Aim. To study the traditional risk factors for cardiovascular disease (CVD), indicators of endothelial function and exercise tolerance in patients received complex treatment for cranial and craniospinal tumors in childhood, including radiation therapy.Material and methods. We compared examination data of 48 patients who underwent treatment for brain tumors using cranial and craniospinal irradiation in childhood (mean age, 21,7±4,3 years, mean period after the end of treatment, 6,9±5,4 years), and 20 healthy volunteers. Examination methods included assessment of lipid profile, vascular stiffness and endothelial function using the Photoplethysmography and occlusion test, cardiopulmonary test, and in patients who underwent craniospinal irradiation, also echocardiography and duplex ultrasound of extracranial arteries.Results. Compared to healthy individuals, patients after a brain tumor were found to have lower blood pressure, higher heart rate (HR), significantly lower exercise performance (peak oxygen consumption, 19,8±6,4 ml×min-1×kg vs 30,3±5,8 ml×min-1×kg, p<0,0001) and a higher prevalence of dyslipidemia (56% vs 5%, p<0,0001), as well as an increase in the augmentation index, indicating higher stiffness of large vessels (-7,3±16,3 vs -20,3±7,9, p=0,001), and a trend towards a decrease in the occlusion index (p=0,051). Echocardiography and duplex ultrasound revealed no radiation-associated abnormalities.Conclusion. Determining the mechanisms and prognostic significance of the identified risk factors for CVD (dyslipidemia, decreased exercise tolerance, increased heart rate and vascular stiffness) in this category of patients requires further research. Regular monitoring of risk factors, primarily the lipid profile, and the use of preventive measures for individuals with an increased risk of CVD should be recommended.

State-of-the-art therapy improves the five-year survival rate of patients under the age of 20 with cranial and craniospinal tumors by up to 74%. The urgency of dealing effectively with late treatment-associated cardiovascular complications is rising. Objective: We aimed to assess echocardiographic parameters and exercise performance in subjects with a history of complex treatment for cranial and craniospinal tumors in childhood. Methods: the study of 48 subjects who underwent cranial and craniospinal irradiation for CNS tumors in childhood and 20 healthy age- and sex-matched volunteers was conducted. The examination included hormone studies, cardiopulmonary exercise testing, and, in the main group, echocardiography (ECHO). Results: In five (10.4%) patients, ECHO changes were detected after complex anti-cancer treatment: thickening and calcification of the aortic valve leaflets (2%), and reduction in the systolic LV and RV function (8% and 6%, respectively). Irradiation of various areas was a significant predictor for reduced exercise tolerance, hyperventilation at rest and upon exertion, and an increased ventilatory equivalent for carbon dioxide. Low exercise tolerance was associated with a younger age at the time of treatment initiation. Significant differences were noted between the control group and the childhood cancer survivors with endocrine disorders. Conclusions: The obtained data confirm the importance of regular cardiovascular and endocrine monitoring of this group of cancer survivors.

Background: Endothelial dysfunction is recognized as one of the early markers of cardiovascular disorders. It is supposed to be a potential predictor of cardiovascular complications in patients receiving adjuvant and neoadjuvant chemotherapy. Aim: To estimate the prevalence of endothelial dysfunction in solid cancer patients compared to that in individuals without any malignancies. Materials and methods: This observational study included 74 patients with solid malignancies, mostly gastrointestinal. Prior to polychemotherapy, all patients were examined for endothelial function of small and large arteries (AngioScan-01, Fiton, Russia) and peripheral artery stiffness (pulse wave contour analysis and occlusion test). The results were compared with those of the Russian population trials of endothelial dysfunction – Meridian-RO (Ryazan region) and trial in the rural population of the Krasnodar region. Results: Compromised vasodilation and smaller arteries tone were found in 64.9% (48/74) of the cancer patients, while impaired vasodilation of larger muscular arteries was present in 94.6% (70/74) of the patients. According to the Meridian-RO trial in the Ryazan region, endothelial dysfunction had been found in 51.2% (n = 341) of women and 52.4% (n = 300) of men, whereas the Krasnodar regional population data had shown it in 68.4% (n = 353) of women and 71.7% (n = 253) of men. Conclusion: The prevalence of endothelial dysfunction in the patients with solid malignancies, who have not undergone any chemo- or radiation therapy, is significantly higher than in the population of comparable age, conventional cardiovascular risk factors, and comorbidities. No significant increase of vascular stiffness was identified.

