Rational Pharmacotherapy in Cardiology

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Vol 18, No 2 (2022)
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118-126 334

Aim. To assess long-term sequelae of COVID-19 in hospitalized patients at 3 to 7 months after discharge.

Material and Methods. The whole of 700 patients hospitalized to the temporary COVID-19 treatment center hosted by the FSBI “National Medical Research Center of Cardiology” of the Ministry of Health of Russia from April to June 2020 were invited to participate in a follow-up study. At 3-7 months after the index hospitalization, patients or their proxies were contacted via telephone in order to obtain information on their vital status, cardiovascular and other conditions or their complications, and new hospitalizations. In addition, patients were invited to an outpatient visit under the "COVID-19-follow-up" program, encompassing physical examination and a comprehensive battery of laboratory and instrumental tests, including spirometry, chest computed tomography (CT) and the six minute walk test (6MWT). Further, dyspnea was assessed using the mMRC (Modified Medical Research Council) Dyspnea Scale. 

Results: We were able to contact 87.4% (612/700) of patients or their proxies. At follow-up, 4.4% (27) patients died, of which 96.3% (26) had cardiovascular diseases (CVD). A total of 213 patients aged 19 to 94 years old (mean age 56.8±12.5, median 57 years [49.0; 64.0]; men, 55.4%) agreed come for an outpatient visit and to participate in the “COVID-19-follow-up” program. Since discharge, 8% (17) of patients required new hospitalizations, and more than a half of these patients (58.8%; 10/17) had CVD-related hospitalizations. A total of 8.4% (18) patients experienced worsening of hypertension, 9 (4.2%) patients had newly diagnosed hypertension, 2 (0.9%) – coronary artery disease patients experienced new/recurrent angina symptoms. 4 (1.9%) patients had newly diagnosed coronary artery disease, and one patient had an ischemic stroke. At the outpatient visit, 114 (53.5%) patients had some symptoms, most frequently, shortness of breath (33%), fatigue (27.4%), chest pain (11.3%), and abnormal heartbeats (8.5%). Based on the mMRC Scale, 59% of patients had dyspnea of varying severity. Most patients had a normal vital capacity (VC), which was moderately reduced in 3.3% and severely reduced in 0.5% of patients. Chest CT scans were obtained in 78 (36.6%) patients, whose worst lung damage scores during hospitalization were CT3 or CT4. One in ten patients (10.8%) with severe lung damage during acute infection had persisting ground glass opacities, 35.9% developed fibrotic changes, 79.6% of patients had linear or fine focal opacities. According to the 6MWT data, 12.3% of patients walked less than 70% of the predicted distance, 67% walked 71 to 99% of the predicted distance, and 20.7% of patients were able to walk 100% of their predicted distance.

Conclusion. These data suggest long-term negative sequelae of COVID-19 in more than half of hospitalized patients.

127-134 386

Aim. To study the effects of azilsartan medoxomil/chlorthalidone (AZM/CTD) and losartan/hydrochlorothiazide (LOS/HCT) combinations for NTproBNP levels, 6-minute walk test results, hydration status along with their antihypertensive efficacy according to clinical and 24-hour blood pressure in patients with hypertension and heart failure with preserved ejection fraction (HFpEF).

Material and methods. An open randomized study included 56 patients with uncontrolled or untreated hypertension and HFpEF. Patients randomized to receive the AZM/CTD 40/12.5 mg/day (group 1; n=28) or LOS/HCT 100/12.5 (group 2; n=28) within 4 weeks. Patients who did not achieve the target BP <140/<90 mm Hg study drug dose was intensified: in the first group, an increase in the dose of AZM/CTD 40/25 mg/day, in the second group, an increase in the dose of LOS/HCT 100/25 mg/day. The observation period was 12 weeks. All patients underwent a clinical examination with an assessment of symptoms and/or signs of HF, laboratory and instrumental studies, including NT-proBNP, ambulatory blood pressure (BP) monitoring, applanation tonometry, a 6-minute walk test (6MWT), echocardiography. In order to assess the status of hydration, bioimpedance vector analysis (BIVA) was performed. HFpEF was diagnosed according to the HFA-PEFF algorithm. The results were considered statistically significant at p<0.05.

