Contents of Russian Journal of Cardiology 2019, 24 (10)

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Russian Journal of Cardiology. 2019;24(10):5

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ORIGINAL ARTICLES

POLYMORPHIC VARIANT RS1739843 OF HEAT SHOCK PROTEIN BETA-7 (HSPB7) GENE AND ITS RELATIONSHIP WITH ON CLINICAL PROFILE AND OUTCOMES IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY (RESULTS OF A 10-YEAR FOLLOW-UP)

Streltsova A. A.1, Gudkova A. Ya.1,2, Polyakova A. A.1,2, Pyko S. A.3, Kostareva A. A.1,2

Abstract

Aim. To determine the impact of polymorphic variant rs1739843 of the HSPB7 gene on clinical profile and outcomes in patients with hypertrophic cardiomyopathy (HCM).

Material and methods. The study population consisted of 108 patients with HCM ≥45 years old. The control group included 192 healthy donors. The design of the study included an assessment of the clinical course, determining the outcome of HCM using a new methodological approach proposed by Rowin EJ, et al. (2017). Polymorphic variant rs1739843 of the HSPB7 gene was genotyped by allele-specific real-time polymerase chain reaction (PCR) assay.

Results. It was found a significant increase in frequency of TT genotype of rs1739843 of the HSPB7 gene in patients with HCM — 20,4%, compared with control group — 4,2% (ТТ: ТС+СС, odds ratio (OR) =5,88, 95% confidence interval (CI) =2,52-13,75, p<0,001). High prevalence of CC genotype of rs1739843 of the HSPB7 gene was observed in control group — 80,2% vs 31,5% in HCM group (CC: ТС+TT, OR=0,11, 95% CI=0,07-0,19, p<0,001). The allele frequency (С:Т) also differs between HCM and control groups — 55,6:44,4% in HCM vs 88,02:11,98% in control group (OR=5,88, 95% CI=3,91-8,85, p<0,001). It was also found a significant increase in frequency of TT genotype and T allele of rs1739843 of the HSPB7 gene in HCM patients with oligosymptomatic HCM course — 16,7%, compared with control group — 4,2% (ТТ: ТС+СС, OR=4,60, 95% CI=1,63-12,99, p<0,001). HCM patients ≥45 years old showed a significant increase in T allele frequency in cases of presence of 2 (FC III-IV CHF (chronic heart failure)+AF (atrial fibrillation), 18,8% vs 6,6%) and 3 adverse pathways (FC III-IV CHF+AF+SCD (sudden cardiac death), 4,2% vs 1,6%).

Conclusion. HCM progression along 2 and more adverse pathways in patients ≥45 years old has been characterized with adverse outcome. The T allele and TT genotype of rs1739843 of the HSPB7 gene were more frequent in patients with HCM ≥45 years old, compared with control group. It was also found a significant increase in frequency of TT genotype and T allele of rs1739843 of the HSPB7 gene in HCM patients with oligosymptomatic HCM course, compared with control group. Allele T of rs1739843 of the HSPB7 gene is associated with 2 and more adverse pathways of HCM progression.

Key words: hypertrophic cardiomyopathy, syndrome, chronic heart failure with preserved ejection fraction, polymorphic variant rs1739843 of the HSPB7 gene.

Conflicts of Interest: nothing to declare.

Funding. This study was carried out as part of the State assignment of the Ministry of Health of the Russian Federation on the topic: “Molecular genetic predictors and morphological and functional phenotypes of heart failure with a preserved ejection fraction of the left ventricle in cardiomyopathies of various genesis” State Authorization № AAAA-A18-118070690073-2.

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

Streltsova A. A. ORCID: 0000-0002-2766-8946, Gudkova A. Ya. ORCID: 0000-0003-0156-8821, Polyakova A. A. ORCID: 0000-0002-6655-5274, Pyko S. A. ORCID: 0000-0001-6625-3770, Kostareva A. A. ORCID: 0000-0002-9349-6257.

Received: 31.01.2019

Revision Received: 13.03.2019

Accepted: 20.03.2019

For citation: Streltsova A. A., Gudkova A. Ya., Polyakova A. A., Pyko S. A., Kostareva A. A. Polymorphic variant rs1739843 of heat shock protein beta-7 (HSPB7) gene and its relationship with on clinical profile and outcomes in patients with hypertrophic cardiomyopathy (results of a 10-year follow-up). Russian Journal of Cardiology. 2019;24(10):7–15 doi:10.15829/1560-4071-2019-10-7-15

ASSOCIATION OF POLYMORPHIC VARIANTS RS6684209 AND RS7521023 OF THE CALSEQUESTRIN GENE (CASQ2) WITH CONTRACTILE MYOCARDIAL FUNCTION IN PATIENTS WITH CORONARY ARTERY DISEASE

Muslimova E. F., Rebrova T. Yu., Archakov E. A., Kondratieva D. S., Lugacheva Yu. G., Batalov R. E., Afanasiev S. A.

Abstract

Aim. To study the association between polymorphic rs6684209 and rs7521023 variants of the CASQ2 gene and myocardial contractile function and risk factors for the development of chronic heart failure (CHF).

Material and methods. The study included 172 patients with CHF developing on the background of coronary artery disease. We identified polymorphic variants rs6684209 and rs7521023 of the CASQ2 gene by real-time polymerase chain reaction.

Results. There was no association of the rs6684209 variant with CHF and the frequency of cardiac arrhythmias. It was revealed that the carriage of the GG genotype of rs7521023 variant is associated with a higher frequency of dilatation of the left atrium (p=0,044) and an increased end-systolic volume (p=0,045).

Conclusion. Among patients with coronary artery disease, there was no correlation between the rs7521023 and rs6684209 variants of the calsequestrin gene (CASQ2) with the frequency of cardiac arrhythmias. There was no association of the rs6684209 variant with CHF risk factors and parameters of myocardial contractile function. A relationship was found between the GG genotype of the rs7521023 variant and a higher frequency of left atrium dilatation. Among patients taking betablockers, the GG genotype is associated with an increase in end-systolic volume.

Key words: heart failure, dilatation of the left atrium, polymorphism, calsequestrin, CASQ2.

Conflicts of Interest: nothing to declare.

Funding. The study was conducted with the support of the fundamental scientific research topic № AAAA-A15-115123110026-3 and the RFBR project № 17-04-01450.

Research Institute of Cardiology, Tomsk National Research Medical Center, Tomsk, Russia.

Muslimova E. F. ORCID: 0000-0001-7361-2161, Rebrova T. Yu. ORCID: 0000-0003-3667-9599, Archakov E. A. ORCID: 0000-0002-2530-361X, Kondratieva D. S. ORCID: 0000-0002-4004-2497, Lugacheva Yu. G. ORCID: 0000-0002-5417-1038, Batalov R. E. ORCID: 0000-0003-1415-3932, Afanasiev S. A. ORCID: 0000-0001-6066-3998.

