[Ferroptosis-associated lesion as a potential target for cardiovascular disease: A review].

Cell death is an important feature of the development of multicellular organisms, a critical factor in the occurrence of cardiovascular diseases. Understanding the mechanisms that control cell death is crucial to determine its role in the development of the pathological process. However, the most well-known types of cell death cannot fully explain the pathophysiology of heart disease. Understanding how cardiomyocytes die and why their regeneration is limited is an important area of research. Ferroptosis is an iron-dependent cell death that differs from apoptosis, necrosis, autophagy, and other forms of cell death in terms of morphology, metabolism, and protein expression. Ferroptotic cell death is characterized by the accumulation of reactive oxygen species resulting from lipid peroxidation and subsequent oxidative stress, which can be prevented by iron chelates (eg, deferoxamine) and small lipophilic antioxidants (eg, ferrostatin, liproхstatin). In recent years, many studies have been carried out on ferroptosis in the context of the development of atherosclerosis, myocardial infarction, heart failure, and other diseases. In addition to cardiovascular diseases, the review also presents data on the role of ferroptosis in the development of other socially significant diseases, such as COVID-19, chronic obstructive pulmonary disease. With the study of ferroptosis, it turned out that ferroptosis participates in the development of bacterial infection associated with the persistence in the host body of Pseudomonas aeruginosa. The review summarizes the recent advances in the study of ferroptosis, characterizing this type of cell death as a novel therapeutic target.

Arterial Hypertension and Severe COVID-19 in Hospitalized Patients: Data from a Cohort Study

Aim. To assess the association of hypertension with the severe forms and fatal outcomes of Coronavirus disease 2019 (COVID-19). Material and Methods. This retrospective cohort study involved adult patients (>= 18 years old), admitted to the University hospital No 4 of Sechenov University (Moscow, Russia) between 08 April 2020 and 19 November 2020 with clinically diagnosed or laboratory -confirmed COVID-19. The cohort included 1637 patients. The primary outcome was all-cause in-hospital mortality. The secondary out-comes included intensive care unit admission (ICU) and invasive ventilation. Multiple logistic regression was performed to assess the in-dependent association between risk factors and endpoints. Results. A total of 1637 patients were included in the study. 51.80% (n=848) of the subjects were males. The median age was 59.0 (48.0;70.0) years and 55.90% (n=915) had pre-existing diagnosis of hypertension. Patients with hypertension had significantly more severe lung injury based on chest CT scan findings as well as lower oxygen saturation (SpO(2)). More of them were admitted to ICU and placed on invasive ventilation. The hypertension group also had higher mortality. Age, hypertension, glucose, C-reactive protein and decreased platelet count were independently associated with mortality, hypertension having the strongest association (OR 1.827, 95% CI 1.174-2.846, p=0.008). Age, hypertension, neutrophil count, platelet count, glucose, and CRP were independently associated with ICU admission, with hypertension having the strongest association (OR 1.595, 95% CI 1.178-2.158, p=0.002). Age, hypertension, glucose, CRP and decreased platelet count were independently associated with invasive ventilation, with hypertension having the strongest association (OR 1.703, 95% CI 1.151-2.519, p=0.008).Based on the multiple logistic regression models, odds of death, ICU admission, and invasive ventilation were higher in the hypertension group as compared to the group without hyperten-sion. Conclusion. Hypertension can be an independent predictor of severe COVID-19 and adverse outcomes, namely death, ICU admission, and invasive ventilation in hospitalized patients.

Arterial Hypertension and Severe COVID-19 in Hospitalized Patients: Data from a Cohort Study

