[Cardiac Dysfunction and Arterial Hypertension as Manifestations of Cardiovasculotoxicity of iVEGF-Containing Chemotherapy. Clinical Case].

Significant advances in timely diagnosis and modern antitumor therapy have led to a considerable increase in the survival rate of cancer patients. On the other hand, the incidence of cardiovascular (CV) diseases and their complications is increasingly growing, including due to side effects of anticancer drugs. CV complications are the most common cause of non-oncological death of cancer patients. The development of polychemotherapy-induced arterial hypertension (AH) is closely associated with the use of certain groups of drugs, for example, inhibitors of vascular endothelial growth factor (iVEGF). Such AH is generally dose-dependent and reversible after interruption or termination of treatment. However, systemic AH, regardless of its genesis, is one of the key risk factors for many CV events (myocardial infarction, stroke, heart failure, arrhythmias) and kidney disease. Therefore, thorough blood pressure monitoring and its timely and adequate correction if needed are indicated when using certain groups of chemotherapy drugs. This article describes a clinical follow-up of a patient with induced AH associated with the iVEGF antitumor therapy for advanced uterine cancer with a rapid development of left ventricular myocardial dysfunction.

Cardio-oncology today: digest of the first European clinical guidelines (2022).

Over the past few decades, due to the extensive implementation of cancer screening programs, up-to-date early diagnostic methods, and effective combinations of antitumor therapy, it has become possible to significantly improve survival of cancer patients. At the same time, despite the effective treatment of malignancies, most patient face adverse and often life-threatening effects of specific treatment on the heart and blood vessels. All this resulted in active development of a new field in cardiology, cardio-oncology. In recent years, based on the experience of leading experts, data from large studies, and meta-analyses, both international and Russian Consensuses, conciliation documents, have been formed and published. These documents regulate principal methodological approaches to management and control of the cardiovascular conditions in cancer patients. Finally, 2022 was marked by issuing the first official European Guidelines on Cardio-Oncology in the history of medicine. This article highlights the most relevant, in our opinion, positions of these guidelines as well as controversial and unresolved issues.

Relationship Between Markers of the Acute Phase of Inflammation, Parameters of Blood Lipid Composition and Intracardiac Hemodynamics During Chemotherapy in Patients With Multiple Myeloma.

Aim      To evaluate in a pilot study time-related changes in the clinical state, indexes of the acute phase of inflammation, parameters of blood lipid profile, intracardiac hemodynamics, and disorders of cardiac rhythm/conduction in patients who are not candidates for autologous hemopoietic stem cell transplantation, during three bortezomib-containing chemotherapy courses (VCD) followed by a correlation analysis.Material and methods  This pilot study included 20 patients diagnosed with myeloma, who were not candidates for autologous hemopoietic stem cell transplantation and who had undergone three courses of VCD chemotherapy (bortezomib, cyclophosphamide and dexamethasone). In addition to mandatory examinations, measurement of blood lipid profile, transthoracic echocardiography (EchoCG), and 24-h Holter electrocardiogram (ECG) monitoring were performed for all participants before and after a specific therapy.Results Following three bortezomib-containing courses of chemotherapy, patients of the study group had significant increases in the neutrophil-lymphocyte ratio (NLR) (1.6±0.2 and 2.5±0.4; р=0.05), cholesterol concentration (4.8±1.1 and 5.6±1.1 mmol/l, р=0.05), and low-density lipoprotein concentration (2.8±0.4 and 3.5±0.8 mmol/l, р=0.02). In comparing the changes in parameters of intracardiac hemodynamics, criteria for genuine cardiotoxicity were not met, however, a tendency to emergence/progression of myocardial diastolic dysfunction was noted. No clinically significant disorders of cardiac rhythm/conduction were observed. The correlation analysis performed prior to the start of chemotherapy, showed significant strong, direct correlations between the C-protein concentration and left atrial (LA) volume (r=0.793; p=0.006), right atrial (RA) volume (r=0.857; p=0.002), left ventricular (LV) end-diastolic dimension (EDD) (r=0.589; p=0.043), and LV end-diastolic volume (EDV) (r=0.726; p=0.017). Following the specific treatment, significant, medium-power and strong correlations were found between NLR and EDV (r= -0.673; p=0.033), NLR and end systolic volume (ESV) (r= -0.710; p=0.021), respectively. Significant direct correlations were found between the bortezomib dose per one injection and the serum concentration of triglycerides following the treatment (r=0.78; p=0.05); a single bortezomib dose and parameters of intracardiac hemodynamics: LA (r=0.71; p=0.026), RA (r=0.74; p=0.014), EDD (r=0.837; p=0.003), EDV (r=0.749; p=0.013), ESV (r=0.553; p=0.049).Conclusion      For the first time, a comprehensive evaluation was performed in patients with multiple myeloma, including the dynamics of blood lipid profile, intracardiac hemodynamics and disorders of cardiac rhythm/conduction during bortezomib-containing antitumor therapy, with an analysis of correlation with levels of acute inflammation phase markers. Although in the observation window for genuine cardiotoxicity, clinically significant cardiovascular complications were not detected, the found correlations may evidence a potential role of systemic inflammation activity in myocardial remodeling in the studied patient cohort.

