Aim      To evaluate the clinical picture and factors associated with unfavorable outcomes in admitted patients with COVID-19.

Material and methods This study included all patients admitted to the COVID Center of the National Research Center of Cardiology of the Russian Ministry of Health Care from May 1 through May 31, 2020. Clinical demographic, laboratory, and instrumental indexes and associated factors were studied with one-way and multivariate logistic regression analysis.

Results This study included 402 patients aged 18 to 95 years (mean age, 62.9±14.6 years); 43.0 % of them were older than 65 years. COVID-19 was frequently associated with chronic comorbidities, including arterial hypertension (74.4 %), obesity (41.6 %), history of ischemic heart disease (12.9 %), atrial fibrillation (18.9 %), type 2 diabetes mellitus (DM) (13.0 %), and oncological diseases (9.2 %). 13.0 % of patients were smokers; less than 10% had chronic lung diseases. 3.9% of patients had a combination of COVID-19 and acute coronary pathology, including acute myocardial infarction (MI) in 3.2 % (13) and unstable angina in 0.7 % (3). The most frequent clinical manifestation of COVID-19 were four symptoms: cough (81.1 %), weakness (80.3 %), shortness of breath (71.6 %), and fever (62.7 %). 46.5% of patients had shortage of breath and chest pain/compression, 40.3% had headache, 31.1% had myalgia, 28.8% had anosmia, and 25.5% had ageusia. Arterial oxygen saturation was <93.0 % in 55.7 % of cases. According to laboratory blood tests the patients had anemia (58.2 %), lymphopenia (34.8 %), neutropenia (19.2 %), thrombocytopenia (11.9 %), and increased levels of high-sensitivity C-reactive protein (hsCRP, 87.3 %), interleukin-6 (89.3 %), ferritin (62.1 %), and D-dimer (49.2 %). 56.2% of patients required various regimens of oxygen support. 83 (20.6%) patients were admitted to intensive care and resuscitation units; invasive artificial ventilation was performed only for 34 (8.5 %) patients. In-hospital mortality was 7.7 % (31 / 402). One-way regression analysis identified major factors associated with death during the stay in the hospital: age >55 years, NEWS scale score >4.0, oxygen saturation <92.0 %, blood glucose >5.4 mmol/l, hs-CRP >25.7 mg/l, and creatinine clearance <72.0 ml/min. Furthermore, the risk increased with increasing degree of changes in each factor. According to results of the multivariate regression analysis, three most significant predictors of the hard endpoint, all-cause death during the stay in the hospital, were more than 5-fold increases in aspartate aminotransferase and/or alanine aminotransferase compared to normal levels (relative risk (RR) 16.8 at 95 % confidence interval (CI) 5.0–56.3, р<0.001), pronounced changes in the lungs consistent with a CT-4 picture as shown by computed tomography (CT) (RR 13.4; 95 % CI 3.9–45.5, р<0.001), and MI/unstable angina during the stay in the hospital (RR 11.3; 95 % CI 1.4–90.6, р=0.023). The probability of death was also considerably increased by chronic obstructive pulmonary disease, impaired kidney function (creatinine clearance estimated by Cockcroft-Gault <60.0 ml/min), type 2 DM, oncological diseases, and dementia.

Conclusion      This study established factors associated with unfavorable outcomes in admitted patients with COVID-19. This will allow identifying in advance patients with a high risk of complications that require increased attention to take more active diagnostic and therapeutic measures at prehospital and hospital stages.

 

Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7–9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.
Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.
Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient’s clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].
Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).
The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.
Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

