The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased in recent years. The leading cause of death of these patients is ischemia/reperfusion (I/R) cardiac injury. It is quite obvious that there is an urgent need to create new drugs for the treatment of STEMI based on knowledge about the pathogenesis of I/R cardiac injury, in particular, based on knowledge about the molecular mechanism of ferroptosis. In this study, it was demonstrated that ferroptosis is involved in the development of I/R cardiac injury, antitumor drug-induced cardiomyopathy, diabetic cardiomyopathy, septic cardiomyopathy, and inflammation. There is indirect evidence that ferroptosis participates in stress-induced cardiac injury. The activation of AMPK, PKC, ERK1/2, PI3K, and Akt prevents myocardial ferroptosis. The inhibition of HO-1 alleviates myocardial ferroptosis. The roles of GSK-3β and NOS in the regulation of ferroptosis require further study. The stimulation of Nrf2, STAT3 prevents ferroptosis. The activation of TLR4 and NF-κB promotes ferroptosis of cardiomyocytes. MiR-450b-5p and miR-210-3p can increase the tolerance of cardiomyocytes to hypoxia/reoxygenation through the inhibition of ferroptosis. Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p and miR-15a-5p can aggravate myocardial ferroptosis.

Aim. Evaluate the one­year results and clinical outcomes of a multi­center randomized clinical trial FRIDOM1.Material and methods. The study FRIDOM1 was conducted in 11 clinical centers of the Russian Federation in the period 2014­2016. The study included 382 patients with acute ST­elevated myocardial infarction (STEMI), who were randomly divided into the Fortelyzin® and Metalyse®. Thrombolysis was accompanied by anticoagulant and dual antiplatelet therapy followed by percutaneous coronary intervention (PCI). One­year patient status, all­cause mortality, including cardiovascular diseases (CVD), hospitalization, and one­year survival were assessed by telephone contact.Results. The one­year patient status was determined in 186 out of 191 (97,4%) in the Fortelyzin® group and in 185 out of 191 (96,9%) patients in the Metalyse® group. One­year all­cause mortality was 5,9% and 6,5% in the Fortelyzin® and Metalyse® groups, respectively (p=0,83; OR 0,91; 95% CI — 0,42­1,98). One­year mortality from CVD in the Fortelyzin® group is 5,4%, in the Metalyse® group — 6,5% (p=0,67; OR 0,83; 95% CI — 0,37­1,83). All­cause mortality between 30 days and 1 year in the Fortelyzin® group was in 2,2% of patients, CVD — in 1,6%, in the group of Metalise® mortality was in 2,7% of patients (all — CVD). One­year survival was 94,1% and 93,5% in the Fortelyzin® and Metalyse® groups, respectively.Conclusion. The one­year results of the FRIDOM1 study showed the efficacy and safety of a single bolus administration of Fortelyzin® as part of a pharmaco­invasive strategy for treating patients with STEMI, as well as clinical outcomes that are comparable with Metalyse®, including high survival rates and low CVD mortality.

Aim. To analyze the long-term effect of microvascular injury various types on the structural and functional parameters of the left ventricle assessed by echocardiography in patients with primary ST-segment elevation myocardial infarction (STEMI).Materials and methods. The study included 60 patients with primary STEMI admitted within the first 12 hours after the onset of disease who underwent stenting of the infarct-associated coronary artery. Each patient included in the study underwent CMR imaging on the second day post-STEMI. MVO and IMH were assessed using late gadolinium enhancement and T2-weighted CMR imaging. Subsequently, all patients underwent the standard echocardiographic protocol on the 7th day and 3 months after MI. Results. We divided all patients into 4 groups: the 1st group didn’t have any phenomena of IMH and MVO, the 2nd group had only MVO, patients of the 3rd group had only IMH and in the 4th group there was a combination of MVO and IMH. LV ejection fraction was significantly lower in patients with combination of MVO and IMH, if compared to those without it. Correlation analysis showed a moderate inverse correlation between the MVO area and LV contractile function: the larger the area, the lower the LVEF (R=-0,60; p=0,000002).Conclusions. The combination of IMH and MVO is a predictor of a reduction in LVEF and an increase of volumetric measurements within 3 months after MI. In comparison with patients without microvascular injury isolated MVO is associated with lower LVEF. The size of MVO is directly correlated with the LV contractile function decrease. Isolated IMH was not associated with deterioration of left ventricular function.

