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.

[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.