[Vasculotoxicity of Chemotherapy: Assessment оf Endothelial Dysfunction Biomarkers' Levels in Gastric Cancer Patients].

Aim To evaluate dynamics of biomarkers for endothelial dysfunction (ED), including endothelin-1 (ET-1) and von Willebrand factor (VWF) in patients with stomach cancer (adenocarcinoma) before and after polychemotherapy (PCT); to compare these results with respective values in healthy volunteers and patients with cardiovascular diseases (CVD); to study correlations of the ED biomarkers with indexes of instrumental evaluation of endothelial dysfunction.Material and methods The study included 75 participants, including 25 healthy volunteers (control group), 25 patients with documented CVDs (arterial hypertension + ischemic heart disease), and 25 patients of the main group with histologically documented stage II-IV stomach cancer (adenocarcinoma) who received different courses of PCT with platinum-based agents (oxaliplatin, cisplatin) and fluoropyrimidines (5 fluorouracil, capecitabin). Laboratory measurement of ED biomarkers, computerized nailfold video capillaroscopy (CNVC), and finger laser photoplethysmography (PPG) (methods for noninvasive evaluation of vascular wall and ED), electrocardiography, 24-h ECG Holter monitoring, and echocardiography (EchoCG) were performed for all patients of the main group prior to PCT and within one months after the last course completion. This evaluation was performed once for healthy volunteers and patients of the CVD group upon inclusion into the study.Results In the main group, ET-1 levels were non-significantly lower than normal and did not change during the courses of antitumor treatment (0.95 [0.6; 1.4] and 0.94 [0.7; 1.4] pg /ml (р<0.9) before and after PCT, respectively). Statistically significant differences were found between the control group and oncological patients after the treatment (р<0.04). Levels of VWF remained within the normal range in all examined participants and did not significantly differ between study groups, including oncological patients before and after the specific treatment (р>0.05 for all comparisons). The correlation analysis detected significant correlations of ET-1 levels with functional disorders of microcirculation, ET-1 with the occlusion index (rs=0.56; p=0.005), ЕТ-1 with percentage of capillary restoration (PCR, rs= -0.72; p=0.018) and with the incidence rate of supraventricular extrasystole (rs=0.48; p=0.032).Conclusion The dynamics of ED biomarkers was studied for the first time in patients with stomach cancer receiving a specific antitumor therapy. Although no significant changes in ЕТ-1 and VWF were observed during the PCT (probably due to exhaustion of the endothelial system and a small patient sample), these indexes can be considered as early vasculotoxicity markers due to the presence of significant correlations with indexes of impaired endothelial function according to the results of instrumental evaluation.

[Treatment and secondary prevention of venous thromboembolism in cancer patients].

Oncological patients are a high-risk group for venous thromboembolic complications. These complications significantly impair the outcome of antitumor treatment and take a leading place in the structure of mortality. Treatment of venous thromboembolic complications in oncological patients is a serious challenge. When selecting an anticoagulant, the physician should consider its efficacy and safety and possible drug interactions. Based on results of multiple studies presented in this article, physicians will be able to choose an optimum therapeutic tactics and secondary prevention of thromboembolic complications for this group of patients.

[The effect of chemotherapy on endothelial function and microcirculation in patients with gastric cancer].

