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Russian Journal of Cardiology 2020, 25 (10)

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ORIGINAL ARTICLES

CARDIOMETABOLIC RISK FACTORS AND THEIR RELATIONSHIP WITH THE INTERLEUKIN-6 RECEPTOR GENE POLYMORPHISM (RS2228145) IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Bezhanishvili T. G.1, Gudkova A. Ya.1,2, Davydova V. G.2, Andreeva S. E.2, Krutikov A. N.2, Semernin E. N.1,2, Kudryavtsev B. N.1, Pyko S. A.3, Kostareva A. A.1,2, Shlyakhto E. V.1,2

Abstract

Aim. To analyze associations of interleukin-6 receptor gene (IL6R) polymorphism (rs2228145) with the clinical course characteristics of hypertrophic cardiomyopathy (HCM) in groups of patients with various cardiometabolic risk factors.

Material and methods. The sample consisted of 123 patients with HCM. The age of the included patients ranged from 18 to 91 years (59 [41; 66.5]), of whom 59 were men, 64 — women. Two age groups were identified: the first group included patients

from 18 to 44 years old, the second — 45 years and older. The control group consisted of 200 people without cardiovascular diseases and other severe comorbidities. For genetic testing, DNA was isolated from peripheral blood lymphocytes. Genotyping of the IL6R gene polymorphism (rs2228145) was carried out by realtime polymerase chain reaction.

Results. A significant prevalence of CC genotype of the IL6R gene polymorphism (rs2228145) was revealed in patients aged ≥45 years compared with the control group, which occurred in 14,1% and 3,0% of cases, respectively (CC:AC+AA, odds ratio (OR), 0,885, 95% confidence interval (CI), 1,051-0,691, p=0,006), and insignificant prevalence of C allele in this group, which does not reach the level of significance (A:C, OR, 0,870, 95% CI, 0,427-1,02, p=0,06). The prevalence of CC genotype (15,1% vs 3,0%) and C allele (39,0% vs 29,0%) was revealed in patients with HCM in combination with hypertension (HTN) compared with the control group (CC:AS+AA, OR=0,174, 95% CI, 0,047-0,650), p=0,004); (A:C, OR=0,638, 95% CI, 0,406-1,002), p=0,05).

Conclusion. The relationship between the IL6R gene polymorphism (rs2228145) and HTN in patients with HCM was confirmed. The presence of CC genotype and C allele of the rs2228145 polymorphism is significantly more common in patients with HCM with the disease onset ≥45 years of age. The presence of CC genotype and C allele of the IL6R gene polymorphism (rs2228145) is associated with HTN in patients with HCM.

Key words: hypertrophic cardiomyopathy, interleukin-6, interleukin-6 receptor gene, hypertension.

1First Pavlov State Medical University of St. Petersburg, St. Petersburg; 2Almazov National Medical Research Center, St. Petersburg; 3Saint Petersburg Electrotechnical University “LETI”, Saint Petersburg, Russia.

Relationships and Activities: none.

Bezhanishvili T. G.* ORCID: 0000-0002-3167-6340, Gudkova A. Ya. ORCID: 0000-0003-0156-8821, Davydova V. G. ORCID: 0000-0002-0233-5555, Andreeva S. E. ORCID: 0000-0001-7306-9525, Krutikov A. N. ORCID: 0000-0001-6897-6171, Semernin E. N. ORCID: 0000-0001-8447-6919, Kudryavtsev B. N. ORCID: 0000-0002-1236-822Х, Pyko S. A. ORCID: 0000-0001-6625-3770, Kostareva A. A. ORCID: 0000-0002-9349-6257, Shlyakhto E. V. ORCID: 0000-0003-2929-0980.

*Corresponding author: tinatin93@rambler.ru

Received: 07.09.2020

Revision Received: 24.09.2020

Accepted: 30.09.2020

For citation: Bezhanishvili T. G., Gudkova A. Ya., Davydova V. G., Andreeva S. E., Krutikov A. N., Semernin E. N., Kudryavtsev B. N., Pyko S. A., Kostareva A. A., Shlyakhto E. V. Cardiometabolic risk factors and their relationship with the interleukin-6 receptor gene polymorphism (rs2228145) in patients with hypertrophic cardiomyopathy. Russian Journal of Cardiology. 2020;25(10):4098. (In Russ.) doi:10.15829/1560-4071-2020-4098

POLYMORPHISMS IN F2, F7, AND PAI1 GENES IN MEN WITH CORONARY ATHEROSCLEROSIS

Stryukova E. V.1, Maksimov V. N.1, Ragino Yu. I.1, Polonskaya Ya. V.1, Murashov I. S.2, Volkov A. M.2, Kurguzov A. V.2, Chernyavsky A. M.2, Kashtanova E. V.1

Abstract

Aim. To study the associations of polymorphisms in F2, F7, and PAI1 genes with the presence of vulnerable plaque in coronary arteries (CA) and the blood concentration of proteins encoded by these genes.

Material and methods. The study included 101 men 40-70 years old with documented coronary atherosclerosis, who underwent coronary artery bypass grafting. According to the histological analysis of atherosclerotic plaques, men were divided into 2 groups:

40 men (39,6%) with stable plaque; 61 men (60,4%) with vulnerable plaques in CA. Genotyping of rs1799963 and rs6046 was performed by reverse transcription polymerase chain reaction, rs1799889 — by polymerase chain reaction. Statistical processing was performed using the SPSS 16.0 software package.

Results. In patients with stable plaques, allele A of rs6046 polymorphism in the F7 gene was observed in 2,9 times more often (95% confidence interval (CI), 1,20-7,20, p=0,021) than in men with vulnerable plaques. The odds ratio of the GA genotype carriage is 4,03 times higher among patients with stable plaques in CA compared with vulnerable plaques (95% CI, 1,49-10,93, p=0,006). The odds ratio of the 5G/4G genotype carriage among patients with stable plaques in CA is 2,47 times higher than in patients with vulnerable plaques (95% CI, 1,08-5,62, p=0,039). The 4G/4G genotype carriage is 5,85 times much more common in men with stable plaques (95% CI, 1,61-21,34, p=0,003).

Conclusion. Polymorphism in the PAI1 (rs1799889) and F7 (rs6046) genes are associated with the presence of vulnerable plaques in CA in men with verified coronary atherosclerosis. There were no differences between the groups in the frequencies of genotypes and alleles of the rs1799963 polymorphism of the F2 gene. Also, no significant differences were found in the blood levels of PAI-1 and factor VII in groups with different genotypes.

Key words: hemostasis, factor II, factor VII, PAI1, stable and vulnerable atherosclerotic plaques in coronary arteries, single-nucleotide polymorphism, rs6046, rs1799889, rs1799963.

Relationships and Activities. The study was carried out within the state assignments № AAAA-A17-117112850280-2 and № 0324-2017-0048 and with the financial support of the Russian Foundation for Basic Research grant № 19-015-00055a.

1Research Institute of Internal and Preventive Medicine, Federal Research Center Institute of Cytology and Genetics, Novosibirsk; 2Meshalkin National Medical Research Center, Novosibirsk, Russia.

Stryukova E. V.* ORCID: 0000-0001-5316-4664, Maksimov V. N. ORCID: 0000-0002-7165-4496, Ragino Yu. I. ORCID: 0000-0002-4936-8362, Polonskaya Ya. V. ORCID: 0000-0002-3538-0280, Murashov I. S. ORCID: 0000-0002-3712-1258, Volkov A. M. ORCID: 0000-0001-9697-7091, Kurguzov A. V. ORCID: 0000-0003-1345-2199, Chernyavsky A. M. ORCID: 0000-0001-9818-8678, Kashtanova E. V. ORCID: 0000-0003-2268-4186.

*Corresponding author: stryukova.j@mail.ru

Received: 21.01.2020

Revision Received: 29.02.2020

Accepted: 13.03.2020

For citation: Stryukova E. V., Maksimov V. N., Ragino Yu. I., Polonskaya Ya. V., Murashov I. S., Volkov A. M., Kurguzov A. V., Chernyavsky A. M., Kashtanova E. V. Polymorphisms in F2, F7, and PAI1 genes in men with coronary atherosclerosis. Russian Journal of Cardiology. 2020;25(10):3721. (In Russ.) doi:10.15829/1560-4071-2020-3721

NEXT GENERATION SEQUENCING IN SUDDEN CARDIAC DEATH (PILOT STUDY)

Maksimov V. N.1,2, Ivanoshchuk D. E.1, Orlov P. S.1, Ivanova A. A.1, Malyutina S. K.1,2, Maksimova S. V.2, Rodina I. A.3, Khamovich O. V.3, Novoselov V. P.2,3, Voevoda M. I.1,2

Abstract

Aim. To search for causal mutations in candidate genes responsible for the development of sudden cardiac death (SCD) in men who died under the age of 45.

Material and methods. The SCD group (n=37) was formed using the criteria the World Health Organization and the European Society of Cardiology. Autopsy material was collected from men who died suddenly outside medical institutions and underwent

forensic medical examination according to the standard protocol. Autopsy revealed no morphological changes that could explain sudden death. The mean age was 32,4±6,4 years. Genomic DNA was isolated from myocardial tissue using phenol-chloroform

extraction. Clinical exome sequencing was performed. At first, we analyzed the results of sequencing of 24 genes, mutations in which lead to cardiovascular diseases associated with an increased risk of SCD: KCNQ1, KCNH2, SCN5A, AKAP9, ANK2, CACNA1C, CALM1, CALM2, CAV3, KCNE1, KNCJNE2, KCNE2, SCN4B, SNTA1, MYH2, APOB, KCNA5, TGFB3, NEB, PDX1, FLNC, PLEC, KCND3.

Results. Of 37 samples, we revealed 13 probable pathogenic missense mutations in 9 samples (24,3%). Of 13 probable pathogenic variants, 5 were new.

Conclusion. This pilot study provides following conclusions: it is necessary to continue molecular autopsy research in Russia; to increase the effectiveness of detecting causal mutations, it is necessary to reduce the age of patients with SCD included in the study; studying the families of deceased; cooperation of experienced specialists — forensic pathologist, laboratory geneticist, cardiologist.

Key words: sudden cardiac death, mutation, NGS, gene panel, exome, molecular autopsy.

Relationships and Activities. This paper was supported by the Russian Foundation for Basic Research grant № 17-29-06026, partially by the grant № NSh-2595.2020.7, and budget projects № 0324-2016-0002, № 0120.0502961.

1Research Institute of Therapy and Preventive Medicine, Federal Research Center Institute of Cytology and Genetics, Novosibirsk; 2Novosibirsk State Medical University, Novosibirsk; 3Novosibirsk Regional Clinical Bureau of Forensic Medicine, Novosibirsk, Russia.