Background: High dose chemotherapy (HDCT) preceding autologous hematopoietic stem cell transplantation (autoSCT) can be toxic for cardiovascular system, which can be mediated with the development of endothelial dysfunction. No studies on the assessment of arterial stiffness and endothelial function after HDCT and autoSCT have been performed before. Aim: To evaluate endothelial function and arterial rigidity parameters by photoplethysmography in patient candidates for HDCT with autoSCT, to identify associated factors and to analyze changes of these parameters over time after HDCT and autoSCT. Materials and methods: In this cohort prospective observational study in 71 patients with verified hemoblastosis (mean age 43.8 ± 12.6 years) we assessed endothelial function and stiffness by photoplethysmography (AngioScan-01, Russia) before and after HDCT with autoSCT. Thirty two (32, 45%) patients had multiple myeloma (ММ), 39 (55%), lymphoproliferative disorders (LPD). We measured the stiffness index (SI), reflection index (RI), augmentation index normalized by heart rate of 75 beats per minute (AIp75) and performed the occlusion test with measurement of occlusion index (ОI) and phase shift (PS). Results: Mean RI in the total study group before HDCT with autoSCT was increased to RI 34.9% [24.5; 50.6], OI decreased to OI 1.5 [1.25; 1.80], and PS module decreased to PS 6.7 ms [3.9; 8.9]. After HDCT with autoSCT the PS module increased to 8.4 ms [5.0; 12.4] (p = 0.001) and OI increased to 1.7 [1.3; 2.2] (p = 0,007), which indicates an improvement in endothelial function. Changes in other parameters of arterial function were non-significant. We also analyzed a selected group of the patients with MM who had higher cardiovascular risk, compared to the LPD patients: they were older (53 vs 36.1 years; p 0.001), had higher rates of arterial hypertension (p 0.001) and diabetes mellitus (p = 0.048). Compared to the LPD patients, the MM patients had higher baseline values of SI (7.5 m/s [7.3; 7.9]), RI (42.9% [32.1; 53.6]), and AIp75 (6.3% [-1.65; 13.8]), indicating higher vascular stiffness. They also had lower PS module values (5.0 ms [2.1; 8.5]). The LPD patients had been more frequently treated with anthracyclines (p 0.001) and radiation (p = 0.002). After HDCT with autoSCT, they had a higher increment of OI, namely, from 1.4 [1.3; 1.8] to 1.7 [1.4; 2.1] (p = 0.003). Conclusion: This study was the first to show a high rate of endothelial dysfunction and vascular stiffness abnormalities in patients with hemoblastoses who were candidates for HDCT with autoSCT. After HDCT with autoSCT, changes of endothelial function and stiffness were multidirectional. Despite a significant improvement, endothelial function parameters were not normalized. We were unable to find any predictors of the abnormalities. Thus, the identified baseline abnormalities in stiffness and endothelial function cannot be a contraindication to HDCT with autoSCT.

