Background. Oxidative stress is crucial in developing broad spectrum of diseases, including atherosclerosis and related life-threatening conditions, such as acute coronary syndrome (ACS) mainly caused by atherosclerotic plaque vulnerability. Objective. To clarify the relation between oxidative stress and plaque instability we decided to compare oxidative profiles of patients with acute coronary syndrome (ACS) and with chronic coronary syndrome (CCS), evaluated at admission to the coronary care unit (CCU) of LTD Clinic-LJ (Kutaisi, Georgia) in April 2018 - June 2019, who underwent successful primary percutaneous coronary intervention (PCI). Methods. 191 patients were enrolled (100 patients with ACS in Group 1 and 91 patients with CCS in Group 2) into the study. Using the CR3000 FORM PLUS (Callegari Srl, Catellani Group, Italy) – Callegari Point of Care instrument we evaluated free oxygen radical test (FORT), free oxygen radicals defense (FORD), calculated REDOX Index and the overall Profile of oxidative stress. Results. The mean/median concentration of Free Oxygen Radicals was significantly higher in the patients with ACS (404.37±9.83 Fort units/2.36 mmol/l H2O2 eq. vs 282.34±9.83 Fort units/2.36 mmol/l H2O2 eq., p<0.0001). Significant correlation was found between advanced oxidative stress and acute coronary syndrome (OR 14.42 95% CI (7.08-29.4), RR 3.26 95% CI (2.31-4.60) with high diagnostic characteristics (sensitivity of 82% and specificity of 92.3%; positive predictive value of 92% and positive likelihood ratio of 11). Conclusion. Oxidative stress is crucial in life-threatening acute coronary events. Measurement of overall oxidative stress profile, as a surrogate of plaque instability and rupture predictor, could help the clinicians in risk stratification and prevention of acute coronary syndrome (ACS).

Since the establishment of the anthracycline drugs cardiotoxigenic effect, the most widely accepted mechanistic base for their iatrogenic cardiotoxicity was connected with excessive and inadequate intensification of LPO. However, ineffectiveness of the antioxidant and multivitamin regimens of cardio-protection caused the necessity of finding new pathogenic targets, exposure to which will prevent the development of cardiovascular symptoms. Such a target became the nuclear topoisomerases, the study results of which served as the foundation for the creation of dexrazoxan, the only drug with this regard approved by the FDA. However, our interest was attracted towards the mitochondrial topoisomerases, since the integrity of the mitochondrial apparatus of cardiomyocytes is the basic link in maintaining the physiological morpho-functional balance of cardiomyocytes. At the same time, it is established that in the cell doxorubicin is predominantly accumulated in the mitochondria, which also makes emphasizes onto the prospects of studying this issue. Purpose Purpose of the study was to investigate the influence of AC mode of chemotherapy (adriamicin (doxorubicin) + cyclophosphomide) on the mitochondrial topoisomerases levels. Methods 60 inbred mice of the C57BL/6J line with genotype a,H-2b were used. The experimental animals were divided into 2 groups: in the first group polychemotherapy in AC mode was applied; in the second group (placebo group) saline solution was used. Doxorubicin (Sigma Aldrich) was administered at a dose of 4 mg/kg and cyclophosphamid (Sigma Aldrich) at a dose of 2 mg/kg were administered intravenously. There were 4 courses conducted with the intervals of 21 days between them. The study results were recorded in 6 days after the last cycle of chemotherapy. The total duration of experiment was 90 days. The following types of topoisomerases have been studied: Top2β, Top3α, and Top1mt. Results The results of the first group showed a decrease in the Top2β level by 2.4±0.4%, Top3α - by 0.7±0.5, and Top1mt - by 49.5±11.7% (p=0.05). When analyzing the results of the second group no statistically significant changes were recorded. Conclusion The fact of AC mode of chemotherapy administered should be taken as a predictor of destabilization of the mitochondrial topoisomerases signaling, in particular of the Top1mt, which in turn, causes the development of mitochondrial dysfunction and results the energy imbalance in cardiomyocytes. Funding Acknowledgement Type of funding source: None

The goal of training competitive athletes is to provide training loads that will improve performance. When prolonged, excessive training occurs concurrent with other stressors and insufficient recovery, performance decrement can result first in functional overreaching (FO), then extreme overreaching or non-functional overreaching (NFO) and overtraining. Chronic maladaptations may lead then to the overtraining syndrome (OTS). As it is possible to recover from functional overreaching within a period of 2 weeks, the recovery from NFO needs several weeks or even months. Athletes who suffer from OTS may need months or even years to completely recover (1). Early diagnostic of overreaching is of high importance for prevention of overtraining as well as for interruption of progression of NFO/OTS. The purpose of the study was detection of nonfunctional overreaching and overtraining with use of contemporary diagnostic criteria. Diagnosis of OTS was based on the checklist provided by the consensus statement of the European College of Sports Science (ECSS) and the American College of Sports Medicine (ACSM) (3). Examination of 348 high level athletes revealed 43 subjects with NFO/OTS, among them 37 with NFO and 6 athletes with OTS. Prevalence of NFO and OTS was seen in sporting disciplines with mixed high intensity workload-27(62,8%) NFO and 4 (9,3%) OTS, particularly, majority of NFO/OTS was revealed in wrestling: NFO – 19 (44,2%) and OTS – 4 (9,3%). Checklist criteria elaborated by ECSS and ACSM is efficient and flexible tool for diagnosing overreaching and overtraining in athletes. Most frequently NFO/OTS is seen in wrestling, which needs further investigation and regular medical monitoring.

