RISK SCORE MODEL FOR PREDICTING CARDIOTOXICITY IN BREAST CANCER: DIAGNOSTIC VALUE OF HIGH-SENSITIVITY CARDIAC TROPONIN T. / ШКАЛА РИЗИКУ КАРДІОТОКСИЧНОСТІ У ХВОРИХ НА РАК ГРУДНОЇ ЗАЛОЗИ: ДІАГНОСТИЧНЕ ЗНАЧЕННЯ ВИСОКОЧУТЛИВОГО СЕРЦЕВОГО ТРОПОНІНУ Т.

Cardiovascular diseases are the second leading cause of death among breast cancer (BC) patients. Prediction of cardiovascular toxicity (CT) is an important part of the successful treatment and survival of patients. OBJECTIVE: to develop a risk score model for cardiovascular toxicity (CT) predicting, based on cardiovascular risk factors (RFs), RFs associated with cancer therapy, and troponin levels. MATERIAL AND METHODS: The study included 76 BC patients with a prospective analysis of their clinical and treatment data, RFs, echocardiographic indicators before the start of treatment and after 6 months, and an increase in troponin level. Among all RFs, the most significant RFs of CT were: radiation therapy, treatment with anthracyclines, and cardiovascular diseases. Based on the obtained results, a combined CT risk score was developed and proposed.According to the sum of points, patients were divided into groups: group 1 - with a low risk of CT development, the sum of points < 5; group 2 - moderate risk, 6-7 points; group 3 - high risk, > 8 points. RESULTS: In a pilot prospective study, an analysis of the RFs of CT was provided, compared to echocardiography data and the degree of troponin increase in dynamic observation; the risk score model for the CT prediction was developed for BC patients stratification. According to the developed score, BC patients with a total of > 8 points are considered to have a high risk of CT complications. CONCLUSIONS: The use of the proposed risk model score with calculation of the RFs of CT along with high-sensitivity troponin increase during cancer treatment allows predicting the risk of CT developing at the early stages - before the onset of clinical manifestations. Accordingly, these BC patients have a high risk of CT, and the use of personalized cardiac monitoring together with cardioprotective therapy can prevent cardiovascular complications.

CARDIOTOXICITY IN BREAST CANCER PATIENTS: RELATIONSHIP OF HS-TROPONIN T CHANGES AND HEART FUNCTION IN CANCER TREATMENT. / KARDIOTOKSYChNIST' U KhVORYKh NA RAK GRUDNOÏ ZALOZY: VZAIeMOZVIaZOK ZMIN TROPONINU T TA FUNKTsIÏ SERTsIa NA FONI KOMPLEKSNOÏ PROTYPUKhLYNNOÏ TERAPIÏ.

Breast cancer patients (BC) have a high risk of cardiotoxicity (CT) due to a combination of cancer treatments.Cardiovascular (CV) complications lead to delay or withdrawal of BC therapy and worsen the survival. Therefore, it isimportant to detect CT at the early stages before the occurrence of cardiac dysfunction and heart failure (HF) signs. OBJECTIVE: to study the dynamic changes of high-sensitivity (hs) troponin (Tn) T (hs-TnT) level in BC patients during cancer treatment with the use of chemotherapy and radiation therapy (RT) to predict and prevent CV complications during individualized management. MATERIAL AND METHODS: 40 BC patients were included in the pilot study. The analysis of the dynamic changes of hs-TnT and ejection fraction (EF) of the left ventricle (LV) was performed before and within 6 months of cancer treatment. Based on the data analysis, a definition of a significant increase in hs-TnT was developed and proposed. Therise of hs-TnT was calculated by the difference (%) between its baseline level and in the 6 months of cancer treatment. BC patients are grouped into tertiles according to the hs-TnT increase: group 1 - low level (0-50 %), group 2 -moderate level (> 50-100 %), and group 3 - high level (> 100 %). RESULTS: Before the start of cancer treatment, LVEF did not differ significantly between groups (mean EF (62.6 ± 1.0) %)and the hs-TnT level was also within normal values (0.008±0.001 ng/ml). In 6 months of cancer treatment, LVEF waswithin the normal ranges and did not differ significantly in patients of group 1. However, in patients of groups 2and 3 - LVEF drop (δLV EF) was 5.7 % (р < 0.01) and 10.8 % (р < 0.01), consequently. According to the correlationanalysis, the percentage of increase in hs-TnT (δhs-TnT) was associated with δEF LV (r = 0.39, р < 0.05) and the useof anthracyclines (AC) (r = 0.37, р < 0.05). Using logistic regression and ROC analysis, the diagnostic threshold valueof the hs-TnT increase > 165 % was defined, which can be considered as a reliable marker of early biochemical CT,with a sensitivity of 99 % and a specificity of 56 %. CONCLUSIONS: In BC patients, based on the level of hs-TnT increase, proposed a new early biochemical CT detectionmethod. Under the new approach, BC patients with hsTnT increase of > 165 % from baseline can be considered as areliable marker of early biochemical CT, with a sensitivity of 99 % and a specificity of 56 %.