Maksimov V. N.* ORCID: 0000-0002-7165-4496, Ivanoshchuk D. E. ORCID: 0000-0002-0403-545X, Orlov P. S. ORCID: 0000-0001-9371-2178, Ivanova A. A. ORCID: 0000-0002-9460-6294, Malyutina S. K. ORCID: 0000-0001-6539-0466, Maksimova S. V. ORCID: 0000-0002-2472-181X, Rodina I. A. ORCID: 0000-0003-2799-0756, Khamovich O. V. ORCID: 0000-0002-2960-193Х, Novoselov V. P. ORCID: 0000-0002-6312-5543, Voevoda M. I. ORCID: 0000-0001-9425-413X.

*Corresponding author: medik11@mail.ru

Received: 04.05.2020

Revision Received: 22.06.2020

Accepted: 09.08.2020

For citation: Maksimov V. N., Ivanoshchuk D. E., Orlov P. S., Ivanova A. A., Malyutina S. K., Maksimova S. V., Rodina I. A., Khamovich O. V., Novoselov V. P., Voevoda M. I. Next generation sequencing in sudden cardiac death (pilot study). Russian Journal of Cardiology. 2020;25(10): 3880. (In Russ.) doi:10.15829/1560-4071-2020-3880

DEOXYRIBONUCLEIC ACID METHYLATION IN THE ENHANCER REGION OF THE CDKN2A/2B AND CDKN2B-AS1 GENES IN BLOOD VESSELS AND CELLS IN PATIENTS WITH CAROTID ATHEROSCLEROSIS

Koroleva Yu. A.1, Markov A. V.1, Goncharova I. A.1, Sleptsov A. A.1, Babushkina N. P.1, Valiakhmetov N. R.2, Sharysh D. V.1, Zarubin A. A.1, Kuznetsov M. S.2, Kozlov B. N.2, Nazarenko M. S.1

Abstract

Aim. Comparative analysis of the deoxyribonucleic acid (DNA) methylation level in the enhancer region of the CDKN2A/2B and CDKN2B-AS1 genes (9p21.3 locus) in vessels with/without atherosclerotic lesions, as well as in leukocytes of patients with clinically relevant carotid artery (CA) atherosclerosis and healthy individuals.

Material and methods. The group of patients with clinically relevant athero-sclerosis included 22 individuals with severe stenosis (>80%) of CA. Samples of atherosclerotic plaques, presenting CA regions, and great saphenous veins, as well as peripheral blood samples (leukocytes) were obtained from patients. The control group consisted of 14 individuals with the mild CA stenosis (≤24%) and without hemodynamically relevant changes; peripheral blood samples were obtained from each of them. DNA methylation level was assessed by targeted bisulfite sequencing of amplicons.

Results. The tissue-specific methylation of 31 CpG-site in the CDKN2A/2B and CDKN2B-AS1 gene enhancer was established: the vascular tissues significantly differed from the peripheral blood leukocytes. At the same time, there was an increase in the methylation level of both certain CpG sites and whole analyzed CA region affected by atherosclerosis (48,6 [34,8; 62,0]%), compared with intact vessels, both arteries (25,2 [23,1; 41,60]%, p=0,0001) and veins (35,0 [31,6; 40,0]%, p=0,0039). Patients had lower methylation levels in all CpG sites in blood leukocytes compared to blood vessel samples (8,7 [6,1; 9,7]%; p<0,05). At the same time, the level of DNA methylation in the blood leukocytes of atherosclerotic patients does not differ from that in healthy individuals (9,3 [8,3; 13,6]%; p>0,8).

Conclusion. In the present study, the relationship between an increase in the DNA methylation in the enhancer of the CDKN2A/2B and CDKN2B-AS1 genes in CA and their atherosclerotic lesions was revealed, as well as the tissue-specific DNA methylation between vessels and peripheral blood leukocytes.

Key words: atherosclerosis, DNA methylation, 9p21.3, CDKN2A/2B, CDKN2B-AS1.

Relationships and Activities: none.

1Research Institute of Medical Genetics, Tomsk National Research Medical Center, Tomsk; 2Cardiology Research Institute, Tomsk National Research Medical Center, Tomsk, Russia.

Koroleva Yu. A.* ORCID: 0000-0003-1498-6934, Markov A. V. ORCID: 0000-0002-5824-6439, Goncharova I. A. ORCID: 0000-0002-9527-7015, Sleptsov A. A. ORCID: 0000-0003-3226-1750, Babushkina N. P. ORCID: 0000-0001-6133-8986, Valiakhmetov N. R. ORCID: 0000-0001-7969-7020, Sharysh D. V. ORCID: 0000-0003-2173-2772, Zarubin A. A. ORCID: 0000-0001-6568-6339, Kuznetsov M. S. ORCID: 0000-0002-1975-043X, Kozlov B. N. ORCID: 0000-0002-0217-7737, Nazarenko M. S. ORCID: 0000-0002-0673-4094.

*Corresponding author: yuliya.koroleva@medgenetics.ru

Received: 13.08.2020

Revision Received: 31.08.2020

Accepted: 07.09.2020

For citation: Koroleva Yu. A., Markov A. V., Goncharova I. A., Sleptsov A. A., Babushkina N. P., Valiakhmetov N. R., Sharysh D. V., Zarubin A. A., Kuznetsov M. S., Kozlov B. N., Nazarenko M. S. Deoxyribonucleic acid methylation in the enhancer region

of the CDKN2A/2B and CDKN2B-AS1 genes in blood vessels and cells in patients with carotid atherosclerosis. Russian Journal of Cardiology. 2020;25(10):4060. (In Russ.) doi:10.15829/1560-4071-2020-4060

INTERLEUKIN 18 LEVELS IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE IS ASSOCIATED WITH IL18RAP AND IL18R1 GENE POLYMORPHISM AND THE RISK OF MYOCARDIAL INFARCTION

Ponasenko A. V.1, Tsepokina A. V.1, Khutornaya M. V.1, Malyshev I. Yu.2, Barbarash O. L.1

Abstract

Aim. To determine the relationship between the serum interleukin (IL) 18 level, the carriage of variant alleles IL18, IL18R1, IL18RAP and the risks of myocardial infarction (MI), hypertension, multifocal atherosclerosis in patients with stable coronary artery disease (CAD).

Material and methods. Two hundred and sixty patients with stable coronary artery disease living in a large industrial region of Western Siberia were examined. Serum IL18 concentrations was determined by the enzyme immunoassay. Genotyping was performed by real-time polymerase chain reaction using TaqMan technology.

Results. We revealed associations of rs13015714 IL18R1 and rs917997 IL18RAP sites with the MI risk (odds ratio (OR), 1,95 [95% confidence interval (CI), 1,06-3,58], p=0,029; OR, 2,01 [95% CI, 1,11-3,64], p=0,018, respectively). Associations of rs13015714 and rs917997 sites with high IL18 concentrations (genotypes C/T + T/T 488,0 [321,0, 687,2] pg/ml and T/G + G/G 504,2 [275,6; 655,5] pg/ml) was observed.

Conclusion. The relationship between the minor alleles of rs13015714 IL18R1 and rs917997 IL18RAP sites with an increased risk of MI in patients with stable CAD was shown. Also, polymorphism at rs13015714 and rs917997 sites provides different levels of circulating IL18. In particular, the carriage of minor alleles is associated with increased IL-18 levels in patients with previous MI and multifocal atherosclerosis or hypertension, as well as with an increase in the risk of these pathologies.

Key words: atherosclerosis, coronary artery disease, gene, IL18, IL18R1, IL18RAP, serum concentrations, interleukin 18.

Relationships and Activities. This paper was supported by the complex program of fundamental research of the Siberian Branch of the Russian Academy of Sciences within the fundamental theme of the Research Institute for Complex Issues of Cardiovascular Diseases № 0546-2019-0003 “Multifocal atherosclerosis and comorbidities. Features of diagnostics, risk management in a large industrial region of Siberia”.

1Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo; 2A. I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia.

Ponasenko A. V. ORCID: 0000-0002-3002-2863, Tsepokina A. V.* ORCID: 0000-0002-4467-8732, Khutornaya M. V. ORCID: 0000-0002-9714-4080, Malyshev I. Yu. ORCID: 0000-0002-2381-9612, Barbarash O. L. ORCID: 0000-0002-4642-3610.

*Corresponding author: cepoav1991@gmail.com

Received: 22.06.2020

Revision Received: 10.08.2020

Accepted: 31.08.2020

For citation: Ponasenko A. V., Tsepokina A. V., Khutornaya M. V., Malyshev I. Yu., Barbarash O. L. Interleukin 18 levels in patients with stable coronary artery disease is associated with IL18RAP and IL18R1 gene polymorphism and the risk of myocardial infarction. Russian Journal of Cardiology. 2020;25(10):3977. (In Russ.) doi:10.15829/1560-4071-2020-3977

EXPRESSION OF MATRIX METALLOPROTEINASES 1, 2, 9, 12 IN XENOGENIC TISSUES OF EPOXY-CROSSLINKED BIOPROSTHETIC HEART VALVES EXPLANTED DUE TO DYSFUNCTION

Kostyunin A. E., Glushkova T. V.

Abstract

Aim. To study the expression of matrix metalloproteinases (MMPs) 1, 2, 9, 12 in the leaflets of epoxy-crosslinked bioprosthetic heart valves (BHVs) explanted due to dysfunction and to study the possibility to accumulate these enzymes in xenogenic tissues.

Material and methods. We examined 19 leaflets of 7 mitral and aortic BHVs removed during re-replacement. Tissue sections for microscopy were prepared using a cryotome. Сellular typing and detection of MMP 1, 2, 9, 12 expression in samples were performed using immunohistochemical staining with antibodies to PTPRC/CD45, CD68, myeloperoxidase, and the corresponding MMPs. Analysis of samples was performed by light microscopy.

Results. In 17 studied leaflets from 6 explanted BHVs, sporadic infiltrates consisting of macrophages (PTPRC/CD45+, CD68+) were revealed. A positive staining for MMP 1, 2, 9, 12 was colocalized with immune cell infiltrates. Also, positive staining was observed without cell infiltration. The pericardial BHV removed due to thrombosis 2 days after implantation did not show signs of macrophage infiltration or MMP expression in xenogenic tissues, but the thrombus stained positive for MMP-9 and included a large number of neutrophils positive for myeloperoxidase.

Conclusion. Macrophages and other immune cells infiltrating xenogenic tissues of epoxy-crosslinked BHV are sources of MMPs 1, 2, 9, 12. In addition, MMP-9 can diffuse into BHV leaflets from the blood plasma of patients. The deposition of MMP may contribute to rupture and calcification of the leaflets leading to the implant dysfunction.

Key words: bioprosthetic heart valves, structural valve degeneration, cell infiltration, matrix metalloproteinases.

