EDITORIAL
Major principles for treatment of chronic heart failure with reduced left ventricular ejection fraction <40% (HFrEF) include a “triple neurohormonal blockade” as a main approach. However, in recent 6 years, two new classes of drugs for the treatment of HFrEF have appeared, which beneficially influence the prognosis. These drugs are angiotensin receptor neprilysin inhibitors (ARNI) and type 2 sodium-glucose cotransporter 2 (SGLT2) inhibitors.
Aim To compare the net effect of simultaneous treatment with ARNI and SGLT2 inhibitors with the triple neurohormonal blockade in stable or decompensated patients with CHF based on Russian data.
Material and methods We analyzed the risk of death per 100 patient-years in patients with HFrEF. Stable patients were followed up at the A.L. Myasnikov Institute of Cardiology (presently, A.L. Myasnikov Research Institute of Clinical Cardiology of the National Medical Research Center of Cardiology) from 2006 through 2007; data from the EPOCH-Decompensation-CHF study were used for decompensated patients (12.2 % and 36.8 %, respectively).
Results When patients with stable HFrEF were successively switched from renin-angiotensin-aldosterone system (RAAS) inhibitors to ARNI (–16 %) and subsequently supplemented with SGLT2 (–13 %) the risk of death per 100 patient-years decreased from 12.2 % to 8.9 % (total risk decreased by 27 %; to save one patient the ARNI+ SGLT2 combination has to be prescribed to 30 patients). The estimated risk of death upon discharge from the hospital for the patients with decompensated CHF switched from RAAS inhibitors to ARNI (–16 %) and subsequently supplemented with SGLT2 (–13 %) was 26.9 deaths per 100 patient-years, whereas the number of patients to be treated for saving one life was only 10. Based on available data that demonstrate a greater effect of ARNI+ SGLT2 in patients immediately after CHF aggravation, the risk of death was recalculated. According to this analysis, the death rate per 1000 patient-years decreased from 36.8 to 19.9 % (relative risk decrease, 46 %), and to save one life only 6 patients had to be treated after they have achieved compensation of HFrEF.
Conclusions This analysis shows the importance of early initiation of the ARNI+ SGLT2 therapy in patients with both decompensated and with stable HFrEF.
RESEARCH ARTICLES
Aim To study clinical features of myoendocarditis and its possible mechanisms, including persistence of SARS-Cov-2 in the myocardium, in the long-term period following COVID-19.
Material and methods This cohort, prospective study included 15 patients aged 47.8±13.4 years (8 men) with post-COVID myocarditis. The COVID-19 diagnosis was confirmed for all patients. Median time to seeking medical care after COVID-19 was 4 [3; 7] months. The diagnosis of myocarditis was confirmed by magnetic resonance imaging (MRI) of the heart (n=10) and by endomyocardial biopsy of the right ventricle (n=6). The virus was detected in the myocardium with PCR; immunohistochemical (IHC) study with antibody to SARS-Cov-2 was performed; anticardiac antibody level was measured; and echocardiography and Holter monitoring were performed. Hemodynamically significant coronary atherosclerosis was excluded for all patients older than 40 years.
Results All patients showed a clear connection between the emergence or exacerbation of cardiac symptoms and COVID-19. 11 patients did not have any signs of heart disease before COVID-19; 4 patients had previously had moderate arrhythmia or heart failure (HF) without myocarditis. Symptoms of myocarditis emerged at 1–5 months following COVID-19. MRI revealed typical late gadolinium accumulation, signs of hyperemia, and one case of edema. The level of anticardiac antibodies was increased 3-4 times in 73 % больных. Two major clinical variants of post-COVID myocarditis were observed. 1. Arrhythmic (n=6), with newly developed extrasystole or atrial fibrillation without systolic dysfunction. 2. Decompensated variant with systolic dysfunction and biventricular HF (n=9). Mean left ventricular ejection fraction was 34.1±7.8 %, and left ventricular end-diastolic dimension was 5.8±0.7 cm. In one case, myocarditis was associated with signs of IgG4‑negative aortitis. SARS-Cov-2 RNA was found in 5 of 6 biopsy samples of the myocardium. The longest duration of SARS-Cov-2 persistence in the myocardium was 9 months following COVID-19. By using antibody to the Spike antigen and nucleocapsid, SARS-Cov-2 was detected in cardiomyocytes, endothelium, and macrophages. Five patients were diagnosed with lymphocytic myocarditis; one with giant-cell myocarditis; three patients had signs of endocarditis (infectious, lymphocytic with mural thrombosis).