Actuality One of the most widely discussed treatments for patients with COVID-19, especially at the beginning of the epidemy, was the use of the antimalarial drug hydroxychloroquine (HCQ). The first small non-randomized trials showed the ability of HCQ and its combination with azithromycin to accelerate the elimination of the virus and ease the acute phase of the disease. Later, large, randomized trials did not confirm it (RECOVERY, SOLIDARITY). This study is a case-control study in which we compared patients who received and did not receive HCQ.
Material and Methods 103 patients (25 in the HCQ treatment group and 78 in the control group) with confirmed COVID-19 (SARS-CoV-2 virus RNA was detected in 26 of 73 in the control group (35.6%) and in 10 of 25 (40%) in the HCQ group) and in the rest - a typical picture of viral pneumonia on multislice computed tomography [MSCT]) were included in the analysis. The severity of lung damage was limited to stages I-II, the CRP level should not exceed 60 mg/dL, and oxygen saturation in the air within 92-98%. We planned to analysis the duration of treatment of patients in the hospital, the days until the normalization of body temperature, the number of points according to the original SHOCS-COVID integral scale, and changes in its components (C-reactive protein (CRP), D-dimer, and the percentage of lung damage according to MSCT).
Results Analysis for the whole group revealed a statistically significant increase in the time to normalization of body temperature from 4 to 7 days (by 3 days, p<0.001), and the duration of hospitalization from 9.4 to 11.8 days (by 2.4 days, p=0.002) when using HCQ in comparison with control. Given the incomplete balance of the groups, the main analysis included 46 patients who were matched by propensity score matching. The trend towards similar dynamics continued. HCQ treatment slowed down the time to normalization of body temperature by 1.8 days (p=0.074) and lengthened the hospitalization time by 2.1 days (p=0.042). The decrease in scores on the SHOCS -COVID scale was statistically significant in both groups, and there were no differences between them (delta - 3.00 (2.90) in the HCQ group and - 2.69 (1.55) in control, p=0.718). At the same time, in the control group, the CRP level returned to normal (4.06 mg/dl), and with the use of GC, it decreased but remained above the norm (6.21 mg/dl, p=0.05). Side effects requiring discontinuation of treatment were reported in 3 patients in the HCQ group and none in the control group.
Conclusion We have not identified any positive properties of HCQ and its ability to influence the severity of COVID-19. This antimalarial agent slows down the normalization of the body's inflammatory response and lengthens the time spent in the hospital. HCQ should not be used in the treatment of COVID-19.

Aim      To study time-related changes in bone remodeling markers in patients with ischemic heart disease (IHD) associated with type 2 diabetes mellitus (DM) and disorders of carbohydrate metabolism (CM). Also, a possibility was studied of using these markers for evaluation of breast bone reparative regeneration in early and late postoperative periods following coronary bypass (CB).

Materials and methods           This study included 28 patients with IHD and functional class II-III exertional angina after CB. Patients were divided into 2 groups based on the presence (group 1) and absence (group 2) of CM disorders. Contents of osteocalcin (OC), C-terminal telopeptide (CTTP) of type 1 collagen, deoxypyridinoline (DPD), and alkaline phosphatase bone isoenzyme (ALPBI) were measured by enzyme immunoassay on admission (Т1) and at early (Т2) and late (Т3) postoperative stages. Sternal scintigraphy with a radiopharmaceutical (RP) was performed at stage 3 following sternotomy.

Results The content of OC and CTTP was reduced in group 1 compared to the values in the group without CM disorders (р<0.005) at stages Т1 and Т2. There were no significant intergroup differences in concentrations of ALPBI and DPD throughout the study. Time-related changes in OC, CTTP, and DPD had some intergroup differences: the increase in biomarkers was observed in group 1 considerably later, at stage Т3 (р<0.005), while in group 2, it was observed at stage T2 after sternotomy. Scintigraphy revealed significant intergroup differences in the intensity of RP accumulation in sternal tissue.

Conclusion      The intergroup differences in the content of biomarkers evidenced a disbalance among processes of formation and resorption of bone tissue and delayed remodeling processes in patients with IHD associated with type 2 DM and CM disorders. The study confirmed significance of comprehensive evaluation of time-related changes in markers for bone tissue metabolism and sternal scintigraphy for diagnosis and evaluation of sternal reparative regeneration following sternotomy in patients with IHD associated with type 2 DM and disorders of CM metabolism.