Aim. To assess the association of hypertension with the severe forms and fatal outcomes of Coronavirus disease 2019 (COVID-19). Material and Methods. This retrospective cohort study involved adult patients (>=18 years old), admitted to the University hospital 4 of Sechenov University (Moscow, Russia) between 08 April 2020 and 19 November 2020 with clinically diagnosed or laboratory-confirmed COVID-19. The cohort included 1637 patients. The primary outcome was all-cause in-hospital mortality. The secondary outcomes included intensive care unit admission (ICU) and invasive ventilation. Multiple logistic regression was performed to assess the independent association between risk factors and endpoints. Results. A total of 1637 patients were included in the study. 51.80% (n=848) of the subjects were males. The median age was 59.0 (48.0;70.0) years and 55.90% (n=915) had pre-existing diagnosis of hypertension. Patients with hypertension had significantly more severe lung injury based on chest CT scan findings as well as lower oxygen saturation (SpO2). More of them were admitted to ICU and placed on invasive ventilation. The hypertension group also had higher mortality. Age, hypertension, glucose, C-reactive protein and decreased platelet count were independently associated with mortality, hypertension having the strongest association (OR 1.827, 95% CI 1.174-2.846, p=0.008). Age, hypertension, neutrophil count, platelet count, glucose, and CRP were independently associated with ICU admission, with hypertension having the strongest association (OR 1.595, 95% CI 1.178-2.158, p=0.002). Age, hypertension, glucose, CRP and decreased platelet count were independently associated with invasive ventilation, with hypertension having the strongest association (OR 1.703, 95% CI 1.151-2.519, p=0.008).Based on the multiple logistic regression models, odds of death, ICU admission, and invasive ventilation were higher in the hypertension group as compared to the group without hypertension. Conclusion. Hypertension can be an independent predictor of severe COVID-19 and adverse outcomes, namely death, ICU admission, and invasive ventilation in hospitalized patients.Copyright © 2023 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

Arterial Hypertension and Severe COVID-19 in Hospitalized Patients: Data from a Cohort Study.

Aim. To assess the association of hypertension with the severe forms and fatal outcomes of Coronavirus disease 2019 (COVID-19). Material and Methods. This retrospective cohort study involved adult patients (>=18 years old), admitted to the University hospital 4 of Sechenov University (Moscow, Russia) between 08 April 2020 and 19 November 2020 with clinically diagnosed or laboratory-confirmed COVID-19. The cohort included 1637 patients. The primary outcome was all-cause in-hospital mortality. The secondary outcomes included intensive care unit admission (ICU) and invasive ventilation. Multiple logistic regression was performed to assess the independent association between risk factors and endpoints. Results. A total of 1637 patients were included in the study. 51.80% (n=848) of the subjects were males. The median age was 59.0 (48.0;70.0) years and 55.90% (n=915) had pre-existing diagnosis of hypertension. Patients with hypertension had significantly more severe lung injury based on chest CT scan findings as well as lower oxygen saturation (SpO2). More of them were admitted to ICU and placed on invasive ventilation. The hypertension group also had higher mortality. Age, hypertension, glucose, C-reactive protein and decreased platelet count were independently associated with mortality, hypertension having the strongest association (OR 1.827, 95% CI 1.174-2.846, p=0.008). Age, hypertension, neutrophil count, platelet count, glucose, and CRP were independently associated with ICU admission, with hypertension having the strongest association (OR 1.595, 95% CI 1.178-2.158, p=0.002). Age, hypertension, glucose, CRP and decreased platelet count were independently associated with invasive ventilation, with hypertension having the strongest association (OR 1.703, 95% CI 1.151-2.519, p=0.008).Based on the multiple logistic regression models, odds of death, ICU admission, and invasive ventilation were higher in the hypertension group as compared to the group without hypertension. Conclusion. Hypertension can be an independent predictor of severe COVID-19 and adverse outcomes, namely death, ICU admission, and invasive ventilation in hospitalized patients.Copyright © 2023 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

Effect of spironolactone therapy on the activity of the matrix metalloproteinase system in patients with heart failure after COVID-19

Aim. To assess the change in the activity of the matrix metalloproteinase (MMP) system after 6-month spironolactone therapy in patients with heart failure (HF) with preserved (HFpEF) and mildly reduced ejection fraction (HFmrEF) after coronavirus disease 2019 (COVID-19). Material and methods. The study included 90 patients treated at the University Clinical Hospital 4 of the I. M. Sechenov First Moscow State Medical University with a laboratory-confirmed COVID-19. There were following inclusion criteria: age of 18-85 years;the presence of HFpEF and HFmrEF. The patients were randomized into two groups: group I (n=60) - patients with 6-month spironolactone therapy (25 mg/day) in addition to the standard therapy for HF, spironolactone was taken at a dose of 25 mg/day;Group II (comparison group, n=30) - patients who received standard therapy without spironolactone. All patients were determined plasma MMP concentrations. Results. There were no significant differences in the levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) between the groups when included in the study. A repeated investigation revealed a significant decrease in the concentrations of MMP-9 and TIMP-1 only in group I. In patients of group II, there were no significant changes in the plasma concentrations of MMP-9 and TIMP-1. The MMP-9/TIMP-1 ratio during the initial examination of patients did not have significant differences. After 6-months therapy, a significant decrease in the ratio of MMP-9/TIMP-1 was observed only in patients taking spironolactone. Conclusion. The results obtained confirm a significant decrease in MMP system activity after 6-month spironolactone therapy in patients with HFpEF and HFmrEF after COVID-19. The described antifibrotic effects of spironolactone make it possible to recommend the use of this drug in this category of patients to reduce the negative effect of MMPs on cardiovascular system. Copyright © 2022 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved.

