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The study aimed to compare composition of peripheral blood T-cell subsets and assess their surface expression of CD39 and CD73 ectonucleotidases in patients with severe and moderate aortic stenosis (AS) as well as to evaluate involvement of T-cell-mediated immune processes in valve calcification. The study was performed with 38 patients suffering from severe calcified aortic stenosis (SAS), 33 patients with MAS, and 30 apparently healthy volunteers (HVs). The relative distribution and percentage of T-cell subsets expressing CD39 and CD73 were evaluated by flow cytometry. T helper (Th) and cytotoxic T-cell subsets (Tcyt) were identified by using CD3, CD4, and CD8 antibodies. Regulatory T cells (Tregs) were characterized by the expression of CD3, CD4, and high IL-2R alpha chain (CD25high) levels. CD45R0 and CD62L were used to assess differentiation stage of Th, Tcyt, and Treg subsets. It was found that MAS and SAS patients differed in terms of relative distribution of Tcyt and absolute number of Treg. Moreover, the absolute number of Tcyt and terminally differentiated CD45RA-positive effector T-cells (TEMRA) subset was significantly higher in SAS vs. MAS patients and HVs. However, the absolute and relative number of naïve Th and the absolute number of Treg were significantly higher in MAS vs. SAS patients; the relative number of naïve Tregs was significantly ( p < 0.01) decreased in SAS patients. It was shown that CD73 expression was significantly higher in SAS vs. MAS patients noted in all EM, CM, TEMRA, and naïve Th cell subsets. However, only the latter were significantly increased ( p = 0.003) in patients compared with HVs. SAS vs. MAS patients were noted to have significantly higher percentage of CD73+ EM Tcyt ( p = 0.006) and CD73+ CM Tcyt ( p = 0.002). The expression of CD73 in patients significantly differed in all three Treg populations such as EM ( p = 0.049), CM ( p = 0.044), and naïve ( p < 0.001). No significant differences in CD39 expression level was found in MAS and SAS patients compared with the HV group. Overall, the data obtained demonstrated that purinergic signaling was involved in the pathogenesis of aortic stenosis and calcification potentially acting via various cell types, wherein among enzymes, degrading extracellular ATP CD73 rather than CD39 played a prominent role.

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Цель. Оценить концентрацию остеопротегерина (OPG) и растворимого лиганда рецептора активатора фактора транскрипции каппа-В (sRANKL) в сыворотке крови у больных с различной степенью тяжести аортального стеноза (АС). Материал и методы. Обследовано 247 больных с АС различной степени тяжести: 46 пациентов с легкой степенью тяжести, 53 пациента с умеренным АС и 149 с тяжелым АС. Из них 132 (53%) пациента с бикуспидальным аортальным клапаном (БАК) и 115 (47%) с трикуспидальным аортальным клапаном (ТАК). Контрольную группу составили 58 пациентов без клапанной патологии сердца и ишемической болезни сердца. У всех пациентов определяли липидный профиль, сывороточный уровень С-реактивного белка (СРБ), OPG и sRANKL. Результаты. Во всех исследуемых группах больных с АС выявлено повышение содержания sRANKL в сыворотке крови в сравнении с контрольной группой (БАК =0,37 [0,32;0,53] пмоль/л, ТАК =0,38 [0,33;0,50] пмоль/л, контрольная группа 0,30 [0,21;0,39] пмоль/л; р<0,0001. Концентрация OPG была повышена только у больных с ТАК: 6,99 [5,19;9,90] пмоль/л; по сравнению с 5,23 [4,30;7,09] пмоль/л у пациентов с БАК (р=0,0008). Высказана гипотеза, что рост концентрации OPG является компенсаторным и возникает в ответ на повышение уровня или нарушение чувствительности к sRANKL. Заключение. Развитие АС сопряжено с нарушениями в системе OPG/RANKL, а выявление этих изменений может иметь важное диагностическое и прогностическое значение, особенно у пациентов с ТАК. Российский кардиологический журнал 2018, 2 (154): 39-43 http://dx.Ключевые слова: аортальный стеноз, кальциноз, биомаркеры, остеопротегерин, sRANKL. Russ J Cardiol 2018, 2 (154): 39-43 http://dx.