 

Aim To study the effect of various types of respiratory muscle training (RMT) in patients with functional class (FC) II-III chronic heart failure (CHF) and more than 70% preserved diaphragm muscle mass.
Material and methods 53 patients (28 men and 25 women) aged 50-75 years with NYHA FC II-III ischemic heart disease (IHD) and arterial hypertension with more than 70% preserved diaphragm muscle mass of >70% were randomized to one of four RMT types: static loads, dynamic loads, their combination, and breathing without applied resistance as a control. Peak oxygen consumption (VO2 peak) and maximum inspiratory pressure (MIP) were evaluated at baseline and in 6 months.
Results All study groups showed significant improvement of physical endurance indexes compared to baseline values (р<0.05). In pairwise comparison, the groups significantly differed (р<0.01). The greatest improvement was observed for patients of dynamic and combined training groups. Furthermore, in the combined training group, results were significantly higher than in the group of isolated dynamic loads. The most significant (р <0.01), positive changes in the force of inspiratory muscles were observed in groups of dynamic and combined trainings with the best results displayed by patients of the combined training group.
Conclusion With preserving more than 70 % of diaphragm muscle tissue (as determined by MIP >60 cm H2O), a combination of static and dynamic RMT is most effective for patients with FC II-III CHF.

Goal The E / (Ea×Sa) index is an echocardiographic parameter to determine a patient’s left ventricular filling pressure. This study aims to determine the safety and efficacy of the echocardiographic E / (Ea×Sa) index guided diuretic therapy compared to urine output (conventional) guided diuretic treatment.
Material and Methods In this cross-sectional study, patients with heart failure with reduced ejection fraction (HFrEF) who were hospitalized due to acute decompensation episode were consecutively allocated in a 1:1 ratio to monitoring arms. The diuretic dose, which provided 20 % reduction in the E / (Ea×Sa) index value compared to initial value, was determined as adequate dose in echocardiography guided monitoring group. The estimated glomerular filtration rate (eGFR), change in weight, NT pro-BNP level and dyspnea assessment on visual analogue scale (VAS) were analyzed at the end of the monitoring.
Results Although the similar doses of diuretics were used in both groups, the patients with E / (Ea×Sa) index guided strategy had the substantial lower NT pro-BNP level within 72 hours after diuretic administration (2172 vs.2514 pg / mL, p= 0.036). VAS score on dyspnea assessment was significantly better in the patients with E / (Ea×Sa) index guided strategy (52 vs. 65; p= 0.04). And, in term of body weight loss (4.93 vs.5.21 kg, p=0.87) and e-GFR (54.58±8.6 vs. 52.65±9.1 mL / min / 1.73 m2p=0.74) in both groups are associated with similar outcomes. In both groups, there was no worsening renal function and electrolyte imbalance that required stopping or decreasing loop diuretic dosing.
Conclusions The E / (Ea×Sa) index guidance might be a safe strategy for more effective diuretic response that deserves consideration for selected a subgroup of acute decomposed HFrEF patients.

Goal In this study, it was investigated whether the age, creatinine, and ejection fraction (ACEF) score [age (years) / ejection fraction (%) +1 (if creatinine >2 mg / dL)] could predict in-hospital mortality in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and its relationship with the Global Record of Acute Coronary Events (GRACE) risk score were investigated.
Material and methods The study enrolled 658 NSTE-ACS patients from January 2016 to August 2020. The patients were divided into two groups according to the ACEF score with an optimum cut-off value of 1.283 who were divided into two groups according to the ACEF score: low ACEF (≤1.283, n:382) and high ACEF (>1.283, n: 276). The primary outcome of the study was in-hospital all-cause mortality. The primary outcome of the study was in-hospital all-cause mortality. Statistically accuracy was defined with area under the curve by receiver-operating characteristic curve analysis.
Results In total, 13 (4.71 %) patients had in-hospital mortality. The ACEF score was significantly higher in the group with higher mortality than in the group with low mortality (2.1±0.53 vs. 1.34±0.56 p=0.001). The ACEF score was positively correlated with GRACE risk score (r=0.188 p<0.0001). In ROC curve analysis, the AUC of the ACEF score for predicting in-hospital mortality was 0.849 (95 % CI, 0.820 to 0.876; p<0.0001); sensitivity, 92.3 %; specificity, 59.2 %, and the optimum cut-off value was >1.283.
Conclusion The ACEF score presented excellent discrimination in predicting in-hospital mortality. We obtained an easier and more useful result by dividing the ACEF score into two groups instead of three in NSTE-ACS patients. As a simple, useful, and easily applicable risk stratification in the evaluation of an emergency event such as the ACEF score, it can significantly contribute to the identification of patients at high risk.