Received: 12.03.2019

Revision Received: 18.04.2019

Accepted: 25.04.2019

For citation: Muslimova E. F., Rebrova T. Yu., Archakov E. A., Kondratieva D. S., Lugacheva Yu. G., Batalov R. E., Afanasiev S. A. Association of polymorphic variants rs6684209 and rs7521023 of the calsequestrin gene (CASQ2) with contractile myocardial function in patients with coronary artery disease. Russian Journal of Cardiology. 2019;24(10):16–21 doi:10.15829/1560-4071-2019-10-16-21

ASSOCIATION OF T715P (RS6136), M62I (RS2228315), S290N (RS6131), V640L (RS6133) POLYMORPHISMS IN THE P-SELECTIN GENE AND ITS LIGAND WITH ACETYLSALICYLIC ACID RESISTANCE IN PATIENTS WITH CORONARY ARTERY DISEASE AFTER CORONARY ARTERY BYPASS GRAFTING

Kosinova A. A.1, Mongush T. S.1,2, Goncharov M. D.1,2, Subbotina T. H.3, Semashchenko K. S.3, Kochmareva G. Yu.3, Grinshteyn Yu. I.1

Abstract

Aim. To study the association of T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) polymorphisms in the P-selectin gene with resistance to acetylsalicylic acid (ASA) in patients with coronary artery disease after coronary artery bypass grafting (CABG).

Material and methods. The study included 90 patients aged 61,5±6,9 years (70 men and 20 women) with II-IV functional class (FC) angina pectoris, according to the Canadian Cardiovascular Society grading. The atherosclerotic nature of coronary artery disease is confirmed by coronary angiography. Patients stopped taking antiplatelet agents before CABG for at least 5 days. The aggregation study was carried out with an optical aggregometer using ADP inducers (5 μM) and arachidonic acid (1 μM) before CABG, on 1-3 and 8-10 days after surgical treatment. DNA samples were examined for the presence of T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) polymorphisms in the P-selectin gene using realtime PCR with allele-specific primers.

Results. When comparing aPTT, fibrinogen level, platelet aggregation activity with ADP inducers (5 μM) and arachidonic acid (1 μМ), no differences were found among groups of patients with homozygous and heterozygous variants of the studied polymorphisms genotypes, both before and on 1-3, 8 -10 days after CABG. Regarding presence of ASA resistance, patient groups with homozygous variants of genotypes (T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133)) did not statistically differ in prevailing or rare alleles from the corresponding groups with heterozygous genotypes. In the first 10 days of the postoperative period, thrombotic events (4,4%) were observed in 4 patients in the study group: acute myocardial infarction, acute cerebrovascular accident. Regarding frequency of adverse events in the first 10 days after CABG, between groups of patients with homozygous variants of the studied genotypes (T715Р (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) in prevailing allele and groups with heterozygous variants of the corresponding genotypes there were also no statistically significant differences.

Conclusion. Rs6133, rs6163, rs2228315, rs6131 polymorphisms in the platelet P-selectin gene are not associated with ASA resistance and are not associated with increased platelet aggregation activity in patients with coronary artery disease. The rare T, C, G, A alleles of the studied polymorphisms do not lead to an increase in the risks of adverse events in the first 10 days after CABG.

Key words: rs6133, rs6136, rs2228315, rs6131, acetylsalicylic acid, P-selectin.

Conflicts of Interest: nothing to declare.

Funding. The study was financially supported by the Russian Foundation for Basic Research, the Government of the Krasnoyarsk Territory, the Krasnoyarsk Regional Science Fund as part of a scientific project: № 18-415-243003 “Characterization of antiplatelet therapy of patients with coronary artery disease (CAD) depending on the level of expression of the P-selectin gene, the pronouncement of intercellular interaction and inflammation”.

1Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk; 2Federal Center for Cardiovascular Surgery, Krasnoyarsk; 3Siberian Federal University, Krasnoyarsk, Russia.

Kosinova A. A. ORCID: 0000-0002-7412-2516, Mongush T. S. ORCID: 0000-0003-4530-8730, Goncharov M. D. ORCID: 0000-0001-5583-7412, Subbotina T. H. ORCID: 0000-0001-7790-5033, Semashchenko K. S. ORCID: 0000-0002-8735-2716, Kochmareva G. Yu. ORCID: 0000-0001-7570-0835, Grinshteyn Yu. I. ORCID: 0000-0002-4621-1618.

Received: 11.03.2019

Revision Received: 19.04.2019

Accepted: 25.04.2019

For citation: Kosinova A. A., Mongush T. S., Goncharov M. D., Subbotina T. H., Semashchenko K. S., Kochmareva G. Yu., Grinshteyn Yu. I. Association of T715P (RS6136), M62I (RS2228315), S290N (RS6131), V640L (RS6133) polymorphisms in the P-selectin gene and its ligand with acetylsalicylic acid resistance in patients with coronary artery disease after coronary artery bypass grafting. Russian Journal of Cardiology. 2019;24(10):22–28 doi:10.15829/1560-4071-2019-10-22-28

ASSOCIATION OF RS2230806 POLYMORPHISM WITH THE DEVELOPMENT OF ACUTE CEREBROVASCULAR ACCIDENT IN PATIENTS WITH CARDIOVASCULAR DISEASE

Nikulina S. Yu.1, Shulman V. A.1, Chernova A. A.1, Prokopenko S. V.1, Nikulin D. A.1,3, Platunova I. M.4, Tretyakova S. S.1, Semenchukov A. A.1, Marilovtseva O. V.1, Maksimov V. N.2, Gurazheva A. A.2

Abstract

Aim. To study the association of single nucleotide polymorphism (SNP) rs2230806 (C>T) with the development of acute cerebrovascular accident (CVA) in East Siberian patients with cardiovascular pathology and risk factors.

Material and methods. The study involved 260 patients with acute CVA (age [57,0; 51,0-62,0]) and 272 patients of control group (age [55,0; 51,0-62,0]). Among patients with acute CVA there were 157 men and 103 women. The control group included 170 men and 102 women. Examination of the experimental group included: acquisition of complaints, anamnesis, clinical examination, computed cerebral tomography, electrocardiography, echocardioscopy, ultrasound duplex scanning of extracranial brachiocephalic arteries, 24-hour monitoring of blood pressure and heart rate, analysis of the blood coagulation system. In patients of the experimental group, the following cardiovascular pathology and risk factors were present: arterial hypertension, paroxysmal supraventricular tachycardia, dyslipidemia, atherosclerosis of the brachiocephalic arteries, hemostatic system disorders. The control group was examined as part of the international HAPIEE project. Molecular genetic studies were performed by real-time PCR.

Results. In all analyzed groups and subgroups of patients, a statistically significant relationship was found between the CC genotype and the C SNP allele rs662799 (A>G) and an increased risk of stroke.

Conclusion. The CC genotype and the C SNP allele rs2230806 (C>T) increases the risk of acute cerebrovascular accident in patients regardless of previous cardiovascular pathology and risk factors, including in patients with arterial hypertension, supraventricular tachyarrhythmias, atherosclerosis of brachiocephalic arteries, and disorders of lipid metabolism and hemostatic system.

Key words: acute CVE, supraventricular tachycardia, arterial hypertension, BCA atherosclerosis, rs2230806.

Conflicts of Interest: nothing to declare.

Funding. This work was supported by a grant from the President of the Russian Federation MD-58887.2018.7.

1Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk; 2Scientific Research Institute of Therapy and Preventive Medicine — branch of Federal Research Center of ICG, Novosibirsk; 3Federal Siberian Research Clinical Centre, Krasnoyarsk; 4Berzon Krasnoyarsk Interdistrict Clinical Hospital № 20, Krasnoyarsk, Russia.