Relationships and Activities. This study was carried within the program of basic research on the fundamental subject of Research Institute for Complex Issues of Cardiovascular Diseases № 0546-2019-0002 “Pathogenetic rationale for the development of implants for cardiovascular surgery based on biocompatible materi als, with the implementation of a patient-centered approach using mathematical modeling, tissue engineering methods and genomic predictors”.

Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia.

Kostyunin A. E.* ORCID: 0000-0001-6099-0315, Glushkova T. V. ORCID: 0000-0003-4890-0393.

*Corresponding author: Rhabdophis_tigrina@mail.ru

Received: 22.06.2020

Revision Received: 04.08.2020

Accepted: 06.08.2020

For citation: Kostyunin A. E., Glushkova T. V. Expression of matrix metalloproteinases 1, 2, 9, 12 in xenogenic tissues of epoxy-crosslinked bioprosthetic heart valves explanted due to dysfunction. Russian Journal of Cardiology. 2020;25(10):3978. (In Russ.) doi:10.15829/1560-4071-2020-3978

RELATIONSHIP OF MATRIX METALLOPROTEINASE-3 -1171 5A/6A POLYMORPHISM (RS35068180) AND DILATED CARDIOMYOPATHY

Nikulina S. Yu.1, Kuznetsova O. O.1,2, Chernova A. A.1, Maksimov V. N.3

Abstract

Aim. To study the relationship of matrix metalloproteinase-3 (MMP3) genetic polymorphism and dilated ischemic cardiomyopathy (DCM), as well as idiopathic cardiomyopathy (ICM) of unknown etiology.

Material and methods. A total of 221 patients with DCM and ICM were examined (mean age, 55,30±9,69 years). The group of ischemic DCM consisted of 111 people (99 men (89,2%) and 12 women (10,8%)). The mean age of DCM subjects was 51,73±9,74 years (male subgroup, 51,00±8,96 years; female subgroup, 57,75±3,71 years). The ICM group consisted of 110 people (100 men (91,5%) and 10 women (8.5%)). The mean age of ICM subjects was 58,68±8.38 years (male subgroup, 58,29±8.,6 years; female subgroup, 62,90±6,29 years). The control group of subjects (n=121) consisted of healthy people without cardiovascular diseases

(mean age, 53,6±4,8 years). All patients of the experimental group underwent routine diagnostic tests, as well as coronary angiography. In case of suspected myocarditis, cardiac magnetic resonance imaging was performed. All patients underwent polymerase chain reaction to determine the MMP3-1171 5A/6A polymorphism (rs35068180).

Results. In patients with cardiomyopathy, regardless of the disease origin, significant differences were verified in comparison with the control group. Allele 6A (65,8% vs 59,3%, p=0,044) and genotype 6A/6A (42,1% vs 32,6%, p=0,099) were found significantly more frequently in patients with cardiomyopathy than in the control group. In addition, despite various etiological factors, the pathogenetic involvement of MMP3 is likely to have a general direction.

Conclusion. In all patients with cardiomyopathy, the prevalence of MMP3 gene A allele was shown. Due to decrease in the transcription activity in homozygous 6A allele, the stromelysin level in arterial walls also decreases. This promotes the activation of procollagenase-1, the deposition of extracellular matrix and cardiac remodeling.

Key words: dilated cardiomyopathy, genetic polymorphism, matrix metalloproteinase-3.

1V.F. Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk; 2Federal center for cardiovascular surgery of the Ministry of Health of Russia, Krasnoyarsk; 3Research Institute of Therapy and Preventive Medicine, Novosibirsk, Russia.

Relationships and Activities: none.

Nikulina S. Yu. ORCID: 0000-0002-6968-7627, Kuznetsova O. O.* ORCID: 0000-0003-2247-4242, Chernova A. A. ORCID: 0000-0003-2977-1792, Maksimov V. N. ORCID: 0000-0002-7165-4496.

*Corresponding author: Isachenko102@inbox.ru

Received: 10.06.2020

Revision Received: 10.08.2020

Accepted: 17.08.2020

For citation: Nikulina S. Yu., Kuznetsova O. O., Chernova A. A., Maksimov V. N. Relationship of matrix metalloproteinase-3 -1171 5A/6A polymorphism (rs35068180) and dilated cardiomyopathy. Russian Journal of Cardiology. 2020;25(10):3960. (In Russ.) doi:10.15829/1560-4071-2020-3960

LEFT VENTRICULAR NONCOMPACTION ASSOCIATED WITH TITIN-TRUNCATING VARIANTS IN THE TTN GENE

Vakhrushev Yu. A., Vershinina T. L., Fedotov P. A., Kozyreva A. A., Kiselev A. M., Fomicheva Yu. V., Vasichkina E. S., Pervunina T. M., Kostareva A. A.

Abstract

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 the Almazov National Medical Research Center. 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.

Key words: left ventricular noncompaction, titin, cardiomyopathy.

Relationships and Activities. The study was supported by a grant from the Russian Science Foundation (project № 18-75-00006).

Almazov National Medical Research Center, St. Petersburg, Russia.

Vakhrushev Yu. A.* ORCID: 0000-0001-8911-1927, Vershinina T. L. ORCID: 0000-0003-1311-2020, Fedotov P. A. ORCID: 0000-0002-7452-1971, Kozyreva A. A. ORCID: 0000-0003-0656-7967, Kiselev A. M. ORCID: 0000-0002-5524-6900, Fomicheva Yu. V. ORCID: 0000-0001-8950-8617, Vasichkina E. S. ORCID: 0000-0001-7336-4102, Pervunina T. M. ORCID: 0000-0001-9948-7303, Kostareva A. A. ORCID: 0000-0002-9349-6257.

*Corresponding author: thevakhr@gmail.com

Received: 20.07.2020

Revision Received: 25.08.2020

Accepted: 01.09.2020

For citation: Vakhrushev Yu. A., Vershinina T. L., Fedotov P. A., Kozyreva A. A., Kiselev A. M., Fomicheva Yu. V., Vasichkina E. S., Pervunina T. M., Kostareva A. A. Left ventricular noncompaction associated with titin-truncating variants in the TTN gene.

Russian Journal of Cardiology. 2020;25(10):4027. (In Russ.) doi:10.15829/1560-4071-2020-4027

MOLECULAR BIOMARKER PROFILE OF HEART FAILURE WITH MID-RANGE AND PRESERVED EJECTION FRACTION IN PATIENTS WITH TYPE 2 DIABETES

Lebedev D. A., Lyasnikova E. A., Vasilyeva A. A., Vasilyeva E. Yu., Babenko A. Yu., Shlyakhto E. V.

Abstract

Aim. To study molecular biomarkers in patients with type 2 diabetes (T2D) in combination with heart failure with preserved (HFpEF) and mid-range ejection fraction (HFmrEF) and compare the data obtained with clinical characteristics of myocardial remodeling.

Material and methods. The study included 42 patients with T2D (men — 53%, mean age — 60 years) with clinical manifestations of class II HF: 29 patients with HFpEF (group 1) and 13 patients with HFmrEF (group 2). The control group consisted of 13 healthy people, which were comparable in sex and age and had a normal body mass index (BMI). Patients received stable glucose-lowering and optimal drug therapy for HF for 3 months prior to enrollment in the study. Patients with HFpEF and HFmrEF were comparable in clinical and demographic parameters, had glycated hemoglobin (HbA1c) of 8,5% and 8,8%, respectively (p>0,05), increased BMI or grade I-II obesity. We studied following biomarkers: NT-proBNP, highly sensitive C-reactive protein (hsCRP), sST2, galectin-3, procollagen type I C-terminal propeptide (PICP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1).

Results. Volumetric parameters of the left ventricle (LV), LV mass indexed to growth and NT-proBNP were higher in the group of HFpEF patients (p<0,05 for all). The concentrations of galectin-3, PICP were higher, and the MMP-9/TIMP-1 ratio decreased in patients with T2D compared with the control group (p<0,05 for all). PICP values were higher in patients with HFmrEF compared with patients with HFpEF (106,4 (85,4; 140,4) ng/ml vs 46,8 (12,6; 98,6 ng/ml), respectively, p=0,043). In patients with T2D and HF, a relationship was found between TIMP-1 and LV end-diastolic volume (r=-0,68; p=0,042).

Conclusion. Patients with HFmrEF and T2D have higher LV volume and mass, higher concentrations of NT-proBNP and PICP in comparison with patients with HFpEF. The direction of MMP-9/TIMP-1 changes may reflect a decrease in antifibrotic processes. Further prospective studies on large samples using a multiple biomarker model are required in T2D and various HF phenotypes.

Key words: heart failure, diabetes, biomarkers, mid-range ejection fraction, preserved ejection fraction, fibrosis.

Relationships and Activities. This work was supported by a grant from the Russian Science Foundation № 17-75-30052.

Almazov National Medical Research Center, St. Petersburg, Russia.

Lebedev D. A.* ORCID: 0000-0003-1808-1331, Lyasnikova E. A. ORCID: 0000-0003-0613-829X, Vasilyeva A. A. ORCID: 0000-0003-0919-7607, Vasilyeva E. Yu. ORCID: 0000-0003-3185-3957, Babenko A. Yu. ORCID: 0000-0002-0559-697X, Shlyakhto E. V. ORCID: 0000-0003-2929-0980.

*Corresponding author: doctorlebedev@yandex.ru

Received: 11.06.2020

Revision Received: 29.06.2020

Accepted: 06.07.2020

For citation: Lebedev D. A., Lyasnikova E. A., Vasilyeva A. A., Vasilyeva E. Yu., Babenko A. Yu., Shlyakhto E. V. Molecular biomarker profile of heart failure with mid-range and preserved ejection fraction in patients with type 2 diabetes. Russian Journal

of Cardiology. 2020;25(10):3967. (In Russ.) doi:10.15829/1560-4071-2020-3967

TRANSCRIPTOME ANALYSIS OF SKELETAL MUSCLES REVEALED THE EFFECT OF EXERCISE ON THE MOLECULAR MECHANISMS REGULATING MUSCLE GROWTH AND METABOLISM IN PATIENTS WITH HEART FAILURE

Ivanova O. A.1,2, Ignatieva E. V.1, Lelyavina T. A.1, Galenko V. L.1, Komarova M. Yu.1, Bortsova M. A.1, Sitnikova M. Yu.1, Kostareva A. A.1,3, Sergushichev A. A.2, Dmitrieva R. I.1

Abstract

Aim. Heart failure (HF) is accompanied by skeletal muscle atrophy and exercise intolerance. The aim was to study the molecular mechanisms underlying the therapeutic effect of personalized exercise in patients with HF.

Material and methods. RNA sequencing obtained from skeletal muscle biopsies before and after a 12-week exercise course was used to identify changes in gene expression and signaling pathways induced by the physical rehabilitation program for patients with HF.