Predictors of atrial fibrillation in patients with COVID-19

Early diagnosis of atrial fibrillation (AF) predictors in coronavirus disease 2019 (COVID-19) and the appointment of additional therapy to prevent arrhythmias will improve the prognosis of patients. Aim. To identify predictors of AF in patients with COVID-19. Material and methods. This retrospective study included 1473 patients hospitalized with COVID-19. Depending on AF occurrence, the patients were divided into 2 groups as follows: group I included 95 patients with AF episodes during hospitalization;group II consisted of 1378 patients who did not have AF during hospitalization. All patients underwent a complete blood count and urine tests, a biochemical and coagulation blood tests, 12-lead electrocardiography, chest computed tomography (CT), and echocardiography. Results. Chest CT found that lung tissue involvement in patients of group I was significantly greater than in group II (p<0,05). The number of patients with significant lung involvement >50% (CT-3 and CT-4) was significantly higher in the AF group than in the control group. The average room air oxygen saturation upon admission to the hospital were significantly lower in patients with AF than in the comparison group (p<0,05). Multivariate analysis showed that following factors have a significant effect on AF development in COVID-19 patients: age >60 years, hypertension, coronary artery disease, heart failure, increased left atrial volume, large lung tissue involvement, and increased interleukin-6 level. Conclusion. There are two following groups of predictors initiating AF in COVID-19: generally known (older age, cardiovascular disease, increased left atrial volume) and those that determine the severe COVID-19 course (large lung damage and high interleukin-6 levels).

Damage to the Cardiovascular System in Patients with SARS-CoV-2 Coronavirus Infection. Part 2: Correction of Myocardial Systolic Dysfunction

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. © 2022 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

Damage to the Cardiovascular System in Patients with SARS-CoV-2 Coronavirus Infection. Part 1: Predictors of the Development of an Unfavorable Prognosis

Aim. To evaluate the effect of sinus tachycardia and reduced left ventricular ejection fraction (LVEF) on the prognosis of patients with a verified diagnosis of a new coronavirus infection SARS-CoV-2. Material and methods. The study included 1,637 patients with a verified diagnosis of a new coronavirus infection SARS-CoV-2. The average age of the patients was 58.8±16.1 years. More than half of the patients admitted to the hospital had a history of cardiovascular diseases: hypertension was diagnosed in 915 (56%) patients, coronary artery disease – in 563 (34%), chronic heart failure – in 410 (25%). 294 (17.9%) patients suffered from diabetes mellitus. The unfavorable course of new coronavirus infection was assessed by the fact of being in the intensive care unit (ICU), the use of mechanical ventilation and death. Results. An unfavorable course of coronavirus infection was observed in 160 (9.8%) patients. Statistical analysis revealed that 341 (20.8%) patients with COVID-19 were diagnosed with sinus tachycardia, which required the appointment of pulse-reducing therapy. The occurrence of sinus tachycardia in patients with COVID-19 significantly increased the risk of death (odds ratio [OR] 1.248, confidence interval [CI] 1.038-1.499, p=0.018), increased the likelihood of mechanical ventilation use (OR 1.451, CI 1.168-1.803, p<0.001) and stay in the ICU (OR 1.440, CI 1.166-1.778, p<0.001). In 97 (5.9%) patients during hospital stay during echocardiography, a decrease in LVEF of less than 50% was diagnosed. A decrease in myocardial contractile function in patients with COVID-19 with high reliability increased the risk of death (OR 1.744, CI 1.348-2.256, p<0.001), increased the likelihood of using the mechanical ventilation (OR 1.372, CI 1.047-1.797, p=0.022) and stay in the ICU (OR 1.360, CI 1.077-1.716, p=0.010). Conclusion. The appearance of sinus tachycardia and reduced LVEF are in dependent predictors of the unfavorable course of COVID-19 in relation to factors such as death, the use of mechanical ventilation and the stay of patients in the ICU. Early pharmacological correction of cardiovascular lesions should be one of the goals of the management theese patients. © 2021 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

[New clinical opportunities for mineralocorticoid receptor antagonists: focus on antifibrotic effects].