Nikulina S. Yu. ORCID: 0000-0002-6968-7627, Shulman V. A. ORCID: 0000-0002-1968-3476, Chernova A. A. ORCID: 0000-0003-2977-1792, Prokopenko S. V. ORCID: 0000-0002-4778-2586, Nikulin D. A. ORCID: 0000-0003-1591-035X, Platunova I. M. ORCID: 0000-0002-7688-3079, Tretyakova S. S. ORCID: 0000-0003-0529-3001, Semenchukov A. A. ORCID: 0000-0003-4750-8680, Marilovtseva O. V. ORCID: 0000-0002-1323-2367, Maksimov V. N. ORCID: 0000-0002-3157-7019, Gurazheva A. A. ORCID: 0000-0003-1547-624Х.

Received: 13.05.2019

Revision Received: 03.07.2019

Accepted: 10.07.2019

For citation: Nikulina S. Yu., Shulman V. A., Chernova A. A., Prokopenko S. V., Nikulin D. A., Platunova I. M., Tretyakova S. S., Semenchukov A. A., Marilovtseva O. V., Maksimov V. N., Gurazheva A. A. Association of rs2230806 polymorphism with the development of acute cerebrovascular accident in patients with cardiovascular disease. Russian Journal of Cardiology. 2019;24(10):29–34 doi:10.15829/1560-4071-2019-10-29-34

ASSOCIATION OF SINGLE NUCLEOTIDE POLYMORPHISMS RS7164665, RS71461059, RS74765750, RS6762529 WITH SUDDEN CARDIAC DEATH

Ivanova A. A.1, Maksimov V. N.1,2, Malyutina S. K.1,2, Novoselov V. P.3, Voevoda M. I.1

Abstract

Aim. To confirm the association between sudden cardiac death (SCD) and single nucleotide polymorphisms rs7164665, rs71461059, rs74765750, rs6762529, identified in own genome-wide associative study as new molecular genetic markers of SCD.

Material and methods. As design we used case-control study. The SCD group was formed using the SCD criteria of the European Society of Cardiology (n=438, average age 53,2±9,1 years, male — 72,7%, women — 28,3%). The control group (n=435, average age 53,2±8,9 years, men — 70,0%, women — 30,0%) was selected by gender and age for the SCD group from the DNA bank of the international projects MONICA and HAPIEE. DNA was isolated by phenol-chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. The results are statistically processed using the SPSS 16.0 software package.

Results. No carriers of the rare allele A of the single nucleotide polymorphism rs74765750 were found in the SCD group and the control group. No statistically significant differences were found between the SCD group and the control group relating to frequencies of genotypes and alleles of single nucleotide polymorphisms rs7164665 and rs71461059. In the age group older than 50 years, the proportion of carriers of the heterozygous CT genotype of the single nucleotide polymorphism rs6762529 in the SCD group is statistically significantly lower compared to the control group (CT vs CC+TT: OR=0,686, 95% CI 0,483-0,967, p=0,035).

Conclusion. The CT genotype of the single nucleotide polymorphism rs6762529 is associated with a protective effect on SCD for people over 50 years of age. The association with single nucleotide polymorphisms rs7164665, rs71461059, rs74765750 with SCD has not been confirmed.

Key words: sudden cardiac death, GWAS, single nucleotide polymorphism, rs7164665, rs71461059, rs74765750, rs6762529.

Conflicts of interest: nothing to declare.

Funding. The study was supported by a scholarship of the President of the Russian Federation for young scientists and graduate students engaged in advanced research and development in priority areas of modernization of the Russian economy (SP-625.2018.4).

Acknowledgments. The authors are deeply grateful to Academician of the Russian Academy of Sciences Yuri Petrovich Nikitin for the opportunity to form a control group based on HAPIEE and MONICA cohorts.

1Scientific Research Institute of Therapy and Preventive Medicine — branch of Federal Research Center of ICG, Novosibirsk; 2Novosibirsk State Medical University, Novosibirsk; 3Novosibirsk Regional Office of the Chief Medical Examiner, Novosibirsk, Russia.

Ivanova A. A. ORCID: 0000-0002-9460-6294, Maksimov V. N. ORCID: 0000-0002-7165-4496, Malyutina S. K. ORCID: 0000-0001-6539-0466, Novoselov V. P. ORCID: 0000-0002-6312-5543, Voevoda M. I ORCID: 0000-0001-9425-413X.

Received: 01.06.2019

Revision Received: 05.07.2019

Accepted: 12.07.2019

For citation: Ivanova A. A., Maksimov V. N., Malyutina S. K., Novoselov V. P., Voevoda M. I. Association of single nucleotide polymorphisms rs7164665, rs71461059, rs74765750, rs6762529 with sudden cardiac death. Russian Journal of Cardiology. 2019;24(10):35–41 doi:10.15829/1560-4071-2019-10-35-41

THE EFFECT OF GENE POLYMORPHISM OF CERTAIN CYTOKINES ON ECHOCARDIOGRAPHIC PARAMETERS IN PATIENTS WITH CHRONIC RHEUMATIC HEART DISEASE

Petrov V. S.

Abstract

Aim. To assess the effect of polymorphism of tumor necrosis factor-α (TNF-α) cytokines and interleukin (IL-17A, IL-17F, IL-10) on echocardiographic parameters in patients with chronic rheumatic heart disease (RHD).

Material and methods. A total of 128 patients with RHD were examined, average age was 58,96±0,34 years. Echocardiography was performed on a Philips Affinity 50 machine. Genotyping was carried out using polymorphic TNF-α markers (G308A, IL-10 G1082A, IL-17A G197A, IL-17F А161H0 by polymerase chain reaction with an electrophoretic scheme for detecting the result of “SNP-EXPRESS”.

Results. RHD homozygotes for TNF-α A308A had the largest linear dimensions of the left ventricle (left ventricle end-diastolic dimension (LVED) — 5,80±0,22 cm, left ventricle end-systolic dimension (LVES) — 3,93±0,27 cm), as well as the studied homozygous for IL-17A A197A (LVED — 5,81±0,13 cm, LVES — 3,78±0,11 cm). In group of TNF-α G308G homozygotes, values of right heart (right ventricle — 2,75±0,05 cm, right atrium — 4,80±0,11 cm) were the largest and mitral valve orifice area (MVOA) was smallest — 1,52±0,04 cm2. Heterozygous patients with IL-17F A161H also had a greater dilatation of the ventricles compared with homozygotes of IL-17F H161H, in which parameters were close to normal (LVED 5,58±0,05 cm, LVES 3,68±0,04 cm). There was no statistically significant difference in linear sizes of the left and right heart in patients with IL-10 polymorphism. IL-10 polymorphism patients had statistically significant MVOA differences: minimum MVOA in G1082A heterozygotes — 1,40±0,06 cm2 and maximum — 1,64±0,04 cm2 in G1082G homozygotes. IL-10 G1082G homozygotes was characterized by maximum values of interventricular septum — 1,13±0,04 cm, left ventricular posterior wall — 1,10±0,03 cm.

Conclusion. Homozygosity of TNF-α A308A and IL-17A A197A in RHD patients leads to the largest linear sizes of the left ventricle, and homozygosity for TNF-α G308G — to the maximum sizes of the right heart and left atrium against the background of the minimum sizes of MVOA. IL-10 polymorphism has not effect on heart linear dimensions, but IL-10 G1082G leads to maximum MVOA size.

Key words: rheumatic heart disease, cytokines gene polymorphism, echocardiography.

Conflicts of Interest: nothing to declare.

Ryazan State Medical University n.a. acad. I.P. Pavlov, Ryazan, Russia.

Petrov V. S. ORCID: 0000-0001-8631-8826.

