2020 Clinical practice guidelines for Hypertrophic cardiomyopathy

Russian Society of Cardiology (RSC)With the participation: Russian Association of Cardiovascular SurgeonsEndorsed by: Research and Practical Council of the Ministry of Health of the Russian Federation Task Force: Gabrusenko S.A. (Chairman), Gudkova A.Ya.* (Chairman), Koziolova N.A. (Chairman), Alexandrova S.A., Berseneva M.I., Gordeev M.L., Dzemeshkevich S.L., Zaklyazminskaya E.V., Irtyuga O.B., Kaplunova V.Yu., Kostareva A.A., Krutikov A.N., Malenkov D.A., Novikova T.N., Saidova M.A., Sanakoev M.K., Stukalova O.V

Ventricular arrhythmias. Ventricular tachycardias and sudden cardiac death. 2020 Clinical guidelines

Russian Society of Cardiology (RSC).With the participation of Russian Scientific Society of Clinical Electrophysiology, Arrhythmology and Cardiac Pacing, Russian Association of Pediatric Cardiologists, Society for Holter Monitoring and Noninvasive Electrocardiology.Approved by the Scientific and Practical Council of the Russian Ministry of Health

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

The research of ammonium hexafluorosilicate desublimation

The authors have studied the laws of ammonium hexafluorosilicate desublimation on a pilot production unit. The proposed explanation of desublimation was proved by a set of investigations of physical and mechanical properties of desublimate samples. The paper introduces the construction of the improved desublimator, cyclone type advective desublimator

MODERN VIEWS ON THE GENE NOTCH1 MUTATIONS ROLE FOR AORTIC COARCTATION

Aim. By the observation of aortic coarctation victims families, to reveal factors predisposing to the disease development, and to evaluate the prevalence of NOTCH1 genes mutation/replacements in patients with this kind of defect. Material and methods. Totally 68 patients included with aortic coarctation. All patients underwent echocardiographic investigation, direct and indirect manometry, multispiral computed aortography and intraoperational revision of coarctation zone. 51 patient underwent screening of 10 from 34 exones of NOTCH1 gene. Control group consisted 200 patients without IHD.Results. In more than a half of the cases coarctation coexisted with bicuspid aortic valve and in circa a hlaf of the cases there was combination of coarctation with arc or descending hypoplasia. Totally 29 NOTCH1 gene types were found. Four from those led to aminoacids exchange, of those only one, R1279H, was revealed in patients group and control group either. This type was much more prevalent in patients with aortic coarctation comparing to control group (p<0,05).Conclusion. The most important factors in coarctation development are heredity (33,8%) and complicated pregnancy (57,4%). The exchange of R1279H in gene NOTCH1 was much more prevalent in patients with the defect studied and might be an associated with the disease allele

BARTH SYNDROME IN PRACTICE OF CARDIOLOGY

Barth syndrome is an X-bound inherited recessive disorder with the prevalenсe 1:300000 — 1:400000 of live bornt, caused by mutations in the gene TAZ; manifesting with dilation cardiomyopathy, neutropenia, proxymal myopathy, delayed physical and motoric development. In the article, a clinical case provided of the Barth syndrome, confirmed by target sequencing of TAZ gene in a boy of 1st year of life, presented in 3 months age by an episode of infectious disease and dilation cardiomyopathy, with family anamnesis of sudden death at the moment of infectious disease in the grand uncle of proband. In dynamics, the patient showed delayed motoric development, as the delay in mass and height (<3 percentile), persistent absolute neutropenia, stable high levels of cardiospecific enzymes, NT-proBNP, symptomes of severe heart failure with following fatal outcome at age of 12 months from sudden death during an episode of infectious disease. The multidisciplinarity presented, as the necessity for clear understanding by practitioners of the specific

POLYMORPHISMS OF MATRIX METALLOPROTEASES 2 AND 9 GENES IN ASCENDING AORTA ANEURISM PATIENTS

Aim. To study the role of mononucleotide polymorphisms of the matrix metalloproteases genes MMP2 and MMP9 in the development of ascending aorta aneurism (AOA).Material and methods. Totally 287 patients included with AOA and 227 persons of control group. All patients underwent echocardiography and assessment of mononucleotide gene polymorphisms of MMP2 (rs2285053) and MMP9 (rs11697325, rs2274755, rs17577) real-time, by PCR.Results. The association of MMP9 (rs11697325) is confirmed for the formation of AOA. AA genotype was significantly more prevalent among AOA patients (c2 =7,2; p=0,01). AA genotype carriers had higher ascending aorta diameter comparing to other persons with different variants (p=0,02). The relation is shown of the polymorphism ММР2 (rs2285053) and AOA development. Persons with CC genotype were more prevalent in the group of the aorta pathology patients (c2 =7,0; р=0,03).Conclusion. Genetic variants ММР9 and ММР2 can be additional risk factors of ascending aorta aneurism development. Therefore the assessment of different polymorphisms of matrix metalloproteases genes is useful for the risk stratification of the patients with ascending aorta dilation

Left ventricular noncompaction associated with titin-truncating variants in the TTN gene

Aim. To study the association of genetic variants in the titin gene (TTN) with the development and clinical course of left ventricular noncompaction in different age groups.Material and methods. The article discusses three clinical cases of patients with left ventricular noncompaction who were treated at theAlmazovNationalMedicalResearchCenter. We performed a new-generation sequencing of 108 genes associated with cardiomyopathies, as well as whole exome sequencing and Sanger sequencing.Results. We identified genetic variants in the TTN gene leading to the synthesis of truncated protein: in the first two cases, the cause of noncompaction was a thirteen nucleotide deletion with a reading frame shift, in the second, a nonsense mutation. An algorithm for assessing the pathogenicity of the identified variants and a scheme of diagnostic genetic search are presented.Conclusion. Causal role of TTN-truncating variants in development of cardiomyopathies and, in particular, left ventricular noncompaction, requires a comprehensive clinical, segregation and bioinformatic analysis using international databases and the use of bioinformatics software