Aim      To evaluate the effect of the total time of myocardial ischemia on results of the treatment of patients with ST segment elevation acute myocardial infarction (STEMI) who underwent percutaneous coronary interventions (PCI).

Material and methods This study used data from a hospital register for PCI in STEMI from 2006 through 2017. 1649 patients were included. Group 1 consisted of 604 (36.6 %) patients with a total time of myocardial ischemia not exceeding 1880 min; group 2 included 531 (32.2 %) patients with a duration of myocardial ischemia from 180 to 360 min; and group 3 included 514 (31.2 %) patients with a duration of myocardial ischemia longer than 360 min.

Results Mortality was lower in group 1 (2.3 %) than in groups 2 and 3 (6.2 and 7.2 %, respectively; p1–2=0.001; p1–3<0.001; p2–3=0.520). The incidence of major cardiac complications (“adverse cardiac events”, MACE) was lower in group 1 (4.1 %) than in groups 2 and 3 (7.3 and 9.5 %, respectively, p_1–2=0.020; p_1–3<0.001; p_2–3=0.200). The incidence of no-reflow phenomenon was higher in group 3 (9.7 %) than in groups 2 and 3 (4.5 and 5.3 %, respectively (p_1–2=0.539; p_1–3=0.001; p_2–3=0.005). The major factors associated with the increased total time of myocardial ischemia >180 min were age (odd ratio, OR, 1.01 at 95 % confidence interval, CI, 1.0 to 1.02; р=0.044), female gender (OR, 1.64 at 95 % CI 1.26 to 2.13; р<0.001), chronic kidney disease (OR 1.82 at 95 % CI 1.21 to 2.74; р=0.004). Performing prehospital thrombolysis was associated with a decrease in the total time of myocardial ischemia (OR 0.4 at 95 % CI 0.31 to 0.51; р<0.001). A strong direct correlation was observed between the total time of myocardial ischemia and the time from the onset of pain syndrome to hospitalization (r=0.759; р<0.001).

Conclusion      The total time of myocardial ischemia >180 min was associated with increased mortality and development of MACE. The total time of myocardial ischemia > 360 min was associated with increased incidence of the no-reflow phenomenon. The major predictors for the time of myocardial ischemia >180 min included age, female gender, and chronic kidney disease. The use of pharmacoinvasive strategy was associated with an increased number of patients with a total duration of myocardial ischemia <180 min. The contribution of the time of prehospital delay to the total time of myocardial ischemia was greater than the contribution of the “door-to-balloon” time. The time of prehospital delay showed a strong direct correlation with the total time of myocardial ischemia.

 

Aim      To determine diagnostic capabilities of the expanded protocol for stress echocardiography (stress-EchoCG) with comprehensive evaluation of clinical and echocardiographic indexes in differential diagnosis of dyspnea.

Material and methods This study included 243 patients (123 women and 120 men) who were referred to outpatient stress-EchoCG during one calendar month. For 80 patients complaining about shortness of breath, the expanded stress-EchoCG protocol with treadmill exercise was performed. During the exercise, E / e’ and tricuspid regurgitation velocity were determined, and clinical features and possible nature of dyspnea were evaluated.

Results Shortness of breath had an ischemic origin in 17.5 % of 80 patients; 13.8 % had criteria of elevated left ventricular end-diastolic pressure; 17.5 % of patients had clinical signs of bronco-pulmonary pathology; 5.0 % had moderate and severe mitral regurgitation; 20 % displayed signs of chronotropic insufficiency during exercise including on the background of beta-blocker therapy; 15.0 % of patients displayed a hypertensive response to exercise, which was associated with signs of chronotropic insufficiency in 50 % of them; and 1.3 % had signs of hyperventilation syndrome. In addition to diagnosis of transient ischemia, additional information about the nature of shortness of breath was obtained for 72.5 % of patients. Based on results of the test, objective causes for dyspnea were not identified for 10.0 % of patients.