Results. We have shown that personalized exercise program in patients with HF stimulates the activation of molecular pathways regulating the differentiation and functioning of skeletal muscles: commitment of muscle progenitor cells; mechanisms regulating the calcium release and sensitivity of myofibrillar contraction, electrical excitability of the muscle membrane, synaptic vesicle proton gradient creation, maintenance of electrochemical gradients of Na+/K+. Also, the analysis of differentially expressed genes revealed an increase in the expression of transcription factors MyoD and MEF2, which are responsible for the differentiation of muscle stem cells, and sarcomeric genes MYOM1, MYOM2, MYH7. Along with this, we observed activation of the CYR61 expression — a potential prognostic biomarker for HF patients.

Conclusion. Our data show that the beneficial effect of personalized aerobic exercise in patients with HF depends, at least in part, on an improvement in the physiological and biochemical parameters of skeletal muscle.

Key words: heart failure, exercise, skeletal muscle atrophy, RNA sequencing, signaling pathways, gene expression.

Relationships and Activities. This work was supported by the Russian Science Foundation (grant № 16-15-10178).

1Almazov National Medical Research Center, St. Petersburg, Russia; 2ITMO University, St. Petersburg, Russia; 3Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.

Ivanova O. A. ORCID: 0000-0002-6163-2162, Ignatieva E. V. ORCID: 0000-0002-1423-6562, Lelyavina T. A. ORCID: 0000-0001-6796-4064, Galenko V. L. ORCID: 0000-0002-0503-167X, Komarova M. Yu. ORCID: 0000-0002-7520-090X, Bortsova M. A. ORCID: 0000-0002-9694-7850, Sitnikova M. Yu. ORCID: 0000-0002-0139-5177, Kostareva A. A. ORCID: 0000-0002-9349-6257, Sergushichev A. A. ORCID: 0000-0003-1159-7220, Dmitrieva R. I.* ORCID: 0000-0002-3073-7914.

*Corresponding author: renata.i.dmitrieva@gmail.com

Received: 30.09.2020

Revision Received: 15.10.2020

Accepted: 15.10.2020

For citation: Ivanova O. A., Ignatieva E. V., Lelyavina T. A., Galenko V. L., Komarova M. Yu., Bortsova M. A., Sitnikova M. Yu., Kostareva A. A., Sergushichev A. A., Dmitrieva R. I. Transcriptome analysis of skeletal muscles revealed the effect of exercise on the molecular mechanisms regulating muscle growth and metabolism in patients with heart failure. Russian Journal of Cardiology. 2020;25(10):4132. (In Russ.) doi:10.15829/1560-4071-2020-4132

BIOCHEMICAL PROFILE AND PROGNOSIS OF PATIENTS WITH HEART FAILURE AND DIABETES

Mardanov B. U.1, Kokozheva M. A.2, Mamedov M. N.1

Abstract

Aim. To study clinical and hemodynamic and laboratory parameters for the 2-year prognosis of patients with chronic heart failure (CHF) and type 2 diabetes mellitus (DM).

Material and methods. The study included 90 patients (61,4±8,6 years old) with NYHA class II-IV CHF related to coronary artery disease and hypertension. All patients underwent clinical examination, resting 12-lead electrocardiography, transthoracic echocardiography, and blood chemistry testing. Two-year follow-up was conducted to determine the prognosis of patients with CHF and DM.

Results. CHF duration in patients with DM was 17% more, despite a comparable average age of patients. Echocardiography showed significant left ventricular dilatation and, as a result, systolic dysfunction in patients of the I group (with DM). Hypoalbuminemia was detected in both groups, but it was more pronounced in patients with CHF and DM. With comparable average creatinine concentrations, patients with CHF and DM had higher blood urea levels (13,2±2,1 μmol/L and 9,4±2,6 μmol/L, respectively). Patients of group I had significantly lower glomerular filtration rate (GFR) compared to the comparison group (by 13%). In group I, there were 42 rehospitalizations during the follow-up period, while in the comparison group — 29. Acute cerebrovascular accident was recorded in 7% and 4% of cases, respectively. Myocardial infarction (MI), including recurrent MI, was registered 50% more often in patients with DM. The mortality rate in patients of the group I was 3,5 times higher than in the comparison group.

Conclusion. Features of the course of CHF depending on the presence of concomitant type 2 DM were revealed. These include the relatively early manifestation of CHF symptoms, the prevalence of patients with moderate to severe CHF and severe left ventricular systolic dysfunction. The results of a biochemical study of the blood of group I patients were characterized by hypoalbuminemia, hypertriglyceridemia, and a significant decrease in GFR. It is noted that the presence of concomitant DM aggravates the course of CHF of ischemic and nonischemic genesis, which is manifested by an increase in the frequency of repeated hospitalizations and deaths during 2-year follow-up.

Key words: heart failure, diabetes, biochemical parameters, prognosis.

Relationships and Activities: none.

1National Medical Research Center for Therapy and Preventive Medicine, Moscow; 2N. V. Sklifosovsky Clinical and Research Institute for Emergency Medicine, Moscow, Russia.

Mardanov B. U.* ORCID: 0000-0002-8820-9436, Kokozheva M. A. ORCID: 0000-0002-2211-8160, Mamedov M. N. ORCID: 0000-0001-7131-8049.

*Corresponding author: mb_sky@inbox.ru

Received: 14.04.2020

Revision Received: 20.05.2020

Accepted: 29.06.2020

For citation: Mardanov B. U., Kokozheva M. A., Mamedov M. N. Biochemical profile and prognosis of patients with heart failure and diabetes. Russian Journal of Cardiology. 2020;25(10):3841. (In Russ.) doi:10.15829/1560-4071-2020-3841

CLINIC AND PHARMACOTHERAPY

EFFECT OF DAPAGLIFLOZIN IN PATIENTS WITH HEART FAILURE ON REDUCING CARDIOVASCULAR MORTALITY

Zhuravleva M. V.1,2, Tereshchenko S. N.3, Zhirov I. V.3, Villevalde S. V.4, Marin T. V.2, Gagarina Yu. V.2

Abstract

Aim. To assess the effect of dapagliflozin in patients with heart failure with reduced ejection fraction (HFrEF) on reducing cardiovascular mortality as the main goal of a federal project on the prevention of cardiovascular diseases.

Material and methods. All adult Russian patients with a documented NYHA class II-IV HFrEF (EF ≤40%) were considered the target population. The characteristics of the patients corresponded to those of the Russian Hospital Heart Failure Registry (RUS-HFR). The study looked at an increase in the dapagliflozin use in addition to standard therapy by 10% of patients annually in 2021-2023 and calculated the number of deaths that could be prevented. Cardiovascular mortality curve was created by extrapolation of the DAPA-HF study results using the Kaplan-Meier method. Further, the contribution of prevented deaths with dapagliflozin to the achievement of regional and federal targets for reducing cardiovascular mortality was calculated for 1, 2, and 3 years.

Results. In case of 10% annual increase in dapagliflozin use in patients with NYHA class II-IV HFrEF, this will allow: — to prevent an additional 1,736 cardiovascular deaths in the first year, achieving the target of federal project on the prevention of cardiovascular diseases in 2021 by 5,9%; — to prevent an additional 3,784 cardiovascular deaths in the second year, achieving

the target of federal project on the prevention of cardiovascular diseases in 2022 by 12,9%; — to prevent an additional 5,485 cardiovascular deaths in the third year, achieving the target of federal project on the prevention of cardiovascular diseases in 2023

by 18,7%.

Conclusion. The use of dapagliflozin in patients with HFrEF will reduce mortality from cardiovascular diseases.

Key words: dapagliflozin, heart failure, targets, cardiovascular mortality, federal project on the prevention of cardiovascular diseases.

Relationships and Activities. The study was supported by AstraZeneca.

1Scientific Centre for Expert Evaluation of Medicinal Products, Moscow; 2I. M. Sechenov First Moscow State Medical University, Moscow; 3National Medical Research Center of Cardiology, Moscow; 4Almazov National Medical Research Center, St. Petersburg, Russia.

Zhuravleva M. V.* ORCID: 0000-0002-9198-8661, Tereshchenko S. N. ORCID: 0000-0001-9234-6129, Zhirov I. V. ORCID: 0000-0002-4066-2661, Villevalde S. V. ORCID: 0000-0001-7652-2962, Marin T. V. ORCID: 0000-0002-8974-4457, Gagarina Yu. V. ORCID: 0000-0002-4459-3034.

*Corresponding author: doc@pharmset.ru

Received: 26.08.2020

Revision Received: 15.09.2020

Accepted: 22.09.2020

For citation: Zhuravleva M. V., Tereshchenko S. N., Zhirov I. V., Villevalde S. V., Marin T. V., Gagarina Yu. V. Effect of dapagliflozin in patients with heart failure on reducing cardiovascular mortality. Russian Journal of Cardiology. 2020;25(10):4142.

(In Russ.) doi:10.15829/1560-4071-2020-4142

TRIPLE FIXED-DOSE COMBINATION IN THE TREATMENT OF HYPERTENSION: THE RESULTS OF THE RUSSIAN OBSERVATIONAL STUDY TRICOLOR

Karpov Yu. A.1, Gorbunov V. M.2, Logunova N. A.3 on behalf of the TRICOLOR research team#

Abstract

The article presents the main results of the Russian post-marketing multicenter open-label program TRICOLOR (Triple fixed-dose combination in the treatment of hypertension).

Aim. To evaluate the antihypertensive efficacy and tolerability of the triple amlodipine/indapamide/perindopril fixed-dose combination, as well as the adherence of hypertensive (HTN) patients to this therapy in actual clinical practice.

Material and methods. The program enrolled 1247 outpatients aged 18 to 79 of both sexes with essential HTN. All patients included in the study receive amlodipine/indapamide/perindopril fixed-dose combination. The patient’s condition was assessed according to four visits: visit 1 — at inclusion, visit 2 — after 2 weeks, visit 3 — after 4 weeks, visit 4 — after 12 weeks of follow-up. At each visit, the achievement of the target blood pressure (BP) <140/90 mm Hg and <130/80 mm Hg. At enrollment and visit 4, quality of life was analyzed using the SF-36 questionnaire and adherence to therapy using a validated 6-question questionnaire.

Results. After 12 weeks, a significant decrease in systolic and diastolic BP was recorded — by 33,5 and 14,3 mm Hg, respectively (p<0,001). Target BP <140/90 mm Hg after 12-week follow-up was achieved by the overwhelming majority (93,4%) of patients. After 12 weeks, the proportion of patients with good medical adherence increased from 18,8% to 49,0%, while the proportion of patients with low adherence, on the contrary, decreased from 46,3% to 5,1%.

Conclusion. The results of the TRICOLOR program demonstrate a high antihypertensive efficacy, good tolerance and medical adherence of triple amlodipine/indapamide/perindopril fixed-dose combination in patients with essential HTN in actual clinical practice in Russia.