Received: 08.08.2019

Revision Received: 10.09.2019

Accepted: 17.09.2019

For citation: Petrov V. S. The effect of gene polymorphism of certain cytokines on echocardiographic parameters in patients with chronic rheumatic heart disease. Russian Journal of Cardiology. 2019;24(10):42–47 doi:10.15829/1560-4071-2019-10-42-47

POLYMORPHIC VARIANTS OF GENES ENCODING CA(2+)-TRANSPORTING SARCOPLASMIC RETICULUM PROTEINS IN THE PROGRESSION OF CHRONIC HEART FAILURE

Muslimova E. F., Rebrova T. Yu., Archakov E. A., Akhmedov Sh. D., Budnikova O. V., Batalov R. E., Afanasiev S. A.

Abstract

Aim. To study the association between polymorphic rs1860561 variants of Ca(2+)- ATPase SERCA2a (ATP2A2) gene and rs3766871 of ryanodine receptor (RYR2) gene and the severity of chronic heart failure (CHF).

Material and methods. We determined rs1860561 and rs3766871 variants of the ATP2A2 and RYR2 genes, respectively, in 168 patients with coronary artery disease (CAD) and CHF using real-time polymerase chain reaction.

Results. A statistically significant (p=0,046) decrease in the left ventricular ejection fraction in AA homozygotes of the ATP2A2 gene compared to carriers of the G allele was shown. But among GG homozygotes, patients with FC II CHF prevailed and participants with FC I CHF were less common than among patients with genotype GA (p=0,041).

Conclusion. The association of the AA genotype carriage for the rs1860561 variant of the ATP2A2 gene encoding Ca(2+)-ATPase SERCA2a, with a decrease in the left ventricle ejection fraction in patients with CHF and CAD was revealed. At the same time, among the GG homozygotes, FC I CHF was the least prevalent. There was no association of the rY3766871 variant of the RYR2 gene with CHF severity.

Key words: heart failure, ATP2A2, RYR2, polymorphic variant.

Conflicts of Interest: nothing to declare.

Funding. This work was financially supported by the Russian Foundation for Basic Research (project № 17-04-01450).

Research Institute of Cardiology, Tomsk National Research Medical Center, Tomsk, Russia.

Muslimova E. F. ORCID: 0000-0001-7361-2161, Rebrova T. Yu. ORCID: 0000-0003-3667-9599, Archakov E. A. ORCID: 0000-0002-2530-361X, Akhmedov Sh. D. ORCID: 0000-0002-0791-7466, Budnikova O. V. ORCID: 0000-0001-5004-1896, Batalov R. E. ORCID: 0000-003-1415-3932, Afanasiev S. A. ORCID: 0000-0001-6066-3998.

Received: 04.12.2018

Revision Received: 06.02.2019

Accepted: 13.02.2019

For citation: Muslimova E. F., Rebrova T. Yu., Archakov E. A., Akhmedov Sh. D., Budnikova O. V., Batalov R. E., Afanasiev S. A. Polymorphic variants of genes encoding Ca(2+)-transporting sarcoplasmic reticulum proteins in the progression of chronic heart failure. Russian Journal of Cardiology. 2019;24(10):48–52 doi:10.15829/1560-4071-2019-10-48-52

GENETIC MARKERS OF RISK FOR ST-ELEVATED MYOCARDIAL INFARCTION

Lozhkina N. G.1, Kozik V. A.1, Tolmacheva A. A.1, Khasanova M. Kh.1, Naydena E. A.1, Stafeeva E. A.1, Barbarich V. B.1,3, Kuimov A. D.1, Maksimov V. N.2, Voevoda M. I.2

Abstract

Aim. To identify genetic markers of risk for ST-elevated myocardial infarction (STEMI).

Material and methods. The study included 210 patients (119 men, 91 women) with STEMI, hospitalized from December 21, 2016 to June 16, 2017. The average age of men was 55,5±9,5 years, women — 57,5±9,1 years. The diagnosis of STEMI was verified according to the criteria of the European Society of Cardiology (2015, 2017). During hospitalization, patients underwent clinical and instrumental examination, stipulated by medical care standards and clinical guidelines We also conducted a genetic study of single nucleotide polymorphisms (SNPs), which showed their association with the risk of coronary artery disease (CAD) and acute myocardial infarction (AMI) according to the GWAS: rs2820315 of the LMOD1 gene (Leiomodin 1, mapped on chromosome 1), rs9349379 of the PHACTR1 gene (regulator 1 of actin and phosphotase, localized on chromosome 6p24.1), rs867186 of the PROCR gene (Protein C receptor, located on chromosome 20q11.22), rs1799883 of the FABP2 gene (Fatty acid-binding protein 2, located on chromosome 4q26). Statistical data analysis was performed using the SPSS 17.0.5 software package and authorial odds ratio (OR) calculator.

Results. Carriage of the CC genotype of rs2820315 polymorphism of the LMOD gene is associated with an increased risk of STEMI by 1,87 times (95% CI 1,286-2,722, p=0,016). Carriers of the CT genotype of rs2820315 polymorphism have a reduced risk of STEMI (OR 0,633; 95% CI 0,436-0,918, p=0,016).

Conclusion. In order to identify risk groups for STEMI development, the study of the rs2820315 polymorphism of the LMOD gene is recommended. This will define the high-risk group for STEMI for developing of personalized programs for primary and secondary prevention of cardiovascular events in practical health care, which will contribute to reducing of STEMI mortality.

Key words: ST-elevated myocardial infarction, myocardial infarction, coronary artery disease, single nucleotide polymorphisms, genetic markers.

Conflicts of Interest: nothing to declare.

Funding. The study was carried out as part of the state assignment of the Ministry of Health of Russia on the topic: “The effect of various treatment strategies using genetic markers on the long-term outcomes of acute coronary syndrome” (Reg. № AAAA-A18-118030790009-4).

1Novosibirsk State Medical University, Novosibirsk; 2Research Institute of Therapy and Preventive Medicine, Institute of Cytology and Genetics, Novosibirsk; 3City Clinical Hospital № 1, Novosibirsk, Russia.

Lozhkina N. G. ORCID: 0000-0002-4832-3197, Kozik V. A. ORCID: 0000-0001-7128-7887, Tolmacheva A. A. ORCID: 0000-0003-1687-4100, ResearcherID: T-6052-2018, Khasanova M. Kh. ORCID: 0000-0003-1610-4069, Naydena E. A. ORCID: 0000-0002-0927-5962, Stafeeva E. A. ORCID: 0000-00033684-5526, Barbarich V. B. ORCID: 0000-0001-9987-8574, Kuimov A. D. ORCID: 0000-0002-2998-2322, Maksimov V. N. ORCID: 0000-0002-7165-4496, ResearcherID H-7676-2012, Voevoda M. I. ORCID: 0000-0001-9425-413X, ResearcherID: N-6713-2015.

Received: 29.07.2019

Revision Received: 24.08.2019

Accepted: 02.09.2019

For citation: Lozhkina N. G., Kozik V. A., Tolmacheva A. A., Khasanova M. Kh., Naydena E. A., Stafeeva E. A., Barbarich V. B., Kuimov A. D., Maksimov V. N., Voevoda M. I. Genetic markers of risk for ST-elevated myocardial infarction. Russian Journal of Cardiology. 2019;24(10):53–57 doi:10.15829/1560-4071-2019-10-53-57

THE ROLE OF MUSCLE TISSUE IN THE PATHOGENESIS OF CHRONIC HEART FAILURE — THE POTENTIAL OF EXPOSURE (FORMA STUDY)

Lelyavina T. A., Sitnikova M. Yu., Galenko V. L., Kozlov P. S., Bortsova M. A., Demchenko E. A., Ganenko O. S., Golovkin A. S., Kostareva A. A., Dmitrieva R. I.