Conclusion Subacute/chronic post-COVID myocarditis with isolated arrhythmias or systolic dysfunction is characterized by long-term (up to 9 months) persistence of SARS-Cov-2 in the myocardium in combination with a high immune activity. Endocarditis can manifest either as infectious or as nonbacterial thromboendocarditis. A possibility of using corticosteroids and anticoagulants in the treatment of post-COVID myoendocarditis should be studied.
Aim To present clinical observations of the novel coronavirus infection (COVID-19) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after a surgical intervention in the form of thromobendarterectomy from pulmonary artery branches.
Material and methods The Acad. E.N. Meshalkin National Medical Research Center performed 127 open surgical interventions for CTEPH in the form of thromobendarterectomy from 2016 through 2020. The present study enrolled 113 patients included into the follow-up care group and into the Center Registry who were followed up for more than 6 months after the surgery. Clinical and functional features of COVID-19 were evaluated in the studied group.
Results In the follow-up care group, 5 (4.4%) postoperative CTEPH patients had COVID-19. One patient had asymptomatic disease, and others had typical clinical symptoms and bilateral polysegmental pneumonia. There were no cases requiring artificial ventilation and no lethal outcomes. All patients with COVID-19 received anticoagulants as a basis therapy for CTEPH, and two patients who had residual pulmonary arterial hypertension (PAH) additionally received a PAH-specific therapy. During the treatment of COVID-19, no adjustment of the anticoagulant or PAH-specific therapy was required.
Conclusion The group of patients with CTEPH is a unique pathophysiological model for studying the effect of COVID-19 under the conditions of compromised pulmonary circulation. In the studied follow-up care group, the COVID-19 morbidity was 4.4 % without fatal outcomes. Evaluation of the role of chronic anticoagulant and PAH-specific therapy in COVID-19 postoperative patients as well as evaluation of the role of COVID-19 in CTEPH progression merit further investigation.
Aim To identify clinical and laboratory indexes related with the atherosclerotic plaque (ASP) echogenicity based on results of the analysis of grey-scale median (GSM) in patients aged 40–64 years.
Material and methods The study included patients aged 40–64 years with carotid atherosclerosis. The carotid duplex scanning was performed for all patients. The GSM analysis of obtained images was performed with the Adobe Photoshop CS6 software.
Results Atherosclerotic cardiovascular diseases were found in 31 (21.4 %) patients. Correlation analysis determined inverse interrelationships between GSM and the body weight index (BWI) (r=–0.359; p<0.0001), waist circumference (r=–0.357; p<0.0001), and levels of uric acid (r=–0.244; p=0.021) and glucose (r=–0.205; p=0.032). According to the regression, statistically significant correlations remained between GSM and BWI as well as the waist circumference after the adjustment for sex and age.
Conclusion In patients with carotid atherosclerosis aged 40–64 years, the decrease in ASP GSM was associated with increases in BWI and waist circumference.
Aim To study features of diagnosis and treatment of acute myocardial infarction (AMI) in Russian hospitals, results of the treatment, and early and late outcomes (6 and 12 months after AMI diagnosis); to evaluate the consistence of the treatment with clinical guidelines; and to evaluate patients’ compliance with the treatment.
Material and methods The program was designed for 3 years, including 24 months for recruitment of patients to the study. The study will include 10, 000 patients hospitalized with a confirmed diagnosis (I21 according to ICD-10) of ST segment elevation acute myocardial infarction (MI) (STEMI) or non-ST segment elevation MI (NSTEMI) based on criteria of the European Society of Cardiology Guidelines on Forth Universal Definition of Myocardial Infarction (2018). The follow-up period was divided into three stages: observation during the stay in the hospital and at 6 and 12 months following inclusion into the registry. The primary endpoint included cardiac death, nonfatal MI during the hospitalization and after one-year follow-up. Secondary endpoints were 6-months and one-year incidence of repeated MI, heart failure, ischemic stroke, clinically significant hemorrhage, unscheduled revascularization after discharge from the hospital, and the proportion of patients who continue on statins, antiplatelet drugs, and drugs of other groups for 6 months and 1 year.
Results The inclusion of patients into the registry started in 2020 and will continue for 24 months. By the time of the article publication (June, 2021), more than 2,000 patients will be included.