Цель. Оценить данные реальной клинической практики по ведению больных с застойной сердечной недостаточностью в условиях городской больницы скорой медицинской помощи для разработки ключевых направлений программы по совершенствованию медицинской помощи больным хронической сердечной недостаточностью (ХСН). Материал и методы. Проанализировано 343 случая госпитализации в связи с декомпенсацией ХСН. При поступлении 88% больных имели III-IV функциональный класс ХСН. Качество оказания медицинской помощи оценивалось согласно критериям, утвержденным Минздравом России и обществом специалистов по сердечной недостаточности. Результаты. Наряду с практически 100% выполнением рутинного инструментального обследования (электрокардиография, рентгенография органов грудной клетки), эхокардиография проведена у 64%, а суточное мониторирование электрокардиограммы у 3% больных. Стандартное лабораторное обследование только в 15% и 14% случаев включало определение концентрация калия и натрия в сыворотке крови. Уровень лактатдегидрогеназы, щелочной фосфатазы и γ-глутамилтранспептидазы оценивался менее чем у 5% больных. В стационаре 94% пациентов получали терапию β-адреноблокаторами, 93% ингибиторами ангиотензипревращающего фермента/блокаторами рецепторов ангиотензина II типа, 74% антагонистами минералокортикоидных рецепторов и 88% диуретиками. Однако 48% пациентов получали парентеральную диуретическую терапию до выписки из стационара и не были адаптированы к приему пероральных диуретиков. Динамика веса на фоне диуретической терапии контролировалась только у 13% больных. Вместе с тем, при выписке количество пациентов, имеющих III-IV функциональный класс ХСН, составило 38%. Заключение. Несмотря на положительную динамику клинического состояния пациентов за время госпитализации, выявлены недостатки, которые могут повлиять на эффективность лечения больных ХСН. Вместе с тем, частота повторных госпитализаций, прежде всего, обусловлена отсутствием преемственности в оказании стационарной и амбулаторной помощи. Поэтому разработка системы автоматизированного получения, интеграции, хранения и обработки медицинской информации будет способствовать совершенствованию медицинской помощи больным ХСН.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Grant of Russian Foundation for Basic Research Introduction Long existing pressure overload results in left ventricular (LV) hypertrophy in severe aortic stenosis (AS). Post-TAVI left ventricular remodeling after relief of the high-pressure overload could lead to manifestation of postprocedural midventricular obstruction caused mostly by marked LV wall hypertrophy with the interposition of the hypertrophic papillary muscle in small LV chamber.  Our aim was to evaluate the incidence and predictors of midventricular obstruction during 1-year follow-up in patients with AS who underwent transcatheter aortic valve implantation.  Methods  30 consecutive patients (mean age: 82.3 ± 5.6 years) with symptomatic severe AS who underwent TAVI in 2018-2019 in Almazov centre and survived &gt;12 months were enrolled in our observational, prospective, single-center study. Evolut R and Sapien-XT valves were used. All patients underwent transthoracic echocardiography before TAVI and at 3, 6, and 12 months after the procedure. There were no patients with baseline midventricular obstruction or concomitant hypertrophic obstructive cardiomyopathy.  Results Procedure was successful in all cases. During 1 year of follow-up after TAVI, 3 patients (10%) demonstrated postprocedural midventricular obstruction with peak gradient ­– 36,3 ± 24,3 mm Hg.   There was no difference in prosthetic diameter between obstructive and non-obstructive patients (27.0 ± 3,4 vs. 27.7 ± 5,1 mm, p = 0.85 - nonparametric Mann-Whitney U test for all comparisons). At baseline echocardiography, patients with midventricular obstruction had a significantly thicker interventricular septum (14.7 ± 2.5 vs. 11.5 ± 1.6mm, p &lt; 0.05), higher LV mass index (170.3 ± 63.6 vs. 121.0 ± 39.5 g/m2, p &lt; 0.05) and relative wall thickness (0.59 ± 0.03 vs. 0.49 ± 0.05 mm, p &lt; 0.02) compared with non-obstructive patients.  