CARDIOTOXICITY RISK PREDICTION IN BREAST CANCER PATIENTS. / PROGNOZUVANNIa RYZYKU KARDIOTOKSYChNOSTI U KhVORYKh NA RAK GRUDNOÏ ZALOZY.

Breast cancer patients receive combined antitumor treatment (surgery, chemotherapy, targeted drugs and radia-tion), so they are considered to be the patients with potentially high risk of cardiotoxicity (CT). Risk stratificationof cardiovascular complications before the beginning and during the cancer treatment is an important issue. OBJECTIVE: to develop a CT risk model score taking into account cardiological, oncological and individual risks. MATERIAL AND METHODS: The study included 52 breast cancer patients with retrospective analysis of their medicalhistory, risk factors, and echocardiographic parameters before the onset and in 12 months follow up. Based on theanalysis of the data, a CT risk model score was developed and recommended. The patients were divided into groupsaccording to the score: Group 1 - low risk of CT development - score < 4 points, Group 2 - moderate risk - 5-7points, Group 3 - high risk > 8 points. According to the scale, BC patients with a total of > 8 points are consideredto be at high risk for CT complications. Radiation therapy and anthracyclines, as well as associated cardiovasculardiseases were the most important risk factors of CT. RESULTS: Based on the study of retrospective analysis of risk factors, data of heart function monitoring during follow-up,the risk model score of cardiotoxicity has been developed for the BC patients' stratification. According to the proposedscore risk model, BC patients with a total score of > 8 points considered to have high risk of cardiotoxic complications. CONCLUSIONS: Using of the proposed risk model score with calculation of CT risk factors both before the beginningand during cancer therapy is important, because it allows predicting the risk of CT development - to identify high-risk patients, accordingly, to develop an individualized plan for cardiac function monitoring and to start timely cardioprotective therapy.

RADIOTHERAPY-ASSOCIATED CARDIOVASCULAR COMPLICATIONS IN CANCER (review). / SERTsEVO-SUDYNNI USKLADNENNIa, ASOTsIIOVANI Z PROMENEVOIu TERAPIIeIu (ogliad literatury).

The review is devoted to the current issues of radiation-induced cardiovascular complications, their diagnostics andincidence depending on the radiation doses and exposure regimens, potential efficiency of the screening strategiesfor cardiotoxicity monitoring after radiotherapy in cancer patients by analyzing the data from literature and clinical trials, based on recommendations of European Society of Cardiology and European Society of Medical Oncology.

[Impact of renal dysfunction on clinical course of myocardial infarction complicated by acute heart failure in patients with preserved systolic function].