Key words: hypertension, triple fixed-dose combination, amlodipine/indapamide/perindopril.

Relationships and Activities. This study was funded by Servier. Karpov Yu. A. and Gorbunov V. M. reported being the national coordinating investigators. Logunova N. A. reported being the Servier employee.

Acknowledgements. The authors are grateful to all researchers who took part in the TRICOLOR study.

1National Medical Research Center of Cardiology, Moscow; 2National Medical Research Center for Therapy and Preventive Medicine, Moscow; 3Servier Laboratories, Moscow, Russia.

Karpov Yu. A. ORCID: 0000-0003-1480-0458, Gorbunov V. M. ORCID: 0000-0001-5195-8997, Logunova N. A.* ORCID: 0000-0001-5683-5902.

*Corresponding author: Logunova N., natalya.logunova@servier.com

Received: 25.09.2020

Revision Received: 08.09.2020

Accepted: 15.10.2020

For citation: Karpov Yu. A., Gorbunov V. M., Logunova N. A. on behalf of the TRICOLOR research team. Triple fixed-dose combination in the treatment of hypertension: the results of the Russian observational study TRICOLOR. Russian Journal of Cardiology. 2020;25(10):4130. (In Russ.) doi:10.15829/1560-4071-2020-4130

RISK MANAGEMENT IN PATIENTS WITH ATRIAL FIBRILLATION AND COMORBID CONDITIONS: POTENTIALITIES OF EDOXABAN

Barbarash O. L., Kashtalap V. V.

Abstract

The review article presents current data on the clinical and prognostic significance, as well as on the prevalence of comorbidities in patients with atrial fibrillation (AF). The prevalence of hypertension, diabetes and heart failure in patients with AF is discussed according to the Russian and foreign registry studies, randomized clinical trials. The problem of the effect of comorbidity on the risk of embolism and bleeding in AF is outlined. Potentialities of a novel oral anticoagulant edoxaban (based on the ENGAGE AF-TIMI 48 trial) for managing the risks of thromboembolic and bleeding events in AF and comorbidities. Sub-analyzes of the ENGAGE AF-TIMI 48 trial were discussed, which demonstrated efficacy comparable to warfarin in the embolism prevention and higher safety against bleeding, regardless of the comorbidity profile.

Key words: atrial fibrillation, comorbidity, direct oral anticoagulants, edoxaban.

Relationships and Activities. The study was conducted as part of the fundamental theme № 0546-2019-003 “Multifocal atherosclerosis and comorbidities. Features of diagnosis, risk management in a large industrial region of Siberia”, approved by the Ministry of Science and Higher Education of the Russian Federation.

Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia.

Barbarash O. L. ORCID: 0000-0002-4642-3610, Kashtalap V. V.* ORCID: 0000-0003-3729-616X.

*Corresponding author: v_kash@mail.ru

Received: 29.09.2020

Revision Received: 09.10.2020

Accepted: 15.10.2020

For citation: Barbarash O. L., Kashtalap V. V. Risk management in patients with atrial fibrillation and comorbid conditions: potentialities of edoxaban. Russian Journal of Cardiology. 2020;25(10):4131. (In Russ.) doi:10.15829/1560-4071-2020-4131

PROBLEMATIC ARTICLE

A PARADIGM SHIFT IN THE CONCEPT OF ARRHYTHMOGENIC CARDIOMYOPATHY: EXPANDING THE CLINICAL AND GENETIC SPECTRUM, NEW DIAGNOSTIC CRITERIA FOR LEFT VENTRICULAR PHENOTYPES

Vaikhanskaya T. G.1, Sivitskaya L. N.2, Kurushko T. V.1, Rusak T. V.1, Levdansky O. D.2, Danilenko N. G.2, Davydenko O. G.2

Abstract

Recent multicenter studies using high-tech cardiac imaging and novel translational technologies have shown that cardiac fibrofatty replacement, characteristic of arrhythmogenic cardiomyopathy (ACM), is observed in both ventricles; left ventricular (LV) involvement may be minimal, on par with the right ventricle (RV), or dominant. In 2019, the Heart Rhythm Society (HRS) proposed a new approach to the assessment of arrhythmic and genetic diseases with the inclusion of new phenotypes — left-dominant ACM and biventricular ACM. In 2020, to improve the diagnosis of left ventricular phenotypes, European experts revised ACM criteria (based on the 2010 ITF criteria), which are called the Padua criteria. The presented article highlights the clinical and genetic aspects of the new concept and the difficulties in ACM diagnosis, the practical experience of using new diagnostic algorithm. To help practitioners, step-by-step differential diagnosis and risk stratification of right and left ventricular phenotypes are presented using clinical examples (leftdominant ACM with a pathogenic variant in the LMNA gene; right-dominant ACM associated with a desmoplakin gene mutation, with predominant RV and moderate LV involvement; and an isolated RV ACM associated with a mutation in the plakophilin 2 gene).

Key words: arrhythmogenic cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, phenotype, genotype, ventricular tachycardia.

Relationships and Activities: none.

1Republican Scientific and Practical Center “Cardiology”, Minsk; 2Institute of Genetics and Cytology, Minsk, Belarus.

Vaikhanskaya T. G.* ORCID: 0000-0002-2127-8525, Sivitskaya L. N. ORCID: 0000-0001-6359-4967, Kurushko T. V. ORCID: 0000-0001-5727-3219, Rusak T. V. ORCID: 0000-0003-4318-9977, Levdansky O. D. ORCID: 0000-0002-3325-0917, Danilenko

N. G. ORCID: 0000-0002-3270-3080, Davydenko O. G. ORCID: 0000-0002-9790-2953.

*Corresponding author: tat_vaikh@mail.ru

Received: 26.04.2020

Revision Received: 23.06.2020

Accepted: 02.07.2020

For citation: Vaikhanskaya T. G., Sivitskaya L. N., Kurushko T. V., Rusak T. V., Levdansky O. D., Danilenko N. G., Davydenko O. G. A paradigm shift in the concept of arrhythmogenic cardiomyopathy: expanding the clinical and genetic spectrum, new diagnostic criteria for left ventricular phenotypes. Russian Journal of Cardiology. 2020;25(10):3863. (In Russ.) doi:10.15829/1560-4071-2020-3863

BIOMARKERS OF MYOCARDIAL FIBROSIS AND THEIR GENETIC REGULATION IN PATIENTS WITH HEART FAILURE

Pecherina T. B., Kutikhin A. G.

Abstract

Currently, the development of chronic heart failure (CHF) is considered from the perspective of pathological structural remodeling of myocardium and fibrosis. Despite the widespread use of molecular genetic markers in clinical practice, only a small number of them are used to evaluate remodeling processes, as well as to predict potential complications associated with heart failure (HF). In addition, the relationship between many biomarkers with instrumental and histological confirmation of myocardial fibrosis has not yet been determined. Myocardial fibrosis remains quite debatable and controversial subject, which actualizes the further study of this direction. The discovery of pathogenetic and diagnostic markers of myocardial fibrosis could contribute to the development of targeted therapy. Of particular interest is the search for possible pathogenetic markers, since this is relevant for clinical practice.

Key words: heart failure, myocardial fibrosis, biomarkers, genetic regulation.

Relationships and Activities. The study was financially supported by the Russian Foundation for Basic Research and the Kemerovo Region within the project № 18-415-420004 “Molecular genetic markers of fibrosis in postinfarct myocardial remodeling”.

Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russia.

Pecherina T. B.* ORCID: 0000-0002-4771-484X, Kutikhin A. G. ORCID: 0000-0001-8679-4857.

*Corresponding author: tb.pechorina@gmail.com

Received: 28.05.2020

Revision Received: 29.06.2020

Accepted: 14.07.2020

For citation: Pecherina T. B., Kutikhin A. G. Biomarkers of myocardial fibrosis and their genetic regulation in patients with heart failure. Russian Journal of Cardiology. 2020;25(10):3933. (In Russ.) doi:10.15829/1560-4071-2020-3933

ROLE OF RATIO-BASED METRICS IN CARDIOLOGY

Konradi A. O.1, Maslyansky A. L.1, Kolesova E. P.1, Shlyakhto E. V.1, Peter L. M. Kerkhof2

Abstract

In cardiovascular studies, two related parameters that determine the same physical variable are often recorded. Interpretation of the calculated indicators presented in the form of ratios and differences is difficult, since they can be associated with several combinations of primary data giving the same value.

Aim. To find a way to overcome this limitation and take a more comprehensive approach.

Material and methods. We analyzed the data on left ventricular volume and blood pressure (BP) in 275 patients (women — 207), obtained using echocardiography and BP monitor. To calculate a lost companion (c) value based on a difference or dimensionless ratio, we applied the Pythagorean theorem. The lost companion is defined as the hypotenuse in each study area. To calculate the pulse pressure companion (PP), the following formula was used: PP(c)=√(SBP2+SBP2). Similar methods were applied to ejection fraction (EF), augmentation pressure (AG) and AG/PP ratio, resulting in the ratio called augmentation index (AIx).

Results. 1. Mean blood pressure (MBP) acts as a surrogate for the PP companion (PPc) values (R=0,970, N=257,2). We have identified correlations between PPc and pulse wave velocity (R=0,397, N=193), and AGc with AIx (75) (R=0,662, N=198). 3. EF has an inverse relationship with the end diastolic volume (EDV) (R=-0,559, N=187), and the ventricular-arterial coupling (VAC) correlates with ESV (r=-0,627, N=180). 4. Comparison of EDV and VACc revealed R of 0,949.

Conclusion. Companions calculated from the available data can have significant additional diagnostic value without the need for additional measurements. It is important to note that the combination of traditional ratio-based and suggested companions allows for more accurate data on individual patients.

Key words: ejection fraction, mean blood pressure, pulse pressure, augmentation index, pulse wave velocity, statistics.

Relationships and Activities. The study was supported by the Russian Science Foundation (project № 17-75-30052).

1Almazov National Medical Research, St. Petersburg, Russia; 2Department of Radiology and Nuclear Medicine, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, VUmc, Amsterdam, The Netherlands.

Konradi A. O.* ORCID: 0000-0001-8169-7812, Maslyansky A. L. ORCID: 0000-0003-2427-4148, Kolesova E. P. ORCID: 0000-0002-1073-3844, Shlyakhto E. V. ORCID: 0000-0003-2929-0980, Peter L. M. Kerkhof ORCID: 0000-0001-9488-633X.

*Corresponding author: konradi@almazovcentre.ru

Received: 25.05.2020

Revision Received: 06.06.2020

Accepted: 01.07.2020

For citation: Konradi A. O., Maslyansky A. L., Kolesova E. P., Shlyakhto E. V., Peter L. M. Kerkhof. Role of ratio-based metrics in cardiology. Russian Journal of Cardiology. 2020;25(10):3929. (In Russ.) doi:10.15829/1560-4071-2020-3929

ORGANIZATION OF CARDIAC CARE

PROSPECTS FOR THE IMPLEMENTATION OF A BACHELOR’S DEGREE IN MEDICINE

Sirotkina O. V., Ischuk T. N., Golubeva I. S., Parmon E. V., Shlyakhto E. V.

