Vol 52, No 2 (2024)
ARTICLES
Electrocardiogram abnormalities in patients with hematological malignancies before and after high dose chemotherapy and autologous hematopoietic stem cell transplantation
Abstract
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.
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The association between exosomal proteins and the efficacy of thermoradiochemotherapy in overweight/obese rectal cancer patients: a pilot prospective cohort study
Abstract
Background: Overweight and especially obesity are associated with the risk of the development and progression of colorectal cancer. It can be assumed that there are multifaceted interactions between the tumor and adipose tissue during anti-tumor treatment. Cancer cells secrete exosomes, extracellular vesicles affecting the microenvironment of the tumor and promoting its progression or regression. The presence of transcription/translation/folding factors (heat shock proteins (HSPs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in exosomes secreted by irradiated cells and cells exposed to hyperthermia, indicates the cell adaptation to the thermal and radiation stress.
Aim: To analyze the MMPs, TIMP1, and HSPs on CD9-positive (CD9+) exosomes, as well as on exosomes of adipocytic origin (FABP4+) in rectal cancer patients with overweight/obesity under thermoradiochemotherapy (TRCT) and their association with the immediate treatment efficacy.
Methods: Since 2021, 20 patients (of those 8 men; median age 59.0 [52.0; 63.0] years, median body mass index 29.6 [28.5; 33.1] kg/m2) with morphologically verified rectal cancer (T3-4N0M0 and T3-4N1M0, differentiation grade G1–G3) have been participating in the study. They were treated with TRCT: external gamma therapy (2 Gy, 1 fraction/day, 5 days/week, total focal dose 54 Gy), chemotherapy with capecitabine (825 mg/m2 twice daily) combined with local hyperthermia (42–44 °C, 60 min, 3 times/week, 10 sessions). The TRCT efficacy was assessed by RECIST 1.1 and ESGAR criteria. Blood samples for exosomes were taken from the patients at baseline (point 1), in the middle of the treatment course (point 2), at 6 to 10 weeks after the end of TRCT (point 3), and at 6 months after point 1 (point 4). Small extracellular vesicles were isolated from plasma by ultrafiltration with double ultracentrifugation. The isolated exosomes were characterized by transmission electronic microscopy, flow cytometry and nanoparticle trajectory analysis (NTA).
Results: TRCT resulted in complete tumor regression in 13/20 of the rectal cancer patients and partial regression or stabilization in 7/20. Four subpopulations of CD9+ and FABP4+ exosomes associated with the TRCT efficacy were identified (CD9+MMP2+, СD9+MMP2+9+TIMP1+, СD9+MMP2+9+TIMP1-, and FABP4+MMP2+9-TIMP1+). Compared to the CD9+ exosomes, the adipocytic vesicles had higher MMP2 expression (p = 0.026); however, the adipocyte vesicles subpopulation were virtually free of vesicles with combined MMP2 and MMP9 gelatinase expression. The HSPs expression by circulating exosomes at various TRCT steps was associated neither with direct treatment efficacy nor with the vesicle type.
Conclusion: The expression of MMPs and TIMP1 on CD9+ and FABP4+ exosomes is associated with TRCT efficacy. In the future, vesicular markers could be used to build prognostic models, to identify patient groups with an unfavorable prognosis, and to personalize treatment and follow-up.
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The value of percutaneous transcatheter mitral valve regurgitation repair in the combination treatment of chronic heart failure patients: Results from a 6-month observational prospective study
Abstract
Rationale: Surgical interventions have been recognized as the main method to repair of valvular disorders. Percutaneous transcatheter intervention with a clipping system is being actively introduced into the treatment of chronic heart failure (CHF) patients and mitral valve insufficiency (MVI) for correction of mitral regurgitation (MR), along with drug therapy.
Aim: To establish the effect of the mitral valve leaflet clipping in the combination treatment of CHF patients on the clinical course of heart failure and the remodeling process.
Methods: This single center prospective comparative study included 80 patients with CHF NYHA class II–IV and secondary MR grade 3–4. The patients were on optimal medical treatment (OMT) for CHF for at least 3 months before inclusion into the study. The main group included 55 patients who underwent transcatheter mitral valve repair with the use of MitraClip system, and the control group consisted of 25 patients in whom the surgery for MR was waived for various reasons (refusal of the surgery by the patient, some valve characteristics), and only OMT for CHF was used. At baseline, main clinical and demographic characteristics of the patients in the both groups were comparable. The duration of the follow-up was 6 months. Echocardiography (echoCG), a 6-minute walk test, and measurements of the brain natriuretic propeptide level were performed in all patients at baseline and at 6 months of the follow-up.