Abstract

Aim. To determine whether the skeletal muscle of patients with chronic heart failure (CHF) retains the ability to regenerate and grow; to compare the effectiveness of long aerobic trainings, calculated by an individualized method, and conventionally calculated trainings (VO2peak values), in relation to the severity of heart failure, exercise tolerance (ET), and ergoreflex activity (ERGO).

Material and methods. The study included 297 patients with stable III functional class (FC) CHF, receiving optimal therapy. The presence of heart failure was found in all patients at least 6 months before the start of the study (age — 18-65 years, body mass index (BMI) — 19-28 kg/height, m2. Initially, the study performed a cardiorespiratory test (CRT) with an assessment of gas composition, acid-base balance of the blood and ERGO activity. Patients were randomized into 2 groups: experimental (EG) and control (CG). For EG, based on the determination of the lactate threshold (LT), after 1 and 3 months the CRT was repeated and the training walking mode was dynamically recounted according to the new LT level. For CG, the training walking mode was calculated based on the VO2peak values. All patients trained for 6 months. At the end of the training, diagnostic CRT was performed, and the activity of EGO was evaluated. Eleven patients with CHF and 3 healthy donors before the start of the training underwent a biopsy of the gastrocnemius muscle.

Results. It was shown that the potential for muscle differentiation of satellite skeletal muscle precursor cells obtained from patients with CHF with a reduced ejection fraction (HFrEF) does not differ in vitro from the potential of satellite cells of healthy donors. After 6 months of training, the severity of CHF decreased to FC II in 75% of EG patients, and among CG patients — in 44%; the main indicators of the stages of compensatory mechanisms activation during physical exertion (VO2LT and VO2peak) in EG increased more than in the CG (10,8±0,4, 18,7±0,7 ml/min/kg and 9,5±0,8, 15,3±0,9 ml/min/kg, with p1<0,01, p2<0,05, p3<0,01, respectively).

Conclusion. In vitro, the potential for muscle differentiation, regeneration and growth of satellite skeletal muscle precursor cells obtained from patients with HFrEF does not differ from the potential of satellite cells of healthy donors. Aerobic training in patients with III FC chronic heart failure calculated by definition of LT, relating to safety is not worse than the results calculated by the level of VO2peak. Aerobic training in patients with III FC chronic heart failure calculated by definition of LT, compared with the usual mode of training walking, significantly reduce the activity of ergoreflex, increase ET, reduce the severity of CHF. In patients with III FC CHF, training walking for more than 1,5 hours/day determined by the level of LT, contributes to the development of physiological reverse myocardial remodeling to a greater extent than aerobic training calculated by the conventional method.

Key words: heart failure, long aerobic training, ergoreflex, inversion of myocardial remodeling, skeletal muscle satellite cells, muscle tissue regeneration.

Conflicts of Interest: nothing to declare.

Funding. This study was partially supported by the Russian Science Foundation grant № 16-15-1017.

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

Lelyavina T. A. ORCID: 0000-0001-6796-4064, Sitnikova M. Yu. ORCID: 0000-0002-0139-5177, Galenko V. L. ORCID: 0000-0002-0503-167X, Kozlov P. S. ORCID: 0000-0001-5886-7908, Bortsova M. A. ORCID: 0000-0002-9694-7850, Demchenko E. A. ORCID: 0000-0002-0009-9106, Ganenko O. S. ORCID: 0000-0001-7989-3785, Golovkin A. S. ORCID: 0000-0002-7577-628X, Kostareva A. A. ORCID: 0000-0002-9349-6257, Dmitrieva R. I. ORCID: 0000-0002-3073-7914.

Received: 19.03.2019

Revision Received: 23.05.2019

Accepted: 30.05.2019

For citation: Lelyavina T. A., Sitnikova M. Yu., Galenko V. L., Kozlov P. S., Bortsova M. A., Demchenko E. A., Ganenko O. S., Golovkin A. S., Kostareva A. A., Dmitrieva R. I. The role of muscle tissue in the pathogenesis of chronic heart failure — the potential of exposure (FORMA study). Russian Journal of Cardiology. 2019;24(10):58–65 doi:10.15829/1560-4071-2019-10-58-65

THE RELATIONSHIP OF GENETIC RISK FACTORS WITH THE DEVELOPMENT OF ARTERIAL HYPERTENSION TAKING INTO ACCOUNT ETHNIC DIFFERENCES

Kovaleva A. Ya.1, Kokh N. V.1, Voronina E. N.1, Donirova O. S.2, Zelenskaya E. M.1, Lifshits G. I.1,3

Abstract

Aim. To study the influence of genetic factors on the risk of essential arterial hypertension (AH) and the course in patients of Russian and Buryat ethnicity.

Material and methods. The study included 248 patients of the Russian and 92 patients of the Buryat ethnic group. All patients were evaluated for genotypes by ACE, ADRB1, ADRB2, ADRB3, CAT, NOS3, CYP11B2, AGT, STK39, EDN1, GNB3 markers. Following clinical data were determined: age, body mass index, smoking history, stage and degree of AH, the presence and nature of target organ damage, hereditary history. In the study, patients of the two ethnic groups were divided into the case and control groups depending on the presence or absence of AH.

Results. In patients of the Russian ethnic group, an association of a more severe AH course with a burdened family history was revealed, in contrast to patients of Buryat nationality. In the Buryat group, the development of AH is associated with polymorphisms of the candidate genes ADRB3 (rs4994), GNB3 (rs5443), ACE (rs464994), STK39 (rs3754777), EDN1 (rs9349379). In the Russian group, ACE, EDN1, CYP11B2 (rs1799998), GNB3, NOS3 (rs1799983), ADRB1 (rs1801253) genes had a significant contribution. When comparing the assortment of allele frequency of the ACE gene polymorphic marker among two ethnic groups, the “I” allele was found significantly more frequently in patients of Russian group.

Conclusion. The results of the study revealed ethnic differences in the genetic features of essential AH. For the first time, an association between genetic markers encoding elements of the renin-angiotensin system, sympathoadrenal system, endothelial system and AH risk in patients of Buryat nationality was established. The identification of ethnic differences and genetic predisposition to AH, makes it possible to understand the role of the hereditary component of hypertension. We suppose that these data in conjunction with the influence of the environment, can help to develop one of the areas of personalized medicine.

Key words: arterial hypertension, ethnos, Buryats, genetic markers.

1Institute of Chemical Biology and Fundamental Medicine, Novosibirsk; 2Semashko Republican Clinical Hospital of the Republic of Buryatia, Ulan-Ude; 3State Medical University, Novosibirsk, Russia.

Kovaleva A. Ya. ОRCID: 0000-0002-7041-5071, Kokh N. V. ОRCID: 0000-0001-6374-1728, Voronina E. N. ОRCID: 0000-0002-3405-6980, Donirova O. S. ORCID: 0000-0002-7409-9096, Zelenskaya E. M. ОRCID: 0000-0001-9513-0366, Lifshits G. I.

ОRCID: 0000-0001-9048-7710.