Reductions in LV mass index were more significant in non-obstructive patients (49.8 ± 27.3 vs. 15.3 ± 15.0 g/m2, p &lt; 0.04); however, obstructive patients demonstrated higher reductions in end-systolic diameter (8.7 ± 7.1 vs. 0.3 ± 3.9 mm, p &lt; 0.05) and volume (21.7 ± 20.0 vs. 1.2 ± 8.4 mm, p &lt; 0.01) than non-obstructive patients throughout the 1-year follow-up.  Midventricular obstruction peak gradient correlates strongly with preoperative relative wall thickness (rs=.73; p &lt; 0.001), moderate negatively with end-systolic LV diameter (rs=-.45; p &lt; 0.05).  In the multiple regression analyses, preoperative relative wall thickness (p &lt; 0.001), reductions in interventricular septum (p &lt; 0.05) and posterior wall (p &lt; 0.05) thickness were identified as risk factors of postprocedural midventricular obstruction.  Conclusions  10% of patients during 1 year of follow-up after TAVI demonstrate midventricular obstruction of various severity with poor reverse LV remodeling. Patients with a small hypertrophic left ventricle and high preoperative relative wall thickness, are at greater risk of development of the postprocedural midventricular obstruction.

Background Aortic stenosis (AS) is the most common acquired valvular heart disease. Calcification of the aortic valve (AV) cusps is the main pathogenetic mechanism of AS formation, however triggering and progression mechanisms of it are not fully understood. Aortic valve interstitial cells (AVIC) are one of the main cell populations responsible for the AV structure and homeostasis. The aim of the study was to characterize the ability of AVIC to osteogenic differentiation using the model of the primary culture of AVIC of patients with aortic stenosis and assess the expression of genes involved in osteogenesis (RUNX2, BMPG2, SPRY1, SOX9, CTNNB1, POSTN, OPG and OPN). Materials and methods The study was carried out on primary human AVIC culture obtained by enzymatic dissociation of experimental valve specimens from patients with AS (n=15) and the control specimens from the orthotopic heart transplantation recipients (n=10). To assess the osteogenic potential of AVIC, the routine stem cell osteodifferentiation protocol based on the culture medium with addition of inductors (10 mM β-glycerophosphate, 0.1 μM dexamethasone, and 50 μg/ml ascorbic acid) was used. Calcium deposits were demonstrated by Alizarin Red staining. Analysis of the expression of osteogenic differentiation genes, such as RUNX2 (runtrelated transcription factor 2), BMP2 (bone morphogenetic protein 2), SPRY1 (Sprouty RTK signaling antagonist 1), SOX-9 (SRY-box9), CTNNB1 (β-catenin1), POSTN (periostin), OPG (osteoprotegerin), and OPN (osteopontin), was performed by real-time PCR. Results The inductors of osteogenic differentiation provoked greater mineralization of AVIC cultures derived from the patients with AS than that observed in control group (p=0.0003). The expression of RUNX2 and SPRY1 in non-differentiated cells was reduced compared with control cells in patients with bicuspid AV (p=0.02). After 21 days of the osteogenic induction, the expression of RUNX2 and SPRY1 increased in all three groups. At the same time, the expression of SPRY1 was lower in the group with bicuspid AV compared with tricuspid AV (p=0.007). The expression level of BMP2 did not differ between groups in unstimulated AVIC, however, it increased after osteogenic differentiation in the group of patients with tricuspid AV (p=0.017). OPN expression was higher in cells from tricuspid AV, while OPG expression was reduced in patients with both bicuspid and tricuspid AV (p<0.01), No differences were found between the groups) for the remaining genes (POSTIN, CTNNB1, SOX9) before and after stimulation with an osteogenic medium. Conclusions The osteogenic potential of AVIC is increased in patients with aortic stenosis. The gene expression profile of osteogenic differentiation differs in patients with a bicuspid and tricuspid aortic valve. Damage of protective mechanisms may be a potential mechanism for accelerated valve calcification mostly in patients with tricuspid aortic valve. Acknowledgement/Funding Russian Foundation for Basic Research, project 18-015-00016

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