Results. After 12 weeks, 92% of patients in the first and 78% of patients in the second group reached the target clinical BP (р<0,05). Average daily BP <130/ <80 mm Hg was reached by 82% of patients treated with the combination of AZM/CTD, compared with 67% treated with the combination of losartan/HCT (p<0.05). After 12 weeks, patients from both groups showed a significant decrease in systolic and diastolic blood pressure, central blood pressure, and a decrease in pulse wave velocity, which was more significantly significant in the first group of patients (p<0.05). During therapy in both groups of patients, a significant decrease in the level of NT-proBNP was observed: in the first group from 300 [199; 669] pg/ml to 156 [157; 448] pg/ml (p=0,003), in the second group from 298 [180; 590] pg/ml to 194 [140; 360] pg/ml (p=0,006), an increase in the distance during the 6MWT from 317 [210; 398] m to 380 [247; 455] m (p=0,006) in in the first group and an improvement in the hydration status according to the BIA data, but more significantly significant in the first group (p<0.001).

Conclusion. In patients with hypertension and HFpEF, therapy with the AZM/CTD combination compared with LOS/HCT is accompanied by a more pronounced antihypertensive effect in terms of ambulatory and peripheral blood pressure, central blood pressure, NTproBNP levels, increased distance in 6MWT and achievement of euvolemia status. 

135-142 429

Aim. To perform the analysis of antithrombotic therapy and immediate prognosis in patients with pulmonary embolism (PE) in routine clinical practice.

Materials and methods. During 13 months of follow-up (2018-2019) within the framework of the Russian SIRENA registry, the study included patients (n=103) with verified PE who were hospitalized at the regional vascular center. 

Main results. Thrombolytic therapy was performed in 63 patients (61.2% of the sample), of which 48 (76.2%) had no indications. In these cases, the most common reason for performance was the results of the PESI score (n=17) and/or a significant amount of damage to the pulmonary artery (n=10) and/or severe shortness of breath (n=3) and/or the presence of a thrombus in the right parts of the heart or deep veins of the lower extremities (n=2), in addition, in a number of medical records, the cause is indicated as “for health reasons” (n=6) or there were no data (n=10). Patients who underwent thrombolysis had a larger volume of pulmonary lesions, more pronounced signs of respiratory failure and overload of the right heart, as well as a shorter duration of clinical manifestations. Anticoagulant therapy was used in 94.2% of cases, of which 90.3% of patients used parenteral forms at the start, then direct oral anticoagulants were mainly used, the frequency of warfarin prescription was only 5.8% of cases. Bleeding was registered in 19.4% of patients (significant – in 11.7%). PE recurrence after diagnosis and initiation of therapy was observed in 4 cases (3.9%). Hospital mortality was 9.7%. Predictors of poor prognosis were hospitalization with a different diagnosis (risk ratio [RR] 16.2; p=0.001), advanced age (RR 10.1; p=0.028), unstable hemodynamics (RR 7.6; p=0.002), chronic kidney disease C3- 5 (RR 5.6; p=0.03), history of stroke (RR 5.3; p=0.016) and chronic heart failure (RR 3.9; p=0.035).

Conclusion. In modern clinical practice, the indications for thrombolysis often differ from those recommended, which leads to an increase in the number of bleeding and leveling of the positive effect on the prognosis. Factors such as advanced age, chronic heart failure and atrial fibrillation, stroke, chronic kidney disease, hemodynamic instability, hospitalizations with a different primary diagnosis, and the need for oxygen therapy increase the risk of early mortality. 

