Vol 51, No 5 (2023)

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ARTICLES

Arterial structure and function in patients with hemoblastoses before and after high-dose chemotherapy and autologous hematopoietic stem cell transplantation

Potemkina N.A., Glezer M.G., Zeynalova P.A., Chomakhidze P.S., Novikova A.I., Petrova G.D., Poltavskaya M.G.

Abstract

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.

Almanac of Clinical Medicine. 2023;51(5):259-269
pages 259-269 views

The relationship of asymmetric dimethylarginine levels with uncontrolled arterial hypertension and hypertension disease stage

Stafeev A.N., Logvinenko N.I., Astrakov S.V.

Abstract

Background: Patients with treatment-resistant hypertension have a worse cardiovascular prognosis compared to those who achieve their target levels of blood pressure (BP). One of biochemical and clinical markers of a decreased response to antihypertensive therapy can be asymmetric dimethylarginine (ADMA), a molecule that reduces formation of nitric oxide and promotes endothelial dysfunction and vasoconstriction.

Aim: To assess the status of the nitrogen oxide synthesis system and clinical and laboratory profile in patients, depending on the hypertensive disease stage, who achieved or not achieved their target BP levels during hospitalization.

Materials and methods: We performed аn observational retrospective uncontrolled study in a consecutive sample of 192 patients aged 45–65 years who were admitted to the City Clinical Hospital No. 25 (city of Novosibirsk) with a diagnosis of uncomplicated hypertensive crisis. On the day of discharge, the patients were retrospectively divided into 2 groups. Group 1 included patients who achieved their target BP during hospitalization (target BP group, n = 116). Group 2 included patients with uncontrolled hypertension, in whom the administration of three antihypertensive drugs including a diuretic in optimal or maximal tolerated doses did not result in the achievement of the target BP below 140 and/or 90 mm Hg during hospitalization (non-target BP group, n = 76).

The following parameters were measured: ADMA, symmetrical dimethylarginine (SDMA), N-monomethyl-L-arginine (NMMA), and total nitric oxide.

Results: Serum ADMA concentrations (Me [Q25%; Q75%] were increasing with the stage of hypertension: stage I, 0.75 µmol/L [0.66; 0.78], stage II, 1.14 µmol/L [0.87; 1.39], stage III, 1.38 µmol/L [1.22; 1.49] (p < 0.0001, Kruskal-Wallis test). In the pairwise comparison, the difference between all these subgroups was significant at p < 0.01. In the patients with uncontrolled arterial hypertension ADMA levels were increased compared to those in the target BP group: 1.2 µmol/L [0.99; 1.47] vs 1.07 [0.79; 1.34] µmol/L (p = 0.002). The proportion of patients with type 2 diabetes mellitus among those with uncontrolled arterial hypertension was 31.2% (24/76), while in the target BP group there were only 3.5% of such patients (4/116) (odds ratio 12.57, 95% confidence interval 4.15–38.05; p = 0.00001).

Conclusion: ADMA measurement may help identify patients with a potential poor response to antihypertensive therapy. This should be taken into account when choosing a treatment regimen and BP monitoring. In addition, ADMA seems to be a promising target for the development of new drug classes.

Almanac of Clinical Medicine. 2023;51(5):270-278
pages 270-278 views

Characteristics of the basal psychoautonomous indicators in patients after coronary artery stent placement at various stages of rehabilitation

Mirzoev R.A., Malchikova S.V., Sherman M.A.

Abstract

Background: Clinically significant psychoautonomous syndrome, along with other modifiable factors (obesity, dyslipidemia, low physical activity, smoking, arterial hypertension, etc.) increases the risk of development and progression of coronary artery disease (CAD). In particular, patients who have undergone coronary interventions and have a higher anxiety level are prone to the development of CAD complications.

Aim: To characterize the basal parameters of clinically significant psychoautonomous syndrome and their changes over time under combination therapy, including anxiolytics, at various stages of rehabilitation of the patients after endovascular myocardial revascularization.