Received: 16.07.2019

Revision Received: 24.08.2019

Accepted: 02.09.2019

For citation: Kovaleva A. Ya., Kokh N. V., Voronina E. N., Donirova O. S., Zelenskaya E. M., Lifshits G. I. The relationship of genetic risk factors with the development of arterial hypertension taking into account ethnic differences. Russian Journal of Cardiology. 2019;24(10):66–71 doi:10.15829/1560-4071-2019-10-66-71

SUPPORTING A PRACTITIONER

CLINICAL AND DIAGNOSTIC DIFFICULTIES IN MANAGEMENT OF PATIENTS WITH LAMINOPATHIES

Melnik O. V.1, Malashicheva A. B.1,2, Fomicheva Yu. V.1, Khudyakov A. A.1,2, Gudkova A. Ya.3, Rudenko D. I.3, Simonenko M. A.1, Mikhailov E. N.1, Lebedev D. S.1, Vasichkina E. S.1, Pervunina T. M.1, Kostareva A. A.1

Abstract

Mutations in the LMNA gene cause developing of several phenotypes, both with isolated involvement of cardiac, muscle, adipose and bone tissues, and with their combination. The dominance of cardiovascular signs in the clinical performance and false clarity in nosology definition can cause underestimation of subclinical markers of other systems partaking. It leads to an incorrect interpretation of the true disease etiology, failure in genetic diagnostics, and untimely determination of the correct management and prognosis. The article presents clinical cases that demonstrate both the most typical manifestations of laminopathy and rare combinations of symptoms, which represent a certain diagnostic difficulty.

Key words: lamin A/C, cardiomyopathy, arrhythmia, neuropathy, heart failure, mutations.

Conflicts of Interest: nothing to declare.

Funding. The study was supported by a grant from the Russian Foundation for Basic Research 19-015-00313 and a grant from Saint Petersburg State University № 11934817.

1Almazov National Medical Research Center, St. Petersburg; 2Pavlov First Saint Petersburg State Medical University, St. Petersburg; 3Saint Petersburg State University, St. Petersburg, Russia.

Melnik O. V. ORCID: 0000-0001-6727-4231, Malashicheva A. B. ORCID: 0000-0002-0820-2913, Fomicheva Yu. V. ORCID: 0000-0001-8950-8617, Khudyakov A. A. ORCID: 0000-0001-9214-0868, Gudkova A. Ya. ORCID: 0000-0003-0156-8821, Rudenko D. I. ORCID: 0000-0001-5101-1007, Simonenko M. A. ORCID: 0000-0003-3228-1188, Mikhailov E. N. ORCID: 0000-0002-6553-9141, Lebedev D. S. ORCID: 0000-0002-2334-1663, Vasichkina E. S. ORCID: 0000-0001-7336-4102, Pervunina T. M. ORCID: 0000-0001-9948-7303, Kostareva A. A. ORCID: 0000-0002-9349-6257.

Received: 28.11.2018

Revision Received: 10.01.2019

Accepted: 17.01.2019

For citation: Melnik O. V., Malashicheva A. B., Fomicheva Yu. V., Khudyakov A. A., Gudkova A. Ya., Rudenko D. I., Simonenko M. A., Mikhailov E. N., Lebedev D. S., Vasichkina E. S., Pervunina T. M., Kostareva A. A. Clinical and diagnostic difficulties in management of patients with laminopathies. Russian Journal of Cardiology. 2019;24(10):72–77 doi:10.15829/1560-4071-2019-10-72-77

GENETIC RISK FACTORS FOR VASCULAR AGING: MOLECULAR MECHANISMS, POLYMORPHISM OF CANDIDATE GENES AND GENE NETWORKS

Slepukhina A. A.1, Zelenskaya E. M.1, Lifshits G. I.1,2

Abstract

Age is considered an independent and primary risk factor in the development of cardiovascular disease. Aging of vascular cells induces complex changes in the structure and functions of the vasculature. The article discusses a number of molecular genetic mechanisms involved in the pathogenesis of vascular aging: cell and mitochondrial dysfunction, endothelial dysfunction, depletion of the progenitor cell pool, shortening and damage to telomeres, chronic inflammation, oxidative stress, and dysregulation of vascular tone. There is more and more evidence of cross-involvement in the vascular aging processes of candidate genes (such as ACE, SIRT1, TERC, FOXO1, FOXO3, APOE, NOS3) associated with life expectancy and cardiovascular diseases. For 26 genes involved in the presented molecular mechanisms of vascular aging, sites of functional polymorphisms are given. Understanding the main pathophysiological changes caused by vascular aging makes it possible to choose a preventive strategy. Modern approaches for better predicting of genetic risk are discussed in conclusion using the example of visualization of vascular aging genes network.

Key words: vascular aging, endothelial dysfunction, arterial stiffness, oxidative stress, genetic risk, gene network.

Conflicts of Interest: nothing to declare.

Funding. The study was financially supported by the RFBR in the framework of scientific project № 19 315-80032.

1Institute of Chemical Biology and Fundamental Medicine, Novosibirsk; 2Novosibirsk State Medical University, Novosibirsk, Russia.

Slepukhina A. A. ORCID: 0000‑0001‑5069-8193, Zelenskaya E. M. ОRCID: 0000-0001-9513-0366, Lifshits G. I. ОRCID: 0000-0001-9048-7710.

Received: 23.06.2019

Revision Received: 31.07.2019

Accepted: 08.08.2019

For citation: Slepukhina A. A., Zelenskaya E. M., Lifshits G. I. Genetic risk factors for vascular aging: molecular mechanisms, polymorphism of candidate genes and gene networks. Russian Journal of Cardiology. 2019;24(10):78–85 doi:10.15829/1560-4071-2019-10-78-85

GENETIC PREDICTORS OF FIVE-YEAR OUTCOMES OF ACUTE CORONARY SYNDROME

Lozhkina N. G.1, Tolmacheva A. A.1, Khasanova M. X.1, Kozik V. A.1, Stafeeva E. A.1, Naydena E. A.1, Mukaramov I.1, Barbarich V. B.1,2, Parkhomenko O. M.2, Kuimov A. D.1, Maksimov V. N.3, Voevoda M. I.3

Abstract

Aim. To determine the genetic predictors of five-year outcomes in patients with acute coronary syndrome (ACS).

Material and methods. The study included patients admitted to the City clinical hospital № 1 (CCH №1) in Novosibirsk with a diagnosis of ACS in the period 2010-2011 (n=280). All patients were examined in accordance with clinical guidelines and standards of care, genetic markers were assessed. Genotyping included determination of single nucleotide polymorphisms (SNPs), confirming its association with the development of the ACS according to the results of an international genome associated studies: rs1376251, rs4804611, rs1333049, rs619203, rs10757278, rs2549513, rs499818, rs17465637. All patients are kept in touch from the moment of initial contact to the present time, with the help of available means of communication and annual examinations in order to assess the end points. “End points” included: repeated nonfatal myocardial infarction (MI), hospitalization for myocardial ischemia, re-revascularization or chronic heart failure (CHF), nonfatal acute cerebrovascular accident (NACA), cardiovascular death.

Results. We revealed SNPs, which play a role in predicting long-term outcomes of ACS: rs10757278, rs 4804611, rs 1333049, rs 2549513. The genotype of rs2549513 as 2,9-fold (95% CI 1,06-8,03; p=0,041) increases the risk of unfavorable long-term prognosis in the subgroup of men older than 55 years. The AA genotype rs10757278 and GG genotype rs1333049 are associated with a favorable long-term prognosis (OR=0,47, 95% CI 0,23-0,96; p=0,042 and OR=0,41, 95% CI 0,22-0,78; p=0,049, respectively) in the group of patients older than 55 years. For the GG genotype rs1333049 association was characteristic only for women. The AA genotype rs4804611 is associated with a favorable outcome of ACS at the age of 55 years (OR=0,036, 95% CI 0,14-0,96; p=0,053), significant differences were obtained in the group of men (p=0,36).