Conclusion      The expanded stress-EchoCG protocol with exercise allows obtaining information about the nature of dyspnea for most patients with shortness of breath of a non-ischemic origin. For this patient category, expanding the stress-EchoCG protocol does not increase duration of the study and is economically beneficial for diagnosis of chronic heart failure and other causes for shortness of breath.

Aim      To compare the antihypertensive effectivity of renal denervation in patients with diabetes mellitus (DM) and associated refractory arterial hypertension (rfAH) (treated with 5 or more classes of antihypertensive drugs, including a thiazide diuretic and a mineralocorticoid receptor antagonist) and uncontrolled resistant AH (ucAH) (treated with 3-4 drugs).

Material and methods  This interventional study with renal denervation included 18 DM patients with rfAH and 40 DM patients with ucAH; 16 and 36 of them, respectively, completed the study in 6 months. At baseline, patients were sex- and age-matched. Study methods included measurement of office blood pressure (BP; systolic/diastolic BP, SBP/DBP); outpatient BP monitoring; evaluation of kidney function (estimated glomerular filtration rate by the CKD-EPI formula); diurnal diuresis volume; diurnal urinary excretion of albumin, potassium and sodium; diurnal excretion of metanephrines and normetanephrines; and plasma levels of glucose and glycated hemoglobin, aldosterone, and active renin. Patients were instructed about maintaining compliance with their antihypertensive and hypoglycemic therapy throughout the study.

Results At baseline, patients of both groups were comparable by BP and major clinical indexes, except for higher values of nocturnal SBP variability (p<0.05) in patients with rfAH. At 6 months following renal denervation, both groups displayed significant decreases in office and average daily SBP and also in the “load” with increased mean diurnal SBP. However, the decrease in average daily SBP was almost 4 times greater in the rfAH group than in the ucAH group ( –19.9 and –5.1 mm Hg, respectively, р=0.02). Moreover, 81 % of patients in the rfAH group responded to the intervention (average daily SBP decrease ≥10 mm Hg) while the number of responders in the ucAH group was considerably smaller (42 %; p=0.02). In patients with rfAH, renal denervation was associated with a significant decrease in pulse BP and nocturnal SBP variability and with the increase in diurnal diuresis. No other alterations were noted in laboratory test results in either group.

Conclusion      DM patients with rfAH may be the best candidates for the procedure of renal denervation.

Takotsubo syndrome (TS) is characterized with a reversible disorder of left ventricular contractility. At present time, it is established that various factors, both psycho-emotional and clinical, can trigger this disease. Notably, according to current opinions, coronary atherosclerosis may accompany TS and not be its exclusion criteria as it was previously thought. This article presents a clinical case of TS relapse in a female patient aged 83 years at 5 years following the first episode associated with progression of coronary atherosclerosis.

Despite successful and timely revascularization of the infarct-related artery, myocardial tissue remains underperfused in some patients. This condition is known as the no-reflow phenomenon, which is associated with a worse prognosis. The first part of the systematic review on no-reflow focuses on description of the no-reflow pathogenesis and predictors. This phenomenon has a complicated, multifactorial pathogenesis, including distal embolization, ischemic injury, reperfusion injury, and a component of individual predisposition. Meanwhile, this phenomenon undergoes spontaneous regression in some patients. Several studies have demonstrated the role of definite biomarkers and clinical indexes as risk predictors for no-reflow. The significance of each pathogenetic component of no-reflow is suggested to be different in different patients, which may warrant an individualized approach in the treatment.

 

This review focuses on major causes and risk factors for death of patients with atrial fibrillation (AF). The authors analyzed current therapeutic strategies for managing patients with AF with respect of their effects on prediction and mortality. Special attention is paid to the strategy of rhythm control and the clinical significance of catheter ablation in the treatment of patients with AF and heart failure.