Conclusion REGION-MI (Russian rEGIstry Of acute myocardial iNfarction) is a multicenter, retrospective and prospective observational cohort study that excludes any interference with the clinical practice. Results of the registry will help to analyze a real picture of medical care provided to patients with myocardial infarction and to schedule ways to improve the situation.
Aim To evaluate outcomes in patients with acute coronary syndrome and atrial fibrillation who receive rivaroxaban and the patients’ compliance with the antithrombotic therapy.
Material and methods The study was performed from October 2017 through December 2019 and included 129 patients. Events between the discharge from the hospital and 12 months of follow-up were recorded. The primary endpoint was development of major, minor or requiring medical attention bleeding according to the TIMI scale. The secondary endpoint was a combination of recurrent myocardial infarction, nonfatal acute ischemic cerebrovascular disease, nonfatal systemic embolism, stent thrombosis, and cardiovascular mortality.
Results 32 (24.8%) patients early terminated the antiplatelet treatment and 22 (17.1%) patients terminated the rivaroxaban treatment. 26 (20.2 %) patients had hemorrhagic complications. The highest incidence of hemorrhage was observed within the first 2 months after the discharge. None of the bleedings was fatal. Composite endpoint events were observed in 24 (18.6 %) patients, including 14 (10.9 %) who died from cardiovascular causes.
Conclusion The compliance with the antiplatelet therapy was insufficient. The incidence of hemorrhagic complications was relatively high; minor and requiring medical attention hemorrhages mostly contributed to the structure of these complications. The observed incidence of recurrent ischemic events associated with a high mortality presents a more serious problem compared to hemorrhagic complications of the combination antiplatelet therapy and warrants a more aggressive tactics of the antiplatelet treatment in high-risk patients.
Aim To study the effect of hypoxia on the activity of epithelial-mesenchymal transition (EMT) in epicardial cells, which provides formation of a specialized microenvironment.
Material and methods This study used a model of experimental myocardial infarction created by ligation of the anterior descendent coronary artery. The activity of epicardial cells after a hypoxic exposure was studied with the hypoxia marker, pimonidazole, bromodeoxyuridine, immunofluorescent staining of heart cryosections, and in vitro mesothelial cell culture.
Results The undamaged heart maintained the quiescent condition of mesothelial cells and low levels of their proliferation, extracellular matrix protein production, and of the EMT activity. Acute ischemic injury induced moderate hypoxia in the epicardial/subepicardial region. This caused a global rearrangement of this region due to the initiation of EMT in cells, changes in the cell composition, and accumulation of extracellular matrix proteins. We found that the initiation of EMT in mesothelial cells may result in the formation of smooth muscle cell precursors, fibroblasts, and a population of Sca-1+ cardiac progenitor cells, which may both participate in construction of new blood vessels and serve as a mesenchymal link for the paracrine support of microenvironmental cells. In in vitro experiments, we showed that 72‑h hypoxia facilitated activation of EMT regulatory genes, induced dissembling of intercellular contacts, cell uncoupling, and increased cell plasticity.
Conclusion The epicardium of an adult heart serves as a “reparative reserve” that can be reactivated by a hypoxic exposure. This creates a basis for an approach to influence the epicardium to modulate its activity for regulating reparative processes.
Aim To study features of the psychological status, job burnout syndrome (JBS)m and quality of life (QoL) in outpatient physicians.
Material and methods This cross-sectional study was performed at 16 randomly selected municipal outpatient hospitals of Moscow and included physicians (district physicians, primary care physicians, and cardiologists). The participants signed an informed consent form and then filled out a registration card that included major social and demographic (sex, age, education, position) and professional characteristics (specialization, work experience, qualification category), and questionnaires. The degree of job burnout was evaluated with the Maslach Burnout Inventory (MBI-HSS), and the presence of anxio-depressive symptoms was evaluated with the Hospital Anxiety and Depression Scale (HADS). The level of stress was assessed with a visual analogue scale (VAS) in a score range from 0 to 10. The QoL of physicians was assessed with the short version of the World Health Organization Quality of Life (HOQOL-BREF) questionnaire.
