The article focuses on effective treatment of the novel coronavirus infection (COVID-19) at early stages and substantiates the requirement for antiviral therapy and for decreasing the viral load to prevent the infection progression. The absence of a specific antiviral therapy for the SARS-CoV-2 virus is stated. The authors analyzed results of early randomized studies using lopinavir/ritonavir, remdesivir, and favipiravir in COVID-19 and their potential for the treatment of novel coronavirus infection. Among the drugs blocking the virus entry into cells, the greatest attention was paid to the antimalaria drugs, chloroquine and hydroxychloroquine. The article addresses in detail ineffectiveness and potential danger of hydroxychloroquine, which demonstrated neither a decrease in the time of clinical recovery nor any improvement of prognosis for patients with COVID-19. The major objective was substantiating a possible use of bromhexine, a mucolytic and anticough drug, which can inhibit transmembrane serin protease 2 required for entry of the SARS-CoV-2 virus into cells. Spironolactone may have a similar feature. Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2. In addition to slowing the virus entry into cells, spironolactone decreases severity of fibrosis in different organs, including the lungs. The major part of the article addresses clinical examples of managing patients with COVID-19 at the University Clinic of the Medical Research and Educational Centre of the M. V. Lomonosov Moscow State University, including successful treatment with schemes containing bromhexine and spironolactone. In conclusion, the authors described the design of a randomized, prospective BISCUIT study performed at the University Clinic of the M. V. Lomonosov Moscow State University with an objective of evaluating the efficacy of this scheme.

Aim      To evaluate changes in 12-lead ECG in patients with coronavirus infection.

Materials and methods This article describes signs of electrocardiographic right ventricular “stress” in patients with COVID-19. 150 ECGs of 75 COVID-19 patients were analyzed in the Institute of Cardiology of the National Medical Research Centre for Therapy and Preventive Medicine. The diagnosis was based on the clinical picture of community-acquired pneumonia, data of chest multispiral computed tomography, and a positive test for COVID-19. ECG was recorded both in 3-6 and in 12 leads. Signs of right ventricular (RV) stress, so-called systolic overload (high R and inverted T_V1–3 and T_{II, III, aVF}), and diastolic overload (RV wall hypertrophy and cavity dilatation; complete or incomplete right bundle branch block) were evaluated.

Results The most common signs for impaired functioning of the right heart include emergence of the RV P wave phase (41.3 %), incomplete right bundle branch block (42.6 %), ECG of the S_IQ_IIIT_III type (33.3 %) typical for thromboembolic complications, and signs of RV hypertrophy, primarily increased S_V5–6 (14.7 %). These changes are either associated with signs of RV myocardial stress (16 %) or appear on the background of signs for diffuse hypoxia evident as tall, positive, sharp-ended T waves in most leads (28 %).

Conclusion      A conclusive, comprehensive assessment of the reversal of hemodynamic disorders and electrocardiographic dynamics in patients with COVID-19 will be possible later, when more data become available.

In the recent months of the COVID-19 pandemics, the cardiological society has faced a new challenge, myocardial injury by the coronavirus infection. According to statistics, 20-40% of hospitalized patients have chest pain, heart rhythm disorders, heart failure, and sudden cardiac death syndrome. This review focuses on recent studies and clinical cases related with this issue.

The article describes a clinical case of myopericarditis as a late manifestation of possible COVID-19.

Aim      Searching for clinical, angiographic, and biochemical predictors of cardiovascular complications (CVC) and hemorrhagic complications in patients with atrial fibrillation (AF) receiving a multicomponent antithrombotic therapy (MAT) for an elective percutaneous coronary intervention (PCI). Patients with ischemic heart disease (IHD) and AF who require MAT for PCI are at a high risk of thrombotic complications (stroke, systemic embolism, coronary events) and hemorrhage. This warrants searching for new risk factors determining prediction of the outcome.