143-152 245

Aim. To describe prognostic meaning of cardiac and other principal clinical manifestations of systemic AL-amyloidosis in their interrelations.
Material and methods. It has been made long-time survival analysis of 147 patients with systemic AL-amyloidosis. In the special investigation group (n=58) of AL (n=55) and ATTR (n=3) amyloidotic cardiopathy patients there were evaluated prognostically important structural and functional changes in myocardium with standard and impulse-wave tissue dopplerometric echocardiography in comparison with NTproBNP serum levels.
Results. Even though significantly increased nowadays surviving of AL-amylodotic patients (Me=90 months) it has been found that as at previously time orthostatic hypotension and amyloid cardiopathy are being most severe initial syndromes (median 25 months), but after 1 year from diagnosis influence of these syndromes on surviving had decreased and most low surviving was more common in patients with CKD 3-5 (median 28 months). Influence of CKD 3-5 on surviving was associated predominantly with intracardial hemodynamics deterioration. Together with decreased systolic shortening strain rate (48,5%) decreased filtration rate (47,9%) was second of main factors contributing into NTproBNP increasing in effective multiple regression model (R=0,702, F(4,21)=5,095, p=0,005). NTproBNP level in less degree depended on renal clearance.
Conclusion. Heart damage is one of the most prognostically unfavorable manifestations of systemic amyloidosis due to a sharp deterioration in the elastic properties of the myocardium, in the process of further development of amyloidosis, the leading factor in progression is the deterioration of the profile of cardiorenal interactions, the marker of which is the level of NTproBNP.


153-159 368

Aim. To assess the effect of renal dysfunction on the galectin-3 level in patients with chronic heart failure (HF) with preserved, intermediate and reduced left ventricular ejection fraction (EF).
Material and methods. Along with a clinical examination, 69 patients with HF (NYHA class II-IV) underwent tests for the level of NT-proBNP and galectin-3 in serum using enzyme immunoassay.
Results. Study participants were divided into 3 groups: 23 patients with preserved EF (HFpEF), 26 patients with midrange EF (HFmrEF), 20 patients with reduced EF (HFrEF). There was a trend to increase the concentration of galectin-3 with increase in NT-proBNP level. Correlation analysis showed significant feedback (r=−0.41, p<0.05) between galectin-3 and EF only in patients with preserved systolic function. In the same group of HFpEF patients, the maximum serum galectin-3 level was 10.5 [6.5; 14.5] ng/ml. Serum galectin-3 level showed negative correlated with the GFR in patients with CHF (r=−0.513, p<0.05). In patients with HF and glomerular filtration rate (GFR) <60 ml/min/1.73 m2 it was higher than in patients with GFR>60 ml/min/1.72 m2 (9 [5.3; 12.6] ng/mL vs 11.8 [6.2; 15.3] ng/mL, p<0.05). According to the ROC-analysis data, galectin-3 level >10.3 ng/ml indicates a high risk of chronic kidney disease stage 3-4 stage development (sensitivity 60%, specificity 75%) and can be considered as a risk factor for development of cardiorenal syndrome in HF patients.
Conclusion. Galectin-3 level in patients with HF is more influenced by the degree of reduction in GFR rather than the left ventricular systolic function impairment.

160-164 179

Aim. To study the factors associated with the development of postoperative atrial fibrillation (POAF) with single- or two- or more vascular bypass grafting in elderly patients with coronary heart disease.
Methods. The study included 454 patients with coronary artery disease who underwent CABG. Patients were divided into 4 groups: 1 group – with single-vessel bypass, 2 group – with 2-vessels, 3 group – with 3-vessels and 4 group with 4-vessels bypass. During the observation period postoperative atrial fibrillation (POAF) occurred in 7.5% of patients in group 1, 18.4% in group 2, 17.5% in group 3 and 19.2% of patients in group 4. Since there were no significant differences in the incidence of POAF in patients with 2-4-vessels bypass grafting, these groups were combined for further analysis. 2 groups are allocated: Group I comprised patients with single-vessel bypass graft (79 patients, 76.0% of males, the average age of 65.0 [63.0;68.0] years), Group II – with 2-4-vessels bypass grafts (357 patients, 78.4% of males, the median age of 67.5 [64.5;69.0] years).
Results. POAF occurred in 7.5% of patients in group I and in 18.4% of patients in group II (p=0.03) on the median 4.9 [1.2;8.7] day after coronary artery bypass graft. The multivariate regression analysis showed that indicators, associated with POAF development in patients undergoing CABG were the following: aortic cross-clamping time >36 min (odds ratio [OR)]1.4; 95% confidence interval (CI) 1.1-2.8; p=0.030), time of ischemia >19 min (OR 1.7; 95% CI 1.2-3.3; p=0.020), age >65 years (OR 1.8; 95% CI 1,1-4,1; p=0.010), left atrium diameter >39 mm (OR 2.9; 95% CI 1.5-5.4; p=0.005), left ventricular ejection fraction <51% (OR 1.9; 95% CI 1.2-3.0; p=0.04).
Conclusion. In our study, atrial fibrillation in the early postoperative period was more common in patients undergoing multivessel coronary bypass surgery. Indicators, significantly associated with POAF in patients undergoing Coronary artery bypass graft were aortic cross-clamping time >36 minutes, time of ischemia >19 minutes, age >65 years, left atrium diameter >39 mm and left ventricular ejection fraction <51%.

