[Immune checkpoint inhibitors related cardiovascular toxicity: 3­mounth follow-up].

AIM: To analyze the condition of the cardiovascular system in oncological patients receiving immune antitumor therapy with immune checkpoint inhibitors (CPIs) based on results of laboratory and instrumental examinations during a 3-month follow-up. MATERIAL AND METHODS: This multicenter prospective observational study included 49 patients (25 men and 24 women aged 65.6±8.7 and 64.3±9.6 years, respectively). A laboratory screening (C-reactive proteins, troponin I, N-terminal pro-brain natriuretic peptide), EchoCG, and carotid ultrasound were performed for all patients. 27 patients were followed up at 3 months after the antitumor therapy initiation. Statistical analysis was performed with the StatPlus 8.0.3 software. RESULTS: Incidence of cardiovascular complications was 16.3 %. The following significant changes in EchoCG parameters were observed: LV EF; (p=0.017), increased LV end-systolic volume (ESV) (р=0.023), and increased LV index of myocardial performance (LIMP; р=0.016). The degree of changes in ESV (ΔESV) depended on a history of chronic heart failure (р=0.03), whereas the degree of changes in EF (ΔEF) depended on the patient's age at the initiation of antitumor therapy (р=0.006). Ultrasound showed an increase in maximum carotid stenosis (р=0.018). CONCLUSION: The study showed a high incidence of newly developed cardiovascular complications associated with the CPI treatment as well as the presence of changes in EchoCG parameters and data of carotid ultrasound.

[Experience with Selexipag to Treat Pulmonary Arterial Hypertension].

Aim To present an own experience in using a medication selexipag in patients with pulmonary arterial hypertension (PAH) included into the V. A. Almazov National Medical Research Center registry and participating in the GRIPHON and GRIPHON OL clinical studies.Material and methods 26 patients with PAH were included into this study since 2010: 20 patients with idiopathic PAH, 4 patients with PAH associated with systemic scleroderma, and 2 patients with corrected congenital heart defects. At the time of randomization, 19 patients had been receiving therapy with phosphodiesterase type 5 inhibitors for at least one month. Among the patients treated with selexipag (n=14), 4 patients reached a high individual maintenance dose (1200-1600 µg b.i.d.), 4 patients reached a medium dose (600-1000 µg b.i.d.), and 6 patients reached a low dose (200-400 µg b.i.d.).Results The selexipag therapy exerted a positive effect on secondary endpoints, specifically, on changes in the functional class of pulmonary hypertension, serum concentration of NT-proBNP, and physical working capacity of patients. Adverse events associated with the selexipag treatment, which resulted in termination of study participation, were observed in one patient.Conclusion To achieve the main goal of drug therapy, low risk of death with selexipag it is critical to observe the titration schedule and to aim at reaching the highest individual maintenance dose.

[The study of circulating endothelial precursor cells in patients with chronic heart failure].

We examined 41 patients with ischemic heart disease (n=26) and dilated cardiomyopathy (DCM) (n=15). Control group comprised 15 practically healthy subjects. We found no substantial differences in the presence of CD34+CD133- and CD34+CD133-VEGFR-2+ cells in peripheral blood of patients with chronic heart failure (CHF) but noted lowering of level of CD34-CD133+VEGFR-2+ cells mainly in DCM group. Most significant factors determining lowering of number of circulating endothelial precursor cells (EPC) were age, level of low density lipoprotein cholesterol, and intima media thickness of common carotid arteries. We found lowering of colony forming ability of EPC in patients with CHF first of all in the group of patients with DCM. Abnormality of qualitative and quantitative composition of EPC can be considered as one of risk factors of endothelial dysfunction, pathological remodeling of cardiovascular system and CHF progression.

[Effect of therapy with rosuvastatin on circulating endothelial progenitor cells in patients with chronic heart failure].

We assessed effect of therapy with HMG--CoA reductase inhibitor rosuvastatin on the number of circulating hemopoietic stem CD34+, CD133+ cells in peripheral blood of patients with systolic left ventricular dysfunction of ischemic genesis. Number of circulating hemopoietic stem CD34+, CD133+ cells in patients with chronic heart failure did not differ from their number in control group, however we revealed tendency to increase of number of endothelial CD34+, CD133+, VEGFR-2+ progenitor cells. We confirmed presence of relationship between quantity of circulating stem and progenitor cells and traditional risk factors of cardiovascular events: age, excessive body mass, arterial hypertension, and intima media thickness of common carotid arteries. Besides lipid lowering effect therapy with rosuvastatin was associated with lowering of C-reactive protein level and increase of number of circulating CD34+, CD133+ cells.