Materials and methods This study included 207 patients (146 males aged 70.1±8.3 years) with IHD and AF who received direct oral anticoagulants (DOAC) as a part of their MAT therapy. Median duration of the follow-up was 12 [8.0; 12.0] months. The efficacy endpoint was a sum of CVCs combining cardiovascular death, ischemic stroke, venous thromboembolic complications, acute coronary syndrome (ACS), and requirement for an unscheduled PCI. “Coronary events”, including ACS and requirement for an unscheduled PCI were analyzed separately. The safety endpoint was BARC type 2-5 bleeding. Upon admission, biomarkers (growth-differentiation factor 15 (GDF-15), D-dimer, thrombin-activated fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor-1 (PAI-1)) were measured for all patients. Searching for prognostically significant indexes was performed with the Cox proportional hazards regression.

Results Incidence of all CVCs was 16.4 %. Independent predictors of CVC included the DOAC treatment at a reduced dose (odds ratio (OR) 2.5 at 95 % confidence interval (CI) 1.02-6.15; p=0.0454), GDF-15 >1191 pg /ml (OR 3.76 at 95 % CI, 1.26-11.18; p=0.0172), PAI-1 >13.2 U/ml (OR 2.67 at 95 % CI, 1.13-6,26; p=0.0245). Incidence of coronary complications was 9.2 %. Independent predictors of coronary complications included a SYNTAX index >26.5 (OR 4.5 at 95 % CI, 1.45-13.60; p=0.0090), PCI for chronic coronary occlusion (OR 3.21 at 95 % CI, 1.10-9.33; p=0.0326), a GDF-15 >1191 pg/ml (ОR 4.70 at 95 % CI, 1.32-16.81; p=0.0172). Incidence of BARC type 2-5 bleeding was 26.1 %. The only independent predictor for hemorrhage complications was the total PRECISE-DAPT score >30 (ОR 3.22; 95 % CI, 1.89-5.51; р<0.0001).

Conclusion      Three independent predictors of CVC were identified for patients with IHD and AF treated with MAT following an elective PCI: treatment with a reduced dose of DOAC, GDF-15 >1191 pg /ml, and PAI-1>13.2 U/ml. Independent predictors of coronary complications included a SYNTAX index >26.5, PCI for chronic coronary occlusion, and GDF-15 >1191 pg/ml. The factor associated with a risk of bleeding was the total PRECISE-DAPT score >30.

 

Aim      To develop a model for evaluating the risk of stroke in patients after exacerbation of ischemic heart disease who were admitted to the hospitals included into a vascular program.

Materials and methods This study included 1803 patients with acute coronary syndrome (ACS) from four institutions of Moscow, Kazan, Astrakhan, and Krasnodar where the vascular program was established. Mean age of patients was 64.9±12.78 years, 62,1 % of them were men. The patients were followed up for one year after the discharge from the hospital. External validation of the developed prognostic model was performed on a cohort of patients with ACS included into the RECORD-3 study.

Results During the follow-up period, 42 cases of ischemic stroke were observed. The risk of ischemic stroke was associated with the presence of atrial fibrillation (odd ratio (OR) 2.640; р=0.037), diabetes mellitus (OR 2.718; р=0.041), and chronic heart failure (OR 7.049; р=0.011). Protective factors were high-density lipoprotein cholesterol >1 mmol/l (OR 0.629; р=0.041), percutaneous coronary intervention during an index hospitalization (OR 0.412; р=0.042), anticoagulant treatment (OR 0.670; р=0.049), and achieving the blood pressure goal (OR 0.604; р=0.023). The prognostic model developed on the basis of regression analysis showed a good predictive value (area under the ROC curve, 0.780), sensitivity of 80 %, and specificity of 64.6 %. The diagnostic value of other scales for risk assessment was somewhat lower. The area under the ROC curve was 0.692±0.0245 for the GRACE scale and 0.708±0.0334 for CHA₂DS₂‑VASc. In the external validation of the scale based on data of the RECORD-3 study, the diagnostic value was lower although satisfactory as well (area under the ROC curve, 0.651); sensitivity was 78.9 %, and specificity was 52.3 %.