OBJECTIVE: To evaluate and study the dynamics of endothelial dysfunction instrumental indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer (adenocarcinoma) before and after chemotherapy; compare it with the results obtained from healthy volunteers and patients with cardio-vascular diseases. MATERIALS AND METHODS: The study included 65 people: 25 healthy volunteers, 15 patients with known cardio-vascular diseases (CVD) and 25 patients with histologically confirmed gastric cancer (adenocarcinoma) stage 2-4 who underwent surgical treatment followed by chemotherapy according to the FOLFOX, XELOX, and XP regimes. For non-invasive assessment of the vascular wall's state of large vessels and microcirculation, all patients in the main group underwent computer nailfold capillaroscopy and finger photoplethysmography before chemotherapy and within a month after the completion of the last course. For healthy volunteers and patients with CVD, the above studies were performed once during the examination. RESULTS: The data obtained indicate a significant increase in the reflection index of small muscle arteries (RI) and the stiffness index of large conducting arteries (aSI) during chemotherapy. In cancer patients, even before the treatment, endothelial dysfunction was detected, which significantly worsened after treatment (occlusion index (IO) before and after chemotherapy 1.7 (1.38; 1.9) vs. 1.3 (1.2; 1.5), p<0.0002, respectively). Significant differences in the compared indices in cancer patients and CVD group were revealed only after chemotherapy. Significant structural and functional disorders of capillaries were noted in the studied groups, which also worsened during chemotherapy in the main group (density of the capillary network at rest 43.23cap/mm2 vs. 42.19cap/mm2, p <0.01, respectively; density of the capillary network after the reactive hyperemia test 46.77cap/mm2 vs. 44.11cap/mm2, p<0,02, respectively). CONCLUSION: In this study, for the first time, the dynamics of endothelial dysfunction indicators, vascular wall stiffness and microcirculation state in patients with gastric cancer were studied, and a reliable increasing of these changes was proved during chemotherapy. The results indicate the need for a further search for accurate and effective methods of identifying early signs of close and distant vasculotoxicity, the development of individual prevention programs in order to significantly reduce the risk of cardiovascular events during and after chemotherapy.

[Assessment of the Role of Oxidative Stress Indicators and Early Markers of Myocardial Injury and Disfunction in Patients with Lymphoproliferative Diseases].

PURPOSE: to study dynamics of indicators of oxidative stress and their role in development of cardiotoxicity in patients with lympho-proliferative diseases at the background of polychemotherapy. MATERIALS AND METHODS: We included into this study 30 patients with newly detected Non-Hodgkin lymphomas. The control group comprised 15 healthy volunteers. For registration of dynamics of formation of oxygen active forms (OAF), we used highly sensitive chemiluminescence assay. The state of initial stage of lipoperoxidation OAF and radicals of organic compounds) was assessed by dynamics of the leukocyte chemiluminescence. The state of final stage of lipoperoxidation (formation of nonmetabolizing lipid hydroperoxides and other compounds) was assessed by the level of malonic dialdehyde. We also determined indicator of leukocyte chemiluminescence intensity (both basal and zymosan-stimulated). For assessment of the cardiovascular system functional state before and after chemotherapy we used electrocardiography (ECG), echocardiography (EchoCG) and 24-hour ECG monitoring. RESULTS: The data obtained were indicative of increased generation of free radicals by leukocytes during polychemotherapy. After chemotherapy course we detected various types of cardiotoxicity. We noted substantial elevation of frequency of supraventricular and ventricular extrasystoles. There was direct correlation between rate of appearance of supraventricular extrasystoles and level of chemiluminescence of leukocytes (r=0.7; p=0.03). According to data of EchoCG although the left ventricular ejection fraction remained within the normal range during chemotherapy, there was a persistent tendency to its decrease (р<0.001). CONCLUSION: In this study we for the first time in patients with Non-Hodgkin lymphomas detected an elevation of level of free radical reactions and lipid peroxidation with simultaneous lowering of antiperoxidative activity of blood plasma and their relation to development of cardiotoxic effects. The results obtained indicate to necessity of search for novel early markers of oxidative stress activation, myocardial injury and disfunction able to help to substantially decrease risk of development of cardiovascular complications during and after chemotherapy.