BackgroundA variety of cardiovascular abnormalities have been found to be responsible for sudden cardiac death(SCD) in competitive athletes. The lesions responsible for athletic field deaths differ with regard to age and vast majority of SCD occur in athletes aged <18 yrs. Appropriate pre-participation screening (PPS) of young competitive athletes can reduce their risk for SCD.ObjectiveTo analyse cardiovascular findings obtained in the pre-participation screening of elite Georgian adolescent athletes.DesignObservational follow-up study.SettingSports Medicine and Rehabilitation Clinical Centre.Patients227 asymptomatic elite adolescent athletes (83% males), age 15,4±1,6 years, representatives of national teams of 9 sporting disciplines.InterventionsThe participants underwent cardiovascular(CV) evaluation with medical history, physical examination, 12-lead resting and exercise ECG, and transthoracic echocardiography (TTE) in 2013–2015.Main Outcome MeasurementsThe participants were followed prospectively until July 2015 with respect to clinically significant cardiovascular abnormalities, and until July 2016 with respect to safe return to sport.ResultsResting ECG revealed common/training–related ECG alterations in 70 (31%) athletes, as well as uncommon/training-unrelated changes in 5 (2,2%). TTE revealed mitral valve prolapse in 8(3,5%) athletes, bicuspid aortic valve in 1(0,4%), and signs consistent with anomalous origin of left coronary artery from the pulmonary artery(ALCAPA) in 1 (0,4%) athlete. Stress test revealed decreased exercise tolerance and negative T-waves in V4-V6 in this athlete. Athlete was directed to further CV investigation and CT angiography led to the diagnosis of ALCAPA. Coronary artery bypass grafting was performed. After treatment athlete underwent cardiac rehabilitation program and risk-stratification before entering sports activity. As subendocardial ischemic pattern still existed, the athlete was advised against current participation in competitive sports. Follow-up over a longer period has been planned.ConclusionsPPS is significant tool to identify adolescent athletes at risk for exercise-induced SCD. As coronary anomalies are among the common reasons for SCD in young athletes, timely identification and appropriate clinical management, including considerations regarding safe return to sport are necessary.

BackgroundThere are a large number of studies which have focused on left ventricular (LV) structural and functional characteristics, however insufficient data exist concerning right heart response to exercise in elite athletes of different sporting disciplines.ObjectiveTo investigate right ventricular (RV) dimensions and function in top-level athletes.DesignRetrospective study.SettingSports Medicine Clinical Centre.Participants124 top-level male athletes (18 cyclists, 62 football and 21 basketball players, 23 wrestlers) and 57 age-matched healthy sedentary controls were studied.All subjects were evaluated with 2D, spectral conventional, and tissue Doppler echocardiography. According to the guidelines of American Society of Echocardiography (ASE), RV subcostal wall thickness, RV diameters (RVD1, RVD2, RVD3, RVOT-Prox, RVOT-Distal) indexed by BSA, and functional parameters (TAPSE, FAC, TD MPI, E/A, E/E') were evaluated.Main outcome measurementsAthletes of various sport disciplines with respect to RV remodeling.ResultsMorphologic parameters in most of the athletes and in all controls were within normal limits. Increased RV dimensions were found in 43(35%) athletes. RV wall thickness (3,82±0,71 vs. 3,51±0,32 mm) and RV diameters were significantly greater in athletes than in controls (P<.001). Most of the RV parameters in athletes were within the range of Mean and Upper Reference Values (URV), however RVD1 in 34 (27%) and RVD2 in 22 (18%) athletes exceeded URV by ASE criteria. By sporting disciplines RVD1 exceeded URV in 39% cyclists, 25% basketball players, 23% football players, 22% wrestlers. Interestingly, less than half of these athletes (47%) exhibited concomitant LV enlargement. RV functional parameters were in normal limits in athletes as in controls and did not differ (P>.20).ConclusionsIn elite athletes long-term intensive training was associated with RV remodeling, particularly of RV base. RV function was not altered despite significant chamber dilatation. The extent of changes in RV morphology varied between sports: cyclists were more prone to exercise-induced RV structural remodeling.