Conclusion      The study resulted in development of a simple clinical scale, which will probably allow identifying groups at risk of stroke more precisely than with standard scales.

 

Aim      Comprehensive evaluation of blood flow in the thoracic aorta using a software for 4D processing of magnetic resonance (MR) images of the heart and blood vessels (4D Flow) in patients with aortic coarctation in the late postoperative period.

Materials and methods The MR study of the heart was performed for 10 patients (7 boys and 3 girls) aged 8 to 13 years (median, 9.5 [8.3; 10.8] years) who underwent resection with end-to-end anastomosis for aortic coarctation at age of 2 weeks to 10 months. MR tomography was performed on a 1.5 T MR scanner using a multichannel surface coil for scanning, electrocardiographic synchronization, and a specialized package of pulse sequences for scanning of the heart. Blood flow was evaluated with a 4D data handling software for processing of MR images of heart and blood vessels (4D Flow). The following blood flow parameters were analyzed: blood flow volume per second, peak blood flow velocity, peak and minimum blood flow area at the levels of ascending aorta, arch, isthmus, and descending aorta, and pressure gradient at the level of maximum narrowing of the aorta. 3D-MR images were used for evaluation of aortic geometry. Blood flow formation, distribution, and trajectories were analyzed by maps of vectors, particle trace, and stream lines. Statistical analysis was performed with a Statistica (v. 6.0 StatSoft Inc.) package.

Results Accelerated flow in the region of residual aortic stenosis in systole was observed in all patients; 4 patients had an additional vortex flow below the aortic stenosis and a spiral flow in the descending aorta. The pressure gradient on the aortic isthmus was directly correlated with the left ventricular myocardial mass index (r=0.65; р=0.04) and indexes of blood flow in the ascending and descending aorta (р=0.03; р=0.026). No significant correlation was found for blood flow indexes and geometry of the aortic arch (H / L). Delayed contrast enhancement MR imaging did not detect any fibrotic changes in the myocardium in only one patient. The fibrosis severity inversely correlated with the right ventricular ejection fraction (r=0.65; р=0.04) and directly correlated with the pressure gradient at the aortic isthmus (r=0.63; p=0.05).

Conclusion      The 4D MR image processing software for the heart and blood vessels allows studying the blood flow in detail under natural conditions, provides potential advantages in comprehensive evaluation of patients with aortic coarctation during a dynamic follow-up. For a definitive conclusion about the relationship between the altered blood flow in the thoracic aorta and markers of residual, post-correction pathology, larger studies are required as well as long-term follow-up of patients with documented pathological patterns of blood flow (changes in blood flow velocity and volume throughout the entire thoracic aorta in combination with disorders in the normal flow geometry during the cardiac cycle).

 

 

Aim      To evaluate the effect of 12-month perindopril treatment on structure and function of microvasculature (MV) in patients with chronic heart failure with preserved (HFpEF) and intermediate (HFiEF) left ventricular ejection fraction.

Material and methods  30 patients with HFpEF and HFiEF were evaluated. Perindopril at a maximum tolerated dose was administered to all patients for 12 months. Changes in MV structure and function were assessed with photoplethysmography and capillaroscopy prior to the treatment onset and at 12 months, i.e., after completion of the perindopril treatment.

Results The 12-month perindopril treatment was associated with improvement of the endothelial function evident as increases in the occlusion index (OI) and the phase shift (PS). OI increased from 1.45 [1.3; 1.6] to 1.8 [1.6; 2.2] (p=0.00004). PS increased from 7.1 ms [4.8; 10.2] to 9.2 ms [6.7; 13.2] (p=0.0003). Stiffness of muscular large blood vessels was decreased. Arterial stiffness index (aSI) decreased from 8.8 [6.6; 11.0] to 7.45 [6.5; 9.4] m /s (р=0.01). The perindopril treatment was associated with increased density of the capillary network at rest (р=0.008) and in tests with venous occlusion (р=0.003) and reactive hyperemia (р=0.0003).