Aiming to assess the relationships between renal function and ST-segment elevation myocardial infarction (MI) clinical course and remote outcomes in patients with preserved systolic left ventricular (LV) function (LV ejection fraction > 40%) estimated glomerular filtration rates (eGFR) were evaluated on 1st and 3rd -10th MI day (n = 491). On 3rd-10th day of MI in patients with acute heart failure (HF) symptoms on admission day (1st group, n = 153) eGFR < 70 ml/min x per body surface unit was independent marker of re-infarction (Hazzard Ratio (HR) with 95% confidence intervals (95% CI) = 4,08 [1,72 -11,73], P < 0,01) and cardiovascular death (CVD) (HR [95% CI] = 3,61 [1,09 - 11,99], P = <0,05) during three years of follow-up. In patient without acute HF (2nd group, n = 338) eGFR < 68 ml/min was predictive of CVD within three years post-MI (HR [95% CI] = 7,13 [2,06 - 24,74], P = 0,002). eGFR did not correlate with myocardial damage markers. In the 1st group eGFR on the 3rd MI day was negatively correlated with tumor-necrosis factor alpha (TNF-alpha) and vascular endothelial growth factor levels. There were no correlation between systemic inflammation activation with eGFR in 2nd study group indicating different mechanisms of renal dysfucntion in patients with and without acute HF and preserved LV function.

[Cytokine profile of mononuclear leukocytes in patients with myocardial infarction complicated by cardiac insufficiency].

Between the pro- and antiinflammatory components of the immune system there is a dynamic balance, violation of which is an important mechanism of development of many pathological states, in particular, cardiac insufficiency. The purpose of the work was a study of secretion of cytokines by mononuclears in patients under myocardial infarction, uncomplicated (1 group) and complicated (2 group) acute cardiac insufficiency, and determination of balance between pro-(TNF-alpha, IL-6, IL-8) and antiinflammatory (1L-10) factors in development of acute cardiac insufficiency in patients with myocardial infarction. The results indicate that in patients of group 1 there is initially a high level of both proinflammatory and antiinflammatory cytokines. After 10 days, we observed a decline in the IL-6 level and an increase in the TNF-alpha and IL-10 levels. In patients of group 2 we observed initially high levels of TNF-alpha and IL-6 and a reduced levels of IL-8 and 1L-10, as compared to patients of group 1. In dynamics of supervision of this group, further increase of all proinflammatory cytokines and a decline of IL-10 was registered. Balance between the pro- and antiinflammatory cytokines reflects the index of inflammatory activity, determined by formula (TNFalpha+IL-6+IL-8)/IL-10 and testifying that in patients of group 1 in the dynamics of treatment there is normalization of cytokin's balance, accompanied by decline of the index, while in patients of group 2 the index rose at 10th day.

[Metabolic activity of neutrophilic granulocytes and possible ways of its correction in patients with acute coronary syndrome].

The present study aimed to investigate the metabolic activity of neutrocytes and the action of corvitin on the level of superoxide anion and myeloperoxidases of cells in vitro with the calculation of index of consumption of myeloperoxidase in patients with ST-elevation acute coronary syndrome. Patient were divided into 2 groups according to the level of superoxide anion. Group 1 included the patients (68%) with the initially low level of superoxide anion, and adding of corvitin to the cells of such patients promoted normalization of this index. In this group we observed also neutrocytosis, low index of consumption of myeloperoxidase and a high level of this enzyme in general population of neutrocytes. Group 2 included patients (32%) with initially normal level of superoxide anion. In this group, corvitin did not influence substantially this factor. Such patients had a level ofmyeloperoxidase within control values and the index of consumption of this enzyme was also within control values. The analysis of hospital period showed that the patients of group 1 had a higher frequency of ventricular tachycardia/ventricular fibrillation, paroxysms of atrial fibrillation, bundle-branch blocks and worsening of the kidney function. We suppose that a low level of superoxide anion in neutrocytes play a major role in the development of complications in patients with acute coronary syndrome. An intravenous administration of corvitin was effective in restoring the metabolic activity of neutrocytes.