was observed in 15 (55.6%) patients, which was combined with diastolic left ventricle filling by the type of relaxation violation in 8 (29.6%) cases. Mitral valve insufficiency of 1 degree was identified in 11 (40.7%) HFRS patients, insufficiency of the tricuspid valve of 1 degree was identified in 4 (14.8%) patients. Pericardial effusion was detected in 2 (7.4%) patients. In 7 (25.9%) patients in the first 3 weeks after discharge from the hospital, additional floating echoes were detected on the leaves and fibrous ring of the aortic valve, which were considered as a manifestation of thromboendocarditis.

Conclusion. Further investigation is necessary to assess the prognostic value (including the risk of thromboembolic complication developing) of the changes revealed in HFRS convalescents and to support the inclusion of echocardiography in the examination program during dispensary observation of HFRS-convalescents.

456-461 300

Aim. to study the levels of procalcitonin in patients with various forms of acute coronary syndrome (ACS), depending on the presence of adverse hospital outcomes.

Materials and Methods. The study included 222 patients admitted to the emergency cardiology department with a diagnosis of ACS in the period from March 2014. until January 2017. Of these, 106 (47.7 %) patients were diagnosed with unstable angina (NS) and 116 (52.3%) with myocardial infarction (MI). Non ST segment elevation MI (NSTEMI) was diagnosed in 47 (40.5%) patients with MI, and ST elevation MI (STEMI) – in 69 (59.5%) patients with MI. After the assessment of the patient's compliance with the criteria for inclusion/exclusion in the study, the procedure for signing the patient's informed consent form was carried out. The protocol of the study was approved by the local Ethics committee of the M. E. Zhadkevich State Clinical Hospital. In each study subgroup, the presence of adverse outcomes during the current hospitalization was assessed: cardiovascular death, nonfatal MI, nonfatal acute cerebrovascular accident, acute heart failure, as well as a combined endpoint, including all of the listed adverse outcomes. All patients, in addition to routine laboratory methods of investigation, were examined for the level of procalcitonin at admission to the hospital, on 2-3 and 4-5 days.

Results. Patients with MI compared to patients with NS were characterized by a large number of registered endpoints in general (24.1% vs. 6.6%, p<0.001), while in the group of patients with MI, cardiovascular death was more often recorded (10.3% vs. 0.9%, p<0.001) and acute heart failure (12.9% vs. 5.6%, p=0.009). Patients with MI, in particular with STEMI, who had adverse hospital outcomes, were characterized by statistically significantly higher levels of procalcitonin compared to patients without adverse hospital outcomes. Patients with STEMI showed significantly higher levels of procalcitonin at all stages of the disease, and patients with MI-only at 2-3 and 4-5 days. There were no statistically significant differences in the level of procalcitonin at all stages of the disease in patients with NSTEMI and with unstable angina, depending on the hospital outcomes.

Conclusion. Elevated procalcitonin levels in patients with MI, in particular with STEMI, are associated with adverse hospital outcomes; for other forms of ACS, no statistically significant differences were observed with different hospital outcomes.