Background Athlete's heart should be differentiated from the hypertrophic cardiomyopathy (HCM)-leading cause of exercise related sudden cardiac death in young athletes. Some genetic variations of HCM are characterized by a benign clinical course and a delayed onset of the disease. Therefore, substantial increase of left ventricular wall thickness (LVWT) in adolescent athletes needs relevant strategies in pre-participation screening (PPS). Objective To identify adolescent athletes with left ventricular hypertrophy (LVH) and differentiate physiological LVH from HCM. Design Observational follow-up study. Setting: Sports Medicine Clinical Centre. Participants 978 asymptomatic and normotensive highly trained (≥12 h/week) adolescent athletes (92.9% males) aged 12–18 years, representatives of national teams of 14 sporting disciplines. Interventions Cardiovascular evaluation with medical history, physical examination, 12-lead resting and stress electrocardiography, and echocardiography. LV structure and function were measured in 2002–2006. Main outcome measurements The participants were followed prospectively until 2008 with respect to LVH, and until 2012 with respect to HCM. Results 12 (1.2%) athletes, all males had LVWT ≥12 mm (12–15) and normal ECG pattern: 10 of them had normal diastolic indices and LV end diastolic diameter (LVEDD) 52.6±4.8mm (46–61); other 2 athletes had LVEDD<45mm. One of them had normal diastolic function and peak oxygen uptake (VO2max) of 58.8 mL/kg/min. An other athlete (15 yrs) with LVWT 15 mm, LVEDD 43 mm, and decreased VO2max of 41.5 mL/kg/min,Tissue Doppler Imaging (TDI) revealed mildly reduced É-9cm/s and heightened E/É-8.8. Three months of detraining slightly decreased LVWT but did not improve LVEDD and TDI indices. The athlete was advised against competitive sports and referred for further cardiovascular evaluation. Follow-up over a longer period revealed advanced changes in LVWT and diastolic indices, and confirmed HCM. Conclusions Substantial LVH in Georgian elite adolescent athletes is rare. PPS with systematical approach can be a valuable tool in differentiation between physiological LVH and mild expression of HCM.

BACKGROUND.The growing evidence indicates the importance of non-obstructive coronary artery disease (NOCAD), with a high-risk of MACEs. The relevance of antiplatelet therapy is high and depends on a type of MINOCA. However, the effectiveness of different antiplatelet treatment regimens and secondary prevention strategies for patients with non-obstructive coronary artery disease is still unclear. OBJECTIVES In our previous cohort study, we found that secondary prevention with dual antiplatelet therapy with aspirin and P2Y12 receptor antagonist clopidogrel in patients with NOCAD was not significantly effective than aspirin alone in reducing 1-year MACEs. Because the development and validation cohorts of patients with NOCAD were heterogeneous in terms of cardiovascular risk, in the current study we aimed to compare the preventive effect of DAPT with aspirin alone in high cardiovascular-risk patients. METHODS Following the aim of our study, we selected 15 of 55 MINOCA patients with a high 10-year risk for ASCVD (≥20%) from the DAPT group and 19 of 60 patients with the same risk from the no-DAPT group. RESULTSThe results of our previous and present studies corroborate previously published data. DAPT had no secondary preventive effect on one-year MACE in MINOCA patients with different cardiovascular risks. CONCLUSIONS The use of DAPT in patients with MINOCA is a topic for discussion and requires further investigations with a long-term follow-up period. KEYWORDS Atherosclerotic cardiovascular disease (ASCVD) risk; dual antiplatelet therapy (DAPT); myocardial infarction with non-0bstructive coronary artery (MINOCA) disease; non-obstructive coronary disease (NOCAD).

BACKGROUND.Myocardial infarction with non-obstructive coronary artery disease (MINOCA) accounts for 5-20% of all cases of myocardial infarction. The growing evidence indicates the importance of oxidative stress and chronic inflammation in the heterogenous pathophysiology of MINOCA. OBJECTIVES In the present study, we aimed to evaluate oxidative and inflammatory statuses in patients with MINOCA and compare them with the same indices of patients with obstructive coronary disease non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS Overall, 165 of 1018 patients admitted to the Coronary Care Unit of Tsinamdzgvrishvili Center of Cardiology LTD (Tbilisi, Georgia) because of the first episode of acute coronary syndrome (ACS) was divided into two groups: 115 patients with MINOCA were distributed into the group 1, and 50 patients with obstructive coronary disease NSTE-ACS into the group 2. Oxidative stress and inflammatory markers were evaluated in study patients. RESULTSWe found an increase in free radical concentrations in both groups of study patients, but there was no difference in the mean amount of overall organic radicals (FORT)(p=0.412). We also found a significantly lower mean concentration of plasmatic antioxidant compounds (FORD) in patients with MINOCA (p=0.036) compared with NSTE-ACS patients, indicating a more pronounced depletion of antioxidant potential in MINOCA patients. The results of admission inflammatory markers, such as hs-CRP and hemogram-derived NLR, suggest significantly higher inflammatory status in MINOCA patients than in those with NSTE-ACS. CONCLUSIONSThe results of the present study emphasize the significance of oxidative stress and inflammation in the pathogenesis of MINOCA. KEYWORDS Free Oxygen Radical Defense (FORD); Free Oxygen Radical Test (FORT); Myocardial infarction with non-obstructive coronary artery disease (MINOCA); Oxidative profile; Oxidative stress; Oxidative-reductive balance (REDOX index).