Conclusion      The study showed an improvement of endothelial function associated with the 12-month perindopril therapy in patients with HFpEF and HFiEF.

 

 

Aim To study the efficacy and safety of alirocumab in patients with high and very high cardiovascular risk in the Republic of Karelia and to evaluate their compliance with the alirocumab therapy.
Materials and methods Study design: observational, noncomparative. The observation group consisted of 9 patients receiving alirocumab (Praluent®) (mean age, 48.6±4.7 years; 7 men). 7 patients had familial hypercholesterolemia of the type diagnosed by DLCN criteria; five patients had MI. Lipid profile, concentrations of transaminases, creatinine, glucose, and lipoprotein a (LP(a)) were measured at 3, 6, 12, and 18 months. Electrocardiography was performed, and the clinical picture (development of acute coronary syndrome, acute cerebrovascular disease, transient ischemic attacks, myocardial revascularization, and cardiovascular death) was evaluated. Efficacy criteria included the absence of these clinical conditions, the proportion of patients who achieved the LDL CS goal, and the decrease in LP(a). Safety was evaluated by clinical and laboratory data, such as levels of transaminases, total bilirubin, creatinine, and blood glucose. The observation lasted for 6 months to 1.5 years.
Results LDL CS goals were achieved in 7 (77.8%) patients receiving alirocumab. The mean level of LP(a) decreased from 0.39 to 0.28 g/l; the degree of decrease ranged from 20 to 33 %. No cases of IHD instability (acute coronary syndrome) or new cases of acute cerebrovascular disease and transient ischemic attacks were observed. None of the patients had to stop the alirocumab treatment; adverse effects, including local ones, were not observed.
Conclusion LDL CS goals were achieved in 7 (77.8%) patients. The level of LP(a) decreased by 20-33% in patients receiving the PCSK9 inhibitor. In real-life clinical practice, the alirocumab treatment was characterized with high compliance and good tolerability without side effects, including local ones.

Aim To study the involvement of cytokine polymorphous loci in development of arterial hypertension (AH) in men from the Central Black Earth region of Russia.
Materials and methods 821 men were evaluated, including 564 patients with AH and 257 individuals of the control group. Analysis of 8 cytokine mononucleotide polymorphisms (MNP) was performed using the real-time polymerase chain reaction with TagMan probes. Statistical analysis was performed with the STATISTICA (v.10.0) and PLINK (v.1.06) software. The regulatory potential of MNP was analyzed with the HaploReg (v.4.1) service (http://archive.broadinstitute.org).
Results The rs1061624 ТNFR2 polymorphous locus was associated with development of AH in men in recessive (odd ratio (OR), 0.33; 95 % confidence interval (CI): 0.18–0.61, рperm=0.0004) and additive (OR, 0.50, 95 % CI: 0.34–0.74, рperm=0.0006) genetic models and exerted a protective effect in development of AH. The rs1061624 MNP of the ТNFR2 gene has a regulatory significance; it is located in the DNA sites hypersensitive to the action of DNAase 1 and in binding sites for transcriptional factors and histones that mark enhancers and promoters in different organs and tissues.
Conclusion The rs1061624 ТNFR2 gene polymorphism is involved in the development of AH in men of the Central Black Earth region of Russia.

Aim To compare Russian versions of the scales for assessment of self-care ability in patients with chronic heart failure (CHF), European Heart Failure Self-Care Behavior Scale (EHFScBS_9) and The Self-Сare of Heart Failure Index (SCHFI, version 6.2).
Materials and methods Assessment of the self-care ability was performed with Russian versions of EHFScBS_9 and SCHFI (version 6.2) scales in 130 patients with NYHA functional class II-IV CHF primarily of ischemic origin (78.5 %). Mean age of patients was 63.2±9.6 years; most of the patients were men (n=92; 70.8 %). Patients were managed in accordance with effective guidelines ESC / HFA 2016 and Russian guidelines 2018.
Results Along with an increase in SСHFI scores, a decrease in EHFScBS_9 scores was observed (r= –0.31, p<0.001). The patients participating in the study showed a low self-care ability at baseline according to results of both scales.
Conclusion The presence of certain differences between the study scales does not exclude a possibility of using them alone or together for more detailed assessment of the self-care ability.