Materials and methods: This open-label randomized controlled prospective study included 60 patients aged 45 to 75 years admitted to our in-patient department for rehabilitation treatment after coronary stent placement. The patients from the intervention group (n = 30), in addition to basic treatment for CAD, were administered anxiolytic therapy (alimemazine tartrate at daily dose of 12.5 to 25 mg i. m. at the early rehabilitation step and at 5 to 10 mg during their out-patient follow-up). The in-patient study period included 3 study visits (at admittance, i. e., Day 1, at Days 5 or 6, and at discharge at Day 10 to 14). Two further study visits were performed during the out-patient rehabilitation period at Days 30 and 60. At each visit, the emotional state, sleep quality, subjective signs of autonomous dysregulation, autonomous background and suprasegmental vegetative regulation, including temporal and spectral indicators of heart rate variability, were evaluated.

Results: After endovascular myocardial revascularization (the in-patient study period, Day 1) patients of the intervention and control groups (n = 30 in both groups) demonstrated comparable moderate levels of state anxiety (median [Q1; Q3]: 42 [40; 46] and 42 [36; 43], respectively) and trait anxiety (45 [41; 48] and 42 [40; 46], associated with insomnia (PSQI score: 8 [6; 12] and 6 [3; 9]) and autonomous imbalance (SDNN: 73 [61; 89] and 70 [44; 95]) with a shift to sympathetic hyperactivity. Addition of an anxiolytic initiated the regression of psychoautonomous abnormalities already by the end of the early in-patient rehabilitation period) (Days 10 to 14), with a subsequent decrease in state anxiety to 36 [33; 39] and trait anxiety to 33 [32; 37] (p < 0.001), regression of insomnia according to PSQI to 2 [2; 4] (p < 0.001), and an improvement of autonomous balance (SDNN) to 113 [81; 132] (p < 0.001) at days 45 to 60 of the outpatient follow-up. The only adverse event in the patients receiving the treatment for psychoautonomous dysfunction was increased sleepiness at daytime, which was registered in most of them at initiation of the therapy for 2 to 3 days and did not require any dose modification. There were no other clinically significant adverse events, including cardiovascular.

Conclusion: Patients with an increased level of anxiety after endovascular myocardial revascularization are characterized by an autonomous imbalance with sympathetic hyperactivity. Addition of an anxiolytic to the basic treatment for CAD allows for a reduction of both components of the psychoautonomous syndrome, which may be an additional factor for successful patient rehabilitation and as a consequence for the prevention of CAD progression.

Almanac of Clinical Medicine. 2023;51(5):279-289
pages 279-289 views

Clinical particulars of acute coronary syndrome course in patients with COVID-19

Izmozherova N.V., Popov A.A., Tsvetkov A.I., Kadnikov L.I., Ispavskii V.E., Shambatov M.A.

Abstract

Background: Cardiovascular complications of COVID-19 result in challenges for differential diagnosis, patient’s referral and treatment, which negatively affect the outcomes.

Aim: To identify clinical particulars of various types acute coronary syndrome course in patients with COVID-19.

Materials and methods: This retrospective cross-sectional study included 202 patients with COVID-19 and acute coronary syndrome (ACS) admitted to a primary vascular medicine center from September to December 2020. Their medical records were used for the analysis of ACS and COVID-19 clinical course, including physical and history data, laboratory and instrumental work-up. For the analysis, the patient sampling was divided into three study groups: 50 patients with unstable angina (UA), 107 patients with acute myocardial infarction with ST segment elevation (STEMI), and 45 patients with acute myocardial infarction without ST segment elevation (non-STEMI).