Results This study included 108 physicians from 16 municipal outpatient clinics aged 24 to 70 years (mean age, 44.0±13.1 years), mostly women (87.0 %). Among JBS components, a high level of emotional exhaustion was observed in 50.0 % of physicians, a high level of depersonalization in 34.1 %, and a severe reduction of personal accomplishment in 37.5 %. A high level of stress (VAS score ≥7) was observed in 66.3 % of physicians; symptoms of anxiety and depression of any degree (HADS-A and HADS-D subscale score ≥ 8) were found in 23.8 and 22.7 % of participants, respectively. 42.0% of physicians evaluated their QoL lower than “good” and 41.6% of physicians evaluated their health condition lower than “good”. Most of the studied factors did not significantly depend on the gender and the duration of work, except for emotional exhaustion (55.3 % of women and 16.7 % of men; p=0.0086) and a high level of stress (72.2 % of women and 28.6 % of men; р=0.002).
Conclusion The study showed a high prevalence of personal factors that potentially adversely affect the work of outpatient physicians. These factors included high degrees of stress, anxio-depressive symptoms, job burnout, unsatisfactory QoL, and low satisfaction with own health. Management decisions and actions are required to create the optimum psychological climate at the workplace of physicians, to develop new strategies for prophylaxis and correction of their psychological condition, and to implement comprehensive programs for improving the professional environment to maintain and enhance the mental health and to increase the professional prestige of the medical speciality.
REVIEWS
Senile patients with atrial fibrillation (AF) are at a higher risk of thromboembolism and hemorrhage than younger patients. Three direct oral anticoagulants (DOAC), apixaban, dabigatran, and rivaroxaban, are registered in the Russian Federation and are extensively used for prevention of stroke in patients with AF. The DOAC treatment of older patients requires considering peculiarities of these patients, clinical situation and properties of individual drugs to achieve the balance of efficiency and safety and a comprehensive protection. According to studies of real clinical practice DOAC may have advantages over warfarin (reduced risk of fractures, diabetes mellitus, and dementia). Compliance with and constancy of the DOAC treatment are important for its efficiency, particularly in senile age. Results of clinical trials and real clinical practice studies have confirmed that rivaroxaban may provide a comprehensive protection for a senile patient with AF due to favorable indexes of efficiency and safety, beneficial effect on the risk of coronary events and impairment оf renal function, whereas once a day dosing of rivaroxaban improves the compliance with this treatment and its constancy.
Along with increased levels of low-density cholesterol, lipid factors of the risk of cardiovascular complications (CVC) include hypertriglyceridemia, particularly increased plasma levels of remnant particles. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are essential for normal functioning of cell membranes, retina, nerve tissue, skeletal muscles, etc. Among the large family of fatty acids (FA), eicosapentaenoic (EPC) and docosahexaenoic (DHX) FA are most studied. The beneficial effect of ω-3 PUFA consumption on the cardiovascular system is related with improvement of blood rheology, antiarrhythmic and anti-inflammatory effects, and a decrease in triglycerides. Large randomized studies of ω-3 PUFA (mixed EPC and DHX or only EPC) have demonstrated their efficiency and safety and a capability for reducing the incidence of CVC and sudden death as well as improvement of the prognosis in various patient populations. In the STRENGTH study (combination of omega-3 and statins), no significant decrease in the risk of CVC was achieved in patients with high triglycerides and low high-density lipoproteins. The ω-3 PUFA treatment is regulated by current international Guidelines and Consensuses as a part of combination therapy with statins for reduction of the risk of CVC and correction of pronounced hypertriglyceridemia.
The emergence of more effective methods for treatment of pulmonary arterial hypertension (PAH) has called for more reliable methods of diagnostics, monitoring, and evaluating responses to the treatment. More reports have become available about the relevance of using magnetic resonance imaging (MRI) for examination of patients with PAH. This review provides data on the significance of MRI for noninvasive evaluation of the heart structure and function in patients with PAH, as well as for visualization and evaluation of the remodeling of the pulmonary circulation. According to the data presented in this review, the results obtained with various, modern MRI technologies can be used for monitoring the effect of treatment and for risk stratification in patients with PAH.
The number of people involved in regular exercise and sports is increasing. Not infrequently, this is associated with intake of sports biologically active food supplements (BAS) and stimulators of physical ability. Data has been reported on the frequency of use of physical ability stimulators among professional athletes and on the use of the most popular food supplements among young people. Special attention is paid to the effect of such use on the cardiovascular system of athletes. This review describes negative cardiac effects and clinical cases of death of athletes due to the use of such supplements and stimulators.
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