165-169 168

Aim. To study the structural and functional features of the carotid and femoral arteries using ultrasound duplex scanning of them in patients with hypertension undergoing periodic preventive medical examination.
Material and methods. Periodic preventive examination was carried out for 2431 employees (1311 men and 1120 women) aged 20-65 years using a specially developed questionnaire, blood pressure measurement, anthropometry, total cholesterol test. Hypertensive men were assessed for preclinical manifestations of atherosclerosis by ultrasound duplex scanning of the carotid and femoral arteries.
Results. Hypertensive men (BP ≥140/90 mmHg and/or taking antihypertensive drugs; n=176, mean age 43.5 years) were included in the study. An increase in the thickness of the intima-media complex in the carotid arteries was found in 22.2% (n=38) people, in the femoral arteries – in 34.1% (n=60) people, in both basins – in 16.5% (n= 29) man. Atherosclerotic plaques in the carotid arteries were found in 40.3% of people (n=71), and in the femoral arteries – in 34.7% (n=61) of people, in both pools – in 23.9% (n=42) of men.
Conclusion. Ultrasound diagnostic using modern ultrasound scanners is a highly informative method for non-invasive diagnosis of atherosclerosis in the arteries of the carotid and femoral basins in employees of a large industrial enterprise with arterial hypertension in the conditions of the medical and sanitary department. Carrying out these diagnostic approaches is advisable when organizing periodic medical examinations in order to improve primary prevention, as well as to prevent the aggravation of the identified pathological process, reduce complications, improve quality and increase life expectancy.

170-175 299

Aim. To study changes in myocardial contractile function when prescribing mineralocorticoid receptor antagonists of spironolactone in patients after coronavirus infection SARS-CoV-2 with symptoms of chronic heart failure (CHF).
Materials and methods. The study included 90 hospitalized patients with a diagnosis of SARS-CoV-2 coronavirus infection. The inclusion criteria were: age from 18 to 85 years; the presence of CHF with a preserved or mildly reduced left ventricular ejection fraction (LVEF). The patients were randomized into two groups: group I (n=60) included patients who, for 6 months after discharge from the hospital, in addition to standard drug therapy for CHF, took spironolactone at a dose of 25 mg per day; group II (comparison group; n=30) included patients who received standard drug therapy without additional prescription of spironolactone. The study groups were comparable in age, gender, prevalence of hypertension, coronary heart disease, diabetes mellitus, obesity and severity of CHF; the drug therapy given to the patients had no significant differences. Assessment of LV systolic function, exercise tolerance (six-minute walk test, TSW), quality of life (questionnaire EQ-5D-5L) were performed.
Results. When repeated echocardiography was performed after 6 months of treatment, there was a significant improvement in LV systolic function in group I patients. In group I, after 6 months of treatment, there was a significant decrease in the proportion of patients with moderately reduced LVEF (from 30 [50%] to 12 [20%]; p<0.001), and a significant increase in the number of patients with preserved LVEF (from 30 [50%] to 48 [80%], p=0.002). In group II, the number of patients with moderately reduced LVEF did not significantly change. After 6 months of treatment, all patients showed an increase in exercise tolerance. During the test with a six-minute walk, group I patients showed an increase in the index from 316.8±63.5 to 432.9±41.3 meters; group II patients from 337.6±42.7 to 407.6±38.9 meters. The values of the six-minute walking test after 6 months of treatment were significantly higher in group I patients when compared with group II patients. When assessing the quality of life using the EQ-5D-5L questionnaire, it was found that at the time of inclusion of patients in the study, all patients noted the presence of any health problems in one or more components. The average indicator of health status, measured by a 100-point visual analog scale, after 6 months was 71.8±9.2 in patients of group I and was significantly higher than the same indicator in group II – 63.7±9.1. There were no adverse events in the study groups during the entire observation period.
Conclusion. A significantly more pronounced improvement in systolic and diastolic left ventricle function, as well as quality of life, was found in the group of CHF patients with preserved or moderately reduced LVEF, who received spironolactone for 6 months after the SARS-CoV-2 infection in addition to standard therapy, compared with patients without aldosterone antagonists.