Aim. To assess the impact of comprehensive anticancer therapy on lipid and hormonal profile markers in individuals who underwent treatment for central nervous system (CNS) tumors during childhood.Material and methods. A single-center, cross-sectional study included 48 patients who underwent surgical, chemotherapeutic, and radiation treatment for CNS tumors in childhood. Lipid and hormonal profiles were analyzed.Results. In young patients (21.7±4.3 years) who had undergone comprehensive treatment, including surgery, chemotherapy, and cranial radiation for CNS tumors in childhood, the cumulative cranial dose of radiation therapy was found to be an independent predictor of dyslipidemia development and low-density lipoprotein cholesterol (LDL-C) levels >3,0 mmol/l. Correlation analysis revealed a positive relationship between LDL-C level and the cumulative cranial dose (r=0.414; p=0.007). Statistically significant correlations were also observed between total cholesterol (TC) values and insulin-like growth factor-1 (IGF-1) (r=-0.41; p=0.028), LDL-C and IGF-1 (r=-0,44; p=0,028), very-low-density lipoprotein cholesterol and somatotropin (r=-0.44; p=0.033). Furthermore, LDL-C level was associated with changes in thyrotropine (TSH) (r=-0.39; p=0.017), and VLDL-C was correlated with TSH (r=-0.42; p=0.016).Conclusion. Patients who underwent complex treatment of CNS tumors in childhood demonstrated a high frequency of dyslipidemia associated with the cumulative cranial dose of radiation therapy. Considering the presence of endocrinological disorders, in particular somatotropic insufficiency and hypothyroidism, their influence on dyslipidemia development can be assumed. The potential influence of glucocorticoid therapy during oncological treatment on lipid profiles cannot be ruled out. These findings support the necessity of developing practical recommendations for dynamic follow-up of patients who have undergone comprehensive treatment for malignant CNS tumors during childhood, to ensure timely detection of cardiovascular diseases.

Rationale: Electrocardiography (ECG) is an objective and widely available method for the diagnosis of cardiovascular disorders recommended for identification of abnormalities, including those in patients with malignancies. A few studies have been published on the assessment of changes in ECG over time in patients with hemoblastoses under high-dose chemotherapy (HDCT) with subsequent transplantation of autologous hematopoietic stem cells (autoHSCT). Aim: To study ECG abnormalities before HDCT with autoHSCT and after treatment and their association with cardiac dysfunction in patients with hematological malignancies. Materials and methods: This prospective cohort observational study included 71 patients with confirmed hemoblastoses. Before HDCT with autoHSCT and at the average of 20 weeks thereafter, a 12-lead standard ECG, echocardiography, and measurement of cardiac biomarkers (troponin T [TnT] and N-terminal pro-peptide of brain natriuretic peptide (NT-proBNP) were performed. We assessed P wave abnormalities, PQ duration, QRS, ST segment, and T wave. The following cut-off values were considered abnormal: duration of P wave above 110 ms, of PQ interval above 210 ms, of QRS above 110 ms. The QTc intervals were calculated according to Bazett and Fridericia. QTc above 450 ms in men and above 460 in women was considered as prolonged. Results: After HDCT with autoHSCT, increased left ventricular myocardial mass index (LVMMI) was more commonly found in the patients with prolonged P wave ( 110 ms) at baseline (χ2 = 7.214; odds ratio (OR) 4.179; 95% confidence interval [CI] 1.425–12.250; p = 0.015), and increased left atrial volume index (LAVI) was more common for those with initially two-humped P wave (χ2 = 11.169; OR 19.231; 95% CI 2.064–179.212; p = 0.004). Before HDCT with autoHSCT, flattened T wave was present in 14 (19.7%) of the study patients. After the treatment, 8 (11.3%) of the patients demonstrated a new T wave abnormalities, associated with more frequent new TnT increase ( 14 pg/mL) (χ2 = 7.945; p = 0.025), as well as with increased LAVI (p = 0.018) and LVMMI (p = 0.018). Before HDCT with autoHSCT, 10 (14.1%) of the study patients had a prolonged QTc interval, which correlated to the increased NT-proBNP level ( 125 pg/mL) (r = 0.247; p = 0.038). The assessment of the QTc length after HDCT with autoHSCT showed, that the increase of NT-proBNP levels by 1 pg/mL was associated with an increase of the QTc duration by 0.003 mc(p = 0.027). Conclusion: In patients with hematological malignancies, baseline P wave abnormalities are the risk factor for increased LVMMI and LAVI after HDCT with autoHSCT. New T wave abnormalities and QTc prolongation after HDCT with autoHSCT are associated with the signs of myocadial injury and dysfunction.