Aim To compare the efficacy of radiofrequency ablation (RFA) and antiarrhythmic therapy (AAT) in patients with atrial fibrillation (AF) and chronic heart failure (CHF) during 12-month observation.
Materials and methods This prospective, nonrandomized comparative observational study included 130 patients with AF (men, 65 %; mean age, 62.8±11.8 years) and CHF with left ventricular ejection fraction (LV EF) <50 %. Paroxysmal AF was observed in 60 (46 %) patients and persistent AF was observed in 70 (54 %) patients. According to results of transthoracic echocardiography (EchoCG) 107 (82 %) patients had intermediate LV EF (40–49 %) and 23 (18 %) patients had reduced LV EF (<40 %). RFA of AF was performed for 65 patients whereas 65 patients received an optimal AAT. The 24-h electrocardiogram monitoring, EchoCG, and assessment of the quality of life (QoL) with the SF-36 questionnaire were performed for all patients on admission and at 12 months of observation. Stability of sinus rhythm, EchoCG, QoL, and exercise tolerance were evaluated at 12 months of observation.
Results 49 (75%) of patients in the RFA group and 26 (40%) of patients in the AAT group had stable sinus rhythm (SR) at 12 months. Repeated RFA for relapse of AF was performed for 6 (12 %) of 49 patients; repeated cardioversion was performed for 16 (61.5 %) of 26 patients. In the AAT group, there were more interventions for maintaining SR than in the RFA group (p<0.001). In patients with SR of the RFA group at 12 months of observation, LV EF was increased (р<0.001), left ventricular dimension (р<0.001) and volume (р<0.001) were decreased, and mental (р<0.001) and physical (p<0.001) components of health were improved according to the SF-36 questionnaire. In patients with SR of the AAT group, only improvement of mental (р<0.001) and physical (р<0.001) components of health was observed according to the SF-36 questionnaire.
Conclusion RFA provided a considerable decrease in the frequency of AF relapse and improvement of LV EF in patients with CHF. The effectiveness of RFA did not depend on the type of arrhythmia. For 12 months of observation, the number of hospitalizations for decompensated CHF and interventions to maintain SR decreased in the RFA group compared to the AAT group.

Aim To study the role of inflammation markers and endothelial dysfunction in predicting the risk of cardiovascular event following a percutaneous coronary intervention (PCI) in patients with ischemic heart disease (IHD) and metabolic syndrome (MS).
Materials and methods 80 patients (72 men; median age, 56 (50;63) years) with IHD and PCI were evaluated. Based on the presence of MS according to NCEP-ATP III criteria, patients were divided into two groups, group 1 without MS (n=32) and group 2 with MS (n=48). The control age- and sex-matched group included 15 people without cardiovascular diseases. Serum concentrations of tumor necrosis factor α (TNFα), interleukin 6 (IL-6), IL-10, lipoprotein-associated phospholipase A2 (LP-PLA2), and endothelin 1 were measured by enzyme-linked immunosorbent assay (ELISA). Patients were followed up for 12 months after PCI with evaluation of the incidence of adverse cardiovascular events. Statistical analysis was performed with Statistica 10.0 and Medcalc 19.2.6 software. Differences between variables were considered statistically significant at р<0.05. Potential predictors were determined by the ROC analysis with construction of ROC curves, calculation of AUC (area under the curve), identification of COP (cut-off point by the Youden’s index), and sensitivity (Se) and specificity corresponding to the COP.
Results Patients with MS had statistically significantly higher serum levels of inflammatory markers than patients of the control group. Concentration of the intravascular inflammation marker, PL-PLA2, was 2.7 times higher in group 1 and 5.1 times higher in group 2 than in the control group (р<0.001). Concentrations of endothelin 1 were 1.9 times higher in group 1 and 3.7 times higher in the MS group compared to the control. At one year after PCI, the incidence of adverse outcomes in the form of cardiovascular events was higher for patients with MS: 10 (20.8 %) cases of stent restenosis and 13 (27.1 %) episodes of coronary atherosclerosis progression according to results of repeated coronarography vs. 2 (6.3%) restenosis cases (χ2–10.853; р=0.002) and 2 (6.3%) episodes of atherosclerosis progression (χ2–23.651; р=0.001) for patients without MS. The groups did not differ in rates of myocardial infarction and cardiac death. The most significant predictors of unfavorable prognosis were LP-PLA2 concentration >983.83 ng/ml (area under the ROC curve, 0.867; sensitivity, 80 %; specificity, 100%; р<0.001) and endothelin 1 overexpression >0.852 fmol/ml (area under the ROC curve, 0.885; sensitivity, 85.5 %; specificity, 83.6 %; р<0.001).
Conclusion Patients with MS were characterized by more pronounced imbalance of pro- and anti-inflammatory factors. Concentrations of LP-PLA2 >983.83 ng/ml and endothelin 1 >0.852 fmol/ml were shown to be predictors of unfavorable prognosis for patients with IHD and MS after PCI with coronary stenting.