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Antigenic and metabolic integration of the intestinal microbiota into the homeostasis of the human body is a factor that claims to play a key role in the pathogenesis of cardiovascular diseases. It acquires special significance against the background of the decrease in blood circulation and congestion in the digestive system during chronic heart failure. Aim of the review is analysis and synthesis of studies results on the role of intestinal microbiocenosis in the pathogenesis of heart remodeling and chronic heart failure. The search for articles was conducted in databases eLIBRARY.RU and Medline for the key terms "gut microbiota (microbiome, microbiocenosis)", "dysbiosis (dysbacteriosis)", "excessive bacterial growth syndrome", "lipopolysaccharide (endotoxin)", "trimethylamine-N-oxide" in combination with the terms "heart failure", "myocardial remodeling", "myocardium" in Russian and English, respectively. We selected articles containing the results of clinical and experimental studies published from 1995 to 2020. Review articles were considered only on the subject of the cited original publications. Most researchers have established the relationship between chronic heart failure and dysfunction and changes in the qualitative and quantitative composition of intestinal microbiocenosis. As negative changes, it is customary to note the proliferation of gram-negative opportunistic bacteria with concomitant endotoxinemia and a decrease in the pool of commensal microbiota. The available data suggest that the participation of the intestinal microbial-tissue complex in the pathogenesis of chronic heart failure and heart remodeling is realized through the activation of a local and then systemic inflammatory response, accompanied by cardiodepressive action of pro-inflammatory cytokines and universal proliferation factors, an imbalance of matrix metalloproteinases and their inhibitors, the initiation of apoptosis, fibrosis, and loss of contractile myocardium. Besides, a decrease in the production of short-chain and polyunsaturated fatty acids and vitamins by the commensal microbiota may be associated with changes in the electrical properties of cardiomyocyte membranes, a decrease in the systolic function of the left ventricle of the heart, and an increase in the risk of sudden cardiac death. It's also shown that the direct cardiotoxic effect of microbial molecules (lipopolysaccharides, peptidoglycans, trimethylamine-N-oxide, etc.), which interact with the receptors of cardiomyocytes and microenvironment cells, can cause the development of myocardial remodeling and its dysfunction. Recent studies have established mechanisms of myocardial remodeling mediated by microbial molecules, which may be associated with new strategies for the treatment and prevention of heart failure.


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The seasonal blood pressure variability (BPV) is known to demonstrate a typical winter peak. Recently, more attention is paid to the opposite situation: the summer BP levels being higher than those in winter. This phenomenon is called inverse BPV. The present article summarizes recent data on this topic. The data of the HOMED-BP project, as well as the results of the original prospective study in 770 hypertensive patients from two Russian Federation regions (mean follow-up duration 6.4 years), were used. According to the preliminary knowledge, the prevalence of inverse BPV in hypertensive patients is relatively high (15-25%). This phenomenon is more typical for treated patients, particularly for those on combination therapy, and is associated with beta-blocker intake. Higher duration of hypertension and higher levels of some risk factors (smoking) characterize the patients with inverse BPV. According to the HOMED-BP data, patients with inverse BPV had the highest overall cardiovascular risk (hazard ratio in comparison with the reference group of “minimal” “normal” BPV was 3.07; p=0.004). In summary, inverse BPV is a potentially unfavorable BP phenotype. However, its reproducibility and prospective value deserve further investigation. The absolute magnitude of seasonal BPV in these patients, calculated using different BP measurement methods, warrants special attention.

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Heart failure with preserved ejection fraction (HFpEF) is a syndrome associated with high morbidity and mortality rates. Little progress has been in the treatment of this condition since its introduction some 30 years ago. It's accepted that HFpEF is heterogeneous in many ways, ethologically and phenotypically. The underlying mechanisms of the syndrome are not clear. Recently, it has been shown that the diagnostic criteria for HFpEF lacks sensitivity and specificity. Novel treatment approaches, which were developed based on current HFpEF pathophysiological concepts, did not show either clinical or prognostic benefit for patients. Therefore, there is an urgent need to revise current diagnostic approaches and to further investigate the underlying mechanisms. Recently, two novel diagnostic score systems were proposed: H2PEF and HFA-PEFF. Recently, a number of phase II and III randomized control trials have been completed. Here, the authors discuss the potential novel diagnostic approaches to HFpEF and treatment perspectives.