176-182 244

Aim. The aim of the research was to study the dynamics of distant cases of the disease that underwent AMI in 2005-2007 (LIS registry) and in 2014 and 2018 (LIS-3 registry), discharged from the same hospital of the Lyubertsy District Hospital (LDH).
Material and methods. The study was conducted on the basis of two registries - a retrospective-prospective register LIS (Lyubertsy investigation of death), which was conducted in the Lyubertsy district of the Moscow region, all cases of check-ups in the AMI hospital for a 3-year period (2005- 2007) and the prospective register LIS-3 (11/01/2013 – to the present), which included patients admitted to the cardiology department of the Lyubertsy District Hospital No. 2 with the correct diagnosis of Acute coronary syndrome with and without ST segment elevation. With patients discharged from the hospital, a telephone contact was established no earlier than 1 year after discharge to clarify the life status, and in case of death – to find out its causes. Search for patients who did not answer the phone call, was using by the study of the archive of the polyclinic, with database statistics. Longterm cases of the LIS were compared with LIS-3 registers, clinical demographic characteristics and risk indicators in patients in the LIS and LIS-3 registers were also compared, differences in drug therapy before the onset of AMI and after discharge from the hospital register between LIS and LIS3 were analyzed.
Results. Out of 327 patients, the registry included 104 (31.8%) patients discharged in 2014 and 223 (68.2%) in 2018. When comparing the longterm mortality curves of the LIS and LOS-3 registers, a significant difference was noted. The LIS-3 study revealed more frequent referrals for antiplatelet agents (20% vs 16%), statins (11.6% vs 2.0%). Less commonly, diuretics began to be prescribed at the prehospital level. After discharge from the hospital in the LIS-3 registry, a decrease compared to the LIS registry, more frequent prescription of antiplatelet agents (97.5% vs 85.0%), anticoagulants (1.1% vs 0%), statins (96.5% vs 67.0%), beta-blockers (93.3% vs 81.0%). Less commonly, diuretics are prescribed at discharge from the hospital.
Conclusion. The present study of the LIS-3 registry showed a significant decrease in the incidence of those who had AMI, which occurred 15-20 years after the LIS registry was conducted.


183-190 170

Nonspecific aortoarteritis (Takayasu's disease) is a systemic inflammatory disease characterized by granulomatous lesions of the aorta and its large branches. The article describes the clinical manifestations, methods of diagnosis and treatment of this pathology. It also describes a clinical observation that illustrates the delayed diagnosis of the disease in a 47-year-old man, where Takayasu arteritis with lesions of the root, ascending aorta, both common carotid arteries, thoracic and abdominal aorta (type V according to the angiographic classification proposed by Moriwaki R.) manifested a syncopal state, just a few days before the development of a life – threatening complication-aortic dissection of type I according to the DeBakey classification. From a clinical point of view, it is important that Takayasu's disease does not always develop in young people, women, and Asian origin, and, unfortunately, it is often very late to diagnose, although the effectiveness of therapy, including surgical correction of this disease, is entirely determined by the timeliness of its diagnosis.


191-199 146

The review presents the main aspects of the relationship between psychoemotional factors, hostility, anger and cardiovascular diseases. The first chapter describes the main historical stages in the study of this problem, starting from the Middle Ages and ending with fundamental research of the 19-20 centuries. In the second part, the authors demonstrated that hostility/anger are a risk factor for the CVD development and affect the prognosis and course of CVD (hypertension, ischemic heart disease, various cardiac arrhythmias, etc.). In the third chapter, there were studies that found that high rates of hostility/ anger reduced the effectiveness of cardiovascular therapy. In the fourth part, there are the main correlation mechanisms of negative emotions, hostility/anger and the cardiovascular system, carried out through the relationships with the activation of the hypothalamic-pituitary-adrenal, autonomic nervous system, platelet activation, with the changes in the risk factors characteristics etc. In the final chapter, the authors suggested prospects for further study of the problem, probably associated with the assessment of behavioral interventions, pharmacological or complex effects on the severity of hostility/anger to reduce CVD mortality in individuals with high rates of hostility / anger.