Abstract

According to modern healthcare requirements, it is necessary to increase workforce capacity of primary care practice, therefore, improving the specialist training is one of the high-priority problems of medical education. Not enough attention is paid to paramedic education and their role in Russian healthcare. The presented analysis of the paramedic profession history and the current state of high-quality healthcare in Russia shows the need to create a regulatory basis for the training of paramedics in the higher education system — a bachelor’s degree.

Key words: paramedic, medical education, general medicine, bachelor’s degree, rural health care, labor market monitoring in health care.

Relationships and Activities. The socially significant project “Improvement of continuous medical training of medical specialists” is supported by the Presidential grants fund.

Almazov National Medical Research Center, St. Petersburg, Russia.

Sirotkina O. V. ORCID: 0000-0003-3594-1647, Ischuk T. N.* ORCID: 0000-0001-7326-8241, Golubeva I. S. ORCID: 0000-0003-0594-4476, Parmon E. V. ORCID: 0000-0002-0852-631X, Shlyakhto E. V. ORCID: 0000-0003-2929-0980.

*Corresponding author: tatischuk@mail.ru

Received: 04.09.2020

Revision Received: 16.09.2020

Accepted: 17.09.2020

For citation: Sirotkina O. V., Ischuk T. N., Golubeva I. S., Parmon E. V., Shlyakhto E. V. Prospects for the implementation of a bachelor’s degree in medicine. Russian Journal of Cardiology. 2020;25(10):4092. (In Russ.) doi:10.15829/1560-4071-2020-4092

CLINICAL AND INVESTIGATIVE MEDICINE

RUSSIAN REGISTER OF ACUTE PULMONARY EMBOLISM SIRENA: CHARACTERISTICS OF PATIENTS AND IN-HOSPITAL TREATMENT

Erlikh A. D.1,2, Atakanova A. N.1, Neeshpapa A. G.3, Cherepanova N. A.4,5, Mullova I. S.4,5, Barbarash O. L.3, Berns S. A.3, Shmidt E. A.3, Duplyakov D. V.4,5

Abstract

Aim. To assess the features of diagnosis, treatment and outcomes of pulmonary embolism (PE) in patients of Russian hospitals.

Material and methods. The register included all hospitalized patients with PE identified by any diagnostic method. Duration of inclusion was 12 months. In-hospital period management was assessed. Information about the included patients was provided by 20 hospitals from 15 Russian cities.

Results. For the period from April 15, 2018 to April 15, 2019, 609 patients were included in the register (women — 50,7%, mean age — 63,0±14,5 years, minimum-maximum — 19-94 years). Among the known risk factors for PE, the most common were lower limb varicose veins (31,4%), heart failure (23,3%), previous deep vein thrombosis (19,4%), cancer (17,1%). The median time from

symptom onset to suspicion/confirmation of PE was 4 days (1-3 quartiles — 1-8 days). Shortness of breath, syncope/presyncope, chest pain/discomfort, cough, leg pain or lower extremity asymmetry and hemoptysis were noted in 88,7%, 30,0%, 29,8%, 17,3%, 9,4% and 8,5% of patients, respectively. Echocardiography was performed in 89,5%, and Doppler ultrasound of lower limb veins — in 85,9% of patients. Signs of venous thrombosis were found in 57,8% of patients. Computed tomographic (CT) pulmonary angiography was performed in 89,2% of patients, pulmonary scintigraphy and pulmonary angiography — 0,8% each. In total, imaging technologies were used in 90,6% of patients, and signs confirming PE were found in 92,7%. Thrombolytic therapy (TLT) was performed in 25,0%; 92,0% of patients received anticoagulants. At the same time, unfractionated heparin (UFH) was injected subcutaneously in 26,3% of cases, and in one third of patients the drug was injected in doses unadjusted by body weight. In 42,7% of patients received UFH, the target activated partial thromboplastin time was not achieved. With warfarin treatment, the target international normalized ratio was achieved in only 48,4% of patients. Inferior vena cava filter placement and thrombectomy were performed in 1,3% each. During hospitalization (median — 11 days), 9,9% of patients died.

Conclusion. Symptoms and main risk factors for PE in Russian patients did not fundamentally differ from those previously known. There was good adherence to modern guidelines for the diagnosis of PE, but adherence to guidelines on drug therapy met requirements only in half of the cases. There was an excessive use of TLT, as well as the use of ineffective methods of administering and monitoring anticoagulant therapy.

Key words: pulmonary embolism, register, SIRENA, deep vein thrombosis, anticoagulants, thrombolysis, outcomes.

Relationships and Activities: none.

Register participants: Birobidzhan. Zhukova N. Yu., Kazan. Mayanskaya S. D., Gilmanov A. A., Akhundov R. N., Safina E. I., Rudneva T. V., Salakhutdinova L. M., Rizatdinova F. N., Kemerovo. Barbarash O. L., Kheraskov V. Yu., Shmidt E. A., Klimenkova A. V., Neeshpapa A. G., Maikop. Khatkhokhu M. G., Moscow. Merai I. A., Babaeva L. A., Teterina M. A., Romanenko K. V., Aryutina O. V., Berns S. A., Erlikh A. D., Ignatenko O. V., Callagov D. Z., Kuzub A. A., Klimenko A. S., Strelnikova Yu. S., Veselov G. A., Pichugina T. D., Kurenkov D. A., Kulakov V. F., Piksina G. F., Andreev D. A., Baturina O. A., Chashkina M. I., Nizhny Novgorod. Botova S. N., Pochinka I. G., Yurkova K. N., Koroleva L. Yu., Kovaleva G. V., Zlobina D. S., Perm. Lapin O. M., Syromyatnikova L. I., Dukhanina E. A., Pankova E. V., Shkuratova E. N., Zhuikova T. A., Kachina I. I., Alieva E. Kh., Ryazan. Nikulina N. N., Terekhovskaya Yu. V., Samara. Duplyakov D. V., Antimonova M. A., Mullova I. S., Cherepanova N. A., Leksina A. A., St. Petersburg. Cherkashin M. A., Rykov I. V., Naperov E. V., Sochi. Zykov M. V., Bedikyan A. H., Kruberg L. K., Selivanova N. B., Martirosyan E. F., Tver. Alekseev D. V., Razygraev R. A., Golubeva M. A., Polevova I. V., Tomsk. Ryabov V. V., Vasiltseva O. Ya., Syrkina A. G., Lebedeva M. V., Ulan-Ude. Donirova O. S., Donirov B. A., Bulutova N. O., Ulyanovsk. Menzorov M. V., Kasalinskaya V. V.

1Pirogov Russian National Research Medical University, Moscow; 2N. E. Bauman City Clinical Hospital № 29, Moscow; 3Research Institute of Complex Issues of Cardiovascular Diseases, Kemerovo; 4Samara State Medical University, Samara; 5V. P. Polyakova Samara Regional Clinical Cardiology Dispensary, Samara, Russia.

Erlikh A. D. ORCID: 0000-0003-0607-2673, Atakanova A. N. ORCID: 0000-0002-3000-1202, Neeshpapa A. G. ORCID: 0000-0002-6808-9959, Cherepanova N. A. ORCID: none, Mullova I. S.* ORCID: 0000-0002-9321-6251, Barbarash O. L. ORCID: 0000-0002-4642-3610, Berns S. A. ORCID: 0000-0003-1002-1895, Shmidt E. A. ORCID: 0000-0003-3215-2140, Duplyakov D. V. ORCID: 0000-0002-6453-2976.

*Corresponding author: irinamullova@gmail.com

Received: 19.04.2020

Revision Received: 25.05.2020

Accepted: 28.05.2020

For citation: Erlikh A. D., Atakanova A. N., Neeshpapa A. G., Cherepanova N. A., Mullova I. S., Barbarash O. L., Berns S. A., Shmidt E. A., Duplyakov D. V. Russian register of acute pulmonary embolism SIRENA: characteristics of patients and in-hospital treatment. Russian Journal of Cardiology. 2020;25(10):3849. (In Russ.) doi:10.15829/1560-4071-2020-3849

PREVALENCE OF GERIATRIC SYNDROMES IN PERSONS OVER 65 YEARS: THE FIRST RESULTS OF THE EVCALIPT STUDY

Tkacheva O. N.1, Vorob’eva N. M.1, Kotovskaya Yu. V.1, Ostroumova O. D.2, Chernyaeva M. S.3, Silyutina M. V.4, Chernov A. V.4, Testova S. G.4, Ovcharova L. N.5, Selezneva E. V.5

Abstract

Aim. To study the prevalence of geriatric syndromes and assess their relationship with senile asthenia in persons aged ≥65 years living in Russian regions with different demographic, climatic and socio-economic characteristics.

Material and methods. We examined 664 patients aged 65-107 years (mean age, 79±9 years; men, 25%) living in Moscow (n=365) and Voronezh (n=299). All patients underwent a comprehensive geriatric examination, which consisted of two stages:

a survey with original questionnaire and an objective examination.

Results. The prevalence of senile asthenia was 66,4%, including 47,4% in people aged 65-74, 71,1% — 75-84 years, and 82,8% — ≥85 years (p for trend <0,001). Senile asthenia was associated with age (odds ratio (OR), 2,36; 95% confidence interval (CI), 1,89-2,93; p<0,001) and female sex (OR, 1,52; 95% CI 1,06-2,18; p=0,024). Patients with senile asthenia had a lower socioeconomic status. Also, close associations of senile asthenia with other geriatric syndromes (dementia, depression, vision and hearing impairment, incontinence, falls, high risk of falls, functional decline, failure to thrive) with OR from 1,32 to 7,22 were revealed.

Conclusion. The first results of the EVCALIPT study indicate a high incidence of senile asthenia in persons aged ≥65 years and its close association with other geriatric syndromes and socio-economic factors.

Key words: geriatric syndrome, senile asthenia, epidemiological study, elderly patient.

Relationships and Activities. The paper was performed within the state assignment of the Pirogov Russian National Research Medical University.

1Russian Clinical and Research Center of Gerontology, Pirogov Russian National Research Medical University, Moscow; 2Russian Medical Academy of Continuous Professional Education, Moscow; 3Hospital for War Veterans № 2, Moscow; 4N.N. Burdenko Voronezh State Medical University, Voronezh; 5National Research University Higher School of Economics, Moscow, Russia.