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Atrial fibrillation (AF) is a complex pathology that requires an integrated approach in both diagnosis and treatment, including optimal prevention of thrombosis, control of clinical symptoms, and identification and treatment of cardiovascular risk factors and comorbidities. The article analyzes some of the new positions of the recommendations of the European Society of Cardiology on atrial fibrillation, presented in 2020. Effective diagnostic and therapeutic approaches are discussed in the management of patients with AF in conditions of multimorbidity. The basic principles of the CC to ABC concept, introduced with the aim of improving a structured approach to the treatment of patients with AF, and the 4S-AF regimen necessary for decision on the use of oral anticoagulants, choosing a method of control of the rhythm and / or its frequency, choosing between ablation, cardioversion and antiarrhythmic drugs, as well as to determine the mode of treatment of major cardiovascular diseases. To improve the prognosis and achieve the best results in these patients, the most important is to reduce the risk of stroke, control cardiovascular risks and comorbidities, and ensure high adherence to the therapy within the framework of the concept of comprehensive patient protection. Rivaroxaban is considered by the authors of the article as one of the drugs that provides comprehensive anticoagulant protection of patients with AF. The efficacy profile of rivaroxaban in the prevention of acute cerebrovascular accident and high safety rates were confirmed in a population of multimorbid AF patients of different ages and the highest risk of stroke and / or bleeding.

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Congenital long QT syndrome is a pathology that requires special attention and knowledge about the safety and effectiveness of various medications. Prolongation of the QT interval due to congenital or acquired causes is an important factor in the development of an unfavorable life forecast with the formation of an elongated QT syndrome. With an unfavorable course, patients suffer from loss of consciousness, episodes of tachycardia. Often, stable polymorphic ventricular tachycardia develops. The risk of sudden cardiac death in this pathology can vary from 0.33% to 5%. In people who have suffered an episode of cardiac arrest, and do not have a permanent prescribed antiarrhythmic therapy, the mortality rate reaches 50% within 15 years. Preventive administration of antiarrhythmic drugs is not always effective. A positive result of treatment depends on the severity of long QT syndrome and its genotype. Beta-blockers are often prescribed to patients of different ages with various cardiac pathologies, including for the prevention of arrhythmia in long QT syndrome. Beta-blockers differ in various pharmacokinetic and pharmacodynamic parameters (lipophilicity/hydrophilicity, selectivity, presence/absence of internal sympathomimetic activity), which, along with the variant of the disease genotype, can affect their effectiveness and safety in the considered pathology. This review article presents the results of major studies on the safety and effectiveness of different groups of beta blockers in various variants of long QT syndrome. The preferred beta-blockers for various genotypes of the syndrome were determined, and a comparative characteristic of beta-blockers for their safety and preventive effectiveness was given.

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Combination therapy is the standard of treatment for virtually all current non-communicable diseases, primarily chronic coronary heart disease, in modern terminology - "chronic coronary syndrome" (CSS), arterial hypertension, chronic heart failure, diabetes mellitus. The need for a combination of drugs increases even more with comorbidity, which is a typical situation in clinical practice. The recently accumulated material requires a review of the possibility of percutaneous coronary intervention and coronary bypass surgery in prolonging the life of patients with CCS, focusing on providing optimal medical therapy (OMT) for each patient with CCS, based on long-term treatment with antiplatelet agents, statins, angiotensin converting enzyme in-hibitors/angiotensin receptor blockers, beta-blockers. OMT aimed at preventing cardiovascular events and relieving symptoms in patients with CCS requires maximum commitment - a key factor in achieving therapeutic goals. Insufficient adherence of patients to prescribed therapy and its absence are the main barriers to increasing the survival rate of patients with cardiovascular diseases in primary and secondary prevention in the Russian Federation, as evidenced by numerous registers. The desire of the doctor to individualize treatment, which inevitably complicates the use of drugs, pushes patient adherence to treatment into the background. As a result, the patient's lack of commitment to each of the pharmaceuticals destroys the applicability of the OMT concept. A great achievement of the current stage of development of clinical cardiology and the pharmaceutical industry is the ability to offer patients optimal single pill combinations (SPC) in terms of effectiveness, tolerability, drug interactions, and ease of use. The article substantiates the prospects for a successful solution of this key problem by using a new generation of SPC components belonging to different pharmacological groups. The combination of three components (lisinopril, amlodipine and rosuvastatin), each of which has pleiotropic effects, provides a multi-targeted effect with a single dose, with the possibility of individualization of therapy, which is provided by four dosage options within this SPC.

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