Conclusion. The use of identified genetic predictors to assess the risk of five-year outcomes will strengthen a personalized approach to patients and, together with conventional prevention measures, will reduce cardiovascular mortality.

Key words: acute coronary syndrome, single nucleotide polymorphisms, coronary heart disease, genetic markers, five-year follow-up.

Conflicts of Interest: nothing to declare.

Funding. The study was carried out as part of the state assignment of the Ministry of Health of Russia on the topic: “The effect of various treatment strategies using molecular genetic markers on the long-term outcomes of acute coronary syndrome” (Reg. №. AAAA-A18-118030790009-4).

1Novosibirsk State Medical University, Novosibirsk; 2City Clinical Hospital № 1, Novosibirsk; 3Scientific Research Institute of Therapy and Preventive Medicine — branch of Federal Research Center of ICG, Novosibirsk, Russia.

Lozhkina N. G. ORCID: 0000-0002-4832-3197, Tolmacheva A. A. ORCID: 0000-0003-1687-4100, ResearcherID: T-6052-2018, Khasanova M. X. ORCID: 0000-0003-1610-4069, Kozik V. A. ORCID: 0000-0001-7128-7887, Stafeeva E. A. ORCID: 0000-0003-3684-5526, Naydena E. A. ORCID: 0000-0002-0927-5962, Mukaramov I. ORCID: 0000-0002-2172-6797, Barbarich V. B. ORCID: 0000-0001-9987-8574, Parkhomenko O. M. ORCID: 0000-0003-4736-6491, Kuimov A. D. ORCID: 0000-0002-2998-2322, Maksimov V. N. ORCID: 0000-0002-7165-4496, ResearcherID: H-7676-2012, Voevoda M. I. ORCID: 0000-0001-9425-413X, ResearcherID: N-6713-2015.

Received: 30.06.2019

Revision Received: 01.08.2019

Accepted: 08.08.2019

For citation: Lozhkina N. G., Tolmacheva A. A., Khasanova M. X., Kozik V. A., Stafeeva E. A., Naydena E. A., Mukaramov I., Barbarich V. B., Parkhomenko O. M., Kuimov A. D., Maksimov V. N., Voevoda M. I. Genetic predictors of five-year outcomes of acute coronary syndrome. Russian Journal of Cardiology. 2019;24(10):86–90 doi:10.15829/1560-4071-2019-10-86-90

CLINICAL CASE

VARIANTS OF RBM20 GENE IN PEDIATRIC PATIENTS WITH DILATED CARDIOMYOPATHY

Kiselev A. M., Vershinina T. L., Tarnovskaya S. I., Yakovleva E. V., Butish L., Fomicheva Yu. V., Fedotov P. A., Kozyreva A. A., Vakhrushev Yu. A., Latypov A. K., Morozov A. A., Kozyrev I. A., Pervunina T. M., Vasichkina E. S., Kostareva A. A.

Abstract

Aim. Description of three clinical cases of pediatric patients with dilated cardiomyopathy (DCMP) and an analysis of their genetic causes.

Material and methods. Using the method of targeted sequencing, data were obtained on the presence of pathogenic variants of the RBM20 gene in three pediatric patients with DCMP.

Results. Three cases of childhood DCMP development, associated with structural disorders in the RBM20 gene, are particularly described. It is known that RBM20 is involved in the splicing of mRNA of the TTN gene encoding the titin protein. A splicing disorder associated with pathogenic variants in the RBM20 gene can lead to a change in biomechanical and signaling processes in myocardial cells, causing pathological dilated remodeling and rhythm disorders.

Conclusion. Variants in the RBM20 gene are associated with severe DCMP with a childhood debut. In some cases, the progression of RBM20-associated cardiomyopathies is associated with an infectious disease. Further study of the molecular mechanisms of the pathogenesis of DCMP associated with pathogenic variants in the TTN and RBM20 genes is extremely relevant for both clinical cardiology and fundamental medicine.

Key words: dilated cardiomyopathy, RBM20, titin.

Conflicts of Interest: nothing to declare.

Funding. This work was financially supported by the Russian Science Foundation (RSF) grant № 18-75-00006.

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

Kiselev A. M. ORCID: 0000-0002-5524-6900, Vershinina T. L. ORCID: 0000-0003-1311-2020, Tarnovskaya S. I. ORCID: 0000-0002-6777-0785, Yakovleva E. V. ORCID: 0000-0002-7758-5102, Butish L. ORCID: 0000-0003-4040-2824, Fomicheva Yu. V. ORCID: 0000-0001-8950-8617, Fedotov P. A. ORCID: 0000-0002-7452-1971, Kozyreva A. A. ORCID: 0000-0003-0656-7967, Vakhrushev Yu. A. ORCID: 0000-0001-8911-1927, Latypov A. K. ORCID: 0000-0002-5459-6765, Morozov A. A. ORCID: 0000-0001-9350-8804, Kozyrev I. A. ORCID: 0000-0002-2533-5339, Pervunina T. M. ORCID: 0000-0001-9948-7303, Vasichkina E. S. ORCID: 0000-0001-7336-4102, Kostareva A. A. ORCID: 0000-0002-9349-6257.

Received: 13.05.2019

Revision Received: 07.07.2019

Accepted: 15.07.2019

For citation: Kiselev A. M., Vershinina T. L., Tarnovskaya S. I., Yakovleva E. V., Butish L., Fomicheva Yu. V., Fedotov P. A., Kozyreva A. A., Vakhrushev Yu. A., Latypov A. K., Morozov A. A., Kozyrev I. A., Pervunina T. M., Vasichkina E. S., Kostareva

A. A. Variants of RBM20 gene in pediatric patients with dilated cardiomyopathy. Russian Journal of Cardiology. 2019;24(10):92–98 doi:10.15829/1560-4071-2019-10-92-98

LITERATURE REVIEWS

RESTRICTIVE CARDIOMYOPATHY: DIFFICULTIES DESMINOPATHY DIAGNOSTICS

Vaikhanskaya T. G.1, Kaptsiukh T. M.1, Kurushko T. V.1, Sivitskaya L. N.2, Liaudanski O. D.2, Danilenko N. G.2

Abstract

The article provides a brief overview of the problems of diagnostics and etiological verification of restrictive cardiomyopathy (RCMP). Multiple causes lead to the restrictive phenotype of intracardiac hemodynamics and diastolic dysfunction of the heart: infiltrative (amyloidosis, sarcoidosis, elastoma, metabolic syndrome, tumor metastasis to the myocardium); endomyocardial (tropical endomyocardial fibrosis, hypereosinophilic syndrome, carcinoid, radiation damage); accumulation diseases (hemochromatosis, Pompe and Gaucher diseases, Fabry disease). RKMP is also characteristic for desminopathy — so-called desmin storage disease. This is a disease caused by mutations in the desmin gene (DES) that determine the development of cardiomyopathy or myofibrillar myopathy, and in some cases cause a combined phenotype of the disease. Desmin belongs to the group of intermediate filaments that maintain the structural and functional integrity of myofibrils. Mutations in DES lead to disruption of the assembly of filaments and a change in the myofibrillar cell lattice, which contributes to an increased vulnerability of myocytes to mechanical stress. The article presents a clinical case of familial desminopathy associated with a new missense R118P mutation of DES gene, characterized by dominant cardiac RCMP phenotype and subclinical manifestations of myofibrillar myopathy.