200-208 210

The pandemic of coronavirus infection, the complex and insufficiently studied mechanisms of which cause disorders in the functions of many organs and systems of the body, has led to the emergence of new problems that are far from being resolved. Researchers note the difficulty in predicting the course of the disease and outcome due to the detection of many symptoms that arose at the height of the disease and persisted for 3-6 months after recovery. The term "post-COVID-19syndrome" has appeared, reflecting the condition of a patient who has undergone COVID-19, with a negative PCR test, and with symptoms lasting more than 12 weeks from the onset of the disease, which cannot be explained by an alternative diagnosis. Postural orthostatic tachycardia as a manifestation of the post-COVID-19syndrome has been described in young women who have undergone coronavirus infection of varying severity. In the case of the development of the syndrome of postural orthostatic tachycardia, the quality of life deteriorates, and the ability to work of patients is limited. There is no evidence base for drug therapy of postural tachycardia syndrome, in most cases empirical drug and non-drug methods of treatment are used.


209-217 177

This review presents the results of previously performed epidemiological, experimental and clinical studies indicating the use of ω-3 PUFA (polyunsaturated fatty acids) contributes to reduce the risk of developing cardiovascular diseases. Experimental studies have shown ω-3 PUFA are exhibiting antiarrhythmic effects, improving endothelial function, showing an anti- inflammatory effect, affecting the rheological properties of blood, reducing triglyceride concentrations, and increasing the stability of atheromatous plaque. Wide-scale clinical trials have established high efficacy of ω-3 PUFA in primary and secondary prevention of coronary heart disease. It is found to reduce the risk of ventricular arrhythmias and sudden cardiac death. Also, reduces overall mortality and hospitalization rates due to cardiovascular causes in patients with chronic heart failure. Clinical efficacy among cardiovascular diseases of the prescription drugs ω-3 PUFA standardized by qualitative and quantitative compositions to be studied further in a comparison to the other medications with similar make-up.

218-224 122

The review article is aimed at providing a recent update on the use of levosimendan, an inotropic drug in current use for the treatment of heart failure. The review discusses its mechanisms of action, main hemodynamic effects, clinical trials and obtained evidences that have formed the basis of the current guidelines on its use, as well as the latest clinical and experimental trials evaluating its organ-protective effects. Conclusion: levosimendan has a promising potential for treating heart failure, prescribed even in low doses, and may be regarded as a drug with cerebroprotective and possible nephroprotective effects, requiring further large randomized clinical trials.

225-230 153

An increase in the life expectancy of the population and the number of polymorbid patients with a combination of two or more diseases in different age categories, including among young people, has led to a significant increase in the cost of medical care in the field of public health. The transition from original drugs to generic ones has become a common measure to contain these costs. While this is an important goal for healthcare systems around the world, the impact of this practice on patient outcomes needs to be carefully considered. In some cases, generics may represent a suitable alternative to branded products, but this is not always the case. In particular, studies have shown that changing the drug can negatively affect not only patients' adherence to treatment, but also clinical outcomes, and a subsequent increase in the total cost of treatment, therefore, the use of generics in clinical practice still causes caution and concerns on the part of both the doctor and the patient. Due to the high prevalence of dyslipidemia and hypercholesterolemia both worldwide and in Russia, in this review the problem of choosing an original drug or generic is described by the example of such a hypolipidemic agent as rosuvastatin. According to numerous studies, rosuvastatin is one of the most potent and widely prescribed statins. Considering that most of the clinically significant effects of this drug are demonstrated in relation to its original form, the review emphasizes the importance of prescribing the original drug rosuvastatin in routine clinical practice.

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ISSN 2225-3653 (Online)