Aim.To study the effectiveness of Fortelyzin® in subgroups with different body weights in patients with ST-segment elevation acute myocardial infarction (STEMI) in the FRIDOM1 study and real clinical practice.Material and methods.Fortelyzin® was administered in a single-bolus dose of 15 mg over 10 seconds, regardless of the body weight of patients. Metalyse® was administered in a single-bolus dose of 30-50 mg over 10 seconds, depending on body weight. The one-year results of the FRIDOM1 study were evaluated by the clinical centers using telephone contact. Monitoring of Fortelyzin® use was carried out by inpatient physicians, emergency doctors and paramedics by filling out a monitoring sheet in the period from June 2013 to December 2021 in 19243 patients with STEMI.Results.In the FRIDOM1 study, the distribution of patients depending on body weight in the Fortelyzin® (n=190) and Metalyse® (n=191) drug groups was as follows: up to 60 kg — 4 people each (p=1,00); from 60 to 70 kg — 21 and 23 (p=0,87); from 70 to 80 kg — 39 and 43 (p=0,71), from 80 to 90 kg — 63 and 47 (p=0,07); from 90 to 100 kg — 30 and 41 (p=0,19); over 100 kg — 33 people (p=1,00) in each group. The effectiveness of thrombolysis according to electrocardiographic (ECG) data in the Fortelyzin® and Metalyse® groups was as follows: up to 60 kg — 75% each (p=1,00); from 60 to 70 kg — 76% vs 83% (p=0,72); from 70 to 80 kg — 82% vs 86% (p=0,76); from 80 to 90 kg — 81% vs 77% (p=0,64); from 90 to 100 kg — 80% vs 81% (p=1,00); over 100 kg — 79% vs 76% (p=1,00); in total — 80% vs 80% (p=0,87). The effectiveness of thrombolysis according to coronary angiography (CAG) (TIMI 2-3) in the Fortelyzin® and Metalyse® groups was as follows: up to 60 kg — 100% vs 50% (p=0,43); from 60 to 70 kg — 81% vs 67% (p=0,48); from 70 to 80 kg — 74% vs 84% (p=0,41); from 80 to 90 kg — 70% vs 72% (p=1,00); from 90 to 100 kg — 67% vs 66% (p=1,00); over 100 kg — 58% vs 64% (p=0,80); in total — 70% vs 71% (p=0,76). The one-year survival rate in the FRIDOM1 study in the Fortelyzin® and Metalyse® groups was 94% (p=0,91). The administration of Fortelyzin® in patients with STEMI caused blood flow restoration according to ECG data in 14624 of 19243 patients (76%), while according to CAG (TIMI 2-3) — in 3422 of 4805 patients (71%). Inhospital mortality was 5% (n=962), while intracranial hemorrhage developed in 0,5% (n=92).Conclusion.The use of Fortelyzin® in the FRIDOM1 study and in real clinical practice in a single-bolus (10 sec) dose of 15 mg in patients with STEMI with any body weight showed its high efficacy and safety, including at the prehospital stage.

Aim. The aim of this study was to evaluate the prevalence of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH), their combination, and relationship to the clinical and anamnestic characteristics in patients with primary STEMI after coronary reperfusion.Material and Methods. A single-center observational cohort study comprised a total of 60 patients with primary STEMI and successful coronary reperfusion within 12 hours of the onset of symptoms. All patients were studied using a contrast-enhanced cardiac magnetic resonance imaging (CE-MRI) at day 2 after STEMI. The study protocol was registered on ClinicalTrials.gov (Identifier: NCT03677466).Results. The total occurrence rate of MVO and IMH phenomena was 68.3% including MVO only in 17% of patients, IMH only in 15% of cases, combination of MVO and IMH in 36% cases, and without a microvascular myocardial injury in 32% of cases. The patients with MVO only and combination of MVO and IMH experienced a longer time of ischemia versus patients without these conditions: 205 (140–227) and 193 (95–400) versus 130 (91–160) min (p = 0.049). On the contrary, the time of myocardial ischemia did not differ between patients with IMH only (113 min) and patients without it. Then, patients were assigned to the group of pharmaco-invasive strategy of coronary reperfusion (PIS) (n = 39) and the group of primary percutaneous intervention (PPCI) (n = 21). The incidence of MVO only and IMH only was equal in PIS and PPCI groups: 17.9% versus 14.2% and 12.8% versus 19.1% in PIS and PPCI groups, respectively. The tendency to a decrease in the incidence of combined MVO and IMH was observed in PIS group compared to PPCI group: 30.8% versus 47.6% (p = 0.09).Conclusion. The combination of MVO and IMH phenomena in patients with primary STEMI after coronary reperfusion developed more often than each of these phenomena separately. The development of MVO only and combination of MVO and IMH was associated with a longer duration of myocardial ischemia. A total frequency of combination of MVO and IMH phenomena in patients with primary STEMI after coronary reperfusion was as high as 68.3%. Combination of these phenomena developed more frequently than each of them separately: 36% versus 17% (MVO only) and 15% (IMH only). No difference was observed in the duration of myocardial ischemia between the groups with MVO only and without it. The thrombolysis did not increase the occurrence of IMH in PIS group compared with PPCI group. There was a tendency to a decrease in the incidence of combination of MVO and IMH in PIS group compared to PPCI group: 30.8 versus 47.6% (р = 0.09).

Microvascular obstruction (MVO) of coronary arteries increases the mortality rate and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). According to preliminary data platelets, inflammation, Ca2+ overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. Many questions related to the pathogenesis of MVO remain unanswered. The role of endothelial cell damage in the formation of MVO in patients with AMI and PCI is unknown. It is unclear whether nitric oxide (NO) production reduces or decreases sensitivity of smooth muscle cells of coronary arteries to NO in patients with MVO. It was obtained only indirect evidence on the involvement of inflammation in the development of MVO. The role of ROS in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied.The significance of thromboxane A, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is unknown before. It was not obtained conclusive evidence on the involvement of coronary artery spasm in the development of MVO. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI was not performed. It is not clear whether endogenous adrenaline exacerbates MVO or, conversely, prevents MVO.