Key words: restrictive cardiomyopathy, desminopathy, myofibrillar myopathy, desmin gene, atrioventricular block.

Conflicts of Interest: nothing to declare.

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

Vaikhanskaya T. G. ORCID: 0000-0002-2127-8525, Kaptsiukh T. M. ORCID: 0000-0001-7503-9936, Kurushko T. V. ORCID: 0000-0001-5727-3219, Sivitskaya L. N. ORCID: 0000-0001-6359-4967, Liaudanski O. D. ORCID: 0000-0002-3325-0917, Danilenko N. G. ORCID: 0000-0002-3270-3080.

Received: 29.12.2018

Revision Received: 03.02.2019

Accepted: 11.02.2019

For citation: Vaikhanskaya T. G., Kaptsiukh T. M., Kurushko T. V., Sivitskaya L. N., Liaudanski O. D., Danilenko N. G. Restrictive cardiomyopathy: difficulties desminopathy diagnostics. Russian Journal of Cardiology. 2019;24(10):100–108 doi:10.15829/1560-4071-2019-10-100-108

ISOLATED GLYCOGEN STORAGE DISEASE OF THE HEART

Komissarova S. M.1, Rineiskaya N. M.1, Chakova N. N.2, Niyazova S. S.2, Plashchinskaya L. I.1

Abstract

Isolated glycogen storage disease of the heart (PRKAG2 syndrome) is a form of glycogenosis, which is characterized by left ventricular hypertrophy, similar to the phenotype of hypertrophic cardiomyopathy, associated with pre-excitation of the ventricles and conduction disorders. The disease is caused by mutations in the gene PRKAG2 encoding for the 5’Adenosine Monophosphate-Activated Protein Kinase (AMPK), specifically for its γ2 regulatory subunit, inheritance — autosomal dominant. A review of the literature data and clinical observation of two patients from the same family with the mutation с.905C>A (p.Arg302Gln) in the PRKAG2 gene associated with WPW syndrome and early development of conduction disorders requiring implantation of a pacemaker are presented. The issues of diagnosis and treatment strategy of the disease were discussed.

Key words: PRKAG2 syndrome, isolated glycogen storage disease of the heart, WPW syndrome, mutations, binodal disease.

Conflicts of Interest: nothing to declare.

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

Komissarova S. M. ORCID: 0000-0001-9917-5932, Rineiskaya N. M. ORCID: 0000-0002-1986-1367, Chakova N. N. ORCID: 0000-0003-4721-9109, Niyazova S. S. ORCID: 0000-0002-3566-7644, Plashchinskaya L. I. ORCID: 0000-0001-8815-3543.

Received: 24.06.2019

Revision Received: 31.07.2019

Accepted: 07.08.2019

For citation: Komissarova S. M., Rineiskaya N. M., Chakova N. N., Niyazova S. S., Plashchinskaya L. I. Isolated glycogen storage disease of the heart. Russian Journal of Cardiology. 2019;24(10):110–117 doi:10.15829/1560-4071-2019-10-110-117

THE POTENTIAL ROLE OF MIRNAS IN CALCIFICATION OF CARDIOVASCULAR DISEASES

Ibragimova A. G.1,2, Shakhmaeva K. R.1, Stanishevskaya I. E.1, Shindyapina A. V.2,3

Abstract

MicroRNA is a class of endogenous noncoding 17-25 nucleotides RNAs that regulate gene expression. Recently, more and more works have been appeared confirming the important role of miRNAs in the development and progression of cardiovascular diseases. Calcification mechanisms include impaired regulation of calcium and phosphate metabolism, activation of the signaling

pathways that regulate bone formation, and suppression of the signaling pathways responsible for maintaining the smooth muscle cell phenotype. The involvement of microRNAs was demonstrated for each of these mechanisms, which emphasizes the significant contribution of microRNAs to the development of calcification of blood vessels. This review summarizes the scientific data on microRNAs that are proven to be involved in the development of in vitro and in vivo calcification of their targets, as well as the latest achievements in microRNA studies in the context of vascular calcification. We also discuss the possibility of their use for early diagnostics and treatment of calcification in cardiovascular diseases.

Key words: microRNA, cardiovascular disease, biomarkers, calcification, diagnostics, coronary artery disease.

Conflicts of Interest: nothing to declare.

Funding. This study was supported by OOO MineGenics company and the Institute of Biochemical Technology and Nanotechnology of RUDN University.

1Peoples’ Friendship University of Russia, Moscow, Russia; 2OOO MineGenics, Moscow, Russia; 3Brigham and Women’s Hospital, Harvard Medical School, USA.

Ibragimova A. G. ORCID: 0000-0002-5379-6650, Shakhmaeva K. R. ORCID: 0000-0003-2412-510X, Stanishevskaya I. E. ORCID: 0000-0002-7336-3086, Shindyapina A. V. ORCID: 0000-0002-0334-9190.

Received: 02.04.2019

Revision Received: 14.05.2019

Accepted: 21.05.2019

For citation: Ibragimova A. G., Shakhmaeva K. R., Stanishevskaya I. E., Shindyapina A. V. The potential role of miRNAs in calcification of cardiovascular diseases. Russian Journal of Cardiology. 2019;24(10):118–125 doi:10.15829/1560-4071-2019-10-118-125

CARDIOGENIC SHOCK — THE CURRENT STATE OF THE PROBLEM

Boytsov S. A., Akchurin R. S., Pevzner D. V., Shakhnovich R. M., Ruda M. Ya.

Abstract

Today the incidence of cardiogenic shock (CS) among the patients with myocardial infarction (MI) is on average in 7-8%. Despite the fact that CS is not the most frequent complication of MI, it is the most common cause of death in this disease. The standard and new perspective treatment approaches are being reviewed in this article with emphasis on the method of mechanical circulatory support (MCS). According to a data from large registries, a new approach of utilization of contemporary MCS devices has demonstrated its efficiency in reducing mortality in the patients with MI complicated by CS. At the present stage, universal treatment protocols for CS are being designed. The central element of these protocols is MCS with the use of contemporary devices, implemented according to a scheme that has demonstrated its effectiveness.

Key words: cardiogenic shock, myocardial infarction, mechanical circulatory support, IABP, Impella, ECMO.

Conflicts of interest: nothing to declare.

Acknowledgments. The authors are grateful to the residents of the emergency cardiology department of the National Medical Research Center of Cardiology: Merkulova I. A., Avetisyan E. A.

National Medical Research Center of Cardiology, Moscow, Russia.

Boytsov S. A. ORCID: 0000-0001-6998-8406, Akchurin R. S. ORCID: 0000-0002-2105-8258, Pevzner D. V. ORCID: 0000-0002-5290-0065, Shakhnovich R. M. ORCID: 0000-0003-3248-0224, Ruda M. Ya.

Received: 27.08.2019

Revision Received: 06.09.2019

Accepted: 13.09.2019

For citation: Boytsov S. A., Akchurin R. S., Pevzner D. V., Shakhnovich R. M., Ruda M. Ya. Cardiogenic shock — the current state of the problem. Russian Journal of Cardiology. 2019;24(10):126–136 doi:10.15829/1560-4071-2019-10-126-136

8 ноября 2019 г.

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