Results: There were no differences in clinical manifestations of ACS in the study groups. As far as clinical manifestations of coronavirus infections are concerned, the patients differed significantly as per prevalence of fever and dry cough. Fever was present in 22 (44%) UA patients, 18 (17%) of STEMI patients and in 10 (22%) of non-STEMI patients (p < 0.001 for comparison of 3 groups, Kruskall-Wallis test), whereas dry cough was present in 18 (36%), 19 (18%), and 14 (31%) patients, respectively (p = 0.029). Paired comparison (Mann-Whitney test with Bonferroni adjustment) showed significant differences between US and STEMI groups for both symptoms. The number of involved vessels (median [25%; 75%]) in UA patients was 0 [0; 2], in STEMI and non-STEMI patients 2 [1; 3] (p < 0.001). A left coronary artery stenosis was detected in 2 (6%) of the UA patients, 13 (14%) of the STEMI and 4 (13%) of the non-STEMI patients (p = 0.452); left anterior descending artery stenosis, in 12 (36%), 67 (72%) and 23 (72%) patients, respectively (p < 0.001). In the pairwise comparison, there were differences between UA and STEMI groups and between UA and non-STEMI groups. A left circumflex artery stenosis was found in 7 (21%) of the UA patients, 45 (48%) of the STEMI and 18 (56%) of the non-STEMI patients (p = 0.008); the pairwise comparisons showed the difference between UA and non-STEMI study groups. A right coronary artery stenosis was identified in 9 (27%), 64 (69%) and 18 (56%) of the study patients, respectively (p < 0.001); in the pairwise comparison the difference was found between the UA and STEMI group. There were significant differences in the percentage of the right descendent and right coronary artery stenosis: the right descending artery stenosis was 70% [45; 80] in the UA patients, 90% [70; 100] in the STEMI and 95% [70; 100] in the non-STEMI patients (p = 0.013), whereas the right coronary artery stenosis was 50% [45; 80], 90% [70; 100], 90% [60; 100], respectively (p = 0.018). In the pairwise comparison, the differences were found between the UA and STEMI patients in both arteries. The STEMI patients had higher TIMI thrombus grade scores than those with non-STEMI: 3 [0; 5] vs 0 [0; 4] (p = 0.023). The rates of successful percutaneous coronary intervention and achievement of TIMI flow grade 3 between them was not significantly different (p = 0.170).

Conclusion: The ACS patients with ACS and COVID-19 have high thrombotic load according to coronary angiography and TIMI score in the case of STEMI and more frequent absence of hemodynamically significant stenosis in those with UA and non-STEMI. The absence of any difference in clinical manifestations of ACS and viral infection between the study groups (except fever and dry cough difference between the UA and STEMI patients) indicates that specific characteristics of the ACS course in COVID-19 patients can be identified only by coronaroangiography.

Almanac of Clinical Medicine. 2023;51(5):290-300
pages 290-300 views

REVIEW ARTICLE

Diagnostic algorithms for acute ankle injury imaging

Trufanov G.E., Aleksandrovich V.Y., Menkova I.S.

Abstract

Ankle trauma is the most prevalent low extremity injury among urgent referral patients. Up to 85% of acute ankle traumas lead to an isolated ligament injury, with up to 50% of these patients would have chronic pain syndrome in the future, related to inaccurate diagnosis and resulting inappropriate treatment strategy and rehabilitation term.

We analyzed publications on the state-of-the-art aspects of radiation diagnostics of acute ankle injury available from PubMed/MEDLINE databases and in the Russian Index of Scientific Citation (Elibrary.ru) for the last ten years; some earlier essential publications on certain aspects were also considered.

Up to now, there have been no unified guidelines on the radiation diagnosis of ankle injury depending on the trauma type, mechanism, and severity. The Ottawa ankle rules (1994) are the basic guidelines for selection of the patients with acute trauma who should be offered X-rays. Primary X-ray would allow for the choice of the treatment strategy or further diagnostic assessment of the patient. Computed tomography is done for multi-fragment intra-articular fractures and for the control after their reposition. Computed tomography is used in patients with severe pain syndrome and other absolute and relative contraindications for magnetic resonance imaging. The latter allows for the imaging of all injured structures within a single assessment procedure and by such to make the diagnosis of ligament and tendon ruptures, to visualize osteochondral injuries, hidden and stress fractures and many other acute ankle injuries. Ultrasound assessment can considerably add to clinical understanding of the patient during acute trauma, if magnetic resonance imaging is contraindicated.

Based on the analysis performed, we propose the algorithms for diagnostic assessment in various clinical situations.

Almanac of Clinical Medicine. 2023;51(5):301-313
pages 301-313 views

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