Chronic heart failure (CHF) is a wide-spread disease (from 7 to 10% in the Russian Federation) and tends to grow. Frequent, repeated hospitalizations of CHF patients are due to insufficient compliance of patients with the treatment and the absence of continuity in management of patients between the hospital and out-patient clinic. Developing a structure of specialized care could provide improvement of treatment quality, a decrease in the number of hospitalizations, and better prognosis. International experience shows that creation of specialized clinics for heart failure improves quality of medical care in CHF and decreases the frequency of re-hospitalizations and mortality. In the Russian Federation, such clinics were created in Nizhniy Novgorod, Ufa, Saint Petersburg, and several other cities. The article presents an expert consensus on the structure, functions, and equipment of departments and offices for patients with heart failure.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a precapillary type of pulmonary hypertension with chronic obstruction of large and medium branches of pulmonary arteries along with secondary alterations in pulmonary microcirculation, which cause progressive increases in pulmonary vascular resistance and pulmonary arterial pressure and ensuing severe right heart dysfunction and heart failure. Pulmonary thromboendarterectomy (PTE) is the treatment of choice for CTEPH; however, this procedure is available not for all patients. Although the surgery performed in the conditions of centers with advanced experience generally shows good results, up to 40% of patients are technically inoperable or PTE is associated with a high risk of complications. At present, riociguat, the only officially approved drug from the class of soluble guanylate cyclase stimulators, is considered as a first-line treatment for inoperable and residual forms of STEPH. Introduction of riociguat to clinical practice can be called a real breakthrough in the treatment of patients with STEPH who cannot undergo PTE or those with relapse or persistent STEPH after the surgery.

This review analyzes results of a large prospective, randomized, double-blind, placebo-controlled clinical study ENGAGE AF-TIMI 48 that compared efficacy and safety of warfarin, a vitamin K antagonist, and edoxaban, an oral inhibitor of activated coagulation factor X. The review addresses important practical aspects of using edoxaban in patients with nonvalvular atrial fibrillation.

The article discusses results of secondary analysis of the data obtained in the SPRINT study and published in recent years. Unresolved issues in the tactics of managing patients with arterial hypertension are discussed. One of such issues is choosing an optimum level of blood pressure (BP) for a subgroup of patients with certain characteristics, including elderly and senile patients, patients with chronic kidney disease, and patients with arterial hypertension who continue smoking. The article discusses calculation of a threshold of risk for complications of cardiovascular diseases, at which a maximum advantage of intensified regimens of antihypertensive therapy could be achieved. In addition, the article addresses approaches to selection of antihypertensive drugs in the current conditions. The authors discussed the role of candesartan in the treatment of arterial hypertension, a sartan most studied in a broad range of patients. The issue of a rapid increase in BP without a damage to target organs is addressed; evidence for the role of captopril in such clinical situation is provided.