Mineralocorticoid receptor antagonists have been successfully used for many years to treat patients with primary hyperaldosteronism, refractory arterial hypertension and chronic heart failure. The increased interest in this drug in recent years is due to new information about its antifibrotic and antiproliferative effects, both cardiac and extracardiac. The article also discusses the possibility of using spironolactone in patients with the new coronavirus infection SARS-CoV-2 (COVID-19).

[Tactics of antihypertensive therapy during COVID-19 pandemic].

Results of foreign and Russian studies indicate a higher mortality rate of patients with concomitant cardiovascular diseases (CVD) due to the new coronavirus infection COVID-19. It has been proven that arterial hypertension, as one of the significant risk factors for the development of concomitant cardiovascular diseases, is associated with a more severe prognosis of COVID-19. This article presents the results of modern studies and large meta-analyzes of necessity and safety of the use of blockers of the renin-angiotensin-aldosterone system in patients with arterial hypertension and COVID-19. The data of studies show that an angiotensin-converting enzyme inhibitor (ACE inhibitor) and a thiazide-like diuretic is a pathogenetically rational combination. It realizes various ways of lowering blood pressure by reducing the activity of the renin-angiotensin-aldosterone system, which is achieved by using an ACE inhibitor, and natriuresis due to diuretics. As an example, a highly effective fixed combination of drugs is considered, characterized by good tolerance, which consists of an ACE inhibitor lisinopril and a thiazide-like diuretic indapamide of prolonged action. The authors expressed the opinion that the appointment of the fixed combination drug Diroton Plus (Gedeon Richter) will contribute to effective control of blood pressure and organoprotection in conditions of increased thrombogenic and prooxidative potential, characteristic of COVID-19 both in the acute stage and within the post-COVID Syndrome.

Post-COVID Syndrome and Tachycardia: Theoretical Base and Treatment Experience

The coronavirus pandemic showed not only an increase in levels of excess morbidity and mortality in the acute phase, but also persisting symptoms 4 weeks after the onset of the disease. A review of international studies on the prevalence and diversity of the manifestations of postcoid syndrome is presented. The data on such a manifestation of post-COVID syndrome as postural orthostatic tachycardia syndrome (POTS) are accumulating. Pathogenetic mechanisms, modern diagnostic criteria and research data on the prevalence of this syndrome are presented in the article. The Canadian Cardiovascular Society has proposed medications as a treatment for POTS, including the sinus node If channel inhibitor ivabradine. Data from several studies showing the effectiveness of this drug for POTS, including after suffering COVID-19, are presented in the article. Clinical data on the prevalence of tachycardia among patients admitted to the Sechenov University hospital are presented. About 18% of patients with hypertension and 21% of patients with normal blood pressure had a high heart rate. A clinical example of the use of ivabradine in a patient after a coronavirus infection is presented. Drug interactions and individual tolerance of ivabradine in patients after coronavirus infection are being discussed. The authors put forward the hypothesis about the further prospect of using ivabradine in the treatment of clinical manifestations of postcoid syndrome on the basis of literature data and their own experience.

The Importance of Antihypertensive and Lipid-Lowering Therapy in the Treatment of Patients with a New Coronavirus Infection COVID-19

At the end of 2020, a new term "post-COVID-19 syndrome" appeared in the medical community. The prevalence of this syndrome reaches more than 30% among patients who have had COVID-19, and its duration can vary from 12 weeks to 6 months. One of the most severe consequences of COVID19 is the defeat of the cardiovascular system, which has a variety of mechanisms: dysregulation of the renin-angiotensin-aldosterone system;pathological systemic inflammatory response;direct action of the virus on the myocardium with the development of myocarditis;respiratory failure with hypoxia, leading to damage to cardiomyocytes;microvascular damage due to hypoperfusion, increased vascular permeability, angiospasm and the direct damaging effect of the virus on the endothelium of the coronary arteries;thrombotic complications due to the procoagulant and prothrombogenic effect of systemic inflammation. One of the most promising directions in the treatment and prevention of damage to the cardiovascular system in patients with hypertension who have undergone COVID-19 is the appointment of antihypertensive drugs that have the most pronounced organoprotective properties together with statins. The single pill combination of lisinopril, amlodipine and rosuvastatin is an effective drug that allows achieving not only adequate hypotensive and lipid-lowering effects, but also due to its pronounced organoprotective properties, to expect a reduction in cardiovascular risk and complications in patients who have suffered a new coronavirus infection caused by the SARS-CoV-2 virus.