Tkacheva O. N. ORCID: 0000-0002-4193-688X, Vorob’eva N. M.* ORCID: 0000-0002-6021-7864, Kotovskaya Yu. V. ORCID: 0000-0002-1628-5093, Ostroumova O. D. ORCID: 0000-0002-0795-8225, Chernyaeva M. S. ОRCID: 0000-0003-3091-7904, Silyutina M. V. ОRCID: 0000-0001-7670-2947, Chernov A. V. ОRCID: 0000-0001-8462-7270, Testova S. G. ОRCID: 0000-0001-6921-3002, Ovcharova L. N. ORCID: 0000-0002-7266-707X, Selezneva E. V. ORCID: 0000-0001-6623-6815.

*Corresponding author: natalyavorobjeva@mail.ru

Received: 29.06.2020

Revision Received: 08.08.2020

Accepted: 14.08.2020

For citation: Tkacheva O. N., Vorob’eva N. M., Kotovskaya Yu. V., Ostroumova O. D., Chernyaeva M. S., Silyutina M. V., Chernov A. V., Testova S. G., Ovcharova L. N., Selezneva E. V. Prevalence of geriatric syndromes in persons over 65 years: the first results of the EVCALIPT study. Russian Journal of Cardiology. 2020;25(10):3985. (In Russ.) doi:10.15829/1560-4071-2020-3985

ASCENDING AORTIC ANEURYSM: PROPENSITY SCORE MATCHING ANALYSIS OF HEMIARCH AND NON-HEMIARCH REPLACEMENT

Kozlov B. N.1, Panfilov D. S.1, Sonduev E. L.1, Lukinov V. L.2

Abstract

Aim. To compare the short- and medium-term outcomes of hemiarch and nonhemiarch replacement for ascending aortic aneurysm (AAA).

Material and methods. The study included 151 patients with non-syndromic AAA who underwent an elective replacement. Patients were divided into two groups: group 1 (non-hemiarch, n=40) — standard ascending aortic replacement; group 2 (hemiarch, n=111) — ascending aortic replacement with the hemiarch anastomosis in conditions of moderate hypothermia and circulatory arrest with unilateral antegrade cerebral perfusion. To eliminate systematic differences between the compared groups, the propensity score matching (PSM) method was used.

Results. Before PSM, there were no significant intergroup differences in the incidence of neurological complications, myocardial infarction, prolonged ventilation, or acute kidney injury. Bleeding-related reoperation rates and hospital mortality significantly differed between groups. After pseudo-randomization between the non-hemiarch and hemiarch groups, there were no significant differences in the incidence of neurological events, myocardial infarction, prolonged ventilation, reoperations for bleeding, acute renal injury, and hospital mortality. Median-term survival and freedom from aortic reoperations also did not show significant intergroup differences.

Conclusion. Hemiarch replacement for AAA does not lead to an increase in the incidence of postoperative complications, as well as the risk of short- and mediumterm mortality compared with non-hemiarch.

Key words: aortic aneurysm, prosthetics, postoperative complications, hospital mortality, reoperation.

Relationships and Activities. Study registration № ACTRN12619001583134.

1Cardiology Research Institute, Tomsk National Research Medical Center, Tomsk; 2Institute of Computational Mathematics and Mathematical Geophysics, Novosibirsk, Russia.

Kozlov B. N. ORCID: 0000-0002-0217-7737, Panfilov D. S. ORCID: 0000-0003-2201-350X, Sonduev E. L.* ORCID: 0000-0002-0835-022X, Lukinov V. L. ORCID: 0000-0002-3411-508X.

*Corresponding author: erdeniooo@mail.ru

Received: 06.05.2020

Revision Received: 01.08.2020

Accepted: 11.09.2020

For citation: Kozlov B. N., Panfilov D. S., Sonduev E. L., Lukinov V. L. Ascending aortic aneurysm: propensity score matching analysis of hemiarch and non-hemiarch replacement. Russian Journal of Cardiology. 2020;25(10):3887. (In Russ.) doi:10.15829/1560-4071-2020-3887

DISTANCE LEARNING IN CARDIOLOGY: THE USE OF MULTIMEDIA CLINICAL DIAGNOSTIC TASKS

Karas S. I.1,2, Grakova E. V.1, Balakhonova M. V.2, Arzhanik M. B.2, Kara-Sal E. E.3

Abstract

Aim. To create a methodological base for distance learning of cardiology healthcare professionals — multimedia clinical diagnostic tasks.

Material and methods. The interdisciplinary team used text and multimedia formats for clinical diagnostic data. Web technologies provided remote access to information located on the server.

Results. The report presents the experience of the practical implementation of multimedia clinical diagnostic tasks in cardiology, including the augmented reality. The variability of presenting information to students is implemented in the multimedia clinical diagnostic tasks, which is integrated with the rating system for evaluating decisions. The solution paths are determined by the actions of the students in the trigger interactive blocks and is evaluated by the rating system. Personal rating is a numerical value that integrally characterizes the decisionmaking competence of students. The conversion of the quantitative rating into the conventional form (‘pass/fail’, ‘excellent’, ‘good’, ‘passing grade’) will be provided after the trial period of the software.

Conclusion. The created Web service and computer simulations can become a methodological basis for the distance learning in cardiology. This technology can be in demand in the continuing medical education.

Key words: virtual patients, computer simulations, professional development, continuing medical education, Web service, distance learning.

Relationships and Activities. This work was supported by the Russian Foundation for Basic Research within the grant № 19-013-00231 “Information and communication technologies for the formation and improvement of clinical and diagnostic competencies of students in the system of postgraduate medical education.”

Acknowledgements. The authors are gratitude to Usov V. Yu., Zavadovskiy K. V., Vaizov V. Kh., Baev A. E., Gulyaev V. M., Vesnina Zh. V., staff of the Cardiology Research Institute, Tomsk National Research Medical Center, for the multimedia materials provided; Dorofeev K. A., Kochetkov S. B., Datsyuk V. V., Nozdrin G. K., Kasinskaya E. S., staff of the OOO Elecard-Med, for analytics and software implementation of clinical diagnostic tasks.

1Cardiology Research Institute, Tomsk National Research Medical Center, Tomsk; 2Siberian State Medical University, Tomsk; 3National Research Tomsk Polytechnic University, Tomsk, Russia.

Karas S. I.* ORCID: 0000-0001-6716-856X, Grakova E. V. ORCID: 0000-0003-4019-3735, Balakhonova M. V. ORCID: 0000-002-5510-4589, Arzhanik M. B. ORCID: 0000-0003-4844-9803, Kara-Sal E. E. ORCID: 0000-0003-3184-4268.

*Corresponding author: ksi@cardio-tomsk.ru

Received: 21.09.2020

Revision Received: 30.09.2020

Accepted: 09.10.2020

For citation: Karas S. I., Grakova E. V., Balakhonova M. V., Arzhanik M. B., Kara-Sal E. E. Distance learning in cardiology: the use of multimedia clinical diagnostic tasks. Russian Journal of Cardiology. 2020;25(10):4116. (In Russ.) doi:10.15829/1560-4071-2020-4116

CLINICAL OBSERVATION

MIXED CARDIOMYOPATHY ASSOCIATED WITH A DSP GENE VARIANT: A CASE REPORT AND LITERATURE REVIEW

Shlyk I. V.1, Streltsova A. A.2, Teplov V. M.1, Gavrilova E. G.1, Kulikov A. N.1,3, Krutikov A. N.2, Rybakova M. G.1, Kuznetsova I. A.1, Andreeva S. E.2, Bezhanishvili T. G.1, Khudyakov A. A.2, Kostareva A. A.1,2, Gudkova A. Ya.1,2

Abstract

A case report of mixed cardiomyopathy (combination of non-compaction cardiomyopathy and arrhythmogenic right ventricular dysplasia) associated with a DSP gene variant is presented. The first and only symptom of the disease was sudden cardiac death.

Key words: sudden cardiac death, long QT syndrome, myocardial electrical instability, arrhythmogenic cardiomyopathy, non-compaction cardiomyopathy, genetic variants DSP and KCNH2.

Relationships and Activities. This work was supported by the Russian Science Foundation grant 20-15-00271.

1First Pavlov State Medical University of St. Petersburg, St. Petersburg; 2Almazov National Medical Research Center, St. Petersburg; 3Kirov Military Medical Academy, St. Petersburg, Russia.

Shlyk I. V. ORCID: 0000-0003-0977-8081, Streltsova A. A. ORCID: 0000-0002-2766-8946, Teplov V. M. ORCID: 0000-0002-4299-4379, Gavrilova E. G. ORCID: 0000-0002-9126-3206, Kulikov A. N. ORCID: 0000-0002-4544-2967, Krutikov A. N. ORCID: 0000-0001-6897-6171, Rybakova M. G. ORCID: 0000-0002-8404-1859, Kuznetsova I. A. ORCID: 0000-0003-4368-7810, Andreeva S. E.* ORCID: 0000-0001-7306-9525, Bezhanishvili T. G. ORCID: 0000-0002-3167-6340, Khudyakov A. A. ORCID: 0000-0001-9214-0868, Kosta reva A. A. ORCID: 0000-0002-9349-6257, Gudkova A. Ya. ORCID: 0000-0003-0156-8821.

*Corresponding author: andreeva.sofi2012@yandex.ru

Received: 09.09.2020

Revision Received: 23.09.2020

Accepted: 28.09.2020

For citation: Shlyk I. V., Streltsova A. A., Teplov V. M., Gavrilova E. G., Kulikov A. N., Krutikov A. N., Rybakova M. G., Kuznetsova I. A., Andreeva S. E., Bezhanishvili T. G., Khudyakov A. A., Kostareva A. A., Gudkova A. Ya. Mixed cardiomyopathy associated with a DSP gene variant: a case report and literature review. Russian Journal of Cardiology. 2020;25(10):4102. (In Russ.) doi:10.15829/1560-4071-2020-4102

THE COMBINATION OF LEFT VENTRICULAR NON-COMPACTION AND HYPERTROPHIC CARDIOMYOPATHY IN ONE FAMILY WITH A PATHOGENIC VARIANT IN THE MYBPC3 GENE (RS397516037)

Myasnikov R. P.1, Kulikova O. V.1, Meshkov A. N.1, Mershina E. A.2, Kiseleva A. V.1, Klimushina M. V.1, Divashuk M. G.1,3, Kurilova O. V.1, Pilyus P. S.2, Kharlap M. S.1, Koretsky S. N.1, Larina O. M.2, Sinitsyn V. E.2, Gandaeva L. A.4, Barsky V. I.4, Basargina E. N.4, Boytsov S. A.5, Drapkina O. M.1

Abstract

The article presents the results of clinical, instrumental and molecular genetic tests of three generations of a family with inherited cardiomyopathy caused by a new variant in the MYBPC3 gene. A specific feature of this case is the phenotypic heterogeneity of the mutation — a combination of hypertrophic cardiomyopathy and left ventricular non-compaction in family members. Attention is drawn to the various severity of clinical manifestations in relatives of carriers of mutation: from asymptomatic to severe heart failure and acute cerebrovascular accident.