Results: At 6 months, there was a significant reduction in CHF NYHA class and an increase in the 6-minute walk test distance and a decrease in diuretic requirements (converted to furosemide, from 58.4 ± 17.2 to 38.1 ± 20.7 mg daily, р = 0.02) in the group with the MitraClip implant, but not in the control group. In the OMT only group, there were no changes over 6 months in the diuretic requirements (48.1 ± 6.68 and 43.8 ± 27.15 mg daily, respectively, р = 0.8). The number of hospital readmissions due to CHF decompensation was 7 (12.7%) in the implanted MitraClip group and 4 (16%) in the OMT group (р = 0.69). EchoCG performed at 6 months after the surgical intervention identified no cases of MR grade > 2. In the MitraClip implant group, there was a decrease in the size and volumes of the left atrium (р = 0.02 and р = 0.05, respectively), left ventricle (for end-diastolic diameter p = 0.002, end-diastolic volume p = 0.03), mean pulmonary artery pressure (p = 0.03), as well as an increase in cardiac output (р = 0.04). In the patients receiving OMT only, there were no significant changes in EchoCG parameters over time.
Conclusion: Our study has shown benefits of the implantation of the mitral valve leaflet clipping system, compared to OMT only, in CHF. The clipping procedure promotes a significant improvement in clinical course of CHF, reverse myocardial remodeling, and reduction in diuretic requirements.
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Dynamic contrast enhancement and wall enhancement index for the quantitative assessment of vascular wall abnormalities in intracranial atherosclerosis: a pilot study
Abstract
Background: Breakthrough neurotechnologies have allowed for new understanding of some brain disorders; however, identification and differential diagnosis of intracranial stenotic and occlusive lesions remains challenging. Magnetic resonance imaging (MRI) with dynamic contrast enhancement (DCE) is a tool that could be used for the quantitative assessment of endothelial permeability and microvascular volume in atherosclerotic plaques (AP).
Aim: To assess quantitative parameters of vascular wall abnormalities in AP area and in obviously unchanged wall of intracranial arteries with MRI DCE and high spatial resolution Т1-weighed images before and after contrast injection, with calculation of the wall enhancement index (WEI) by mathematical modelling.
Methods: This was a pilot cross-sectional uncontrolled study with consecutive recruitment of 29 patients with atherosclerotic abnormalities of brachiocephalic arteries, including intracranial. The patients’ median age was 66 [57; 72] years; they were mostly men (75.9%, n = 22). For the assessment of any brain abnormalities, MRI (magnetic induction 3 Tesla, Magnetom Prisma, Siemens) was performed in patients with standard sequence (Т2, T2-FLAIR), as well as MRI DCE for the assessment of intracranial arteries, before and after intravenous contrast injection, with high spatial resolution T1-weighed imaging and suppression of the signal from bloodstream and fat, with the calculation of WEI.
Results: There were significant differences in WEI in AP and in unchanged wall (0.962 [0.686; 1.387] vs. 0.111 [0.014; 0.206], p < 0.001). No significant differences were found between WEI values in internal carotid arteries APs (0.722 [0.573; 1.580]), middle cerebral arteries (0.921 [0.725; 1.183]), and basilar artery (1.343 [1.002; 1.419]) (p = 0.381). We also found significant difference (p = 0.034) in the extravascular extracellular fraction volumes ve (Tofts) in AP located in the basilar artery (0.171 [0.146; 0.325]), internal carotid arteries (0.579 [0.358; 1.000]), and middle cerebral arteries (0.134 [0.101; 0.269]).
Conclusion: This is the first description of quantitative parameters characterizing vascular wall abnormalities in intracranial atherosclerosis. Despite its obviously intact state, vascular walls outside the intracranial AP was shown to be abnormal as well.
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REVIEW ARTICLE
NLRP3 inflammasomes as a target for hesperidin and diosmin flavonoids in varicose vein disease and its complications
Abstract
Varicose vein disease of the lower extremities is an inflammatory disorder with abnormal structure and functional activity of the venous valves, venous walls and cells, as well as with abnormal activity of the infiltrating leukocytes. The abnormally changed varicose vein are characterized by increased venous pressure, blood accumulation and congestion, ischemia, and metabolic and energy turnover derangement, which result in clinical manifestations of complications, such as pain, edema and formation of trophic ulcers. For many years, flavonoids have been used to treat varicose veins. The most effective flavonoids used in varicose vein disease and its complications, are hesperidin and diosmin, as well as their combinations.
The review sets forth the state-of-the-art knowledge on the universal inflammatory processes playing a leading role in the pathophysiology of many cardiovascular disorders, including venous ones.
In the recent years, it has been found that one of the main causes of inflammation is the formation of intracellular protein complexes (inflammasomes), which both produce a set of proinflammatory cytokines and are responsible for their excretion from the cells. In addition, inflammasomes control the development of regulated necrosis (pyroptosis) that takes part in the process of ulceration. The inflammasome activity can be modified by various mechanisms, of which the gene independent synthesis of the inflammasomal proteins has been recognized as the leading one. It has been shown that flavonoids inhibit the activation of a key factor NF-kappa B and suppress the synthesis of proteins, including NOD-like receptor protein 3 (NLRP3) inflammasome components, decrease the expression of NLRP3 receptor, protein ASC and caspase 1, as well as diminish interleukin 1 beta, interleukin 6 and tumor necrosis factor-alpha expression. Thus, this is the explanation of positive effects observed with the use of hesperidin, diosmin and their combination in clinical practice.
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