Key words: left ventricular non-compaction, hypertrophic cardiomyopathy, heart failure, sudden cardiac death, family forms, thromboembolism, acute cerebrovascular accident, MYBPC3.

Relationships and Activities: none.

1National Medical Research Center for Therapy and Preventive Medicine, Moscow; 2Medical Research and Education Center, Lomonosov Moscow State University, Moscow; 3All-Russian Research Institute of Agricultural Biotechnology, Kurchatov Genomics Center, Moscow; 4National Medical Research Center for Children’s Health, Moscow; 5National Medical Research Center of Cardiology, Moscow, Russia.

Myasnikov R. P. ORCID: 0000-0002-9024-5364, Kulikova O. V.* ORCID: 0000-0002-3138-054X, Meshkov A. N. ORCID: 0000-0001-5989-6233, Mershina E. A. ORCID: 0000-0002-1266-4926, Kiseleva A. V. ORCID: 0000-0003-4765-8021, Klimushina M. V. ORCID: 0000-0002-7876-9325, Divashuk M. G. ORCID: 0000-0001-6221-3659, Kurilova O. V. ORCID: 0000-0003-3082-5161, Pilyus P. S. ORCID: 0000-0001-7802-2734, Kharlap M. S. ORCID: 0000-0002-6855-4857, Koretsky S. N. ORCID: 0000-0001-6009-5775, Larina O. M. ORCID: 0000-0002-2484-5249, Sinitsyn V. E. ORCID: 0000-0002-5649-2193, Gandaeva L. A. ORCID: 0000-0003-0890-7849, Barsky V. I. ORCID: 0000-0003-1267-1517, Basargina E. N. ORCID: 0000-0002-0144-2885, Boytsov S. A. ORCID: 0000-0001-6998-8406, Drapkina O. M. ORCID: 0000-0002-4453-8430.

*Corresponding author: olgakulikova2014@mail.ru

Received: 21.09.2020

Revision Received: 30.09.2020

Accepted: 09.10.2020

For citation: Myasnikov R. P., Kulikova O. V., Meshkov A. N., Mershina E. A., Kiseleva A. V., Klimushina M. V., Divashuk M. G., Kurilova O. V., Pilyus P. S., Kharlap M. S., Koretsky S. N., Larina O. M., Sinitsyn V. E., Gandaeva L. A., Barsky V. I., Basargina E. N., Boytsov S. A., Drapkina O. M. The combination of left ventricular non-compaction and hypertrophic cardiomyopathy in one family with a pathogenic variant in the MYBPC3 gene (rs397516037). Russian Journal of Cardiology. 2020;25(10):4115. (In Russ.) doi:10.15829/1560-4071-2020-4115

LITERATURE REVIES

FIBROSIS IN THE CARDIOVASCULAR AND RESPIRATORY SYSTEMS AFTER COVID-19: A CONTRIBUTION OF IMMUNE FACTORS AND GENETIC PREDISPOSITION

Golovkin A. S.1, Kudryavtsev I. V.2, Dmitriev A. V.2, Kalinina O. V.1

Abstract

In February 2020, a pandemic of a SARS-CoV-2 infection was declared. The number of people who have been exposed to the novel coronavirus infection is steadily increasing around the world. Comparison of data on pathogenesis, clinical course, complications and outcomes with other respiratory viral infections, primarily caused by Betacoronavirus, gives reason to expect an increase in the number of patients after COVID-19 with long-term cardiovascular, respiratory and other complications. In the pathogenesis of possible complications, the leading role will be played by impaired immune function, primarily the adaptive immunity. This review examines the involvement of T-helpers and the humoral factors they produce in the pathogenesis of complications of viral (coronavirus) infections with cardiovascular and respiratory injury, as well as the known data on the genetic determination of cytokine-producing activity of these cells.

Key words: COVID-19, fibrosis, T-helper subpopulations, humoral factors.

Relationships and Activities. The study was supported by a grant from the Russian Science Foundation (project № 19-75-20076).

1Almazov National Medical Research Center, St. Petersburg; 2Institute for Experimental Medicine, St. Petersburg, Russia.

Golovkin A. S.* ORCID: 0000-0002-7577-628X, ResearcherID: I-2583-2014, Kudryavtsev I. V. ORCID: 0000-0001-7204-7850, ResearcherID: D-2124-2013, Dmitriev A. V. ORCID: 0000-0002-6214-9770, Kalinina O. V. ORCID: 0000-0003-1916-5705, ResearcherID: L-1822-2017.

*Corresponding author: golovkin_a@mail.ru

Received: 04.09.2020

Revision Received: 11.09.2020

Accepted: 15.09.2020

For citation: Golovkin A. S., Kudryavtsev I. V., Dmitriev A. V., Kalinina O. V. Fibrosis in the cardiovascular and respiratory systems after COVID-19: a contribution of immune factors and genetic predisposition. Russian Journal of Cardiology. 2020;25(10):4087. (In Russ.) doi:10.15829/1560-4071-2020-4087

EXTRACELLULAR VESICLE THERAPY: EFFECTIVENESS, MECHANISMS AND APPLICATION POTENTIALS

Velikonivtsev F. S., Golovkin A. S.

Abstract

Extracellular vesicles are biological membrane objects sized <1000 nm, transporting many biologically active molecules (proteins, microRNA, mRNA, DNA, etc.) and performing many biological functions and providing intercellular interactions. At present, the possibilities of their therapeutic use in various pathological conditions and diseases are being actively studied. In most cases, mesenchymal stem cells are considered as a cellular source of extracellular vesicles, and the realized therapeutic effects are associated with the transferred microRNAs. In vitro studies have shown that intracellular vesicles can stimulate regeneration and angiogenesis, have antiinflammatory and antiapoptotic effects. The studies considered I current review demonstrate the prospects for the clinical use of extracellular vesicles in the treatment of pathological conditions such as oxidative stress, ischemia-reperfusion injury, tumor growth, etc.

Key words: extracellular vesicles, therapeutic use, microRNA.

Relationships and Activities. The study was supported by a grant from the Russian Science Foundation (project № 19-75-20076).

Almazov National Medical Research Center, St. Petersburg, Russia.

Velikonivtsev F. S. ORCID: 0000-0002-1830-8340, ResearcherID: AAY-4886-2020, Golovkin A. S.* ORCID: 0000-0002-7577-628X, ResearcherID: I-2583-2014.

*Corresponding author: golovkin_a@mail.ru

Received: 01.09.2020

Revision Received: 07.09.2020

Accepted: 15.09.2020

For citation: Velikonivtsev F. S., Golovkin A. S. Extracellular vesicle therapy: effectiveness, mechanisms and application potentials. Russian Journal of Cardiology. 2020;25(10):4081. (In Russ.) doi:10.15829/1560-4071-2020-4081

SOME PRO- AND ANTI-INFLAMMATORY CYTOKINES, THEIR GENETIC POLYMORPHISM AND POSTINFARCT CARDIAC REMODELING

Nikolaeva A. M.1, Babushkina N. P.2, Ryabov V. V.1,3,4

Abstract

The role of molecular genetic factors in cardiovascular disease (CVD) development has been actively studied in recent years. In patients with acute myocardial infarction and heart failure, the genetic component contributes to the determination of inflammation

and persistence of inflammatory mediators in the myocardium. The genetic component in combination with traditional CVD risk factors determines the clinical course of the disease, the severity and its outcome. This review summarizes the data on relationship of pro- and anti-inflammatory cytokines with coronary artery disease and its clinical manifestations.

Key words: myocardial infarction, heart failure, genetic polymorphism, cytokines, angiogenic growth factors, postinfarct cardiac remodeling.

Relationships and Activities: none.

1Cardiology Research Institute, Tomsk National Research Medical Center, Tomsk; 2Research Institute of Medical Genetics, Tomsk National Research Medical Center, Tomsk; 3National Research Tomsk State University, Tomsk; 4Siberian State Medical University, Tomsk, Russia.

Nikolaeva A. M.* ORCID: 0000-0002-1632-6342, Babushkina N. P. ORCID: 0000-0001-6133-8986, Ryabov V. V. ORCID: 0000-0002-4358-7329.

*Corresponding author: tonya_nikolaeva93@mail.ru

Received: 09.07.2020

Revision Received: 29.08.2020

Accepted: 11.09.2020

For citation: Nikolaeva A. M., Babushkina N. P., Ryabov V. V. Some pro- and anti-inflammatory cytokines, their genetic polymorphism and postinfarct cardiac remodeling. Russian Journal of Cardiology. 2020;25(10):4007. (In Russ.) doi:10.15829/1560-4071-2020-4007

BLOOD PRESSURE TELEMONITORING AND REMOTE COUNSELING OF HYPERTENSIVE PATIENTS: PROS AND CONS

Ionov M. V.1,2, Zvartau N. E.1,2, Konradi A. O.1,2, Shlyakhto E. V.1

Abstract

Home blood pressure monitoring (HBPM) is strongly recommended by current guidelines as an effective out-of-office diagnostic and monitoring tool in patients with hypertension (HTN). However, there are personal, cultural, logistic difficulties owing to low effectiveness of HBPM. These put HBPM at a disadvantage in routine clinical practice. As such, telehealth solutions are of special interest nowadays, particularly blood pressure telemonitoring (BPTM) with or without remote counseling. BPTM might become something of digital assistant in the long-term patients’ follow-up and it fits well into the practice of continuity of medical care. The purpose of this review is to highlight not only the benefits of BPTM, but important discrepancies that may impede its widespread implementation in everyday clinical work. Critical comments address the lack of long-term, high-quality studies, absence of hard clinical outcomes and uncertainty on the best technical performance.

Key words: hypertension, e-health, telemedicine, blood pressure telemonitoring, m-health, blood pressure self-monitoring.

Relationships and Activities. The study was supported by a Russian Science Foundation grant № 17-15-01177.

1Almazov National Medical Research Center, St. Petersburg; 2ITMO University, St. Petersburg, Russia.

Ionov M. V.* ORCID: 0000-0002-3664-5383, Zvartau N. E. ORCID: 0000-0001-6533-5950, Konradi A. O. ORCID: 0000-0001-8169-7812, Shlyakhto E. V. ORCID: 0000-0003-2929-0980.

*Corresponding author: ionov_mv@almazovcentre.ru

Received: 17.08.2020

Revision Received: 01.09.2020

Accepted: 02.09.2020

For citation: Ionov M. V., Zvartau N. E., Konradi A. O., Shlyakhto E. V. Blood pressure telemonitoring and remote counseling of hypertensive patients: pros and cons. Russian Journal of Cardiology. 2020;25(10):4066. (In Russ.) doi:10.15829/1560-4071-2020-4066

7 декабря 2020 г.

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